Decreased role of neuropeptides in the microvascular function in migraine patients with polycystic ovary syndrome

Paroxysmal Cerebral Disorder

Male breast cancer

Male breast cancer (MBC) is a rare disease representing less than 1% of all breast cancers (BC) and less than 1% of cancers in men. Age at presentation is mostly in the late 60s. MBC is recognized as an estrogen-driven disease, specifically related to hyperestrogenism. About 20% of MBC patients have family history for BC. Mutations in BRCA1 and, predominantly, BRCA2, account for approximately 10% of MBC cases. Because of its rarity, MBC is often compared with female BC (FBC). Based on age-frequency distribution, age-specific incidence rate patterns and prognostic factors profiles, MBC is considered similar to late-onset, postmenopausal estrogen/progesterone receptor positive (ER+/PR+) FBC. However, clinical and pathological characteristics of MBC do not exactly overlap FBC. Compared with FBC, MBC has been reported to occur later in life, present at a higher stage, and display lower histologic grade, with a higher proportion of ER+ and PR+ tumors. Although rare, MBC remains a substantial cause for morbidity and mortality in men, probably because of its occurrence in advanced age and delayed diagnosis. Diagnosis and treatment of MBC generally is similar to that of FBC. Men tend to be treated with mastectomy rather than breast-conserving surgery. The backbone of adjuvant therapy or palliative treatment for advanced disease is endocrine, mostly tamoxifen. Use of FBC-based therapy led to the observation that treatment outcomes for MBC are worse and that survival rates for MBC do not improve like FBC. These different outcomes may suggest a non-appropriate utilization of treatments and that different underlying pathogenetic mechanisms may exist between male and female BC

Association between XPF Polymorphisms and Cancer Risk: A Meta-Analysis

Background: Xeroderma pigmentosum complementation group F (XPF or ERCC4) plays a key role in DNA repair that protects against genetic instability and carcinogenesis. A series of epidemiological studies have examined associations between XPF polymorphisms and cancer risk, but the findings remain inconclusive. Methodology/Principal Findings: In this meta-analysis of 47,639 cancer cases and 51,915 controls, by searching three electronic databases (i.e., MEDLINE, EMBASE and CNKI), we summarized 43 case-control studies from 29 publications on four commonly studied polymorphisms of XPF (i.e., rs1800067, rs1799801, rs2020955 and rs744154), and we did not find statistical evidence of any significant association with overall cancer risk. However, in stratification analyses, we found a significant association of XPF-rs1799801 with a reduced cancer risk in Caucasian populations (4,845 cases and 5,556 controls; recessive model: OR = 0.87, 95% CI = 0.76–1.00, P = 0.049, P = 0.723 for heterogeneity test, I2 = 0). Further genotype-phenotype correlation analysis showed that the homozygous variant CC genotype carriers had higher XPF expression levels than that of the TT genotype carriers (Student’s t test for a recessive model: P = 0.046). No publication bias was found by using the funnel plot and Egger’s test. Conclusion: This meta-analysis suggests a lack of statistical evidence for the association between the four XPF SNPs and overall risk of cancers. However, XPF-rs1799801 may be associated with cancer risk in Caucasian populations, which needs to be further validated in single large, well-designed prospective studies

Endogenous sex hormones and risk of venous thromboembolism in young women

Thrombosis and Hemostasi

A new selection method to increase the health benefits of CVD prevention strategies.

Background Cardiovascular disease (CVD) prevention is commonly focused on providing individuals at high predicted CVD risk with preventive medication. Whereas CVD risk increases rapidly with age, current risk-based selection of individuals mainly targets the elderly. However, the lifelong (preventable) consequences of CVD events may be larger in younger individuals. The purpose of this paper is to investigate if health benefits from preventive treatment may increase when the selection strategy is further optimised. Methods Data from three Dutch cohorts were combined ( n = 47469, men:women 1:1.92) and classified into subgroups based on age and gender. The Framingham global risk score was used to estimate 10-year CVD risk. The associated lifelong burden of CVD events according to this 10-year CVD risk was expressed as quality-adjusted life years lost. Based on this approach, the additional health benefits from preventive treatment, reducing this 10-year CVD risk, from selecting individuals based on their expected CVD burden rather than their expected CVD risk were estimated. These benefits were expressed as quality-adjusted life years gained over lifetime. Results When using the current selection strategy (10% risk threshold), 32% of the individuals were selected for preventive treatment. When the same proportion was selected based on burden, more younger and fewer older individuals would receive treatment. Across all individuals, the gain in quality-adjusted life years was 217 between the two strategies, over a 10-year time horizon. In addition, when combining the strategies 5% extra eligible individuals were selected resulting in a gain of 628 quality-adjusted life years. Conclusion Improvement of the selection approach of individuals can help to reduce further the CVD burden. Selecting individuals for preventive treatment based on their expected CVD burden will provide more younger and fewer older individuals with treatment, and will reduce the overall CVD burden

A new selection method to increase the health benefits of CVD prevention strategies

Background Cardiovascular disease (CVD) prevention is commonly focused on providing individuals at high predicted CVD risk with preventive medication. Whereas CVD risk increases rapidly with age, current risk-based selection of individuals mainly targets the elderly. However, the lifelong (preventable) consequences of CVD events may be larger in younger individuals. The purpose of this paper is to investigate if health benefits from preventive treatment may increase when the selection strategy is further optimised. Methods Data from three Dutch cohorts were combined ( n = 47469, men:women 1:1.92) and classified into subgroups based on age and gender. The Framingham global risk score was used to estimate 10-year CVD risk. The associated lifelong burden of CVD events according to this 10-year CVD risk was expressed as quality-adjusted life years lost. Based on this approach, the additional health benefits from preventive treatment, reducing this 10-year CVD risk, from selecting individuals based on their expected CVD burden rather than their expected CVD risk were estimated. These benefits were expressed as quality-adjusted life years gained over lifetime. Results When using the current selection strategy (10% risk threshold), 32% of the individuals were selected for preventive treatment. When the same proportion was selected based on burden, more younger and fewer older individuals would receive treatment. Across all individuals, the gain in quality-adjusted life years was 217 between the two strategies, over a 10-year time horizon. In addition, when combining the strategies 5% extra eligible individuals were selected resulting in a gain of 628 quality-adjusted life years. Conclusion Improvement of the selection approach of individuals can help to reduce further the CVD burden. Selecting individuals for preventive treatment based on their expected CVD burden will provide more younger and fewer older individuals with treatment, and will reduce the overall CVD burden

Western blot analysis of pHu-E16 variants.

<p><b>A</b>. Designs of Hu-E16 variants in this study. <b>B–D</b>. Western blot analysis. Hu-E16 variants were extracted from <i>N. benthamiana</i> leaves, separated on SDS-PAGE gels under reducing (<b>B</b> and <b>C</b>) or non-reducing (<b>D</b>) conditions, and blotted onto PVDF membranes. The membranes were incubated with a goat anti-human gamma chain antibody or a goat anti-human kappa chain antibody to detect heavy chain (<b>B</b> and <b>Lane 7 of D</b>) or light chain (<b>C</b> and <b>Lanes 1–6 of D</b>). Lane 1, pHu-E16 as a reference standard; lane 2, Protein sample extracted from leaves co-infiltrated with pHu-E16 HC and pHu-E16scFv-C_L constructs; lane 3, Sample from leaves co-infiltrated with pHu-E16scFv-C_H^1-3 and pHu-E16scFv-C_L; lane 4, Sample from leaves co-infiltrated with pHu-E16scFv-C_H^1-3 and pHu-E16 LC; lanes 5 and 7, Sample from leaves infiltrated with pHu-E16scFv-C_H^1-3; lane 6, Sample from un-infiltrated leaves. HC: heavy chain, scFv: single-chain variable fragment; C_H^1-3: the constant region domains 1 to 3 of HC; LC: light chain; C_L: Constant region of LC; V_L: variable region of LC; V_H: variable region of HC.</p