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

Differentiation of neurons from neural precursors generated in floating spheres from embryonic stem cells

<p>Abstract</p> <p>Background</p> <p>Neural differentiation of embryonic stem (ES) cells is usually achieved by induction of ectoderm in embryoid bodies followed by the enrichment of neuronal progenitors using a variety of factors. Obtaining reproducible percentages of neural cells is difficult and the methods are time consuming.</p> <p>Results</p> <p>Neural progenitors were produced from murine ES cells by a combination of nonadherent conditions and serum starvation. Conversion to neural progenitors was accompanied by downregulation of <it>Oct4 </it>and <it>NANOG </it>and increased expression of <it>nestin</it>. ES cells containing a GFP gene under the control of the <it>Sox1 </it>regulatory regions became fluorescent upon differentiation to neural progenitors, and ES cells with a tau-GFP fusion protein became fluorescent upon further differentiation to neurons. Neurons produced from these cells upregulated mature neuronal markers, or differentiated to glial and oligodendrocyte fates. The neurons gave rise to action potentials that could be recorded after application of fixed currents.</p> <p>Conclusion</p> <p>Neural progenitors were produced from murine ES cells by a novel method that induced neuroectoderm cells by a combination of nonadherent conditions and serum starvation, in contrast to the embryoid body method in which neuroectoderm cells must be selected after formation of all three germ layers.</p

Outcome After Surgical Stabilization of Rib Fractures Versus Nonoperative Treatment in Patients With Multiple Rib Fractures and Moderate to Severe Traumatic Brain Injury (CWIS-TBI)

BACKGROUND Outcomes after surgical stabilization of rib fractures (SSRF) have not been studied in patients with multiple rib fractures and traumatic brain injury (TBI). We hypothesized that SSRF, as compared with nonoperative management, is associated with favorable outcomes in patients with TBI. METHODS A multicenter, retrospective cohort study was performed in patients with rib fractures and TBI between January 2012 and July 2019. Patients who underwent SSRF were compared to those managed nonoperatively. The primary outcome was mechanical ventilation-free days. Secondary outcomes were intensive care unit length of stay and hospital length of stay, tracheostomy, occurrence of complications, neurologic outcome, and mortality. Patients were further stratified into moderate (GCS score, 9–12) and severe (GCS score, ≤8) TBI. RESULTS The study cohort consisted of 456 patients of which 111 (24.3%) underwent SSRF. The SSRF was performed at a median of 3 days, and SSRF-related complication rate was 3.6%. In multivariable analyses, there was no difference in mechanical ventilation-free days between the SSRF and nonoperative groups. The odds of developing pneumonia (odds ratio [OR], 0.59; 95% confidence interval [95% CI], 0.38–0.98; p = 0.043) and 30-day mortality (OR, 0.32; 95% CI, 0.11–0.91; p = 0.032) were significantly lower in the SSRF group. Patients with moderate TBI had similar outcome in both groups. In patients with severe TBI, the odds of 30-day mortality was significantly lower after SSRF (OR, 0.19; 95% CI, 0.04–0.88; p = 0.034). CONCLUSION In patients with multiple rib fractures and TBI, the mechanical ventilation-free days did not differ between the two treatment groups. In addition, SSRF was associated with a significantly lower risk of pneumonia and 30-day mortality. In patients with moderate TBI, outcome was similar. In patients with severe TBI a lower 30-day mortality was observed. There was a low SSRF-related complication risk. These data suggest a potential role for SSRF in select patients with TBI. LEVEL OF EVIDENCE Therapeutic, level IV

Effects of Changing the Supply of Nitrogen and Phosphorus on Growth and Interactions between 'Eucalyptus globulus' and 'Acacia mearnsii' in a Pot trial

Significant increases in aboveground biomass production have been observed in mixed plantations of 'Eucalyptus globulus' and 'Acacia mearnsii' when compared to monocultures. However, this positive growth response may be enhanced or lost with changes in resource availability. Therefore this study examined the effect of the commonly limiting resources soil N, P and moisture on the growth of 'E. globulus' and 'A. mearnsii' mixtures in a pot trial. Pots containing two 'E. globulus' plants, two 'A. mearnsii' plants or one of each species were treated with high and low levels of N and P fertiliser. After 50 weeks, 'E. globulus' plants grew more aboveground biomass in mixtures than monocultures. 'A. mearnsii' were larger in mixtures only at low N, where both species were similar in size and the combined aboveground biomass of both species in mixture was greater than that of monocultures. At high N and both high and low levels of P fertiliser 'E. globulus' appeared to dominate and suppress 'A. mearnsii'. In these treatments, the faster growth of 'E. globulus' in mixture did not compensate the reduced growth of 'A. mearnsii', so mixtures were less productive than (or not significantly different from) E. globulus monocultures. The greater competitiveness of 'E. globulus' in these situations may have resulted from its higher N and P use efficiency and greater growth response to N and P fertilisers compared to 'A. mearnsii'. This trial indicates that the complex interactions between species in mixtures, and thus the success of mixed plantations, can be strongly influenced by site factors such as the availability of N and P