Estrogen receptor beta polymorphisms are associated with bone mass in women and men: the Framingham Study.

ESR2 is expressed in bone cells, yet few studies have tested its variation for association with BMD, an important determinant of osteoporotic fractures. This was investigated in 723 men and 795 women from the Framingham study. Results show association of variation in this gene with BMD in both women and men. INTRODUCTION: Osteoporotic fracture risk is highly dependent on bone density, a quantitative multifactorial trait with a substantial genetic component. In contrast to the growing body of evidence that estrogen receptor alpha (ESR1) plays a role in bone metabolism, few studies have examined the estrogen receptor beta (ESR2) gene for association with BMD. An ESR2 CA repeat polymorphism, D14S1026, was associated with BMD in two small studies, each with <200 women. MATERIALS AND METHODS: The objective of this investigation was to assess whether D14S1026 or four other intronic polymorphisms were associated with BMD in 723 men and 795 women (mean age, 60 years) from the offspring cohort of the population-based Framingham Study. BMD was measured at the femur (neck, trochanter, and Ward's area) and the lumbar spine (L(2)-L(4)). RESULTS: In both women and men, there was significant association of D14S1026 genotype with measures of femoral but not spinal BMD. In addition, genotypes of two common single nucleotide polymorphisms, rs1256031 and rs1256059, in strong linkage disequilibrium with one another but not with D14S1026, were associated with measures of femoral BMD in men. The rs1256031 genotypes had up to a 4.0% difference in mean femoral BMD. An inferred rs1256031-D14S1026-rs1256059 haplotype C-23CA-T was significantly associated with reduced femoral BMD in women (p = 0.03, 0.003, and 0.01 for neck, trochanter, and Ward's area, respectively). Haplotype-based BMD differences ranged from 3.0% to 4.3%. CONCLUSIONS: We have observed significant association of common ESR2 variants with measures of femoral BMD in both men and women.     

The effect of parental race on fetal and infant mortality in twin gestations

Previous work has found that singleton birth outcomes are better if the father is black and the mother is white than if the father is white and the mother is black. We sought to examine the effects of parental race on fetal and infant mortality in twins. We analyzed the fetal and infant mortality rates in four groups [both parents white (W-W), both parents black (B-B), father black and mother white (FB-MW), and father white and mother black (FW-MB)], using the 1995--1997 U.S. twin registry data (249,221 twins). Compared to W-W, the infant mortality for B-B, FW-MB, and FB-MW (respectively, relative risk [RR] 1.84, 95% confidence interval [CI] 1.73-1.95; RR 1.39, 95% CI 1.03-1.51; and RR 1.49, 95% CI 1.26-1.77) were all significantly different from W-W but not from each other. When fetal mortality was added to infant mortality, the combined mortality was highest for B-B (RR 1.66, 95% CI 1.58-1.75), intermediate for FW-MB (RR 1.18, 95% CI 0.92-1.51) and FB-MW (RR 1.37, 95% CI 1.19-1.58) and lowest for W-W. Thus, twin infants born to black parents have higher risk of fetal and infant mortality compared with twin infants born to white parents and infants of mixed race parents generally have intermediate outcomes.     

The contribution of mild and moderate preterm birth to infant mortality. Fetal and Infant Health Study Group of the Canadian Perinatal Surveillance System

CONTEXT: The World Health Organization defines preterm birth as birth at less than 37 completed gestational weeks, but most studies have focused on very preterm infants (birth at <32 weeks) because of their high risk of mortality and serious morbidity. However, infants born at 32 through 36 weeks are more common and their public health impact has not been well studied. OBJECTIVE: To assess the quantitative contribution of mild (birth at 34-36 gestational weeks) and moderate (birth at 32-33 gestational weeks) preterm birth to infant mortality. DESIGN, SETTING, AND PARTICIPANTS: Population-based cohort study using linked singleton live birth-infant death cohort files for US birth cohorts for 1985 and 1995 and Canadian birth cohorts (excluding Ontario) for 1985-1987 and 1992-1994. MAIN OUTCOME MEASURES: Relative risks (RRs) and etiologic fractions (EFs) for overall and cause-specific early neonatal (age 0-6 days), late neonatal (age 7-27 days), postneonatal (age 28-364 days), and total infant death among mild and moderate preterm births vs term births (at >/=37 gestational weeks). RESULTS: Relative risks for infant death from all causes among singletons born at 32 through 33 gestational weeks were 6.6 (95% confidence interval [CI], 6.1-7.0) in the United States in 1995 and 15.2 (95% CI, 13.2-17.5) in Canada in 1992-1994; among singletons born at 34 through 36 gestational weeks, the RRs were 2.9 (95% CI, 2.8-3.0) and 4.5 (95% CI, 4.0-5.0), respectively. Corresponding EFs were 3.2% and 4.8%, respectively, at 32 through 33 gestational weeks and 6.3% and 8.0%, respectively, at 34 through 36 gestational weeks; the sum of the EFs for births at 32 through 33 and 34 through 36 gestational weeks exceeded those for births at 28 through 31 gestational weeks. Substantial RRs were observed overall for the neonatal (eg, for early neonatal deaths, 14.6 and 33.0 for US and Canadian infants, respectively, born at 32-33 gestational weeks; EFs, 3.6% and and 6. 2% for US and Canadian infants, respectively) and postneonatal (RRs, 2.1-3.8 and 3.0-7.0 for US and Canadian infants, respectively, born at 32-36 gestational weeks; EFs, 2.7%-5.8% and 3.0%-7.0% for the same groups, respectively) periods and for death due to asphyxia, infection, sudden infant death syndrome, and external causes. Except for a reduction in the RR and EF for neonatal mortality due to infection, the patterns have changed little since 1985 in either country. CONCLUSIONS: Mild- and moderate-preterm birth infants are at high RR for death during infancy and are responsible for an important fraction of infant deaths. JAMA. 2000;284:843-849     

Consumption of sugary foods and drinks and risk of endometrial cancer

Consumption of foods high in sugar promotes insulin production, which has been linked to endometrial carcinogenesis. We evaluated the impact of dietary intake of sugary foods and beverages, as well as added sugar and total sugar on endometrial cancer risk in a population-based case–control study, including 424 cases and 398 controls. Participants completed an interview and food frequency questionnaire, and provided self-recorded waist and hip measurements. Women in the highest quartile of added sugar intake had significantly increased endometrial cancer risk (OR = 1.84, 95 % CI 1.16–2.92). Among women with waist-to-hip ratio ≥0.85, risk was significantly higher for the highest versus lowest tertile of added sugar intakes (OR = 2.50, 95 % CI 1.38–4.52). The association with added sugar also became stronger when analyses were restricted to never users of hormone replacement therapy (OR = 2.03; 95 % CI 1.27–3.26, for highest versus lowest tertile). There was little evidence of effect modification by body mass index or physical activity. Given the high prevalence of intake of sugary foods and drinks in Western populations, additional research is warranted to confirm our findings on endometrial cancer.     

Prevalence of Disability and Associated Factors among Registered Leprosy Patients in All Africa Tb and Leprosy Rehabilitation and Training Centre (ALERT), Addis Ababa,Ethiopia

Background

Delay in leprosy diagnosis and treatment causes disabilities due to nerve damage, immunological reactions and bacillary infiltration. Leprosy disability leads not only to physical dysfunction and activity limitation but also disrupts social interaction of affected individuals by creating stigma and discrimination. This study was aimed at assessing leprosy disability status in patients registered at All African TB and Leprosy Rehabilitation and Training Centre.

Methods

Medical records of leprosy patients registered from September 11, 2010 to September 10, 2013 G.C were reviewed. Prevalence of disability calculated, bivariate and multiple logistic regressions were used to determine crude and adjusted odds ratios with 95% confidence interval.

Results

The overall prevalence of disability was found to be 65.9% from all categories of patients (40.2% Grade I and 25.7% Grade II). The Prevalence among the new category was 62.8% (39.1% Grade 1 and 23.7% Grade 2). Those ageed above 30 years, with duration of symptoms 6–12 months and above 24 months, with sensory loss, nerve damage and reversal reaction were more likely to develop disability.

Conclusion

In this study the prevalence of disability, both Grade I and II, is very high. Disability was associated with age, duration of symptom, sensory loss, signs of nerve damage and reversal reaction. These risk factors indicate the existence of delay in diagnosis and treatment of leprosy cases. Therefore, the national leprosy control program should investigate leprosy case detection and diagnosis system in the country and work on improving early case detection and prevention of disability.     

Variation in estrogen-related genes and cross-sectional and longitudinal blood pressure in the Framingham Heart Study

OBJECTIVE: To examine the association between variation in estrogen-related genes and cross-sectional and longitudinal blood pressure in men and women. DESIGN: In 1780 unrelated members of the community-based Framingham Heart Study offspring cohort, systolic blood pressure and diastolic blood pressure were measured over a total of six examination cycles encompassing 24 years of follow-up. Multivariate regression analyses were used to assess the relation between untreated cross-sectional and longitudinal blood pressure and polymorphisms at the estrogen receptor-alpha (ESR1), estrogen receptor-beta (ESR2), aromatase (CYP19A1), and nuclear receptor coactivator 1 (NCOA1) genes after adjustment for common risk factors. RESULTS: In men, systolic blood pressure and pulse pressure (systolic blood pressure minus diastolic blood pressure) were associated with two polymorphisms in ESR1, while pulse pressure was also associated with variations in NCOA1 and CYP19A1. Polymorphisms in ESR1, CYP19A1, and NCOA1 were associated with diastolic blood pressure in women. CONCLUSIONS: Although the underlying relations between genes involved in estrogen action and hypertension remain to be completely understood, our findings provide suggestive evidence of gender-specific contributions of estrogen-related genes to blood pressure variation. As no correction for multiple testing was performed in the analyses, we view these results as suggestive and not definitive. Further studies are warranted to confirm these results using a comprehensive set of polymorphisms in order to shed more light on the involvement of estrogen in blood pressure regulation.     

Variation in PTX3 Is Associated with Primary Graft Dysfunction after Lung Transplantation

Rationale: Elevated long pentraxin-3 (PTX3) levels are associated with the development of primary graft dysfunction (PGD) after lung transplantation. Abnormalities in innate immunity, mediated by PTX3 release, may play a role in PGD pathogenesis. Objectives: Our goal was to test whether variants in the gene encoding PTX3 are risk factors for PGD. Methods: We performed a candidate gene association study in recipients from the multicenter, prospective Lung Transplant Outcomes Group cohort enrolled between July 2002 and July 2009. The primary outcome was International Society for Heart and Lung Transplantation grade 3 PGD within 72 hours of transplantation. Targeted genotyping of 10 haplotype-tagging PTX3 single-nucleotide polymorphisms (SNPs) was performed in lung transplant recipients. The association between PGD and each SNP was evaluated by logistic regression, adjusting for pretransplantation lung disease, cardiopulmonary bypass use, and population stratification. The association between SNPs and plasma PTX3 levels was tested across genotypes in a subset of recipients with idiopathic pulmonary fibrosis. Measurements and Main Results: Six hundred fifty-four lung transplant recipients were included. The incidence of PGD was 29%. Two linked 5' region variants, rs2120243 and rs2305619, were associated with PGD (odds ratio, 1.5; 95% confidence interval, 1.1 to 1.9; P = 0.006 and odds ratio, 1.4; 95% confidence interval, 1.1 to 1.9; P = 0.007, respectively). The minor allele of rs2305619 was significantly associated with higher plasma PTX3 levels measured pretransplantation (P = 0.014) and at 24 hours (P = 0.047) after transplantation in patients with idiopathic pulmonary fibrosis. Conclusions: Genetic variants of PTX3 are associated with PGD after lung transplantation, and are associated with increased PTX3 plasma levels.     

The impact of introducing new vaccines on the health system: Case studies from six low- and middle-income countries

Objective

We aimed to explore the impacts of new vaccine introductions on immunization programmes and health systems in low- and middle-income countries.

Methods

We conducted case studies of seven vaccine introductions in six countries (Cameroon, PCV; Ethiopia, PCV; Guatemala, rotavirus; Kenya, PCV; Mali, Meningitis A; Mali, PCV; Rwanda, HPV). Interviews were conducted with 261 national, regional and district key informants and questionnaires were completed with staff from 196 health facilities. Routine data from districts and health facilities were gathered on vaccination and antenatal service use. Data collection and analysis were structured around the World Health Organisation health system building blocks.

Findings

The new vaccines were viewed positively and seemed to integrate well into existing health systems. The introductions were found to have had no impact on many elements within the building blocks framework. Despite many key informants and facility respondents perceiving that the new vaccine introductions had increased coverage of other vaccines, the routine data showed no change. Positive effects perceived included enhanced credibility of the immunisation programme and strengthened health workers’ skills through training. Negative effects reported included an increase in workload and stock outs of the new vaccine, which created a perception in the community that all vaccines were out of stock in a facility. Most effects were found within the vaccination programmes; very few were reported on the broader health systems. Effects were primarily reported to be temporary, around the time of introduction only.

Conclusion

Although the new vaccine introductions were viewed as intrinsically positive, on the whole there was no evidence that they had any major impact, positive or negative, on the broader health systems.