Search

Showing total 29 results
Start Over Topic medicine.disease Language undetermined
29 results

1. Development and Psychometric Evaluation of the Diabetes Self-Efficacy Scale

Author

Bruce Paper, Susan Grinslade, Hongjuan Jing, and Laurie Quinn

Subjects
Adult, Gerontology, Psychometrics, United Kingdom Prospective Diabetes Study, Population, Type 2 diabetes, Surveys and Questionnaires, Diabetes mellitus, medicine, Humans, education, General Nursing, Aged, Glycemic, Aged, 80 and over, Type 1 diabetes, education.field_of_study, business.industry, Reproducibility of Results, Type 2 Diabetes Mellitus, General Medicine, Middle Aged, medicine.disease, Obesity, Self Efficacy, Self Care, Diabetes Mellitus, Type 2, Female, Factor Analysis, Statistical, business
Abstract

Background and Purpose: No scales measure self-efficacy in women with Type 2 diabetes. A scale was developed and tested. Methods: Items generated, content validity index (CVI) assessed by experts, the 2-part Diabetes Self-Efficacy Scale (DSLF-I and DSLF-II) was piloted with 62 women, administered to 208 women, and then readministered to 30 women to determine initial reliability. Factor analysis was conducted for construct validity. Discriminant, convergent, and predictive validity was examined. Results: The CVI index was 98%. Cronbach's alphas were 0.88 (DSLF-I) and 0.82 (DSLF-II; pilot) and 0.87 and 0.86, respectively (main study); test-retest correlation was .60 (DSLF-I) and .69 (DSLF-II). There were 3 factors that emerged: diabetes knowledge of self-care activity, diabetes diet self-care, and diabetes medication self-care. Conclusions: The Diabetes Self-Efficacy Scale demonstrates good initial reliability and validity.Keywords: instrument development; self-efficacy; diabetes mellitus Type 2; reliability; validity; factor analysisDiabetes mellitus affects 8.3% of the population in the United States, or 25.8 million people. More than 7 million people are estimated to be undiagnosed and unaware they have the disease (Center for Disease Control and Prevention [CDC], 2011). Approximately 90%-95% of persons with diabetes have Type 2 diabetes mellitus (T2DM). The San Antonio Heart Study revealed a rising incidence of T2DM, with age, ethnicity, and neighborhood as significant predictors of T2DM (Burke et al., 1999).Although T2DM affects all ethnic and gender groups, there is a disparate effect. For example, African Americans are 1.6 times more likely to have diabetes than Whites and are more likely to go undiagnosed American Diabetes Association (ADA, 2005a). Complications from T2DM are also more prevalent in minority populations (Carter, Pugh, & Monterosa, 1996). In addition, diabetic women, compared to diabetic men, have a significantly higher prevalence of cardiovascular disease and suffer greater adverse outcomes (D'Arrigo, 1999; Gu, Cowie, & Harris, 1999; Howard et al., 1998; Smitherman & Reis, 1997). Further, Sowers (1998) reported that the gender protectiveness for coronary heart disease (CHD) declines in women between the ages of 50 and 59 years, and that the loss of gender protectiveness increases the risk ratio for CHD to 3.5 for women with diabetes compared to 2.4 for men with diabetes (p. 618). Koerbel and Korytkowski (2003) stated that women with diabetes not only have greater risk for cardiovascular disease but they also suffer greater adverse outcomes. They cite several factors, which increase this risk in women: poorer glycemic control, elevated blood pressure and lipids, central obesity, increased depression and lower socioeconomic status. These factors contribute to increased morbidity and health care costs for women with diabetes. These data support the need for more research into prevention, detection, and cost-effective methods to effectively manage T2DM and prevent its complications in women.Maintenance of health and prevention of diabetic complications require significant changes in lifestyle management and adherence to a therapeutic diabetic regimen. Behavior change and adherence are not only difficult but are also often inadequate to maintain recommended glycemic control (Anderson, Fitzgerald, & Oh, 1993; Skelly, Marshall, Haughey, Davis, & Dunford, 1995). The importance of participation in diabetic self-care behavior in achieving glycemic control has been demonstrated by the Diabetes Control and Complications Trial Research Group (1993) for individuals with Type 1 diabetes mellitus (T1DM) and by the United Kingdom Prospective Diabetes Study Group (1998) for individuals with T2DM. This goal is accomplished through a therapeutic alliance among clients, family, and health care providers to promote self-care behaviors and therapeutic modalities (ADA, 2005b). Self-care behaviors include a combination of changing or modifying eating habits, maintaining weight or achieving weight loss, participating in a physical exercise program, self-monitoring of blood glucose, and/or taking oral or injectable medication. …

Published
2015

2. Tacrolimus monotherapy in membranous nephropathy: A randomized controlled trial

Author

Praga, M., Barrio, V., Juárez, G. Fernández, Luño, J., and For the GRUPO ESPAÑOL DE ESTUDIO DE LA NEFROPATÍA MEMBRANOSA (Members of the Group listed at the end of the paper)

Subjects
medicine.medical_specialty, Creatinine, Proteinuria, nephrotic syndrome, business.industry, Urology, membranous nephropathy, Renal function, Spontaneous remission, medicine.disease, Tacrolimus, Surgery, law.invention, chemistry.chemical_compound, Membranous nephropathy, chemistry, Randomized controlled trial, Nephrology, law, medicine, medicine.symptom, tacrolimus, business, Nephrotic syndrome
Abstract

Membranous nephropathy is a common cause of nephrotic syndrome in adults. Although some patients with membranous nephropathy achieve a spontaneous remission, renal function continues to deteriorate in others. We conducted a prospective randomized trial evaluating monotherapy with tacrolimus to achieve complete or partial remission in patients with biopsy-proven membranous nephropathy. Twenty-five patients received tacrolimus (0.05mg/kg/day) over 12 months with a 6-month taper, whereas 23 patients were in the control group. The probability of remission in the treatment group was 58, 82, and 94% after 6, 12, and 18 months but only 10, 24, and 35%, respectively in the control group. The decrease in proteinuria was significantly greater in the treatment group. Notably, six patients in the control group and only one in the treatment group reached the secondary end point of a 50% increase in their serum creatinine. No patient in the tacrolimus group showed a relapse during the taper period. Nephrotic syndrome reappeared in almost half of the patients who were in remission by the 18th month after tacrolimus withdrawal. We conclude that tacrolimus is a very useful therapeutic option for patients with membranous nephropathy and preserved renal function. The majority of patients experienced remission with a significant reduction in the risk for deteriorating renal function.

Published
2007

3. In vivo treatment with the herbal phenylethanoid acteoside ameliorates intestinal inflammation in dextran sulphate sodium-induced colitis

Author

D. H. Paper, Juergen Schoelmerich, Florian Obermeier, Nadja Dunger, K. Menzel, Werner Falk, Gerhard Rogler, Martin Hausmann, K. Balan, and Hans H Herfarth

Subjects
Necrosis, Colon, medicine.medical_treatment, Immunology, Enzyme-Linked Immunosorbent Assay, Inflammatory bowel disease, Antioxidants, Mice, Glucosides, Phenols, Weight Loss, medicine, Animals, Immunology and Allergy, Mesenteric lymph nodes, Intestinal Mucosa, Colitis, Acute colitis, Peroxidase, Respiratory Burst, Mice, Inbred BALB C, business.industry, Macrophages, Dextran Sulfate, Interleukin, medicine.disease, Respiratory burst, Cytokine, medicine.anatomical_structure, Acute Disease, Chronic Disease, Animal Studies, Cytokines, Female, Lymph Nodes, Inflammation Mediators, medicine.symptom, business
Abstract

Summary Recently we demonstrated that in inflammatory bowel disease (IBD) macrophage-oxidative burst activity is increased and NADPH oxidase mRNA is induced. The herbal phenylethanoid acteoside isolated from Plantago lanceolata L. was shown to exhibit anti-oxidative potential. Using the dextran sulphate sodium (DSS)-induced colitis model, in this study we have assessed whether systemic application of acteoside affects colitis. Colitis was induced by DSS in Balb/c mice. Treatment with acteoside (120, 600 µg/mouse/day) was performed intraperitoneally. The colon lengths were determined. Colonic tissue was scored histologically (max. score 8) by a blinded investigator. T cells isolated from mesenteric lymph nodes (MLN) were stimulated with anti-CD3 antibody in the presence of interleukin (IL)-2 (final concentration 10 U/ml). After incubation for 24 h, IL-1β, IL-6, IL-12 tumour necrosis factor (TNF)-α and interferon (IFN)-γ levels in supernatants were analysed by the beadlyte® cytokine detection system. Histological scoring of colonic tissue revealed that application of acteoside was followed by a significantly improved histological score. In acute colitis the histological score was 3·2 with acteoside versus 5·2 with phosphate-buffered saline (PBS) (P

Published
2007

4. Natural Products as Angiogenesis Inhibitors

Author

D. H. Paper

Subjects
Adult, Angiogenesis, Pharmaceutical Science, Inflammation, Endogeny, Biology, Analytical Chemistry, Neovascularization, Pathogenesis, Drug Discovery, medicine, Animals, Humans, Pharmacology, Molecular Structure, Neovascularization, Pathologic, Plant Extracts, Organic Chemistry, Cancer, medicine.disease, Angiogenesis inhibitor, Complementary and alternative medicine, Immunology, Cancer research, Molecular Medicine, medicine.symptom, Wound healing
Abstract

Angiogenesis is a strictly controlled process in the healthy, adult human body. It is regulated by a variety of endogenous angiogenic and angiostatic factors. It is only switched on, e.g., during wound healing. Pathological angiogenesis occurs, for example, in cancer, chronic inflammation, or atherosclerosis. Angiogenesis inhibitors are able to interfere with various steps of angiogenesis, like basement destruction of blood vessels, proliferation and migration of endothelial cells, or the lumen formation. Among the known angiogenesis inhibitors compounds derived from natural sources, like flavonoids, sulphated carbohydrates, or triterpenoids are playing a prominent role.

Published
1998

6. Changes in Default Alarm Settings and Standard In-Service are Insufficient to Improve Alarm Fatigue in an Intensive Care Unit: A Pilot Project

Author

Charles Reed, Azizeh K. Sowan, Albert Tarriela, Bruce Paper, and Tiffany Michelle Gomez

Subjects
Quality management, default alarm settings, Health Informatics, Human Factors and Ergonomics, intensive care unit, in-service, law.invention, 03 medical and health sciences, ALARM, Patient safety, 0302 clinical medicine, cardiac monitors, nursing, law, 030225 pediatrics, Intensive care, Alarm management, Medicine, survey, Nurse education, alarm fatigue, Original Paper, 030504 nursing, business.industry, Usability, medicine.disease, Intensive care unit, Medical emergency, 0305 other medical science, business
Abstract

Background: Clinical alarm systems safety is a national concern, specifically in intensive care units (ICUs) where alarm rates are known to be the highest. Interventional projects that examined the effect of changing default alarm settings on overall alarm rate and on clinicians’ attitudes and practices toward clinical alarms and alarm fatigue are scarce. Objective: To examine if (1) a change in default alarm settings of the cardiac monitors and (2) in-service nursing education on cardiac monitor use in an ICU would result in reducing alarm rate and in improving nurses’ attitudes and practices toward clinical alarms. Methods: This quality improvement project took place in a 20-bed transplant/cardiac ICU with a total of 39 nurses. We implemented a unit-wide change of default alarm settings involving 17 parameters of the cardiac monitors. All nurses received an in-service education on monitor use. Alarm data were collected from the audit log of the cardiac monitors 10 weeks before and 10 weeks after the change in monitors’ parameters. Nurses’ attitudes and practices toward clinical alarms were measured using the Healthcare Technology Foundation National Clinical Alarms Survey, pre- and postintervention. Results: Alarm rate was 87.86 alarms/patient day (a total of 64,500 alarms) at the preintervention period compared to 59.18 alarms/patient day (49,319 alarms) postintervention ( P =.01). At baseline, Arterial Blood Pressure (ABP), Pair Premature Ventricular Contractions (PVCs), and Peripheral Capillary Oxygen Saturation (SpO2) alarms were the highest. ABP and SpO2 alarms remained among the top three at the postproject period. Out of the 39 ICU nurses, 24 (62%) provided complete pre- and postproject survey questionnaires. Compared to the preintervention survey, no remarkable changes in the postproject period were reported in nurses’ attitudes. Themes in the narrative data were related to poor usability of cardiac monitors and the frequent alarms. The data showed great variation among nurses in terms of changing alarm parameters and frequency of replacing patients' electrodes. Despite the in-service, 50% (12/24) of the nurses specified their need for more training on cardiac monitors in the postproject period. Conclusions: Changing default alarm settings and standard in-service education on cardiac monitor use are insufficient to improve alarm systems safety. Alarm management in ICUs is very complex, involving alarm management practices by clinicians, availability of unit policies and procedures, unit layout, complexity and usability of monitoring devices, and adequacy of training on system use. The complexity of the newer monitoring systems requires urgent usability testing and multidimensional interventions to improve alarm systems safety and to attain the Joint Commission National Patient Safety Goal on alarm systems safety in critical care units. [JMIR Hum Factors 2016;3(1):e1]

Published
2016

7. Becoming a partner in your healthcare

Author

R. Paper

Subjects
Receipt, Service (business), medicine.medical_specialty, business.industry, media_common.quotation_subject, Control (management), Hematology, General Medicine, Haemophilia, medicine.disease, Intimidation, Quality of life (healthcare), Nursing, Feeling, Health care, medicine, business, Psychiatry, Genetics (clinical), media_common
Abstract

Chronic disorders such as haemophilia and von Willebrand disease can rob people of a feeling of control over their lives. Added to this is often a feeling of confusion or intimidation when dealing with the healthcare system. People may begin to feel like victims of their disorders and of the healthcare system. The healthcare system defines people who are in receipt of care as patients. The word patient comes from the Latin word patiens, which means to suffer, endure, allow, permit or undergo. Even the term implies a sense of victimization. People who become partners in their care and view the receipt and delivery of healthcare as a service wherein they are the consumer and the doctor or clinician is the provider, will feel more in control and will likely have better outcomes than people who assume the more traditional role of 'patient'.

Published
2002

8. Detained adolescents' attitudes about pregnancy and parenthood

Author

Bruce Paper, Patricia J. Kelly, and Janna Lesser

Subjects
Male, Parents, Adolescent, Population, Logistic regression, Developmental psychology, Pregnancy, medicine, Juvenile, Pediatric Nurse Practitioner, Humans, Justice (ethics), education, education.field_of_study, people.profession, medicine.disease, Juvenile detention, Health promotion, Cross-Sectional Studies, Adolescent Behavior, Pediatrics, Perinatology and Child Health, Female, Psychology, people, Attitude to Health
Abstract

Introduction The purpose of this study was to examine attitudes and behaviors associated with parenthood and pregnancy among adolescents in the juvenile justice system. Method A cross-sectional survey of attitudes and behaviors about parenthood was conducted with 300 adolescents residing in three juvenile detention centers. Results Data revealed high rates of risky behaviors that resulted in parenthood/pregnancy and generally positive attitudes about being an adolescent parent. Positive attitudes about parenthood (P = .000) and lower self-efficacy to not have sex (P = .021) were significantly correlated with having been pregnant or having fathered a child. Logistic regression showed positive attitudes about parenthood and the combination of drinking and driving together were significant predictors of pregnancy (P ≤ .05). Discussion Pediatric nurse practitioners working with adolescents in the juvenile justice system who routinely provide prevention counseling and implement health promotion programs must take into account the reality that many adolescents in this population are or will become parents and do not consider pregnancy as an outcome to be necessarily avoided. Moving beyond primary and secondary prevention strategies to implement programs to prevent second pregnancies and enhance parenting skills will provide needed health benefits to these adolescent parents.

Published
2007

9. Can you recognize and respond to von Willebrand disease?

Author

Renee Paper

Subjects
Advanced and Specialized Nursing, business.industry, Anti-Inflammatory Agents, Non-Steroidal, Estrogens, Assessment and Diagnosis, Emergency Nursing, LPN and LVN, Critical Care Nursing, Bioinformatics, medicine.disease, Nurse's Role, Antifibrinolytic Agents, Hemostatics, Patient Care Planning, von Willebrand Diseases, Patient Education as Topic, Adaptation, Psychological, Von Willebrand disease, Medicine, Humans, Deamino Arginine Vasopressin, Blood Coagulation Tests, business, Progesterone
Published
2003

10. A Case Study of the Military Utility of Telemedicine

Author

Parag C. Pendharkar, David Paper, and James A. Rodger

Subjects
Telemedicine, Decision support system, medicine, Business, Medical emergency, medicine.disease
Abstract

In order to meet the medical management challenges presented by increasing global crises, the U.S. military must find ways to more effectively manage manpower and time. In response, Joint Medical Operations –Telemedicine (JMO-T) has been developed by the Department of Defense (DOD) to collect and transmit near-real-time, far-forward medical data and to assess how this improved capability enhances medical management of the battlespace. JMO-T has been successful in resolving uncertain organizational and technological military deficiencies and in improving medical communications and information management. Deployable, mobile telemedicine teams are the centerpieces of JMO-T. These teams have the capability of inserting essential networking and communications capabilities into austere theaters and establishing an immediate means for enhancing health protection, collaborative planning, situational awareness and strategic decision-making. One objective of this chapter is to relate the rationale used by the DOD to determine the military utility of the Joint Medical Operations–Telemedicine Advanced Concept Technology Demonstration (JMO-T ACTD) or ACTD for short. ACTD is a JMO-T initiative developed for the purpose of improving joint medical planning capabilities, access and timeliness of medical care, and integration of medical situational awareness. The chapter discusses in detail the complexities involved in the ACTD initiative. A second objective of the chapter is to articulate the development of Critical Operational Issues (COIS) and Measures of Effectiveness (MOE) as methodologies for investigating the military utility of telemedicine.

Published
2001

12. Requirement of H-2 heterozygosity for autoimmunity in (NZB × NZW)F1 hybrid mice

Author

Short Paper, Sachiko Hirose, Genjiro Ueda, Kazuo Noguchi, Takashi Okada, Iwao Sekigawa, Hidetoshi Sato, and Toshikazu Shirai

Subjects
Heterozygote, Receptors, Antigen, T-Cell, alpha-beta, Immunology, Receptors, Antigen, T-Cell, Congenic, chemical and pharmacologic phenomena, urologic and male genital diseases, medicine.disease_cause, Immunoglobulin G, Autoimmune Diseases, Autoimmunity, Pathogenesis, Loss of heterozygosity, Mice, Immune system, immune system diseases, medicine, Animals, Immunology and Allergy, skin and connective tissue diseases, Autoimmune disease, Mice, Inbred NZB, biology, H-2 Antigens, DNA, medicine.disease, Peptide Fragments, biology.protein, Hybridization, Genetic, Antibody
Abstract

In the F1 hybrid of autoimmune New Zealand Black (NZB) and phenotypically normal New Zealand White (NZW) mice, there occurs a severe systemic lupus erythematosus (SLE)-like autoimmune disease more fulminant than that found in the parental NZB mice. To determine the role of the H-2 complex in the pathogenesis of autoimmune disease of the (NZB X NZW)F1 hybrid, we developed H-2-congenic NZB (NZB.H-2z) and NZW (NZW.H-2d) strains, and compared the degree of autoimmune features between congenic H-2d/H-2d and H-2z/H-2z homozygous F1 hybrids and the original H-2d/H-2z heterozygous (NZB X NZW)F1 hybrid. We found that autoimmune features such as productions of IgG class anti-DNA antibodies and retroviral gp70 immune complexes and the development of renal disease were to a great extent reduced in both H-2 homozygous F1 hybrids, as compared with the H-2 heterozygous (NZB X NZW)F1 hybrid. It would thus appear that the heterozygosity of H-2d haplotype derived from NZB and H-2z from NZW is essential for the autoimmune disease characteristic of the (NZB X NZW)F1 hybrid.

Published
1986

14. Toward a General Calculus of Phonemic Distribution

Author

Herbert H. Paper and Frank Harary

Subjects
Linguistics and Language, Distribution (number theory), Computer science, medicine, Calculus, medicine.disease, Language and Linguistics, Calculus (medicine)
Published
1957

15. Critical reappraisal of Balangero chrysotile and mesothelioma risk

Author

Yumi M Kumiya, Edward B. Ilgren, John A. Hoskins, Frederick D. Pooley, and Dr Ilgren wrote this paper when a Consultant to companies in asbestos litigation

Subjects
lcsh:R5-920, Epidemiology, business.industry, lcsh:Public aspects of medicine, lcsh:RA1-1270, Diagnostic accuracy, medicine.disease, Pleural disease, Cross matching, Tremolite Asbestos, Environmental health, Chrysotile, medicine, Amphibole asbestos, Tremolite, Mesothelioma, lcsh:Medicine (General), business
Abstract

BackgroundBalangero, 40 km northwest of Torino in the Piedmonte Region, was home to the largest and most active chrysotile mine in Europe operating from 1916 - 1990 and employed over 300 men at any one time. The chrysotile was thought to be pure. Despite this some claim it has been responsible for causing numerous mesotheliomas. This report refutes this claim on the grounds that it is not pure but potentially contaminated by tremolite asbestos. In addition there are numerous alternate sources of naturally occurring and commercially available amphibole asbestos in the region.MethodsGeological studies illustrate the presence of naturally occurring tremolite and various analyses have shown naturally occurring and commercially used amphibole its presence in animal and human tissue. The diagnostic criteria used to study pleural disease in the Balangero cohort were examined on a case by case basis. ResultsSeveral authors have searched available registries for post-mortem information and listed possible mesothelioma cases. Cross matching these searches has been attempted and the strength of their diagnoses examined. Conclusion.There is good evidence that crocidolite, amosite and tremolite are responsible for the alleged mesothelioma cases at Balangero. Myriad sources of naturally occurring and commercial amphibole asbestos exist in the region to account for the alleged cases. Regrettably, necessary information is incomplete and insufficient for the cohort which calls the diagnostic accuracy of the cases into question. The problem is further compounded by confusion surrounding job titles and raises the question if any of cases actually ever occurred in ‘miners’ per se.

Published
2022

16. The association between objective vision impairment and mild cognitive impairment among older adults in low- and middle-income countries

Author

Hans Oh, Ai Koyanagi, Guillermo F. López-Sánchez, Jae Il Shin, Yvonne Barnett, Lee Smith, Pinar Soysal, Louis Jacob, Laurie T. Butler, Nicola Veronese, Shahina Pardhan, Université de Versailles Saint-Quentin-en-Yvelines - UFR Sciences de la santé Simone Veil (UVSQ Santé), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), National Institute on Aging, NIA: 08-CN-0020, OGHA 04034785, R01-AG034479, R21-AG034263, Y1-AG-1005, YA1323, This paper uses data from WHO?s Study on Global Ageing and Adult Health (SAGE). SAGE is supported by the U.S. National Institute on Aging through Interagency Agreements OGHA 04034785, YA1323?08-CN-0020, Y1-AG-1005?01 and through research grants R01-AG034479 and R21-AG034263., Smith, L., Shin, J.I., Jacob, L., López-Sánchez, G.F., Oh, H., Barnett, Y., Pardhan, S., Butler, L., Soysal, P., Veronese, N., Koyanagi, A., and SOYSAL, PINAR

Subjects
Male, Gerontology, China, Aging, medicine.medical_specialty, Visual acuity, genetic structures, Epidemiology, [SDV]Life Sciences [q-bio], Visual impairment, Vision impairment, Logistic regression, Odds, 03 medical and health sciences, 0302 clinical medicine, Prevalence, Humans, Medicine, Dementia, Cognitive Dysfunction, 030212 general & internal medicine, Association (psychology), Developing Countries, Aged, Low- and middle-income countries, business.industry, Mild cognitive impairment, medicine.disease, eye diseases, Smith L., Shin J. I. , Jacob L., López-Sánchez G. F. , Oh H., Barnett Y., Pardhan S., Butler L., Soysal P., Veronese N., et al., -The association between objective vision impairment and mild cognitive impairment among older adults in low- and middle-income countries.-, Aging clinical and experimental research, 2021, Vision impairment, Mild cognitive impairment, Older adults, Low- and middle-income countries, Epidemiology, Cross-Sectional Studies, Ageing, Older adults, Female, Geriatrics and Gerontology, medicine.symptom, business, 030217 neurology & neurosurgery
Abstract

Aim: The association between visual impairment and mild cognitive impairment (MCI) has not been investigated to date. Thus, we assessed this association among older adults from six low- and middle-income countries (LMICs) (China, India, Ghana, Mexico, Russia, and South Africa) using nationally representative datasets. Methods: Cross-sectional, community-based data from the WHO Study on global AGEing and adult health (SAGE) were analyzed. Visual acuity was measured using the tumbling ElogMAR chart, and vision impairment (at distance and near) was defined as visual acuity worse than 6/18 (0.48 logMAR) in the better-seeing eye. The definition of MCI was based on the National Institute on Aging-Alzheimer’s Association criteria. Multivariable logistic regression was conducted. Results: Data on 32,715 individuals aged ≥ 50years [mean (SD) age 62.1 (15.6) years; 51.2% females] were analyzed. Compared to those without far or near vision impairment, those with near vision impairment but not far vision impairment (OR = 1.33; 95% CI = 1.16–1.52), and those with both far and near vision impairment (OR = 1.70; 95% CI = 1.27–2.29) had significantly higher odds for MCI. Only having far vision impairment was not significantly associated with MCI. Conclusions: Visual impairment is associated with increased odds for MCI among older adults in LMICs with the exception of far vision impairment only. Future longitudinal and intervention studies should examine causality and whether improvements in visual acuity, or early intervention, can reduce risk for MCI and ultimately, dementia. © 2021, The Author(s), under exclusive licence to Springer Nature Switzerland AG part of Springer Nature.

Published
2021

17. Metabolic perturbations prior to hepatocellular carcinoma diagnosis: Findings from a prospective observational cohort study

Author

Eva Ardanaz, Agnetha Linn Rostgaard-Hansen, Alessio Naccarati, Elisabete Weiderpass, Pekka Keski-Rahkonen, Rudolf Kaaks, Tilman Kühn, Anna Winkvist, Jośe Mariá Huerta, H. B. Bueno-De-Mesquita, Guri Skeie, Pietro Ferrari, Krasimira Aleksandrova, Gabriel Perlemuter, Augustin Scalbert, Olatz Mokoroa, Giovanna Tagliabue, Marc J. Gunter, Kim Overvad, José Ramón Quirós, Agneta Kiss, Marie-Christine Boutron-Ruault, Yahya Mahamat-Saleh, Talita Duarte-Salles, Nivonirina Robinot, Anne Tjønneland, Antonia Trichopoulou, Julie A. Schmidt, Christina C. Dahm, Roel Vermeulen, Rosario Tumino, Núria Sala, Joseph A. Rothwell, Sophia Harlid, Magdalena Stepien, Klas Sjöberg, Vivian Viallon, Neil Murphy, Anna Karakatsani, Salvatore Panico, Nicholas J. Wareham, María José Sánchez, Francesca Mancini, Domenico Palli, Mazda Jenab, Elio Riboli, Bodil Ohlsson, Kay-Tee Khaw, Centre de recherche en épidémiologie et santé des populations (CESP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Institut National Du Cancer, INCa: 2014-1-RT-02-CIRC-1 Ministerie van Volksgezondheid, Welzijn en Sport, VWS Cancer Research UK, CRUK: C570/A16491 Ministerie van Volksgezondheid, Welzijn en Sport, VWS Ligue Contre le Cancer German Cancer Research Center, DKFZ Bundesministerium für Bildung und Forschung, BMBF Institut National de la Santé et de la Recherche Médicale, Inserm Kræftens Bekæmpelse, DCS National Research Council, NRC 6236 Hellenic Health Foundation, HHF Fondation Gustave Roussy European Commission, EC Centre International de Recherche sur le Cancer, CIRC Associazione Italiana per la Ricerca sul Cancro, AIRC RD06/0020 Deutsche Krebshilfe World Cancer Research Fund, WCRF Cancerfonden Medical Research Council, MRC: MR/M012190/1, This work was supported by the French National Cancer Institute (L'Institut National du Cancer, INCA) (grant number 2014-1-RT-02-CIRC-1, PI: M. Jenab). The coordination of EPIC is financially supported by the European Commission (DG-SANCO), and the International Agency for Research on Cancer. The national cohorts are supported by Danish Cancer Society (Denmark), Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle G?n?rale de l'Education Nationale, and Institut National de la Sant? et de la Recherche M?dicale (INSERM) (France), Deutsche Krebshilfe, Deutsches Krebsforschungszentrum (DKFZ), and Federal Ministry of Education and Research (Germany), Hellenic Health Foundation (Greece), Italian Association for Research on Cancer (AIRC), National Research Council, and AIRE-ONLUS Ragusa, AVIS Ragusa, Sicilian Government (Italy), Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), and Statistics Netherlands (the Netherlands), and Nordic Center of Excellence Programme on Food, Nutrition and Health (Norway), Health Research Fund (FIS), Regional Governments of Andaluc?a, Asturias, Basque Country, Murcia (No. 6236) and Navarra, and ISCIII RETIC (RD06/0020) and the Catalan Institute of Oncology (Spain), Swedish Cancer Society, Swedish Scientific Council, and Regional Government of Sk?ne and V?sterbotten (Sweden), Cancer Research UK (14136 for EPIC-Norfolk and C570/A16491 for EPIC-Oxford) and the Medical Research Council (1000143 for EPIC-Norfolk and MR/M012190/1 for EPIC-Oxford) (UK). The funding sources had no influence on the design of the study, the collection, analysis, and interpretation of data, the writing of the report, and or the decision to submit the paper for publication. Disclaimer: Where authors are identified as personnel of the International Agency for Research on Cancer/World Health Organization, the authors alone are responsible for the views expressed in this article and they do not necessarily represent the decisions, policy or views of the International Agency for Research on Cancer/World Health Organization.

Subjects
Male, Oncology, Cancer Research, medicine.medical_specialty, Carcinoma, Hepatocellular, prospective observational cohort, Glycocholic acid, [SDV.CAN]Life Sciences [q-bio]/Cancer, Mass Spectrometry, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Dehydroepiandrosterone sulfate, Internal medicine, Biomarkers, Tumor, medicine, Humans, Metabolomics, Prospective Studies, Aged, Hepatitis, business.industry, Liver Neoplasms, Cancer, Feeding Behavior, hepatocellular carcinoma, Middle Aged, medicine.disease, 3. Good health, European Prospective Investigation into Cancer and Nutrition, untargeted metabolomics, chemistry, Case-Control Studies, 030220 oncology & carcinogenesis, Hepatocellular carcinoma, Cohort, Female, business, Metabolic Networks and Pathways, Chromatography, Liquid, Cohort study
Abstract

International audience; Hepatocellular carcinoma (HCC) development entails changes in liver metabolism. Current knowledge on metabolic perturbations in HCC is derived mostly from case-control designs, with sparse information from prospective cohorts. Our objective was to apply comprehensive metabolite profiling to detect metabolites whose serum concentrations are associated with HCC development, using biological samples from within the prospective European Prospective Investigation into Cancer and Nutrition (EPIC) cohort (>520 000 participants), where we identified 129 HCC cases matched 1:1 to controls. We conducted high-resolution untargeted liquid chromatography-mass spectrometry-based metabolomics on serum samples collected at recruitment prior to cancer diagnosis. Multivariable conditional logistic regression was applied controlling for dietary habits, alcohol consumption, smoking, body size, hepatitis infection and liver dysfunction. Corrections for multiple comparisons were applied. Of 9206 molecular features detected, 220 discriminated HCC cases from controls. Detailed feature annotation revealed 92 metabolites associated with HCC risk, of which 14 were unambiguously identified using pure reference standards. Positive HCC-risk associations were observed for N1-acetylspermidine, isatin, p-hydroxyphenyllactic acid, tyrosine, sphingosine, l,l-cyclo(leucylprolyl), glycochenodeoxycholic acid, glycocholic acid and 7-methylguanine. Inverse risk associations were observed for retinol, dehydroepiandrosterone sulfate, glycerophosphocholine, γ-carboxyethyl hydroxychroman and creatine. Discernible differences for these metabolites were observed between cases and controls up to 10 years prior to diagnosis. Our observations highlight the diversity of metabolic perturbations involved in HCC development and replicate previous observations (metabolism of bile acids, amino acids and phospholipids) made in Asian and Scandinavian populations. These findings emphasize the role of metabolic pathways associated with steroid metabolism and immunity and specific dietary and environmental exposures in HCC development.

Published
2020

18. Statin Use and Skin Cancer Risk: A Prospective Cohort Study

Author

Trude Eid Robsahm, Agnès Fournier, Yahya Mahamat-Saleh, Reza Ghiasvand, Marina Kvaskoff, Manon Cairat, Marie-Christine Boutron-Ruault, Iris Cervenka, Marie Al Rahmoun, Gianluca Severi, Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Oslo University Hospital [Oslo], Cancer Registry of Norway, International Agency for Cancer Research (IACR), Università degli Studi di Firenze = University of Florence (UniFI), 2102 918823, NCT03285230, Centre International de Recherche sur le Cancer, CIRC, Agence Nationale de la Recherche, ANR: ANR-10-COHO-0006, Institut National de la Santé et de la Recherche Médicale, Inserm, Institut National Du Cancer, INCa: INCa_13539, Institut Gustave-Roussy, Mutuelle Générale de l'Education Nationale, MGEN, We are grateful to the study participants for their continued participation and to practitioners for providing pathology reports. We also thank all members of the E3N study group, particularly Rafika Cha?t, Ghizlane Bajawi-Esselma, Amandine Gelot, Marie Fangon, Pascale Gerbouin-R?rolle, Sabine Moreira-Faria, Nad?ge Senina, Sofiane Harizi, Lyan Hoang, Anita Kowal, and Camille Laplanche for their technical assistance. The E3N cohort from the French National Institute of Health and Medical Research (Inserm) was supported by the Mutuelle G?n?rale de l'Education Nationale, the Gustave Roussy Institute, and the French League against Cancer. E3N-E4N is also supported by the French National Research Agency under the Investment for the Future Program (ANR-10-COHO-0006) and by the French Ministry of Higher Education, Research and Innovation (subsidy for public service charges #2102 918823). MAR, YMS, and IC were supported by research scholarships from the French National Cancer Institute (MAR: INCa_13539), the Paris Ile-de-France region, and the French Ministry of Research, respectively. This study is listed at ClinicalTrials.gov as NCT03285230. The work reported in this paper was performed during Agn?s Fournier's term as a Visiting Scientist at the International Agency for Research on Cancer. Conceptualization: MK, AF, Data Curation: MAR, AF, Formal Analysis: MAR, Funding Acquisition: MAR, MK, AF, Investigation: MAR, MK, AF, Methodology: MK, AF, Project Administration: MK, AF, Resources: GS, MCBR, MK, AF, Software: MAR, AF, Supervision: MK, AF, Visualization: MAR, Validation: MK, AF, Writing - Original Draft Preparation: MAR, RG, TER, MK, AF, Writing - Review and Editing: MAR, RG, MC, YMS, IC, GS, MCBR, TER, MK, AF, Funding sources had no role in study design, collection, analysis, and interpretation of data, writing of the report, and the decision to submit the article for publication., ANR-10-COHO-0006,E4N,Etude Epidémiologique des Enfants de femmes de l'Education Nationale(2010), HAL UVSQ, Équipe, and Cohortes - Etude Epidémiologique des Enfants de femmes de l'Education Nationale - - E4N2010 - ANR-10-COHO-0006 - COHO - VALID

Subjects
Male, medicine.medical_specialty, Skin Neoplasms, [SDV]Life Sciences [q-bio], [SDV.CAN]Life Sciences [q-bio]/Cancer, Dermatology, Biochemistry, Cohort Studies, [SDV.CAN] Life Sciences [q-bio]/Cancer, Risk Factors, Internal medicine, Epidemiology, medicine, Humans, Basal cell carcinoma, Prospective Studies, Prospective cohort study, Melanoma, Molecular Biology, Proportional Hazards Models, Aged, 80 and over, business.industry, Hazard ratio, Cell Biology, [SDV.MHEP.DERM] Life Sciences [q-bio]/Human health and pathology/Dermatology, medicine.disease, Confidence interval, [SDV] Life Sciences [q-bio], Defined daily dose, Carcinoma, Basal Cell, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, [SDV.SP.PHARMA] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Carcinoma, Squamous Cell, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Female, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Skin cancer, business, Body mass index, [SDV.MHEP.DERM]Life Sciences [q-bio]/Human health and pathology/Dermatology
Abstract

International audience; Epidemiological studies on statin use in relation to skin cancer risk are scarce and yielded conflicting results. We explored this association in Etude Epidémiologique auprès de femmes de l'Education Nationale, a prospective cohort of French women born in 1925–1950. Health and lifestyle data were self-reported biennially and matched with drug reimbursement data, allowing the identification of participants’ statin use since 2004. Multivariable cause-specific hazards regression models adjusted for skin cancer risk factors estimated hazard ratios with 95% confidence intervals. Over 2004–2014, 455 cutaneous melanoma, 1,741 basal cell carcinoma, and 268 squamous cell carcinoma cases were ascertained among 62,473 women. Compared with never use, there were no associations between ever use of statins and melanoma (hazard ratio = 1.16, 95% confidence interval = 0.94–1.44) or squamous cell carcinoma (hazard ratio = 0.89, 95% confidence interval = 0.66–1.19) risks and a decrease in basal cell carcinoma risk with ever use of statins (hazard ratio = 0.89, 95% confidence interval = 0.79–0.996). We found no trend of increasing or decreasing risks with dose, duration of use, time since first use, or age at first use and no statistically significant effect modification by pigmentary traits or residential UVR exposure. Because of the limited number of studies evaluating the associations between the use of statins and the risks of melanoma, basal cell carcinoma, and squamous cell carcinoma, these findings would deserve further investigation in other settings.

Published
2022

19. Phenotypic expansion of CACNA1C-associated disorders to include isolated neurological manifestations

Author

Lance H. Rodan, Rebecca C. Spillmann, Harley T. Kurata, Shawn M. Lamothe, Jasmine Maghera, Rami Abou Jamra, Anna Alkelai, Stylianos E. Antonarakis, Isis Atallah, Omer Bar-Yosef, Frédéric Bilan, Kathrine Bjorgo, Xavier Blanc, Patrick Van Bogaert, Yoav Bolkier, Lindsay C. Burrage, Björn U. Christ, Jorge L. Granadillo, Patricia Dickson, Kirsten A. Donald, Christèle Dubourg, Aviva Eliyahu, Lisa Emrick, Kendra Engleman, Michaela Veronika Gonfiantini, Jean-Marc Good, Judith Kalser, Chiara Kloeckner, Guus Lachmeijer, Marina Macchiaiolo, Francesco Nicita, Sylvie Odent, Emily O’Heir, Xilma Ortiz-Gonzalez, Marta Pacio-Miguez, María Palomares-Bralo, Loren Pena, Konrad Platzer, Mathieu Quinodoz, Emmanuelle Ranza, Jill A. Rosenfeld, Eliane Roulet-Perez, Avni Santani, Fernando Santos-Simarro, Ben Pode-Shakked, Cara Skraban, Rachel Slaugh, Andrea Superti-Furga, Isabelle Thiffault, Richard H. van Jaabrsveld, Marie Vincent, Hong-Gang Wang, Pia Zacher, Mercedes E. Alejandro, Mahshid S. Azamian, Carlos A. Bacino, Ashok Balasubramanyam, Hsiao-Tuan Chao, Gary D. Clark, William J. Craigen, Hongzheng Dai, Shweta U. Dhar, Lisa T. Emrick, Alica M. Goldman, Neil A. Hanchard, Fariha Jamal, Lefkothea Karaviti, Seema R. Lalani, Brendan H. Lee, Richard A. Lewis, Ronit Marom, Paolo M. Moretti, David R. Murdock, Sarah K. Nicholas, James P. Orengo, Jennifer E. Posey, Lorraine Potocki, Susan L. Samson, Daryl A. Scott, Alyssa A. Tran, Tiphanie P. Vogel, Michael F. Wangler, Shinya Yamamoto, Christine M. Eng, Pengfei Liu, Patricia A. Ward, Edward Behrens, Matthew Deardorff, Marni Falk, Kelly Hassey, Kathleen Sullivan, Adeline Vanderver, David B. Goldstein, Heidi Cope, Allyn McConkie-Rosell, Kelly Schoch, Vandana Shashi, Edward C. Smith, Jennifer A. Sullivan, Queenie K.-G. Tan, Nicole M. Walley, Pankaj B. Agrawal, Alan H. Beggs, Gerard T. Berry, Lauren C. Briere, Laurel A. Cobban, Matthew Coggins, Cynthia M. Cooper, Elizabeth L. Fieg, Frances High, Ingrid A. Holm, Susan Korrick, Joel B. Krier, Sharyn A. Lincoln, Joseph Loscalzo, Richard L. Maas, Calum A. MacRae, J. Carl Pallais, Deepak A. Rao, Edwin K. Silverman, Joan M. Stoler, David A. Sweetser, Melissa Walker, Chris A. Walsh, Cecilia Esteves, Emily G. Kelley, Isaac S. Kohane, Kimberly LeBlanc, Alexa T. McCray, Anna Nagy, Surendra Dasari, Brendan C. Lanpher, Ian R. Lanza, Eva Morava, Devin Oglesbee, Guney Bademci, Deborah Barbouth, Stephanie Bivona, Olveen Carrasquillo, Ta Chen Peter Chang, Irman Forghani, Alana Grajewski, Rosario Isasi, Byron Lam, Roy Levitt, Xue Zhong Liu, Jacob McCauley, Ralph Sacco, Mario Saporta, Judy Schaechter, Mustafa Tekin, Fred Telischi, Willa Thorson, Stephan Zuchner, Heather A. Colley, Jyoti G. Dayal, David J. Eckstein, Laurie C. Findley, Donna M. Krasnewich, Laura A. Mamounas, Teri A. Manolio, John J. Mulvihill, Grace L. LaMoure, Madison P. Goldrich, Tiina K. Urv, Argenia L. Doss, Maria T. Acosta, Carsten Bonnenmann, Precilla D’Souza, David D. Draper, Carlos Ferreira, Rena A. Godfrey, Catherine A. Groden, Ellen F. Macnamara, Valerie V. Maduro, Thomas C. Markello, Avi Nath, Donna Novacic, Barbara N. Pusey, Camilo Toro, Colleen E. Wahl, Eva Baker, Elizabeth A. Burke, David R. Adams, William A. Gahl, May Christine V. Malicdan, Cynthia J. Tifft, Lynne A. Wolfe, John Yang, Bradley Power, Bernadette Gochuico, Laryssa Huryn, Lea Latham, Joie Davis, Deborah Mosbrook-Davis, Francis Rossignol, null Ben Solomon, John MacDowall, Audrey Thurm, Wadih Zein, Muhammad Yousef, Margaret Adam, Laura Amendola, Michael Bamshad, Anita Beck, Jimmy Bennett, Beverly Berg-Rood, Elizabeth Blue, Brenna Boyd, Peter Byers, Sirisak Chanprasert, Michael Cunningham, Katrina Dipple, Daniel Doherty, Dawn Earl, Ian Glass, Katie Golden-Grant, Sihoun Hahn, Anne Hing, Fuki M. Hisama, Martha Horike-Pyne, Gail P. Jarvik, Jeffrey Jarvik, Suman Jayadev, Christina Lam, Kenneth Maravilla, Heather Mefford, J. Lawrence Merritt, Ghayda Mirzaa, Deborah Nickerson, Wendy Raskind, Natalie Rosenwasser, C. Ron Scott, Angela Sun, Virginia Sybert, Stephanie Wallace, Mark Wener, Tara Wenger, Euan A. Ashley, Gill Bejerano, Jonathan A. Bernstein, Devon Bonner, Terra R. Coakley, Liliana Fernandez, Paul G. Fisher, Laure Fresard, Jason Hom, Yong Huang, Jennefer N. Kohler, Elijah Kravets, Marta M. Majcherska, Beth A. Martin, Shruti Marwaha, Colleen E. McCormack, Archana N. Raja, Chloe M. Reuter, Maura Ruzhnikov, Jacinda B. Sampson, Kevin S. Smith, Shirley Sutton, Holly K. Tabor, Brianna M. Tucker, Matthew T. Wheeler, Diane B. Zastrow, Chunli Zhao, William E. Byrd, Andrew B. Crouse, Matthew Might, Mariko Nakano-Okuno, Jordan Whitlock, Gabrielle Brown, Manish J. Butte, Esteban C. Dell’Angelica, Naghmeh Dorrani, Emilie D. Douine, Brent L. Fogel, Irma Gutierrez, Alden Huang, Deborah Krakow, Hane Lee, Sandra K. Loo, Bryan C. Mak, Martin G. Martin, Julian A. Martínez-Agosto, Elisabeth McGee, Stanley F. Nelson, Shirley Nieves-Rodriguez, Christina G.S. Palmer, Jeanette C. Papp, Neil H. Parker, Genecee Renteria, Rebecca H. Signer, Janet S. Sinsheimer, Jijun Wan, Lee-kai Wang, Katherine Wesseling Perry, Jeremy D. Woods, Justin Alvey, Ashley Andrews, Jim Bale, John Bohnsack, Lorenzo Botto, John Carey, Laura Pace, Nicola Longo, Gabor Marth, Paolo Moretti, Aaron Quinlan, Matt Velinder, Dave Viskochil, Pinar Bayrak-Toydemir, Rong Mao, Monte Westerfield, Anna Bican, Elly Brokamp, Laura Duncan, Rizwan Hamid, Jennifer Kennedy, Mary Kozuira, John H. Newman, John A. PhillipsIII, Lynette Rives, Amy K. Robertson, Emily Solem, Joy D. Cogan, F. Sessions Cole, Nichole Hayes, Dana Kiley, Kathy Sisco, Jennifer Wambach, Daniel Wegner, Dustin Baldridge, Stephen Pak, Timothy Schedl, Jimann Shin, Lilianna Solnica-Krezel, Eric Rush, Geoffrey S. Pitt, Ping Yee Billie Au, Boston Children's Hospital, University of Alberta, Universität Leipzig [Leipzig], Geneva University Hospital (HUG), Tel Aviv University [Tel Aviv], Service Génétique Médicale [CHU Poitiers], Centre hospitalier universitaire de Poitiers (CHU Poitiers), Cibles moléculaires et thérapeutiques de la maladie d'Alzheimer (CIMoTHeMA), Université de Poitiers, Laboratoire Jacques-Louis Lions (LJLL (UMR_7598)), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Baylor College of Medicine (BCM), Baylor University, Washington University School of Medicine in St. Louis, Washington University in Saint Louis (WUSTL), CHU Pontchaillou [Rennes], Institut de Génétique et Développement de Rennes (IGDR), Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Centre National de la Recherche Scientifique (CNRS)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS), Lausanne University Hospital, Centre de référence Maladies Rares CLAD-Ouest [Rennes], Broad Institute of MIT and Harvard (BROAD INSTITUTE), Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston], Children’s Hospital of Philadelphia (CHOP ), Hospital Universitario La Paz, unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Centre hospitalier universitaire de Nantes (CHU Nantes), Duke University [Durham], University of Kansas Medical Center [Lawrence], University of Missouri System, Children's Mercy Hospital [Kansas City], Weill Cornell Medicine [New York], University of Calgary, Research reported in this paper was supported by the NIH Common Fund, through the Office of Strategic Coordination/Office of the NIH Director under award number(s) (U01HG007709 [Baylor College of Medicine] and U01HG007672 [Duke University to V.S.]). Additional funding for this project was under award number 1RO1HD090132-01A1 (Cornell University to G.P.). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Additional funding was provided by a Canadian Institutes of Health Research Grant (MOP-97988 to H.T.K.), and a Rowland and Muriel Haryett Fellowship (University of Alberta, to S.M.L.) and a fellowship from the Ministry of Education and Research of the Community of Madrid to M.P.M. (B2017/BMD-3721), and microgrant from the Rare Disease Foundation (P.Y.B.A. and H.T.K.). Sequencing and analysis was supported by the National Human Genome Research Institute grants UM1 HG008900 and R01 HG009141. K.A.D., B.C., and E.O. were supported the National Institute of Mental Health U01 MH119689., Universität Leipzig, Columbia University Medical Center (CUMC), Columbia University [New York], Tel Aviv University (TAU), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Unité de recherche de l'institut du thorax (ITX-lab), University of Kansas Medical Center [Kansas City, KS, USA], Weill Cornell Medicine [Cornell University], and Cornell University [New York]

Subjects
Ataxia, Calcium Channels, L-Type, Long QT syndrome, Timothy syndrome, Bioinformatics, Article, 03 medical and health sciences, Epilepsy, 0302 clinical medicine, Intellectual disability, medicine, Missense mutation, Humans, Autistic Disorder, Genetics (clinical), 030304 developmental biology, 0303 health sciences, [SDV.GEN]Life Sciences [q-bio]/Genetics, business.industry, medicine.disease, Hypotonia, Long QT Syndrome, Phenotype, Autism, Syndactyly, medicine.symptom, business, 030217 neurology & neurosurgery
Abstract

International audience; Purpose:CACNA1C encodes the alpha-1-subunit of a voltage-dependent L-type calcium channel expressed in human heart and brain. Heterozygous variants in CACNA1C have previously been reported in association with Timothy syndrome and long QT syndrome. Several case reports have suggested that CACNA1C variation may also be associated with a primarily neurological phenotype.Methods:We describe 25 individuals from 22 families with heterozygous variants in CACNA1C, who present with predominantly neurological manifestations.Results:Fourteen individuals have de novo, nontruncating variants and present variably with developmental delays, intellectual disability, autism, hypotonia, ataxia, and epilepsy. Functional studies of a subgroup of missense variants via patch clamp experiments demonstrated differential effects on channel function in vitro, including loss of function (p.Leu1408Val), neutral effect (p.Leu614Arg), and gain of function (p.Leu657Phe, p.Leu614Pro). The remaining 11 individuals from eight families have truncating variants in CACNA1C. The majority of these individuals have expressive language deficits, and half have autism.Conclusion:We expand the phenotype associated with CACNA1C variants to include neurodevelopmental abnormalities and epilepsy, in the absence of classic features of Timothy syndrome or long QT syndrome.

Published
2020

20. Current use of inotropes in circulatory shock

Author

Michael R. Pinsky, Maria Cronhjort, Thomas Kaufmann, Rupert M Pearse, Ludhmila Abrahão Hajjar, Daniel A. Reuter, Jean Louis Vincent, Daniel De Backer, Martin W. Dünser, Maurizio Cecconi, Xavier Monnet, Iwan C. C. van der Horst, Vanina Siham Kanoore Edul, Bernard Cholley, Claude Martin, Thomas Scheeren, Yasser Sakr, Philippe Vignon, Didier Payen, Olfa Hamzaoui, Bernd Saugel, E. Christiaan Boerma, Pierre Squara, Alexandre Mebazaa, Geert Koster, Djillali Annane, Andrea Morelli, Arnaldo Dubin, Marc Leone, Pierre Asfar, Mervyn Singer, Anthony C. Gordon, Jan Bakker, Antoine Vieillard-Baron, Giovanni Landoni, Michael Sander, Michelle S Chew, Jean-Louis Teboul, Simon T. Vistisen, Glenn Hernandez, Peter Radermacher, Jacques Duranteau, Bruno Levy, Critical care, Anesthesiology, Peri-operative and Emergency medicine (CAPE), RS: Carim - V04 Surgical intervention, Intensive Care, MUMC+: MA Medische Staf IC (9), MUMC+: MA Intensive Care (3), University of Groningen [Groningen], University Medical Center Groningen [Groningen] (UMCG), New York University Langone Medical Center (NYU Langone Medical Center), NYU System (NYU), Columbia University Medical Center (CUMC), Columbia University [New York], Erasmus University Medical Center [Rotterdam] (Erasmus MC), Hôpital Raymond Poincaré [AP-HP], Université de Versailles Saint-Quentin-en-Yvelines - UFR Sciences de la santé Simone Veil (UVSQ Santé), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), MitoVasc - Physiopathologie Cardiovasculaire et Mitochondriale (MITOVASC), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Medical Centre Leeuwarden, Istituto Clinico Humanitas [Milan] (IRCCS Milan), Humanitas University [Milan] (Hunimed), Linköping University (LIU), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Université Paris Cité - UFR Médecine [Santé] (UPCité UFR Médecine), Université Paris Cité (UPCité), Karolinska Institutet [Stockholm], Centre Hospitalier Interrégional Edith Cavell (CHIREC), Universidad Nacional de la Plata [Argentine] (UNLP), Johannes Kepler University Linz [Linz] (JKU), Kepler University Hospital, AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Imperial College London, Universidade de São Paulo = University of São Paulo (USP), AP-HP - Hôpital Antoine Béclère [Clamart], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Pontificia Universidad Católica de Chile (UC), Hospital Juan A. Fernandez [Buenos Aires, Argentina], Universita Vita Salute San Raffaele = Vita-Salute San Raffaele University [Milan, Italie] (UniSR), Hôpital Nord [CHU - APHM], Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Département d’Anesthésie-Réanimation-SMUR [Hôpital Lariboisière], Hôpitaux Universitaire Saint-Louis, Lariboisière, Fernand-Widal, Centre de Référence de l’Hypertension Pulmonaire Sévère [CHU Le Kremlin Bicêtre], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Ecotaxie, microenvironnement et développement lymphocytaire (EMily (UMR_S_1160 / U1160)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Hôpital Lariboisière-Fernand-Widal [APHP], William Harvey Research Institute, Barts and the London Medical School, Queen Mary University of London (QMUL), University of Pittsburgh Medical Center [Pittsburgh, PA, États-Unis] (UPMC), Universitätsklinikum Ulm - University Hospital of Ulm, University Medical Center Rostock, Jena University Hospital [Jena], Justus-Liebig-Universität Gießen = Justus Liebig University (JLU), Universitaetsklinikum Hamburg-Eppendorf = University Medical Center Hamburg-Eppendorf [Hamburg] (UKE), University College of London [London] (UCL), Clinique Ambroise Paré [Centres Médico-Chirurgicaux Ambroise Pré, Pierre Cherest, Hartmann], Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Centre d'Investigation Clinique de Limoges (CIC1435), CHU Limoges-Institut National de la Santé et de la Recherche Médicale (INSERM), Université libre de Bruxelles (ULB), Maastricht University Medical Centre (MUMC), Maastricht University [Maastricht], Aarhus University Hospital, European Society of Intensive Care Medicine, ESICM, This work has received the endorsement of the European Society of Intensive Care Medicine. The authors would like to thank Hannah Wunsch and Anders Perner, who provided their expertise as experts but abstained from being listed as co-author of this paper., HAL UVSQ, Équipe, NIHR, Scheeren, T. W. L., Bakker, J., Kaufmann, T., Annane, D., Asfar, P., Boerma, E. C., Cecconi, M., Chew, M. S., Cholley, B., Cronhjort, M., De Backer, D., Dubin, A., Dunser, M. W., Duranteau, J., Gordon, A. C., Hajjar, L. A., Hamzaoui, O., Hernandez, G., Kanoore Edul, V., Koster, G., Landoni, G., Leone, M., Levy, B., Martin, C., Mebazaa, A., Monnet, X., Morelli, A., Payen, D., Pearse, R. M., Pinsky, M. R., Radermacher, P., Reuter, D. A., Sakr, Y., Sander, M., Saugel, B., Singer, M., Squara, P., Vieillard-Baron, A., Vignon, P., Vincent, J. -L., van der Horst, I. C. C., Vistisen, S. T., and Teboul, J. -L.

Subjects
Inotrope, PDE-inhibitors, Levosimendan, [SDV]Life Sciences [q-bio], 030204 cardiovascular system & hematology, Critical Care and Intensive Care Medicine, GUIDELINES, 0302 clinical medicine, Catecholamines, CARDIAC-OUTPUT SYNDROME, Septic shock, Inotropes, Cardiogenic shock, lcsh:Medical emergencies. Critical care. Intensive care. First aid, Acute circulatory failure, 3. Good health, [SDV] Life Sciences [q-bio], Shock (circulatory), Sepsis, Resuscitation, Vasoactive agents, Cardiac output, medicine.symptom, Life Sciences & Biomedicine, CRITICALLY-ILL PATIENTS, medicine.drug, medicine.medical_specialty, Anestesi och intensivvård, Medicina, Context (language use), VASOPRESSORS, 1117 Public Health and Health Services, 03 medical and health sciences, Critical Care Medicine, acute circulatory failure, cardiac output, cardiogenic shock, catecholamines, inotropes, levosimendan, resuscitation, sepsis, septic shock, vasoactive agents, General & Internal Medicine, Anesthesiology, medicine, Intensive care medicine, METAANALYSIS, Science & Technology, Anesthesiology and Intensive Care, business.industry, Research, 1103 Clinical Sciences, 030208 emergency & critical care medicine, lcsh:RC86-88.9, Guideline, medicine.disease, DYSFUNCTION, CARDIOGENIC-SHOCK, Dobutamine, business
Abstract

Background: Treatment decisions on critically ill patients with circulatory shock lack consensus. In an international survey, we aimed to evaluate the indications, current practice, and therapeutic goals of inotrope therapy in the treatment of patients with circulatory shock. Methods: From November 2016 to April 2017, an anonymous web-based survey on the use of cardiovascular drugs was accessible to members of the European Society of Intensive Care Medicine (ESICM). A total of 14 questions focused on the profile of respondents, the triggering factors, first-line choice, dosing, timing, targets, additional treatment strategy, and suggested effect of inotropes. In addition, a group of 42 international ESICM experts was asked to formulate recommendations for the use of inotropes based on 11 questions. Results: A total of 839 physicians from 82 countries responded. Dobutamine was the first-line inotrope in critically ill patients with acute heart failure for 84% of respondents. Two-thirds of respondents (66%) stated to use inotropes when there were persistent clinical signs of hypoperfusion or persistent hyperlactatemia despite a supposed adequate use of fluids and vasopressors, with (44%) or without (22%) the context of low left ventricular ejection fraction. Nearly half (44%) of respondents stated an adequate cardiac output as target for inotropic treatment. The experts agreed on 11 strong recommendations, all of which were based on excellent (> 90%) or good (81–90%) agreement. Recommendations include the indications for inotropes (septic and cardiogenic shock), the choice of drugs (dobutamine, not dopamine), the triggers (low cardiac output and clinical signs of hypoperfusion) and targets (adequate cardiac output) and stopping criteria (adverse effects and clinical improvement). Conclusion: Inotrope use in critically ill patients is quite heterogeneous as self-reported by individual caregivers. Eleven strong recommendations on the indications, choice, triggers and targets for the use of inotropes are given by international experts. Future studies should focus on consistent indications for inotrope use and implementation into a guideline for circulatory shock that encompasses individualized targets and outcomes., La lista completa de autores que integran el documento puede consultarse en el archivo., Facultad de Ciencias Médicas

Published
2020

21. Variation in Anopheles distribution and predictors of malaria infection risk across regions of Madagascar

Author

Marcia C. Castro, Gauthier N. Emile, Romain Girod, Christopher D. Golden, Benjamin L. Rice, Hervet J. Randriamady, Nicholas J. Arisco, Luciano Michaël Tantely, Harvard T.H. Chan School of Public Health, Harvard University [Cambridge], Unité d'Entomologie Médicale [Antananarivo, Madagascar] (IPM), Institut Pasteur de Madagascar, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Madagascar Health and Environmental Research [Maroantsetra, Madagascar] (MAHERY), and We are grateful for the support from the United States Agency for International Development (Grant AID-FFP-A-14-00,008) implemented by Catholic Relief Services (CRS) in consortium with four local implementing partners in Madagascar. The views and opinions expressed in this paper are those of the authors and not necessarily the views and opinions of the United States Agency for International Development. GeoStore funds provided by Airbus Defense & Space (Grant AH08211501).

Subjects
Male, Environmental change, Range (biology), [SDV]Life Sciences [q-bio], Distribution (economics), MESH: Madagascar, 0302 clinical medicine, MESH: Aged, 80 and over, Risk Factors, Planetary health, MESH: Demography, MESH: Risk Factors, MESH: Child, Disease ecology, MESH: Animals, MESH: Ecosystem, 030212 general & internal medicine, Child, Land use change, Aged, 80 and over, MESH: Aged, 2. Zero hunger, MESH: Middle Aged, biology, Multilevel model, Anopheles, Middle Aged, MESH: Infant, Infectious Diseases, Geography, MESH: Young Adult, Child, Preschool, Female, MESH: Mosquito Vectors, Adult, MESH: Socioeconomic Factors, lcsh:Arctic medicine. Tropical medicine, Adolescent, lcsh:RC955-962, 030231 tropical medicine, MESH: Malaria, Mosquito Vectors, lcsh:Infectious and parasitic diseases, MESH: Anopheles, 03 medical and health sciences, Young Adult, MESH: Cross-Sectional Studies, Deforestation, Environmental health, Vector-borne disease, parasitic diseases, medicine, Madagascar, Animals, Humans, lcsh:RC109-216, Socioeconomic status, Ecosystem, Aged, Demography, MESH: Adolescent, MESH: Humans, business.industry, Research, MESH: Child, Preschool, MESH: Animal Distribution, Infant, MESH: Adult, 15. Life on land, medicine.disease, biology.organism_classification, MESH: Male, Malaria, Cross-Sectional Studies, Socioeconomic Factors, Parasitology, business, Animal Distribution, MESH: Female
Abstract

Background Deforestation and land use change is widespread in Madagascar, altering local ecosystems and creating opportunities for disease vectors, such as the Anopheles mosquito, to proliferate and more easily reach vulnerable, rural populations. Knowledge of risk factors associated with malaria infections is growing globally, but these associations remain understudied across Madagascar’s diverse ecosystems experiencing rapid environmental change. This study aims to uncover socioeconomic, demographic, and ecological risk factors for malaria infection across regions through analysis of a large, cross-sectional dataset. Methods The objectives were to assess (1) the ecological correlates of malaria vector breeding through larval surveys, and (2) the socioeconomic, demographic, and ecological risk factors for malaria infection in four ecologically distinct regions of rural Madagascar. Risk factors were determined using multilevel models for the four regions included in the study. Results The presence of aquatic agriculture (both within and surrounding communities) is the strongest predictive factor of habitats containing Anopheles larvae across all regions. Ecological and socioeconomic risk factors for malaria infection vary dramatically across study regions and range in their complexity. Conclusions Risk factors for malaria transmission differ dramatically across regions of Madagascar. These results may help stratifying current malaria control efforts in Madagascar beyond the scope of existing interventions.

Published
2020

22. The coming age of flavonoids in the treatment of diabetic complications

Author

Gema Marín-Royo, Carmen Gomez-Guerrero, Lucas Opazo-Ríos, Luna Jimenez-Castilla, Jesús Egido, Teresa Caro-Ordieres, Juan Antonio Moreno, Instituto de Investigación Sanitaria Fundación Jiménez Díaz (IIS-FJD), UAM. Departamento de Medicina, Instituto de Investigación Sanitaria Fundación Jiménez Díaz (ISS-FJD), [Caro-Ordieres,T] Research Discovery and Innovation Department, FAES FARMA, S.A, Department of Physiology, Faculty of Medicine and Nursing, University of the Basque Country, Leioa (Bizkaia), Spain. [Marín-Royo,G, Opazo-Ríos,L, Jiménez-Castilla,L, Gómez-Guerrero,C, Egido,J] Renal, Vascular and Diabetes Research Laboratory, IIS-Fundación Jiménez Díaz, Universidad Autonoma de Madrid, Spanish Biomedical Research Centre in Diabetes and Associated Metabolic Disorders (CIBERDEM), Madrid, Spain. [Moreno,JA] Department of Cell Biology, Physiology and Immunology, University of Córdoba, Córdoba, Spain. [Moreno,JA] Maimonides Biomedical Research Institute of Cordoba (IMIBIC), University of Córdoba, Córdoba, Spain. [Moreno,JA] Hospital Universitario Reina Sofía, Córdoba, Spain., and This paper was not funded. The authors work has been supported by FEDER-ISCIII Funds (PI17/00130, PI17/01495), Spanish Ministry of Economy and Competitiveness (RTI2018-098788-B-100, DTS17/00203, DTS19/00093, RYC-2017-22369), Spanish Society of Cardiology (SEC), Spanish Society of Nephrology (SEN) and Spanish Society of Atherosclerosis (SEA). TCO is an employee of FAES Pharma. The authors (except JAM) have an ongoing research project in common with FAES Pharma on Flavonoids in diabetic complications under the auspices of the joint-RETOS Collaborations Project 2017 (RTC-2017-6089-1), program supported by Spanish Ministry of Economy and Competitiveness. No other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Subjects
medicine.medical_specialty, Microvascular complications, Nefropatías Diabéticas, Medicina, Terapéutica, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Therapeutics [Medical Subject Headings], lcsh:Medicine, Diseases::Endocrine System Diseases::Diabetes Mellitus::Diabetes Complications::Diabetic Nephropathies [Medical Subject Headings], Review, Diabetic nephropathy, Therapeutics, Controlled studies, Chemicals and Drugs::Heterocyclic Compounds::Pyrans::Benzopyrans::Chromones::Flavonoids [Medical Subject Headings], Unmet needs, 03 medical and health sciences, Diabetes mellitus, 0302 clinical medicine, medicine, Flavonoides, Phenomena and Processes::Metabolic Phenomena::Metabolism::Oxidative Stress [Medical Subject Headings], Intensive care medicine, Diseases::Cardiovascular Diseases [Medical Subject Headings], Beneficial effects, Enfermedades Cardiovasculares, 030304 developmental biology, Flavonoids, Inflammation, 0303 health sciences, Inflamación, Diseases::Endocrine System Diseases::Diabetes Mellitus [Medical Subject Headings], business.industry, lcsh:R, Diabetes, General Medicine, medicine.disease, Cardiovascular disease, Clinical trial, Clinical research, Tolerability, Oxidative stress, 030220 oncology & carcinogenesis, business, Diseases::Pathological Conditions, Signs and Symptoms::Pathologic Processes::Inflammation [Medical Subject Headings], Estrés Oxidativo
Abstract

Diabetes mellitus (DM), and its micro and macrovascular complications, is one of the biggest challenges for world public health. Despite overall improvement in prevention, diagnosis and treatment, its incidence is expected to continue increasing over the next years. Nowadays, finding therapies to prevent or retard the progression of diabetic complications remains an unmet need due to the complexity of mechanisms involved, which include inflammation, oxidative stress and angiogenesis, among others. Flavonoids are natural antioxidant compounds that have been shown to possess anti-diabetic properties. Moreover, increasing scientific evidence has demonstrated their potential anti-inflammatory and anti-oxidant effects. Consequently, the use of these compounds as anti-diabetic drugs has generated growing interest, as is reflected in the numerous in vitro and in vivo studies related to this field. Therefore, the aim of this review is to assess the recent pre-clinical and clinical research about the potential effect of flavonoids in the amelioration of diabetic complications. In brief, we provide updated information concerning the discrepancy between the numerous experimental studies supporting the eficacy of flavonoids on diabetic complications and the lack of appropriate and well-designed clinical trials. Due to the well-described beneficial effects on different mechanisms involved in diabetic complications, the excellent tolerability and low cost, future randomized controlled studies with compounds that have adequate bioavailability should be evaluated as add-on therapy on well-established anti-diabetic drugs, This paper was not funded. The authors work has been supported by FEDER-ISCIII Funds (PI17/00130, PI17/01495), Spanish Ministry of Economy and Competitiveness (RTI2018-098788-B-100, DTS17/00203, DTS19/00093, RYC-2017-22369), Spanish Society of Cardiology (SEC), Spanish Society of Nephrology (SEN) and Spanish Society of Atherosclerosis (SEA). TCO is an employee of FAES Pharma. The authors (except JAM) have an ongoing research project in common with FAES Pharma on Flavonoids in diabetic complications under the auspices of the joint-RETOS Collaborations Project 2017 (RTC-2017-6089-1), program supported by Spanish Ministry of Economy and Competitiveness.

Published
2020

23. Sleep problems and mild cognitive impairment among adults aged ≥50 years from low- and middle-income countries

Author

Yvonne Barnett, Christina Carmichael, Guillermo F. López Sánchez, Pinar Soysal, Ai Koyanagi, Louis Jacob, Damiano Pizzol, Nicola Veronese, Lee Smith, Hans Oh, Mark A. Tully, Laurie T. Butler, Jae Il Shin, SOYSAL, PINAR, Université de Versailles Saint-Quentin-en-Yvelines - UFR Sciences de la santé Simone Veil (UVSQ Santé), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), National Institute on Aging, NIA: OGHA 04034785, R01-AG034479, R21-AG034263, Y1-AG-1005-01, YA1323-08-CN-0020, This paper uses data from WHO's Study on Global Ageing and Adult Health (SAGE). SAGE is supported by the U.S. National Institute on Aging through Interagency Agreements OGHA 04034785, YA1323-08-CN-0020, Y1-AG-1005-01 and through research grants R01-AG034479 and R21-AG034263 ., Smith, L., Shin, J.I., Jacob, L., Carmichael, C., López Sánchez, G.F., Oh, H., Butler, L.T., Barnett, Y., Pizzol, D., Tully, M.A., Soysal, P., Veronese, N., and Koyanagi, A.

Subjects
Male, Aging, Low- and middle-income countries, [SDV]Life Sciences [q-bio], Middle-aged adults, Psychological intervention, Sleep problems, Logistic regression, Biochemistry, 0302 clinical medicine, Endocrinology, Prevalence, Mild cognitive impairment, Medicine, 030212 general & internal medicine, Cognitive impairment, Morning, Older adults, Aged, 80 and over, Middle Aged, Sleep in non-human animals, 3. Good health, Female, Sleep Wake Disorders, Dementia, Odds, 03 medical and health sciences, mental disorders, Genetics, Humans, Cognitive Dysfunction, Developing Countries, Molecular Biology, Aged, business.industry, Cell Biology, medicine.disease, Cross-Sectional Studies, Ageing, Smith L., Shin J. I. , Jacob L., Carmichael C., López Sánchez G. F. , Oh H., Butler L. T. , Barnett Y., Pizzol D., Tully M. A. , et al., -Sleep problems and mild cognitive impairment among adults aged ≥50 years from low- and middle-income countries.-, Experimental gerontology, ss.111513, 2021, Mild cognitive impairment, Dementia, Sleep problems, Low- and middle-income countries, Middle-aged adults, Older adults, business, 030217 neurology & neurosurgery, Demography
Abstract

Background-\ud \ud The limited available literature suggests that sleep problems are linked to an increased risk of mild cognitive impairment (MCI). However, this association has been little studied to date in low-income settings.\ud \ud Objective-\ud \ud To investigate the association between sleep problems and MCI in a large sample of adults from six low-and middle-income countries (LMICs).\ud \ud Design-\ud \ud Cross-sectional.\ud \ud Setting-\ud \ud Study on Global Ageing and Adult Health (SAGE).\ud \ud Subjects-\ud \ud 32,715 individuals aged ≥50 years with preservation in functional abilities [age range 50–114 years; 51.7% females].\ud \ud Methods-\ud \ud MCI was defined using the National Institute on Aging-Alzheimer's Association criteria. Sleep problems were assessed by the question “Overall in the last 30 days, how much of a problem did you have with sleeping, such as falling asleep, waking up frequently during the night or waking up too early in the morning?” and categorized as “None”, “Mild”, “Moderate”, “Severe/Extreme”. Multivariable logistic regression analysis and meta-analysis were conducted.\ud \ud Results-\ud \ud Compared to no sleep problems, mild, moderate, and severe/extreme sleep problems were associated with significant 1.40, 1.83, and 2.69 times higher odds for MCI with similar associations being observed between age groups and sex. Severe/extreme sleep problems were positively associated with MCI (i.e., OR > 1) in the six countries studied with the overall estimate being OR = 1.80 (95% CI = 1.50–2.16), and a low level of between-country heterogeneity was observed (I2 = 28.2%).\ud \ud Conclusions-\ud \ud Sleep problems were associated with higher odds for MCI. Interventions to improve sleep quality among middle-aged and older adults in LMICs may be an effective strategy in reducing risk of MCI and dementia.

Published
2021

24. Gene editing rescue of a novel MPL mutant associated with congenital amegakaryocytic thrombocytopenia

Author

Eun Ho Eunice Choi, Thierry Lavabre-Bertrand, Cédric Cleyrat, Serge Carillo, Romain Girard, Sylvie Hermouet, Bridget S. Wilson, Eric Jeziorski, The University of New Mexico [Albuquerque], Département Pédiatrie [CHRU Montpellier], Pôle Femme Mère Enfant [CHRU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Laboratoire de Cytologie Clinique et de Cytogénétique [CHU Nîmes], Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Molecular Mechanisms of Chronic Inflammation in Hematological Diseases (CRCINA-ÉQUIPE 16), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), This work was supported in part by grants from the Department of Defense, Congressionally Directed Medical Research Program (CA140409) (C.C. and B.S.W.), the American Cancer Society (126768-IRG-14-187-19) (C.C.), and Ligue contre le Cancer, comité du Gard (S.C.). Images in this paper were generated in the University of New Mexico (UNM) Cancer Center Fluorescence Microscopy Shared Resource supported by National Institutes of Health, National Cancer Institute (NCI) grant P30CA118110 and National Institutes of Health, National Institute of General Medical Science grant., Bernardo, Elizabeth, Institut des Biomolécules Max Mousseron [Pôle Chimie Balard] (IBMM), Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Institut de Chimie du CNRS (INC)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), and Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)

Subjects
0301 basic medicine, Mutation, Mutant, Hematopoietic stem cell, [SDV.CAN]Life Sciences [q-bio]/Cancer, Hematology, Biology, medicine.disease_cause, medicine.disease, Virology, Molecular biology, 3. Good health, 03 medical and health sciences, 030104 developmental biology, medicine.anatomical_structure, [SDV.CAN] Life Sciences [q-bio]/Cancer, medicine, biology.protein, Congenital amegakaryocytic thrombocytopenia, Thrombopoiesis, Stem cell, Calreticulin, Thrombopoietin
Abstract

International audience; Thrombopoietin (Tpo) and its receptor (Mpl) are the principal regulators of early and late thrombopoiesis and hematopoietic stem cell maintenance. Mutations in MPL can drastically impair its function and be a contributing factor in multiple hematologic malignancies, including congenital amegakaryocytic thrombocytopenia (CAMT). CAMT is characterized by severe thrombocytopenia at birth, which progresses to bone marrow failure and pancytopenia. Here we report unique familial cases of CAMT that presented with a previously unreported MPL mutation: T814C (W272R) in the background of the activating MPL G117T (K39N or Baltimore) mutation. Confocal microscopy, proliferation and surface biotinylation assays, co-immunoprecipitation, and western blotting analysis were used to elucidate the function and trafficking of Mpl mutants. Results showed that Mpl protein bearing the W272R mutation, alone or together with the K39N mutation, lacks detectable surface expression while being strongly colocalized with the endoplasmic reticulum (ER) marker calreticulin. Both WT and K39N-mutated Mpl were found to be signaling competent, but single or double mutants bearing W272R were unresponsive to Tpo. Function of the deficient Mpl receptor could be rescued by using 2 separate approaches: (1) GRASP55 overexpression, which partially restored Tpo-induced signaling of mutant Mpl by activating an autophagy-dependent secretory pathway and thus forcing ER-trapped immature receptors to traffic to the cell surface; and (2) CRISPR-Cas9 gene editing used to repair MPL T814C mutation in transfected cell lines and primary umbilical cord blood–derived CD34+ cells. We demonstrate proof of principle for rescue of mutant Mpl function by using gene editing of primary hematopoietic stem cells, which indicates direct therapeutic applications for CAMT patients.

Published
2017

25. Randomised, double-blind, placebo-controlled clinical trial for evaluating the efficacy of intracoronary injection of autologous bone marrow mononuclear cells in the improvement of the ventricular function in patients with idiopathic dilated myocardiopathy: a study protocol

Author

Miguel Romero, José Suárez-de-Lezo, Concha Herrera, Manuel Pan, José López-Aguilera, Flor Baeza-Garzón, Francisco Javier Hidalgo-Lesmes, Olga Fernández-López, Juliana Martínez-Atienza, Eva Cebrián, Vanesa Martín-Palanco, Rosario Jiménez-Moreno, Rosario Gutiérrez-Fernández, Sonia Nogueras, Maria Dolores Carmona, Soledad Ojeda, Natividad Cuende, Rosario Mata, [Romero,M, Suárez-de-Lezo, Pan,M, López-Aguilera,J, Suárez-de-Lezo Jr,J, Baeza-Garzón,F, Hidalgo-Lesmes,FJ, Cebrián,E, Ojeda,S] Cardiology Unit, Reina Sofía University Hospital, Córdoba, Spain. [Herrera,C, Martín-Palanco,V, Jiménez-Moreno,R, Gutiérrez-Fernández,R, Nogueras,S, Carmona,MD] Cell Production Unit, Reina Sofía University Hospital, Córdoba, Spain. [Fernández-López,O, Martínez-Atienza,J, Cuende,N, Mata,R] Andalusian Initiative for Advanced Therapies, Andalusian Public Foundation Progress and Health, Seville, Spain., and This paper presents an investigator-driven Clinical trial partially funded by research grant provided by the Regional Ministry of Health of Andalusia (Grant Reference Number salud-201600073587-tra).

Subjects
Male, lcsh:Diseases of the circulatory (Cardiovascular) system, Time Factors, Ensayo clínico controlado aleatorio, 030204 cardiovascular system & hematology, Cell therapy, Ventricular Function, Left, law.invention, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], Study Protocol, Cardiomiopatía dilatada, 0302 clinical medicine, Randomized controlled trial, law, Dilated myocardiopathy, Multicenter Studies as Topic, 030212 general & internal medicine, Myocardial infarction, Diseases::Cardiovascular Diseases::Heart Diseases::Cardiomyopathies::Cardiomyopathy, Dilated [Medical Subject Headings], Bone Marrow Transplantation, Randomized Controlled Trials as Topic, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Evaluation Studies as Topic::Clinical Trials as Topic::Controlled Clinical Trials as Topic::Randomized Controlled Trials as Topic [Medical Subject Headings], Diseases::Cardiovascular Diseases::Vascular Diseases::Myocardial Ischemia::Myocardial Infarction [Medical Subject Headings], Ejection fraction, Middle Aged, Treatment Outcome, Disciplines and Occupations::Natural Science Disciplines::Science::Research::Biomedical Research [Medical Subject Headings], Female, Cardiology and Cardiovascular Medicine, Adult, Cardiomyopathy, Dilated, medicine.medical_specialty, Information Science::Information Science::Communications Media::Publications [Medical Subject Headings], Adolescent, Cell- and tissue-based therapy, Células de la médula ósea, Bone Marrow Cells, Placebo, Transplantation, Autologous, Young Adult, 03 medical and health sciences, Clinical Trials, Phase II as Topic, Double-Blind Method, Tratamiento basado en trasplante de células y tejidos, Internal medicine, medicine, Humans, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Therapeutics::Biological Therapy::Cell- and Tissue-Based Therapy [Medical Subject Headings], Aged, Angiology, Anatomy::Cells::Bone Marrow Cells [Medical Subject Headings], business.industry, Consolidated Standards of Reporting Trials, Recovery of Function, medicine.disease, Interim analysis, Clinical trial, lcsh:RC666-701, Spain, Bone marrow mononuclear cells, business
Abstract

Cellular therapies have been increasingly applied to diverse human diseases. Intracoronary infusion of bone marrow-derived mononuclear cells (BMMNC) has demonstrated to improve ventricular function after acute myocardial infarction. However, less information is available about the role of BMMNC therapy for the treatment of dilated myocardiopathies (DCs) of non-ischemic origin. This article presents the methodological description of a study aimed at investigating the efficacy of intracoronary injection of autologous BMMNCs in the improvement of the ventricular function of patients with DC. This randomised, placebo-controlled, double-blinded phase IIb clinical trial compares the improvement on ventricular function (measured by the changes on the ejection fraction) of patients receiving the conventional treatment for DC in combination with a single dose of an intracoronary infusion of BMMNCs, with the functional recovery of patients receiving placebo plus conventional treatment. Patients assigned to both treatment groups are monitored for 24 months. This clinical trial is powered enough to detect a change in Left Ventricular Ejection Fraction (LVEF) equal to or greater than 9%, although an interim analysis is planned to re-calculate sample size. The study protocol was approved by the Andalusian Coordinating Ethics Committee for Biomedical Research (Comite Coordinador de Etica en Investigacion Biomedica de Andalucia), the Spanish Medicines and Medical Devices Agency (Agencia Espanola de Medicamentos y Productos Sanitarios), and is registered at the EU Clinical Trials Register (EudraCT: 2013–002015-98). The publication of the trial results in scientific journals will be performed in accordance with the applicable regulations and guidelines to clinical trials. ClinicalTrials.gov Identifier NCT02033278 (First Posted January 10, 2014): https://clinicaltrials.gov/ct2/show/NCT02033278 ; EudraCT number: 2013–002015-98, EU CT Register: https://www.clinicaltrialsregister.eu/ctr-search/search?query=2013-002015-98 . Trial results will also be published according to the CONSORT statement at conferences and reported peer-reviewed journals.

Published
2019

26. Plasmodium falciparum merozoite surface antigen-specific cytophilic IgG and control of malaria infection in a Beninese birth cohort

Author

Gregory Nuel, Paulin Sonon, Adrian J. F. Luty, Gilles Cottrell, Ibrahim Sadissou, André Garcia, Roukiyath Amoussa, Tania d’Almeida, Ambaliou Sanni, Shirley Longacre, D. Courtin, Aziz Bouraima, Florence Migot-Nabias, Rafiou Adamou, Célia Dechavanne, Michael Theisen, Kabirou Moutairou, Edmond J. Remarque, Achille Massougbodji, Jacqueline Milet, Agnès Le Port, Mère et enfant en milieu tropical : pathogènes, système de santé et transition épidémiologique (MERIT - UMR_D 216), Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5), Laboratoire de Biochimie et de Biologie Moléculaire (Université d'Abomey Calavi, Cotonou, Bénin) (LBBM), Université d’Abomey-Calavi = University of Abomey Calavi (UAC), Universidade de São Paulo = University of São Paulo (USP), Statens Serum Institut [Copenhagen], University of Copenhagen = Københavns Universitet (UCPH), Biomedical Primate Research Centre [Rijswijk] (BPRC), Vaccinologie Parasitaire, Institut Pasteur [Paris] (IP), Laboratoire de Probabilités, Statistique et Modélisation (LPSM (UMR_8001)), Université Paris Diderot - Paris 7 (UPD7)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), This paper describes work undertaken in the context of the PALNOUGENENV, 'Paludisme-Nouvéau-né-Génétique et Environnement', a project supported by Agence Nationale pour la Recherche (projet SEST2006/040/001), Ministère des Affaires Etrangères français (projet REFS No.2006-22) for their financial support. This publication was made possible through the Faculté des Sciences de la Santé (FSS), the Institut des Sciences Biomédicales Appliquées de Cotonou (ISBA), the Programme National de Lutte contre le Paludisme (PNLP) for their institutional support and the Institut de Recherche et de Développment AIRD-ARTS and Ambassade de France à Cotonou (SCAC) for their PhD scholarships to Rafiou ADAMOU and Ibrahim SADISSOU., ANR-06-SEST-0040,PALNOURGENENV,survenue des premières infections palustres chez le noueau-né : déterminants génétiques, biologiques et environnementaux(2006), Mère et enfant face aux infections tropicales (MERIT - UMR_D 216), University of Abomey Calavi (UAC), University of São Paulo (USP), University of Copenhagen = Københavns Universitet (KU), Institut Pasteur [Paris], and Laboratoire de Probabilités, Statistiques et Modélisations (LPSM (UMR_8001))

Subjects
Male, Protozoan Proteins, Antibodies, Protozoan, MESH: Malaria, Falciparum/immunology, 0302 clinical medicine, MESH: Pregnancy, MESH: Antigens, Protozoan/immunology, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Pregnancy, Surveys and Questionnaires, Benin, 030212 general & internal medicine, MESH: Plasmodium falciparum/immunology, Longitudinal Studies, Malaria, Falciparum, MESH: Longitudinal Studies, MESH: Antibodies, Protozoan/blood, biology, Malaria vaccine, MESH: Infant, Newborn, MESH: Enzyme-Linked Immunosorbent Assay, MESH: Infant, 3. Good health, Infectious Diseases, [SDV.IMM.IA]Life Sciences [q-bio]/Immunology/Adaptive immunology, Cytophilic IgG, Female, Merozoite vaccine candidate antigens, Antibody, medicine.symptom, lcsh:Arctic medicine. Tropical medicine, lcsh:RC955-962, 030231 tropical medicine, Plasmodium falciparum, Context (language use), Antigens, Protozoan, Enzyme-Linked Immunosorbent Assay, Asymptomatic, lcsh:Infectious and parasitic diseases, 03 medical and health sciences, MESH: Benin, Antigen, Immunity, parasitic diseases, medicine, Humans, lcsh:RC109-216, MESH: Surveys and Questionnaires, MESH: Humans, business.industry, Research, Infant, Newborn, Infant, biology.organism_classification, medicine.disease, MESH: Protozoan Proteins/immunology, MESH: Male, Malaria, Immunoglobulin G, Immunology, biology.protein, Parasitology, business, MESH: Immunoglobulin G/blood, MESH: Female
Abstract

BACKGROUND: Substantial evidence indicates that cytophilic IgG responses to Plasmodium falciparum merozoite antigens play a role in protection from malaria. The specific targets mediating immunity remain unclear. Evaluating antibody responses in infants naturally-exposed to malaria will allow to better understand the establishment of anti-malarial immunity and to contribute to a vaccine development by identifying the most appropriate merozoite candidate antigens.METHODS: The study was based on parasitological and clinical active follow-up of infants from birth to 18 months of age conducted in the Tori Bossito area of southern Benin. For 399 infants, plasma levels of cytophilic IgG antibodies with specificity for five asexual stage malaria vaccine candidate antigens were determined by ELISA in infants' peripheral blood at 6, 9, 12 and 15 months of age. Multivariate mixed logistic model was used to investigate the association between antibody levels and anti-malarial protection in the trimester following the IgG quantification. Moreover, the concentrations of merozoite antigen-specific IgG were compared between a group of infants apparently able to control asymptomatic malaria infection (CAIG) and a group of infants with no control of malaria infection (Control group (NCIG)). Protective effect of antibodies was also assessed after 15 months of malaria exposure with a Cox regression model adjusted on environmental risk.RESULTS: Cytophilic IgG responses to AMA1, MSP1, MSP2-3D7, MSP2-FC27, MSP3 and GLURP R2 were associated with increasing malarial infection risk in univariate analysis. The multivariate mixed model showed that IgG1 and IgG3 to AMA1 were associated with an increased risk of malarial infection. However infants from CAIG (n = 53) had significantly higher AMA1-, MSP2-FC27-, MSP3-specific IgG1 and AMA1-, MSP1-, MSP2-FC27-, MSP3 and GLURP-R2-specific IgG3 than those from NCIG (n = 183). The latter IgG responses were not associated with protection against clinical malaria in the whole cohort when protective effect is assessed after 15 months of malaria exposition.CONCLUSION: In this cohort, merozoite antigen-specific cytophilic IgG levels represent a marker of malaria exposure in infants from 6 to 18 months of age. However, infants with resolution of asymptomatic infection (CAIG) seem to have acquired naturally immunity against P. falciparum. This observation is encouraging in the context of the development of multitarget P. falciparum vaccines.

Published
2019

27. Social and non-social autism symptoms and trait domains are genetically dissociable

Author

Freddy Cliquet, Varun Warrier, Roberto Toro, Hyejung Won, Richard Delorme, Thomas Bourgeron, Anders D. Børglum, Janita Bralten, Claire S. Leblond, Geert Poelmans, Jakob Grove, Ward De Witte, Bhismadev Chakrabarti, David A. Hinds, Simon Baron-Cohen, Toro, Roberto [0000-0002-6671-858X], Cliquet, Freddy [0000-0002-9989-0685], Chakrabarti, Bhismadev [0000-0002-6649-7895], Børglum, Anders D. [0000-0001-8627-7219], Grove, Jakob [0000-0003-2284-5744], Hinds, David A. [0000-0002-4911-803X], Apollo - University of Cambridge Repository, University of Cambridge [UK] (CAM), Génétique humaine et fonctions cognitives - Human Genetics and Cognitive Functions (GHFC (UMR_3571 / U-Pasteur_1)), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), University of North Carolina [Chapel Hill] (UNC), University of North Carolina System (UNC), Child and Adolescent Psychiatry Department [AP- HP Hôpital Robert Debré], AP-HP Hôpital universitaire Robert-Debré [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Radboud University Medical Center [Nijmegen], Radboud University [Nijmegen], University of Reading (UOR), The Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH), Aarhus University [Aarhus], 23andMe Inc., V.W. was funded by St. John’s College, Cambridge, and the Cambridge Commonwealth Trust. This study was funded by grants to SBC from the Medical Research Council, the Wellcome Trust, the Autism Research Trust, the Templeton World Charity Foundation, and to T.B. from the Institut Pasteur, the CNRS, the INSERM, The Fondamental Foundation, the APHP, the BioPsy Labex and the University Paris Diderot. The research was conducted in association with the National Institute for Health Research (NIHR) Collaboration for Leadership in Applied Health Research and Care East of England at Cambridgeshire and Peterborough NHS Foundation Trust. We also received support from the NIHR Cambridge Biomedical Research Centre. We acknowledge with gratitude the generous support of Drs Dennis and Mireille Gillings in strengthening the collaboration between S.B.-C. and T.B., and between Cambridge University and the Institut Pasteur. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health. Data obtained from 23andMe was supported by the National Human Genome Research Institute of the National Institutes of Health (grant number R44HG006981). The UK Medical Research Council and Wellcome (grant ref: 102215/2/13/2) and the University of Bristol provide core support for ALSPAC. GWAS data were generated by Sample Logistics and Genotyping Facilities at Wellcome Sanger Institute and LabCorp (Laboratory Corporation of America) using support from 23andMe. This publication is the work of the authors who will serve as guarantors for the content of this paper. The iPSYCH (The Lundbeck Foundation Initiative for Integrative Psychiatric Research) team acknowledges funding from The Lundbeck Foundation (grant nos. R102-A9118 and R155-2014-1724), the Stanley Medical Research Institute, the European Research Council (project no.: 294838), the Novo Nordisk Foundation for supporting the Danish National Biobank resource, and grants from Aarhus and Copenhagen Universities and University Hospitals, including support to the iSEQ Center, the GenomeDK HPC facility, and the CIRRAU Center. The project leading to this application has received funding from the Innovative Medicines Initiative 2 Joint Undertaking (JU) under grant agreement no. 777394. The JU receives support from the European Union’s Horizon 2020 research and innovation programme and EFPIA and AUTISM SPEAKS, Autistica, SFARI. We thank the iPSCH-Broad Autism Group and the EU-AIMS LEAP group for sharing data. A full list of the authors and affiliations in the iPSYCH-Broad autism group and the EU-AIMS LEAP group is provided in the Supplementary Information., The 23andMe Research Team : Michelle Agee, Babak Alipanahi, Adam Auton, Robert K. Bell, Katarzyna Bryc, Sarah L. Elson, Pierre Fontanillas, Nicholas A. Furlotte, Karen E. Huber, Aaron Kleinman, Nadia K. Litterman, Jennifer C. McCreight, Matthew H. McIntyre, Joanna L. Mountain, Carrie A.M. Northover, Steven J. Pitts, J. Fah Sathirapongsasuti, Olga V. Sazonova, Janie F. Shelton, Suyash Shringarpure, Chao Tian, Joyce Y. Tung, Vladimir Vacic & Catherine H. Wilson, European Project: 294838,EC:FP7:ERC,ERC-2011-ADG_20110310,EIMS(2012), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), and Radboud university [Nijmegen]

Subjects
Male, DIAGNOSTIC OBSERVATION SCHEDULE, LD SCORE REGRESSION, 45/43, Medicine (miscellaneous), Genome-wide association study, Genome-wide association studies, Developmental psychology, FUNCTIONING AUTISM, Cohort Studies, 0302 clinical medicine, Heritability of autism, MESH: Cohort Studies, lcsh:QH301-705.5, GENERAL-POPULATION, 631/208/366/1373, 0303 health sciences, MESH: Genetic Predisposition to Disease, article, Autism spectrum disorders, MESH: Reproducibility of Results, Phenotype, Autistic traits, 631/208/727/2000, Trait, Female, General Agricultural and Biological Sciences, Psychology, MESH: Social Behavior, EMPATHY QUOTIENT, MESH: Autistic Disorder, 631/208/205/2138, Genetic predisposition to disease, MESH: Phenotype, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, PSYCHOMETRIC ANALYSIS, All institutes and research themes of the Radboud University Medical Center, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], mental disorders, medicine, Humans, REPETITIVE BEHAVIOR, Autistic Disorder, GENOME-WIDE ASSOCIATION, Social Behavior, Association (psychology), 030304 developmental biology, SYSTEMATIZING QUOTIENT, Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7], MESH: Humans, Reproducibility of Results, SPECTRUM QUOTIENT AQ, medicine.disease, MESH: Male, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, lcsh:Biology (General), MESH: Genome-Wide Association Study, Autism, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], MESH: Female, 030217 neurology & neurosurgery, Genome-Wide Association Study
Abstract

The core diagnostic criteria for autism comprise two symptom domains – social and communication difficulties, and unusually repetitive and restricted behaviour, interests and activities. There is some evidence to suggest that these two domains are dissociable, though this hypothesis has not yet been tested using molecular genetics. We test this using a genome-wide association study (N = 51,564) of a non-social trait related to autism, systemising, defined as the drive to analyse and build systems. We demonstrate that systemising is heritable and genetically correlated with autism. In contrast, we do not identify significant genetic correlations between social autistic traits and systemising. Supporting this, polygenic scores for systemising are significantly and positively associated with restricted and repetitive behaviour but not with social difficulties in autistic individuals. These findings strongly suggest that the two core domains of autism are genetically dissociable, and point at how to fractionate the genetics of autism., Varun Warrier et al. report a genome-wide association study of systemising, a non-social trait associated with autism. They find 3 loci associated with systemising and show that this trait has no significant genetic correlations to social phenotypic measures, demonstrating that the social and non-social aspects of autism are genetically distinct.

Published
2019
Full Text
View/download PDF

28. The association between the incidence of postmenopausal breast cancer and concentrations at street-level of nitrogen dioxide and ultrafine particles

Author

Mark S. Goldberg, France Labrèche, Scott Weichenthal, Eric Lavigne, Marie-France Valois, Marianne Hatzopoulou, Keith Van Ryswyk, Maryam Shekarrizfard, Paul J. Villeneuve, Daniel Crouse, Marie-Élise Parent, Research Institute of the McGill University Hospital Centre, Department of Medecine [Montréal], McGill University = Université McGill [Montréal, Canada], Department of Environmental and Occupational Health, School of Public Health, Université de Montréal (UdeM), Department of Epidemiology, Biostatistics and Occupational Health [Montréal], Health Canada, Air Health Science Division, Health Canada, Department of Epidemiology, Public Health and Preventive Medicine, University of Ottawa [Ottawa], Department of Civil Engineering, University of Toronto, Department of Health Sciences, School of Mathematics and Statistics, Carleton University, Department of Sociology, and New Brunswick Institute for Research, Data, and Training, University of New Brunswick (UNB), Institut Armand Frappier (INRS-IAF), Réseau International des Instituts Pasteur (RIIP)-Institut National de la Recherche Scientifique [Québec] (INRS), and The data collection for the breast cancer study was funded by the Quebec Breast Cancer Foundation and analyses for this paper were funded by Health Canada. Dr. Weichenthal also received support from a GRePEC salary award funded by the Cancer Research Society, the Quebec Ministry of Economy, Science and Innovation, and les Fonds de Recherche du Québec- Santé (FRQS). Marie-Élise Parent held a career award from the FRQS

Subjects
Postmenopausal breast cancer, [SDV]Life Sciences [q-bio], 010501 environmental sciences, 01 natural sciences, Biochemistry, 0302 clinical medicine, Interquartile range, Ultrafine particle, Medicine, General Environmental Science, education.field_of_study, Air Pollutants, Incidence (epidemiology), Incidence, Quebec, Case-control study, Environmental exposure, Middle Aged, 3. Good health, Postmenopause, 030220 oncology & carcinogenesis, Female, Environmental Monitoring, Diesel exhaust, Population, Nitrogen Dioxide, [SDV.CAN]Life Sciences [q-bio]/Cancer, Breast Neoplasms, 03 medical and health sciences, Breast cancer, Traffic-related air pollution, Occupational Exposure, Humans, Particle Size, education, 0105 earth and related environmental sciences, Aged, business.industry, Odds ratio, Environmental Exposure, medicine.disease, [SDE.ES]Environmental Sciences/Environmental and Society, Logistic Models, Ultrafine particles, [SHS.ENVIR]Humanities and Social Sciences/Environmental studies, Case-Control Studies, Particulate Matter, business, Demography
Abstract

International audience; There is scant information as to whether traffic-related air pollution is associated with the incidence of breast cancer. Nitrogen dioxide (NO2) and ultrafine particles (UFPs

Published
2017

29. Evaluation of anti-diabetic and anti-tumoral activities of bioactive compounds from Phoenix dactylifera L's leaf: In vitro and in vivo approach

Author

Mohamed Bouaziz, Mohamed Makni, Naziha Marrakchi, Bassem Khemakhem, M Chakroun, Hazem Ben Mabrouk, Noureddine Drira, Hanen El Abed, Hafedh Mejdoub, Faculté des Sciences de Sfax, Université de Sfax - University of Sfax, University of Gabes, Laboratoire des Venins et Biomolécules Thérapeutiques - Laboratory of Venoms and Therapeutic Biomolecules (LR11IPT08), Institut Pasteur de Tunis, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), École Nationale d'Ingénieurs de Sfax | National School of Engineers of Sfax (ENIS), and The major part of this work was accomplished at the Faculty of Sciences of Sfax. The authors would like to thank Prof. Monique Simmonds from Jodrell Laboratory, Kew Gardens UK, for her help with LC–MS/MS analysis. Special thanks are also go to Pr. Hafedh Bejaoui, from the English department at the Faculty of Science of Sfax and to Sana Chakroun (Rudolf-Bultmann Str. 4. 35039 Marburg) for carefully proofreading and polishing the language of the present paper, to Zaineb Kammoun (Sfax Faculty of Science) for her invaluable assistance in this project.

Subjects
0301 basic medicine, Male, MESH: Polyphenols/pharmacology, MESH: Plant Extracts/pharmacology, [SDV]Life Sciences [q-bio], Flavonoid, Phytochemicals, Pharmacology, MESH: Hyperglycemia/complications, MESH: Plant Leaves/chemistry, Mice, Oral administration, Tandem Mass Spectrometry, inhibitors, MESH: Hypoglycemic Agents/pharmacology, MESH: Phytochemicals/pharmacology, MESH: Animals, α-Glucosidase and α-Amylase, Acarbose, chemistry.chemical_classification, Cell Death, MESH: Antineoplastic Agents/pharmacology, MESH: Polyphenols/therapeutic use, Phoeniceae, 04 agricultural and veterinary sciences, General Medicine, MESH: Hyperglycemia/drug therapy, Postprandial Period, 040401 food science, Postprandial, Biochemistry, MESH: Phytotherapy, MESH: Hypoglycemic Agents/therapeutic use, MESH: Postprandial Period, MESH: Antineoplastic Agents/therapeutic use, medicine.drug, LC–MS/MS analysis, MESH: Phoeniceae/chemistry, MESH: Cell Line, Tumor, MESH: Phytochemicals/therapeutic use, MESH: Diabetes Mellitus, Experimental/complications, MESH: Diabetes Mellitus, Experimental/drug therapy, Antineoplastic Agents, MESH: alpha-Amylases/metabolism, Diabetes Mellitus, Experimental, 03 medical and health sciences, 0404 agricultural biotechnology, In vivo, MESH: Enzyme Assays, Diabetes mellitus, Cell Line, Tumor, medicine, [SDV.BV]Life Sciences [q-bio]/Vegetal Biology, Animals, Humans, Hypoglycemic Agents, MTT assay, IC50, MESH: Mice, Enzyme Assays, MESH: Plant Extracts/therapeutic use, MESH: Humans, Cytotoxic activity, Plant Extracts, MESH: Tandem Mass Spectrometry, Polyphenols, alpha-Glucosidases, medicine.disease, IGR-39 cancer cell lines, MESH: Diabetes Mellitus, Type 2/drug therapy, Phoenix dactylifera L.’s leaves, MESH: Male, [SDV.BV.PEP]Life Sciences [q-bio]/Vegetal Biology/Phytopathology and phytopharmacy, MESH: Cell Death/drug effects, MESH: Diabetes Mellitus, Type 2/complications, Plant Leaves, 030104 developmental biology, Antidiabetic activity, chemistry, Diabetes Mellitus, Type 2, Hyperglycemia, alpha-Amylases, MESH: alpha-Glucosidases/metabolism, MESH: Chromatography, Liquid, Chromatography, Liquid, Phytotherapy
Abstract

International audience; Among various chronic disorders, cancer and diabetes mellitus are the most common disorders. This study was designed to evaluate the effectiveness of hydroalcoholic extract of Phoenix dactylifera L. leaves (HEPdL) in animal models of type II diabetes in vitro/in vivo and in a human melanoma-derived cell line (IGR-39). A liquid chromatography–tandem mass spectrometry (LC–MS/MS) analysis was also performed to determine the amount of phenolic and flavonoid compounds in this plant. The physicochemical results by LC–MS/MS analysis of HEPdL showed the presence of 10 phenolic compounds. The in vitro study showed that the extract exhibited a more specific and potent inhibitor of α-glucosidase than α-amylase with an IC50 value of 20 ± 1 μg/mL and 30 ± 0.8 μg/mL, respectively. More importantly, the in vivo study of the postprandial hyperglycemia activity with (20 mg/kg) of HEPdL showed a decrease in plasma glucose levels after 60 min in resemblance to the glucor (acarbose) (50 mg/kg) effect. The oral administration of HEPdL (20 mg/kg) in alloxan-induced diabetic mices for 28 days showed a more significant anti-diabetic activity than that of the drug (50 mg/kg). Moreover, cytotoxicity effects of HEPdL in IGR-39 cancer cell lines were tested by MTT assay. This extract was effective in inhibiting cancer cells growth (IGR-39) at dose 35 and 75 μg/mL. These results confirm ethnopharmacological significance of the plant and could be taken further for the development of an effective pharmaceutical drug against diabetes and cancer

Published
2016