Second to fourth digit ratio (2D:4D) and concentrations of circulating sex hormones in adulthood

<p>Abstract</p> <p>Background</p> <p>The second to fourth digit ratio (2D:4D) is used as a marker of prenatal sex hormone exposure. The objective of this study was to examine whether circulating concentrations of sex hormones and SHBG measured in adulthood was associated with 2D:4D.</p> <p>Methods</p> <p>This analysis was based on a random sample from the Melbourne Collaborative Cohort Study. The sample consisted of of 1036 men and 620 post-menopausal women aged between 39 and 70 at the time of blood draw. Concentrations of circulating sex hormones were measured from plasma collected at baseline (1990-1994), while digit length was measured from hand photocopies taken during a recent follow-up (2003-2009). The outcome measures were circulating concentrations of testosterone, oestradiol, dehydroepiandrosterone sulphate, androstenedione, Sex Hormone Binding Globulin, androstenediol glucoronide for men only and oestrone sulphate for women only. Free testosterone and oestradiol were estimated using standard formulae derived empirically. Predicted geometric mean hormone concentrations (for tertiles of 2D:4D) and conditional correlation coefficients (for continuous 2D:4D) were obtained using mixed effects linear regression models.</p> <p>Results</p> <p>No strong associations were observed between 2D:4D measures and circulating concentrations of hormones for men or women. For males, right 2D:4D was weakly inversely associated with circulating testosterone (predicted geometric mean testosterone was 15.9 and 15.0 nmol/L for the lowest and highest tertiles of male right 2D:4D respectively (<it>P</it>-<it>trend </it>= 0.04). There was a similar weak association between male right 2D:4D and the ratio of testosterone to oestradiol. These associations were not evident in analyses of continuous 2D:4D.</p> <p>Conclusions</p> <p>There were no strong associations between any adult circulating concentration of sex hormone or SHGB and 2D:4D. These results contribute to the growing body of evidence indicating that 2D:4D is unrelated to adult sex hormone concentrations.</p

Exploring the use of ultrasound imaging by physiotherapists: An international survey

Background: National surveys in New Zealand, Australia and the United Kingdom suggest ultrasound imaging (USI) use by physiotherapists is increasing. However, concerns exist regarding clarity for scopes of practice, and availability and standardisation of training. Objectives: To investigate physiotherapists' understanding of scopes of practice for the use of USI; clarify the professional contexts, clinical uses and levels of training; and identify barriers preventing physiotherapists' USI use. Design: A cross-sectional, observational survey. Methods: An Internet-based survey, offered in 20 different languages, was used including items covering five domains: (1) demographic and professional characteristics; (2) knowledge of scope of practice; (3) USI use; (4) USI training content and duration; and (5) perceived barriers to physiotherapists' use of USI. Results: 1307 registered physiotherapists from 49 countries responded; 30% were unsure of the scope of practice for physiotherapists' USI use. 38% of participants were users of USI, reporting varied contexts and clinical uses, reflected in the broader categories of: (i) biofeedback; (ii) diagnosis; (iii) assessment; (iv) injection guidance; (v) research; (vi) and teaching. The training users received varied, with formal training more comprehensive. 62% were non-users, the most common barrier was lack of training (76%). Conclusion: These findings suggest physiotherapists' USI use is increasing in various contexts; however, there is uncertainty regarding scopes of practice. There are discrepancies in training offered, with a lack of training the most common barrier to physiotherapists' use of USI. International guidelines, including a USI training framework, are needed to support the consistent and sustainable use of USI in physiotherapy

Expressions 1980

Expressions contains selected work from the 1980 Creative Writing Contest winners and honorable mentions, Campus Chronicle Photography Contest entrants, and the Commercial Art students at Des Moines Area Community College. Design, typography and layout was done by Journalism students.https://openspace.dmacc.edu/expressions/1002/thumbnail.jp

Metabolome and microbiome profiling of a stress-sensitive rat model of gut-brain axis dysfunction

peer-reviewedStress negatively impacts gut and brain health. Individual diferences in response to stress have been linked to genetic and environmental factors and more recently, a role for the gut microbiota in the regulation of stress-related changes has been demonstrated. However, the mechanisms by which these factors infuence each other are poorly understood, and there are currently no established robust biomarkers of stress susceptibility. To determine the metabolic and microbial signatures underpinning physiological stress responses, we compared stress-sensitive Wistar Kyoto (WKY) rats to the normoanxious Sprague Dawley (SD) strain. Here we report that acute stress-induced strain-specifc changes in brain lipid metabolites were a prominent feature in WKY rats. The relative abundance of Lactococcus correlated with the relative proportions of many brain lipids. In contrast, plasma lipids were signifcantly elevated in response to stress in SD rats, but not in WKY rats. Supporting these fndings, we found that the greatest diference between the SD and WKY microbiomes were the predicted relative abundance of microbial genes involved in lipid and energy metabolism. Our results provide potential insights for developing novel biomarkers of stress vulnerability, some of which appear genotype specifc

Human Bone Marrow Organoids for Disease Modeling, Discovery, and Validation of Therapeutic Targets in Hematologic Malignancies

A lack of models that recapitulate the complexity of human bone marrow has hampered mechanistic studies of normal and malignant hematopoiesis and the validation of novel therapies. Here, we describe a step-wise, directed-differentiation protocol in which organoids are generated from induced pluripotent stem cells committed to mesenchymal, endothelial, and hematopoietic lineages. These 3D structures capture key features of human bone marrow— stroma, lumen-forming sinusoids, and myeloid cells including proplatelet-forming megakaryocytes. The organoids supported the engraftment and survival of cells from patients with blood malignancies, including cancer types notoriously difficult to maintain ex vivo. Fibrosis of the organoid occurred following TGFβ stimulation and engraftment with myelofibrosis but not healthy donor–derived cells, validating this platform as a powerful tool for studies of malignant cells and their interactions within a human bone marrow–like milieu. This enabling technology is likely to accelerate the discovery and prioritization of novel targets for bone marrow disorders and blood cancers. SIGNIFICANCE: We present a human bone marrow organoid that supports the growth of primary cells from patients with myeloid and lymphoid blood cancers. This model allows for mechanistic studies of blood cancers in the context of their microenvironment and provides a much-needed ex vivo tool for the prioritization of new therapeutics.</p

Whole-Genome Sequencing of a Single Proband Together with Linkage Analysis Identifies a Mendelian Disease Gene

Although more than 2,400 genes have been shown to contain variants that cause Mendelian disease, there are still several thousand such diseases yet to be molecularly defined. The ability of new whole-genome sequencing technologies to rapidly indentify most of the genetic variants in any given genome opens an exciting opportunity to identify these disease genes. Here we sequenced the whole genome of a single patient with the dominant Mendelian disease, metachondromatosis (OMIM 156250), and used partial linkage data from her small family to focus our search for the responsible variant. In the proband, we identified an 11 bp deletion in exon four of PTPN11, which alters frame, results in premature translation termination, and co-segregates with the phenotype. In a second metachondromatosis family, we confirmed our result by identifying a nonsense mutation in exon 4 of PTPN11 that also co-segregates with the phenotype. Sequencing PTPN11 exon 4 in 469 controls showed no such protein truncating variants, supporting the pathogenicity of these two mutations. This combination of a new technology and a classical genetic approach provides a powerful strategy to discover the genes responsible for unexplained Mendelian disorders

Fatty Acid Biomarkers of Dairy Fat Consumption and Incidence of Type 2 Diabetes: A Pooled Analysis of Prospective Cohort Studies

Background We aimed to investigate prospective associations of circulating or adipose tissue odd-chain fatty acids 15:0 and 17:0 and trans-palmitoleic acid, t16:1n-7, as potential biomarkers of dairy fat intake, with incident type 2 diabetes (T2D). Methods and findings Sixteen prospective cohorts from 12 countries (7 from the United States, 7 from Europe, 1 from Australia, 1 from Taiwan) performed new harmonised individual-level analysis for the prospective associations according to a standardised plan. In total, 63,682 participants with a broad range of baseline ages and BMIs and 15,180 incident cases of T2D over the average of 9 years of follow-up were evaluated. Study-specific results were pooled using inverse-variance±weighted meta-analysis. Prespecified interactions by age, sex, BMI, and race/ethnicity were explored in each cohort and were meta-analysed. Potential heterogeneity by cohort-specific characteristics (regions, lipid compartments used for fatty acid assays) was assessed with metaregression. After adjustment for potential confounders, including measures of adiposity (BMI, waist circumference) and lipogenesis (levels of palmitate, triglycerides), higher levels of 15:0, 17:0, and t16:1n-7 were associated with lower incidence of T2D. In the most adjusted model, the hazard ratio (95% CI) for incident T2D per cohortspecific 10th to 90th percentile range of 15:0 was 0.80 (0.73±0.87); of 17:0, 0.65 (0.59± 0.72); of t16:1n7, 0.82 (0.70±0.96); and of their sum, 0.71 (0.63±0.79). In exploratory analyses, similar associations for 15:0, 17:0, and the sum of all three fatty acids were present in both genders but stronger in women than in men (pinteraction \u3c 0.001). Whereas studying associations with biomarkers has several advantages, as limitations, the biomarkers do not distinguish between different food sources of dairy fat (e.g., cheese, yogurt, milk), and residual confounding by unmeasured or imprecisely measured confounders may exist. Conclusions In a large meta-analysis that pooled the findings from 16 prospective cohort studies, higher levels of 15:0, 17:0, and t16:1n-7 were associated with a lower risk of T2D