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1. Exploring the effect of sedentary behavior on increased adiposity in middle-aged adults.

Author

Macías, Nayeli, Monterrubio-Flores, Eric, Salmerón, Jorge, Meneses-León, Joacim, Flores, Yvonne, Jáuregui, Alejandra, Salvo, Deborah, Villa, Umberto, Olvera, Armando, and Gallegos-Carrillo, Katia

Subjects
Body fat, Cohort study, Middle-aged adults, Sedentary behavior, Self-report correction, Humans, Sedentary Behavior, Male, Female, Middle Aged, Adult, Adiposity, Accelerometry, Cohort Studies, Absorptiometry, Photon, Self Report, Surveys and Questionnaires
Abstract

BACKGROUND: Sedentary behavior is linked to excess fat mass; however, this association may be inconclusive due to potential measurement errors in self-reported sedentary behavior. OBJECTIVE: To assess the association between changes in sedentary behavior and fat mass in a Cohort of Health Workers (HWCS) from 2004 to 2010. METHODS: A total of 1,285 adults participating in the Cohort of Health Workers were evaluated in 2004 and 2010. Fat mass (kg) was measured by dual X-ray absorptiometry. A self-administered questionnaire was used to estimate the sedentary behavior. Sedentary behavior was also estimated using accelerometry in a sample of 142 health workers. Accelerometry data were used to correct self-reported sedentary behavior using a generalized linear model, which included values for sleeping time, age, sex, sedentary behavior, glucose, and triglycerides. Concordance between both methods was assessed using a kappa and Bland-Altman analysis. Once sedentary behavior was corrected, the values were used to evaluate the association between changes in sedentary behavior and body fat mass using a fixed effect model in the cohort, adjusting for confounders. RESULTS: Self-reported sedentary behavior was 2.8 ± 1.8 and 2.3 ± 1.6 h/day, and body fat mass was 24.9 ± 8.1 and 26.8 ± 8.5 kg in 2004 and 2010, respectively. After applying the correction model, the self-reported sedentary behavior was 7.6 ± 1.2 and 7.5 ± 1.2 h/day in 2004 and 2010, respectively. For every hour increase in corrected sedentary behavior, there was an observed increase of 0.847 (p > 0.001) kg in body fat mass during the 6.8 years in the Cohort of Health Workers from 2004 to 2010. Conversely, non-corrected self-reported sedentary behavior was associated with a non-significant reduction of 0.097 kg (p = 0.228) for every hour of sedentary behavior. CONCLUSIONS: Increased sedentary behavior was associated with increased body fat mass when corrected self-reported sedentary behavior was used. Implementing public health strategies to reduce sedentary behavior is imperative.

Published
2024

2. Fibrosis Progression Rate in Biopsy-Proven Nonalcoholic Fatty Liver Disease Among People With Diabetes Versus People Without Diabetes: A Multicenter Study

Author

Huang, Daniel Q, Wilson, Laura A, Behling, Cynthia, Kleiner, David E, Kowdley, Kris V, Dasarathy, Srinivasan, Amangurbanova, Maral, Terrault, Norah A, Diehl, Anna Mae, Chalasani, Naga, Neuschwander-Tetri, Brent A, Sanyal, Arun J, Tonascia, James, Loomba, Rohit, Allende, Daniela, Bellar, Annette, Dasarathy, Jaividhya, Welch, Nicole, Yerrapothu, Rahul, Bashir, Mustafa, Guy, Cynthia, Kopping, Mariko, Piercy, Dawn, Suzuki, Ayako, Tawadrou, Naglaa, Cruz, Mandy, Cummings, Oscar W, Garrison, Lisa, Gawrieh, Samer, Samala, Niharika, Vuppalanchi, Raj, Carpenter, Danielle, Cattoor, Theresa, Freebersyser, Janet, Angkanaworakul, Pannapat, Berihun, Achashman, Buysse, Andrew, Dorrian, Theresa, Gulati, Breanna, Liu, Kevin, Misic, Sandra, Sohal, Adam, Vuong, Joseph, Ajmera, Veeral, Madamba, Egbert, Middleton, Michael S, Richards, Lisa, Singh, Seema, Sirlin, Claude, Gill, Ryan, Hameed, Bilal, Awe, Remilekun, Olvera, Daisy, Terrault, Norah, Yuan, Liyun, Yeh, Matthew, Albhaisi, Somaya, Asgharpour, Amon, Boyett, Sherry, Contos, Melissa J, Luketic, Velimir AC, Schlosser, Jolene, Siddiqui, Mohammad S, Adamo, Peggy, Belt, Patricia, Clark, Jeanne M, DeSanto, Jennifer M, Meinert, Jill, Miriel, Laura, Mitchell, Emily P, Shade, Carrie, Smith, Jacqueline, Smith, Michael, Sternberg, Alice, Van Natta, Mark L, Wagoner, Annette, Woreta, Tinsay, and Yates, Katherine P

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Hepatitis, Liver Disease, Digestive Diseases, Chronic Liver Disease and Cirrhosis, Clinical Research, Diabetes, Obesity, Metabolic and endocrine, Good Health and Well Being, Adult, Humans, Female, Male, Non-alcoholic Fatty Liver Disease, Diabetes Mellitus, Type 2, Cohort Studies, Liver Cirrhosis, Biopsy, Nonalcoholic Steatohepatitis, NAFLD, Cirrhosis, Type 2 Diabetes Mellitus, NASH Clinical Research Network, Neurosciences, Paediatrics and Reproductive Medicine, Gastroenterology & Hepatology, Clinical sciences, Nutrition and dietetics
Abstract

Background & aimsThere are limited data regarding fibrosis progression in biopsy-proven nonalcoholic fatty liver disease (NAFLD) in people with type 2 diabetes mellitus (T2DM) compared with people without T2DM. We assessed the time to fibrosis progression in people with T2DM compared with people without T2DM in a large, multicenter, study of people with NAFLD who had paired liver biopsies.MethodsThis study included 447 adult participants (64% were female) with NAFLD who had paired liver biopsies more than 1 year apart. Liver histology was systematically assessed by a central pathology committee blinded to clinical data. The primary outcome was the cumulative incidence of a ≥1-stage increase in fibrosis in participants with T2DM compared with participants without T2DM.ResultsThe mean (SD) age and body mass index (calculated as weight in kilograms divided by the square of the height in meters) were 50.9 (11.5) years and 34.7 (6.3), respectively. The median time between biopsies was 3.3 years (interquartile range, 1.8-6.1 years). Participants with T2DM had a significantly higher cumulative incidence of fibrosis progression at 4 years (24% vs 20%), 8 years (60% vs 50%), and 12 years (93% vs 76%) (P = .005). Using a multivariable Cox proportional hazards model adjusted for multiple confounders, T2DM remained an independent predictor of fibrosis progression (adjusted hazard ratio, 1.69; 95% CI, 1.17-2.43; P = .005). The cumulative incidence of fibrosis regression by ≥1 stage was similar in participants with T2DM compared with participants without T2DM (P = .24).ConclusionsIn this large, multicenter cohort study of well-characterized participants with NAFLD and paired liver biopsies, we found that fibrosis progressed faster in participants with T2DM compared with participants without T2DM. These data have important implications for clinical practice and trial design.

Published
2023

3. Nutrition assessment and MASH severity in children using the Healthy Eating Index

Author

Jain, Ajay Kumar, Buchannan, Paula, Yates, Katherine P, Belt, Patricia, Schwimmer, Jeffrey B, Rosenthal, Philip, Murray, Karen F, Molleston, Jean P, Scheimann, Ann, Xanthakos, Stavra A, Behling, Cynthia A, Hertel, Paula, Nilson, Jamie, Neuschwander-Tetri, Brent A, Tonascia, James, Vos, Miriam B, Cavallo, Laurel, Garner, Donna, Hertel, Paula M, Mysore, Krupa R, Ortega, Taira Illescas, Tessier, Mary Elizabeth, Triggs, Nicole, Tsai, Cynthia, Arce-Clachar, Ana Catalina, Bramlage, Kristin, Cecil, Kim, Mouzaki, Marialena, Popelar, Ann, Trout, Andrew, Xanthakos, Stavra, Allende, Daniela, Bellar, Annette, Dasarathy, Jaividhya, Dasarathy, Srinivasan, Welch, Nicole, Yerrapothu, Rahul, Bashir, Mustafa, Diehl, Anna Mae, Guy, Cynthia, Kopping, Mariko, Piercy, Dawn, Suzuki, Ayako, Alazraki, Adina, Garcia, Carmen, Jara-Garra, Jorge, Karpen, Saul, Vos, Miriam, Chalasani, Naga, Cruz, Mandy, Cummings, Oscar W, Garrison, Lisa, Gawrieh, Samer, Adams, Kathryn Harlow, Jarasvaraparn, Chaowapong, Klipsch, Ann, Morlan, Wendy, Ragozzino, Emily, Samala, Niharika, Vuppalanchi, Raj, Angkanaworakul, Pannapat, Berihun, Achashman, Buysse, Andrew, Dorrian, Theresa, Gulati, Breanna, Kowdley, Kris V, Liu, Kevin, Misic, Sandra, Sohal, Adam, Anthony, Angela, Chapin, Catherine, Fishbein, Mark H, Carpenter, Danielle, Cattoor, Theresa, Freebersyser, Janet, Jain, Ajay K, Ajmera, Veeral, Alba, Amy, Behling, Cynthia, Goyal, Nidhi, Keyvan, Leila, Loomba, Rohit, Madamba, Egbert, Middleton, Michael S, Morfin, Rebecca, Newton, Kimberly, Richards, Lisa, Singh, Seema, Sirlin, Claude, Skonieczny, Jaret, Ugalde-Nicalo, Patricia, Wang, Andrew, Awe, Remilekun, Gill, Ryan, Hameed, Bilal, Olvera, Daisy, and Terrault, Norah

Subjects
Biomedical and Clinical Sciences, Nutrition and Dietetics, Obesity, Digestive Diseases, Nutrition, Prevention, Clinical Research, Clinical Trials and Supportive Activities, Pediatric, Oral and gastrointestinal, Metabolic and endocrine, Good Health and Well Being, Humans, Male, Child, Female, Diet, Healthy, Nutrition Assessment, Lipids, Sugars, Body Weight, Nonalcoholic Steatohepatitis Clinical Research Network, Clinical sciences
Abstract

BackgroundPediatric metabolic-associated fatty liver disease (MAFLD) is a global health problem, with lifestyle modification as its major therapeutic strategy. Rigorous characterization of dietary content on MAFLD in children is lacking. We hypothesized an objectively measured healthier diet would positively modulate MAFLD.MethodsDiet was assessed using the Nutrition Data System for Research in children enrolled from 10 tertiary clinical centers to determine the Healthy Eating Index (HEI, 0-100) and individual food components.ResultsIn all, 119 children were included (13.3 ± 2.7 y), 80 (67%) male, 67 (18%) White, and 90 (76%) Hispanic, with an average body mass index Z-score of 2.2 ± 0.5. Diet was classified as low HEI < 47.94 (n = 39), mid HEI ≥ 47.94 and < 58.89 (n = 41), or high HEI ≥ 58.89 (n=39). Children with high HEI (healthier diet) had lower body weight (p = 0.005) and more favorable lipids. Mean serum triglycerides for low, mid, and high HEI were 163, 148, and 120 mg/dL, respectively; p = 0.04 mid versus high, p = 0.01 low versus high. Mean HDL was 38, 41 and 43 mg/dL; p = 0.02 low vs high. Less severe steatosis was noted with added sugar ≤ 10% of calories (p = 0.03). Higher lobular inflammation is associated with a higher percentage of calories from fat (OR (95% CI) = 0.95 (0.91-1.00), p = 0.04).ConclusionsIn children with MAFLD, high HEI is associated with lower body weight and more favorable lipids, while added sugar and fat intake has individual histologic features. Differential consumption of major dietary components may modify both metabolic risk factors and histologic liver injury, highlighting the importance of objective diet assessments in children with MAFLD.

Published
2023

4. Association between CLOCK gene polymorphisms and ADHD in Mexican teenagers: A comprehensive assessment

Author

Cabrera Lagunes, Alfonso, Díaz-Anzaldúa, Adriana, Rojas Andrade, Gustavo, Peschard, Vanessa-Giselle, Arias Caballero, Adriana, Gaspar-Barba, César Enrique, Yunes Jimenez, Arlette, De la Peña Olvera, Francisco Rafael, Cruz Fuentes, Carlos Sabas, Feria-Aranda, Miriam, Sosa Mora, Liz, Pérez Molina, Armando, Guizar Sanchez, Diana, and Palacios-Cruz, Lino

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Mental Health, Genetic Testing, Attention Deficit Hyperactivity Disorder (ADHD), Pediatric, Clinical Research, Neurosciences, Genetics, Good Health and Well Being, Adolescent, Female, Humans, Male, Attention Deficit Disorder with Hyperactivity, CLOCK Proteins, Genotype, Polymorphism, Single Nucleotide, Attention deficit disorder with hyperactivity, Risk factors, Single nucleotide polymorphism, Circadian rhythm, Triiodothyronine, Thyroxine, Medical and Health Sciences, Psychology and Cognitive Sciences, Psychiatry, Clinical sciences, Clinical and health psychology
Abstract

This study aimed to evaluate markers of the CLOCK gene rs1801260 and rs4864548 in Mexican adolescents, addressing clinical and biological aspects previously associated with ADHD. 347 Mexican adolescents were assessed for mental disorders, metabolic disruption and related conditions, circadian preference, as well as genotyping for the CLOCK. We found a significant association between ADHD and the AA and AG genotypes of rs1801260. Also, we identified in the ADHD group that the total Triiodothyronine and total Thyroxine values were respectively 10 ng/dl units and 0.58 ug/dl units lower in females than in males. Previously reported common variations of the CLOCK gene have been associated with ADHD like the Rs1801260 polymorphism hereby we could consider it as risk factor, but genetic, biochemical and clinical studies in the Mexican population are entailed.

Published
2022

5. TL1A–DR3 Plasma Levels Are Predictive of HIV-1 Disease Control, and DR3 Costimulation Boosts HIV-1–Specific T Cell Responses

Author

Oriol-Tordera, Bruna, Olvera, Alex, Duran-Castells, Clara, Llano, Anuska, Mothe, Beatriz, Massanella, Marta, Dalmau, Judith, Ganoza, Carmela, Sanchez, Jorge, Calle, Maria Luz, Clotet, Bonaventura, Martinez-Picado, Javier, Negredo, Eugènia, Blanco, Julià, Hartigan-O'Connor, Dennis, Brander, Christian, and Ruiz-Riol, Marta

Subjects
Medical Microbiology, Biomedical and Clinical Sciences, Immunology, Sexually Transmitted Infections, Genetics, Prevention, HIV/AIDS, Infectious Diseases, Clinical Research, Aetiology, 2.1 Biological and endogenous factors, Infection, Good Health and Well Being, Animals, Antibodies, Monoclonal, Murine-Derived, CD4 Lymphocyte Count, CD4-Positive T-Lymphocytes, Female, HIV Infections, HIV-1, Humans, Male, Mice, Receptors, Tumor Necrosis Factor, Member 25, Tumor Necrosis Factor Ligand Superfamily Member 15, Biochemistry and cell biology
Abstract

Relative control of HIV-1 infection has been linked to genetic and immune host factors. In this study, we analyzed 96 plasma proteome arrays from chronic untreated HIV-1-infected individuals using the classificatory random forest approach to discriminate between uncontrolled disease (plasma viral load [pVL] >50,000 RNA copies/ml; CD4 counts 283 cells/mm3, n = 47) and relatively controlled disease (pVL

Published
2020

6. Early precursors and molecular determinants of tissue-resident memory CD8+ T lymphocytes revealed by single-cell RNA sequencing

Author

Kurd, Nadia S, He, Zhaoren, Louis, Tiani L, Milner, J Justin, Omilusik, Kyla D, Jin, Wenhao, Tsai, Matthew S, Widjaja, Christella E, Kanbar, Jad N, Olvera, Jocelyn G, Tysl, Tiffani, Quezada, Lauren K, Boland, Brigid S, Huang, Wendy J, Murre, Cornelis, Goldrath, Ananda W, Yeo, Gene W, and Chang, John T

Subjects
Medical Microbiology, Biomedical and Clinical Sciences, Immunology, Genetics, Infectious Diseases, Immunization, HIV/AIDS, Vaccine Related, Prevention, 1.1 Normal biological development and functioning, Underpinning research, Infection, Inflammatory and immune system, Good Health and Well Being, Animals, CD8-Positive T-Lymphocytes, Cell Differentiation, Female, HEK293 Cells, Humans, Male, Mice, Mice, Inbred C57BL, Mice, Transgenic, Sequence Analysis, RNA, Single-Cell Analysis, Clinical sciences
Abstract

During an immune response to microbial infection, CD8+ T cells give rise to distinct classes of cellular progeny that coordinately mediate clearance of the pathogen and provide long-lasting protection against reinfection, including a subset of noncirculating tissue-resident memory (TRM) cells that mediate potent protection within nonlymphoid tissues. Here, we used single-cell RNA sequencing to examine the gene expression patterns of individual CD8+ T cells in the spleen and small intestine intraepithelial lymphocyte (siIEL) compartment throughout the course of their differentiation in response to viral infection. These analyses revealed previously unknown transcriptional heterogeneity within the siIEL CD8+ T cell population at several stages of differentiation, representing functionally distinct TRM cell subsets and a subset of TRM cell precursors within the tissue early in infection. Together, these findings may inform strategies to optimize CD8+ T cell responses to protect against microbial infection and cancer.

Published
2020

7. Cholesterol-metabolizing enzyme cytochrome P450 46A1 as a pharmacologic target for Alzheimer's disease

Author

Mast, Natalia, Saadane, Aicha, Valencia-Olvera, Ana, Constans, James, Maxfield, Erin, Arakawa, Hiroyuki, Li, Young, Landreth, Gary, and Pikuleva, Irina A

Subjects
Biological Psychology, Pharmacology and Pharmaceutical Sciences, Biomedical and Clinical Sciences, Psychology, Dementia, Acquired Cognitive Impairment, Alzheimer's Disease, Neurodegenerative, Brain Disorders, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Aging, Neurosciences, 2.1 Biological and endogenous factors, Aetiology, Neurological, Administration, Oral, Alkynes, Alzheimer Disease, Animals, Benzoxazines, Brain, Cholesterol, Cholesterol 24-Hydroxylase, Cyclopropanes, Disease Models, Animal, Female, Learning, Liver X Receptors, Male, Memory, Mice, Transgenic, Microglia, Neuroprotective Agents, Plaque, Amyloid, Transcriptome, CYP46A1, Efavirenz, Alzheimer's disease, 24-Hydroxycholesterol, Amyloid, Neurology & Neurosurgery, Pharmacology and pharmaceutical sciences, Biological psychology
Abstract

Cytochrome P450 46A1 (CYP46A1 or cholesterol 24-hydroxylase) controls cholesterol elimination from the brain and plays a role in higher order brain functions. Genetically enhanced CYP46A1 expression in mouse models of Alzheimer's disease mitigates the manifestations of this disease. We enhanced CYP46A1 activity pharmacologically by treating 5XFAD mice, a model of rapid amyloidogenesis, with a low dose of the anti-HIV medication efavirenz. Efavirenz was administered from 1 to 9 months of age, and mice were evaluated at specific time points. At one month of age, cholesterol homeostasis was already disturbed in the brain of 5XFAD mice. Nevertheless, efavirenz activated CYP46A1 and mouse cerebral cholesterol turnover during the first four months of administration. This treatment time also reduced amyloid burden and microglia activation in the cortex and subiculum of 5XFAD mice as well as protein levels of amyloid precursor protein and the expression of several genes involved in inflammatory response. However, mouse short-term memory and long-term spatial memory were impaired, whereas learning in the context-dependent fear test was improved. Additional four months of drug administration (a total of eight months of treatment) improved long-term spatial memory in the treated as compared to the untreated mice, further decreased amyloid-β content in 5XFAD brain, and also decreased the mortality rate among male mice. We propose a mechanistic model unifying the observed efavirenz effects. We suggest that CYP46A1 activation by efavirenz could be a new anti-Alzheimer's disease treatment and a tool to study and identify normal and pathological brain processes affected by cholesterol maintenance.

Published
2017

8. Uterine Cancer After Risk-Reducing Salpingo-oophorectomy Without Hysterectomy in Women With BRCA Mutations

Author

Shu, Catherine A, Pike, Malcolm C, Jotwani, Anjali R, Friebel, Tara M, Soslow, Robert A, Levine, Douglas A, Nathanson, Katherine L, Konner, Jason A, Arnold, Angela G, Bogomolniy, Faina, Dao, Fanny, Olvera, Narciso, Bancroft, Elizabeth K, Goldfrank, Deborah J, Stadler, Zsofia K, Robson, Mark E, Brown, Carol L, Leitao, Mario M, Abu-Rustum, Nadeem R, Aghajanian, Carol A, Blum, Joanne L, Neuhausen, Susan L, Garber, Judy E, Daly, Mary B, Isaacs, Claudine, Eeles, Rosalind A, Ganz, Patricia A, Barakat, Richard R, Offit, Kenneth, Domchek, Susan M, Rebbeck, Timothy R, and Kauff, Noah D

Subjects
Reproductive Medicine, Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Prevention, Clinical Research, Breast Cancer, Rare Diseases, Cancer, Adult, Female, Follow-Up Studies, Genes, BRCA1, Genes, BRCA2, Humans, Hysterectomy, Loss of Heterozygosity, Middle Aged, Mutation, Ovariectomy, Prospective Studies, Risk, Salpingectomy, Uterine Neoplasms, Public Health and Health Services, Oncology and carcinogenesis
Abstract

ImportanceThe link between BRCA mutations and uterine cancer is unclear. Therefore, although risk-reducing salpingo-oophorectomy (RRSO) is standard treatment among women with BRCA mutations (BRCA+ women), the role of concomitant hysterectomy is controversial.ObjectiveTo determine the risk for uterine cancer and distribution of specific histologic subtypes in BRCA+ women after RRSO without hysterectomy.Design, setting, and participantsThis multicenter prospective cohort study included 1083 women with a deleterious BRCA1 or BRCA2 mutation identified from January 1, 1995, to December 31, 2011, at 9 academic medical centers in the United States and the United Kingdom who underwent RRSO without a prior or concomitant hysterectomy. Of these, 627 participants were BRCA1+; 453, BRCA2+; and 3, both. Participants were prospectively followed up for a median 5.1 (interquartile range [IQR], 3.0-8.4) years after ascertainment, BRCA testing, or RRSO (whichever occurred last). Follow up data available through October 14, 2014, were included in the analyses. Censoring occurred at uterine cancer diagnosis, hysterectomy, last follow-up, or death. New cancers were categorized by histologic subtype, and available tumors were analyzed for loss of the wild-type BRCA gene and/or protein expression.Main outcomes and measuresIncidence of uterine corpus cancer in BRCA+ women who underwent RRSO without hysterectomy compared with rates expected from the Surveillance, Epidemiology, and End Results database.ResultsAmong the 1083 women women who underwent RRSO without hysterectomy at a median age 45.6 (IQR: 40.9 - 52.5), 8 incident uterine cancers were observed (4.3 expected; observed to expected [O:E] ratio, 1.9; 95% CI, 0.8-3.7; P = .09). No increased risk for endometrioid endometrial carcinoma or sarcoma was found after stratifying by subtype. Five serous and/or serous-like (serous/serous-like) endometrial carcinomas were observed (4 BRCA1+ and 1 BRCA2+) 7.2 to 12.9 years after RRSO (BRCA1: 0.18 expected [O:E ratio, 22.2; 95% CI, 6.1-56.9; P

Published
2016

9. Metabolites of the Polycyclic Aromatic Hydrocarbon Phenanthrene in the Urine of Cigarette Smokers from Five Ethnic Groups with Differing Risks for Lung Cancer.

Author

Patel, Yesha M, Park, Sungshim L, Carmella, Steven G, Paiano, Viviana, Olvera, Natalie, Stram, Daniel O, Haiman, Christopher A, Le Marchand, Loic, and Hecht, Stephen S

Subjects
Humans, Lung Neoplasms, Phenanthrenes, Glutathione Transferase, Neoplasm Proteins, Risk Factors, Smoking, Gene Dosage, Mutation, Aged, Middle Aged, Female, Male, General Science & Technology
Abstract

Results from the Multiethnic Cohort Study demonstrated significant differences in lung cancer risk among cigarette smokers from five different ethnic/racial groups. For the same number of cigarettes smoked, and particularly among light smokers, African Americans and Native Hawaiians had the highest risk for lung cancer, Whites had intermediate risk, while Latinos and Japanese Americans had the lowest risk. We analyzed urine samples from 331-709 participants from each ethnic group in this study for metabolites of phenanthrene, a surrogate for carcinogenic polycyclic aromatic hydrocarbon exposure. Consistent with their lung cancer risk and our previous studies of several other carcinogens and toxicants of cigarette smoke, African Americans had significantly (p

Published
2016

10. Radiographers supporting radiologists in the interpretation of screening mammography: a viable strategy to meet the shortage in the number of radiologists

Author

Torres-Mejía, Gabriela, Smith, Robert A, Carranza-Flores, María de la Luz, Bogart, Andy, Martínez-Matsushita, Louis, Miglioretti, Diana L, Kerlikowske, Karla, Ortega-Olvera, Carolina, Montemayor-Varela, Ernesto, Angeles-Llerenas, Angélica, Bautista-Arredondo, Sergio, Sánchez-González, Gilberto, Martínez-Montañez, Olga G, Uscanga-Sánchez, Santos R, Lazcano-Ponce, Eduardo, and Hernández-Ávila, Mauricio

Subjects
Health Services and Systems, Biomedical and Clinical Sciences, Health Sciences, Biomedical Imaging, Health Services, Clinical Research, Breast Cancer, Prevention, Cancer, Detection, screening and diagnosis, 4.2 Evaluation of markers and technologies, Adult, Breast Neoplasms, Decision Trees, Early Detection of Cancer, Female, Health Workforce, Humans, Image Interpretation, Computer-Assisted, Male, Mammography, Mass Screening, Mexico, Middle Aged, Models, Theoretical, Observer Variation, Physicians, Professional Competence, Reproducibility of Results, Sensitivity and Specificity, Young Adult, Radiographers, Film readers, Screening mammography, BI-RADS system, Oncology and Carcinogenesis, Public Health and Health Services, Oncology & Carcinogenesis, Oncology and carcinogenesis, Epidemiology
Abstract

BackgroundAn alternative approach to the traditional model of radiologists interpreting screening mammography is necessary due to the shortage of radiologists to interpret screening mammograms in many countries.MethodsWe evaluated the performance of 15 Mexican radiographers, also known as radiologic technologists, in the interpretation of screening mammography after a 6 months training period in a screening setting. Fifteen radiographers received 6 months standardized training with radiologists in the interpretation of screening mammography using the Breast Imaging Reporting and Data System (BI-RADS) system. A challenging test set of 110 cases developed by the Breast Cancer Surveillance Consortium was used to evaluate their performance. We estimated sensitivity, specificity, false positive rates, likelihood ratio of a positive test (LR+) and the area under the subject-specific Receiver Operating Characteristic (ROC) curve (AUC) for diagnostic accuracy. A mathematical model simulating the consequences in costs and performance of two hypothetical scenarios compared to the status quo in which a radiologist reads all screening mammograms was also performed.ResultsRadiographer's sensitivity was comparable to the sensitivity scores achieved by U.S. radiologists who took the test but their false-positive rate was higher. Median sensitivity was 73.3 % (Interquartile range, IQR: 46.7-86.7 %) and the median false positive rate was 49.5 % (IQR: 34.7-57.9 %). The median LR+ was 1.4 (IQR: 1.3-1.7 %) and the median AUC was 0.6 (IQR: 0.6-0.7). A scenario in which a radiographer reads all mammograms first, and a radiologist reads only those that were difficult for the radiographer, was more cost-effective than a scenario in which either the radiographer or radiologist reads all mammograms.ConclusionsGiven the comparable sensitivity achieved by Mexican radiographers and U.S. radiologists on a test set, screening mammography interpretation by radiographers appears to be a possible adjunct to radiologists in countries with shortages of radiologists. Further studies are required to assess the effectiveness of different training programs in order to obtain acceptable screening accuracy, as well as the best approaches for the use of non-physician readers to interpret screening mammography.

Published
2015

11. Recurrent BRCA1 and BRCA2 Mutations in Mexican Women with Breast Cancer

Author

Torres-Mejía, Gabriela, Royer, Robert, Llacuachaqui, Marcia, Akbari, Mohammad R, Giuliano, Anna R, Martínez-Matsushita, Louis, Angeles-Llerenas, Angélica, Ortega-Olvera, Carolina, Ziv, Elad, Lazcano-Ponce, Eduardo, Phelan, Catherine M, and Narod, Steven A

Subjects
Health Services and Systems, Biomedical and Clinical Sciences, Health Sciences, Oncology and Carcinogenesis, Clinical Research, Prevention, Genetics, Ovarian Cancer, Breast Cancer, Genetic Testing, Cancer, Rare Diseases, Adult, Aged, Breast Neoplasms, Case-Control Studies, Female, Genes, BRCA1, Genes, BRCA2, Germ-Line Mutation, Humans, Mexico, Middle Aged, Medical and Health Sciences, Epidemiology, Biomedical and clinical sciences, Health sciences
Abstract

BackgroundGermline mutations in the BRCA1 and BRCA2 genes confer an estimated 58% to 80% lifetime risk of breast cancer. In general, screening is done for cancer patients if a relative has been diagnosed with breast or ovarian cancer. There are few data on the prevalence of mutations in these genes in Mexican women with breast cancer and this hampers efforts to develop screening policies in Mexico.MethodsWe screened 810 unselected women with breast cancer from three cities in Mexico (Mexico City, Veracruz, and Monterrey) for mutations in BRCA1 and BRCA2, including a panel of 26 previously reported mutations.ResultsThirty-five mutations were identified in 34 women (4.3% of total) including 20 BRCA1 mutations and 15 BRCA2 mutations. Twenty-two of the 35 mutations were recurrent mutations (62.8%). Only five of the 34 mutation carriers had a first-degree relative with breast cancer (three with BRCA1 and two with BRCA2 mutations).ConclusionThese results support the rationale for a strategy of screening for recurrent mutations in all women with breast cancer in Mexico, as opposed to restricting screening to those with a sister or mother with breast or ovarian cancer.ImpactThese results will impact cancer genetic testing in Mexico and the identification of at-risk individuals who will benefit from increased surveillance. Cancer Epidemiol Biomarkers Prev; 24(3); 498-505. ©2014 AACR.

Published
2015

12. Reversing bone loss by directing mesenchymal stem cells to bone

Author

Yao, Wei, Guan, Min, Jia, Junjing, Dai, Weiwei, Lay, Yu‐An E, Amugongo, Sarah, Liu, Ruiwu, Olivos, David, Saunders, Mary, Lam, Kit S, Nolta, Jan, Olvera, Diana, Ritchie, Robert O, and Lane, Nancy E

Subjects
Biomedical and Clinical Sciences, Stem Cell Research, Aging, Transplantation, Stem Cell Research - Nonembryonic - Human, Regenerative Medicine, Stem Cell Research - Nonembryonic - Non-Human, Osteoporosis, Underpinning research, Development of treatments and therapeutic interventions, 5.2 Cellular and gene therapies, 1.1 Normal biological development and functioning, Musculoskeletal, Alendronate, Animals, Bone Resorption, Bone and Bones, Cell Differentiation, Cell Movement, Dipeptides, Estrogens, Extracellular Matrix, Female, Humans, Mesenchymal Stem Cell Transplantation, Mesenchymal Stem Cells, Mice, Mice, Inbred C57BL, Osteoblasts, Osteogenesis, Phenylurea Compounds, Phosphorylation, Phosphotyrosine, Proto-Oncogene Proteins c-akt, Bone marrow stromal cells, Cell migration, In vivo tracking, Integrins, Stem cell transplantation, Biological Sciences, Technology, Medical and Health Sciences, Immunology, Biological sciences, Biomedical and clinical sciences
Abstract

Bone regeneration by systemic transplantation of mesenchymal stem cells (MSCs) is problematic due to the inability to control the MSCs' commitment, growth, and differentiation into functional osteoblasts on the bone surface. Our research group has developed a method to direct the MSCs to the bone surface by conjugating a synthetic peptidomimetic ligand (LLP2A) that has high affinity for activated α4β1 integrin on the MSC surface, with a bisphosphonates (alendronate) that has high affinity for bone (LLP2A-Ale), to direct the transplanted MSCs to bone. Our in vitro experiments demonstrated that mobilization of LLP2A-Ale to hydroxyapatite accelerated MSC migration that was associated with an increase in the phosphorylation of Akt kinase and osteoblastogenesis. LLP2A-Ale increased the homing of the transplanted MSCs to bone as well as the osteoblast surface, significantly increased the rate of bone formation and restored both trabecular and cortical bone loss induced by estrogen deficiency or advanced age in mice. These results support LLP2A-Ale as a novel therapeutic option to direct the transplanted MSCs to bone for the treatment of established bone loss related to hormone deficiency and aging.

Published
2013

13. Prolonged alendronate treatment prevents the decline in serum TGF-β1 levels and reduces cortical bone strength in long-term estrogen deficiency rat model

Author

Jia, Junjing, Yao, Wei, Amugongo, Sarah, Shahnazari, Mohammad, Dai, Weiwei, Lay, Yu-An E, Olvera, Diana, Zimmermann, Elizabeth A, Ritchie, Robert O, Li, Chin-Shang, Alliston, Tamara, and Lane, Nancy E

Subjects
Stem Cell Research, Stem Cell Research - Nonembryonic - Non-Human, Osteoporosis, Estrogen, Musculoskeletal, Alendronate, Animals, Biomechanical Phenomena, Bone Density Conservation Agents, Bone and Bones, Estrogens, Female, Immunohistochemistry, Models, Animal, Polymerase Chain Reaction, Rats, Rats, Sprague-Dawley, Signal Transduction, Transforming Growth Factor beta1, TGF-beta 1, Cortical bone, Bone quality, Biological Sciences, Engineering, Medical and Health Sciences, Endocrinology & Metabolism
Abstract

IntroductionWhile the anti-resorptive effects of the bisphosphonates (BPs) are well documented, many questions remain about their mechanisms of action, particularly following long-term use. This study evaluated the effects of alendronate (Ale) treatment on TGF-β1 signaling in mesenchymal stem cells (MSCs) and osteocytes, and the relationship between prolonged alendronate treatment on systemic TGF-β1 levels and bone strength.MethodsTGF-β1 expression and signaling were evaluated in MSCs and osteocytic MLO-Y4 cells following Ale treatment. Serum total TGF-β1 levels, a bone resorption marker (DPD/Cr), three-dimensional microCT scans and biomechanical tests from both the trabecular and cortical bone were measured in ovariectomized rats that either received continuous Ale treatment for 360 days or Ale treatment for 120 days followed by 240 days of vehicle. Linear regression tests were performed to determine the association of serum total TGF-β1 levels and both the trabecular (vertebrae) and cortical (tibiae) bone strength.ResultsAle increased TGF-β1 signaling in the MSCs but not in the MLO-Y4 cells. Ale treatment increased serum TGF-β1 levels and the numbers of TGF-β1-positive osteocytes and periosteal cells in cortical bone. Serum TGF-β1 levels were not associated with vertebral maximum load and strength but was negatively associated with cortical bone maximum load and ultimate strength.ConclusionsThe increase of serum TGF-β1 levels during acute phase of estrogen deficiency is likely due to increased osteoclast-mediated release of matrix-derived latent TGF-β1. Long-term estrogen-deficiency generally results in a decline in serum TGF-β1 levels that are maintained by Ale treatment. Measuring serum total TGF-β1 levels may help to determine cortical bone quality following alendronate treatment.

Published
2013

14. Moderate-intensity physical activity ameliorates the breast cancer risk in diabetic women.

Author

Torres-Mejía, Gabriela, Angeles-Llerenas, Angélica, Ortega-Olvera, Carolina, Lazcano-Ponce, Eduardo, Pulido-Rodríguez, José, García-Solis, Manuel, Murillo-Zamora, Efrén, Vázquez-Lara, Julia, Romieu, Isabelle, and Ziv, Elad

Subjects
Breast Neoplasms, C-Peptide, Case-Control Studies, Exercise, Female, Humans, Insulin-Like Growth Factor Binding Protein 3, Insulin-Like Growth Factor I, Odds Ratio, Postmenopause, Premenopause
Abstract

OBJECTIVE: To evaluate the association between self-reported diabetes and the risk of breast cancer (BC) and its interaction with moderate-intensity physical activity in pre- and postmenopausal Mexican women. RESEARCH DESIGN AND METHODS: A population-based case-control study was conducted using 1,000 incident case subjects and 1,074 control subjects. Blood samples and information on health, diet, physical activity, and anthropometric measurements were obtained. RESULTS: The association between diabetes and BC risk decreased with increasing tertiles of moderate-intensity physical activity (odds ratio [OR] = 4.9 [95% CI 2.3-10.8]; 3.0 [1.3-6.9]; and 1.0 [0.1-9.2], respectively, for each tertile) (test for interaction = 0.04). Compared with the women in the lowest tertiles, increased risk was observed in those premenopausal women with the highest serum C-peptide, IGF-1, and IGF-1 binding protein 3 levels. CONCLUSIONS: Moderate-intensity physical activity can substantially ameliorate the increased BC risk in diabetic women.

Published
2012

15. Integrated genomic analyses of ovarian carcinoma

Author

Bell, D, Berchuck, A, Birrer, M, Chien, J, Cramer, DW, Dao, F, Dhir, R, DiSaia, P, Gabra, H, Glenn, P, Godwin, AK, Gross, J, Hartmann, L, Huang, M, Huntsman, DG, Iacocca, M, Imielinski, M, Kalloger, S, Karlan, BY, Levine, DA, Mills, GB, Morrison, C, Mutch, D, Olvera, N, Orsulic, S, Park, K, Petrelli, N, Rabeno, B, Rader, JS, Sikic, BI, Smith-McCune, K, Sood, AK, Bowtell, D, Penny, R, Testa, JR, Chang, K, Creighton, CJ, Dinh, HH, Drummond, JA, Fowler, G, Gunaratne, P, Hawes, AC, Kovar, CL, Lewis, LR, Morgan, MB, Newsham, IF, Santibanez, J, Reid, JG, Trevino, LR, Wu, Y-Q, Wang, M, Muzny, DM, Wheeler, DA, Gibbs, RA, Getz, G, Lawrence, MS, Cibulskis, K, Sivachenko, AY, Sougnez, C, Voet, D, Wilkinson, J, Bloom, T, Ardlie, K, Fennell, T, Baldwin, J, Nichol, R, Fisher, S, Gabriel, S, Lander, ES, Ding, L, Fulton, RS, Koboldt, DC, McLellan, MD, Wylie, T, Walker, J, O’Laughlin, M, Dooling, DJ, Fulton, L, Abbott, R, Dees, ND, Zhang, Q, Kandoth, C, Wendl, M, Schierding, W, Shen, D, Harris, CC, Schmidt, H, Kalicki, J, Delehaunty, KD, Fronick, CC, Demeter, R, Cook, L, Wallis, JW, Lin, L, Magrini, VJ, Hodges, JS, Eldred, JM, Smith, SM, Pohl, CS, and Vandin, F

Subjects
Biological Sciences, Biomedical and Clinical Sciences, Genetics, Oncology and Carcinogenesis, Biotechnology, Rare Diseases, Human Genome, Ovarian Cancer, Cancer, Aged, Carcinoma, DNA Methylation, Female, Gene Dosage, Gene Expression Profiling, Gene Expression Regulation, Neoplastic, Genomics, Humans, MicroRNAs, Middle Aged, Mutation, Ovarian Neoplasms, RNA, Messenger, Cancer Genome Atlas Research Network, General Science & Technology
Abstract

A catalogue of molecular aberrations that cause ovarian cancer is critical for developing and deploying therapies that will improve patients' lives. The Cancer Genome Atlas project has analysed messenger RNA expression, microRNA expression, promoter methylation and DNA copy number in 489 high-grade serous ovarian adenocarcinomas and the DNA sequences of exons from coding genes in 316 of these tumours. Here we report that high-grade serous ovarian cancer is characterized by TP53 mutations in almost all tumours (96%); low prevalence but statistically recurrent somatic mutations in nine further genes including NF1, BRCA1, BRCA2, RB1 and CDK12; 113 significant focal DNA copy number aberrations; and promoter methylation events involving 168 genes. Analyses delineated four ovarian cancer transcriptional subtypes, three microRNA subtypes, four promoter methylation subtypes and a transcriptional signature associated with survival duration, and shed new light on the impact that tumours with BRCA1/2 (BRCA1 or BRCA2) and CCNE1 aberrations have on survival. Pathway analyses suggested that homologous recombination is defective in about half of the tumours analysed, and that NOTCH and FOXM1 signalling are involved in serous ovarian cancer pathophysiology.

Published
2011

16. The impact of a plant-based diet on indices of cardiovascular health in African Americans: a cross-sectional study

Author

Zachary T. Martin, Guillermo Olvera, Christian A. Villegas, Jeremiah C. Campbell, John D. Akins, Kyrah K. Brown, and R. Matthew Brothers

Subjects
Adult, Male, Nutrition and Dietetics, Physiology, Diet, Vegetarian, Endocrinology, Diabetes and Metabolism, Blood Pressure, Cholesterol, LDL, General Medicine, Lipids, Diet, Black or African American, Young Adult, C-Reactive Protein, Cross-Sectional Studies, Physiology (medical), Humans, Female
Abstract

African-American (AA) individuals are disproportionately affected by cardiovascular diseases. Plant-based diets (PBD) may be cardioprotective in part through their high antioxidant capacity and low inflammatory load. We tested the hypothesis that AA individuals adhering to a 100% PBD would have better vascular health than AA individuals following a typical American diet (TAD). Eighteen AA individuals participated; 9 (24 ± 4 years; 6 females) were following a PBD for 2.4 ± 0.8 years and 9 (21 ± 2 years; 5 females) were following a TAD. Blood lipids and C-reactive protein (CRP) were assessed. Peripheral and central blood pressure (BP) were measured, and vascular function tests included cerebrovascular reactivity to hypercapnia, brachial artery flow-mediated dilation and reactive hyperemia, and local heating-induced cutaneous hyperemia. Total (TC) and low‐density lipoprotein (LDL‐C) serum cholesterol was lower (TC: 142 ± 30 vs. 174 ± 36 mg/dL; LDL‐C: 76 ± 17 vs. 106 ± 33 mg/dL; p 0.80 for both) and serum CRP tended to be lower (0.38 ± 0.18 mg/L vs. 0.96 ± 0.89 mg/L; p = 0.05, d = 0.91) in the PBD cohort. Brachial (b) and central (c) mean arterial BP (MAP) were lower in the PBD cohort (bMAP: 86 ± 5 vs. 91 ± 7 mm Hg; cMAP: 81 ± 5 vs. 87 ± 7 mm Hg; p 0.80 for both). All indices of vascular function were similar between groups ( p > 0.05 for all). A PBD was associated with more optimal blood lipid concentrations and decreased peripheral and central BP in AA individuals, but this association was not present in the various indices of vascular function. Registered at ClinicalTrials.gov: NCT05344287.

Published
2022

17. High mortality at the beginning of the COVID-19 pandemic in a referral center in the metropolitan area of Mexico City

Author

Alberto Ordinola Navarro, Orestes de Jesús Cobos-Quevedo, Javier Cervantes-Bojalil, Esperanza Pérez Álvarez, Andrea González Gil, Ana Lilia Peralta-Amaro, Ana Laura Carrillo-González, Arturo Olvera Acevedo, Luis Francisco Pineda-Galindo, Fernando Briceño-Moya, Olga Lidia Vera-Lastra, and Bruno Ali Lopez Luis

Subjects
Male, COVID-19, General Medicine, Middle Aged, Microbiology, Infectious Diseases, Virology, Humans, Female, Parasitology, Obesity, Mexico, Pandemics, Referral and Consultation, Retrospective Studies
Abstract

Introduction: There is limited information about the coronavirus disease 2019 (COVID-19) disease in Latin-American countries. Our objective was to describe the clinical characteristics and outcomes of COVID-19 patients in Mexico. Methodology: We conducted a retrospective cohort study with 333 consecutive patients who were admitted to Hospital de Especialidades "Dr. Antonio Fraga Mouret" in Mexico City with COVID-19 between April 1, 2020, and June 30, 2020. Demographic, clinical, laboratory data, treatment details and 30-day outcomes were analyzed. Results: The patients studied included 52% men (172/233) and the median age was 45 years. Up to 75% (250/333) of patients were classified as overweight or obese. There were 185 (56%) inpatients; 85% (158/185) were hospitalized in the general ward, and 15% (27/185) in the Intensive Care Unit (ICU). Laboratory measurements showed significant differences between inpatients and outpatients such as lymphocyte-count (median 0.8 vs 1.2×109/L, p < 0.001), LDH (median 650 vs 294 U/L, p < 0.001), CRP (median 147 vs 5 mg/L, p = 0.007), CK-MB (median, 15 vs 10 U/L, p = 0.008), ferritin (median, 860 vs 392 ng/mL, p = 0.02), and D-dimer (median, 780 vs 600 ng/mL, p = 0.15). These differences were seen between survivor and non-survivor patients as well. The rate of death in mechanically ventilated patients was 94% (67/71). Mortality at 30-day follow-up was 57% (105/185). Conclusions: We observed that majority of the non-survivors were obese and young. Complications leading to death was observed in majority of the cases.

Published
2022

18. The effect of the number of biopsies on the delay in the time from the delivery of mammography results to breast cancer histopathological diagnosis

Author

Adriana Garduño-Alanis, Lizbeth Morales-González, Angélica Ángeles-Llerenas, José Zaim Delgado-Ramírez, Carolina Ortega-Olvera, and Gabriela Torres-Mejía

Subjects
Adult, Cancer Research, Time Factors, Oncology, Biopsy, Humans, Breast Neoplasms, Female, Middle Aged, Prognosis, Early Detection of Cancer, Aged, Mammography
Abstract

The delay in the time (in calendar days) from the delivery of mammography results to histopathological breast cancer (BC) diagnosis could be associated with more advanced clinical stages, a worse prognosis and higher mortality. Therefore, we assessed the association between the number of biopsies and the delay in the time (in calendar days) from the delivery of mammography results to histopathological BC.A survey was performed on 563 women aged between 35 and 69 years with histopathologically confirmed BC who attended 11 Mexican hospitals.After adjusting for potential confounders, the odds of having a delay in the time (in calendar days) from the delivery of mammography results to histopathological BC diagnosis (≥ 60 days) among women with ≥ 3 biopsies were 2.99 times the odds of those who had only one biopsy (95% CI 1.35, 6.63).The number of biopsies should be considered as a predictor of the time delay between the delivery of the mammography result and the diagnostic result.

Published
2022

19. 5 Hz of repetitive transcranial magnetic stimulation improves cognition and induces modifications in hippocampal neurogenesis in adult female Swiss Webster mice

Author

Gerardo Bernabé, Ramírez-Rodríguez, David Meneses-San, Juan, and Jorge Julio, González-Olvera

Subjects
Doublecortin Domain Proteins, Calbindins, Mice, Cognition, Neurogenesis, General Neuroscience, Animals, Female, Hippocampus, Proto-Oncogene Proteins c-fos, Transcranial Magnetic Stimulation
Abstract

Adult hippocampal neurogenesis is regulated by several stimuli to promote the creation of a reserve that may facilitate coping with environmental challenges. In this regard, repetitive transcranial magnetic stimulation (rTMS), a neuromodulation therapy, came to our attention because in clinical studies it reverts behavioral and cognitive alterations related to changes in brain plasticity. Some preclinical studies emphasize the need to understand the underlying mechanism of rTMS to induce behavioral modifications. In this study, we investigated the effects of rTMS on cognition, neurogenic-associated modifications, and neuronal activation in the hippocampus of female Swiss Webster mice. We applied 5 Hz of rTMS twice a day for 14 days. Three days later, mice were exposed to the behavioral battery. Then, brains were collected and immunostained for Ki67-positive cells, doublecortin-positive (DCX+)-cells, calbindin, c-Fos and FosB/Delta-FosB in the dentate gyrus. Also, we analyzed mossy fibers and CA3 with calbindin immunostaining. Mice exposed to rTMS exhibited cognitive improvement, an increased number of proliferative cells, DCX cells, DCX cells with complex dendrite morphology, c-Fos and immunoreactivity of FosB/Delta-FosB in the granular cell layer. The volume of the granular cell layer, mossy fibers and CA3 in rTMS mice also increased. Interestingly, cognitive improvement correlated with DCX cells with complex dendrite morphology. Also, those DCX cells and calbindin immunoreactivity correlated with c-Fos in the granular cell layer. Our results suggest that 5 Hz of rTMS applied twice a day modify cell proliferation, doublecortin cells, mossy fibers and enhance cognitive behavior in healthy female Swiss Webster mice.

Published
2022

20. Uric acid is associated with morpho-functional adipose tissue markers in apparently healthy subjects

Author

Juan Reyes-Barrera, Aida X. Medina-Urrutia, Esteban Jorge-Galarza, Horacio Osorio-Alonso, Abraham S. Arellano-Buendía, Gabriela Olvera-Mayorga, Néstor A. Sánchez-Ortiz, Margarita Torres-Tamayo, Armando R. Tovar Palacio, Ivan Torre-Villalvazo, and Juan G. Juárez-Rojas

Subjects
Male, Biochemistry (medical), Clinical Biochemistry, General Medicine, Middle Aged, Biochemistry, Healthy Volunteers, Uric Acid, Adipokines, Adipose Tissue, Plasminogen Activator Inhibitor 1, Humans, Female, Adiponectin, Aged
Abstract

Studies have focused on the search of novel biomarkers that allow to easily identify dysfunctional adipose tissue (AT). Uric acid (UA) could be produced and reabsorbed by AT. It has been suggested that the increases of UA concentrations participates in AT dysfunction. We investigated the association of UA with morpho-functional adipose tissue markers in apparently healthy subjects.Forty apparently healthy individuals were included. Dietary habits and anthropometrical features were evaluated. Circulating concentrations of UA, adiponectin, leptin, and plasminogen activator inhibitor-1 (PAI-1) were quantified. Periumbilical subcutaneous AT samples were obtained and adipocyte number, adipocyte area, and macrophages content were assessed.The present study included 40 healthy subjects (67% women) with an average age of 57 ± 9 y, BMI of 26 ± 4 (kg/mUA concentrations are associated with morpho-functional adipose tissue markers. Our results underscore the importance of UA as one earlier instigator of adipose tissue dysfunction in subjects without metabolic abnormalities.

Published
2022

21. Immunohistochemical Expression of Cell Cycle Proteins E2F-1, Cdk-2, Cyclin E, p27kip1, and Ki-67 in Normal Placenta and Gestational Trophoblastic Disease

Author

Olvera, Maria, Harris, Selena, Amezcua, Charles A, McCourty, Althea, Rezk, Sherif, Koo, Charles, Felix, Juan C, and Brynes, Russell K

Subjects
Reproductive Medicine, Biomedical and Clinical Sciences, Pediatric, Clinical Research, 2.1 Biological and endogenous factors, Aetiology, CDC2-CDC28 Kinases, Cell Cycle Proteins, Choriocarcinoma, Cyclin E, Cyclin-Dependent Kinase 2, Cyclin-Dependent Kinase Inhibitor p27, Cyclin-Dependent Kinases, DNA-Binding Proteins, E2F Transcription Factors, E2F1 Transcription Factor, Female, Humans, Hydatidiform Mole, Immunohistochemistry, Ki-67 Antigen, Pregnancy, Protein Serine-Threonine Kinases, Transcription Factors, Trophoblastic Neoplasms, Tumor Suppressor Proteins, Uterine Neoplasms, Medical and Health Sciences, Pathology, Clinical sciences
Abstract

The role of cell cycle protein expression in gestational trophoblastic disease is poorly understood. In this study we investigated the immunostaining patterns of G(1) restriction point and G(1)-S regulatory proteins E2F-1, Cdk2, cyclin E, p27(kip1), and the proliferation marker Ki-67 on routinely processed sections of 29 hydatidiform moles (10 partial moles and 19 complete moles, including 9 persistent moles), 7 choriocarcinomas, and 7 normal placentas. Ki-67 trophoblast staining decreased with increasing gestational age of the placenta, and showed maximal expression in gestational trophoblastic disease. Cyclin-dependent kinase activity, as reflected by Cdk2 expression patterns, also decreased with placental maturation. E2F-1 was uniquely expressed by trophoblasts of moles and choriocarcinoma. Cyclin E was maximally expressed by complete moles and choriocarcinomas, and showed an inverse relationship with the cyclin-dependent kinase inhibitor p27(kip1). Abnormal trophoblastic proliferations may be mediated through interactions of Cdk-2, E2F-1, cyclin E, and p27(kip1). Overexpression of cyclin E was associated with more aggressive forms of gestational trophoblastic disease. However, we did not find distinguishing features between complete moles that spontaneously resolved after evacuation and persistent moles that required chemotherapy. The different expression patterns of cyclin E and E2F-1 in partial and complete moles may be useful in distinguishing these two entities. Furthermore, loss of p27(kip1) in malignant trophoblast may represent a necessary step in the development of choriocarcinoma.

Published
2001

22. Moderate acute malnutrition prevention with a ready-to-use supplementary food in pre-school children from rural communities

Author

Thanya S. Labrada-Alba, Juan O Talavera, María F. Martínez-Jaureguiberry, Brenda Salgado-Enríquez, Mónica J. García-Vilchis, and Fabián Olvera-Flores

Subjects
Male, Rural Population, medicine.medical_specialty, Time Factors, media_common.quotation_subject, Child Nutrition Disorders, Hygiene, Prevalence, medicine, Humans, Mexico, Proportional Hazards Models, media_common, Gynecology, business.industry, General Medicine, medicine.disease, Supplementary food, Intention to Treat Analysis, Malnutrition, Social Class, Child, Preschool, Acute Disease, Dietary Supplements, Fast Foods, Ready to use, Female, Pre school, business
Abstract

Introduction Child malnutrition in Mexico reaches a prevalence as high as 27.5 % in rural areas. Objective To assess the effectiveness of a ready-to-use supplementary food (RUSF) to correct mild acute malnutrition and prevent moderate acute malnutrition in preschool children from rural communities. Method Randomized clinical trial, with assignment to two groups: group with RUSF (RUSF-g) or group without it (non-RUSF-g); children aged from two to five years, with weight-for-height Z-scores (WHZ) between -2 and -1 and low socioeconomic status were included. All received education on nutrition, health and hygiene twice monthly; the RUSF-g children had to consume one portion of the supplement every day. WHZ was assessed at baseline and at four, six, and 12 months. The comparison between groups was carried out with Cox proportional hazards model. Results With regard to mild acute malnutrition correction in the RUSF-g, 68.7 versus 52.1 % in the control group was observed in the intent-to-treat analysis, with a hazard ratio (HR) = 1.25; in the per-protocol analysis of first semester, a HR = 1.48 was observed, and in the second semester, HR = 1.56. One patient progressed to moderate acute malnutrition. Conclusions The RUSF-g showed a significantly higher resolution of mild acute malnutrition. Introduccion La desnutricion infantil en Mexico alcanza prevalencias de 27.5 % en zonas rurales. Objetivo Evaluar la efectividad de un suplemento alimenticio listo para consumir (SALC) para corregir desnutricion aguda leve y prevenir desnutricion aguda moderada en preescolares de comunidades rurales. Metodo Ensayo clinico aleatorizado por grupos: con y sin SALC (g-SALC y g-S/SALC); se incluyeron ninos de dos a cinco anos, con puntuaciones-Z de peso para la talla (pZ-P/T) mayor de −2 y menor de −1 y nivel socioeconomico bajo. Todos recibieron educacion sobre nutricion, salud e higiene dos veces al mes; los ninos del g-SALC debieron consumir diariamente una porcion del suplemento. Se evaluo pZ-P/T al inicio y a los cuatro, seis y 12 meses. La comparacion entre grupos se realizo con el modelo de riesgos proporcionales de Cox. Resultados Respecto a la recuperacion de desnutricion aguda leve, en g-SALC se observo 68.7 versus 52.1 % en el grupo control en el analisis de intencion para tratar, con una razon de riesgo (HR) = 1.25; en el analisis por protocolo del primer semestre se observo una HR = 1.48 y en el segundo semestre, HR = 1.56. Un paciente progreso a desnutricion aguda moderada. Conclusiones El g-SALC mostro resolucion significativamente mayor de desnutricion aguda leve.

Published
2023

23. Mechanical Ventilation Practices and Low Tidal Volume Ventilation in Air Medical Transport Patients: The AIR-VENT Study

Author

Hawnwan P Moy, B. Daniel Nayman, David Olvera, Karlee De Monnin, Ryan D Pappal, Jane M Hayes, Nicholas M Mohr, Marin H Kollef, Christopher M Palmer, Enyo Ablordeppey, Brian W Roberts, and Brian M Fuller

Subjects
Adult, Male, Pulmonary and Respiratory Medicine, Respiratory Distress Syndrome, Respiration, General Medicine, Critical Care and Intensive Care Medicine, Respiration, Artificial, Cohort Studies, Tidal Volume, Humans, Female, Lung, Original Research, Retrospective Studies
Abstract

BACKGROUND: The management of mechanical ventilation critically impacts outcome for patients with acute respiratory failure. Ventilator settings in the early post-intubation period may be especially influential on outcome. Low tidal volume ventilation in the prehospital setting has been shown to impact the provision of low tidal volume after admission and influence outcome. However, there is an overall paucity of data on mechanical ventilation for air medical transport patients. The objectives of this study were to characterize air medical transport ventilation practices and assess variables associated with nonprotective ventilation. METHODS: This was a multi-center, nationwide (approximately 130 bases) retrospective cohort study conducted on consecutive, adult mechanically ventilated air medical transport patients treated in the prehospital environment. Descriptive statistics were used to assess the cohort; the chi-square test compared categorical variables, and continuous variables were compared using independent samples t test or Mann-Whitney U test. To assess for predictors of nonprotective ventilation, a multivariable logistic regression model was constructed to adjust for potentially confounding variables. Low tidal volume ventilation was defined as a tidal volume of ≤ 8 mL/kg predicted body weight (PBW). RESULTS: A total of 68,365 subjects were studied. Height was documented in only 4,186 (6.1%) subjects. Significantly higher tidal volume/PBW (8.6 [8.3–9.2] mL vs 6.5 [6.1–7.0] mL) and plateau pressure (20.0 [16.5–25.0] cm H(2)O vs 18.0 [15.0–22.0] cm H(2)O) were seen in the nonpro-tective ventilation group (P < .001 for both). According to sex, females received higher tidal volume/PBW compared to males (7.4 [6.6–8.0] mL vs 6.4 [6.0–6.8] mL, P < .001) and composed 75% of those subjects with nonprotective ventilation compared to 25% male, P < .001. After multivariable logistic regression, female sex was an independent predictor of nonprotective ventilation (adjusted odds ratio 6.79 [95% CI 5.47–8.43], P < .001). CONCLUSIONS: The overwhelming majority of air medical transport subjects had tidal volume set empirically, which may be exposing patients to nonprotective ventilator settings. Given a lack of PBW assessments, the frequency of low tidal volume use remains unknown. Performance improvement initiatives aimed at indexing tidal volume to PBW are easy targets to improve the delivery of mechanical ventilation in the prehospital arena, especially for females.

Published
2022

24. Young, non‐Hispanic Black men and women exhibit divergent peripheral and cerebral vascular reactivity

Author

John D. Akins, Zachary T. Martin, Jordan C. Patik, Bryon M. Curtis, Jeremiah C. Campbell, Guillermo Olvera, and R. Matthew Brothers

Subjects
Hypercapnia, Male, Vasodilation, Nutrition and Dietetics, Brachial Artery, Physiology, Physiology (medical), Humans, Female, Hyperemia, General Medicine, Article, White People
Abstract

What is the central question of the study? Do peripheral and cerebral vascular function differ between young non-Hispanic Black men and women? What is the main finding and its importance? The non-Hispanic Black women in this study presented greater peripheral conduit artery and cerebrovascular reactivity, yet similar peripheral microvascular function relative to the non-Hispanic Black men. These preliminary findings suggest that young Black women and men possess divergent vascular function, possibly contributing to the unique non-Hispanic Black sex differences in cardiovascular and cerebrovascular diseases.In the USA, cardiovascular and cerebrovascular diseases remain more prominent in the non-Hispanic Black (BL) population relative to other racial/ethnic groups. Typically, sex differences emerge in the manifestation of these diseases, though these differences may not fully materialize in the BL population. While numerous mechanisms are implicated, differences in vascular function likely contribute. Research has demonstrated blunted vasodilatation in several vascular regions in BL versus non-Hispanic White individuals, though much of this work did not assess sex differences. Therefore, this study aimed to ascertain if indices of vascular function are different between young BL women (BW) and men (BM). Eleven BW and 15 BM (22 (4) vs. 23 (3) years) participated in this study. Each participant underwent testing for brachial artery flow-mediated dilatation (FMD), post-occlusive reactive hyperaemia and cerebral vasomotor reactivity during rebreathing-induced hypercapnia. BW exhibited greater adjusted FMD than BM (P 0.05 for all), but similar or lower reactive hyperaemia when assessed as blood velocity (P 0.39 for all) or blood flow reactivity (P 0.05 for all), respectively. Across a range of hypercapnia, BW had greater middle cerebral artery blood velocity and cerebrovascular conductance index than BM (P 0.001 for both). These preliminary data suggest that young BW have greater vascular function relative to young BM, though this was inconsistent across different indices. These findings provide insight into the divergent epidemiological findings between BM and BW. Further research is needed to elucidate possible mechanisms and relate these physiological responses to epidemiological observations.

Published
2022

25. Intraoperative complexity and risk factors associated with conversion to open surgery during laparoscopic cholecystectomy in eight hospitals in Mexico City

Author

Gabriel Rangel-Olvera, Bianca Alanis-Rivera, Jose Trejo-Suarez, Jose Nicolas Garcia-Martin del Campo, and Jose-Luis Beristain-Hernandez

Subjects
Male, Adult, Cholecystectomy, Laparoscopic, Risk Factors, Humans, Female, Surgery, Middle Aged, Conversion to Open Surgery, Mexico, Hospitals, Retrospective Studies
Abstract

The conversion to open surgery (COS) during the Laparoscopic Cholecystectomy (LC) is reported to occur at a rate of 10-15%. Some preoperative risk factors (RF) have been postulated; however, few studies have evaluated these factors and the intraoperative complexity with the COS rate. The aim of the study was to evaluate the preoperative RF and intraoperative complexity using the Parkland grading scale (PGS) with the COS rate in LC.A retrospective study was done evaluating the demographic and surgical variables from the patients and LC videos from 8 different hospitals of Mexico City from December 2018 to January 2020. The evaluation of the PGS was done by 2 surgeons (one MI and one HPB surgeon); the PGS was also categorized as Non-Complex LC (nCLC, PGS1-2) and Complex LC (CLC, PGS 3-5). Logistic regression was used to evaluate the association of this factors with the COS rate.430 LC were analyzed; 358 (78.61%) were women, 261 (60.7%) were elective and 169(39.3%) urgent LC, the mean age was 44.06 (SD ± 13.16) years. 21 (4.8%) LC were COS; the mean age of this group was 55 (SD ± 12.95), 3 (0.7%) were nCLC and 18 (4.19%) CLC, mean PGS of 3.76 (SD ± 1.09), the mean time to COS was 48.67 (SD ± 41.9), the estimated blood loss (EBL) was 258 (SD ± 260.22) and 6 (1.4%) intraoperative BDI were recognized on this group. Univariate analysis showed a significant association with the COS with male sex, older age, age 45 years, presence of comorbidities, a higher PGS, a CLC, higher EBL and possible BDI; multivariate analysis produced a model using male sex, age, presence of comorbidities and a CLC with a 0.809 area under the ROC curve.The recognition of the associated RF and a CLC can guide the surgeon to establish preoperative and bailout strategies during the procedure, recognizing a higher risk of COS and its higher morbidity.

Published
2022

26. Expansion of Candidate HPV-Specific T Cells in the Tumor Microenvironment during Chemoradiotherapy Is Prognostic in HPV16+ Cancers

Author

Lauren E. Colbert, Molly B. El, Erica J. Lynn, Julianna Bronk, Tatiana V. Karpinets, Xiaogang Wu, Bhavana V. Chapman, Travis T. Sims, Daniel Lin, Ramez Kouzy, Julie Sammouri, Greyson Biegert, Andrea Y. Delgado Medrano, Adilene Olvera, K. Jagannadha Sastry, Patricia J. Eifel, Anuja Jhingran, Lilie Lin, Lois M. Ramondetta, Andrew P. Futreal, Amir A. Jazaeri, Kathleen M. Schmeler, Jingyan Yue, Aparna Mitra, Kyoko Yoshida-Court, Jennifer A. Wargo, Travis N. Solley, Venkatesh Hegde, Sita S. Nookala, Ananta V. Yanamandra, Stephanie Dorta-Estremera, Geena Mathew, Rohit Kavukuntla, Cassidy Papso, Mustapha Ahmed-Kaddar, Minsoo Kim, Jianhua Zhang, Alexandre Reuben, Emma B. Holliday, Bruce D. Minsky, Albert C. Koong, Eugene J. Koay, Prajnan Das, Cullen M. Taniguchi, and Ann Klopp

Subjects
Human papillomavirus 16, Cancer Research, Papillomavirus E7 Proteins, T-Lymphocytes, Papillomavirus Infections, Immunology, Uterine Cervical Neoplasms, Chemoradiotherapy, Oncogene Proteins, Viral, Prognosis, Repressor Proteins, Tumor Microenvironment, Humans, Female
Abstract

Human papillomavirus (HPV) infection causes 600,000 new cancers worldwide each year. HPV-related cancers express the oncogenic proteins E6 and E7, which could serve as tumor-specific antigens. It is not known whether immunity to E6 and E7 evolves during chemoradiotherapy or affects survival. Using T cells from 2 HPV16+ patients, we conducted functional T-cell assays to identify candidate HPV-specific T cells and common T-cell receptor motifs, which we then analyzed across 86 patients with HPV-related cancers. The HPV-specific clones and E7-related T-cell receptor motifs expanded in the tumor microenvironment over the course of treatment, whereas non–HPV-specific T cells did not. In HPV16+ patients, improved recurrence-free survival was associated with HPV-responsive T-cell expansion during chemoradiotherapy.

Published
2022

27. Contributions of endothelin-1 and <scp>l</scp>-arginine to blunted cutaneous microvascular function in young, black women

Author

John D. Akins, Rauchelle E. Richey, Jeremiah C. Campbell, Zachary T. Martin, Guillermo Olvera, and R. Matthew Brothers

Subjects
Endothelin Receptor Antagonists, Receptors, Endothelin, Physiology, Endothelins, Arginine, Nitric Oxide, Peptides, Cyclic, Black or African American, Vasodilation, Young Adult, Cardiovascular Diseases, Physiology (medical), Microvessels, Humans, Female, Cardiology and Cardiovascular Medicine, Research Article
Abstract

Non-Hispanic black (BL) individuals have the greatest prevalence of cardiovascular disease (CVD), relative to other racial/ethnic groups (e.g., non-Hispanic white population; WH), which may be secondary to blunted vascular function. Although women typically present with reduced CVD relative to men of the same racial/ethnic group, the prevalence is similar between BL women and men though the mechanisms differ. This study hypothesized that reduced microvascular function in young, BL women is associated with endothelin-1 (ET-1) overactivity or insufficient l-arginine bioavailability. Nine BL and nine WH women participated (age: 20 ± 2 vs. 22 ± 2 yr). Cutaneous microvascular function was assessed during 39°C local heating, whereas lactated Ringer’s (control), BQ-123 (ET-1 receptor type A antagonist), BQ-788 (ET-1 receptor type B antagonist), or l-arginine were infused via intradermal microdialysis to modify cutaneous vascular conductance (CVC). Subsequent infusion of N(ω)-nitro-l-arginine methyl ester allowed for quantification of the nitric oxide (NO) contribution to vasodilation, whereas combined sodium nitroprusside and 43°C heating allowed for normalization to maximal CVC (%CVC(max)). BL women had blunted %CVC(max) and NO contribution to dilation during the 39°C plateau (P < 0.027 for both). BQ-123 improved this response through augmented NO-mediated dilation (P < 0.048 for both). BQ-788 and l-arginine did not alter the CVC responses (P > 0.835 for both) or the NO contribution (P > 0.371 for both). Cutaneous microvascular function is reduced in BL women, and ET-1 receptor type A may contribute to this reduced function. Further research is needed to better characterize these mechanisms in young, BL women. NEW & NOTEWORTHY Cardiovascular disease remains a burden in the United States non-Hispanic black (BL) population, although its manifestation through blunted vasodilation in this population is different between men and women. Accordingly, this study determined that reduced microvascular function in young, BL women may be partially controlled by endothelin-1 (ET-1) type A receptors, although neither type B receptors nor insufficient l-arginine bioavailability seems to contribute to this response. Accordingly, further research is needed to better characterize these ET-1 related mechanisms and illuminate other pathways that may contribute to this disparate vascular function in young, BL women.

Published
2022

28. Changes in lung function in European adults born between 1884 and 1996 and implications for the diagnosis of lung disease: a cross-sectional analysis of ten population-based studies

Author

Lowie E.G.W. Vanfleteren, Arnulf Langhammer, Shoaib Afzal, Peter Lange, Børge G. Nordestgaard, Helena Backman, Sylvia Hartl, Maarten van den Berge, Eva Rönmark, Marie-Kathrin Breyer, Otto C. Burghuber, Alvar Agusti, Guy Brusselle, Rosa Faner, Bo Lundbäck, Sigrid A Aalberg Vikjord, Jørgen Vestbo, Jadwiga A. Wedzicha, Judith M. Vonk, Robab Breyer-Kohansal, James P. Allinson, Sara R.A. Wijnant, H. Marike Boezen, Gavin C. Donaldson, Nuria Olvera, Bright I Nwaru, Yunus Çolak, Deborah Jarvis, Lies Lahousse, Groningen Research Institute for Asthma and COPD (GRIAC), Life Course Epidemiology (LCE), Epidemiology, and Pulmonary Medicine

Subjects
Adult, Lung Diseases, Male, Pulmonary and Respiratory Medicine, Vital capacity, Cross-sectional study, Vital Capacity, Population, Young Adult, FEV1/FVC ratio, Forced Expiratory Volume, Linear regression, Humans, Medicine, education, Lung, Socioeconomic status, Birth Year, Aged, Aged, 80 and over, education.field_of_study, business.industry, Middle Aged, respiratory system, respiratory tract diseases, Cross-Sectional Studies, medicine.anatomical_structure, Spirometry, Female, business, Demography
Abstract

Background: During the past century, socioeconomic and scientific advances have resulted in changes in the health and physique of European populations. Accompanying improvements in lung function, if unrecognised, could result in the misclassification of lung function measurements and misdiagnosis of lung diseases. We therefore investigated changes in population lung function with birth year across the past century, accounting for increasing population height, and examined how such changes might influence the interpretation of lung function measurements. Methods: In our analyses of cross-sectional data from ten European population-based studies, we included individuals aged 20–94 years who were born between 1884 and 1996, regardless of previous respiratory diagnoses or symptoms. FEV1, forced vital capacity (FVC), height, weight, and smoking behaviour were measured between 1965 and 2016. We used meta-regression to investigate how FEV1 and FVC (adjusting for age, study, height, sex, smoking status, smoking pack-years, and weight) and the FEV1/FVC ratio (adjusting for age, study, sex, and smoking status) changed with birth year. Using estimates from these models, we graphically explored how mean lung function values would be expected to progressively deviate from predicted values. To substantiate our findings, we used linear regression to investigate how the FEV1 and FVC values predicted by 32 reference equations published between 1961 and 2015 changed with estimated birth year. Findings: Across the ten included studies, we included 243 465 European participants (mean age 51·4 years, 95% CI 51·4–51·5) in our analysis, of whom 136 275 (56·0%) were female and 107 190 (44·0%) were male. After full adjustment, FEV1 increased by 4·8 mL/birth year (95% CI 2·6–7·0; p1 and FVC values predicted by published reference equations corroborated these findings. This height-independent increase in FEV1 and FVC across the last century will have caused mean population values to progressively exceed previously predicted values. However, the population mean adjusted FEV1/FVC ratio decreased by 0·11 per 100 birth years (95% CI 0·09–0·14; p

Published
2022

29. Icosapent Ethyl Reduces Ischemic Events in Patients With a History of Previous Coronary Artery Bypass Grafting: REDUCE-IT CABG

Author

Subodh Verma, Deepak L. Bhatt, Ph. Gabriel Steg, Michael Miller, Eliot A. Brinton, Terry A. Jacobson, Nitish K. Dhingra, Steven B. Ketchum, Rebecca A. Juliano, Lixia Jiao, Ralph T. Doyle, Craig Granowitz, C. Michael Gibson, Duane Pinto, Robert P. Giugliano, Matthew J. Budoff, R. Preston Mason, Jean-Claude Tardif, Christie M. Ballantyne, Fabrice M.A.C. Martens, Astrid Schut, Brian Olshansky, Mina Chung, Al Hallstrom, Lesly Pearce, Cyrus Mehta, Rajat Mukherjee, Anjan K. Chakrabarti, Eli V. Gelfand, Megan Carroll Leary, Duane S. Pinto, Yuri B. Pride, Steven Ketchum, Ramakrishna Bhavanthula, Gertrude Chester, Christina Copland, Katelyn Diffin, Ralph Doyle, Kurt Erz, Alex Giaquinto, Paula Glanton, Angela Granger, Richard H. Iroudayassamy, Rebecca Juliano, James Jin, Dimitry Klevak, Hardik Panchal, Robert Wang, Shin-Ru Wang, Gerard Abate, Peggy J. Berry, Rene Braeckman, Declan Doogan, Anne Elson, Amy HauptmannBaker, Isabel Lamela, Catherine Lubeck, Mehar Manku, Sabina Murphy, Monica Sanford, William Stirtan, Paresh Soni, Arnaud Bastien, Demetria Foster, Evangelito Gascon, Judith Johnson, Lasbert Latona, Gang Liu, Sandra Palleja, Nelly Sanjuan, Jimmy Shi, William Stager, Mukund Venkatakrishnan, Ahmed Youssef-Agha, Julie Zhu, Leela Aertker, Suresh Ankolekar, Lisa Goldberg, Natasa Rajicic, Jianfen Shu, Heng Zou, Magdy Mikhail, Gamil Dawood, N. Mathew Koshy, Sandip K. Mukherjee, Rafik Abadier, Andrea L. Lawless, William P. McGuinn, Howard Weintraub, Kathryn Rohr, Edmund Claxton, Robert J. Weiss, Terry D. Klein, Mani Nallasivan, Stephen Crowley, Marilyn King, Anthony D. Alfieri, David Fitz-Patrick, Irving Loh, Nolan J. Mayer, Rakesh Prashad, Samuel Lederman, Debra Weinstein, Harold E. Bays, Keith Chu, Alireza Maghsoudi, Paul D. Thompson, Jeff Carstens, Anna Chang, Kenneth R. Cohen, Julius Dean, Howard S. Ellison, Bernard Erickson, Enrique A. Flores, Daniel W. Gottlieb, Paul Grena, John R. Guyton, Peter H. Jones, John M. Joseph, Norman E. Lepor, Sam Lerman, Robert D. Matheney, Theodore R. Pacheco, Michael B. Russo, John Rubino, Edward S. Pereira, Albert A. Seals, Eduardo Viera, Alan D. Steljes, Jason Thompson, Shaival Kapadia, Michael McIvor, Jorge E. Salazar, Jose O. Santiago, Ralph Vicari, Martin R. Berk, William A. Kaye, Marcus McKenzie, David Podlecki, Brian D. Snyder, Stephen Nash, David M. Herrington, Wallace Johnson, Joseph R. Lee, Ronald Blonder, Alpa M. Patel, Ramon Castello, Susan Greco, Dean J. Kereiakes, Venkatesh K. Nadar, Mark Nathan, Ranganatha P. Potu, Robert Sangrigoli, Richard Smalling, Mitchell Davis, Robert Braastad, James McCriskin, Kunal Bodiwala, Joe L. Hargrove, Mark W. Graves, George Emlein, Raegan W. Durant, James W. Clower, Rohit Arora, Narendra Singh, Lisa Warsinger Martin, W Herbert Haught, Marc P. Litt, Michael D. Klein, Peter Hoagland, Michael Goldstein, Marco S. Mazzella, Daniel H. Dunker, Brian H. Kahn, Carlos S. Ince, Frank A. McGrew, Jay Lee, David Pan, Salman A. Khan, Uri Elkayam, Wasim Deeb, Anne C. Goldberg, Christopher S. Brown, Wayne N. Leimbach, Thomas S. Backer, David R. Sutton, Joel Gellman, Anu R. George, Alan S. Hoffman, Mark Kates, Kishlay Anand, Robert Bear, Brendan J. Cavanaugh, Ramon G. Reyes, Rodolfo Sotolongo, Kenneth Sabatino, Kevin Gallagher, Ehab Sorial, Chris Geohas, Kathleen E. Magness, Bernard P. Grunstra, Frederik A. Martin, William S. Knapp, Mel E. Lucas, John J. Champlin, Jason Demattia, Patrick H. Peters, Judith Kirstein, William J. Randall, Cezar S. Staniloae, Jennifer G. Robinson, Alexander Adler, Christopher Case, Andrew J. Kaplan, Gregory F. Lakin, Krishan K. Goyle, Michael J. DiGiovanna, Chester L. Fisher, Michael Lillestol, Michael Robinson, Robert G. Perry, Lawrence S. Levinson, Brian G. Everhart, Robert D. Madder, Earl F. Martin, Earl E. Martin, Imtiaz Alam, Jose Mari L. Elacion, Robina Poonawala, Taddese T. Desta, Jerome A. Robinson, Gilbert J. Martinez, Jakkidi S. Reddy, Jeffrey D. Wayne, Samuel Mujica Trenche, Westbrook I. Kaplan, Rubin H. Saavedra, Michael D. DiGregorio, Barry D. Bertolet, Neil J. Fraser, Terence T. Hart, Ronald J. Graf, David A. Jasper, Michael Dunn, Dan A. Streja, David J. Strobl, Nan Jiang, Vicki Kalen, Richard Mascolo, Mercedes B. Samson, Michael Stephens, Bret M. Bellard, Mario Juarez, Patrick J. McCarthy, John B. Checton, Michael Stillabower, Edward Goldenberg, Amin H. Karim, Naseem Jaffrani, Robert C. Touchon, Erich R. Fruehling, Clayton J. Friesen, Pradipta Chaudhuri, Frank H. Morris, Robert E. Broker, Rajesh J. Patel, Susan Hole, Randall P. Miller, Francisco G. Miranda, Sadia Dar, Shawn N. Gentry, Paul Hermany, Charles B. Treasure, Miguel E. Trevino, Raimundo Acosta, Anthony Japour, Samuel J. Durr, Thomas Wang, Om P. Ganda, Perry Krichmar, James L. Arter, Douglas Jacoby, Michael A. Schwartz, Amer Al-Karadsheh, Nelson E. Gencheff, John A. Pasquini, Richard Dunbar, Sarah Kohnstamm, Hector F. Lozano, Francine K. Welty, Thomas L. Pitts, Brian Zehnder, Salah El Hafi, Mark A. King, Arnold Ghitis, Marwan M. Bahu, Hooman Ranjbaran Jahromi, Ronald P. Caputo, Robert S. Busch, Michael D. Shapiro, Suhail Zavaro, Munib Daudjee, Shahram Jacobs, Vipul B. Shah, Frank Rubalcava, Mohsin T. Alhaddad, Henry Lui, Raj T. Rajan, Fadi E. Saba, Mahendra Pai N Gunapooti, Tshiswaka B. Kayembe, Timothy Jennings, Robert A. Strzinek, Michael H. Shanik, Pradeep K. Singh, Alastair C. Kennedy, Howard Rubenstein, Ramin Manshadi, Joanne Ladner, Lily Kakish, Ashley Kakish, Amy L. Little, Jaime Gerber, Nancy J. Hinchion, Janet Guarino, Denise Raychok, Susan Budzinski, Kathleen Kelley-Garvin, April Beckord, Jessica Schlinder, Arthur Schwartzbard, Stanley Cobos, Deborah Freeman, David Abisalih, Dervilla McCann, Kylie Guy, Jennifer Chase, Stacey Samuelson, Madeline Cassidy, Marissa Tardif, Jaime Smith, Brenna Sprout, Nanette Riedeman, Julie Goza, Lori Johnson, Chad Kraske, Sheila Hastings, Chris Dutka, Stephanie Smith, Toni McCabe, Kathleen Maloney, Paul Alfieri, Vinay Hosemane, Chanhsamone Syravanh, Cindy Pau, April Limcoiloc, Tabitha Carreira, Taryn S. Kurosawa, Razmig Krumian, Krista Preston, Ashraf Nashed, Daria Schneidman-Fernandez, Jack Patterson, John Tsakonas, Jennifer Esaki, Lynn Sprafka, Porous Patel, Brian Mitchell, Erin M. Ross, Donna Miller, Akash Prashad, Kristina M. Feyler, Natasha Juarbe, Sandra Herrera, Sarah M. Keiran, Becky Whitehead, Whitney Asher, Coury Hobbs, Abbey Elie, Jean Brooks, Amanda L. Zaleski, Brenda Foxen, Barb Lapke, Philippa Wright, Bristol Pavol, Gwen Carangi, Marla Turner, Katharine W. Sanders, Rikita S. Delamar, Virginia L. Wilson, Sarah M. Harvel, Alison M. Cartledge, Kaitlyn R. Bailey, Kathleen Mahon, Timothy Schuchard, Jen Humbert, Mark C. Hanson, Michael P. Cecil, James S. Abraham, Lorie Benedict, Claudia Slayton, Curtis S. Burnett, Rachel W. Ono-Lim, Sharon Budzinski, Shubi A. Khan, Sharon Goss, Terry Techmanski, Farida Valliani, Rimla Joseph, Edith Flores, Laurn Contreras, Ana Aguillon, Carrie-Ann Silvia, Maria Martin, Edmund K. Kerut, Leslie W. Levenson, Louis B. Glade, Brian J. Cospolich, Maureen W. Stein, Stephen P. LaGuardia, Thelma L. Sonza, Tracy M. Fife, Melissa Forschler, Jasmyne Watts, Judy Fritsch, Emese Futchko, Sarah Utech, Scott B. Baker, Miguel F. Roura, Scott A. Segel, James S. Magee, Cathy Jackson, Rebecca F. Goldfaden, Liudmila Quas, Elizabeth C. Ortiz, Michael Simpson, Robert Foster, Christopher Brian, James Trimm, Michael Bailey, Brian Snoddy, Van Reeder, Rachel Wilkinson, Harold Settle, Cynthia Massey, Angela Maiola, Michele Hall, Shelly Hall, Wanda Hall, Mark Xenakis, Janet Barrett, Giovanni Campanile, David Anthou, Susan F. Neill, Steven Karas, Enrique Polanco, Norberto Schechtman, Grace Tischner, Kay Warren, Cynthia St Cyr, Menna Kuczinski, Latrina Alexander, Maricruz Ibarra, Barry S. Horowitz, Jaime Steinsapir, Jeanette Mangual-Coughlin, Brittany Mooney, Precilia Vasquez, Kathleen Rodkey, Alexandria Biberstein, Christine Ignacio, Irina Robinson, Marcia Hibberd, Lisa B. Hoffman, Daniel J. Murak, Raghupathy Varavenkataraman, Theresa M. Ohlson Elliott, Linda A. Cunningham, Heather L. Palmerton, Sheri Poole, Jeannine Moore, Helene Wallace, Ted Chandler, Robert Riley, Farah Dawood, Amir Azeem, Michael Cammarata, Ashleigh Owen, Shivani Aggarwal, Waqas Qureshi, Mohamed Almahmoud, Abdullahi Oseni, Adam Leigh, Erin Barnes, Adam Pflum, Amer Aladin, Karen Blinson, Vickie Wayne, Lynda Doomy, Michele Wall, Valerie Bitterman, Cindi Young, Rachel Grice, Lioubov Poliakova, Jorge Davalos, David Rosenbaum, Mark Boulware, Heather Mazzola, J. Russell Strader, Russell Linsky, David Schwartz, Elizabeth Graf, Alicia Gneiting, Melissa Palmblad, Ashley Donlin, Emily Ensminger, Hillary Garcia, Dawn Robinson, Carolyn Tran, Jeffrey Jacqmein, Darlene Bartilucci, Michael Koren, Barbara Maluchnik, Melissa Parks, Jennifer Miller, Cynthia DeFosse, Albert B. Knouse, Amy Delancey, Stephanie Chin, Thomas Stephens, Mag Sohal, Juana Ingram, Swarooparani Kumar, Heather Foley, Nina Smith, Vera McKinney, Linda Schwarz, Judith Moore, Hildreth Vernon Anderson, Stefano Sdringola-Maranga, Ali Denktas, Elizabeth Turrentine, Rhonda Patterson, John Marshall, Terri Tolar, Donna Patrick, Pamela Schwartzkopf, Anthony M. Fletcher, Frances R. Harris, Sherry Clements, Tiffany Brown, William Smith, Stacey J. Baehl, Robin Fluty, Daniel VanHamersveld, Dennis Breen, Nancy Bender, Beverly Stafford, Tamika Washington, Margaret N. Pike, Mark A. Stich, Evyan Jawad, Amin Nadeem, Jill Nyland, Rhonda Hamer, Kendra Calhoun, Charlotte Mall, Samuel Cadogan, Kati Raynes, Richard Katz, Lorraine Marshall, Rashida Abbas, Jay L. Dinerman, John T. Hartley, Beth Lamb, Lisa Eskridge, Donna Raymond, Kristy Clemmer, Denise M. Fine, Paula Beardsley, Janet Werner, Bette Mahan, Courtney VanTol, Robert Herman, Christine Raiser-Vignola, Felicia McShan, Stefanie A. Neill, David R. Blick, Michael J. Liston, Denetta K. Nelson, Sandra K. Dorrell, Patricia Wyman, Ambereen Quraishi, Fernando Ferro, Frank Morris, Vicki J. Coombs, Autumn M. Mains, Austin A. Campbell, Jeanne Phelps, Cheryl A. Geary, Ellen G. Sheridan, Jean M. Downing, Arie Swatkowski, Tish Redden, Brian Dragutsky, Susan Thomas, Candace Mitchell, Diana Barker, Elanie Turcotte, Deborah Segerson, Jill Guy, Karena De La Mora, Jennifer Hong, Dennis Do, Rose Norris, Faisal Khan, Hector Montero, Stacy Kelly-White, Alan Cleland, Rosalyn Alcalde-Crawford, Melissa Morgan, Brijmohan Sarabu, Megan Minor, Shweta Kamat, Stephanie M. Estes, Nancee Harless, Alicia Disney, Jodi L. Pagano, Chad M. Alford, Noel W. Bedwell, Warren D. Hardy, Kevin DeAndrade, Jessica G. Elmore, Eric Auerbach, Anthony W. Haney, Miriam H. Brooks, Jose Torres, Lois Roper, Terry Backer, Katie Backer, John G. Evans, Ricardo A. Silva, Lorraine H. Dajani, Veronica Yousif, Tammy Ross, Sion K. Roy, Ronald Oudiz, Sajad Hamal, Ferdinand Flores, Amor Leahy, Debra Ayer, Swapna George, Chrisi Carine Stewart, Elvira Orellana, Cristina Boccalandro, Mary Rangel, Suzanne Hennings, Carl Vanselow, Teri Victor, Darlene Birdwell, Paul Haas, Anthony Sandoval, Gina Ciavarella, Caroline Saglam, Amy Bird, Keith Beck, Brian Poliquin, David Dominguez, Brittany Tenorio, Harvonya Perkins, Esther San Roman, Paris Bransford, Christy Lowrance, Marcy Broussard, Mary Ellis, Bobbi Skiles, Jessica Hamilton, Kathryn Hall, Diego Olvera, Julee A. Hartwell, Nevien Sorial, Mary Rickman, Kevin Berman, Nirav Mehta, Annie Laborin, Rodger Rothenberger, Sarah Beauvilliers, Kathy Morrell, Michael P. Schachter, Cindy L. Perkins, Elizabeth A. Gordon, Jennifer Lauer, Kim Bichsel, Kelly Oliver, Leslie J. Mellor, Candice Demattia, Jennifer Schomburg, Yenniffer Moreno, Eduardo Mansur-Garza, Lena Rippstein, Lorie Chacon, Andrea Pena, Michelle King, Susan Richardson, Annette Jessop, Nicole Tucker, Whitney Royer, Gilbert Templeton, Ann Moell, Christine Weller, Melissa J. Botts, Gretel Hollon, Elsa Homberg-Pinassi, Paula Forest, Aref Bin Abhulhak, Devona Chun-Furlong, Deborah Harrington, Emily Harlynn, Marjorie Schmitt, Constance Shelsky, Patricia Feldick, Mary Cherrico, Courtney Jagle, Nicholas Warnecke, Debra Myer, Deanna J. Ruder, Albina Underwood, Alan Rauba, George Carr, Barbara Oberhaus, Jessica Vanderfeltz, Mary Jo Stucky-Heil, Dale R. Gibson, Vonnie Fuentes, Kimberly L. Talbot, William C. Simon, Katlyn J. Grimes, Christina R. Wheeler, Cassaundra Shultz, Rhonda A. Metcalf, Jennifer L. Hill, Michelle R. Oliver, Basharat Ahmad, Fouzal Azeem, Abdul Rahim, George H. Freeman, Dawn Bloch, Heather Freeman, Jamie Brown, Sarah Rosbach, Pamela Melander, Nick Taralson, Alex Liu, Katlyn Harms, Mahfouz Michale, Jose Lopez, Maria Revoredo, Shari Edevane, Sarah Shawley, Timothy L. Jackson, Michael J. Oliver, Dina DeSalle, Patricia J. Matlock, Ionna M. Beraun, Heather Hendrix, Garrett Bromley, Ashley Niemerski, Gabby Teran, Sonia Guerrero, Murtaza Marvi, Zehra Palanpurwala, Andrea Torres, Patty Gloyd, Michelle Conger, Aziz Laurent, Olia Nayor, Catalina S. Villanueva, Munira Khambati, Tabetha J. Mumford, Melanie J. Castillo, Taddese Desta, Jerome Robinson, La Shawn Woods, Anita Bahri, Nancy Herrera, Cecilia Casaclang, Jeffrey R. Unger, Geraldine Martinez, Mia K. Moon, Stephen M. Mohaupt, Larry Sandoval, Louisito Valenzuela, Victora Ramirez, Nelly Mata, Veronica Avila, Marisol Patino, Cynthia Montano-Pereira, Omar Barnett, William M. Webster, Lorraine M. Christensen, Leighna Bofman, Melanie Livingston, Stacey Adams, Joseph Hobbs, Leesa Koskela, Mia Katz, Samuel Mujica-Trenche, Franklin Cala, Noreen T. Rana, Jennifer Scarlett, Milagros Cala Anaya, Marsha R. Jones, Kelly D. Hollis, Debbie Roth, Kristin Eads, Tina Watts, Judy Perkins, Alice Arnold, Daniel C. Ginsberg, Denise Quinn, Nicole Cureton, David B. Fittingoff, Mohammed I. Iqbal, Stephen R. White, Edith Sisneros, Michelle Ducca, David Streja, Danny Campos, Jennifer L. Boak, Farzeen Amir, Felice Anderson, James J. Kmetzo, Mary O. Bongarzone, Dawn Scott, Mary Grace De Leon, Cynthia Buda, William Graettinger, Michelle Alex, Erika Hess, James Govoni, Melissa Bartel, Travis L. Monchamp, Julie S. Roach, Sara Gibson, Amy M. Allfrey, Kristen Timpy, Kathy Bott, Karin A. Soucy, Jean Willis, Cecilia A. Valerio, Anusha Chunduri, Rebecca Coker, Nicole Vidrine, Ellen A. Thompson, Mark A. Studeny, Melissa K. Marcum, Tammy S. Monway, Douglas L. Kosmicki, Melissa J. Kelley, Corey M. Godfrey, Susan L. Krenk, Randy R. Holcomb, Deb K. Baehr, Mary K. Trauernicht, David Rowland Lowry, Betty Bondy Herts, Jeanne E Phelps, Jean-Marie Downing, Carol Gamer Dignon, Elisabeth S. Cockrill, Pravinchandra G. Chapla, Diane Fera, Margaret Chang, Patricia Fredette, Tamie Ashby, Renee Bergin, Zebediah A. Stearns, David B. Ware, Rachael M. Boudreaux, Joanna Rodriguez, Robert McKenzie, Amanda Huber, Rebecca Sommers, Heather Rowe, Stacy McLallen, Michale Haynes, Ashley Adamson, Janice Henderson, Lori McClure, Beverly A. Harris, Laura Ference, Sue Meissner-Dengler, Lisa Treasure, Doreen Nicely, Timothy L. Light, Tracey A. Osborn, Kimberly J. Mai, Pablo Vivas, Jose Rios, Dunia Rodriguez, Roger DeRaad, James Walder, Oscar Bailon, Denice Hockett, Debbie Anderson, Kelli McIntosh, Amber Odegard, Andrew Shepherd, Mary Seifert, Laurence Kelley, Rajendra Shetty, Michael Castine, David Brill, Gregory Fisher, Nicole Richmond, Kathleen Gray, Patricia Miller, Charlene Coneys, Yarixa Chanza, Monica Sumoza, Victoria M. Caudill, Kelly D. Harris, Courtney A. Manion, Melody J. Lineberger-Moore, Julie J. Wolfe, Barbara J. Rosen, Patricia DiVito, Janet L. Moffat, Christina Michaelis, Prashant Koshy, Diana Perea, Ghaith Al Yacoub, Stephanie Sadeghi, Thomas D. LeGalley, Rudolph F. Evonich, William J. Jean, Gary M. Friesen, John M. Pap, David A. Pesola, Mark D. Cowan, Kristofer M. Dosh, Dianna Larson, Adele M. Price, Jodi A. Nease, Jane E. Anderson, Lori A. Piggott, Robert Iwaoka, Kevin Sharkey, Edward McMillan, Laurie Lowder, Latisha Morgan, Kyle Davis, Tara Caldwell, Erica Breglio, Jasmine Summers, Rachel Poulimas, Muhammad Zahid, Hamid Syed, Maria Escobar, Jacob Levy, Rahma Warsi, Carol Ma, Puxiao Cen, Kimberly A. Cawthon, Delores B. Barnes, Deanna G. Allen, Margaret L. Warrington, Carol R. Stastny, Robin J. Michaels, Mohamad Saleh, John Sorin, Sunny Rathod, Urakay Juett, Steven Spencer, Aziza Keval, Jill McBride, Shane Young, Catherine Baxter, Carol Rasmussen, Shari L. Coxe, Luis Campos, Shahin Tavackoli, Diana Beckham, Darlynee Sanchez, Karanjit Basrai, Dorian Helms, Erica Clinton, Kasie Smith, Henry Cusnir, Mary Klaus Clark, Madhavagopal V. Cherukuri, Ameta Scarfaru, Stephen D. Nash, Loretta C. Grimm, Anna Grace, Kylie McElheran, Dino Subasic, Zedrick Buhay, Janet Litvinoff, Deepak Shah, Shannon Cervantes, Freda Usher, Farra Yasser, Theodore Trusevich, Ronnie L. Garcia, Jamison Wyatt, Rahul Bose, Holllilyn Miska, Traci Spivey, Amy B. Wren, Katie E. Vance, Lani L. Holman, Pam Gibbons, Elaine Eby, Sandra Shepard, Soratree Charoenthongtrakul, Brett Snodgrass, Mohammed Nazem, Shelly Keteenburg, Prathima Murthy, Frederic Prater, Ashley Rumfelt, Christina Eizensmits, Lisa Iannuzzi, Pourus R. Patel, Clellia Bergamino, Elizabeth McFeaters, Botros Rizk, Emiljia Pflaum, Danny Kalish, Rex Ambatali, Mona Ameli, Delaina Sanguinetti, Rakesh Vaidya, Martinus A.W. Broeders, Dorman Henrikus, Adrianus F.M. Kuijper, Nadea Al-Windy, Michael Magro, Karim Hamraoui, Ismail Aksoy, Guy L.J. Vermeiren, H.W.O. Roeters van Lennep, Gerard Hoedemaker, Johannes Jacobus Remmen, Kjell Bogaard, Dirk van der Heijden, Nicole MJ Knufman, Joost Frederiks, Johannes Willem Louwerenburg, Piet van Rossum, Johannes Milhous, Peter van der Meer, Arno van der Weerdt, Rob Breedveld, Mitran Keijzers, Walter Hermans, Ruud van de Wal, Peter A.G. Zwart, Marc M.J.M. van der Linden, Gerardus Zwiers, Dirk J. Boswijk, Jan Geert Tans, Jacob van Eck, Maarten V. Hessen, Barnabas J.B. Hamer, Stieneke Zoet-Nugteren, Lucien Theunissen, E.A. van Beek, Remco Nijmeijer, Pieter R. Nierop, Gerard Linssen, H.P. Swart, Timo Lenderink, Gerard L. Bartels, Frank den Hartog, Brian J. Berg van den, Wouter van Kempen, Susanne Kentgens, Gloria M. Rojas Lingan, Martinus M. Peeters, Hilligje Keterberg, Melchior Nierman, Annemieke K. den Hollander, Jacqueline Hoogendijk, Christine Voors-Pette, Vicdan Kose, Peter Viergever, Larysa Yena, Viktor Syvolap, Mykola P. Kopytsya, Olga Barna, Svitlana S. Panina, Mykhailo I. Lutai, Oxana V. Shershnyova, Iryna Luzkiv, Larysa S. Bula, Sergii Zotov, Ivan Vyjhovaniuk, Olena Lysunets, Volodymyr I. Koshlia, Nataliya Sydor, Myroslava F. Vayda, Olexiy Ushakov, Mykola Rishko, Viktor P. Shcherbak, Yevgeniya Svyshchenko, Vira Tseluyko, Andriy Yagensky, Viktoriia I. Zolotaikina, Olga Godlevska, Larysa Ivanova, Olena Koval, Olena I. Mitchenko, Galyna Y. Kardash, Yurii S. Rudyk, Mykola Stanislavchuk, Volodymyr Ivanovych Volkov, Olena G. Karlinskaya, Susanna A. Tykhonova, Nikolay Vatutin, Ganna Smirnova, Volodymyr M. Kovalenko, Viktor Lizogub, Denys Sebov, Oleksandr Dyadyk, Svetlana Andrievskaya, Mykola P. Krasko, Alexander N. Parkhomenko, Lidiya Horbach, Iryna G. Kupnovytska, Tetyana Pertseva, Oleksandr Karpenko, Dmytro Reshotko, Svitlana V. Zhurba, Leonid Rudenko, Viktoriia Yu Zharinova, Valerii B. Shatylo, Yuriy I. Karpenko, Mariya A. Orynchak, Tatiana R. Kameneva, Elena Zherlitsina, Diana N. Alpenidze, Grigoriy P. Arutyunov, Elena Baranova, Boris Bart, Dmitriy I. Belenkiy, Svetlana A. Boldueva, Elena A. Demchenko, Vera V. Eltishcheva, Alexander M. Gofman, Boris M. Goloshchekin, Ivan Gennadyevich Gordeev, Nikolay Gratsianskiy, Gadel Kamalov, Niyaz R. Khasanov, Irina M. Kholina, Zhanna D. Kobalava, Elena V. Kobeleva, Alexandra O. Konradi, Victor A. Kostenko, Andrey Dmitrievich Kuimov, Polina Y. Ermakova, Sofia K. Malyutina, Alexey V. Panov, Natalia V. Polezhaeva, Olga Reshetko, Nataliya P. Shilkina, Sergey B. Shustov, Elena A. Smolyarchuk, Raisa I. Stryuk, Elena Yurievnar Solovieva, Andrey V. Susekov, Natalia Vezikova, Svetlana N. Ivanova, Alexander A. Petrov, Vladimir O. Konstantinov, Alina S. Agafina, Victor Gurevich, Konstantin N. Zrazhevskiy, Tatiana V. Supryadkina, Nikita B. Perepech, Vadim L. Arkhipovskiy, Dmitry Yu Butko, Irina A. Zobenko, Olga V. Orlikova, Viktor Mordovin, Olga L. Barbarash, Anastasiya Lebedeva, Vladimir Nosov, Oleg V. Averkov, Elena P. Pavlikova, Yuri B. Karpov, Marina Lvovna Giorgadze, Oleg A. Khrustalev, Mikhail Arkhipov, Tatiana A. Raskina, Julia V. Shilko, Yulia Samoilova, Elena D. Kosmacheva, Sergey V. Nedogoda, Kathleen Coetzee, Lesley J. Burgess, F.C.R. Theron, Iftikhar O. Ebrahim, Gerbrand A. Haasbroek, Maria Pretorius, Julien S. Trokis, Dorothea V. Urbach, Mark J. Abelson, Adrian R. Horak, Aysha E. Badat, Ellen M. Makotoko, Hendrik Du Toit Theron, Padaruth Ramlachan, Clive H. Corbett, Ismail H. Mitha, Hendrik F.M. Nortje, Dirkie J. Jansen van Rensburg, Peter J. Sebastian, F.C.J. Bester, Louis J. van Zyl, Brian L. Rayner, Elżbieta Błach, Magda Dąbrowska, Grzegorz Kania, Agata E. Kelm-Warchol, Leszek P. Kinasz, Janusz Korecki, Mariusz Kruk, Ewa Laskowska-Derlaga, Andrzej Madej, Krzysztof Saminski, Katarzyna Wasilewska, Katarzyna Szymkowiak, Małgorzata Wojciechowska, Natalia Piorowska, Andrzej Dyczek, Rajpal K. Abhaichand, Ramesh B. Byrapaneni, Basavanagowdappa Hattur, Malipeddi Bhaskara Rao, Nitin Ghaisas, Sujit Shankar Kadam, Jugal B. Gupta, Santhosh M. Jayadev, V.A. Kothiwale, Atul Mathur, Vijay Bhaskar, Ravi K. Aluri, Udaya P. Ponangi, Mukesh K. Sarna, Sunil Sathe, Manish K. Sharma, Jilendra Pal Singh Sawhney, Chakrabhavi B. Keshavamurthy, Arun Srinivas, Hemant P. Thacker, A. Sharda, Johny Joseph, Sunil Dwivedi, Viswanathan Mohan, Rajendra K. Premchand, Jacques Bedard, Jean Bergeron, Ronald Collette, David Crowley, Richard Dumas, Sam Henein, Geoff Moran, William F. O’Mahony, Michael O’Mahony, Sammy Chan, Mark H. Sherman, Graham C. Wong, Brian D. Carlson, Milan K. Gupta, David Borts, Sean R. Peterson, Martyn Chilvers, Allan J. Kelly, Jean C. Gregoire, Simon Kouz, Josep Rodés Cabau, Minodora Andor, Mircea Cinteza, Radu Ciudin, Radu I. Cojan, Roxana O. Darabont, Dan-Lucian Dumitrascu, Carmen Fierbinteanu-Braticievici, Ana Gabriela Fruntelata, Constantin Militaru, Bogdon E. Minescu, Doina Luminita Serban, Florin Mitu, Dorel Nastase Melicovici, Ovidiu Petrascu, Octavian M. Pirvu, Cristian Podoleanu, Calin Pop, Rodica-Valentina V. Stanescu-Cioranu, Adrian Tase, Cristina Voiculet, Constantine N. Aroney, Anthony M. Dart, Timothy Davis, Karam Kostner, David N. O’Neal, Peter W. Purnell, Bhuwanendu B. Singh, David R. Sullivan, Peter Thompson, Gerald F. Watts, Adam F. Blenkhorn, John V. Amerena, Rafeeq Samie, Randall Hendriks, Joseph Proietto, Nikolai Petrovsky, Alan Whelan, David Colquhoun, Russell S. Scott, Simon C. Young, Tammy Pegg, Samuel JS Wilson, Andrew W. Hamer, Richard A. Luke, Hamish H. Hart, Gerard P. Devlin, Gerard T. Wilkins, Ian F. Ternouth, Samraj Nandra, Bruno S. Loeprich, Nicole McGrath, Stuart L. Tie, Rob J. Bos, Alexandra Wils, Tamara Jacobs, Erik A. Badings, Lillian A. Ebels-Tuinbeek, Mayke L. Scholten, Esther Bayraktar-Verver, Debby Zweers, Manoek Schiks, Carolien Kalkman, Tineke Tiemes, Jeanette Mulderij, Katarzyna Dabrowska, Wilma Wijnakker, Riny Van de Loo, Jeanne de Graauw, Giny Reijnierse, Mirjam van der Zeijst, Mariska Scholten, Henk R. Hofmeijer, Antoinette van Dijk-van der Zanden, Dineke J. van Belle, Jan Van Es, Gera Van Buchem, Wendy Zijda, Harald Verheij, Linnea Oldenhof-Janssen, Martina Bader, Marije Löwik, Sandra Stuij, Pascal Vantrimpont, Krista van Aken, Karen Hamilton, Han Blömer, Gabriela van Laerhoven, Raymond Tukkie, Maarten Janssen, Gerard Verdel, Jon Funke Küpper, Bob van Vlies, Caroline Kalkman, Joke Vooges, Marinella Vermaas, Rachel Langenberg, Niek Haenen, Frans Smeets, Arko Scheepmaker, Marcel Grosfeld, Ilvy Van Lieshout, Marleen van den Berg, Marian Wittekoek, Petra Mol, Antionette Stapel, Margaretha Sierevogel, Nancy van der Ven, Annemiek Berkelmans, Eric Viergever, Hanneke Kramer, Wilma Engelen, Karen V. Houwelingen, Thierry X. Wildbergh, Arend Mosterd, Coriet Hobé-Rap, Marjan van Doorn, Petra Bunschoten, Michel Freericks, Mireille Emans, Petra Den Boer-Penning, Els Verlek, Christine Freericks, Cornelis de Nooijer, Christina Welten, Ingrid Groenenberg, Claudia van der Horst, Esther Vonk, Geert Tjeerdsma, Gerard M. Jochemsen, Corinne van Daalen, Ingrid Y. Danse, Lucy Kuipers, Anke Pieterse, Antonius Oomen, Daan de Waard, Willem Jan Flu, Zusan Kromhout, Petra Van der Bij, Rob Feld, Brigitta Hessels-Linnemeijer, Rob Lardinois, Jan L. Posma, Zwanette R. Aukema-Wouda, Marjolijn Hendriks-van Woerden, Desiree van Wijk, Driek P. Beelen, Ingrid H. Hendriks, Jan J. Jonker, Stefanie Schipperen, Vicdan Köse, Gloria Rojas, Linda Goedhart, Hanneke van Meurs, Jacqueline Rijssemus, Lindy Swinkels-Diepenmaat, Marloes de Louw-Jansen, Dominique Bierens-Peters, Willem W. van Kempen, Marianne E. Wittekoek, Irmaina Agous, Geert Schenk, Janneke Wittekoek, Kevin Cox, Deborah F. Julia, Jan J.C. Jonker, Roel Janssen, Melchor Nierman, Hilligje Katerberg, Irene van der Haar, Willem W. Van Kempen, Taco van Mesdag, Leyda M. Alvarez Costa, Manon Schensema, Salomé Zweekhorst, Deborah Font Julia, Lauri Hanewinckel, Joyce Olsthoorn, Johan C. Berends, Arie C. van der Spek, Roy van der Berg, Rob J. Timmermann, Ingrid Boerema, Iryna Mudruk, Anna Khrystoforova, Serhii Kyselov, Yaroslava V. Hilova, Pavlo Logoida, Nataliia A. Sanina, Ilona P. Golikova, Olena O. Nemchyna, Ivan I. Isaichikov, Olga B. Potapova, Iurii V. Gura, Larysa Berestetska, Olena O. Kulianda, Oleksandr Tantsura, Oleksandr S. Kulbachuk, Volodymyr Petsentiy, Ihor Biskub, Tetyana Handych, Oleg Lagkuti, Alyna Gagarina, Taras Chendey, Oksana F. Bilonko, Olena Matova, Larysa Bezrodna, Olena Yarynkina, Tetiana Ovdiienko, Volodymyr Randchenko, Maryna Mospan, Olena Butko, Olga Romanenko, Mykhailo Pavelko, Iryna Sichkaruk, Svitlana O. Lazareva, Olena A. Kudryk, Inessa M. Koltsun, Tetiana Magdalits, Sergei Zadorozhniy, Kira Kompaniiets, Andrii Ivanov, Sergiy Romanenko, Pavlo Kaplan, Vadym Y. Romanov, Oksana P. Mykytyuk, Nataliia S. Zaitseva, Sergiy N. Pyvovar, Lyudmyla Burdeuna, Emerita Serdobinska, Tatiana I. Shevchenko, Igor I. Ivanytskyi, Olena V. Khyzhnyak, Nataliya Kalinkina, Olena Keting, Olena Sklyanna, Olga Kashanska, Anna Shevelok, Marina Khristichenko, Ievgenii Y. Titov, Danilenko O. Oleksander, Nataliia S. Polenova, Nataliia Altunina, Viktoriia Kororaieva, Stanislav Zborovskiy, Leonid Kholopov, Iurii Suliman, Lanna Lukashenko, Stanislav Shvaykin, Olexandr M. Glavatskiy, Roman O. Sychov, Roman L. Kulynych, Oleksandr A. Skarzhevskyi, Nataliia V. Dovgan, Marta Horbach, Olga Cherkasova, Iryna Tyshchenko, Liudmyla Todoriuk, Svitlana Kizim, Nataliia Brodi, Oleksandr Ivanko, Olga Garbarchuk, Liudmyla Alieksieieva, Tetiana L. Shandra, Olena Beregova, Larisa An Bodretska, Svitlana S. Naskalova, Ivanna A. Antoniuk-Shcheglova, Olena V. Bondarenko, Natalia G. Andreeva, Iryna I. Vakalyuk, Olha S. Chovganyuk, Nataliya R. Artemenko, Kiril A. Maltsev, Natalia Kalishevich, Natalia G. Kondratyeva, Svetlana A. Nikitina, Maria V. Martjanova, Anna V. Sokolova, Dmitrii O. Dragunov, Olga Kolesnik, Vera Larina, Oxana V. Tsygankova, Maria Ivanova, Illia A. Karpov, Elena M. Aronova, Ekaterina S. Vedernikova, Ekaterina I. Lubinskaya, Taras Y. Burak, Sergey I. Skichko, Farhad Rasulev, Ekaterina B. Soldatova, Alexander L. Fenin, Ilya I. Laptev, Elena E. Luchinkina, Alexandr Akatov, Natalia V. Polenova, Natalia N. Slavina, Irina N. Korovnika, Marina Yu Prochorova, Regina Shakirova, Elena N. Andreicheva, Olga A. Krasnova, Tinatin V. Lobzhanidze, Tatiana B. Dmitrova, Viktoriya V. Stakhiv, Maria I. Pechatnikova, Alexandra V. Panova, Maria Y. Tipikina, Oxana P. Rotar, Nikolay A. Bokovin, Saule K. Karabalieva, Farid Y. Tumarov, Elena V. Vasileva, Natalya Gennadevna Lozhkina, Ekaterina V. Filippova, Alisa I. Sharkaeva, Ekanerina V. Filippova Deilik, Natalia Yu Tolkacheva, Elena N. Domracheva, Andrey N. Ryabikov, Inga T. Abesadze, Marianna Z. Alugishvili, Elena P. Nikolaeva, Nadezda V. Smirnova, Valentina I. Rodionova, Polina V. Dolovstaya, Igor E. Yunonin, Sergey V. Kadin, Tatyana S. Sveklina, Anna V. Bushmanova, Elena L. Barkova, Irina S. Gomova, Yana V. Brytkova, Tatiana B. Ivanova, Marina Y. Zubareva, Inga Skopets, Lybov A. Galashevskaya, Emilia D. Butinskaya, Olga G. Gusarova, Natalia B. Kalishevich, Yana R. Pavlova, Marianna P Serebrenitskaya, Vitalina F. Grygorieva, Gulnara R. Kuchaeva, Inna A. Vasileva, Gulnara I. Ospanova, Yulia V. Vahrusheva, Irina A. Semenova, Irina E.E. Mikhailova, Olga O. Kvasova, Valeria D. Shurygina, Alexey E. Rivin, Alexey O. Savelyev, Alexey A. Savelyev, Olesya O. Milyaeva, Nadezhda N. Lapshina, Ninel A. Lantsova, Pavel V. Alexandrov, Evgeniy A. Orlikov, Alla Falkovskaya, Tatiana Ripp, Sergei Triss, Stanislav Pekarskiy, Sitkova Ekaterina, Evgeniya N. Zhuravleva, Olga Perova, Galina Kovaleva, Liubov Koroleva, Lydia Mishchenko, Boris P. Garshin, Svetlana A. Kutuzova, Lyudmila I. Provotorova, Igor P. Zadvorny, Olga V. Okhapkina, Anatoly O. Khrustalev, Tatiana Suvorova, Elena S. Shaf, Varvara A. Vershinina, Andrey A. Kozulin, Oxana A. Oleynik, Irina Y. Martynova, Natalia V. Kizhvatova, Alla S. Salasyuk, Vera V. Tsoma, Alla A. Ledyaeva, Elena V. Chumachek, S.C. Blignaut, Tersia Y. Alexander, Chano Du Plessis, Thirumani Govender, Samatha M. Du Toit, Leya Motala, Areesh Gassiep, Christina Naude (Smit), Marli Terblanche, Marlien Snoer (Kruger), Berenice Pillay, De Vries Basson, Marisa E. Theron, Bianca Fouche, Mareli E. Coetzee, Pieter Odendall, Frederik H. Van Wijk, Anna-Mari Conradie, Trudie Van der Westhuizen, Carine Tredoux, Mohamed S. Mookdam, Andie J. Van der Merwe, Karin Snyman, Gerda Smal, Yvonne De Jager, Thomas A. Mabin, Annusca King, Lindy L. Henley, Brenda M. Zwane, Jane Robinson, Marinda Karsten, Andonia M. Page, Valerie Nsabiyumva, Charmaine Krahenbuhl, Jaiprakash D. Patel, Yunus E. Motala, Ayesha Dawood, Nondumiso B. Koza, Lenore M.S. Peters, Shavashni Ramlachan, Wilhelm J. Bodenstein, Pierre Roux, Lizelle Fouche, Cecilia M. Boshoff, Haroon M. Mitha, Fathima Khan, Henry P. Cyster, Helen Cyster, E. C. Wessels, Florence J. Jacobs, Melanie A. Sebastian, Deborah A. Sebastian, Nadia Mahomed, Ignatius P. Immink, Celia Cotzee, Tanja Cronje, Madele Roscher, Maria Le Roux, Yvonne A. Trinder, Renata Wnętrzak-Michalska, Magdalena Piszczek, Andrzej Piela, Ewa Czernecka, Dorota Knychas, Alina Walczak, Izabella Gładysz, Katarzyna Filas, Ewelina Kiluk, Krzysztof Świgło, Iwona Jędrzejczyk, Kamila Łuczyńska, Katarzyna Tymendorf, Wojciech Piesiewicz, Wojciech L. Kinasz, Stefan Samborski, Ilona Bartuś, Gramzyna Latocha Korecka, Ewa Gulaj, Jolanta Sopa, Bogusław Derlaga, Marcin Baisiak, Allicia Kowalisko, Edyta Stainszewska-Marasazlek, Bartosz Szafran, Malgorzata Swiatkiewicz, Artur Racewicz, Sławomir Grycel, Jerzy Supronik, Sylwia Walendziuk, Magdalena Tarantowicz, Agata Stasiak, Anna Sidorowicz-Białynicka, Marek Dwojak, Ewa Jaźwińska-Tarnawska, Katarzyna Kupczyk, Kamila Martowska, Kamila Kulon, Katarzyna Gajda, Bivin Wilson, Krithika Velusamy, Swaidha S. Sadhiq, Bhavani Siddeshi, M. Bhanukumar, Abhishek Srivatsav, Madhan Ramesh, Sri Harsha Chalasani, Mini Johnson, Prashanth Gopu, Jeesa George, Sowmya Reddy, Swetha Tessy Thara Eleena, Damodara Rao Kodem, Haritha N. Nakkella, Padma Kumari Mandula, Anjan Kumar Vuriya, Syamala Rajana, Aruna Kale, Tiwari Rajeev, Raina Jain, Vipin Jain, Srilakshmi Mandayam Adhyapak, Lumin Sheeba, Uma C R, Ramya R, Aditya V. Kulkarni, M.S. Ganachari, Ruma Sambrekar, Mohammad Bilal, Kalyan Chakravarthy, Ravi Badhavath, Sravan Kumar, Meenakshi Simhadri, Farooque Salamuddin, Venkat Prasad, Vivek Dwivedi, Sudha Sarna, Tilak Arora, Deepak Chawla, Archana Sathe, Chaware Gayatree, Ajeet Nanda, Ram Avtar, Jyoti Sharma, Vaibhavi P S, Sasirekha D, Deepthi Kobbajji, Ramya Ningappa, Shwetha Shree, Chandrashekar K, Nandini M R, Sowjanya S, Devika I G, Yashaswini N, Sonika G, Rathna L, Priyanka R, Rupal J. Shrimanker, Lakshmi Vinutha Reddy, K. Sumathi, Babitha Devi, Bina N. Naik, Rohini Manjunath, Rajeshwari Ashok, Tony V. Kunjumon, Jesline Thomas, Shaik Samdhani, Kasthuri Selvam, Poongothai Subramani, Nandakumar Parthasarathy, Nirmal K. Bohra, Anvesh K. Gatla, Cheryl Horbatuk, Julie Sills, E B. Davey, Liz Paramonczyk, Olga Racanelli, Sandy Strybosch, Andre Belanger, Jean Palardy, Alicia Schiffrin, Sylvie Gauthier, Norman Kalyniuk, Shawn D. Whatley, Heather Lappala, Grishma Patel, Matthew Reeve, Catherine Moran, Jody Everitt, Teresa Ferrari, Christine Bouffard, Jirir Frohlich, Gordon Francis, John Mancini, Gregory Bondy, Debbie DeAngelis, Patricia Fulton, David W. Blank, Angela Lombardo, Mylène Roy, Jackie Chow, Hyman Fox, William J. Grootendorst, Angela Hutchinson, Sharon M. Chan, Christie Fitzgerald, Lynn Wilkins, Rebecca L. Raymond, Arlene Reyes, Lavoie Marc André, Denis Fortin, Hélène Ouimet, Thanh-Thao Tôn-Nu, Martine Dussureault, Marie-Hélène Blain, Madeleine Roy, Nathalie Kopajko, Chantal Fleury, Karine Maheux, Gabriela Valentina Ciobotaru, Maria C. Constantinescu, Carmen-Lucia Gherghinescu, Ana-Maria Avram, Ioan Manitiu, Aura Sinpetrean, Lucian Pop, Delia Lupu, Radu Usvat, Ana Petrisor, Nicoleta Dumitru, Camelia Moruju, Adelina Gheorghita, Magda V. Mitu, Cosmin Macarie, Ana Maria Pop, Maria-Catalina Diaconu, Iulia Grancea, Mihaela Cosma, Mihaela Crisan, Elizabeth Herron, Paul Nestel, Sally B. Kay, Kaye S. Carter, Imran Badshah, Ashley Makepeace, Jocelyn Drinkwater, Michelle England, Azette Rafei, Kylie Patterson, Alicia Jenkins, Sybil McAuley, Sue M. Kent, Joy E. Vibert, Leonie Perrett, Thomas David, Samantha L. Kaye, Monika O’Connor, Nimalie J. Perera, Nicole T. Lai, Kerry A. Kearins, Christinia Dicamillo, Heather Anderson, Louise Ferguson, Sharon D. Radtke, Charles T. Thamarappillil, Janice M. Boys, Anita K. Long, Toni Shanahan, Michael Nyguyen, Nicole Forrest, Gill Tulloch, Della Greenwell, Sarah L. Price, Aye N. Tint, Priya K. Sumithran, Tamara L. Debreceni, Lisa Walker, Mary Caruana, Kira Edwards, Maria Stathopoulos, Cilla Haywood, Dimitar Sajkov, Sharen Pringle, Anne Tabner, Kathrina Bartolay, Chamindi Abeyratne, Kylie Bragg, Patrick Mulhern, Peter Purnell, Lyn Williams, Jane Hamlyn, Aurelia Connelly, Jan Hoffman, Samantha Bailey, Jane Kerr, Zarnia Morrison, Sarah Maeder, Roberta McEwan, Prasanna Kunasekera, Patrice McGregor, Jo Young, Sharon Berry, Rick Cutfield, Michelle Choe, Catherine McNamara, Narrinder K. Shergill, Petra Crone, Miles G. Williams, Keith Dyson, Diana H. Schmid, Audrey C. Doak, Melissa Spooner, Colin Edwards, Anne Turner, Grainne M. McAnnalley, Raewyn A. Fisher, Fraser B. Hamilton, Denis H. Friedlander, Melissa R. Kirk, Jayne E. Scales, Marguerite A. McLelland, Neelam A. Dalman, Cathy E. Vickers, Carolyn Jackson, Wendy Coleman, Phillip I. Garden, and Wendy F. Arnold

Subjects
Male, medicine.medical_specialty, Rate ratio, Double-Blind Method, Ischemia, Risk Factors, Physiology (medical), Internal medicine, medicine, Clinical endpoint, Humans, Myocardial infarction, Coronary Artery Bypass, Stroke, Aged, business.industry, Unstable angina, Hazard ratio, Absolute risk reduction, Middle Aged, medicine.disease, Eicosapentaenoic Acid, Number needed to treat, Cardiology, Female, Cardiology and Cardiovascular Medicine, business
Abstract

Background: Despite advances in surgery and pharmacotherapy, there remains significant residual ischemic risk after coronary artery bypass grafting surgery. Methods: In REDUCE-IT (Reduction of Cardiovascular Events With Icosapent Ethyl–Intervention Trial), a multicenter, placebo-controlled, double-blind trial, statin-treated patients with controlled low-density lipoprotein cholesterol and mild to moderate hypertriglyceridemia were randomized to 4 g daily of icosapent ethyl or placebo. They experienced a 25% reduction in risk of a primary efficacy end point (composite of cardiovascular death, myocardial infarction, stroke, coronary revascularization, or hospitalization for unstable angina) and a 26% reduction in risk of a key secondary efficacy end point (composite of cardiovascular death, myocardial infarction, or stroke) when compared with placebo. The current analysis reports on the subgroup of patients from the trial with a history of coronary artery bypass grafting. Results: Of the 8179 patients randomized in REDUCE-IT, a total of 1837 (22.5%) had a history of coronary artery bypass grafting, with 897 patients randomized to icosapent ethyl and 940 to placebo. Baseline characteristics were similar between treatment groups. Randomization to icosapent ethyl was associated with a significant reduction in the primary end point (hazard ratio [HR], 0.76 [95% CI, 0.63–0.92]; P =0.004), in the key secondary end point (HR, 0.69 [95% CI, 0.56–0.87]; P =0.001), and in total (first plus subsequent or recurrent) ischemic events (rate ratio, 0.64 [95% CI, 0.50–0.81]; P =0.0002) compared with placebo. This yielded an absolute risk reduction of 6.2% (95% CI, 2.3%–10.2%) in first events, with a number needed to treat of 16 (95% CI, 10–44) during a median follow-up time of 4.8 years. Safety findings were similar to the overall study: beyond an increased rate of atrial fibrillation/flutter requiring hospitalization for at least 24 hours (5.0% vs 3.1%; P =0.03) and a nonsignificant increase in bleeding, occurrences of adverse events were comparable between groups. Conclusions: In REDUCE-IT patients with a history of coronary artery bypass grafting, treatment with icosapent ethyl was associated with significant reductions in first and recurrent ischemic events. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01492361.

Published
2021

30. The venom of the scorpion Centruroides limpidus, which causes the highest number of stings in Mexico, is neutralized by two recombinant antibody fragments

Author

Baltazar Becerril, Lidia Riaño-Umbarila, Luis Fernando Losoya-Uribe, Alejandro Olvera-Rodríguez, Guillermo Fernández-Taboada, and Ilse V. Gómez-Ramírez

Subjects
Phage display, medicine.drug_class, Immunology, Scorpion, Scorpion Venoms, chemical and pharmacologic phenomena, Venom, medicine.disease_cause, Monoclonal antibody, complex mixtures, law.invention, Scorpions, Mice, Neutralization Tests, law, biology.animal, medicine, Animals, Single-chain variable fragment, Amino Acid Sequence, Mexico, Molecular Biology, Mice, Inbred BALB C, Scorpion Stings, biology, Toxin, Chemistry, Antibodies, Monoclonal, respiratory system, Virology, Recombinant Proteins, Recombinant DNA, Hybridoma technology, Female, Cell Surface Display Techniques, Sequence Alignment, Single-Chain Antibodies
Abstract

Phage display and directed evolution have made it possible to generate recombinant antibodies in the format of single chain variable fragments (scFvs) capable of neutralizing different toxins and venoms of Mexican scorpions. Despite having managed to neutralize a significant number of venoms, some others have not yet been completely neutralized, due to the diversity of the toxic components present in them. An example is the venom of the scorpion Centruroides limpidus, which contains three toxins of medical importance, called Cll1, Cll2 and Cl13. The first two are neutralized by scFv 10FG2, while Cl13, due to its sequence divergence, was not even recognized. For this reason, the aim of the present work was the generation of a new scFv capable of neutralizing Cl13 toxin and thereby helping to neutralize the whole venom of this scorpion. By hybridoma technology, a monoclonal antibody (mAb B7) was generated, which was able to recognize and partially neutralize Cl13 toxin. From mAb B7, its scFv format was obtained, named scFv B7 and subjected to three cycles of directed evolution. At the end of these processes, scFv 11F which neutralized Cl13 toxin was obtained. This scFv, administered in conjunction with scFv 10FG2, allowed to fully neutralize the whole venom of Centruroides limpidus scorpion.

Published
2021

31. Breast Cancer Cells Reprogram the Oncogenic lncRNAs/mRNAs Coexpression Networks in Three-Dimensional Microenvironment

Author

Stephanie I. Nuñez-Olvera, Lorena Aguilar-Arnal, Mireya Cisneros-Villanueva, Alfredo Hidalgo-Miranda, Laurence A. Marchat, Yarely M. Salinas-Vera, Rosalio Ramos-Payán, Carlos Pérez-Plasencia, Ángeles Carlos-Reyes, Jonathan Puente-Rivera, and Cesar López-Camarillo

Subjects
Gene Expression Regulation, Neoplastic, Carcinogenesis, Chromosomal Proteins, Non-Histone, Tumor Microenvironment, Humans, Female, RNA, Long Noncoding, Breast Neoplasms, General Medicine, RNA, Messenger, Oncogenes, breast cancer, organotypic 3D cultures, lncRNAs, co-regulation networks, therapy response
Abstract

Organotypic three-dimensional (3D) cell cultures more accurately mimic the characteristics of solid tumors in vivo in comparison with traditional two-dimensional (2D) monolayer cell models. Currently, studies on the regulation of long non-coding RNAs (lncRNAs) have not been explored in breast cancer cells cultured in 3D microenvironments. In the present research, we studied the expression and potential roles of lncRNAs in estrogen receptor-positive luminal B subtype BT-474 breast cancer cells grown over extracellular matrix proteins-enriched 3D cultures. Global expression profiling using DNA microarrays identifies 290 upregulated and 183 downregulated lncRNAs in 3D cultures relative to 2D condition. Using a co-expression analysis approach of lncRNAs and mRNAs pairs expressed in the same experimental conditions, we identify hundreds of regulatory axes modulating genes involved in cancer hallmarks, such as responses to estrogens, cell proliferation, hypoxia, apical junctions, and resistance to endocrine therapy. In addition, we identified 102 lncRNAs/mRNA correlations in 3D cultures, which were similar to those reported in TCGA datasets obtained from luminal B breast cancer patients. Interestingly, we also found a set of mRNAs transcripts co-expressed with LINC00847 and CTD-2566J3.1 lncRNAs, which were predictors of pathologic complete response and overall survival. Finally, both LINC00847 and CTD -2566J3.1 were co-expressed with essential genes for cancer genetic dependencies, such as FOXA1 y GINS2. Our experimental and predictive findings show that co-expressed lncRNAs/mRNAs pairs exhibit a high degree of similarity with those found in luminal B breast cancer patients, suggesting that they could be adequate pre-clinical tools to identify not only biomarkers related to endocrine therapy response and PCR, but to understand the biological behavior of cancer cells in 3D microenvironments.

Published
2022
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32. Evolving Treatment Patterns and Outcomes of Neovascular Age-Related Macular Degeneration Over a Decade

Author

Bobby Paul, Maria Pikoula, A. K. Patwardhan, Abraham Olvera-Barrios, Andrew J. Lotery, A Davis, Vineeth Kumar, Salim Natha, Toks Akerele, Carolyn J.P. Jones, Usha Chakravarthy, Paul Taylor, Roy Schwartz, Haralabos Eleftheriadis, Sudeshna Patra, Christopher Brand, Peck-Lin Lip, Richard J Antcliff, Aaron Y. Lee, Alasdair Warwick, Geeta Menon, Faruque Ghanchi, U. Chakravarthy, Clare Bailey, Elizabeth Wilkinson, Sajjad Mahmood, Louise Downey, Raj Mukherjee, Catherine A Egan, Spiros Denaxas, James S Talks, Peck Lin Lip, Aires Lobo, Rehna Khan, Narendra Dhingra, Sheena George, Helen Palmer, and Adnan Tufail

Subjects
Male, Vascular Endothelial Growth Factor A, medicine.medical_specialty, Pediatrics, Time Factors, Younger age, Visual acuity, Fundus Oculi, Recombinant Fusion Proteins, Visual Acuity, Angiogenesis Inhibitors, Article, 03 medical and health sciences, 0302 clinical medicine, Ranibizumab, Ophthalmology, Age related, medicine, Electronic Health Records, Humans, Macula Lutea, National level, Fluorescein Angiography, Retrospective Studies, 030304 developmental biology, Aflibercept, 0303 health sciences, business.industry, Middle Aged, Macular degeneration, National health service, medicine.disease, Receptors, Vascular Endothelial Growth Factor, Treatment Outcome, Intravitreal Injections, Wet Macular Degeneration, 030221 ophthalmology & optometry, Female, medicine.symptom, business, Follow-Up Studies, medicine.drug
Abstract

PURPOSE: Management of neovascular age-related macular degeneration (nAMD) has evolved over the last decade with several treatment regimens and different medications. This study describes the treatment patterns and, importantly, visual outcomes over ten years in a large cohort of patients. DESIGN: Retrospective analysis of electronic health records from 27 National Health Service (NHS) secondary care healthcare providers in the UK. PARTICIPANTS: Treatment-naïve patients receiving at least three intravitreal anti-vascular endothelial growth factor (VEGF) injections for nAMD in their first six months of follow-up were included. Patients with missing data for age or gender and those aged less than 55 were excluded. METHODS: Eyes with at least three years of follow-up were grouped by years of treatment initiation, and three-year outcomes were compared between the groups. Data were generated during routine clinical care between 09/2008 and 12/2018. MAIN OUTCOME MEASURES: Visual acuity, number of injections, number of visits. RESULTS: A total of 15,810 eyes of 13,705 patients receiving 194,904 injections were included. Visual acuity (VA) improved from baseline during the first year, but dropped thereafter, resulting in loss of visual gains. This trend remained consistent throughout the past decade. Although an increasing proportion of eyes remained in the driving standard, this was driven by better presenting visual acuities over the decade. The number of injections dropped substantially between the first and subsequent years, from a mean of 6.25 in year 1 to 3 in year 2 and 2.5 in year 3, without improvement over the decade. In a multivariable regression analysis, final VA improved by 0.24 letters for each year since 2008, and younger age and baseline VA were significantly associated with VA at three years. CONCLUSION: Our findings show that despite improvement in functional VA over the years, primarily driven by improving baseline VA, patients continue to lose vision after the first year of treatment, with only marginal change over the past decade. The data suggest that these results may be related to suboptimal treatment patterns, which have not improved over the years. Rethinking treatment strategies may be warranted, possibly on a national level or through the introduction of longer-acting therapies.

Published
2021

33. Differential proMMP-2 and proMMP-9 secretion in human pre-implantation embryos at day 5 of development

Author

Jair Lozano-Cuenca, Jorge Skiold López-Canales, Héctor Flores-Herrera, Esther Iyune-Cojab, Paola Vázquez-Cárdenas, Mauricio Osorio-Caballero, Mercedes Olvera-Valencia, and Ricardo Josué Acuña-González

Subjects
Enzyme Precursors, business.industry, Embryonic Development, Embryo, Biology, General Biochemistry, Genetics and Molecular Biology, Cell biology, Culture Media, Text mining, Matrix Metalloproteinase 9, Gelatinases, Pregnancy, Humans, Matrix Metalloproteinase 2, Secretion, Female, business
Abstract

Background: The most commonly used non-invasive criterion for evaluating the probable success of transferring in vitro human embryos for implantation is their morphological development. With this criterion, however, embryos in cellular arrests go unnoticed. Extracellular matrix metalloproteases type 2 (MMP-2) and MMP-9 are key markers of embryonic development and the implantation process, according to various animal studies. The current study investigated the proMMP-2 and proMMP-9 expression in the culture media developing human embryos that were transferred for implantation. Methods: Forty-two patients were accepted in the Department of Reproductive Biology of a Hospital in México City, based on the Institutional inclusion criteria for in vitro fertilization. On day 5 of development, embryos were transferred to women, and the culture medium was stored at -70 to await assessment of the activity of proMMP-2 and proMMP-9 in substrate gel zymography. Results: The patients showing embryo sac development were assigned to the pregnant group (n =17) or non-pregnant (n =25). In both groups, the activity of proMMP-2 and proMMP-9 was evaluated in substrate gel zymography. Our results indicate for all 17 women able to achieve a full-term pregnancy, the activity band of proMMP-2 was found in the corresponding culture medium. For 11 of them, the band of proMMP-9. Regarding the other 25 patients, the expression band for proMMP-2 detected in 3 and that proMMP-9 in 11 individuals. Conclusions: On day 5 of embryo development, the evaluation of proMMP-2 and proMMP-9 in the embryo culture medium is a reliable indicator of embryo quality and capacity to establish pregnancy.

Published
2022

34. Contextualizing single‐arm trials with real‐world data: An emulated target trial comparing therapies for neovascular age‐related macular degeneration

Author

Philipp L. Müller, Paul Taylor, Roy Schwartz, Praveen J. Patel, Alasdair Warwick, Abraham Olvera-Barrios, Darren S. Thomas, Catherine A Egan, Aaron Y. Lee, Tjebo F. C. Heeren, and Adnan Tufail

Subjects
Counterfactual thinking, Male, 030213 general clinical medicine, Visual acuity, Visual Acuity, 030226 pharmacology & pharmacy, law.invention, Cohort Studies, Macular Degeneration, 0302 clinical medicine, Randomized controlled trial, law, Pro re nata, Multicenter Studies as Topic, General Pharmacology, Toxicology and Pharmaceutics, Aflibercept, Aged, 80 and over, General Neuroscience, General Medicine, Articles, Bevacizumab, Treatment Outcome, Data Interpretation, Statistical, Female, medicine.symptom, Public aspects of medicine, RA1-1270, medicine.drug, medicine.medical_specialty, Recombinant Fusion Proteins, RM1-950, Equivalence Trials as Topic, General Biochemistry, Genetics and Molecular Biology, Article, 03 medical and health sciences, Physical medicine and rehabilitation, medicine, Humans, Computer Simulation, Aged, business.industry, Research, Off-Label Use, Macular degeneration, medicine.disease, Receptors, Vascular Endothelial Growth Factor, Propensity score matching, Observational study, Therapeutics. Pharmacology, business
Abstract

One‐in‐four ophthalmology trials are single‐armed, which poses challenges to their interpretation. We demonstrate how real‐world cohorts used as external/synthetic control arms can contextualize such trials. We herein emulated a target trial on the intention‐to‐treat efficacy of off‐label bevacizumab (q6w) pro re nata relative to fixed‐interval aflibercept (q8w) for improving week 54 visual acuity of eyes affected by neovascular age‐related macular degeneration. The bevacizumab arm (n = 65) was taken from the ABC randomized controlled trial. A total of 4,471 aflibercept‐treated eyes aligning with the ABC trial eligibility were identified from electronic health records and synthetic control arms were created by emulating randomization conditional on age, sex, and baseline visual read via exact matching and propensity score methods. We undertook an inferiority analysis on mean difference at 54 weeks; outcomes regression on achieving a change in visual acuity of greater than or equal to 15, greater than or equal to 10, and less than or equal to −15 Early Treatment Diabetic Retinopathy (ETDRS) letters at week 54; and a time‐to‐event analysis on achieving a change in visual acuity of greater than or equal to 15, greater than or equal to 10, and less than or equal to −15 ETDRS letters by week 54. The findings suggest off‐label bevacizumab to be neither inferior nor superior to licensed aflibercept. Our study highlights how real‐world cohorts representing the counterfactual intervention could aid the interpretation of single‐armed trials when analyzed in accord to the target trial framework. Study Highlights WHAT IS THE CURRENT KNOWLEDGE ON THE TOPIC? One‐in‐four randomized controlled trials in ophthalmology are single‐armed, which poses challenges for interpreting their efficacy relative to standard of care. Recent conceptual advances in the methods of causal inference and in the emulation of target trials suggests that the standard‐of‐care arms representing the counterfactual intervention can be approximated with observational data. WHAT QUESTION DID THIS STUDY ADDRESS? How real‐world cohorts representing the counterfactual intervention can aid the interpretation of single‐armed ophthalmological trials. WHAT DOES THIS STUDY ADD TO OUR KNOWLEDGE? Our study highlights how real‐world cohorts representing the counterfactual intervention could aid the interpretation of single‐armed ophthalmological trials when undertaken in accord with the target trial framework. HOW MIGHT THIS CHANGE CLINICAL PHARMACOLOGY OR TRANSLATIONAL SCIENCE? External counterfactual arms could reduce the time and cost to reach potential regulatory approval.

Published
2021

35. How to deal with this complication: Intraoperative anterior cage migration in L5-S1 resolved with a lumbar hybrid fusion technique

Author

Javier, Quillo-Olvera, Diego, Quillo-Olvera, Javier, Quillo-Reséndiz, and Jin-Sung, Kim

Subjects
Lumbar Vertebrae, Spinal Fusion, Treatment Outcome, Lumbosacral Region, Humans, Female, Retroperitoneal Space, Aged
Abstract

Anterior cage migration is the most infrequent and dangerous complication seen in posterior lumbar interbody fusion (PLIF) procedures. We report the case of a 74-year-old woman who underwent PLIF at the L5-S1 level. During the surgery, one of the PLIF-cages dislodged anteriorly into the abdominal cavity without vascular injury. An anterior retroperitoneal approach to remove the cage and complete the fusion was made. The patient was discharged 2 weeks later with encouraging clinical results. In a patient hemodynamically stable, removing the cage by a vascular surgeon, and complete the Anterior Lumbar Interbody Fusion could be a feasible option at L5-S1.La migración anterior del implante para fusión lumbar es la complicación más infrecuente y peligrosa asociada a la fusión intersomática posterior (PLIF). Reportamos el caso de un paciente femenino de 74 años, operada de PLIF en L5-S1. Durante la cirugía, una de las cajas usadas migró a la cavidad abdominal, sin ocasionar lesión vascular. Para remover el implante y completar la fusión lumbar un abordaje retroperitoneal anterior fue realizado. La paciente fue egresada 2 semanas después con éxito. En un paciente hemodinamicamente estable, este abordaje puede ser una opción para revertir la complicación y completar la fusión lumbar vía anterior.

Published
2021

36. Increased visceral fat accumulation modifies the effect of insulin resistance on arterial stiffness and hypertension risk

Author

Neftali Eduardo Antonio-Villa, Omar Yaxmehen Bello-Chavolla, Arsenio Vargas-Vázquez, Roopa Mehta, Carlos A. Fermín-Martínez, Alexandro J. Martagón-Rosado, Daphne Abigail Barquera-Guevara, Carlos A. Aguilar-Salinas, Olimpia Arellano-Campos, Donaji V. Gómez-Velasco, Tania Viveros-Ruiz, Ivette Cruz-Bautista, Marco A. Melgarejo-Hernandez, Paloma Almeda-Valdés, Liliana Muñoz-Hernandez, Daniel Elias-Lopez, Fabiola Mabel Del Razo-Olvera, Bethsabel Rodríguez Encinas, Renán Fernando Fagoaga Ramírez, Luz E. Guillén, José de Jesús Garduño-García, Ulices Alvirde, Yukiko Ono-Yoshikawa, Ricardo Choza-Romero, Leobardo Sauque-Reyna, Ma. Eugenia Garay-Sevilla, Juan M. Malacara-Hernandez, María Teresa Tusié-Luna, Luis Miguel Gutierrez-Robledo, Francisco J. Gómez-Pérez, and Rosalba Rojas

Subjects
Adult, Blood Glucose, Male, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, Medicine (miscellaneous), Adipose tissue, 030209 endocrinology & metabolism, Intra-Abdominal Fat, 030204 cardiovascular system & hematology, Risk Assessment, Hypertension risk, 03 medical and health sciences, Vascular Stiffness, 0302 clinical medicine, Insulin resistance, Internal medicine, medicine, Humans, Insulin, Arterial Pressure, Prospective Studies, Prospective cohort study, Mexico, Adiposity, Cardiometabolic risk, Nutrition and Dietetics, business.industry, Incidence, Cardiometabolic Risk Factors, nutritional and metabolic diseases, Increased visceral fat, Middle Aged, medicine.disease, Cross-Sectional Studies, Blood pressure, Hypertension, Arterial stiffness, Cardiology, Female, Insulin Resistance, Cardiology and Cardiovascular Medicine, business, Biomarkers
Abstract

Background and aims Both insulin resistance (IR) and visceral adipose tissue (VAT) are related cardiometabolic risk factors; nevertheless, their joint effect on endothelial functionality is controversial. This study aims to evaluate the joint effect of IR and VAT on endothelial functionality using the pulse-waveform analysis and explore the mediating role of VAT on the effect of IR on arterial pressure, arterial stiffness and incident arterial hypertension. Methods and results We measured VAT (n = 586) using two methods (dual-energy X-ray absorptiometry and a clinical surrogate), arterial stiffness (with pulse-waveform velocity), and IR (using three methods: HOMA2-IR (n = 586), a frequently sampled intravenous glucose tolerance test (n = 131) and euglycemic hyperinsulinemic clamping (n = 97)) to confirm the mediator effect of IR on VAT. The incidence of arterial hypertension attributable to the mediating effect of IR related to VAT was evaluated using a prospective cohort (n = 6850). Adjusted linear regression models, causal mediation analysis, and Cox-proportional hazard risk regression models were performed to test our objective. IR and VAT led to increased arterial stiffness and increased blood pressure; the combination of both further worsened vascular parameters. Nearly, 57% (ΔE→MY 95% CI: 31.7–100.0) of the effect of IR on altered pulse-wave velocity (PWV) analysis was mediated through VAT. Moreover, VAT acts as a mediator of the effect of IR on increased mean arterial pressure (ΔE→MY 35.7%, 95% CI: 23.8–59) and increased hypertension risk (ΔE→MY 69.1%, 95% CI: 46.1–78.8). Conclusion VAT acts as a mediator of IR in promoting arterial stiffness and arterial hypertension. Both phenomena should be targeted to ameliorate the cardiometabolic risk.

Published
2021

37. Genetically Defined, Syngeneic Organoid Platform for Developing Combination Therapies for Ovarian Cancer

Author

Wei Wei, Connor Foster, Benjamin G. Neel, Douglas A. Levine, Narciso Olvera, Fanny Dao, Robert A. Weinberg, Shengqing Gu, Shuang Zhang, Sonia Iyer, Hao Ran, Igor Dolgalev, and Cynthia Loomis

Subjects
0301 basic medicine, Chemokine, endocrine system diseases, medicine.medical_treatment, Mice, Transgenic, Biology, medicine.disease_cause, Article, Mice, 03 medical and health sciences, 0302 clinical medicine, Immune system, Tumor Microenvironment, medicine, Organoid, Animals, Fallopian Tube Neoplasms, Humans, CRISPR, Ovarian Neoplasms, Immunotherapy, medicine.disease, Cystadenocarcinoma, Serous, 3. Good health, Gene Expression Regulation, Neoplastic, Mice, Inbred C57BL, Disease Models, Animal, Serous fluid, 030104 developmental biology, Oncology, 030220 oncology & carcinogenesis, Cancer research, biology.protein, Female, KRAS, Ovarian cancer
Abstract

The paucity of genetically informed, immunocompetent tumor models impedes evaluation of conventional, targeted, and immune therapies. By engineering mouse fallopian tube epithelial organoids using lentiviral gene transduction and/or CRISPR/Cas9 mutagenesis, we generated multiple high-grade serous tubo-ovarian cancer (HGSC) models exhibiting mutational combinations seen in patients with HGSC. Detailed analysis of homologous recombination (HR)–proficient (Trp53−/−;Ccne1OE;Akt2OE;KrasOE), HR-deficient (Trp53−/−;Brca1−/−;MycOE), and unclassified (Trp53−/−;Pten−/−;Nf1−/−) organoids revealed differences in in vitro properties (proliferation, differentiation, and “secretome”), copy-number aberrations, and tumorigenicity. Tumorigenic organoids had variable sensitivity to HGSC chemotherapeutics, and evoked distinct immune microenvironments that could be modulated by neutralizing organoid-produced chemokines/cytokines. These findings enabled development of a chemotherapy/immunotherapy regimen that yielded durable, T cell–dependent responses in Trp53−/−;Ccne1OE;Akt2OE;Kras HGSC; in contrast, Trp53−/−;Pten−/−;Nf1−/− tumors failed to respond. Mouse and human HGSC models showed genotype-dependent similarities in chemosensitivity, secretome, and immune microenvironment. Genotype-informed, syngeneic organoid models could provide a platform for the rapid evaluation of tumor biology and therapeutics. Significance: The lack of genetically informed, diverse, immunocompetent models poses a major barrier to therapeutic development for many malignancies. Using engineered fallopian tube organoids to study the cell-autonomous and cell-nonautonomous effects of specific combinations of mutations found in HGSC, we suggest an effective combination treatment for the currently intractable CCNE1-amplified subgroup. This article is highlighted in the In This Issue feature, p. 211

Published
2021

38. TL1A–DR3 Plasma Levels Are Predictive of HIV-1 Disease Control, and DR3 Costimulation Boosts HIV-1–Specific T Cell Responses

Author

Beatriz Mothe, Bonaventura Clotet, Eugenia Negredo, Marta Massanella, Jorge Sanchez, Dennis J. Hartigan-O'Connor, Carmela Ganoza, Christian Brander, Marta Ruiz-Riol, Maria Luz Calle, Julià Blanco, Clara Duran-Castells, Judith Dalmau, Alex Olvera, Javier Martinez-Picado, Bruna Oriol-Tordera, and Anuska Llano

Subjects
CD4-Positive T-Lymphocytes, Male, HIV Infections, Antibodies, Monoclonal, Murine-Derived, Mice, 0302 clinical medicine, immune system diseases, Receptors, Monoclonal, 2.1 Biological and endogenous factors, Immunology and Allergy, Aetiology, biology, 3. Good health, Infectious Diseases, medicine.anatomical_structure, HIV/AIDS, Female, Antibody, Infection, Biotechnology, Tumor Necrosis Factor Ligand Superfamily Member 15, Murine-Derived, Regulatory T cell, T cell, Immunology, Peripheral blood mononuclear cell, Article, Antibodies, Virus, Vaccine Related, 03 medical and health sciences, Immune system, Clinical Research, Genetics, medicine, Animals, Humans, Receptors, Tumor Necrosis Factor, Member 25, Member 25, Prevention, CD4 Lymphocyte Count, Good Health and Well Being, HIV-1, biology.protein, Tumor Necrosis Factor, CD8, 030215 immunology
Abstract

Relative control of HIV-1 infection has been linked to genetic and immune host factors. In this study, we analyzed 96 plasma proteome arrays from chronic untreated HIV-1–infected individuals using the classificatory random forest approach to discriminate between uncontrolled disease (plasma viral load [pVL] >50,000 RNA copies/ml; CD4 counts 283 cells/mm3, n = 47) and relatively controlled disease (pVL

Published
2020

39. Efficacy and Safety of Sodium Hyaluronate/chondroitin Sulfate Preservative-free Ophthalmic Solution in the Treatment of Dry Eye: A Clinical Trial

Author

Belalcázar-Rey, Sandra, Sánchez-Huerta, Valeria, Ochoa-Tabares, Juan, Altamirano-Vallejo, Samuel, Soto-Gómez, Abraham, Suárez-Velasco, Rubén, García-Félix, Filiberto, Baiza-Durán, Leopoldo, Olvera-Montaño, Oscar, and Muñoz-Villegas, Patricia

Subjects
Adult, Male, medicine.medical_specialty, genetic structures, Sodium hyaluronate, Visual Acuity, Administration, Ophthalmic, Ocular surface disease, Fluorophotometry, Young Adult, 03 medical and health sciences, Cellular and Molecular Neuroscience, chemistry.chemical_compound, 0302 clinical medicine, Double-Blind Method, Ophthalmology, Humans, Medicine, In patient, Prospective Studies, Dry eye disease, Chondroitin sulfate, Preservative free, Hyaluronic Acid, Intraocular Pressure, Aged, Aged, 80 and over, business.industry, Chondroitin Sulfates, Preservatives, Pharmaceutical, Middle Aged, Artificial tears, Clinical Trial, eye diseases, Sensory Systems, Clinical trial, Drug Combinations, Treatment Outcome, chemistry, Tears, 030221 ophthalmology & optometry, Dry Eye Syndromes, Female, Ophthalmic Solutions, business, Ocular surface, 030217 neurology & neurosurgery
Abstract

Purpose: The present study was designed to evaluate the efficacy and safety of sodium hyaluronate/chondroitin sulfate, preservative-free ophthalmic solution (SH/CS-PF) in patients with mild-moderate dry eye disease (DED). Methods: This was a randomized phase IV, multicenter, prospective, double-blind, clinical trial. A total of 217 subjects were randomized (1:1:1) and completed the study. Subjects were assigned to receive either SH/CS-PF (n=72), PEG/PG (n=64) or PEG/PG-PF (n=81). Subjects instilled a drop four times a day (QID) for 90 days. The primary efficacy endpoints were conjunctival goblet cell density, Nelson’s grades, fluorescein tear break-up time (TBUT), Ocular Surface Disease Index (OSDI), and, Schirmer’s test. The tolerability was measured by the ocular symptomatology, and safety was assayed by corneal staining, intraocular pressure (IOP), visual acuity (VA) and adverse events (AE).

Published
2020

40. Relación entre la medición por tomografía y ecografía del diámetro de la vaina del nervio óptico como estimador no invasivo de la presión intracraneal

Author

Tania Rojas-Murillo and Natael Olvera-González

Subjects
Male, Humans, Surgery, Female, Optic Nerve, Prospective Studies, Intracranial Hypertension, Tomography, X-Ray Computed, Ultrasonography
Abstract

To compare the ONSD measured by ultrasound and tomography in patients with a diagnosis of intracranial hypertension.Prospective, transversal, observational, analytical study. 105 patients were included, divided into two groups: healthy (control group) and patients presenting clinical data of intracranial hypertension (study group). ONSD was measured by ultrasound and tomography. The Kruskal-Wallis test was used to compare the ONSD between the patients, and the Spearman test was used to assess the correlation between USG and CT. A value of p0.05 was considered statistically significant.Of the 105 patients, 58.1% were men and 41.9% women. The study group included 14 patients with TBI, CVD, intracranial neoplasia, or neuroinfection. The highest median of ONSD by Ultrasound was in the CVD group, followed by TBI, neoplasia and neuroinfection and the lowest was in the control group (7.5, 7.0, 6.8, 6.8 and 5.2 mm respectively); these differences being statistically significant (p0.001). In the correlation analysis between Ultrasound and CT, a good statistically significant positive correlation was found (rho = 0.893, p0.001).The ultrasound evaluation of ONSD has proven to be a reliable test for the diagnosis and non-invasive monitoring of intracranial hypertension.Comparar el diámetro de la vaina del nervio óptico (DVNO) medido por ultrasonografía (USG) y tomografía computarizada (TC) en pacientes con diagnóstico de hipertensión intracraneal.Estudio prospectivo, transversal, observacional y analítico. Se incluyeron 105 pacientes divididos en dos grupos: sanos (grupo control) y pacientes que presentaran datos clínicos de hipertensión intracraneal (grupo de estudio). Se midió el DVNO por USG y TC. Para comparar el DVNO entre los pacientes se utilizó la prueba de Kruskal-Wallis, y para evaluar la correlación entre USG y TC se utilizó la prueba de Spearman. Un valor de p0.05 fue considerado estadísticamente significativo.De los 105 pacientes, el 58.1% eran hombres y el 41.9% mujeres. El grupo de estudio incluyó 14 pacientes con traumatismo craneoencefálico (TCE), evento vascular cerebral (EVC), neoplasia intracraneal o neuroinfección. La mayor mediana de DVNO por USG la tuvo el grupo de EVC, seguido de los pacientes con TCE, neoplasia y neuroinfección, y la menor la tuvo el grupo control (7.5, 7.0, 6.8, 6.8 y 5.2 mm, respectivamente), siendo estas diferencias estadísticamente significativas (p0.001). En el análisis de correlación entre USG y TC se encontró una buena correlación positiva estadísticamente significativa (rho = 0.893, p0.001).La evaluación por USG del DVNO ha demostrado ser una prueba confiable para el diagnóstico y el monitoreo no invasivo de la hipertensión intracraneal.

Published
2022

41. NR3C1 and glucocorticoid-regulatory genes mRNA and protein expression in the endometrium and ampulla during the bovine estrous cycle

Author

Mateo Ruiz-Conca, Jaume Gardela, Sergi Olvera-Maneu, Manel López-Béjar, and Manuel Álvarez-Rodríguez

Subjects
Reumatologi och inflammation, General Veterinary, Cow, Western blot, Estrous Cycle, Glucocorticoid, Cortisol, Steroid receptors, qPCR, Qpcr, Endometrium, Genes, Regulator, Animals, Female, Cattle, RNA, Messenger, Glucocorticoids, Rheumatology and Autoimmunity
Abstract

Altres ajuts: acords transformatius de la UAB The bovine reproductive tract exhibits changes during the estrous cycle modulated by the interplay of steroid hormones. Glucocorticoids can be detrimental when stress-induced but are relevant at baseline levels for appropriate reproductive function. Here, an analysis of quantitative real-time PCR was performed to study the bovine glucocorticoid-related baseline gene transcription in endometrial and ampullar tissue samples derived from three time points of the estrous cycle, stage I (Days 1-4), stage III (Days 11-17) and stage IV (Days 18-20). Our results revealed expression differences during stages, as expression observed in the ampulla was higher during the post-ovulatory phase (stage I), including the glucocorticoid receptor NR3C1, and some of its regulators, involved in glucocorticoid availability (HSD11B1 and HSD11B2) and transcriptional actions (FKBP4 and FKBP5). In contrast, in the endometrium, higher expression of the steroid receptors was observed during the late luteal phase (stage III), including ESR1, ESR2, PGRMC1 and PGRMC2, and HSD11B1 expression decreased, while HSD11B2 increased. Moreover, at protein level, FKBP4 was higher expressed during the late luteal phase, and NR3C1 during the pre-ovulatory phase (stage IV). These results suggest that tight regulation of the glucocorticoid activity is promoted in the ampulla, when reproductive events are taking place, including oocyte maturation. Moreover, most expression changes in the endometrium were observed during the late luteal phase, and may be related to the embryonic maternal recognition. In conclusion, the glucocorticoid regulation changes across the estrous cycle and may be playing a role on the reproductive events occurring in the bovine ampulla and endometrium.

Published
2022

42. Risk profiles and one-year outcomes of patients with newly diagnosed atrial fibrillation in India: Insights from the GARFIELD-AF Registry

Author

Jitendra PS. Sawhney, Veerappa A. Kothiwale, Vikas Bisne, Rajashekhar Durgaprasad, Praveen Jadhav, Manoj Chopda, Velam Vanajakshamma, Ramdhan Meena, Govindan Vijayaraghavan, Kamaldeep Chawla, Jagan Allu, Karen S. Pieper, A. John Camm, Ajay K. Kakkar, Jean-Pierre Bassand, David A. Fitzmaurice, Samuel Z. Goldhaber, Shinya Goto, Sylvia Haas, Werner Hacke, Lorenzo G. Mantovani, Frank Misselwitz, Alexander G.G. Turpie, Martin van Eickels, Freek W.A. Verheugt, Gloria Kayani, Keith A.A. Fox, Bernard J. Gersh, Hector Lucas Luciardi, Harry Gibbs, Marianne Brodmann, Frank Cools, Antonio Carlos Pereira Barretto, Stuart J. Connolly, Alex Spyropoulos, John Eikelboom, Ramon Corbalan, Dayi Hu, Petr Jansky, Jørn Dalsgaard Nielsen, Hany Ragy, Pekka Raatikainen, Jean-Yves Le Heuzey, Harald Darius, Matyas Keltai, Sanjay Kakkar, Jitendra Pal Singh Sawhney, Giancarlo Agnelli, Giuseppe Ambrosio, Yukihiro Koretsune, Carlos Jerjes Sánchez Díaz, Hugo Ten Cate, Dan Atar, Janina Stepinska, Elizaveta Panchenko, Toon Wei Lim, Barry Jacobson, Seil Oh, Xavier Viñolas, Marten Rosenqvist, Jan Steffel, Pantep Angchaisuksiri, Ali Oto, Alex Parkhomenko, Wael Al Mahmeed, David Fitzmaurice, D.Y. Hu, K.N. Chen, Y.S. Zhao, H.Q. Zhang, J.Z. Chen, S.P. Cao, D.W. Wang, Y.J. Yang, W.H. Li, Y.H. Yin, G.Z. Tao, P. Yang, Y.M. Chen, S.H. He, Ying Wang, Yong Wang, G.S. Fu, X. Li, T.G. Wu, X.S. Cheng, X.W. Yan, R.P. Zhao, M.S. Chen, L.G. Xiong, P. Chen, Y. Jiao, Y. Guo, L. Xue, F.Z. Wang, H. Li, Z.M. Yang, C.L. Bai, J. Chen, J.Y. Chen, X. Chen, S. Feng, Q.H. Fu, X.J. Gao, W.N. Guo, R.H. He, X.A. He, X.S. Hu, X.F. Huang, B. Li, J. Li, L. Li, Y.H. Li, T.T. Liu, W.L. Liu, Y.Y. Liu, Z.C. Lu, X.L. Luo, T.Y. Ma, J.Q. Peng, X. Sheng, X.J. Shi, Y.H. Sun, G. Tian, K. Wang, L. Wang, R.N. Wu, Q. Xie, R.Y. Xu, J.S. Yang, L.L. Yang, Q. Yang, Y. Ye, H.Y. Yu, J.H. Yu, T. Yu, H. Zhai, Q. Zhan, G.S. Zhang, Q. Zhang, R. Zhang, Y. Zhang, W.Y. Zheng, B. Zhou, Z.H. Zhou, X.Y. Zhu, S. Kakkar, J.P.S. Sawhney, P. Jadhav, R. Durgaprasad, A.G. Ravi Shankar, R.K. Rajput, K. Bhargava, R. Sarma, A. Srinivas, D. Roy, U.M. Nagamalesh, M. Chopda, R. Kishore, G. Kulkarni, P. Chandwani, R.A. Pothiwala, M. Padinhare Purayil, S. Shah, K. Chawla, V.A. Kothiwale, B. Raghuraman, G. Vijayaraghavan, V.M. Vijan, G. Bantwal, V. Bisne, A. Khan, J.B. Gupta, S. Kumar, D. Jain, S. Abraham, D. Adak, A. Barai, H. Begum, P. Bhattacharjee, M. Dargude, D. Davies, B. Deshpande, P. Dhakrao, V. Dhyani, S. Duhan, M. Earath, A. Ganatra, S. Giradkar, V. Jain, R. Karthikeyan, L. Kasala, S. Kaur, S. Krishnappa, A. Lawande, B. Lokesh, N. Madarkar, R. Meena, P. More, D. Naik, K. Prashanth, M. Rao, N.M. Rao, N. Sadhu, D. Shah, M. Sharma, P. Shiva, S. Singhal, S. Suresh, V. Vanajakshamma, S.G. Panse, Y. Koretsune, S. Kanamori, K. Yamamoto, K. Kumagai, Y. Katsuda, K. Sadamatsu, F. Toyota, Y. Mizuno, I. Misumi, H. Noguchi, S. Ando, T. Suetsugu, M. Minamoto, Hiroshi Oda, K. Shiraishi, S. Adachi, K. Chiba, H. Norita, M. Tsuruta, T. Koyanagi, H. Ando, T. Higashi, K. Okada, S. Azakami, S. Komaki, K. Kumeda, T. Murayama, J. Matsumura, Y. Oba, R. Sonoda, K. Goto, K. Minoda, Y. Haraguchi, H. Suefuji, H. Miyagi, H. Kato, Tadashi Nakamura, Tsugihiro Nakamura, H. Nandate, R. Zaitsu, Yoshihisa Fujiura, A. Yoshimura, H. Numata, J. Ogawa, H. Tatematsu, Y. Kamogawa, K. Murakami, Y. Wakasa, M. Yamasawa, H. Maekawa, S. Abe, H. Kihara, S. Tsunoda, Katsumi Saito, Kazuyuki Saito, T. Fudo, K. Obunai, H. Tachibana, I. Oba, T. Kuwahata, S. Higa, M. Gushiken, T. Eto, H. Yoshida, D. Ikeda, Yoshitake Fujiura, M. Ishizawa, M. Nakatsuka, K. Murata, C. Ogurusu, M. Shimoyama, M. Akutsu, I. Takamura, F. Hoshino, N. Yokota, T. Iwao, K. Tsuchida, M. Takeuchi, Y. Hatori, Y. Kitami, Yoichi Nakamura, R. Oyama, M. Ageta, Hiroyuki Oda, Y. Go, K. Mishima, T. Unoki, S. Morii, Yuhei Shiga, H. Sumi, T. Nagatomo, K. Sanno, K. Fujisawa, Y. Atsuchi, T. Nagoshi, T. Seto, T. Tabuchi, M. Kameko, K. Nii, K. Oshiro, H. Takezawa, S. Nagano, N. Miyamoto, M. Iwaki, Yuichiro Nakamura, M. Fujii, M. Okawa, Masahiko Abe, Masatake Abe, Mitsunori Abe, T. Saito, T. Mito, K. Nagao, J. Minami, T. Mita, I. Sakuma, T. Taguchi, S. Marusaki, H. Doi, M. Tanaka, T. Fujito, M. Matsuta, T. Kusumoto, S. Kakinoki, K. Ashida, N. Yoshizawa, J. Agata, O. Arasaki, M. Manita, M. Ikemura, S. Fukuoka, H. Murakami, S. Matsukawa, Y. Hata, T. Taniguchi, T. Ko, H. Kubo, M. Imamaki, M. Akiyama, M. Inagaki, H. Odakura, T. Ueda, Y. Katsube, A. Nakata, H. Watanabe, M. Techigawara, M. Igarashi, K. Taga, T. Kimura, S. Tomimoto, M. Shibuya, M. Nakano, K. Ito, T. Seo, S. Hiramitsu, H. Hosokawa, M. Hoshiai, M. Hibino, K. Miyagawa, Hajime Horie, N. Sugishita, Yukio Shiga, A. Soma, K. Neya, Tetsuro Yoshida, Tomoki Yoshida, M. Mizuguchi, M. Ishiguro, T. Minagawa, M. Wada, H. Mukawa, F. Okuda, S. Nagasaka, Y. Abe, Sen Adachi, Susumu Adachi, T. Adachi, K. Akahane, T. Amano, K. Aoki, T. Aoyama, H. Arai, S. Arima, T. Arino, H. Asano, T. Asano, J. Azuma, T. Baba, T. Betsuyaku, H. Chibana, H. Date, J. Doiuchi, Y. Emura, M. Endo, Y. Fujii, R. Fujiki, A. Fujisawa, Y. Fujisawa, T. Fukuda, T. Fukui, N. Furukawa, T. Furukawa, W. Furumoto, T. Goto, M. Hamaoka, N. Hanazono, K. Hasegawa, T. Hatsuno, Y. Hayashi, K. Higuchi, K. Hirasawa, H. Hirayama, M. Hirose, S. Hirota, M. Honda, Hideki Horie, T. Ido, O. Iiji, H. Ikeda, K. Ikeda, K. Ikeoka, M. Imaizumi, H. Inaba, T. Inoue, F. Iseki, A. Ishihara, N. Ishioka, N. Ito, T. Iwase, H. Kakuda, J. Kamata, H. Kanai, H. Kanda, M. Kaneko, H. Kano, T. Kasai, T. Kato, Y. Kato, Y. Kawada, K. Kawai, K. Kawakami, S. Kawakami, T. Kawamoto, S. Kawano, J. Kim, T. Kira, H. Kitazawa, H. Kitazumi, T. Kito, T. Kobayashi, T. Koeda, J. Kojima, H. Komatsu, I. Komatsu, Y. Koshibu, T. Kotani, T. Kozuka, Y. Kumai, T. Kumazaki, I. Maeda, K. Maeda, Y. Maruyama, S. Matsui, K. Matsushita, Y. Matsuura, K. Mineoi, H. Mitsuhashi, N. Miura, S. Miyaguchi, S. Miyajima, H. Miyamoto, A. Miyashita, S. Miyata, I. Mizuguchi, A. Mizuno, T. Mori, O. Moriai, K. Morishita, O. Murai, Sho Nagai, Shunichi Nagai, E. Nagata, H. Nagata, A. Nakagomi, S. Nakahara, M. Nakamura, R. Nakamura, N. Nakanishi, T. Nakayama, R. Nakazato, T. Nanke, J. Nariyama, Y. Niijima, H. Niinuma, Y. Nishida, Y. Nishihata, K. Nishino, H. Nishioka, K. Nishizawa, I. Niwa, K. Nomura, S. Nomura, M. Nozoe, T. Ogawa, N. Ohara, M. Okada, K. Okamoto, H. Okita, M. Okuyama, H. Ono, T. Ono, Y. Onuki Pearce, S. Oriso, A. Ota, E. Otaki, Y. Saito, H. Sakai, N. Sakamoto, Y. Sakamoto, Y. Samejima, Y. Sasagawa, H. Sasaguri, A. Sasaki, T. Sasaki, Kazuki Sato, Kiyoharu Sato, M. Sawano, S. Seki, Y. Sekine, Y. Seta, K. Sezaki, N. Shibata, Y. Shiina, H. Shimono, Y. Shimoyama, T. Shindo, H. Shinohara, R. Shinohe, T. Shinozuka, T. Shirai, T. Shiraiwa, Y. Shozawa, T. Suga, C. Sugimoto, Kazuo Suzuki, Keita Suzuki, Shu Suzuki, Shunji Suzuki, Susumu Suzuki, Y. Suzuki, M. Tada, A. Taguchi, T. Takagi, Y. Takagi, K. Takahashi, S. Takahashi, H. Takai, C. Takanaka, S. Take, H. Takeda, K. Takei, K. Takenaka, T. Tana, G. Tanabe, K. Taya, H. Teragawa, S. Tohyo, S. Toru, Y. Tsuchiya, T. Tsuji, K. Tsuzaki, H. Uchiyama, O. Ueda, Y. Ueyama, N. Wakaki, T. Wakiyama, T. Washizuka, M. Watanabe, T. Yamada, T. Yamagishi, H. Yamaguchi, Kenichi Yamamoto, Kentaro Yamamoto, Kunihiko Yamamoto, T. Yamamoto, M. Yamaura, M. Yamazoe, K. Yasui, Y. Yokoyama, K. Yoshida, T.W. Lim, C.K. Ching, C.G. Foo, J.H. Chow, D.D. Chen, F.R. Jaufeerally, Y.M. Lee, G. Lim, W.T. Lim, S. Thng, S.Y. Yap, C. Yeo, S. Oh, H.N. Pak, J.-B. Kim, J.H. Kim, S.-W. Jang, D.H. Kim, D.R. Ryu, S.W. Park, D.-K. Kim, D.J. Choi, Y.S. Oh, M.-C. Cho, S.-H. Kim, H.-K. Jeon, D.-G. Shin, J.S. Park, H.K. Park, S.-J. Han, J.H. Sung, J.-G. Cho, G.-B. Nam, Y.K. On, H.E. Lim, J.J. Kwak, T.-J. Cha, T.J. Hong, S.H. Park, J.H. Yoon, N.-H. Kim, K.-S. Kim, B.C. Jung, G.-S. Hwang, C.-J. Kim, D.B. Kim, J.J. Ahn, H.J. An, H. Bae, A.L. Baek, W.J. Chi, E.A. Choi, E.H. Choi, H.K. Choi, H.S. Choi, S. Han, E.S. Heo, K.O. Her, S.W. Hwang, E.M. Jang, H.-S. Jang, S. Jang, H.-G. Jeon, S.R. Jeon, Y.R. Jeon, H.K. Jeong, I.-A. Jung, Hyeon Jeong Kim, Hyun Ju Kim, Ji Seon Kim, Jung Sook Kim, J.A. Kim, K.T. Kim, M.S. Kim, Sang Hee Kim, Sang Hyun Kim, Y.-I. Kim, C.S. Lee, E.H. Lee, G.H. Lee, H.Y. Lee, H.-Y. Lee, K.H. Lee, K.R. Lee, M.S. Lee, M.-Y. Lee, R.W. Lee, S.E. Lee, S.H. Lee, S. Lee, W.Y. Lee, I.K. Noh, A.R. Park, B.R. Park, H.N. Park, J.H. Park, M. Park, Y. Park, S.-Y. Seo, J. Shim, J.H. Sim, Y.M. Sohn, W.S. Son, Y.S. Son, H.J. Song, H.K. Wi, J.J. Woo, S. Ye, K.H. Yim, K.M. Yoo, E.J. Yoon, S.Y. Yun, P. Angchaisuksiri, S. Chawanadelert, P. Mongkolwongroj, K. Kanokphatcharakun, S. Cheewatanakornkul, T. Laksomya, S. Pattanaprichakul, T. Chantrarat, S. Rungaramsin, S. Silaruks, W. Wongcharoen, K. Siriwattana, K. Likittanasombat, P. Katekangplu, W. Boonyapisit, D. Cholsaringkarl, B. Chatlaong, P. Chattranukulchai, Y. Santanakorn, P. Hutayanon, P. Khunrong, T. Bunyapipat, S. Jai-Aue, P. Kaewsuwanna, P. Bamungpong, S. Gunaparn, S. Hongsuppinyo, R. Inphontan, R. Khattaroek, K. Khunkong, U. Kitmapawanont, C. Kongsin, B. Naratreekoon, S. Ninwaranon, J. Phangyota, A. Phrommintikul, P. Phunpinyosak, K. Pongmorakot, S. Poomiphol, N. Pornnimitthum, S. Pumprueg, S. Ratchasikaew, K. Sanit, K. Sawanyawisuth, B. Silaruks, R. Sirichai, A. Sriwichian, W. Suebjaksing, P. Sukklad, T. Suttana, A. Tangsirira, O. Thangpet, W. Tiyanon, Y. Vorasettakarnkij, T. Wisaratapong, W. Wongtheptien, A. Wutthimanop, S. Yawila, A. Oto, A. Altun, I. Ozdogru, K. Ozdemir, O. Yilmaz, A. Aydinlar, M.B. Yilmaz, E. Yeter, Z. Ongen, M. Cayli, H. Pekdemir, M. Ozdemir, M. Sucu, T. Sayin, M. Demir, H. Yorgun, M. Ersanli, E. Okuyan, D. Aras, H. Abdelrahman, O. Aktas, D. Alpay, F. Aras, M.F. Bireciklioglu, S. Budeyri, M. Buyukpapuc, S. Caliskan, M. Esen, M.A. Felekoglu, D. Genc, B. Ikitimur, E.B. Karaayvaz, S. Kılıç Karataş, S. Okutucu, E. Ozcelik, A. Quisi, H. Sag, L. Sahiner, B.Y. Sayin, T. Seker, D. Uzun Alkan, E. Yildirim, R. Yildirim, F. Yilmaz, V. Yuksekdag, H.L. Luciardi, N. Vensentini, A.C. Ingaramo, G.A. Sambadaro, V. Fernandez Caputi, S.G. Berman, P. Dragotto, A.J. Kleiban, N. Centurion, G. Giacomi, R.A. Ahuad Guerrero, D. Conde, G. Zapata, L.A. Di Paola, J.L. Ramos, R.D. Dran, J. Egido, A.A. Fernandez, M.J. Fosco, S. Sassone, V.A. Sinisi, L.R. Cartasegna, M.A. Berli, O.A. Gomez Vilamajo, F. Ferroni, E.D. Alaguibe, A. Alvarez D'Amelio, C. Arabetti, L. Arias, J.A. Belardi, L. Bergesio, F. Berli, M. Berli, S. Borchowiec, C. Buzzetti, R. Cabrini, V. Campisi, A.L. Cappi, R. Carrizo, F. Colombo Berra, J.P. Costabel, O.J.A. Costamagna, A.A. Damonte, I.N. De Urquiza, F. Diez, M.F. Edén, M. Fanuele, F. Fernandez Voena, M. Foa Torres, C. Funosas, M.P. Giacomi, C.H. Gimenez, E.P. Gurfinkel, M. de L.M. Had, V. Hansen, A.D. Hrabar, M. Ingratta, A. Lopez, G. Maehara, L. Maffei, A. Martinelli, C. Martinelli, J. Matkovich, B. Mautner, A. Meirino, R. Munguia, A. Navarro, V. Novas, G. Perez Prados, J. Pontoriero, R.N. Potito, C. Ricotti, M.A. Rodriguez, F. Rolandi, M.E. Said Palladino, M. Salinger, L.S. Sanziani, P.O. Schygiel, A. Sossich, J.F. Tinto, L. Tonelli, A.L. Tufare, M. Vallejo, M.E. Yunis, M. Zillo, F.J. Zurbrigk, A.C.P. Barretto, D.C. Sobral Filho, J. Jaber, D. Armaganijan, J. Faria Neto, A. Steffens, W. Kunz Sebba Barroso de Souza, J.D. de Souza Neto, J.M. Ribeiro, M. Silveira Teixeira, P.R. Ferreira Rossi, L. Pires, D. Moreira, J.C. Moura Jorge, A. Menezes Lorga Filho, L.C. Bodanese, M. Westerlund Montera, C.H. Del Carlo, T. Da Rocha Rodrigues, F.A. Alves da Costa, A. Lopes, R. Lopes, G.R. Araújo, E.R. Fernandes Manenti, J.F. Kerr Saraiva, J.C. Ferreira Braga, A. Negri, L. Souto, C. Moncada, D. Bertolim Precoma, F. Roquette, G. Reis, R.A. Ramos Filho, E. Lanna Figueiredo, R. Vieira Botelho, C. Munhoz da Fontoura Tavares, C.R. Costantini Frack, J. Abdalla Saad, H.C. Finimundi, C. Pisani, D. Chemello, M. Pereira Martins, C.C. Broilo França, F. Alban, G.B. Aranha Rosito, J.B. de Moura Xavier Moraes Junior, R.T. Tumelero, L. Nigro Maia, R. Simões de Almeida, N.C. do Carmo Borges, L.G. Gomes Ferreira, P. Agliardi, J. Alves de Oliveira Gomes, V. Araujo, M. Arruda Nakazone, T. Barbosa, S. Barroso, E. Belisario Falchetto, H. Bellotti Lopes, M.A. Benez Teixeira Lemos, G. Biazus, L. Borges Queiroz, F.E. Camazzola, M. Caporale, S. Cardoso Boscato, F. Chieza, M.O. Chokr, R. Clemente Mingireanov, N. Codonho Góes, C. Correa, M. Costa, C. Costantini Ortiz, L.S. da Silva, F. da Silva Paulitsch, J.A. da Silveira, E. Daros, G.R. de Araújo, M.I. Del Monaco, C. Dias, M.A. Dias, A.P. Drummond Wainstein, P. Ely Pizzato, D.C. Esteves, P. Fabri, T. 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Houzvic, P. Marin Cuevas, H. Montecinos, A. Forero, F. Lanas, M. Larico Gómez, G. Charme Vilches, C. Rey, C. Astudillo, J. Aguilar, Y. Campisto, C. Lara, E. Molina, J. Munoz Oyarzon, V. Olguin, M. Vergara, C. Villan, C.J. Sánchez Díaz, J. Illescas Diaz, R. Leal Cantú, M.G. Ramos Zavala, R. Cabrera Jardines, N. Espinola Zavaleta, S. Villarreal Umaña, E. López Rosas, G. Llamas Esperón, G. Pozas, E. Cardona Muñoz, N. Matadamas Hernández, A. Leyva Rendón, N. García Hernández, M. de los Ríos Ibarra, L. Virgen Carrillo, D. López Villezca, C. Hernández Herrera, J.J. López Prieto, R. Gaona Rodríguez, E. Villeda Espinosa, D. Flores Martínez, J. Velasco Barcena, R. Yong, I. Rodríguez Briones, J.L. Leiva Pons, H. Álvarez López, R. Olvera Ruiz, C. Díaz de la Vega, C. Cantú Brito, E. Chuquiure Valenzuela, R. Reyes-Sanchez, A. Bazzoni Ruiz, O. Nandayapa Flores, M. Benavides Gonzalez, R. Arriaga Nava, J.D. Morales Cerda, O. Fierro Fierro, P. Fajardo Campos, T.A.A. Alfaro, S. Altamirano Bellorin, R. 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Y., Angchaisuksiri, P., Chawanadelert, S., Mongkolwongroj, P., Kanokphatcharakun, K., Cheewatanakornkul, S., Laksomya, T., Pattanaprichakul, S., Chantrarat, T., Rungaramsin, S., Silaruks, S., Wongcharoen, W., Siriwattana, K., Likittanasombat, K., Katekangplu, P., Boonyapisit, W., Cholsaringkarl, D., Chatlaong, B., Chattranukulchai, P., Santanakorn, Y., Hutayanon, P., Khunrong, P., Bunyapipat, T., Jai-Aue, S., Kaewsuwanna, P., Bamungpong, P., Gunaparn, S., Hongsuppinyo, S., Inphontan, R., Khattaroek, R., Khunkong, K., Kitmapawanont, U., Kongsin, C., Naratreekoon, B., Ninwaranon, S., Phangyota, J., Phrommintikul, A., Phunpinyosak, P., Pongmorakot, K., Poomiphol, S., Pornnimitthum, N., Pumprueg, S., Ratchasikaew, S., Sanit, K., Sawanyawisuth, K., Silaruks, B., Sirichai, R., Sriwichian, A., Suebjaksing, W., Sukklad, P., Suttana, T., Tangsirira, A., Thangpet, O., Tiyanon, W., Vorasettakarnkij, Y., Wisaratapong, T., Wongtheptien, W., Wutthimanop, A., Yawila, S., Oto, A., Altun, A., Ozdogru, I., Ozdemir, K., Yilmaz, O., Aydinlar, A., Yilmaz, M. 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A., Andersson, A., Malmqvist, L., Martinsson, B., Bernsten, F., Engdahl, J., Thulin, J., Hot-Bjelac, A., Stalby, P., Aaröe, H., Ahbeck, E., Ahlmark, H., Al-Khalili, F., Bonkowski, G., Dzeletovic, S., Ekstrand, A. -B., Eriksson, G. -B., Floren, K., Grässjö, C., Hahn, S., Jaensson, P., Jansson, B., Jansson, J. -H., Kangert, R. -M., Koch, A., Kusiak, D., Lettenström, A., Lindberg, A., Lindholm, C. -J., Mannermyr, A., Mansson, K., Millborg, M., Nilsson, C., Ohlin, A. -M., Olofsson, A., Osberg, A., Pedersen, A., Risbecker, K., Rosenberg, K., Samuelsson, J., Shayesteh, M., Skoglund, K., Stjernberg, M., Thorsen, C., Steffel, J., Beer, J. H., Debrunner, J., Amstutz, D., Bruegger, J., Elise, G., Grau, A., Guinand, A., Henriette, I., Saga, E., Winnik, S., Parkhomenko, A., Rudyk, I., Tseluyko, V., Karpenko, O., Zhurba, S., Kraiz, I., Kupnovytska, I., Serediuk, N., Mostovoy, Y., Ushakov, O., Koval, O., Kovalskyi, I., Svyshchenko, Y., Sychov, O., Stanislavchuk, M., Kraydashenko, O., Yagensky, A., Tykhonova, S., Fushtey, I., Belegai, R., Berko, G., Burdeuna, L., Chabanna, O., Daniuk, I., Ivanov, A., Kamenska, E., Kaplan, P., Khyzhnyak, O., Kizim, S., Matova, O., Medentseva, O., Mochonyi, V., Mospan, M., Nemtsova, V., Ovdiienko, T., Palamarchuk, O., Pavelko, M., Petrovskyy, R., Plevak, D., Proshak, O., Pyvovar, S., Rasputina, L., Romanenko, O., Romanova, O., Sapatyi, A., Shumakov, O., Stets, R., Todoriuk, L., Varenov, V., Fitzmaurice, D., Chauhan, N., Goodwin, D., Saunders, P., Evans, R., Leese, J., Jhittay, P. S., Ross, A., Kainth, M. S., Pickavance, G., Mcdonnell, J., Williams, A., Gooding, T., Wagner, H., Suryani, S., Singal, A., Sircar, S., Bilas, R., Hutchinson, P., Wakeman, A., Stokes, M., Paul, N., Aziz, M., Ramesh, C., Wilson, P., Franklin, S., Fairhead, S., Thompson, J., St Joseph, V., Taylor, G., Tragen, D., Seamark, D., Paul, C., Richardson, M., Jefferies, A., Sharp, H., Jones, H., Giles, C., Page, M., Oginni, O., Aldegather, J., Wetherwell, S., Lumb, W., Evans, P., Scouller, F., Macey, N., Stipp, Y., West, R., Thurston, S., Wadeson, P., Matthews, J., Pandya, P., Gallagher, A., Railton, T., Sinha, B., Russell, D., Davies, J. A., Ainsworth, P., Jones, C. P., Weeks, P., Eden, J., Kernick, D., Murdoch, W., Lumley, L., Patel, R. P., Wong, S. W., Saigol, M., Ladha, K., Douglas, K., Cumberlidge, D. F., Bradshaw, C., Van Zon, G., Jones, K. P., Thomas, M. J., Watson, E., Sarai, B., Ahmad, N., Willcock, W., Cairns, J., Sathananthan, S., de Kare-Silver, N., Gilliland, A., Strieder, E., Howitt, A., Vishwanathan, B., Bird, N., Gray, D., Clark, M., Bisatt, J., Litchfield, J., Fisher, E., Fooks, T., Kelsall, A. R., Alborough, E., Wakeling, J., Parfitt, M., Milne, K., Rogers, S., Priyadharshan, R., Oliver, J. L., Davies, E., Abushal, S., Jacobs, M., Hutton, C., Walls, N. I., Thompson, R., Chigbo, C., Zaidi, S. M. A., Howard, M., Butter, K. C., Barrow, S., Little, H., Haq, I. U., Gibbons, L., Glencross, S., Mcleod, A. J., Poland, K., Mulholland, C., Warke, A., Conn, P., Burns, G., Smith, R. N., Lowe, S., Kamath, R., Dau, H. S., Webster, J., Hodgins, I., Vercoe, S., Roome, P. C., Pinnock, H., Patel, J. R. A., Ali, A., Hart, N., Davies, R., Stuart, E., Neden, C. A., Danielsen, M., Heath, R., Sharma, P., Galloway, S., Hawkins, C., Oliver, R., Aylward, M., Mannion, S., Braddick, M., Edwards, D., Rothwell, A. C., Sabir, A., Choudhary, F., Khalaque, S., Wilson, A., Peters, S., Coulson, W., Roberts, N., Heer, A., Coates, S., Ward, B., Jackson, D., Walton, S., Shepherd, D., Sterry, M., Wong, T., Boon, M., Bunney, R., Haria-Shah, R., Baron, R. T., Davies, S., Schatzberger, T., Hargreaves, N., Stephenson, T., Choi, H., Batson, R., Lucraft, L., Myhill, T., Estifano, S., Geatch, D., Wilkinson, J., Veale, R., Forshaw, K., Davies, T., Zaman, K., Vinson, P., Liley, C., Bandrapalli, M., Mcginty, P., Wastling, R., Mceleny, P., Beattie, A., Cooke, P., Wong, M., Gunasegaram, J., Pugsley, M., Ahmad, S., A'Court, C., Ayers, J., Bennett, J., Cartwright, S., Dobson, S., Dooldeniya, C., Flynn, A., Fox, R., Goram, J., Halpin, A., Hay, A., Jacobs, P., Jeffers, L., Lomax, L., Munro, I., Muvva, R., Nadaph, M., Powell, K., Randfield, S., Redpath, D., Reed, R., Rickenbach, M., Rogers, G., Saunders, P. B., Seamark, C., Shewring, J., Simmons, P., Simper, H., Stoddart, H., Sword, A., Thomas, N., Thomson, A., Gibbs, H., Blenkhorn, A., Singh, B., Van Gaal, W., Abhayaratna, W., Lehman, R., Roberts-Thomson, P., Kilian, J., Coulshed, D., Catanchin, A., Colquhoun, D., Kiat, H., Eccleston, D., French, J., Zimmett, L., Ayres, B., Phan, T., Blombery, P., Crimmins, D., O'Donnell, D., Choi, A., Astridge, P., Arstall, M., Jepson, N., Binnekamp, M., Lee, A., Rogers, J., Starmer, G., Carroll, P., Faunt, J., Aggarwala, A., Barry, L., Batta, C., Beveridge, R., Black, A., Bonner, M., Boys, J., Buckley, E., Campo, M., Carlton, L., Connelly, A., Conway, B., Cresp, D., Dimitri, H., Dixon, S., Dolman, M., Duroux, M., Eskandari, M., Eslick, R., Ferreira-Jardim, A., Fetahovic, T., Fitzpatrick, D., Geraghty, R., Gibbs, J., Grabek, T., Modi, M. H., Hayes, K., Hegde, M. P., Hesketh, L., Hoffmann, B., Jacobson, B., Johnson, K., Juergens, C., Kassam, I., Lawlor, V., Lehman, M., Lehman, S., Leung, D., Mackay, S., Mackenzie, M., Mccarthy, C., Mcintosh, C., Mckeon, L., Morrison, H., Mussap, C., Myers, J. -D., Nagalingam, V., Oldfield, G., O'May, V., Palmer, J., Parsons, L., Patching, K., Patching, T., Paul, V., Plotz, M., Preston, S., Rashad, H., Ratcliffe, M., Raynes, S., Rose, J., Sanders, L., Seremetkoska, M., Setio, H., Shone, S., Shrestha, P., Singh, C., Singleton, C., Stoyanov, N., Sutcliffe, S., Swaraj, K., Tarrant, J., Thompson, S., Tsay, I. M., Vorster, M., Waldman, A., Wallis, L., Wilford, E., Wong, K., Connolly, S. J., Spyropoulos, A., Eikelboom, J., Luton, R., Gupta, M., Pandey, A. S., Cheung, S., Leader, R., Beaudry, P., Ayala-Paredes, F., Berlingieri, J., Heath, J., Poirier, G., Du Preez, M., Nadeau, R., Dresser, G., Dhillon, R., Hruczkowski, T., Schweitzer, B., Coutu, B., Angaran, P., Macdonald, P., Vizel, S., Fikry, S., Parkash, R., Lavoie, A., Cha, J., Ramjattan, B., Bonet, J., Ahmad, K., Aro, L., Aves, T., Beaudry, K., Bergeron, C., Bigcanoe, J., Bignell, N., Breakwell, L., Burke, E., Carroll, L., Clarke, B., Cleveland, T., Daheb, S., Dehghani, P., Denis, I., Djaidani, Z., Dorian, P., Douglass, S., Dunnigan, J., Ewert, A., Farquhar, D., Fearon, A., Ferleyko, L., Fournier, D., Fox, B., Grenier, M. -C., Gulliver, W., Haveman, K., Hines, C., Hines, K., Jackson, A. M., Jean, C., Jethoo, G., Kahlon, R., Kelly, S., Kim, R., Korley, V., Kornder, J., Kwan, L., Largy, J., Lewis, C., Lewis, S., Mangat, I., Moor, R., Navratil, J., Neas, I., Otis, J., Otis, R., Pandey, M., Petrie, F., Pinter, A., Raines, M., Roberts, P., Robinson, M., Sas, G., Schulman, S., Snell, L., Spearson, S., Stevenson, J., Trahey, T., Wong, S., Wright, D., Ragy, H., Abd El-Aziz, A., Abou Seif, S. K., El Din, M. G., El Etriby, S., Elbahry, A., El-Etreby, A., Elkhadem, M., Katta, A., Khairy, T., Mowafy, A., Nawar, M., Ohanissian, A., Reda, A., Reda, M., Salem, H., Sami, N., Samir, S., Setiha, M., Sobhy, M., Soliman, A., Taha, N., Tawfik, M., Zaatout, E., Kettles, D., Bayat, J., Siebert, H., Horak, A., Kelfkens, Y., Garda, R., Pillay, T., Guerra, M., van Zyl, L., Theron, H., Murray, A., Louw, R., Greyling, D., Mntla, P., Ueckermann, V., Loghdey, R., Ismail, S., Ahmed, F., Engelbrecht, J., Ramdass, A., Maharajh, S., Oosthuysen, W., Angel, G., Bester, C., Booysen, M., Boshoff, C., Cannon, C., Cassimjee, S., Chami, C., Conway, G., Davids, A., de Meyer, L., Du Plessis, G., Ellis, T., Henley, L., Karsten, M., Loyd, E., Marks, J., Mavhusa, L., Mostert, M., Page, A., Rikhotso, L., Salie, M., Sasto, J., Shaik, F., Skein, A., Smith, L., Tarr, G., Tau, T., van Zyl, F., Al Mahmeed, W., Yousef, G., Agrawal, A., Nathani, M., Ibrahim, M., Esheiba, E. M., Singh, R., Naguib, A., Abu-Mahfouz, M., Al Omairi, M., Al Naeemi, A., Maruthanayagam, R., Bazargani, N., Wassef, A., Gupta, R., Khan, M., Subbaraman, B., Abdul, A., Al Mulla, A., El Bardisy, S., Haridas, P., Jadhav, S., Magdaluyo, K., Makdad, M., Maqsood, I., Mohamed, R., Sharma, N., Sharma, R., Thanzeel, M., Goldhaber, S. Z., Canosa, R., Rama, P., Blumberg, E., Garcia, J., Mullen, P., Wilson, V., Quick, A., Ferrick, K., Kutayli, W. M., Cox, M., Franco, M., Falkowski, S., Mendelson, R., Williams, M., Miller, S., Beach, S., Alfieri, A., Gutowski, T., Haque, I., Reddy, R., Ahmed, W., Delafontaine, P., Diercks, D., Theodoro, D., Remmel, K., Alberts, M., Ison, R., Noveck, H., Duffy, P., Pitta, S., Nishijima, D., Treasure, C., Asafu-Adjaye, N., Ball, K., Bartlett, M., Bentley, M., Bowers, S., Brown, A., Browne, A., Cameron-Watts, J., Canova, M., Cassidy, D., Cervellione, K., Congal, S., Depauw, J., Dickerson, A., Eley, M., Evans, L., Felpel, S., Ferdinand, K., Fielder, D., Gentry, P., Haideri, A., Hakimi, F., Harbour, T., Hartranft, E., Hawkins, B., Headlee, M., Henson, L., Herrick, C., Hicks, T., Jasinski, S., Jones, A., Jones, L., Jones, P., Karl, S., Keeling, M., Kerr, J., Knowles, P., Langdon, J., Lay, M., Lee, J. A., Lincoln, T., Malone, E., Merliss, A., Merritt, D., Minardo, J., Mooso, B., Orosco, C., Palumbo, V., Parker, M., Parrott, T., Paserchia, S., Pearl, G., Peterson, J., Pickelsimer, N., Purcell, T., Raynor, J., Raziano, S., Richard, C., Richardson, T., Robertson, C., Sage, A., Sanghera, T., Shaw, P., Shoemaker, J., Smith, K., Stephanie, B., Thatcher, A., Theobald, H., Thompson, N., Treasure, L., Tripti, T., Verdi, C., and Worthy, V.

Subjects
Registrie, Male, Time Factors, Anticoagulant therapy, Arrhythmia, Atrial fibrillation, GARFIELD-AF, 030204 cardiovascular system & hematology, Electrocardiography, 0302 clinical medicine, Risk Factors, Anticoagulant therapy, Arrhythmia, Atrial fibrillation, GARFIELD-AF, Aged, Atrial Fibrillation, Female, Follow-Up Studies, Humans, Incidence, India, Prevalence, Prognosis, Prospective Studies, Survival Rate, Thromboembolism, Registries, Risk Assessment, Medicine, 030212 general & internal medicine, Prospective cohort study, Incidence (epidemiology), cardiovascular system, medicine.symptom, Cardiology and Cardiovascular Medicine, Risk assessment, Human, medicine.medical_specialty, Time Factor, RD1-811, Prognosi, Follow-Up Studie, 03 medical and health sciences, Internal medicine, Diseases of the circulatory (Cardiovascular) system, cardiovascular diseases, Risk factor, Survival rate, Fibrillation, business.industry, Risk Factor, ta3121, medicine.disease, Clinical trial, Prospective Studie, RC666-701, Surgery, Clinical and Preventive Cardiology, business
Abstract

Background: The Global Anticoagulant Registry in the FIELD–Atrial Fibrillation (GARFIELD-AF) is an ongoing prospective noninterventional registry, which is providing important information on the baseline characteristics, treatment patterns, and 1-year outcomes in patients with newly diagnosed non-valvular atrial fibrillation (NVAF). This report describes data from Indian patients recruited in this registry. Methods and results: A total of 52,014 patients with newly diagnosed AF were enrolled globally; of these, 1388 patients were recruited from 26 sites within India (2012–2016). In India, the mean age was 65.8 years at diagnosis of NVAF. Hypertension was the most prevalent risk factor for AF, present in 68.5% of patients from India and in 76.3% of patients globally (P

Published
2018

43. Validation of the self-administered version of the international Restless Legs Syndrome study group severity rating scale – The sIRLS

Author

Birgit Högl, Irena Laska, Rochelle S. Zak, Lynn Marie Trotti, Hailey Meaklim, Arthur S. Walters, Luigi Ferini Strambi, Marco Zucconi, Laurel A. Schaefer, Evi Holzknecht, Philip M. Becker, Denise Sharon, Richard K. Bogan, Ambra Stefani, Richard P. Allen, John Swieca, Sara Marelli, Mark J. Buchfuhrer, Victoria Olvera, Pablo Martinez-Martin, Jennifer G. Hensley, Sharon, D., Allen, R. P., Martinez-Martin, P., Walters, A. S., Ferini Strambi, L., Hogl, B., Trotti, L. M., Buchfuhrer, M., Swieca, J., Bogan, R. K., Zak, R., Hensley, J. G., Schaefer, L. A., Marelli, S., Zucconi, M., Stefani, A., Holzknecht, E., Olvera, V., Meaklim, H., Laska, I., and Becker, P. M.

Subjects
Adult, Male, medicine.medical_specialty, Patient completed, Psychometrics, Scale (ratio), Intraclass correlation, International Cooperation, Validity/reliability, RLS symptoms, Severity of Illness Index, Diagnostic Self Evaluation, 03 medical and health sciences, 0302 clinical medicine, Cronbach's alpha, Rating scale, Restless Legs Syndrome, Surveys and Questionnaires, Severity scale, medicine, Humans, Restless legs syndrome, Reliability (statistics), Aged, business.industry, Reproducibility of Results, General Medicine, Middle Aged, medicine.disease, Standard error, 030228 respiratory system, Physical therapy, Ceiling effect, Female, business, Self-administered, 030217 neurology & neurosurgery
Abstract

Introduction The International Restless Legs Study Group (IRLSSG) has developed the IRLS (International Restless Legs Syndrome Severity Scale) and validated it as a clinician/researcher administered scale to be used when both patient and examiner are present. The IRLSSG recognized the need for a self-completing scale that can be used economically in clinical practice and in large population-based studies. In this study the validity and the reliability of the IRLS as a self-administered scale (sIRLS) is assessed. Methods Established RLS patients were recruited by eight centers in four countries and consented to participate in this study. The validity of the sIRLS was assessed by patients completing the sIRLS before a clinician administered the IRLS. The reliability of the sIRLS was assessed by patients completing the sIRLS again, two weeks after the first one, provided no change had occurred. Results Overall, 173 patients were recruited and 164 of them were included in the analyses. The sIRLS showed satisfactory scaling assumptions and no relevant floor or ceiling effect. One factor explained 61.3% of the variance. Cronbach's alpha was 0.93 and the item homogeneity index was 0.59. Intraclass correlation coefficient between the sIRLS and the IRLS was 0.94. The sIRLS standard error of measurement was 3.61 (½ SD at baseline = 4.11). The results mostly overlapped those of the IRLS analyzed in parallel. Discussion The sIRLS is a reliable, valid and precise instrument that showed tight association with the IRLS. These findings support the use of the sIRLS for self-evaluation of RLS severity. The responses obtained on the sIRLS and the IRLS scale varied slightly. Therefore, we recommend that either the sIRLS or the IRLS scale be used as the only scale for serial measures over time.

Published
2019

44. Prevalence of open neural tube defects and risk factors related to isolated anencephaly and spina bifida in live births from the 'Dr. Juan I. Menchaca' Civil Hospital of Guadalajara (Jalisco, Mexico)

Author

Adolfo Ruiz-Gómez, Alfredo Corona-Rivera, Christian Peña-Padilla, Sandra Olvera-Molina, Jorge Román Corona-Rivera, J. Jesús Pérez-Molina, Cristian Irela Aranda-Sánchez, Guadalupe Elena Morales-Domínguez, and Lucina Bobadilla-Morales

Subjects
Adult, Male, 0301 basic medicine, Embryology, medicine.medical_specialty, 030105 genetics & heredity, Risk Assessment, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Anencephaly, Prevalence, medicine, Humans, Neural Tube Defects, Registries, Family history, Mexico, Spinal Dysraphism, 030219 obstetrics & reproductive medicine, Obstetrics, Spina bifida, business.industry, General Medicine, Odds ratio, medicine.disease, Confidence interval, Case-Control Studies, Population Surveillance, Pediatrics, Perinatology and Child Health, Gestation, Female, medicine.symptom, business, Live Birth, Body mass index, Weight gain, Developmental Biology
Abstract

We determine the prevalence and trends of open neural tube defects (ONTDs) during 1991 to 2019 at the "Dr. Juan I. Menchaca" Civil Hospital of Guadalajara (Mexico). Also, details of potential risks were obtained in 662 newborns, including those 143 patients with anencephaly and open spina bifida (OSB) classified as isolated (cases) and 519 controls. Data were analyzed using multivariable logistic regression. Among 267 201 live births during the study period, 336 were born with ONTDs, yielding an overall prevalence of 12.6 per 10 000. After folic acid (FA)-related programs began in Mexico (2003-2019), only OSB showed a decline of 20.6%. For anencephaly, associated risks included relatives with neural tube defects (NTDs) (adjusted odds ratio [aOR]: 67.9, 95% confidence interval [95% CI]: 11.3-409.8), pre-pregnancy body mass index (BMI) ≥25 kg/m2 (aOR: 2.6, 95% CI: 1.1-6.0), insufficient gestational weight gain (aOR: 3.0, 95% CI: 1.3-7.1), parity ≥4 (aOR: 3.2, 95% CI: 1.3-7.7), and exposure to analgesic/antipyretic drugs (aOR: 9.0; 95% CI: 2.5-33.0). For OSB, associated risks included consanguinity (aOR: 14.0, 95% CI: 3.5-55.9), relatives with NTDs (aOR: 22.4, 95% CI: 4.5-112.9), BMI ≥25 kg/m2 (aOR: 2.5, 95% CI: 1.6-4.2), insufficient gestational weight gain (aOR: 1.9, 95% CI: 1.1-3.1), and exposures to hyperthermia (aOR: 2.3, 95% CI: 1.2-4.3), common cold (aOR: 6.8, 95% CI: 3.6-12.7), and analgesic/antipyretic drugs (aOR: 3.6, 95% CI: 1.3-10.0). Our high rate probably results from exposures to preventable risks, most related to FA, indicating a need for strengthening existing FA-related programs in Mexico.

Published
2020

45. The content of gonadotropin-releasing hormone (GnRH), kisspeptin, and estrogen receptors (ERα/ERβ) in the anteromedial hypothalamus displays daily variations throughout the rat estrous cycle

Author

Hilda Martinez-Coria, Roberto Domínguez, Esteban Olvera-Juárez, Roger Gutierrez-Juarez, Mario Cárdenas, Isabel Arrieta-Cruz, Héctor E López-Valdés, Angélica Flores, María-Esther Cruz, Carlos-Camilo Silva, and Luciano Mendoza-Garcés

Subjects
0301 basic medicine, endocrine system, medicine.medical_specialty, Histology, Hypothalamus, Estrogen receptor, Estrous Cycle, Gonadotropin-releasing hormone, Biology, Pathology and Forensic Medicine, Gonadotropin-Releasing Hormone, 03 medical and health sciences, 0302 clinical medicine, Kisspeptin, Internal medicine, medicine, Animals, reproductive and urinary physiology, Estrous cycle, Kisspeptins, urogenital system, Cell Biology, Rats, 030104 developmental biology, Endocrinology, Receptors, Estrogen, Female, Luteinizing hormone, Estrogen receptor alpha, hormones, hormone substitutes, and hormone antagonists, 030217 neurology & neurosurgery, Hormone
Abstract

The content of gonadotropin-releasing hormone (GnRH), its mRNA, and estrogen receptor alpha (ERα) and beta (ERβ) in the hypothalamus varies throughout the estrous cycle. Furthermore, the abundance of these molecules displays asymmetry between the right and left side. In the present study, we investigated the changes in the content of ERα, ERβ, kisspeptin, and GnRH by western blot in the left and right anteromedial hypothalamus, at four different times during each stage of the rat estrous cycle. The serum levels of the follicle-stimulating hormone (FSH) and luteinizing hormone (LH) were also measured. ERα and ERβ levels changed depending on the stage of the estrous cycle, meanwhile that of kisspeptin was modified according to both the hour of the day and the stage of the cycle. Except in estrus day, ERβ was higher in the right hypothalamus, while ERα was similar in both sides. During both proestrus and estrus, the content of kisspeptin and GnRH was higher in the right hypothalamus. The highest levels of FSH and LH occurred at 17:00 h of proestrus. But at estrus, the highest FSH levels were observed at 08:00 h and the lowest at 17:00 h. Thus, the current results show that the content of ERα, ERβ, kisspeptin, and GnRH in the anteromedial hypothalamus are regulated as a function of the stage of the estrous cycle and the hour of the day. Furthermore, the content of these proteins is regularly higher in the right anteromedial hypothalamus, regardless of the stage of the cycle or time of the day.

Published
2020

46. Pilot study: Evaluation of potential drug–drug interactions in hospitalized pediatric patients

Author

Estefanía Vázquez-Méndez, Real-Ornelas Gabriel A, Iván Hernández-Cañaveral, Selene G. Huerta-Olvera, Virginia Aleyda Sánchez-López, Edsaul Emilio Perez-Guerrero, and Fabiola Medina-Barajas

Subjects
Male, Drug, medicine.medical_specialty, drug-drug interactions, Adolescent, Hospital setting, media_common.quotation_subject, Pilot Projects, Pharmacokinetics, Internal medicine, Intensive therapy, Humans, Medicine, Drug Interactions, Medical prescription, Child, Prescribed medications, Retrospective Studies, media_common, pediatric patients, business.industry, Infant, Newborn, lcsh:RJ1-570, Infant, lcsh:Pediatrics, Anthropometry, Hospitalization, medication errors, Child, Preschool, Pediatrics, Perinatology and Child Health, potential drug-drug interactions, Female, business
Abstract

Purpose Evaluate the type and severity of potential drug-drug interactions and identify risk factors involved, in pediatric patients admitted in a hospital setting. Methods Transversal retrospective analytical study was carried out with hospitalized pediatric patients from a Hospital in the West of Mexico, second and third level. The patients included were ≤18 years old hospitalized in the children wards; those admitted at the emergency room, neonatal intermediate and intensive therapy units were not included. Medical prescriptions were reviewed taking into consideration anthropometric characteristics, diagnosis and number of drugs prescribed to identify potential drug–drug interactions using Micromedex 2.0 database. Results 88 patients were included, an average of 4.6 ± 2.8 of drugs were prescribed per patient. 37 subjects (42%) presented some degree of potential drug-drug interactions of which 25.5% were major and 27.7% moderate according to the software. Identified risk factors were: age ≥ 4 years (OR 1.917; 95% CI 1.081-3.399), BSA ≥ 0.8m2(OR 1.825; 95% CI 1.021–3.263), height ≥ 1 m (OR 2.556;95% CI 1.322 - 4.941), and number of prescribed medications ≥ 4 (OR 2.106;95% CI 1.248 - 3.556). Conclusion Some of the interactions found were for the benefit of the patient, but others were considered undesirable because they altered the pharmacokinetics of some of the medications administered. Detecting in time the harmful interactions for a patient may favor the patient's safety.

Published
2020

47. Decreased kidney function and agricultural work: a cross-sectional study in middle-aged adults from Tierra Blanca, Mexico

Author

Nadia Olvera, Alejandro Escobar, Ximena Rubilar, Alejandro Raña-Custodio, Antonio R. Villa, Laura G. Sánchez-Lozada, Diego Aguilar-Ramirez, Magdalena Madero, Richard J. Johnson, and Gregorio T. Obrador

Subjects
Adult, Male, Cross-sectional study, Population, 030232 urology & nephrology, Renal function, Kidney, Logistic regression, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, medicine, Albuminuria, Humans, 030212 general & internal medicine, Renal Insufficiency, Chronic, education, Mexico, Transplantation, education.field_of_study, business.industry, Agriculture, Odds ratio, Middle Aged, medicine.disease, Cross-Sectional Studies, Nephrology, Creatinine, Female, medicine.symptom, business, Body mass index, Glomerular Filtration Rate, Demography, Kidney disease
Abstract

Background We aimed to determine the prevalence of decreased kidney function in a potential chronic kidney disease (KD) of unknown aetiology hotspot in Mexico, assess its distribution across occupations and examine the associated risk factors. Methods A cross-sectional study collected sociodemographic, occupational, medical and biometric data from 616 men and women aged 20–60 years who were residents of three communities within the Tierra Blanca region in Mexico. Kidney function was assessed by standardized serum creatinine and estimated glomerular filtration rate (eGFR) and semi-quantitative albumin-to-creatinine ratio (ACR). To examine the distribution of decreased kidney function within the population, age- and sex-adjusted prevalence of low eGFR (≤60 mL/min/1.73 m2) was estimated for all participants and across occupations. Multivariable logistic regression was used to assess the association of occupation with having low eGFR. Results Of the 579 participants analysed (37 excluded due to missing data), the age- and sex-adjusted prevalence of low eGFR was 3.5%. Agriculture was the occupation associated with the highest adjusted prevalence of low eGFR (8.8%), with 1 in every 11 agricultural workers having low eGFR. Working in agriculture was independently associated with more than a 5-fold risk of having low eGFR [odds ratio 5.2 (95% confidence interval 1.1–24.3), P = 0.032], after adjustment for age, sex, diabetes, hypertension, body mass index, ACR and family history of KD. Additionally, a quarter of the population (25%) had either low eGFR or an ACR >30 mg/g, mostly due to albuminuria. Conclusions Our work suggests that there is a high prevalence of decreased kidney function in Tierra Blanca, particularly amongst agricultural workers.

Published
2020

48. Diagnostic accuracy of diabetic retinopathy grading by an artificial intelligence-enabled algorithm compared with a human standard for wide-field true-colour confocal scanning and standard digital retinal images

Author

Ryan Chambers, Catherine A Egan, Adnan Tufail, Tjebo F. C. Heeren, Louis Bolter, Abraham Olvera-Barrios, John Anderson, and Konstantinos Balaskas

Subjects
Adult, Diagnostic Imaging, Male, medicine.medical_specialty, 030209 endocrinology & metabolism, Diagnostic accuracy, Fundus (eye), Slit Lamp Microscopy, Sensitivity and Specificity, Retina, 03 medical and health sciences, Cellular and Molecular Neuroscience, chemistry.chemical_compound, 0302 clinical medicine, Artificial Intelligence, Predictive Value of Tests, Ophthalmology, Image Processing, Computer-Assisted, medicine, Humans, False Positive Reactions, Grading (tumors), Aged, Diabetic Retinopathy, Microscopy, Confocal, Diagnostic Tests, Routine, business.industry, Reproducibility of Results, Retinal, Diabetic retinopathy, Middle Aged, Reference Standards, medicine.disease, Wide field, Sensory Systems, Retinal image, Cross-Sectional Studies, chemistry, 030221 ophthalmology & optometry, Female, business, Algorithms, Retinopathy
Abstract

BackgroundPhotographic diabetic retinopathy screening requires labour-intensive grading of retinal images by humans. Automated retinal image analysis software (ARIAS) could provide an alternative to human grading. We compare the performance of an ARIAS using true-colour, wide-field confocal scanning images and standard fundus images in the English National Diabetic Eye Screening Programme (NDESP) against human grading.MethodsCross-sectional study with consecutive recruitment of patients attending annual diabetic eye screening. Imaging with mydriasis was performed (two-field protocol) with the EIDON platform (CenterVue, Padua, Italy) and standard NDESP cameras. Human grading was carried out according to NDESP protocol. Images were processed by EyeArt V.2.1.0 (Eyenuk Inc, Woodland Hills, California). The reference standard for analysis was the human grade of standard NDESP images.ResultsWe included 1257 patients. Sensitivity estimates for retinopathy grades were: EIDON images; 92.27% (95% CI: 88.43% to 94.69%) for any retinopathy, 99% (95% CI: 95.35% to 100%) for vision-threatening retinopathy and 100% (95% CI: 61% to 100%) for proliferative retinopathy. For NDESP images: 92.26% (95% CI: 88.37% to 94.69%) for any retinopathy, 100% (95% CI: 99.53% to 100%) for vision-threatening retinopathy and 100% (95% CI: 61% to 100%) for proliferative retinopathy. One case of vision-threatening retinopathy (R1M1) was missed by the EyeArt when analysing the EIDON images, but identified by the human graders. The EyeArt identified all cases of vision-threatening retinopathy in the standard images.ConclusionEyeArt identified diabetic retinopathy in EIDON images with similar sensitivity to standard images in a large-scale screening programme, exceeding the sensitivity threshold recommended for a screening test. Further work to optimise the identification of ‘no retinopathy’ and to understand the differential lesion detection in the two imaging systems would enhance the use of these two innovative technologies in a diabetic retinopathy screening setting.

Published
2020

49. Quality of life in patients with kidney stones: translation and validation of the Spanish Wisconsin Stone Quality of Life Questionnaire

Author

Juan P. Flores-Tapia, Mario Basulto-Martínez, Alexander Heinze, Daniel Olvera-Posada, Kristina L. Penniston, Carlos E. Méndez-Probst, María D Guerrero-Putz, and Iván A. Velueta-Martínez

Subjects
Adult, Male, medicine.medical_specialty, Urology, 030232 urology & nephrology, External validity, Kidney Calculi, 03 medical and health sciences, 0302 clinical medicine, Quality of life, Cronbach's alpha, Informed consent, Humans, Medicine, Translations, business.industry, Middle Aged, Institutional review board, medicine.disease, humanities, Readability, Convergent validity, Quality of Life, Physical therapy, Female, Kidney stones, Self Report, business
Abstract

The Spanish version of the Wisconsin Stone Quality of Life (WISQOL) questionnaire was developed and validated. A double-back translation of the WISQOL was conducted and syntactic amendments were made, resulting in the Spanish version of the WISQOL (S-WISQOL) which then went through a readability analysis. Stone formers from two hospitals in Mexico (Merida and Monterrey) filled in the S-WISQOL and the Short Form 36 (SF36). Convergent validity was assessed by the correlation of both questionnaires. Internal consistency was evaluated by Cronbach’s α, and external validity by comparing between centers. The impact of clinical settings on patients’ health-related quality of life (HRQOL) scores was tested. Each hospital’s institutional review board approved the project and informed consent was obtained from all participants. A total of 87 Spanish-speakers patients completed the S-WISQOL and SF36 and a good correlation was found between both (r = 0.75, p

Published
2020

50. Is it possible to incorporate evidence-based professional midwifery practices into public health services in Mexico?

Author

Marisela Olvera García, Alejandra Montoya, Jimena Fritz, Héctor Lamadrid-Figueroa, Mario Salvador Sánchez-Domínguez, Dolores González-Hernández, and Sandra Treviño-Siller

Subjects
Adult, Male, medicine.medical_specialty, Evidence-based practice, Adolescent, Attitude of Health Personnel, Health Personnel, media_common.quotation_subject, Midwifery, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Pregnancy, Maternity and Midwifery, Health care, medicine, Humans, Childbirth, Maternal Health Services, Mexico, Qualitative Research, media_common, 030219 obstetrics & reproductive medicine, 030504 nursing, Obstetrics, business.industry, Public health, Parturition, Obstetrics and Gynecology, Loneliness, Delivery, Obstetric, Cross-Sectional Studies, Feeling, Content analysis, Female, medicine.symptom, 0305 other medical science, business, Psychology, Inclusion (education)
Abstract

Problem and background During the past two decades, Mexico has launched innovative maternal health initiatives to improve maternal and neonatal outcomes, placing emphasis on the incorporation of professional midwifery practices into the healthcare system. This study explored the perceptions of healthcare providers and women using public birth care services regarding professional midwifery practices and how can the inclusion of evidence-based midwifery techniques improve the quality of service. Methodology We conducted a qualitative, cross-sectional study of three healthcare networks in Mexico. A content analysis was performed of data collected through 109 semi-structured interviews: 72 with healthcare providers and 37 with women. Results Healthcare providers and women had minimal knowledge of the competencies and skills of professional midwives. Medical personnel accepted the incorporation of some evidence-based midwifery practices. Women had experienced fear and anguish during childbirth so they considered that incorporating professional midwifery practices into maternal health services would be favourable in that it would render birth care more respectful. Discussion and conclusions Healthcare providers are willing to consider the inclusion of some evidence-based midwifery practices in health services and regard assistance from professional midwives. They believe that structural conditions will complicate their incorporation. Although the women interviewed had experienced fear, anxiety and loneliness during childbirth, most of them admitted to feeling “safer” in a hospital (secondary-care health centre) setting where possible complications could be resolved. This perception of safety served to justify the delivery of healthcare in a manner that is inattentive to women’s needs, which go beyond biomedical issues and include emotions and the positive experience of childbirth.

Published
2020

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