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A study ancillary to a large trial showed that supplemental vitamin D 3 did not lower the risk of fractures among generally healthy midlife and older adults not selected for vitamin D deficiency, low bone mass, or osteoporosis.

This article reports the n−3 fatty acid portion of a randomized, placebo-controlled, two-by-two factorial trial of vitamin D and marine n−3 fatty acids in the primary prevention of cancer and cardiovascular disease. Fatty acids did not lead to a lower incidence of major cardiovascular events or cancer.

Measurement of low-density lipoprotein cholesterol, high-sensitivity C-reactive protein, and lipoprotein(a) predicted the 30-year cardiovascular disease risk among women enrolled in the Women’s Health Study.

Atherosclerosis, the formation of fibrofatty lesions in the artery wall, causes much morbidity and mortality worldwide, including most myocardial infarctions and many strokes, as well as disabling peripheral artery disease. Development of atherosclerotic lesions probably requires low-density lipoprotein, a particle that carries cholesterol through the blood. Other risk factors for atherosclerosis and its thrombotic complications include hypertension, cigarette smoking and diabetes mellitus. Increasing evidence also points to a role of the immune system, as emerging risk factors include inflammation and clonal haematopoiesis. Studies of the cell and molecular biology of atherogenesis have provided considerable insight into the mechanisms that link all these risk factors to atheroma development and the clinical manifestations of this disease. An array of diagnostic techniques, both invasive (such as selective coronary arteriography) and noninvasive (such as blood biomarkers, stress testing, CT and nuclear scanning), permit assessment of cardiovascular disease risk and targeting of therapies. An expanding armamentarium of therapies that can modify risk factors and confer clinical benefit is available; however, we face considerable challenge in providing equitable access to these treatments and in maximizing adherence. Yet, the clinical application of the fruits of research has advanced preventive strategies, enhanced clinical outcomes in affected individuals, and improved their quality of life. Rapidly accelerating knowledge and continued research promise to provide further progress in combating this common chronic disease. Atherosclerosis refers to the accumulation of fatty and fibrous material in the arterial wall. Atherosclerotic plaques can narrow the lumen of the vessel and lead to tissue ischaemia or rupture and trigger the formation of a thrombus.

Dry eye disease affects women twice as often as men, but there is little information on whether dry eye treatments, treatment satisfaction, or the impact of dry eye disease on patients' lives and vision might differ by sex. Questionnaire survey of 4000 participants in the Women's Health Study and the Physicians' Health Studies I and II with a prior report of a diagnosis of DED. Among participants who re-confirmed a diagnosis of dry eye disease, we assessed symptoms, treatments, patient satisfaction and impact of dry eye disease, and analyzed differences between men and women using regression models. The final study population consisted of 1,518 women (mean age 70.7 years) and 581 men (mean age 76.7 years), with a mean reported duration of dry eye disease of 10.5 years and 10.1 years, respectively. The frequency and severity of dry eye disease symptoms were higher among women (each P<0.0001), and women reported a greater impact on everyday activities (P<0.0001). Women were more likely to use artificial tears (P<0.0001) use them more often (P<0.0001), and to use Restasis® (P<0.0001), omega-3 fatty acids (P=0.0006), and have punctal occlusion (P=0.005). Women spent more money per month on dry eye treatments (P<0.0001), but reported greater dissatisfaction with treatment side effects (P=0.001), and the amount of time before treatments started working (P=0.03). These data show that dry eye disease is generally experienced as being more severe among women, having a greater impact on their self-assessed well-being.

This article reports the vitamin D portion of a randomized, two-by-two factorial trial of n−3 fatty acids and vitamin D in the prevention of cancer and cardiovascular disease. Vitamin D did not result in a lower incidence of invasive cancer or cardiovascular events than placebo.

In a randomized trial, patients with type 2 diabetes, hypertriglyceridemia, and low HDL cholesterol who received pemafibrate did not have fewer cardiovascular events, although some lipid levels decreased.

Endometriosis is a heritable hormone-dependent gynecological disorder, associated with severe pelvic pain and reduced fertility; however, its molecular mechanisms remain largely unknown. Here we perform a meta-analysis of 11 genome-wide association case-control data sets, totalling 17,045 endometriosis cases and 191,596 controls. In addition to replicating previously reported loci, we identify five novel loci significantly associated with endometriosis risk ( P <5 × 10 −8 ), implicating genes involved in sex steroid hormone pathways ( FN1 , CCDC170 , ESR1 , SYNE1 and FSHB ). Conditional analysis identified five secondary association signals, including two at the ESR1 locus, resulting in 19 independent single nucleotide polymorphisms (SNPs) robustly associated with endometriosis, which together explain up to 5.19% of variance in endometriosis. These results highlight novel variants in or near specific genes with important roles in sex steroid hormone signalling and function, and offer unique opportunities for more targeted functional research efforts. Endometriosis is a major cause of infertility. Molecular mechanisms underlying the disease involve genetic and environmental risk factors. In a meta-analysis of eleven GWA studies, Sapkota and colleagues identify five novel risk loci, implicating steroid sex hormone pathways in the pathogenesis.

Migraine affects over a billion individuals worldwide but its genetic underpinning remains largely unknown. Here, we performed a genome-wide association study of 102,084 migraine cases and 771,257 controls and identified 123 loci, of which 86 are previously unknown. These loci provide an opportunity to evaluate shared and distinct genetic components in the two main migraine subtypes: migraine with aura and migraine without aura. Stratification of the risk loci using 29,679 cases with subtype information indicated three risk variants that seem specific for migraine with aura (in HMOX2 , CACNA1A and MPPED2 ), two that seem specific for migraine without aura (near SPINK2 and near FECH ) and nine that increase susceptibility for migraine regardless of subtype. The new risk loci include genes encoding recent migraine-specific drug targets, namely calcitonin gene-related peptide ( CALCA/CALCB ) and serotonin 1F receptor ( HTR1F ). Overall, genomic annotations among migraine-associated variants were enriched in both vascular and central nervous system tissue/cell types, supporting unequivocally that neurovascular mechanisms underlie migraine pathophysiology. Genome-wide association analyses identify 123 susceptibility loci for migraine and implicate neurovascular mechanisms in its pathophysiology. Subtype analyses highlight risk loci specific for migraine with or without aura in addition to shared risk variants.