Development of a screening tool to identify female survivors of gender-based violence in a humanitarian setting:qualitative evidence from research among refugees in Ethiopia.

PMC3695841BACKGROUND: High levels of gender-based violence (GBV) persist among conflict-affected populations and within humanitarian settings and are paralleled by under-reporting and low service utilization. Novel and evidence-based approaches are necessary to change the current state of GBV amongst these populations. We present the findings of qualitative research, which were used to inform the development of a screening tool as one potential strategy to identify and respond to GBV for females in humanitarian settings. METHODS: Qualitative research methods were conducted from January-February 2011 to explore the range of experiences of GBV and barriers to reporting GBV among female refugees. Individual interview participants (n=37) included female refugees (≥15 years), who were survivors of GBV, living in urban or one of three camps settings in Ethiopia, and originating from six conflict countries. Focus group discussion participants (11 groups; 77 participants) included health, protection and community service staff working in the urban or camp settings. Interviews and discussions were conducted in the language of preference, with assistance by interpreters when needed, and transcribed for analysis by grounded-theory technique. RESULTS: Single and multiple counts of GBV were reported and ranged from psychological and social violence; rape, gang rape, sexual coercion, and other sexual violence; abduction; and physical violence. Domestic violence was predominantly reported to occur when participants were living in the host country. Opportunistic violence, often manifested by rape, occurred during transit when women depended on others to reach their destination. Abduction within the host country, and often across borders, highlighted the constant state of vulnerability of refugees. Barriers to reporting included perceived and experienced stigma in health settings and in the wider community, lack of awareness of services, and inability to protect children while mothers sought services. CONCLUSIONS: Findings demonstrate that GBV persists across the span of the refugee experience, though there is a transition in the range of perpetrators and types of GBV that are experienced. Further, survivors experience significant individual and system barriers to disclosure and service utilization. The findings suggest that routine GBV screening by skilled service providers offers a strategy to confidentially identify and refer survivors to needed services within refugee settings, potentially enabling survivors to overcome existing barriers.JH Libraries Open Access Fun

Bridging Alone: Religious Conservatism, Marital Homogamy, and Voluntary Association Membership

This study characterizes social insularity of religiously conservative American married couples by examining patterns of voluntary associationmembership. Constructing a dataset of 3938 marital dyads from the second wave of the National Survey of Families and Households, the author investigates whether conservative religious homogamy encourages membership in religious voluntary groups and discourages membership in secular voluntary groups. Results indicate that couples’ shared affiliation with conservative denominations, paired with beliefs in biblical authority and inerrancy, increases the likelihood of religious group membership for husbands and wives and reduces the likelihood of secular group membership for wives, but not for husbands. The social insularity of conservative religious groups appears to be reinforced by homogamy—particularly by wives who share faith with husbands

SNP genotyping to screen for a common deletion in CHARGE Syndrome

BACKGROUND: CHARGE syndrome is a complex of birth defects including coloboma, choanal atresia, ear malformations and deafness, cardiac defects, and growth delay. We have previously hypothesized that CHARGE syndrome could be caused by unidentified genomic microdeletion, but no such deletion was detected using short tandem repeat (STR) markers spaced an average of 5 cM apart. Recently, microdeletion at 8q12 locus was reported in two patients with CHARGE, although point mutation in CHD7 on chromosome 8 was the underlying etiology in most of the affected patients. METHODS: We have extended our previous study by employing a much higher density of SNP markers (3258) with an average spacing of approximately 800 kb. These SNP markers are diallelic and, therefore, have much different properties for detection of deletions than STRs. RESULTS: A global error rate estimate was produced based on Mendelian inconsistency. One marker, rs431722 exceeded the expected frequency of inconsistencies, but no deletion could be demonstrated after retesting the 4 inconsistent pedigrees with local flanking markers or by FISH with the corresponding BAC clone. Expected deletion detection (EDD) was used to assess the coverage of specific intervals over the genome by deriving the probability of detecting a common loss of heterozygosity event over each genomic interval. This analysis estimated the fraction of unobserved deletions, taking into account the allele frequencies at the SNPs, the known marker spacing and sample size. CONCLUSIONS: The results of our genotyping indicate that more than 35% of the genome is included in regions with very low probability of a deletion of at least 2 Mb

Development of trofinetide for the treatment of Rett syndrome: from bench to bedside

Rett syndrome (RTT) is rare neurodevelopmental disorder caused by mutations in the MECP2 gene that encodes methyl-CpG-binding protein 2 (MeCP2), a DNA-binding protein with roles in epigenetic regulation of gene expression. Functional loss of MeCP2 results in abnormal neuronal maturation and plasticity, characterized by loss of verbal communication and loss of fine and gross motor function, among others. Trofinetide, a synthetic analog of glycine-proline-glutamate, was approved by the US Food and Drug Administration for the treatment of RTT in adult and pediatric patients aged 2 years and older. Here, we present the development of trofinetide from bench research to clinical studies and emphasize how the collaboration between academia, the pharmaceutical industry, and patient advocacy led to the recent approval. The bench-to-bedside development of trofinetide underscores the value of collaboration between these groups in the development and approval of treatments for rare diseases

Overexpression of Secreted Frizzled-Related Protein 1 Inhibits Bone Formation and Attenuates Parathyroid Hormone Bone Anabolic Effects

Secreted frizzled-related protein 1 (sFRP1) is an antagonist of Wnt signaling, an important pathway in maintaining bone homeostasis. In this study we evaluated the skeletal phenotype of mice overexpressing sFRP1 (sFRP1 Tg) and the interaction of parathyroid hormone (PTH) treatment and sFRP1 (over)expression. Bone mass and microarchitecture were measured by micro-computed tomography (µCT). Osteoblastic and osteoclastic cell maturation and function were assessed in primary bone marrow cell cultures. Bone turnover was assessed by biochemical markers and dynamic bone histomorphometry. Real-time PCR was used to monitor the expression of several genes that regulate osteoblast maturation and function in whole bone. We found that trabecular bone mass measurements in distal femurs and lumbar vertebral bodies were 22% and 51% lower in female and 9% and 33% lower in male sFRP1 Tg mice, respectively, compared with wild-type (WT) controls at 3 months of age. Genes associated with osteoblast maturation and function, serum bone formation markers, and surface based bone formation were significantly decreased in sFRP1 Tg mice of both sexes. Bone resorption was similar between sFRP1 Tg and WT females and was higher in sFRP1 Tg male mice. Treatment with hPTH(1-34) (40 µg/kg/d) for 2 weeks increased trabecular bone volume in WT mice (females: +30% to 50%; males: +35% to 150%) compared with sFRP1 Tg mice (females: +5%; males: +18% to 54%). Percentage increases in bone formation also were lower in PTH-treated sFRP1 Tg mice compared with PTH-treated WT mice. In conclusion, overexpression of sFRP1 inhibited bone formation as well as attenuated PTH anabolic action on bone. The gender differences in the bone phenotype of the sFRP1 Tg animal warrants further investigation. © 2010 American Society for Bone and Mineral Researc

Neuronal Dysfunction in iPSC-Derived Medium Spiny Neurons from Chorea-Acanthocytosis Patients Is Reversed by Src Kinase Inhibition and F-Actin Stabilization

Chorea-acanthocytosis (ChAc) is a fatal neurological disorder characterized by red blood cell acanthocytes and striatal neurodegeneration. Recently, severe cell membrane disturbances based on depolymerized cortical actin and an elevated Lyn kinase activity in erythrocytes from ChAc patients were identified. How this contributes to the mechanism of neurodegeneration is still unknown. To gain insight into the pathophysiology, we established a ChAc patient-derived induced pluripotent stem cell model and an efficient differentiation protocol providing a large population of human striatal medium spiny neurons (MSNs), the main target of neurodegeneration in ChAc. Patient-derived MSNs displayed enhanced neurite outgrowth and ramification, whereas synaptic density was similar to controls. Electrophysiological analysis revealed a pathologically elevated synaptic activity in ChAc MSNs. Treatment with the F-actin stabilizer phallacidin or the Src kinase inhibitor PP2 resulted in the significant reduction of disinhibited synaptic currents to healthy control levels, suggesting a Src kinase- and actin-dependent mechanism. This was underlined by increased G/F-actin ratios and elevated Lyn kinase activity in patient-derived MSNs. These data indicate that F-actin stabilization and Src kinase inhibition represent potential therapeutic targets in ChAc that may restore neuronal function

Speech Communication

Contains reports on five research projects.C.J. Lebel FellowshipNational Institutes of Health (Grant 5 T32 NS07040)National Institutes of Health (Grant 5 R01 NS04332)National Science Foundation (Grant 1ST 80-17599)U.S. Navy - Naval Electronic Systems Command Contract (N00039-85-C-0254)U.S. Navy - Naval Electronic Systems Command Contract (N00039-85-C-0341)U.S. Navy - Naval Electronic Systems Command Contract (N00039-85-C-0290

A review of equity issues in quantitative studies on health inequalities: the case of asthma in adults

<p>Abstract</p> <p>Background</p> <p>The term 'inequities' refers to avoidable differences rooted in injustice. This review examined whether or not, and how, quantitative studies identifying inequalities in risk factors and health service utilization for asthma explicitly addressed underlying inequities. Asthma was chosen because recent decades have seen strong increases in asthma prevalence in many international settings, and inequalities in risk factors and related outcomes.</p> <p>Methods</p> <p>A review was conducted of studies that identified social inequalities in asthma-related outcomes or health service use in adult populations. Data were extracted on use of equity terms (objective evidence), and discussion of equity issues without using the exact terms (subjective evidence).</p> <p>Results</p> <p>Of the 219 unique articles retrieved, 21 were eligible for inclusion. None used the terms equity/inequity. While all but one article traced at least partial pathways to inequity, only 52% proposed any intervention and 55% of these interventions focused exclusively on the more proximal, clinical level.</p> <p>Conclusions</p> <p>Without more in-depth and systematic examination of inequities underlying asthma prevalence, quantitative studies may fail to provide the evidence required to inform equity-oriented interventions to address underlying circumstances restricting opportunities for health.</p

Mechanisms of ring chromosome formation, ring instability and clinical consequences

<p>Abstract</p> <p>Background</p> <p>The breakpoints and mechanisms of ring chromosome formation were studied and mapped in 14 patients.</p> <p>Methods</p> <p>Several techniques were performed such as genome-wide array, MLPA (Multiplex Ligation-Dependent Probe Amplification) and FISH (Fluorescent <it>in situ </it>Hybridization).</p> <p>Results</p> <p>The ring chromosomes of patients I to XIV were determined to be, respectively: r(3)(p26.1q29), r(4)(p16.3q35.2), r(10)(p15.3q26.2), r(10)(p15.3q26.13), r(13)(p13q31.1), r(13)(p13q34), r(14)(p13q32.33), r(15)(p13q26.2), r(18)(p11.32q22.2), r(18)(p11.32q21.33), r(18)(p11.21q23), r(22)(p13q13.33), r(22)(p13q13.2), and r(22)(p13q13.2). These rings were found to have been formed by different mechanisms, such as: breaks in both chromosome arms followed by end-to-end reunion (patients IV, VIII, IX, XI, XIII and XIV); a break in one chromosome arm followed by fusion with the subtelomeric region of the other (patients I and II); a break in one chromosome arm followed by fusion with the opposite telomeric region (patients III and X); fusion of two subtelomeric regions (patient VII); and telomere-telomere fusion (patient XII). Thus, the r(14) and one r(22) can be considered complete rings, since there was no loss of relevant genetic material. Two patients (V and VI) with r(13) showed duplication along with terminal deletion of 13q, one of them proved to be inverted, a mechanism known as inv-dup-del. Ring instability was detected by ring loss and secondary aberrations in all but three patients, who presented stable ring chromosomes (II, XIII and XIV).</p> <p>Conclusions</p> <p>We concluded that the clinical phenotype of patients with ring chromosomes may be related with different factors, including gene haploinsufficiency, gene duplications and ring instability. Epigenetic factors due to the circular architecture of ring chromosomes must also be considered, since even complete ring chromosomes can result in phenotypic alterations, as observed in our patients with complete r(14) and r(22).</p

Research translation to inform national health policies: learning from multiple perspectives in Uganda

<p>Abstract</p> <p>Background</p> <p>Research and evidence can have an impact on policy and practice, resulting in positive outcomes. However, research translation is a complex, dynamic and non-linear process. Although universities in Africa play a major role in generating research evidence, their strategic approaches to influence health policies and decision making are weak. This study was conducted with the aim of understanding the process of translating research into policy in order to guide the strategic direction of Makerere University College of Health Sciences (MakCHS) and similar institutions in their quest to influence health outcomes nationally and globally.</p> <p>Methods</p> <p>A case study approach using 30 in-depth interviews with stakeholders involved in two HIV prevention research project was purposively selected. The study sought to analyze the research-to-policy discourses for the prevention of mother-to-child transmission (PMTCT) and safe male circumcision (SMC). The analysis sought to identify entry points, strengths and challenges for research-to-policy processes by interviewing three major groups of stakeholders in Uganda – researchers (8), policy makers (12) and media practitioners (12).</p> <p>Results</p> <p>Among the factors that facilitated PMTCT policy uptake and continued implementation were: shared platforms for learning and decision making among stakeholders, implementation pilots to assess feasibility of intervention, the emerging of agencies to undertake operations research and the high visibility of policy benefits to child survival. In contrast, SMC policy processes were stalled for over two years after the findings of the Uganda study was made public. Among other factors, policy makers demanded additional research to assess implementation feasibility of SMC within ordinary health system context. High level leaders also publicly contested the SMC evidence and the underlying values and messages – a situation that reduced the coalition of policy champions.</p> <p>Conclusions</p> <p>This study shows that effective translation of PMTCT and SMC research results demanded a “360 degree” approach to assembling additional evidence to inform the implementation feasibility for these two HIV prevention interventions. MakCHS and similar institutions should prioritize implementation research to guide the policy processes about the feasibility of implementing new and effective innovations (e.g. PMTCT or SMC) at a large scale in contexts that may be different from the research environments.</p