Does the weight loss efficacy of alternate day fasting differ according to sex and menopausal status?

Background and aimsThis study examined if the weight loss and metabolic benefits of alternate day fasting (ADF) varies according to sex and menopausal status in adults with obesity.Methods and resultsThis secondary analysis pooled the data of men and women (n = 75) who participated in three 12-week ADF studies (500 kcal fast day; alternated with an ad libitum intake feast day). Body weight decreased in premenopausal women (?4.6 ± 3.2%), postmenopausal women (?6.5 ± 3.2%) and men (?6.2 ± 4.4%) (main effect of time, P < 0.001), with no difference between groups (no group × time interaction). Energy intake on fast days was higher than prescribed in all groups (～400–500 excess kcal consumed), with no differences between groups. Fat mass, lean mass, fasting insulin, and insulin resistance, and blood pressure decreased similarly in all groups (main effect of time, P < 0.05 for all comparisons). LDL cholesterol decreased more in postmenopausal versus premenopausal women (group × time interaction, P = 0.01). Fasting glucose, HDL cholesterol, and triglycerides remained unchanged in all groups.ConclusionThese findings suggest that the weight loss and metabolic benefits of ADF do not generally vary according to sex or menopausal status in adults with obesity.Trial registrationClinicaltrials.gov, NCT00960505; NCT03528317.     

The Buddy Benefit: Increasing the Effectiveness of an Employee-Targeted Weight-Loss Program

It is well known that significant others (particularly romantic partners) can influence people’s weight management efforts. However, what constitutes effective support—and from which type of individual (e.g., romantic partner, family member, friend)—is unclear. Thus, framed by confirmation theory, we assessed the effectiveness and types of communication of a weight-loss “buddy” through reports of 704 individuals enrolled in a 15-week synchronous online weight-loss program. Roughly 54% of participants chose buddies; and those who did lost more weight and waist inches than those who were involved in the program without buddy support. We also found that a combination of high accepting and high challenging messages from buddies was associated with the greatest decrease in body mass index (BMI) as well as the greatest reduction in waist size. Furthermore, the support by romantic partners paralleled support by other types of buddies. Having a supportive buddy who was not a romantic partner was just as effective as turning to a romantic partner for assistance. This study underscores the important role of a buddy in supporting weight-loss program involvement and encourages individuals to consider enlisting the help of a buddy, as opposed to losing weight alone, in order to maximize weight management effectiveness.     

Sperm methylome alterations following yoga-based lifestyle intervention in patients of primary male infertility: A pilot study

A majority of the cases of primary male infertility are idiopathic with the underlying molecular mechanisms contributing to the pathophysiology as yet unknown. Effects of the environment can alter the sperm epigenome thereby impacting male reproductive health. Epigenetic mechanisms are crucial to understanding health and disease, and methylome alterations are now known to have far-reaching clinical implications. Here, we report the results from our pilot study, a first of its kind analysis of the effect of the traditional practice of yoga on human sperm quality. We find marked improvement in sperm characteristics in patients of idiopathic male infertility following a supervised 21-day yoga regimen. Furthermore, next-generation sequencing-based methylome analysis reveals alterations in the sperm epigenome of these patients. We find that the practice of yoga is associated with DNA methylation changes at nearly 400 genes, 147 of which were hypermethylated while 229 were hypomethylated. These included promoters of several genes linked to maintenance of fertility and genomic integrity. This novel piece of work draws a direct link between positive lifestyle practices and male reproductive health.     

Retina Compatible Interactions and Effective Modulation of Blood Ocular Barrier P-gp Activity by Third-Generation Inhibitors Improve the Ocular Penetration of Loperamide

Effective drug delivery to the deeper ocular tissues remains an unresolved conundrum mainly due to the expression of multidrug resistance efflux proteins, besides tight junction proteins, in the blood ocular barriers (BOBs). Hence, the purpose of the current research was to investigate the ability of the third-generation efflux protein inhibitors, elacridar (EQ), and tariquidar (TQ), to diminish P-glycoprotein (P-gp) mediated efflux transport of loperamide (LOP), a P-gp substrate, across the BOB in Sprague Dawley rats. Initially, Western blot analysis confirmed the expression of P-gp in the iris-ciliary bodies and the retina choroid in the wild type rats. Next, the ocular distribution of LOP, in the presence and absence of EQ/TQ (at 2 doses), was evaluated. The significantly higher aqueous humor/plasma (D_AH) and vitreous humor (VH)/plasma (D_VH) distribution ratios of LOP in the rats pretreated with EQ or TQ demonstrated effective inhibition of P-gp activity in the BOB. Interestingly, the modulation of P-gp activity by EQ/TQ was more pronounced at the lower dose. The normal functioning and architecture of the retina, as indicated by electroretinography studies, confirmed the cytocompatibility of LOP and EQ/TQ interactions at the doses tested.     

Management of traumatic dacryocystitis and failed dacryocystorhinostomy using silicone lacrimal intubation set

The aim of this work is to study the management and success rate of traumatic dacryocystitis and failed dacryocystorhinostomy (DCR) using Silicone lacrimal intubation set. A prospective study was conducted at a tertiary eye care hospital, India from February 2006 to January 2008. This study material comprised 50 patients of traumatic dacryocystitis and failed dacryocystorhinostomy. Anterior single flap external dacryocystorhinostomy with Silicon intubation was performed in all the patients. The patients were followed up at weekly intervals for 1?month and thereafter every 2?months for 1?year post operatively. Criteria determining success were based on resolution of epiphora and patency on syringing. In traumatic dacryocystitis, 21(91.3%) cases fulfilled these criteria while 23(85.2%) cases of failed DCR were successful. The overall success rate (88%) was determined with an average follow-up of 1?year. Globally, the technique was effective in 85% of cases. The results were comparable with other similar studies. This study concludes that performing a DCR in traumatic dacryocystitis and failed DCR taking into consideration the complications and chances of failure is a challenge for the surgeon. We opine that External dacryocystorhinostomy with Silicon Intubation is one of the most effective modality in dealing with such cases.     

Estrogen receptor activation reduces lipid synthesis in pancreatic islets and prevents β cell failure in rodent models of type 2 diabetes

The failure of pancreatic β cells to adapt to an increasing demand for insulin is the major mechanism by which patients progress from insulin resistance to type 2 diabetes (T2D) and is thought to be related to dysfunctional lipid homeostasis within those cells. In multiple animal models of diabetes, females demonstrate relative protection from β cell failure. We previously found that the hormone 17β-estradiol (E2) in part mediates this benefit. Here, we show that treating male Zucker diabetic fatty (ZDF) rats with E2 suppressed synthesis and accumulation of fatty acids and glycerolipids in islets and protected against β cell failure. The antilipogenic actions of E2 were recapitulated by pharmacological activation of estrogen receptor α (ERα) or ERβ in a rat β cell line and in cultured ZDF rat, mouse, and human islets. Pancreas-specific null deletion of ERα in mice (PERα-/-) prevented reduction of lipid synthesis by E2 via a direct action in islets, and PERα-/- mice were predisposed to islet lipid accumulation and β cell dysfunction in response to feeding with a high-fat diet. ER activation inhibited β cell lipid synthesis by suppressing the expression (and activity) of fatty acid synthase via a nonclassical pathway dependent on activated Stat3. Accordingly, pancreas-specific deletion of Stat3 in mice curtailed ER-mediated suppression of lipid synthesis. These data suggest that extranuclear ERs may be promising therapeutic targets to prevent β cell failure in T2D.     

Escherichia coli uropathogenesis in vitro: invasion, cellular escape, and secondary infection analyzed in a human bladder cell infection model

Uropathogenic Escherichia coli (UPEC) strains are capable of invading bladder epithelial cells (BECs) on the bladder luminal surface. Based primarily on studies in mouse models, invasion is proposed to trigger an intracellular uropathogenic cascade involving intracellular bacterial proliferation followed by escape of elongated, filamentous bacteria from colonized BECs. UPEC filaments on the mouse bladder epithelium are able to revert to rod-shaped bacteria, which are believed to invade neighboring cells to initiate new rounds of intracellular colonization. So far, however, these late-stage infection events have not been replicated in vitro. We have established an in vitro model of human bladder cell infection by the use of a flow chamber (FC)-based culture system, which allows investigation of steps subsequent to initial invasion. Short-term bacterial colonization on the FC-BEC layer led to intracellular colonization. Exposing invaded BECs to a flow of urine, i.e., establishing conditions similar to those faced by UPEC reemerging on the bladder luminal surface, led to outgrowth of filamentous bacteria similar to what has been reported to occur in mice. These filaments were capable of reverting to rods that could invade other BECs. Hence, under growth conditions established to resemble those present in vivo, the elements of the proposed uropathogenic cascade were inducible in a human BEC model system. Here, we describe the model and show how these characteristics are reproduced in vitro.     

Plasma cathepsin L: A prognostic marker for pancreatic cancer

AIM: To assess the prognostic significance of cathepsin L, a cysteine protease that degrades the peri-tumoral tissue, in patients with pancreatic cancer.METHODS: Plasma samples from 127 pancreatic cancer patients were analyzed for cathepsin L levels by ELISA. Out of these patients, 25 underwent surgery and their paraffin-embedded tissue was analyzed for cathepsin L expression by immunohistochemistry. Survival of patients and clinicopathological parameters was correlated with cathepsin L expression in plasma and tissue using appropriate statistical analysis.RESULTS: The mean (± SD) cathepsin L in plasma samples of pancreatic cancer patients was 5.98 ± 2.5 ng/mL that was significantly higher compared to the levels in healthy controls (3.83 ± 0.45) or chronic pancreatitis patients (3.97 ± 1.06). Using ROC curve, a cut-off level of 5.0 ng/mL was decided for survival analysis. Elevated plasma levels of cathepsin L were found to be associated with poor prognosis (P = 0.01) in multivariate analysis. The plasma levels of the protease decreased after surgery. Though no significant correlation was seen between plasma and tissue expression of this protease, a trend did emerge that high cathepsin L expression in tissue correlated with its high levels in plasma.CONCLUSION: Cathepsin L levels in plasma of pancreatic cancer patients may be used as a potential prognostic marker for the disease.