New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

Mundos mesclados, espaços segregados: cultura material, mestiçagem e segmentação no sítio Aldeia em Santarém (PA)

This article discusses the processes of cultural exchange between Portuguese, Portuguese-Brazilian, Amerindians, and mestizos based on the analysis of the material culture from households of Santarém (PA), occupied during the eighteenth and nineteenth centuries,. Although these social groups manipulated material culture aiming to express different values, related to hierarchy, social segmentation, and affirmation of identities, ambiguity also characterizes these assemblages. This material ambiguity informs about the mixtures of both practices and cultural references that brought about the building of a mestizo society.Com base na análise da cultura material proveniente de unidades domésticas do núcleo urbano de Santarém (PA), ocupadas nos séculos XVIII e XIX, o presente artigo discute os processos de trocas culturais entre portugueses, luso-brasileiros, indígenas e mestiços. Embora esses grupos sociais tenham manipulado a cultura material visando expressar diferentes valores, relacionados à hierarquia, segmentação social e afirmação de identidades, a ambigüidade é uma característica das amostras analisadas, informando sobre as misturas de práticas e de referenciais culturais que levaram à construção de uma sociedade mestiça

Psychometric properties of the goniometric assessment of the Dart Thrower's Motion

Introduction: The Dart Thrower’s Motion is an important movement for hand function. A goniometric clinical measure on Dart Thrower’s Motion has been developed. However, its validity and reliability in people with wrist and hand injury is not known. This study investigated the inter-rater and test–retest reliability and criterion validity of the Dart Thrower’s Motion measure. Methods: A cross-sectional design was used. Thirty-five participants with hand or wrist injury completed the goniometric assessment of the Dart Thrower’s Motion and goniometric wrist active range of motion assessment three times in a hand clinic. Two assessors and a reader to record the results were involved. Participants also completed the patient-rated wrist and hand evaluation. Results: The intraclass correlation coefficients were 0.70–0.83 and 0.91–0.92, respectively for inter-rater and test–retest reliability in the injured hands indicated moderate to high reliability. The Pearson correlation coefficients between the Dart Thrower’s Motion measure and wrist active range of motion assessment ranged from 0.45 to 0.73, and with patient-rated wrist and hand evaluation ranged from −0.36 to −0.53. The results indicate that goniometric assessment of the Dart Thrower’s Motion has acceptable criterion validity. Conclusion: The goniometric assessment of Dart Thrower’s Motion can be considered a valid and reliable clinical measure for measuring the impact of the injury to one’s hand and wrist range of motion and function. It shows its clinical utility in people with hand and wrist injury. It is hoped this simple measure can be eventually implemented in clinical settings, allowing for an increased understanding of an individual’s functional use of the hand and wrist

Psychometric properties of the goniometric assessment of the Dart Thrower’s Motion

Introduction: The Dart Thrower’s Motion is an important movement for hand function. A goniometric clinical measure on Dart Thrower’s Motion has been developed. However, its validity and reliability in people with wrist and hand injury is not known. This study investigated the inter-rater and test–retest reliability and criterion validity of the Dart Thrower’s Motion measure. Methods: A cross-sectional design was used. Thirty-five participants with hand or wrist injury completed the goniometric assessment of the Dart Thrower’s Motion and goniometric wrist active range of motion assessment three times in a hand clinic. Two assessors and a reader to record the results were involved. Participants also completed the patient-rated wrist and hand evaluation. Results: The intraclass correlation coefficients were 0.70–0.83 and 0.91–0.92, respectively for inter-rater and test–retest reliability in the injured hands indicated moderate to high reliability. The Pearson correlation coefficients between the Dart Thrower’s Motion measure and wrist active range of motion assessment ranged from 0.45 to 0.73, and with patient-rated wrist and hand evaluation ranged from −0.36 to −0.53. The results indicate that goniometric assessment of the Dart Thrower’s Motion has acceptable criterion validity. Conclusion: The goniometric assessment of Dart Thrower’s Motion can be considered a valid and reliable clinical measure for measuring the impact of the injury to one’s hand and wrist range of motion and function. It shows its clinical utility in people with hand and wrist injury. It is hoped this simple measure can be eventually implemented in clinical settings, allowing for an increased understanding of an individual’s functional use of the hand and wrist

Characterization of MenA (isoprenyl diphosphate:1,4-dihydroxy-2-naphthoate isoprenyltransferase) from Mycobacterium tuberculosis.

The menaquinone biosynthetic pathway presents a promising drug target against Mycobacterium tuberculosis and potentially other Gram-positive pathogens. In the present study, the essentiality, steady state kinetics of MenA from M. tuberculosis and the mechanism of MenA inhibition by Ro 48-8071 were characterized. MenA [isoprenyl diphosphate:1,4-dihydroxy-2-naphthoate (DHNA) isoprenyltransferase] catalyzes a critical reaction in menaquinone biosynthesis that involves the conversion of cytosolic DHNA, to membrane bound demethylmenaquinone by transferring a hydrophobic 45-carbon isoprenoid chain (in the case of mycobacteria) to the ring nucleus of DHNA. Rv0534c previously identified as the gene encoding MenA in M. tuberculosis complemented a menA deletion in E. coli and an E. coli host expressing Rv0534c exhibited an eight-fold increase in MenA specific activity over the control strain harboring empty vector under similar assay conditions. Expression of Rv0534c is essential for mycobacterial survival and the native enzyme from M. tuberculosis H37Rv was characterized using membrane preparations as it was not possible to solubilize and purify the recombinant enzyme. The enzyme is absolutely dependent on the presence of a divalent cation for optimal activity with Mg+2 being the most effective and is active over a wide pH range, with pH 8.5 being optimal. The apparent Km values for DHNA and farnesyl diphosphate were found to be 8.2 and 4.3 μM, respectively. Ro 48-8071, a compound previously reported to inhibit mycobacterial MenA activity, is non-competitive with regard to DHNA and competitive with regard to the isoprenyldiphosphate substrate

Alterations in DNA methylation associate with fatty liver and metabolic abnormalities in a multi-ethnic cohort of pre-teenage children

Non-Alcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease in children. Epigenetic alterations, such as through DNA methylation (DNAm), may link adverse childhood exposures and fatty liver and provide non-invasive methods for identifying children at high risk for NAFLD and associated metabolic dysfunction. We investigated the association between differential DNAm and liver fat content (LFC) and liver injury in pre-adolescent children. Leveraging data from the Newborn Epigenetics Study (NEST), we enrolled 90    mother-child dyads and used linear regression to identify CpG sites and differentially methylated regions (DMRs) in peripheral blood associated with LFC and alanine aminotransferase (ALT) levels in 7–12yo children. DNAm was measured using Infinium HumanMethylationEPIC BeadChips (Illumina). LFC and fibrosis were quantified by magnetic resonance imaging proton density fat fraction and elastography. Median LFC was 1.4% (range, 0.3–13.4%) and MRE was 2.5 kPa (range, 1.5–3.6kPa). Three children had LFC ≥ 5%, while six (7.6%) met our definition of NAFLD (LFC ≥ 3.7%). All children with NAFLD were obese and five were Black. LFC was associated with 88 DMRs and 106 CpGs (FDR<5%). The top two CpGs, cg25474373 and cg07264203, mapped to or near RFTN2 and PRICKLE2 genes. These two CpG sites were also significantly associated with a NAFLD diagnosis. As higher LFC associates with an adverse cardiometabolic profile already in childhood, altered DNAm may identify these children early in disease course for targeted intervention. Larger, longitudinal studies are needed to validate these findings and determine mechanistic relevance

Application of The Consolidated Framework for Implementation Research to inform understanding of barriers and facilitators to the implementation of opioid and naloxone training on college campuses

Background The opioid epidemic in the US continues to worsen. Opioid-only and polysubstance-involved opioid overdose deaths are increasing among adolescents and young adults, who have limited knowledge of opioid overdose prevention, including recognition and response. College campuses have infrastructure to support national-level implementation of evidence-based public health strategies for providing opioid overdose prevention and naloxone training programs among this priority population. However, college campuses are an underutilized, understudied setting for this programming. To address this gap, we conducted research assessing barriers and facilitators to planning and implementing this programming on college campuses. Methods We held 9 focus groups among purposively selected campus stakeholders whose perceptions were important to understand in planning for the dissemination and implementation of opioid overdose prevention and naloxone training. Focus group scripts were informed by The Consolidated Framework for Implementation Research (CFIR) to query about perceptions of opioid and other substance use, opioid and other substance use-related resources, and naloxone administration training. We used a deductive-inductive, iterative approach to thematic analysis. Results Themes about implementation barriers included (1) the perception that problematic use of other (non-opioid) substances was more prevalent than opioid use on campus and focus on those substances would be a greater priority on college campuses; (2) student schedules were overwhelmed with academic commitments and extracurricular activities, making delivery of additional training challenging; (3) barriers related to the perceived complexity and decentralization of communication on campus, preventing students from knowing how to access substance use-related resources. Themes about implementation facilitators included (1) framing naloxone training as important in becoming a responsible leader on campus and in the broader community and (2) leveraging existing infrastructure, champions within existing campus groups, and tailored messaging to facilitate participation in naloxone training. Conclusions This is the first study to provide in-depth insights into potential barriers and facilitators to widespread, routine implementation of naloxone/opioid education on undergraduate college campuses. The study captured diverse stakeholder perspectives and was theoretically grounded in CFIR, contributing to the growing literature on the application and refinement of CFIR across diverse community and school contexts