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

Design and baseline characteristics of the finerenone in reducing cardiovascular mortality and morbidity in diabetic kidney disease trial

Background: Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. Patients and Methods: The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate >= 25 mL/min/1.73 m(2) and albuminuria (urinary albumin-to-creatinine ratio >= 30 to <= 5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level alpha = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. Conclusions: FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049

Effect of Solvent Composition on Solubility, Thermodynamics, Metastable Zone Width (MSZW) and Crystal Habit of L-Ascorbic Acid

This work investigates the effect of different solvent systems on solubility, thermodynamics, metastable zone width (MSZW), and crystal habit of ascorbic acid, in order to help optimize its crystallization process. The solubility curves and metastable zone (MSZ) limits were determined experimentally using the polythermal method in pure solvents: water and alcohols (methanol/ethanol/isopropanol), as well as water-alcohol binary solvent systems. The solubility decreases with increasing alcohol composition for all solvent systems. The solubility data were well correlated using the Jouyban–Acree model as a function of two variables: temperature and solvent composition. The dissolution enthalpy (ΔHdiss), dissolution entropy (ΔSdiss), and Gibbs free energy (ΔGdiss) were determined using Van’t Hoff and Jouyban–Acree models. The thermodynamic properties increase with increasing alcohol composition. The lowest and highest values of enthalpy were obtained for water (20.52 kJ mol −1) and isopropanol (35.33 kJ mol−1), respectively. Pure alcohols as solvents widen the metastable zone width, indicating high supersaturation required for the nucleation. Crystal images captured during cooling crystallization in water confirm the cubic crystal habit formation, whereas increasing alcohol composition in the solvent system promotes preferential growth along one crystallographic axis, leading to elongated prism-shaped crystals in methanol and ethanol and needle-shaped crystals in isopropanol

Enhancing the helical distortion in pyrrolo[1,2-a]phenanthrolines

The International Society for Burns Injuries (ISBI) has published guidelines for the management of multiple or mass burns casualties, and recommends that 'each country has or should have a disaster planning system that addresses its own particular needs.' The need for a national burns disaster plan integrated with national and provincial disaster planning was discussed at the South African Burns Society Congress in 2009, but there was no real involvement in the disaster planning prior to the 2010 World Cup; the country would have been poorly prepared had there been a burns disaster during the event. This article identifies some of the lessons learnt and strategies derived from major burns disasters and burns disaster planning from other regions. Members of the South African Burns Society are undertaking an audit of burns care in South Africa to investigate the feasibility of a national burns disaster plan. This audit (which is still under way) also aims to identify weaknesses of burns care in South Africa and implement improvements where necessary

Acute ischemic cholecystitis in Takayasu’s syndrome – a rare finding

Introduction. Takayasu’s arteritis or pulseless disease is a systemic inflammatory disease of an unknown etiology, affecting medium and large arteries and their branches, leading to stenosis, occlusions, or aneurysmal degeneration. It is more frequent in young Asian women. Case presentation. We present a rare case of Takayasu’s disease in a young woman, who initially developed an acute ischemic cholecystitis. Ischemia is one of the mechanisms involved in the pathogenesis of acute acalculous cholecystitis. As this mechanism is most often involved in elderly people, such an uncommon finding at young age should be a reason to suspect a vasculitis with small vessel occlusion. Conclusions. Acute cholecystitis in this patient was the first onset sign of Takayasu’s arteritis. An acute acalculous cholecystitis at young age could be of ischemic origin and should also be considered as a possible epiphenomenon of a generalized vasculitis disease

Styryl-functionalized cage silsesquioxanes as nanoblocks for 3-D assembly

Herein we report the synthesis of a new family of styryl-functionalized polyhedral oligomeric silsesquioxanes (Tn, where n = 8, 10, and 12), in which the organic moiety is linked to all n vertices of the Tn cages via the phenyl ring rather than the vinyl group. In contrast to earlier studies in which the styryl group is linked to the cage via the vinyl moiety, our approach ensures that the vinyl moiety is less sterically hindered and available for postfunctionalization. The functional Tn cages have been characterized by a range of techniques, including single crystal X-ray diffraction, multinuclear solution NMR (1H, 13C, and 29Si), MALDI-MS, and FTIR. The solid-state structure of the T8 compound exhibited two nonequivalent Si8O12 cage atoms, which has not been previously reported in the functionalized T8 system, although all cage atoms in the corresponding T10 and T12 systems were equivalent. In contrast, multinuclear solution NMR data indicated that all cages in the T8 system were equivalent in solution, suggesting that the nonequivalent cage geometries arise in the solid state to optimize the packing of the functionalized cages. These compounds have significant potential for future use in the production of 3D cross-linked polymer networks

SPIEGEL HERNIA – CASE PRESENTATION

he Spieghelian hernia or ventro-lateral hernia is produced through the effect of rupture of the abdominal wall fibers, near the semi lunar line. The hernia sac is usually accompanied by extra peritoneal fatty tissue and is intra parietal, it passes through the aponeurosis of the transverse muscle and internal oblique muscle, and it grows under the aponeurosis of the external oblique muscle. The Spiegel hernia is rare and is difficult to diagnose clinically. In this article we present the case of a 43-year-old patient who presented at the emergency department for a pseudo-tumor mass in the left flank and was diagnosed with Spiegel hernia

Rare small bowel obstruction due to phytobezoar – Case presentation

Phytobezoar is a rare cause of small bowel obstruction. This pathology represents 0.4%-4% of all mechanical bowel obstructions. Symptoms are similar to other small bowel obstructions. The most common localisation of the obstruction is represented by the terminal ileum. Phytobezoars are to be considered in patients who have had gastric surgery, a high fiber intake or psychiatric disorders. Also, multiple sclerosis has shown to affect bowel motility, which is important to our case. Surgery is always indicated. A low fiber diet and prokinetics are indicated for the prevention of this pathology. We present the case of a 43-year-old female who was admitted to the ICU following a car accident. The patient presented bowel obstruction symptoms (nausea and vomiting, bloating, not passing gas and severe abdominal pain) the 5th day after admission and was transferred to the operating room for exploratory laparotomy. Intraoperatively, we discovered a phytobezoar which was confirmed by the histopathological exam