Ethanol affects photoreceptor function at low concentrations that do not disturb retinal morphology. Higher levels of ethanol inhibit photoreceptor development and cause hypoplasia of the optic nerve.

Context The natural histories of obesity subphenotypes are incompletely delineated. Objectives To investigate dynamic changes in obesity subphenotypes and associations with outcomes. Design, Setting, Participants, and Measurements Framingham Offspring Cohort participants (n = 4291) who attended the examination cycles 2 (1979 to 1983) to 7 (1998 to 2001), which included 26,508 participant observations. Obesity subphenotypes [metabolically healthy nonobese (MHNO), metabolically healthy obese (MHO), metabolically unhealthy nonobese (MUNO), and metabolically unhealthy obese (MUO)] were ascertained based on metabolic health (<2 Adult Treatment Panel III criteria). The outcomes were subclinical cardiovascular disease (CVD), incident diseases [diabetes, hypertension, chronic kidney disease (CKD), CVD], and all-cause mortality. Results At baseline, 4% and 31% of participants exhibited the MHO and MUNO subphenotypes, respectively. Four-year probability of MHO participants becoming MUO was 43% in women and 46% in men. Compared with MHNO, MHO participants had 1.28-fold (95% CI, 0.85 to 1.93) and 1.92-fold (95% CI, 1.38 to 2.68) higher odds of subclinical CVD and coronary artery calcification, respectively; corresponding values for MUNO were 1.95 (1.54 to 2.47) and 1.92 (1.38 to 2.68). During follow-up (median of 14 years), 231 participants developed diabetes, 784 hypertension, 423 CKD, 639 CVD, and 1296 died. Compared with MHNO, MHO conferred higher risks of diabetes [hazard ratio (HR), 4.69; 95% CI, 2.21 to 9.96] and hypertension (HR, 2.21; 95% CI, 1.66 to 2.94). Compared with MUO, MHO conferred lower risks of diabetes (0.21; 0.12 to 0.39), CVD (0.64; 0.43 to 0.95), and CKD (0.44; 0.27 to 0.73), but similar hypertension, cardiovascular mortality, and overall mortality risks. Conclusion Over time, most MHO participants developed metabolic abnormalities and clinical disease. The MHO subphenotype is a harbinger of future risk.

OBJECTIVE Based upon evidence in animal and in-vitro studies, we tested the hypothesis that higher serum concentrations of the cytokines interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), and the inflammatory marker C-reactive protein (CRP) would be inversely associated with BMD in a community-based cohort of men and women, with the strongest associations among post-menopausal women not using menopausal hormone therapy (MHT). METHODS We ascertained fasting serum concentrations of IL-6, TNF-α, and CRP and measured BMD at the femoral neck, trochanter, total femur, and spine (L2-L4) using dual energy X-ray absorptiometry in 2,915 members of the Framingham Offspring cohort (1996 to 2001). We used multivariable linear regression to estimate the difference (β) in BMD at each bone site associated with a one-unit increase in log-transformed serum concentrations of IL-6, TNF-α, and CRP separately for men (n=1,293), pre-menopausal women (n=231), post-menopausal women using MHT (n=498), and post-menopausal women not using MHT (n=893). RESULTS Inflammatory biomarkers were not associated with BMD in men. Among premenopausal women, there were statistically significant, modest inverse associations between IL-6 and trochanter BMD (β=−0.030, p<0.01), and between CRP and femoral neck (β=−0.015, p=0.05) and trochanter BMD (β=−0.014, p=0.04). TNF-α, was positively associated with spine BMD (β=0.043, p=0.01). In post-menopausal MHT users, CRP was positively associated with femoral neck BMD (β=0.011, p=0.04). There were no associations among post-menopausal women not using MHT. CONCLUSIONS The lack of consistency in our results suggests that elevated circulating concentration of inflammatory biomarkers may not be a risk factor for low BMD.

Purpose: The Clinical Practice Research Datalink (CPRD) now provides a new medical record database, CPRD Aurum. This is the second of several studies being undertaken to assess the quality of CPRD Aurum data for research. Methods: We included patients aged 20+, with at least one lab test result of any type from a random sample of 50 000 patients in CPRD Aurum. We assessed whether diagnosis codes for type 2 diabetes, hyperlipidemia, and iron deficiency or unspecified anemia were accompanied by supporting codes including lab results and treatments (correctness) and whether lab results, treatments, or other codes indicate a missing diagnosis record (completeness). Results: Among 37 502 patients in CPRD Aurum, correctness of type 2 diabetes, hyperlipidemia, and anemia diagnoses was high (99%, 93%, and 97%, respectively). Completeness was only high for type 2 diabetes (94%-98%); completeness for hypercholesterolemia and anemia diagnoses was modest even when the presence of treatments and lab results indicated the conditions were likely present (51%-59% and 58%-70%, respectively). Conclusions: Our findings indicate that for studies of type 2 diabetes, hyperlipidemia, and iron deficiency or unspecified anemia, the diagnosis code is likely to be correct where present. However, a significant proportion of cases of hyperlipidemia or anemia will be missed if only diagnosis codes are used to select patients with these conditions. Researchers should consider using treatments, supporting codes, and, when available, lab data to supplement diagnosis codes and enhance case capture when including these conditions in studies using CPRD Aurum.

A full‐term pregnancy is associated with reduced endometrial cancer risk; however, whether the effect of additional pregnancies is independent of age at last pregnancy is unknown. The associations between other pregnancy‐related factors and endometrial cancer risk are less clear. We pooled individual participant data from 11 cohort and 19 case‐control studies participating in the Epidemiology of Endometrial Cancer Consortium (E2C2) including 16 986 women with endometrial cancer and 39 538 control women. We used one‐ and two‐stage meta‐analytic approaches to estimate pooled odds ratios (ORs) for the association between exposures and endometrial cancer risk. Ever having a full‐term pregnancy was associated with a 41% reduction in risk of endometrial cancer compared to never having a full‐term pregnancy (OR = 0.59, 95% confidence interval [CI] 0.56‐0.63). The risk reduction appeared the greatest for the first full‐term pregnancy (OR = 0.78, 95% CI 0.72‐0.84), with a further ~15% reduction per pregnancy up to eight pregnancies (OR = 0.20, 95% CI 0.14‐0.28) that was independent of age at last full‐term pregnancy. Incomplete pregnancy was also associated with decreased endometrial cancer risk (7%‐9% reduction per pregnancy). Twin births appeared to have the same effect as singleton pregnancies. Our pooled analysis shows that, while the magnitude of the risk reduction is greater for a full‐term pregnancy than an incomplete pregnancy, each additional pregnancy is associated with further reduction in endometrial cancer risk, independent of age at last full‐term pregnancy. These results suggest that the very high progesterone level in the last trimester of pregnancy is not the sole explanation for the protective effect of pregnancy.