A clinical and computational study on anti-obesity effects of hydroxycitric acid

Hydroxycitric acid (HCA), a major active ingredient of Garcinia cambogia extracts, is known to suppress body weight gain and fat synthesis in animals and humans. But the underlying mechanism of HCA action is not fully understood. Clinical study on 100 obese individuals for a period of 3 months was performed followed by a computational study aimed to investigate the effects of HCA treatment on human subjects at anthropometric and plasma lipid profile levels. A detailed hepatic metabolic model was used to incorporate the effect of HCA at the metabolic pathway level. Perturbation analysis of ATP citrate lyase activity in the metabolic pathway was performed to simulate the net effect of HCA. Significant reductions in body weight, triceps, subscapular, and mid axillary measurements as well as in serum triglyceride, cholesterol, HDL and LDL levels were observed following HCA dosage. During the study, half of the subjects experienced a decline in body weight and the remainder experienced an increase in body weight. However, analysis of fat mass with the help of empirical correlations clearly showed significant reduction in the mean values due to HCA dosage in both cases. An extra increase in fat free mass was responsible for offsetting the decrease in fat mass for the subjects who experienced an increase in body weight during the trials. Perturbation analysis showed a net reduction in fatty acid, triglyceride and cholesterol synthesis along with urea cycle fluxes under lipogenetic conditions. Moreover, protein synthesis fluxes increased under these conditions. These results indicate that HCA treatment can reduce body weight gain and fat accumulation in obese subjects along with improving their anthropometric parameters and metabolic state.

Hydroxycitric acid (HCA), a major active ingredient of Garcinia cambogia extracts, is known to suppress body weight gain and fat synthesis in animals and humans.     

Integrin β3 inhibition is a therapeutic strategy for supravalvular aortic stenosis

The aorta is the largest artery in the body, yet processes underlying aortic pathology are poorly understood. The arterial media consists of circumferential layers of elastic lamellae and smooth muscle cells (SMCs), and many arterial diseases are characterized by defective lamellae and excess SMCs; however, a mechanism linking these pathological features is lacking. In this study, we use lineage and genetic analysis, pharmacological inhibition, explant cultures, and induced pluripotent stem cells (iPSCs) to investigate supravalvular aortic stenosis (SVAS) patients and/or elastin mutant mice that model SVAS. These experiments demonstrate that multiple preexisting SMCs give rise to excess aortic SMCs in elastin mutants, and these SMCs are hyperproliferative and dedifferentiated. In addition, SVAS iPSC-derived SMCs and the aortic media of elastin mutant mice and SVAS patients have enhanced integrin β3 levels, activation, and downstream signaling, resulting in SMC misalignment and hyperproliferation. Reduced β3 gene dosage in elastin-null mice mitigates pathological aortic muscularization, SMC misorientation, and lumen loss and extends survival, which is unprecedented. Finally, pharmacological β3 inhibition in elastin mutant mice and explants attenuates aortic hypermuscularization and stenosis. Thus, integrin β3–mediated signaling in SMCs links elastin deficiency and pathological stenosis, and inhibiting this pathway is an attractive therapeutic strategy for SVAS.The normal arterial wall is histologically divided into three layers: (1) an inner single layer of endothelial cells (ECs), (2) the media with alternating circumferential layers of smooth muscle and elastic lamellae, and (3) an outer adventitial layer, which includes fibroblasts and connective tissue. A critical component of the massive burden of cardiovascular disease on human health is an excessive and ectopic accumulation of arterial smooth muscle cells (SMCs). Unfortunately, therapeutic options for cardiovascular pathologies are hindered by our limited understanding of mechanisms underlying this vascular hypermuscularization (Owens et al., 2004; Seidelmann et al., 2014).In diverse arterial diseases, such as atherosclerosis, restenosis, pulmonary hypertension, and supravalvular aortic stenosis (SVAS), excess SMCs are accompanied by defective elastic lamellae (Sandberg et al., 1981; Raines and Ross, 1993; Karnik et al., 2003). Elastin is a critical component of elastic lamellae, and heterozygous loss of function in the elastin gene (ELN) results in SVAS, a devastating human disease of excessively muscularized arteries (including the ascending and descending aorta; Curran et al., 1993; Li et al., 1998b; Pober et al., 2008). Major surgery is the only therapy for vessel obstruction in elastin arteriopathy. SVAS occurs as an isolated entity or more commonly as the major cause of morbidity in Williams-Beuren syndrome (WBS), which is caused by consecutive deletion of ∼26–28 genes, including ELN, on chromosome 7 (Pober et al., 2008). A mechanism linking elastin defects and hypermuscularization in SVAS or, for that matter, in any vascular disease is not delineated. Integrins are transmembrane receptors that link the extracellular matrix to the actin cytoskeleton and thus are candidates for mediating the effects of defective elastic lamellae on vascular smooth muscle; however, their role in elastin mutant arteriopathy has not been studied.Here, we demonstrate that excess SMCs in elastin mutant mice derive from multiple preexisting SMCs that proliferate, dedifferentiate, and migrate. Integrin β3 expression, activation, and signaling are up-regulated in the aortic media of these mice and SVAS patients and in SVAS induced pluripotent stem cell (iPSC)–derived SMCs. Additionally, our results indicate that enhanced β3-mediated signaling is crucial for SMC misalignment and hyperproliferation in elastin mutants, and genetic or pharmacological inhibition of β3 in elastin mutant mice attenuates aortic hypermuscularization and stenosis. Furthermore, reducing the dosage of Itgb3 (encoding β3) extends elastin-null survival; no prior interventions have increased the viability of elastin mutant mice. Hence, inhibiting integrin β3–mediated signaling in smooth muscle is an attractive pharmacological strategy for SVAS.     

Nerve sparing can preserve orgasmic function in most men after robotic-assisted laparoscopic radical prostatectomy

Study Type – Therapy (case series) Level of Evidence 4 What's known on the subject? and What does the study add? Orgasm has a major influence on patients’ satisfaction with the overall sexual experience, and alternations in orgasm are associated with significant reductions in emotional and physical satisfaction, which in turn may lead to sexual avoidance behaviour, disharmonious relationships and relationship breakdowns. Studies have found a reduction in orgasmic function after retropublic radical prostatectomy. While open radical prostatectomy inevitably damages some pelvic neuronal circuitry, which will thus impact on orgasmic responses, there is a paucity of data investigating the effect on robotic assisted radical prostatectomy on this. To our knowledge this study represents the largest analysis of orgasmic function in the robotic prostatectomy literature, and therefore would be of value to surgeons in counseling candidates for RALP about orgasmic outcomes. In our series, young men (age ≤60 years) and those who underwent bilateral nerve sparing approaches had a better recovery of their premorbid orgasmic function when compared to older men or men with no nerve sparing.

OBJECTIVE

• ? To investigate orgasmic outcomes in patients undergoing robotic‐assisted laparoscopic radical prostatectomy (RALP) and the effects of age and nerve sparing on these outcomes.

PATIENTS AND METHODS

• ? Between January 2005 and June 2007, 708 patients underwent RALP at our institution.
• ? We analysed postoperative potency and orgasmic outcomes in the 408 men, of the 708, who were potent, able to achieve orgasm preoperatively and available for follow‐up.

RESULTS

• ? Of men aged ≤60 years, 88.4% (198/224) were able to achieve orgasm postoperatively in comparison to 82.6% (152/184) of older men (P < 0.001).
• ? Of patients who received bilateral nerve sparing (BNS) during surgery, 273/301 (90.7%) were able to achieve orgasm postoperatively compared with 46/56 (82.1%) patients who received unilateral nerve sparing and 31/51 (60.8%) men who received non‐nerve‐sparing surgery (P < 0.001).
• ? In men ≤60 years who also underwent BNS, decreased sensation of orgasm was present in 3.2% of men, and postoperative orgasmic rates were significantly better than men ≤60 years who underwent unilateral or no nerve sparing (92.9% vs 83.3% vs 65.4%, respectively; P < 0.001).
• ? Potency rates were also significantly higher in men ≤60 years and in those who underwent BNS.

CONCLUSIONS

• ? Age and nerve sparing influence recovery of orgasm and erectile function after RALP.
• ? Men ≤60 years old and those who undergo BNS are most likely to maintain normal sexual function.

     

Quality of Care for Maternal and Newborn Health in Health Facilities in Nepal

Introduction

Nepal has pledged to substantially reduce maternal and newborn death by 2030. Improving quality of intrapartum health services will be vital to reduce these deaths. This paper examines quality of delivery and newborn services in health facilities of Nepal.

Methods

Data were sourced from the Nepal Health Facility Survey 2015, which covered a national representative sample of health facilities. The datasets were analysed to assess service readiness, availability and quality of delivery and newborn care in a sample of 992 health facilities.

Results

Of the 992 facilities in the sample, 623 provided delivery and newborn care services. Of the 623 facilities offering delivery and newborn care services, 13.3% offered comprehensive emergency obstetric care (CEmONC), 19.6% provided basic emergency obstetric care (BEmONC) and 53.9% provided basic delivery and newborn service. The availability of essential equipment for delivery and newborn care was more than 80% in health facilities. Except for the coverage of vitamin K injection, the coverage of immediate newborn care was more than 85% in all health facilities. The coverage of use of chlorhexidine ointment to all newborns was more than 70% in government hospitals and primary health care centers (PHCCs) and only 32.3% in private hospitals.

Conclusions

These findings show gaps in equipment and drugs, especially in PHCCs and private health facilities. Improving readiness and availability of equipment and drugs in PHCCs and private health facility will help improve the quality of care to further reduce maternal and newborn mortality in Nepal.

     

Stunting Among Under 5-Year-Olds in Nepal: Trends and Risk Factors

Maternal and Child Health Journal - Objectives Encouraging key parenting behaviors in early infancy may help decrease income-related developmental disparities. In this study we assessed whether a...     

National Trends and Outcomes in Dialysis-Requiring Acute Kidney Injury in Heart Failure: 2002–2013

Background

Dialysis-requiring acute kidney injury (D-AKI) is a serious complication in hospitalized heart failure (HF) patients. However, data on national trends are lacking after 2002.

Ablating Premature Ventricular Complexes: Justification,Techniques, and Outcomes

We reviewed the underlying principles that allow for safe and effective ablation for premature ventricular complexes. Clinical scenarios that necessitate consideration for ablation, the underlying anatomy, and the unique consideration to maximize energy delivery without compromising safety are sequentially examined.