ABCA4-associated disease as a model for missing heritability in autosomal recessive disorders: novel noncoding splice, cis-regulatory, structural, and recurrent hypomorphic variants

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Family Planning Decisions, Perceptions and Gender Dynamics among Couples in Mwanza, Tanzania: A Qualitative Study.

Contraceptive use is low in developing countries which are still largely driven by male dominated culture and patriarchal values. This study explored family planning (FP) decisions, perceptions and gender dynamics among couples in Mwanza region of Tanzania. Twelve focus group discussions and six in-depth interviews were used to collect information from married or cohabiting males and females aged 18-49. The participants were purposively selected. Qualitative methods were used to explore family planning decisions, perceptions and gender dynamics among couples. A guide with questions related to family planning perceptions, decisions and gender dynamics was used. The discussions and interviews were tape-recorded, transcribed verbatim and analyzed manually and subjected to content analysis. Four themes emerged during the study. First, "risks and costs" which refer to the side effects of FP methods and the treatment of side -effects as well as the costs inherit in being labeled as an unfaithful spouse. Second, "male involvement" as men showed little interest in participating in family planning issues. However, the same men were mentioned as key decision-makers even on the number of children a couple should have and the child spacing of these children. Third, "gender relations and communication" as participants indicated that few women participated in decision-making on family planning and the number of children to have. Fourth, "urban-rural differences", life in rural favoring having more children than urban areas therefore, the value of children depended on the place of residence. Family Planning programs should adapt the promotion of communication as well as joint decision-making on FP among couples as a strategy aimed at enhancing FP use

Body mass index trajectories in young adulthood predict nonâ alcoholic fatty liver disease in middle age: The CARDIA cohort study

Background & AimsNonâ alcoholic fatty liver disease is an epidemic. Identifying modifiable risk factors for nonâ alcoholic fatty liver disease development is essential to design effective prevention programmes. We tested whether 25â year patterns of body mass index change are associated with midlife nonâ alcoholic fatty liver disease.MethodsIn all, 4423 participants from Coronary Artery Risk Development in Young Adults, a prospective populationâ based biracial cohort (age 18â 30), underwent body mass index measurement at baseline (1985â 1986) and 3 or more times over 25 years. At Year 25, 3115 had liver fat assessed by nonâ contrast computed tomography. Nonâ alcoholic fatty liver disease was defined as liver attenuation â ¤40 Hounsfield Units after exclusions. Latent mixture modelling identified 25â year trajectories in body mass index per cent change (%Î ) from baseline.ResultsWe identified four distinct trajectories of BMI%Î : stable (26.2% of cohort, 25â year BMI %Π = 3.1%), moderate increase (46.0%, BMI%Π = 21.7%), high increase (20.9%, BMI%Π = 41.9%) and extreme increase (6.9%, BMI%Π = 65.9%). Y25 nonâ alcoholic fatty liver disease prevalence was higher in groups with greater BMI %Î : 4.1%, 9.3%, 13.0%, and 17.6%, respectively (Pâ trend <.0001). In multivariable analyses, participants with increasing BMI%Î had increasingly greater odds of nonâ alcoholic fatty liver disease compared to the stable group: OR: 3.35 (95% CI: 2.07â 5.42), 7.80 (4.60â 13.23) and 12.68 (6.68â 24.09) for moderate, high and extreme body mass index increase, respectively. Associations were only moderately attenuated when adjusted for baseline or Y25 body mass index.ConclusionsTrajectories of weight gain during young adulthood are associated with greater nonâ alcoholic fatty liver disease prevalence in midlife independent of metabolic covariates and baseline or concurrent body mass index highlighting the importance of weight maintenance throughout adulthood as a target for primary nonâ alcoholic fatty liver disease prevention.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/142937/1/liv13603.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/142937/2/liv13603_am.pd

A sea surface temperature reconstruction for the southern Indian Ocean trade wind belt from corals in Rodrigues Island (19° S, 63° E)

The western Indian Ocean has been warming rapidly over recent decades, causing a greater number of extreme climatic events. It is therefore of paramount importance to improve our understanding of links between Indian Ocean sea surface temperature (SST) variability, climate change and sustainability of tropical coral reef ecosystems. Here we present monthly resolved coral Sr ∕ Ca records from two different locations from Rodrigues Island (63° E, 19° S) in the south-central Indian Ocean trade wind belt. We reconstruct SST based on a linear relationship with the Sr ∕ Ca proxy with records starting from 1781 and 1945, respectively. We assess relationships between the observed long-term SST and climate fluctuations related to the El Niño–Southern Oscillation (ENSO), the Subtropical Indian Ocean Dipole Mode (SIOD) and the Pacific Decadal Oscillation (PDO) between 1945 and 2006, respectively. The reproducibility of the Sr ∕ Ca records is assessed as are the potential impacts of diagenesis and corallite orientation on Sr ∕ Ca–SST reconstructions. We calibrate individual robust Sr ∕ Ca records with in situ SST and various gridded SST products. The results show that the SST record from Cabri provides the first Indian Ocean coral proxy time series that records the SST signature of the PDO in the south-central Indian Ocean since 1945. We suggest that additional records from Rodrigues Island can provide excellent records of SST variations in the southern Indian Ocean trade wind belt to unravel teleconnections with the SIOD/ENSO/PDO on longer timescales

Beyond aggression: Androgen-receptor blockade modulates social interaction in wild meerkats

In male vertebrates, androgens are inextricably linked to reproduction, social dominance, and aggression, often at the cost of paternal investment or prosociality. Testosterone is invoked to explain rank-related reproductive differences, but its role within a status class, particularly among subordinates, is underappreciated. Recent evidence, especially for monogamous and cooperatively breeding species, suggests broader androgenic mediation of adult social interaction. We explored the actions of androgens in subordinate, male members of a cooperatively breeding species, the meerkat (Suricata suricatta). Although male meerkats show no rank-related testosterone differences, subordinate helpers rarely reproduce. We blocked androgen receptors, in the field, by treating subordinate males with the antiandrogen, flutamide. We monitored androgen concentrations (via baseline serum and time-sequential fecal sampling) and recorded behavior within their groups (via focal observation). Relative to controls, flutamide-treated animals initiated less and received more high-intensity aggression (biting, threatening, feeding competition), engaged in more prosocial behavior (social sniffing, grooming, huddling), and less frequently initiated play or assumed a ‘dominant’ role during play, revealing significant androgenic effects across a broad range of social behavior. By contrast, guarding or vigilance and measures of olfactory and vocal communication in subordinate males appeared unaffected by flutamide treatment. Thus, androgens in male meerkat helpers are aligned with the traditional trade-off between promoting reproductive and aggressive behavior at a cost to affiliation. Our findings, based on rare endocrine manipulation in wild mammals, show a more pervasive role for androgens in adult social behavior than is often recognized, with possible relevance for understanding tradeoffs in cooperative systems

Initial Pseudomonas aeruginosa treatment failure is associated with exacerbations in cystic fibrosis

The risk of pulmonary exacerbation following Pseudomonas aeruginosa (Pa) acquisition in children with cystic fibrosis (CF) is unknown

Imported Infectious Diseases in Mobile Populations, Spain

Health screening of immigrant populations is needed to ensure early diagnosis and treatment

Applicability and reproducibility of acute myeloid leukaemia stem cell assessment in a multi-centre setting

Leukaemic stem cells (LSC) have been experimentally defined as the leukaemia-propagating population and are thought to be the cellular reservoir of relapse in acute myeloid leukaemia (AML). Therefore, LSC measurements are warranted to facilitate accurate risk stratification. Previously, we published the composition of a one-tube flow cytometric assay, characterised by the presence of 13 important membrane markers for LSC detection

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Cell-Specific DNA Methylation Patterns of Retina-Specific Genes

Many studies have demonstrated that epigenetic mechanisms are important in the regulation of gene expression during embryogenesis, gametogenesis, and other forms of tissue-specific gene regulation. We sought to explore the possible role of epigenetics, specifically DNA methylation, in the establishment and maintenance of cell type-restricted gene expression in the retina. To assess the relationship between DNA methylation status and expression level of retinal genes, bisulfite sequence analysis of the 1000 bp region around the transcription start sites (TSS) of representative rod and cone photoreceptor-specific genes and gene expression analysis were performed in the WERI and Y79 human retinoblastoma cell lines. Next, the homologous genes in mouse were bisulfite sequenced in the retina and in non-expressing tissues. Finally, bisulfite sequencing was performed on isolated photoreceptor and non-photoreceptor retinal cells isolated by laser capture microdissection. Differential methylation of rhodopsin (RHO), retinal binding protein 3 (RBP3, IRBP) cone opsin, short-wave-sensitive (OPN1SW), cone opsin, middle-wave-sensitive (OPN1MW), and cone opsin, long-wave-sensitive (OPN1LW) was found in the retinoblastoma cell lines that inversely correlated with gene expression levels. Similarly, we found tissue-specific hypomethylation of the promoter region of Rho and Rbp3 in mouse retina as compared to non-expressing tissues, and also observed hypomethylation of retinal-expressed microRNAs. The Rho and Rbp3 promoter regions were unmethylated in expressing photoreceptor cells and methylated in non-expressing, non-photoreceptor cells from the inner nuclear layer. A third regional hypomethylation pattern of photoreceptor-specific genes was seen in a subpopulation of non-expressing photoreceptors (Rho in cones from the Nrl −/− mouse and Opn1sw in rods). These results demonstrate that a number of photoreceptor-specific genes have cell-specific differential DNA methylation that correlates inversely with their expression level. Furthermore, these cell-specific patterns suggest that DNA methylation may play an important role in modulating photoreceptor gene expression in the developing mammalian retina