Polymorphisms of endothelin 1 (G5665T and T-1370G) and endothelin receptor type A (C+70G and G-231A) in Graves' disease

PurposeEndothelin 1 (EDN1) is a strong angiogenic and mitogenic factor, playing a key role in hypervascularization, thyroid follicle cell hyperplasia, and lymphocyte infiltration in the thyroid gland of patients with Graves’ disease (GD). EDN1 induces angiogenesis and mitogenesis via endothelin receptor type A (EDNRA). This study examined the possible association of EDN1 (G5665T and T-1370G) and EDNRA (C + 70G and G-231A) single nucleotide polymorphisms (SNPs) with the occurrence of GD, and evaluates the relationship between genotypes and clinical/laboratory manifestations of GD.Materials and methodsWe analyzed genotype and allele distributions of EDN1 and EDNRA polymorphisms in 165 patients with GD and 181 healthy controls by real-time PCR combined with melting curve analysis.ResultsNo significant associations between GD and variant alleles of the studied polymorphisms were observed. However, the anti-thyroid peroxidase (anti-TPO) and anti-thyroglobulin (anti-TG) levels in EDN1 G5665T GG genotype were higher than those in T allele carriers (GT + TT) (p = 0.001 and p = 0.026, respectively). In addition, anti-TPO levels in EDN1 T-1370G wild-type homozygous patients were found to be higher than in mutant gene carrying patients (GT + GG) (p = 0.006). The presence of EDNRA + 70G allele was associated with 3.37-fold increased risk for development of ophthalmopathy in GD patients (p = 0.009).ConclusionAlthough there were no associations between EDN1 (G5665T and T-1370G) and EDNRA (C + 70G and G-231A) SNPs and susceptibility to GD, EDN1 G5665T and T-1370G polymorphisms were related to alterations of autoantibody production and EDNRA C + 70G polymorphism is related with increased risk for ophthalmopathy in GD patients.     

Health-related effects of welfare-to-work policies

Non-health related policies may have consequences for health that are more important than the outcomes they were originally designed to produce. In this paper we evaluate the effects of welfare-to-work programs (WTW) on physical and mental health status and a variety of health behaviors. The paper is based on data from the minimum income program of Madrid's Government (IMI). We match the program's administrative records (39,200 households) – covering the whole history of the program from the second half of 1990 to 2001 – with a specific survey of former recipients who took part in different work-related activities conducted in 2001 (2300 households). We perform propensity score matching to find that both health status – including physical and mental health problems – and behaviors outcomes were modestly better for those individuals who had taken part in work-related activities. These results offer support for the contention that welfare-to-work policies may have positive unintended health effects.     

Cytogenetic Features and Clinical Outcomes of Patients With Non-secretory Multiple Myeloma in the Era of Novel Agent Induction Therapy

BackgroundNon-secretory multiple myeloma (NSMM) is a rare subtype of multiple myeloma (MM) characterized by the absence of monoclonal protein in the serum and/or urine. We look at the clinical and cytogenetic features of NSMM in this study.Patients and MethodsThis study evaluates a cohort of 30 patients with newly diagnosed NSMM seen at the Mayo Clinic, Rochester, MN, between 2008 and 2018 and treated with novel agent induction therapies. Survival outcomes were estimated using the Kaplan-Meier method and compared using the log-rank test.ResultsThese patients with NSMM appear to have a large disease burden at diagnosis with a median bone marrow plasma cell percentage of 70% and more than one-half of all patients having Multiple Myeloma International Staging System Stage III disease. There was a higher preponderance for t(11;14) primary cytogenetic abnormality in this NSMM cohort, accounting for more than 50% of the cohort. Finally, the overall survival of this cohort appears to be slightly worse than a matched-control group of newly diagnosed patients with MM with secretory disease.ConclusionsFuture multi-institution studies confirming these above findings on this rare entity are warranted.     

Genetic variations in cytotoxic T-lymphocyte antigen-4 and susceptibility to cervical cancer

Cytotoxic T-lymphocyte antigen-4 (CTLA-4), a molecule expressed predominantly on activated T cells, plays an important role in the down-regulation of T-cell activation. To evaluate the potential effects of CTLA-4 gene polymorphisms on susceptibility to cervical cancer, we genotyped polymorphisms in CTLA-4 (− 318 T/C, CT60 G/A, + 49 G/A, − 658 T/C, and − 1661 G/A) and calculated odds ratios for the genotype and allele distributions between patients and controls. We then examined the functional relevance of the polymorphisms using enzyme-linked immunosorbent assays (ELISAs), in vitro lymphocyte proliferation assay, and cytotoxic assay. The CTLA-4 − 318 CC, CT60 AA, and + 49 GG genotype frequencies were lower in patients than in controls (p < 0.05). The frequencies of CTLA-4 − 318 T allele and CT60G allele carriers were significantly higher in patients than in controls (p < 0.05). Upon stimulation, peripheral blood mononuclear cells (PBMCs) carrying the − 318TT and CT60GG genotypes exhibited significantly lower proliferation, IL-2, and IL-4 levels; fewer cytolytic activities; and higher TGF-β levels compared with PBMCs carrying the − 318 CC/CT or CT60 AA/AG genotypes. We also found that CTLA-4 − 318 T/C and CT60 G/A single nucleotide polymorphisms were associated with the severity of cervical cancer. These results indicate that CTLA-4 − 318 T/C and CT60 G/A can affect cervical cancer susceptibility by altering the immune status of an individual.     

The Effect of Technology-Based Interventions on Pain,Depression, and Quality of Life in Patients With Cancer: A Systematic Review of Randomized Controlled Trials

BackgroundThe burden of cancer is increasing; projections over the next 2 decades suggest that the annual cases of cancer will rise from 14 million in 2012 to 22 million. However, cancer patients in the 21st century are living longer due to the availability of novel therapeutic regimens, which has prompted a growing focus on maintaining patients’ health-related quality of life. Telehealth is increasingly being used to connect with patients outside of traditional clinical settings, and early work has shown its importance in improving quality of life and other clinical outcomes in cancer care.ObjectiveThe aim of this study was to systematically assess the literature for the effect of supportive telehealth interventions on pain, depression, and quality of life in cancer patients via a systematic review of clinical trials.MethodsWe searched PubMed, EMBASE, Google Scholar, CINAHL, and PsycINFO in July 2013 and updated the literature search again in January 2015 for prospective randomized trials evaluating the effect of telehealth interventions in cancer care with pain, depression, and quality of life as main outcomes. Two of the authors independently reviewed and extracted data from eligible randomized controlled trials, based on pre-determined selection criteria. Methodological quality of studies was assessed by the Cochrane Collaboration risk of bias tool.ResultsOf the 4929 articles retrieved from databases and relevant bibliographies, a total of 20 RCTs were included in the final review. The studies were largely heterogeneous in the type and duration of the intervention as well as in outcome assessments. A majority of the studies were telephone-based interventions that remotely connected patients with their health care provider or health coach. The intervention times ranged from 1 week to 12 months. In general, most of the studies had low risk of bias across the domains of the Cochrane Collaboration risk of bias tool, but most of the studies had insufficient information about the allocation concealment domain. Two of the three studies focused on pain control reported significant effects of the intervention; four of the nine studies focus on depression reported significant effects, while only the studies that were focused on quality of life reported significant effects.ConclusionsThis systematic review demonstrates the potential of telehealth interventions in improving outcomes in cancer care. However, more high-quality large-sized trials are needed to demonstrate cogent evidence of its effectiveness.     

Predictors of outcomes in the treatment of urge urinary incontinence in women

Introduction and hypothesis  

Women with urge predominant urinary incontinence received active intervention (drug therapy alone or combined with behavioral therapy) for 10 weeks, then stopped all therapy and were followed for 6 months more. In this planned secondary analysis, we aimed to identify predictors of therapeutic success at 10 weeks (≥70% reduction in incontinence) and of ability to discontinue treatment and sustain improvements 6 months later.     

卵巢癌组织中TRAIL和Survivin蛋白与临床病理因素的关系

目的探讨TRAIL和Survivin在卵巢癌组织中的表达及与临床病理因素的关系。方法用免疫组化SP法检测10例正常卵巢、20例良性卵巢肿瘤及60例卵巢癌组织中TRAIL蛋白和Survivin蛋白表达情况,分析TRAIL和Survivin蛋白与卵巢癌临床病理因素的关系。结果①正常卵巢组织、良性卵巢肿瘤、卵巢癌中TRAIL蛋白的表达率分别为90．0％、80．0％、38．3％,Survivin蛋白的表达率分别为0％、20．0％、63．3％。两者间比较：在正常卵巢和良性卵巢肿瘤中TRAIL蛋白、Survivin蛋白的表达差异无显著性意义（P〉0．05）;而良性卵巢肿瘤和恶性卵巢肿瘤中TRAIL蛋白、Survivin蛋白的表达差异均有显著性意义（P〈0．05）;②在卵巢癌中TRAIL蛋白表达与组织学类型、病理分级无关（P〉0．05）,与临床分期期别密切相关（P〈0．05）;Survivin蛋白的表达与组织学类型无关（P〉0．05）,与病理分级、临床分期期别密切相关（P〈0．05）。结论TRAIL蛋白和Survivin蛋白可能共同参与了卵巢癌的发生发展过程。并且可能通过减少TRAIL蛋白表达,升高Survivin蛋白表达,起到协同抑制肿瘤细胞凋亡作用,从而参与了卵巢肿瘤发生过程中细胞凋亡的调控。