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Blood-brain barrier activation and/or dysfunction are a common feature of human neurobrucellosis, but the underlying pathogenic mechanisms are largely unknown. In this article, we describe an immune mechanism for inflammatory activation of human brain microvascular endothelial cells (HBMEC) in response to infection with Brucella abortus. Infection of HBMEC with B. abortus induced the secretion of 1L-6, IE-8, and MCP-1, and the upregulation of CD54 (ICAM-1), consistent with a state of activation. Culture supernatants (CS) from glial cells (astrocytes and microglia) infected with B. abortus also induced activation of HBMEC, but to a greater extent. Although B. abortus-infected glial cells secreted IE-ip and TNF-a:, activation of HBMEC was dependent on IL-1J because CS from B. abortus-infected astrocytes and microglia deficient in caspase-1 and apoptosis-associated speck-like protein containing a CARD failed to induce HBMEC activation. Consistently, treatment of CS with neutralizing anti- IL-lp inhibited HBMEC activation. Both absent in melanoma 2 and Nod-like receptor containing a pyrin domain 3 are partially required for caspase-1 activation and IL-ip secretion, suggesting that multiple apoptosis-associated speck-like protein containing CARD-dependent inflammasomes contribute to IL-lp-induced activation of the brain microvasculature. Inflammasomemediated IL-ip secretion in glial cells depends on TER2 and MyD88 adapter-like/TIRAP. Finally, neutrophil and monocyte migration across HBMEC monolayers was increased by CS from Brucella-infected glial cells in an IL-ip-dependent fashion, and the infiltration of neutrophils into the brain parenchyma upon intracranial injection of B. abortus was diminished in the absence of Nod-like receptor containing a pyrin domain 3 and absent in melanoma 2. Our results indicate that innate immunity of the CNS set in motion by B. abortus contributes to the activation of the blood-brain barrier in neurobrucellosis and IL-ip mediates this phenomenon. [ABSTRACT FROM AUTHOR]

This quasi-experimental study (a community-based, physician-led human papillomavirus [HPV] education campaign and school-based vaccination program) followed 6481 students at eight Pharr-San Juan-Alamo Independent School District (Rio Grande Valley, Texas) middle schools between August 2016 and March 2021. We describe the successes and challenges experienced during the COVID-19 pandemic. HPV vaccine initiation and completion rates increased 1.29-fold and 1.47-fold, respectively, between June 2019 and March 2021. Between March 2020 and March 2021, 268 HPV vaccine doses were provided through 24 school-based interventions. Our program continued successes seen in increasing HPV vaccination rates and reducing possible HPV-associated cancers. ( Am J Public Health . 2022;112(9):1269-1272. https://doi.org/10.2105/AJPH.2022.306970).

Myeloid sarcomas can be detected in up to 30% of acute myeloid leukemia cases or occur de-novo without bone marrow involvement. The most frequent localization of myeloid sarcomas in the abdominal cavity is the small intestine, and gastric presentations are infrequent, frequently misdiagnosed, and a high level of suspicion should exist when the characteristic histomorphology features are present. The current review features a case report with gastric presentation of myeloid sarcoma in a patient with a diagnosis of acute myeloid leukemia with trisomy 8. In addition, a review of the literature of intestinal-type myeloid sarcomas shows that less than 15% of these cases have been reported in the stomach. The most common molecular aberrancy detected in intestinal myeloid sarcomas is the fusion protein CBFB-MYH11. A review of several large studies demonstrates that the presence of myeloid sarcoma does not constitute an independent prognostic factor. The therapeutic approach will be tailored to the specific genetic abnormalities present, and systemic chemotherapy with hematopoietic stem cell transplant is the most efficient strategy., Competing Interests: Competing interests: The authors declare no conflict of Interest.

Introduction: Human papillomavirus (HPV) and HPV vaccine knowledge and awareness are known to be lower among Hispanics compared to non-Hispanic whites. However, Hispanics in the US are a non-homogenous population, with significant differences by nativity, particularly between the US-and foreign-born individuals. We examined HPV and HPV vaccine awareness among foreign-born Hispanics, US-born Hispanics, and US-born non-Hispanic whites., Methods: We analyzed data from the Health Information National Trends Survey (HINTS) 5, cycles 1 (2017) and 2 (2018), the most recent HINTS datasets including nativity information. We used descriptive statistics and multivariable regression to compare awareness of HPV and the HPV vaccine among ethnicity/nativity subgroups., Results: Over 50% of foreign-born Hispanics had not heard of HPV, compared to 32% of US-born Hispanics (P < 0.01) and 33% of non-Hispanic whites (p < 0.01). Lack of HPV vaccine awareness among foreign-born Hispanics was not significantly different from US-born Hispanics (52% vs. 44%, p = 0.12), but was significantly lower compared to non-Hispanic whites (52% vs. 32%, p < 0.01). In multivariable analyses, non-Hispanic whites had over twice the odds of having heard of HPV than foreign-born Hispanics (p < 0.05), while US-born Hispanics had 75% higher odds (p < 0.05). Regarding HPV awareness, non-Hispanic whites had 95% higher odds of having heard of the HPV vaccine than foreign-born Hispanics (p < 0.05), while differences between US and foreign-born Hispanics were not significant., Conclusion: There are significant nativity-related differences in HPV and HPV vaccine awareness and knowledge among US-born Hispanics. Over 50% of foreign-born Hispanic adults are unaware of HPV and the HPV vaccine., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 The Author(s).)

Objective: While disparities in endometrial hyperplasia and endometrial cancer are well documented in Blacks and Whites, limited information exists for Hispanics. The objective is to describe the patient characteristics associated with endometrial hyperplasia symptoms, endometrial hyperplasia with atypia and endometrial cancer, and assess factors contributing to racial/ethnic differences in disease outcomes., Methods: This single-center, retrospective study included women aged ≥50 years with ≥ two encounters for endometrial hyperplasia symptoms, endometrial hyperplasia with atypia and endometrial cancer between 2012 and 2016. Multivariate logistic regression models evaluated the predictors of endometrial cancer and hyperplasia., Results: We included 19,865 women (4749 endometrial hyperplasia symptoms, 71 endometrial hyperplasias with atypia, 201 endometrial cancers) with mean age of 60.45 years (SD 9.94). The odds of endometrial hyperplasia symptoms were higher in non-Hispanic Blacks (Odds Ratio [OR] 1.56, 95% Confidence Interval [CI] 1.20-1.72), Hispanics (OR 1.35, 95% CI 1.22-1.49), family history of female cancer (OR 1.25, 95% CI 1.12-1.39), hypertension (OR 1.24, 95% CI 1.14-1.35), and birth control use (OR 1.29, 95% CI 1.15-1.43). Odds of endometrial cancer and atypical hyperplasia increased for ages 60-64 (OR 7.95, 95% CI 3.26-19.37; OR 3.66, 95% 1.01-13.22) and being obese (OR 1.61, 95% CI 1.08-2.41; OR: 6.60, 95% CI 2.32-18.83). Odds of endometrial cancer increased with diabetes (OR 1.68, 95% CI 1.22-2.32)., Conclusion(s): Patients with obesity and diabetes had increased odds of endometrial cancer and hyperplasia with atypia. Further study is needed to understand the exogenous estrogen effect contributing to the increased incidence among Hispanics., Competing Interests: Declaration of Competing Interest The authors report no conflicts of interest., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Human papillomavirus (HPV)-related disease remains a significant source of morbidity and mortality, and this underscores the need to increase HPV vaccination to reduce the burden of the disease. The objective of this study was to examine the association between the number of HPV vaccine doses and the risk of histologically confirmed preinvasive cervical disease and high-grade cytology., Methods: This retrospective matched cohort study used administrative data from Optum's Clinformatics DataMart Database to identify females aged 9 to 26 years who received 1 or more quadrivalent HPV vaccine doses between January 2006 and June 2015. Cases and controls were matched on region, age, sexually transmitted disease history, and pregnancy. All had a Papanicolaou test ≥1 year after the date of the matched case's final dose. Cox proportional hazards models were used to examine the association between the number of HPV vaccine doses and the incidence of preinvasive cervical disease and high-grade cytology. The Kaplan-Meier method was used to estimate the cumulative incidence rate at the 5-year follow-up., Results: The study included 133,082 females (66,541 vaccinated and 66,541 unvaccinated) stratified by the number of HPV vaccine doses and the vaccine initiation age. Among those aged 15 to 19 years, the hazard ratio (HR) for high-grade cytology for the 3-dose group was 0.84 (95% confidence interval [CI], 0.73-0.97), whereas the HRs for histologically confirmed preinvasive cervical disease for 1, 2, and 3 doses were 0.64 (95% CI, 0.47-0.88), 0.72 (95% CI, 0.54-0.95), and 0.66 (95% CI, 0.55-0.80), respectively., Conclusions: The receipt of 1, 2, or 3 doses of an HPV vaccine by females aged 15 to 19 years was associated with a lower incidence of preinvasive cervical disease in comparison with unvaccinated females, and this supports the use of any HPV vaccination in reducing the burden of the disease., (© 2020 American Cancer Society.)

Objective: Compare the effectiveness of community-based HPV-related education and onsite school-based vaccination versus community-based education only for increasing HPV vaccine uptake in a rural, medically underserved area., Methods: Our cohort included 2307 Rio Grande City Consolidated Independent School District (RGCISD) middle school students from 3 schools enrolled in August 2016 and followed until April 2018. Using a quasi-experimental design, this study implemented an onsite school-based vaccination program and physician-led education on HPV and HPV vaccines for parents/guardians, school nurses/staff, and pediatric/family providers in the surrounding community (15-mile radius of RGCCISD) at 1 middle school ("intervention school"), and education-only for the remaining 2 schools ("comparison schools"). The Centers for Disease Control and Prevention's HPV-related educational materials supplemented the education. HPV vaccine status was obtained from school immunization records and the project's contracted vaccine vendor. HPV vaccine initiation and completion rates were compared pre and post intervention and between the intervention and comparison schools. Logistic regression was used to compare the odds of newly initiating/completing vaccination between the intervention and comparison schools., Results: At baseline, the intervention school had lower HPV vaccine initiation and completion rates than the comparison schools (20.00% and 8.70% vs 28.97% and 14.56%). Post intervention, the intervention school had higher initiation and completion rates than the comparison schools (53.67% and 28.36% vs 41.56% and 20.53%). Students from the intervention school were over 3.6-times more likely to newly initiate/complete the HPV vaccinations than students from the comparison schools., Conclusion: The school with on-site vaccination events and community-based education had a higher adolescent HPV vaccination rate compared to schools that received community-based education only., (Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.)

Objective: Cervical cancer rates in the United States have declined since the 1940's, however, cervical cancer incidence remains elevated in medically-underserved areas, especially in the Rio Grande Valley (RGV) along the Texas-Mexico border. High-resolution microendoscopy (HRME) is a low-cost, in vivo imaging technique that can identify high-grade precancerous cervical lesions (CIN2+) at the point-of-care. The goal of this study was to evaluate the performance of HRME in medically-underserved areas in Texas, comparing results to a tertiary academic medical center., Methods: HRME was evaluated in five different outpatient clinical settings, two in Houston and three in the RGV, with medical providers of varying skill and training. Colposcopy, followed by HRME imaging, was performed on eligible women. The sensitivity and specificity of traditional colposcopy and colposcopy followed by HRME to detect CIN2+ were compared and HRME image quality was evaluated., Results: 174 women (227 cervical sites) were included in the final analysis, with 12% (11% of cervical sites) diagnosed with CIN2+ on histopathology. On a per-site basis, a colposcopic impression of low-grade precancer or greater had a sensitivity of 84% and a specificity of 45% to detect CIN2+. While there was no significant difference in sensitivity (76%, p = 0.62), the specificity when using HRME was significantly higher than that of traditional colposcopy (56%, p = 0.01). There was no significant difference in HRME image quality between clinical sites (p = 0.77) or medical providers (p = 0.33)., Conclusions: HRME imaging increased the specificity for detecting CIN2+ when compared to traditional colposcopy. HRME image quality remained consistent across different clinical settings., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Context: Despite current recommendations, human papillomavirus vaccine uptake remains low. A systematic review and meta-analysis assessed the effectiveness of interventions targeting human papillomavirus vaccine initiation and completion among children, adolescents, and young adults aged 9-26 years., Evidence Acquisition: Three electronic databases (CINAHL, OVID, and Web of Science) were searched for articles published in English peer-reviewed journals between January 2006 and January 2017 of U.S. studies that evaluated intervention strategies and reported post-intervention human papillomavirus vaccine initiation or completion rates among individuals aged 9-26 years. Study characteristics and outcomes were extracted. Data were collected in 2016 and analyzed in 2017., Evidence Synthesis: Reviewers screened 983 unique titles and abstracts, read 241 full-text articles, and extracted data from 30 articles meeting the inclusion criteria (12 behavioral, ten environmental, four informational, and four combination strategies). Published EQUATOR (Enhancing the Quality and Transparency of Health Research) guidelines were used to assess study quality. Random effects meta-analyses were conducted. The meta-analyses included 17 RCTs and quasi-experiments involving 68,623 children, adolescents, and young adults. The pooled relative incidence estimates were 1.84 (95% CI=1.36, 2.48) for human papillomavirus vaccine initiation and 1.50 (95% CI=1.23, 1.83) for completion. Behavioral and informational interventions doubled human papillomavirus vaccine initiation (relative incidence estimate=2.04, 95% CI=1.36, 3.06 and relative incidence estimate=1.92, 95% CI=1.27, 2.91, respectively). Behavioral interventions increased completion by 68% (relative incidence estimate=1.68, 95% CI=1.25, 2.27)., Conclusions: Evidence supports behavioral interventions for increasing human papillomavirus vaccine initiation and completion. Future studies are needed to assess the effectiveness of interventions in reaching diverse populations and reducing missed opportunities for human papillomavirus vaccination., (Copyright © 2018 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.)

A series of novel mimetic peptides were designed, synthesised and biologically evaluated as inhibitors of Aβ 42 aggregation. One of the synthesised peptidic compounds, termed compound 7 modulated Aβ 42 aggregation as demonstrated by thioflavin T fluorescence, acting also as an inhibitor of the cytotoxicity exerted by Aβ 42 aggregates. The early stage interaction between compound 7 and the Aβ 42 monomer was investigated by replica exchange molecular dynamics (REMD) simulations and docking studies. Our theoretical results revealed that compound 7 can elongate the helical conformation state of an early stage Aβ 42 monomer and it helps preventing the formation of β-sheet structures by interacting with key residues in the central hydrophobic cluster (CHC). This strategy where early "on-pathway" events are monitored by small molecules will help the development of new therapeutic strategies for Alzheimer's disease., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objective: The aim of the study was to investigate the effects of 3 or less quadrivalent human papillomavirus (HPV) vaccine doses on anogenital warts in both males and females in the United States., Materials and Methods: We conducted a retrospective database study that included males and females aged 9 to 26 years who received varying numbers of vaccine doses between 2006 and 2015. The primary outcome was the incidence of anogenital warts starting 3 months after the last dose of the HPV vaccine. Proportional hazard regression models were used to examine the association between the number of HPV vaccine doses and the incidence of anogenital warts. The Kaplan-Meier method was used to estimate the proportion of subjects., Results: A total of 440,532 females and 133,394 males were included in the study. We found a significant 2-way interaction (p < .0001) between the number of doses and age. For the group between 15 and 19 years of age, the hazard ratio of anogenital warts for the 3-dose vaccine was 0.58 (95% CI = 0.49-0.70), whereas it was 0.65 (95% CI = 0.49-0.85) and 0.67 (95% CI = 0.51-0.89) for the 1- and 2-dose groups, respectively., Conclusions: Our findings showed that 1, 2, and 3 doses of the quadrivalent HPV vaccine were similarly effective against anogenital warts in 15- to 19-year-old adolescents, irrespective of sex.

Objective: To examine the associations between modifiable health-related factors, such as smoking, low physical activity and higher body mass index (BMI), and annual health care visits and expenditures among adult cancer survivors in the United States., Methods: Using data from the 2010-2014 Medical Expenditures Panel Survey, we identified 4920 cancer survivors (aged 18-64 years) and a matched comparison group. Our outcomes were number of annual health care visits [i.e., outpatient/office-based, hospital discharges and emergency department (ED) visits] and total health care expenditures. We examined health-related factors, demographics, insurance and health status (i.e., comorbidity and mental distress). Bivariate and multivariable analyses examined the associations between outcomes and health-related factors., Results: Of survivors, approximately 21% were current smokers, 52% reported low physical activity and 35% were obese, vs. 19.6, 49.5 and 36.7%, respectively, of the comparison group. These factors were associated with greater comorbidity and mental distress in both groups. Current smokers among survivors were less likely to have outpatient visits [marginal effect on the number of visits (ME) = -3.44, 95% confidence interval (CI) -5.02 to -1.86, P < 0.001] but more likely to have ED visits (ME = 0.11, 95% CI 0.05-0.18, P = 0.001) than non-smokers. Physically active individuals in both groups had fewer ED visits, and lower total expenditures than those who reported low physical activity., Conclusion: Regular assessments of health-related factors should be incorporated in survivorship care to reduce the burden of cancer. Modification of survivors' health-related factors (e.g., low physical activity) may help improve their health outcomes and reduce financial burden.

Purpose: Examine preventive services utilization among female survivors of adolescent and young adult (AYA) cancer compared with women without cancer in the USA., Methods: A total of 1017 women diagnosed with cancer at AYA ages (15-39 years) who were at least 5 years since diagnosis were identified from 2008 to 2012 Medical Expenditure Panel Surveys. A comparison group without cancer was matched on age and other characteristics. General preventive services included dental, medical, blood pressure, and cholesterol checkups, and flu shots in the previous year. Cancer-related services included pap smear and mammography. Preventive services and covariates (demographics, socioeconomics, and health status) were compared between groups using χ 2 tests. Ordinal logistic regression identified covariates associated with general preventive services use., Results: Female survivors reported dental checkups less often (57.8 vs. 72.4 %, p < 0.001) than the comparison group and checked their blood pressure (90 vs. 86.7 %, p = 0.045) and cholesterol (67.5 vs. 61.7 %, p = 0.045) more often. No differences were found in flu shots, medical checkups, and cancer-related services. Survivors without insurance were less likely to use general preventive services (odds ratio [OR] = 0.2, 95 % confidence interval [CI] 0.12-0.35, p < 0.001). Older survivors (OR = 3.09, 95 % CI 1.69-5.62, p < 0.001) and those who speak Spanish or other languages at home (OR = 3.19, 95 % CI 1.33-7.67, p = 0.01) were more likely to use general prevention than their counterparts., Conclusion: Overall, female survivors were as likely as the comparison group to use preventive services, except dental services, blood pressure, and cholesterol checks., Implications for Cancer Survivors: Survivors may require support to use recommended preventive services more effectively, especially the younger and uninsured who may be at greater risk for underuse.

Cervical cancer incidence and mortality rates are significantly higher in low- and middle-income countries compared with the United States and other developed countries. This disparity is caused by decreased access to screening, often coupled with low numbers of trained providers offering cancer prevention and treatment services. However, similar disparities are also found in underserved areas of the United States, such as the Texas-Mexico border, where cervical cancer mortality rates are 30% higher than in the rest of Texas. To address these issues, we have adopted the Project ECHO (Extension for Community Healthcare Outcomes) program, a low-cost telementoring model previously proven to be successful in increasing local capacity, improving patient management skills, and ultimately improving patient outcomes in rural and underserved areas. We use the Project ECHO model to educate local providers in the management of cervical dysplasia in a low-resource region of Texas and have adapted it to inform strategies for the management of advanced cervical and breast cancer in Latin America and sub-Saharan Africa. This innovative approach, using ECHO, is part of a larger strategy to enhance clinical skills and develop collaborative projects between academic centers and partners in low-resource regions., Competing Interests: The following represents disclosure information provided by authors of this manuscript. All relationships are considered compensated. Relationships are self-held unless noted. I = Immediate Family Member, Inst = My Institution. Relationships may not relate to the subject matter of this manuscript. For more information about ASCO's conflict of interest policy, please refer to www.asco.org/rwc or ascopubs.org/jco/site/ifc. Melissa S. LopezNo relationship to discloseEllen S. BakerStock or Other Ownership: MerckAndrea M. MilbourneNo relationship to discloseRose M. GowenNo relationship to discloseAna M. RodriguezNo relationship to discloseCesaltina LorenzoniNo relationship to discloseCatherine MwabaResearch Funding: Mylan Zambia (Inst) Travel, Accommodations, Expenses: Fresenius Kabi South AfricaSusan Citonje MsadabweTravel, Accommodations, Expenses: AstraZenecaJosé Humberto TavaresNo relationship to discloseGeorgia Fontes-CintraNo relationship to discloseGustavo Zucca-MatthesNo relationship to discloseDonato Callegaro-FilhoNo relationship to discloseDanielle Ramos-MartinNo relationship to discloseIcaro Thiago de CarvalhoNo relationship to discloseRobson CoelhoNo relationship to discloseRenato Moretti-MarquesNo relationship to discloseThiago ChulamTravel, Accommodations, Expenses: A.C. Camargo Cancer CenterMila Pontremoli-SalcedoNo relationship to discloseFernanda NozarNo relationship to discloseVeronica FiolTravel, Accommodations, Expenses: UrufarmaMauricio MazaNo relationship to discloseSanjeev AroraNo relationship to discloseErnest T. HawkEmployment: MD Anderson Cancer Center Honoraria: National Cancer Institute, Huntsman Cancer Institute, Mayo Clinic Cancer Center, Kansas University Medical Center, Ohio State University Comprehensive Cancer Center, Roswell Park Cancer Institute, Simmons Comprehensive Cancer Center, University of Nebraska Medical Center, University of South Alabama Mitchell Cancer Institute, Johns Hopkins University, Oncology Nursing Society Conference, Weill Cornell Medical College, ASCO, American Association for Cancer Research Consulting or Advisory Role: Cancer Prevention Pharmaceuticals, PLx Pharma, POZEN Research Funding: National Institutes of Health/National Cancer Institute (Inst), the Cancer Prevention Research Institute of Texas (Inst), Cancer Prevention Pharmaceuticals (Inst) Patents, Royalties, Other Intellectual Property: John Wiley & Sons Travel, Accommodations, Expenses: National Cancer Institute, American Association for Cancer Research, Huntsman Cancer Institute, Kansas University Medical Center, Mayo Clinic Cancer Center, Ohio State University Comprehensive Cancer Center, Roswell Park Cancer Institute, Simmons Comprehensive Cancer Center, University of Nebraska Medical Center, Johns Hopkins University, Oncology Nursing Society Conference, Weill Cornell Medical College, ASCO, American Association for Cancer Research, American Cancer Society, Association of American Cancer Institutes—Cancer Center Administrators Forum, Alliance Prevention Committee, First Annual Meta-ECHO MeetingKathleen M. SchmelerResearch Funding: Becton Dickinson Patents, Royalties, Other Intellectual Property: UpToDate

Objective: The purpose of this study was to explore the endoscopic endonasal approach to the anterior communicating artery complex., Design: Anatomic, morphometric analysis of human cadaver heads., Subjects: Fifteen latex-injected adult cadaver heads., Main Outcome Measures: The anatomic boundaries of the operative field and the dimensions of exposure of the anterior communicating artery (ACoA) complex were measured and clip placement feasibility was assessed., Results: Exposure of the ACoA and bilateral A1 and A2 segments was accomplished in all 15 cadaver heads. Average length of the exposed ACoA was 3 ± 1 mm, the left A1 was 5 ± 3 mm and right A1 was 5 ± 1 mm, while the A2 segment was 5 ± 2 mm bilaterally. The average distance from the alar floor to the ACoA was 95 mm, while proximal lateral limit measured between the alar floor margins was 36 mm. The distal lateral limit as defined by the distance between the lateral most exposed margins of the chiasm was 19 mm. Clip placement was accomplished for the ACoA and the A1 and A2 segments bilaterally in all specimens., Conclusion: The endoscopic, endonasal transtuberculum, transplanum approach is an anatomically feasible alternative to treating select aneurysms of the ACoA complex., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Purpose: To assess how first course of treatment affects cancer-specific survival in women diagnosed with endometrial cancer younger than 50 years old., Methods: Public-use data from the Surveillance, Epidemiology, and End Results program were used. The study included 82,721 women diagnosed with primary, invasive endometrial cancer between 2000 and 2011. We assessed type of treatment using Cox's proportional hazards models to determine survival disparity by age and stage., Results: Cancer-specific survival significantly improved for those aged ≥50 years with late stage, but did not improve for those <50. First course of treatment significantly affected cancer-specific survival for endometrial cancer patients. Regardless of age, survival was greatly improved for late-stage patients who received a combination of surgery and radiation [hazard ratio (HR) 0.62 [95 % confidence interval (CI) 0.47-0.78] and 0.64 (95 % CI 0.59-0.68)] compared to those who received total hysterectomy with removal of ovaries and tubes. However, the proportion of patients who received combination therapy decreased over time. The magnitude of decrease was larger in patients <50 than in those aged ≥50. Overall, about 24-57 % of the difference in cancer-specific survival over time in patients aged <50 was explained by their initial treatment., Conclusions: Improvement in cancer-specific survival was only seen in older women with late-stage diagnosis. Despite improvements in diagnoses and treatments, the difference in age-specific survival indicates that more should be done to understand why these rates are not improving for those younger than 50 years old.

Objective: Our objective was to estimate the incidence of uterine leiomyosarcoma in patients with leiomyomas following laparoscopic supracervical hysterectomy and myomectomy procedures., Study Design: For this study, we analyzed records of 13,964 women aged 25-64 years who underwent laparoscopic supracervical hysterectomies or myomectomies for leiomyomas from 2002 to 2011 using Clinformatics DataMart. Patient records were divided into two groups: history of laparoscopic supracervical hysterectomy and history of myomectomy. Subjects were tracked to identify diagnosis of leiomyosarcoma within 1 year of the procedure. We analyzed data from the 25-39, 40-49, and 50-64 age brackets. Evidence was obtained from a cohort study from national private insurance claims in the US., Results: Our results showed the incidence of occult leiomyosarcoma developing within 1 year following supracervical hysterectomy using a laparoscopic-assisted approach are 9.8, 10.7, and 33.4 per 10,000 for the 25-39, 40-49, and 50-64 age brackets, respectively; the overall incidence rate is 13.1 per 10,000. The incidence rate of occult leiomyosarcoma developing within 1 year following myomectomy using a laparoscopic-assisted approach are 0.0, 33.8, and 90.1 per 10,000 for the 25-39, 40-49, and 50-64 age brackets, respectively; the overall incidence rate is 17.3 per 10,000., Conclusion: Our analysis shows the overall risk of being diagnosed with occult leiomyosarcoma is 12.9 per 10,000 in laparoscopic-assisted supracervical hysterectomy and myomectomy for patients younger than 49. There is no evidence of occult leiomyosarcoma 1 year after operation for patients younger than 40 who underwent laparoscopic myomectomy., (Copyright © 2015. Published by Elsevier Ireland Ltd.)

The inositol 1,4,5-trisphosphate receptor (IP3R) is a ubiquitously expressed endoplasmic reticulum (ER)-resident calcium channel. Calcium release mediated by IP3Rs influences many signaling pathways, including those regulating apoptosis. IP3R activity is regulated by protein-protein interactions, including binding to proto-oncogenes and tumor suppressors to regulate cell death. Here we show that the IP3R binds to the tumor suppressor BRCA1. BRCA1 binding directly sensitizes the IP3R to its ligand, IP3. BRCA1 is recruited to the ER during apoptosis in an IP3R-dependent manner, and, in addition, a pool of BRCA1 protein is constitutively associated with the ER under non-apoptotic conditions. This is likely mediated by a novel lipid binding activity of the first BRCA1 C terminus domain of BRCA1. These findings provide a mechanistic explanation by which BRCA1 can act as a proapoptotic protein., (© 2015 by The American Society for Biochemistry and Molecular Biology, Inc.)

Objective: To compare demographics, tumor characteristics, the first course of treatment, and cancer-specific survival of non-Hispanic White and Hispanic women with endometrial cancer., Methods: We used public-use data from the Surveillance, Epidemiology, and End Results (SEER) Program. The study included 69,764 non-Hispanic White and Hispanic women diagnosed with endometrial cancer between 2000 and 2010. Using Cox proportional hazards models, demographics, tumor characteristics, and treatment were assessed as potential explanatory variables for the survival disparity between non-Hispanic Whites and Hispanics., Results: Kaplan-Meier estimation with Bonferroni correction showed statistically different cancer-specific survival for U.S.-born and foreign-born Hispanics compared to non-Hispanic Whites, but no difference between birthplace-unknown Hispanics and non-Hispanic Whites. In 2000-2005, U.S.-born and foreign-born Hispanics had a higher risk of endometrial cancer death compared to non-Hispanic Whites after full adjustment (hazard rate (HR)=1.61, 95% Confidence Interval (CI):1.44-1.79 and 1.27, 95% CI:1.13-1.43). In 2006-2010, the risk of endometrial death was not statistically significant for U.S.-born Hispanics (HR=1.16, 95% CI:0.99-1.36), but increased for foreign-born Hispanics (HR=1.31, 95% CI:1.12-1.52). Most of the survival disparity between Hispanic and non-Hispanic White women was mediated by cancer characteristics, specifically, stage and node involvement., Conclusions: Hispanic women have higher cancer-specific mortality compared to non-Hispanic Whites. Compared to 2000-2005, more Hispanics were diagnosed at later stages and fewer received combination therapy in 2006-2010. Early detection is vital to improving endometrial cancer survival as most of the disparity was mediated by stage. Increased efforts are needed to improve education and access to care for Hispanic women., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Study Objective: The purpose of this analysis was to compare the trends in undergoing laparoscopic hysterectomy (versus abdominal or vaginal hysterectomy) based on patient age, race, median income and insurance type, from 2003 to 2010., Design: Retrospective study (Canadian Task Force classification II-3)., Setting: National sample of hospital admissions after hysterectomy., Patients: Health Cost and Utilization Project-Nationwide Inpatient Sample database was used to review records of women who underwent hysterectomy for either menorrhagia or leiomyoma from 2003-2010., Intervention: The predicted probability of undergoing laparoscopic hysterectomy was determined for each year according to patient age, race, median income, and insurance type. The slopes of these values (i.e. the trend) was compared for each subgroup (i.e. black, white, Asian, etc.) in these categories., Main Results: A total of 530, 154 cases were included in this study. Total number of hysterectomies decreased by 39% from 60,364 to 36,835 from 2003 to 2010. The percent of hysterectomies that were laparoscopic increased from 11% in 2003 to 29% in 2010. All groups analyzed experienced an increase in predicted probability of undergoing a laparoscopic hysterectomy. Of all women undergoing hysterectomy, the probability of undergoing a laparoscopic hysterectomy remained highest for women who were less than 35 years old, white, with the highest median income, and with private insurance from 2003-2010. The slope was significantly greater for (1) white females versus all other races analyzed (p<0.01), (2) females in the highest income quartile versus females in the lowest income quartile (p<0.01) and (3) females with private insurance versus females with Medicaid (p<0.01) or Medicare (p<0.01)., Conclusions: There remains a gap in distribution of laparoscopic hysterectomies with regards to age, race, median income and insurance type that does not seem to be closing, despite the increased availability of laparoscopic hysterectomies., (Copyright © 2014 AAGL. Published by Elsevier Inc. All rights reserved.)

Because advances in therapy have increased long-term survival for women with cervical cancer, it is important to study the risk of secondary primary malignancies in high-dose organ areas. From the 1973-2009 National Cancer Institute Surveillance, Epidemiology, and End Results (SEER) program, we studied the risk of developing cancer of the colon and rectum in 64,507 cervical cancer patients over 35 years after initial radiation treatment. We also assessed change in risk over time. Kaplan-Meier estimator for survival curve and Cox proportional hazards models was used. More than half (52.6%) of the cervical cancer patients received radiation treatment. In the analyses adjusted for race/ethnicity, age, marital status, surgery status, stage and grade, the risk of colon cancer between those both with and without XRT diverged beginning at approximately 8 years. After 8 years, the hazard ratio for developing colon cancer was 2.00 (95% CI 1.43-2.80) for women with radiation versus those without radiation treatment. The risk of rectal cancer diverged after 15 years of follow-up (HR 4.04, 95% CI 2.08-7.86). After 35 years of follow-up, the absolute risk of developing colon cancer was 6.5% for those who received radiation versus 2.5% for those without, and 3.7 versus 0.8% for rectum. The risk of colon and rectum cancer over 20 years of follow-up after radiation remained the same across three eras (1973-1980, 1981-1990, and 1991-2000). Radiation-induced second cancers of the colon and rectum may occur 8 years after radiation treatment for cervical cancer.

Study Objective: To evaluate 1-year outcomes of robotic sacrocolpopexy (RSC) for pelvic organ prolapse using barbed delayed absorbable sutures., Design: Retrospective cohort study (Class II-3)., Settings: University-based hospital in Southeast Texas., Patients: Patients with symptomatic apical pelvic organ prolapse who underwent RSC using barbed delayed absorbable sutures between January 2011 and August 2012. Patients were examined postoperatively at least twice (after 6 weeks and 1 year)., Interventions: RSC procedure., Measurements and Main Results: The study included a total of 20 patients, of them 15 had grades 3 or 4 whereas 5 had grade 2 apical defects according to the Baden-Walker classification system. Fourteen patients (70%) underwent concomitant hysterectomy while 9 (45%) underwent concomitant anti-incontinence surgery. Mesh suturing times were 46.9 ± 12.6 and 20.5 ± 9.3 minutes in the first 10 versus the last 10 cases, respectively (p < .001). The mean follow-up duration was 17.3 months (range, 12-24 months). There were no recurrences of apical defects or mesh/suture exposure/erosion. However, 1 patient developed a grade 2 cystocele, and another developed new-onset urinary incontinence, both after 1 year. A third patient's urine leakage did not improve postoperatively. Lastly, a fourth patient developed port site incisional hernia and underwent repair 5 months later., Conclusion: Our study suggests that barbed delayed absorbable sutures are safe and effective in RCS procedures over 1 year. Larger, comparative, and randomized trials are recommended for definitive conclusions., (Copyright © 2014 AAGL. Published by Elsevier Inc. All rights reserved.)

Study Objective: To determine patient and hospital characteristics that were associated with undergoing laparoscopic hysterectomy compared with abdominal hysterectomy., Design: Canadian Task Force Classification II-3., Methods: In this retrospective cohort study, we analyzed the 2010 Healthcare Cost and Utilization Project Nationwide Inpatient Sample database. All women who underwent laparoscopic or abdominal hysterectomy for either menorrhagia or leiomyoma were included based on International Classification of Diseases, Ninth Revision coding. A linear model with binomial distribution and logit link function was used to determine patient and hospital characteristics associated with hysterectomy approach., Main Results: A total of 32 436 patients were included in this study. Of these, 32% patients underwent laparoscopic hysterectomies, and 67% underwent abdominal hysterectomies. With regard to patient characteristics, women younger than 35 years old were more likely to undergo laparoscopic hysterectomy when compared with each of the other age categories (p < .001). White women were more likely to undergo laparoscopic hysterectomy than black women, Hispanic women, or women classified as "other" races (p < .001 for all comparisons). With regard to median income, patients from the lowest national quartile were less likely to undergo laparoscopic hysterectomy when compared with each of the other 3 national quartiles for income (p = .01, p < .001, p = .001, respectively). Payment by private insurance was associated with laparoscopic hysterectomy when compared with payment by Medicare or payment by insurance category "other" (p < .001 for both). With regard to hospital characteristics, hospitals in the Northeast were more likely to have laparoscopic hysterectomies than hospitals in the Midwest or South (p < .001 for both comparisons); urban hospitals were more likely than rural hospitals (p < .001); teaching hospitals were more likely than nonteaching hospitals (p < .001); and government-owned hospitals were less likely than private, nonprofit or private, investor owned (p < .001 for both comparisons)., Conclusions: Despite the increased popularity of and training in laparoscopic hysterectomies, there remains an obvious disparity in its delivery with regard to patient and hospital characteristics. Further investigation is needed on the etiology of this disparity and interventions that may alleviate it., (Copyright © 2014 AAGL. Published by Elsevier Inc. All rights reserved.)

Study Objective: To evaluate tubal patency after hysteroscopic sterilization using the Essure microinsert (Conceptus Inc, San Carlos, CA)., Design: A retrospective longitudinal cohort study., Design Classification: II-3., Setting: Patients undergoing hysteroscopic sterilization in the outpatient clinic of a university-based hospital in Southeast Texas from July 2009 to November 2011., Patients: Two hundred twenty-nine women (ages 21-44 yrs, 71% Hispanic) desiring sterilization with a history of regular menses, demonstrated prior fertility (≥1 live birth), and the ability to use an alternative contraceptive method for at least 90 days after coil placement were included. Twenty six patients in this cohort were excluded because of failure to perform a hysterosalpingogram (HSG), tubal perforation, severe dyspareunia, a history of ectopic pregnancy, tubal surgery, or cervical intraepithelial neoplasia., Interventions: Not applicable., Measurements and Main Results: HSGs were assessed for microinsert location and tubal occlusion. Two hundred three patients were included for analysis. After the successful bilateral hysteroscopic placement of Essure microinserts in fallopian tubes, all patients returned for the first follow-up HSG a mean of 103 ± 38 days after the procedure. Patients with fallopian tube patency at the initial HSG returned for second and/or third HSGs as needed at 192 ± 45 and 291 ± 97 days, respectively. Correct device placement was confirmed in 100% of cases at the first HSG. The tubal patency rates at the 90-day and 180-day HSGs were 16.1% (95% confidence interval, 7.4%-31.7%) and 5.8% (95% CI, 1.2%-24.4%), respectively. These rates were estimated by the accelerated failure time model with log normal distribution and interval censored time to event. The 16.1% 90-day tubal patency rate is significantly different from the 8% rate reported by Cooper et al in the 2003 multicenter phase III pivotal trial (p <.001)., Conclusion: Our data indicate that hysteroscopic sterilization with Essure results in a higher initial tubal patency rate than previously reported. Multivariate analyses are needed to identify factors associated with an increased risk of postprocedure tubal patency., (Copyright © 2013 AAGL. Published by Elsevier Inc. All rights reserved.)

BRCA1, a multi-domain protein, is mutated in a large percentage of hereditary breast and ovarian cancers. BRCA1 is most often mutated in three domains or regions: the N-terminal RING domain, exons 11-13, and the BRCT domain. The BRCA1 RING domain is responsible for the E3 ubiquitin ligase activity of BRCA1 and mediates interactions between BRCA1 and other proteins. BRCA1 ubiquitinates several proteins with various functions. The BRCA1 BRCT domain binds to phosphoproteins with specific sequences recognized by both BRCA1 and ATM/ATR kinases. Structural studies of the RING and BRCT domains have revealed the molecular basis by which cancer causing mutations impact the functions of BRCA1. While no structural data is available for the amino acids encoded by exons 11-13, multiple binding sites and functional domains exist in this region. Many mutations in exons 11-13 have deleterious effects on the function of these domains. In this mini-review, we examine the structure-function relationships of the BRCA1 protein and the relevance to cancer progression.

We performed experiments to characterize the inducibility of nucleotide excision repair (NER) in Caenorhabditis elegans, and to examine global gene expression in NER-deficient and -proficient strains as well as germline vs. somatic tissues, with and without genotoxic stress. We also carried out experiments to elucidate the importance of NER in the adult life of C. elegans under genotoxin-stressed and control conditions. Adult lifespan was not detectably different between wild-type and NER-deficient xpa-1 nematodes under control conditions. However, exposure to 6J/m(2)/day of ultraviolet C radiation (UVC) decreased lifespan in xpa-1 nematodes more than a dose of 100 J/m(2)/day in wild-type. Similar differential sensitivities were observed for adult size and feeding. Remarkably, global gene expression was nearly identical in young adult wild-type and xpa-1 nematodes, both in control conditions and 3h after exposure to 50 J/m(2) UVC. Neither NER genes nor repair activity were detectably inducible in young adults that lacked germ cells and developing embryos (glp-1 strain). However, expression levels of dozens of NER and other DNA damage response genes were much (5-30-fold) lower in adults lacking germ cells and developing embryos, suggesting that somatic and post-mitotic cells have a much lower DNA repair ability. Finally, we describe a refinement of our DNA damage assay that allows damage measurement in single nematodes.

Manganese superoxide dismutase (SOD2) has been well established to be essential for protection from a variety of apoptotic stimuli. Here we demonstrate that the antiapoptotic effects of SOD2 are attributed to its ability to generate H(2)O(2) and that its efficient removal resensitizes cells to tumor necrosis factor (TNF)-alpha-induced apoptosis. SOD2 overexpression in HT-1080 cells leads to a decrease in the fluorescence of the superoxidesensitive fluorophore, dihydroethidium, and a concomitant increase in oxidation of the H2O2-sensitive dye, dichlorodihydrofluorescein diacetate (DCFDA). The rate of aminotriazole-inhibited catalase activity also was increased when SOD2 is overexpressed and reflects a 1.6-fold increase in the steady-state production of H(2)O(2). The increase in H(2)O(2) was associated with decreased sensitivity to TNF-alpha-mediated apoptosis, as measured by monitoring the loss of mitochondrial membrane potential (MMP), caspase activation, poly-ADP ribose polymerase (PARP) cleavage, and accumulation of hypodiploid DNA content. Both the increase in H2O2 and resistance to TNF-mediated apoptosis were reversed by coexpression of catalase. The lipid hydroperoxide scavengers, beta-hydroxytoluene and trolox, and the iron chelator, desferroxamine, showed partial recovery of TNF-induced apoptosis. These findings indicate that increases in the intracellular steady-state production of H(2)O(2) by SOD2 can block the activation of key processes fundamental to the process of programmed cell death.

Purpose: Elevated manganese superoxide dismutase (Sod2) levels have been reported to be associated with an increased frequency of tumor invasion and metastasis in certain cancers, and the aim of this study is to examine the molecular mechanisms by which this occurs., Experimental Design: Sod2 and catalase overexpressing HT-1080 fibrosarcoma cell lines were used to evaluate the H(2)O(2)-dependent regulation of matrix metalloproteinase (MMP)-1 promoter activity, mitogen-activated protein (MAP) kinase signaling, DNA-binding activity, and MMP mRNA levels. The invasive and metastatic potential of Sod2 overexpressing cells was characterized using subrenal capsular implantation or tail vein injection of tumor cells into nude mice, respectively., Results: Our data reveal that Sod2 overexpression increases the DNA-binding activity of transcription factors critical for MMP expression but also enhances MMP-1 promoter activity via the Ras//MAP/extracellular signal-regulated kinase (MEK) signaling cascade. A single nucleotide polymorphism that creates an Ets site at position -1607 bp confers Sod2-dependent MMP-1 promoter activity. Sod2 overexpression also increases the mRNA levels of MMPs-2, -3, -7, -10, -9, -11 and enhances the metastatic potential of fibrosarcoma cells when implanted in immunodeficient mice. The Sod2-dependent increases in AP-1 and SP-1 DNA-binding activity, MMP-1 promoter activity, general MMP expression, and collagen degradation can be reversed by the hydrogen peroxide-detoxifying enzyme, catalase., Conclusion: MMPs play a critical role in the process of stromal invasion and metastasis, and these findings suggest that the association between increased Sod2 and poor prognosis in certain cancers may be attributed to elevated MMP production.