294 research outputs found

    Genotypic analyses of cyclosporine-associated lymphoproliferations

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    The influence of rs53576 polymorphism in the oxytocin receptor (OXTR) gene on empathy in healthy adults by subtype and ethnicity: a systematic review and meta-analysis

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    Empathy is essential for navigating complex social environments. Prior work has shown associations between rs53576, a single nucleotide polymorphism (SNP) located in the oxytocin receptor gene (OXTR), and generalized empathy. We undertook a systematic review and meta-analysis to assess the effects of rs53576 on subdomains of empathy, specifically cognitive empathy (CE) and affective empathy (AE), in healthy adults. Twenty cohorts of 8933 participants aged 18-98 were identified, including data from the Sydney Memory and Ageing Study, a cohort of older community adults. Meta-analyses found G homozygotes had greater generalized empathic abilities only in young to middle-aged adults. While meta-analyses of empathy subdomains yielded no significant overall effects, there were differential effects based on ethnicity. G homozygotes were associated with greater CE abilities in Asian cohorts (standardized mean difference; SMD: 0.09 [2.8·10-3-0.18]), and greater AE performance in European cohorts [SMD: 0.12 (0.04-0.21)]. The current literature highlights a need for further work that distinguishes between genetic and ethnocultural effects and explores effects of advanced age on this relationship

    Anesthesia for intra-articular corticosteroid injections in juvenile idiopathic arthritis: A survey of pediatric rheumatologists

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    <p>Abstract</p> <p>Objective</p> <p>To determine the methods of anesthesia currently being used by pediatric rheumatologists when performing intra-articular corticosteroid injections (IACI).</p> <p>Study design</p> <p>A questionnaire was emailed to all members of the Childhood Arthritis & Rheumatology Research Alliance, a pediatric rheumatology research network in North America. The questionnaire consisted of 11 questions ranging from procedure technique, treatments prescribed for topical anesthesia and oral analgesia, and factors that might affect procedural pain.</p> <p>Results</p> <p>Seventy-four of 161 physicians (46%) responded to the questionnaire. On average, each physician injected 33 children (median 25, range 1-160) and 43 joints (median 30, range 1-150) yearly. Local anesthesia was used in children on average ≥ 8 years (range 2-16 years), with general anesthesia being more frequently used for younger children. All respondents used local anesthesia. The most commonly used methods of local anesthesia were EMLA<sup>® </sup>cream plus subcutaneous lidocaine (58.8%), ethyl chloride spray only (39.7%), EMLA<sup>® </sup>cream only (33.8%), subcutaneous lidocaine only (25%), and lidocaine iontophoresis only (11.8%). Buffering of the lidocaine was routinely done only 7.4% of the time.</p> <p>Conclusion</p> <p>Although pediatric rheumatologists in North America perform IACI on a large number of patients each year, a wide variety of methods are used to deliver local anesthesia with no accepted standard of care. More studies are needed to determine the optimal method of local anesthesia delivery to minimize pain associated with IACI.</p

    Cost-Effectiveness of Male Circumcision for HIV Prevention in a South African Setting

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    BACKGROUND: Consistent with observational studies, a randomized controlled intervention trial of adult male circumcision (MC) conducted in the general population in Orange Farm (OF) (Gauteng Province, South Africa) demonstrated a protective effect against HIV acquisition of 60%. The objective of this study is to present the first cost-effectiveness analysis of the use of MC as an intervention to reduce the spread of HIV in sub-Saharan Africa. METHODS AND FINDINGS: Cost-effectiveness was modeled for 1,000 MCs done within a general adult male population. Intervention costs included performing MC and treatment of adverse events. HIV prevalence was estimated from published estimates and incidence among susceptible subjects calculated assuming a steady-state epidemic. Effectiveness was defined as the number of HIV infections averted (HIA), which was estimated by dynamically projecting over 20 years the reduction in HIV incidence observed in the OF trial, including secondary transmission to women. Net savings were calculated with adjustment for the averted lifetime duration cost of HIV treatment. Sensitivity analyses examined the effects of input uncertainty and program coverage. All results were discounted to the present at 3% per year. For Gauteng Province, assuming full coverage of the MC intervention, with a 2005 adult male prevalence of 25.6%, 1,000 circumcisions would avert an estimated 308 (80% CI 189–428) infections over 20 years. The cost is 181(80181 (80% CI 117–306)perHIA,andnetsavingsare306) per HIA, and net savings are 2.4 million (80% CI 1.3millionto1.3 million to 3.6 million). Cost-effectiveness is sensitive to the costs of MC and of averted HIV treatment, the protective effect of MC, and HIV prevalence. With an HIV prevalence of 8.4%, the cost per HIA is 551(80551 (80% CI 344–1,071)andnetsavingsare1,071) and net savings are 753,000 (80% CI 0.3millionto0.3 million to 1.2 million). Cost-effectiveness improves by less than 10% when MC intervention coverage is 50% of full coverage. CONCLUSIONS: In settings in sub-Saharan Africa with high or moderate HIV prevalence among the general population, adult MC is likely to be a cost-effective HIV prevention strategy, even when it has a low coverage. MC generates large net savings after adjustment for averted HIV medical costs

    Effects of adiponectin on breast cancer cell growth and signaling

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    Obesity is a risk factor for postmenopausal breast cancer. Adiponectin/Acrp30 is lower in obese individuals and may be negatively regulating breast cancer growth. Here we determined that five breast cancer cell lines, MDA-MB-231, MDA-MB-361, MCF-7, T47D, and SK-BR-3, expressed one or both of the Acrp30 receptors. In addition, we found that the addition of Acrp30 to MCF-7, T47D, and SK-BR-3 cell lines inhibited growth. Oestrogen receptor (ER) positive MCF-7 and T47D cells were inhibited at lower Acrp30 concentrations than ER-negative SK-BR-3 cells. Growth inhibition may be related to apoptosis since PARP cleavage was increased by Acrp30 in the ER-positive cell lines. To investigate the role of ER in the response of breast cancer cells to Acrp30, we established the MDA-ERα7 cell line by insertion of ER-α into ER-α-negative MDA-MB-231 cells. This line readily formed tumours in athymic mice and was responsive to oestradiol in vivo. In vitro, MDA-ERα7 cells were growth inhibited by globular Acrp30 while the parental cells were not. This inhibition appeared to be due to blockage of JNK2 signalling. These results provide information on how obesity may influence breast cancer cell proliferation and establish a new model to examine interactions between ER and Acrp30

    Robust Antigen Specific Th17 T Cell Response to Group A Streptococcus Is Dependent on IL-6 and Intranasal Route of Infection

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    Group A streptococcus (GAS, Streptococcus pyogenes) is the cause of a variety of clinical conditions, ranging from pharyngitis to autoimmune disease. Peptide-major histocompatibility complex class II (pMHCII) tetramers have recently emerged as a highly sensitive means to quantify pMHCII-specific CD4+ helper T cells and evaluate their contribution to both protective immunity and autoimmune complications induced by specific bacterial pathogens. In lieu of identifying an immunodominant peptide expressed by GAS, a surrogate peptide (2W) was fused to the highly expressed M1 protein on the surface of GAS to allow in-depth analysis of the CD4+ helper T cell response in C57BL/6 mice that express the I-Ab MHCII molecule. Following intranasal inoculation with GAS-2W, antigen-experienced 2W:I-Ab-specific CD4+ T cells were identified in the nasal-associated lymphoid tissue (NALT) that produced IL-17A or IL-17A and IFN-γ if infection was recurrent. The dominant Th17 response was also dependent on the intranasal route of inoculation; intravenous or subcutaneous inoculations produced primarily IFN-γ+ 2W:I-Ab+ CD4+ T cells. The acquisition of IL-17A production by 2W:I-Ab-specific T cells and the capacity of mice to survive infection depended on the innate cytokine IL-6. IL-6-deficient mice that survived infection became long-term carriers despite the presence of abundant IFN-γ-producing 2W:I-Ab-specific CD4+ T cells. Our results suggest that an imbalance between IL-17- and IFN-γ-producing CD4+ T cells could contribute to GAS carriage in humans

    Life experiences throughout the ifespan: What do people say (or not) about them?

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    Life experiences have been a topic of interest for researchers and clinicians for decades. Current knowledge is rooted in two distinct approaches, i.e., personality psychology and psychosomatics. Whereas the first is interested in ordinary life stories of nonclinical individuals, based on a more qualitative, in-depth, and person-driven approach, psychosomatics stresses negative events, mainly in clinical samples, and presents a more quantitative, general, and construct-driven approach. Consequently, available evidence is dispersed and unrelated and many basic questions remain unanswered. This study aimed to explore occurrence, developmental stage, valence, and impact of life experiences and to analyze critical answering patterns (i.e., “I don’t remember,” missingness). Through a cross-sectional retrospective design, 394 adults from the community answered the Lifetime Experiences Scale, which covers 75 life experiences organized in eight domains (i.e., school, job, health, leisure, living conditions, adverse experiences, achievements, and people and relationships). Occurrence of life experiences varied greatly, and the mean number of experiences reported was approximately 30. Regarding developmental stage, most experiences were reported in just one stage—mainly adulthood—however, some could be considered chronic. Globally, life experiences tended to be clearly rated as positive or as negative; additionally, assessed experiences were mainly appraised as positive. Moreover, participants presented their experiences as significant, rating them as high impact. Overall, critical answering patterns were not very expressive: “I don’t remember” and missing answers were below 2 and 5%, respectively, in the majority of experiences. These findings offer several important new insights, suggesting that life experiences are mainly an idiosyncratic topic.This manuscript is part of a doctoral dissertation, which had the support of the Portuguese Foundation for Science and Technology (FCT), through the PhD grant with the reference SFRH/ BD/76022/2011, funded by POPH-QREN-Typology 4.1-Advanced Training, reimbursed by the European Social Fund and national funds from State Budget. This study was conducted at Psychology Research Centre (UID/PSI/01662/2013), University of Minho, and supported by the Portuguese Foundation for Science and Technology and the Portuguese Ministry of Education and Science through national funds and co-financed by FEDER through COMPETE2020 under the PT2020 Partnership Agreement (POCI-01-0145-FEDER-007653).info:eu-repo/semantics/publishedVersio
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