Statistical study and investigation of the cut-resistant and thermo-physiological performance of protective gloves: a new prospective.

Objectives. This research investigated the performance properties of protective gloves alongside improvement in thermo-physiological comfort properties. Methods. Knitted gloves prepared from filament stainless steel, filament Kevlar, staple spun Kevlar and filament glass were used in the core, while 100% viscose rayon and 50/50% polyester/viscose rayon were used in the sheath. Gloves were tested for cut resistance, tear resistance, puncture resistance and abrasion resistance as the prime focus, and thermo-physiological comfort properties were also tested. In this research, a multi-response optimization technique, i.e., principal component analysis, was applied to identify the best yarn combination for gloves based on the aforementioned properties. Thermal images were also taken in constant ambient conditions for temperature distribution maps across the hand's surface. Results. All of the results were evaluated statistically with analysis of variance, and concluded that the effects of the core yarn on thermo-physiological properties were less significant. Conclusion. The results revealed that samples having dual-core yarn exhibited better in terms of overall properties. The sample having dual-core filament Kevlar and staple spun Kevlar ranked the best. In addition, developed samples exhibited better comfort properties than the control sample.

Architecture of androgen receptor pathways amplifying glucagon-like peptide-1 insulinotropic action in male pancreatic ß cells.

Male mice lacking the androgen receptor (AR) in pancreatic ß cells exhibit blunted glucose-stimulated insulin secretion (GSIS), leading to hyperglycemia. Testosterone activates an extranuclear AR in ß cells to amplify glucagon-like peptide-1 (GLP-1) insulinotropic action. Here, we examined the architecture of AR targets that regulate GLP-1 insulinotropic action in male ß cells. Testosterone cooperates with GLP-1 to enhance cAMP production at the plasma membrane and endosomes via: (1) increased mitochondrial production of CO2, activating the HCO3--sensitive soluble adenylate cyclase; and (2) increased Gαs recruitment to GLP-1 receptor and AR complexes, activating transmembrane adenylate cyclase. Additionally, testosterone enhances GSIS in human islets via a focal adhesion kinase/SRC/phosphatidylinositol 3-kinase/mammalian target of rapamycin complex 2 actin remodeling cascade. We describe the testosterone-stimulated AR interactome, transcriptome, proteome, and metabolome that contribute to these effects. This study identifies AR genomic and non-genomic actions that enhance GLP-1-stimulated insulin exocytosis in male ß cells.

Efficacy of glucagon-like peptide-1 and estrogen dual agonist in pancreatic islets protection and pre-clinical models of insulin-deficient diabetes.

We study the efficacy of a glucagon-like peptide-1 (GLP-1) and estrogen dual agonist (GLP1-E2) in pancreatic islet protection. GLP1-E2 provides superior protection from insulin-deficient diabetes induced by multiple low-dose streptozotocin (MLD-STZ-diabetes) and by the Akita mutation in mice than a GLP-1 monoagonist. GLP1-E2 does not protect from MLD-STZ-diabetes in estrogen receptor-α (ERα)-deficient mice and fails to prevent diabetes in Akita mice following GLP-1 receptor (GLP-1R) antagonism, demonstrating the requirement of GLP-1R and ERα for GLP1-E2 antidiabetic actions. In the MIN6 ß cell model, GLP1-E2 activates estrogen action following clathrin-dependent, GLP-1R-mediated internalization and lysosomal acidification. In cultured human islet, proteomic bioinformatic analysis reveals that GLP1-E2 amplifies the antiapoptotic pathways activated by monoagonists. However, in cultured mouse islets, GLP1-E2 provides antiapoptotic protection similar to monoagonists. Thus, GLP1-E2 promotes GLP-1 and E2 antiapoptotic signals in cultured islets, but in vivo, additional GLP1-E2 actions in non-islet cells expressing GLP-1R are instrumental to prevent diabetes.

Emerging diabetes therapies: Bringing back the ß-cells.

BACKGROUND: Stem cell therapies are finally coming of age as a viable alternative to pancreatic islet transplantation for the treatment of insulin-dependent diabetes. Several clinical trials using human embryonic stem cell (hESC)-derived ß-like cells are currently underway, with encouraging preliminary results. Remaining challenges notwithstanding, these strategies are widely expected to reduce our reliance on human isolated islets for transplantation procedures, making cell therapies available to millions of diabetic patients. At the same time, advances in our understanding of pancreatic cell plasticity and the molecular mechanisms behind ß-cell replication and regeneration have spawned a multitude of translational efforts aimed at inducing ß-cell replenishment in situ through pharmacological means, thus circumventing the need for transplantation. SCOPE OF REVIEW: We discuss here the current state of the art in hESC transplantation, as well as the parallel quest to discover agents capable of either preserving the residual mass of ß-cells or inducing their proliferation, transdifferentiation or differentiation from progenitor cells. MAJOR CONCLUSIONS: Stem cell-based replacement therapies in the mold of islet transplantation are already around the corner, but a permanent cure for type 1 diabetes will likely require the endogenous regeneration of ß-cells aided by interventions to restore the immune balance. The promise of current research avenues and a strong pipeline of clinical trials designed to tackle these challenges bode well for the realization of this goal.

NF-кB pathway genes expression in chicken erythrocytes infected with avian influenza virus subtype H9N2.

1. Chicken erythrocytes in blood vessels are the most abundant circulating cells, which participate in the host's immune responses. The transcription factor nuclear factor-kappa B (NF-κB) plays a vital role in the inflammatory response following viral infections. However, the expression of the NF-κB pathway, and other immune-related genes in chicken erythrocytes infected with low pathogenic avian influenza virus (LPAIV H9N2), has not been extensively studied.2. The following study determined the interaction of LPAIV H9N2 with chicken erythrocytes using indirect immunofluorescence microscopy. This was followed by investigating myeloid differentiation primary response 88 (MyD88), C-C motif chemokine ligand 5 (CCL5), melanoma differentiation-associated protein 5 (MDA5), the inhibitor of nuclear factor-kappa B kinase subunit epsilon (IKBKE), NF-κB inhibitor alpha (NFKBIA), NF-κB inhibitor epsilon (NFKBIE), interferon-alpha (IFN-α), colony-stimulating factor 3 (CSF3) and tumour necrosis factor receptor-associated factor 6 (TRAF6) by mRNA expression using quantitative real-time PCR (qRT-PCR) at four different time intervals (0, 2, 6 and 10 h).3. There was a significant interaction between erythrocytes and LPAIV H9N2 virus. Furthermore, the mRNA expression of the NF-κB pathway and other immune-related genes were significantly up-regulated at 2 h post-infection in infected chicken erythrocytes, except for TRAF6, which were significantly downregulated. While at 0 h post-infection, IFN-α and CSF3 were significantly upregulated, whereas NFKBIA was significantly downregulated. Further expression of MDA5, CCL5 and NFKBIA was upregulated, while TRAF6 was downregulated at 6 h post-infection. In infected erythrocytes, expression of MyD88, CCL5 and IKBKE was upregulated. However, IFN-α and TRAF6 were downregulated at 10 h post-infection.4. These results give initial evidence that the NF-κB pathway, and other genes related to immunity, in chicken erythrocytes may contribute to LPAIV subtype H9N2 and induce host immune responses.

Chylothorax caused by blunt chest trauma: a review of literature.

Chylothorax is the accumulation of chyle in the pleural cavity that typically contains a high concentration of triglycerides. Blunt chest trauma is a rare cause. The aim of this study is to review all of the reported cases of chylothorax caused by blunt chest trauma. Available databases were explored systematically for the condition and the eligible papers were included. The literature search revealed 30 studies with 39 cases, 72.3% of the cases were male, and 21.7% of the patients were female. The age range varied between 4 and 75 years with a mean age of 35.8 years. All of the patients were diagnosed after fluid sampling from the pleural fluid by thoracentesis and/or chest tube insertion. About 71.4% of the patients were treated successfully by conservative management: others (28.6%) were managed surgically. Although it is a rare condition, persistent milky drainage after blunt chest trauma should raise the suspicion of chylothorax. Pleural fluid sampling is the cornerstone of the diagnosis. In the majority of the cases, conservative treatment is quite enough. Surgery is indicated whenever non-operative measures failed.

Intracrine Testosterone Activation in Human Pancreatic ß-Cells Stimulates Insulin Secretion.

Testosterone (T) affects ß-cell function in men and women. T is a prohormone that undergoes intracrine conversion in target tissues to the potent androgen dihydrotestosterone (DHT) via the enzyme 5α-reductase (5α-R) or to the active estrogen 17ß-estradiol (E2) via the aromatase enzyme. Using male and female human pancreas sections, we show that the 5α-R type 1 isoform (SRD5A1) and aromatase are expressed in male and female ß-cells. We show that cultured male and female human islets exposed to T produce DHT and downstream metabolites. In these islets, exposure to the 5α-R inhibitors finasteride and dutasteride inhibited T conversion into DHT. We did not detect T conversion into E2 from female islets. However, we detected T conversion into E2 in islets from two out of four male donors. In these donors, exposure to the aromatase inhibitor anastrozole inhibited E2 production. Notably, in cultured male and female islets, T enhanced glucose-stimulated insulin secretion (GSIS). In these islets, exposure to 5α-R inhibitors or the aromatase inhibitor both inhibited T enhancement of GSIS. In conclusion, male and female human islets convert T into DHT and E2 via the intracrine activities of SRD5A1 and aromatase. This process is necessary for T enhancement of GSIS.

Montgomery in, Bolam out: are trainee surgeons 'material risks' when taking consent for cataract surgery?

Trainee involvement in cataract surgery is vital to allow proper training of the next generation of ophthalmic surgeons. However, recent changes in the UK Law, coupled with open publication of National Cataract Dataset results, lead us to conclude that the status of being a trainee is itself a material risk that now needs to be divulged to patients during the consent process. The opinions of current trainee surgeons in the UK were sampled via questionnaire and clinical negligence counsel was involved in the authorship of the paper in order to analyse the legal issues at stake. Attitudes towards consent regarding trainee involvement in UK cataract surgery need to change.

Primary drug resistance in extra-pulmonary tuberculosis: a hospital-based prospective study from Pakistan.

SETTING: Tertiary level specialised tuberculosis (TB) hospital.OBJECTIVE: To determine the prevalence of antimicrobial resistance in new extra-pulmonary tuberculosis (EPTB) cases.DESIGN: Prospective cross-sectional study. Presumptive EPTB patients with enlarged lymph nodes or pleural effusion having no history of TB treatment were enrolled. Specimens were tested for smear, Xpert® MTB/RIF and culture. Indirect drug susceptibility testing (DST) was performed using MGIT 960 and line-probe assays (LPA).RESULTS: Among 671 cases, 255 were bacteriologically confirmed and 185 DSTs were performed. Multidrug resistance (MDR-TB) was reported in 2.2% (95%CI 0.6-5.4), any resistance to rifampicin (RMP) in 2.7% (95%CI 0.9-6.2), isoniazid (INH) in 7.6% (95%CI 4.1-12.4), ethambutol in 1.1% (95%CI 0.1-3.9), pyrazinamide in 2.2% (95%CI 0.9-5.5) and fluoroquinolones (FQ) in 6.0% (95%CI 3.0-10.4). The sensitivity and specificity of LPA-DST was 100% and >98.8% respectively for RMP, INH and FQ. Among 82 cases with RMP of the results available for all three methods used, five were reported to be resistant on Xpert but all five were susceptible on MGIT 960 and four on MTBDRplus.CONCLUSION: Prevalence of RMP resistance in new EPTB cases is 2.7% (95%CI 0.9-6.2). Caution is warranted for RMP resistance detected using Xpert in EPTB samples with a very low bacterial load.

First chikungunya outbreak in Pakistan: a trail of viral attacks.

Despite explicit warning from the National Institute of Health, Pakistan experienced its first chikungunya outbreak in the metropolis of Karachi. We underscore the attention of health authorities and healthcare professionals towards contributing factors associated with this outbreak and the measures required to combat this viral disease.

Evaluation of nephroprotective activity of Musa paradisiaca L. in gentamicin-induced nephrotoxicity.

The objective of the study was to investigate the nephroprotective activity of methanolic extract of different morphological parts (bract, flower, trachea and tracheal fluid) of Musa paradisiaca L. (Family: Musaceae) against gentamicin-induced nephrotoxicity in mice. Gentamicin produced significant changes in biochemical (increased levels of blood urea nitrogen level, blood urea, and serum creatinine), and histological parameters in mice. Treatment with methanolic extract of bract (100 and 250mg/kg, b.w) and flowering stalk (trachea) (250 and 500mg/kg, b.w) significantly prevented biochemical and histological changes produced by gentamicin toxicity. The extracts of M. paradisiaca (bract and flowering stalk) could contribute a lead to discovery of a new drug for the treatment of drug-induced nephrotoxicity.

Signaling lansdscape of prostate cancer.

Research over the decades has gradually and sequentially shown that both intratumor heterogeneity and multifocality make prostate cancer difficult to target. Different challenges associated with generation of risk-stratification tools that correlate genomic landscape with clinical outcomes severely influence clinical efficacy of therapeutic strategies. Androgen receptor mediated signaling has gained great appreciation and rewiring of AR induced signaling cascade in absence of androgen, structural variants of AR have provided near complete resolution of genomic landscape and underlying mechanisms of prostate cancer. In this review we have attempted to provide an overview of most recent advancements in our knowledge related to different signaling cascades including TGF, SHH, Notch, JAK-STAT in prostate cancer progression and development.

Development and Validation of New HPLC Method for Simultaneous Estimation of L-Lysine Hydrochloride and L-Carnitine-L-Tartrate in Pharmaceutical Dosage Form.

A new analytical method is developed and validates for simultaneous estimation of L-lysine hydrochloride and L-carnitine-L-tartrate in single pharmaceutical dosage form by means of high resolution HPLC. The chromatographic procedure was carried out using C18-5 µm (4.6 mm × 250 mm), column. Optimally suited mobile phase was made to run in an isocratic elution mode whose composition was 10 mM of potassium dihydrogen phosphate adjusted with triethylamine to a pH of 7.5 and pumped at a flow rate of 0.50 ml/min through chromatographic system. The detector's wavelength was 214 nm. The accuracy of the analytical method was determined keeping into account the recovery of analytes, which in this case remains well within the accepted standards that is 95-105%. Detection limit for L-lysine hydrochloride and L-carnitine-L-tartrate are 1.47 µg/ml and 0.85 µg/ml while quantitation limit for L-lysine hydrochloride and L-carnitine-L-tartrate is 4.41 and 2.55 µg/ml, respectively. All the statistical results were validated performing precision, accuracy, linearity, specificity studies for analytes concentration from 70-130%. The outcome of results confirmed that the method was in consonance with the acceptance criteria.

Stability-indicating High-performance Liquid Chromatography Method for Simultaneous Determination of Aminophylline and Chlorpheniramine Maleate in Pharmaceutical Formulations.

The present work deals with the development and validation of method for simultaneous determination of antihistaminic drugs in pharmaceutical formulations. A precise, specific and accurate reverse phase-high-performance liquid chromatography method for the simultaneous measurement of aminophylline and chlorpheniramine maleate was developed. The separation of drugs was achieved on C-18 (5 µm, 250×4.6 mm) high-performance liquid chromatography column. The runtime for analysis was 10 min. Mobile phase is mixture containing dilute H2SO4:methanol (60:40% v/v) with flow rate adjusted at 1.5 ml/min. The detection of components was performed at a wavelength of 264 nm. Retention times of aminophylline and chlorphinramine maleate were found to be 2.00 and 3.25 min, respectively. Linearity was found in the range of 16-24 µg/ml for chlorpheniramine maleate and 102.4-153.6 µg/ml for aminophylline with a correlation coefficient of 0.9998 and 0.9996, respectively. High peak purity index of 99.99% indicated the complete separation of analytes in the presence of degradation products is justification of method stability. Linearity, accuracy, specificity, precision and robustness studies were performed for method validation.

Risk for oral cancer from smokeless tobacco.

Tobacco products which are used in a way other than smoking are known as smokeless tobacco. The most common smokeless tobaccos are chewing tobacco, naswar, snuff, snus, gutka, and topical tobacco paste. Any product which contains tobacco is not safe for human health. There are more than twenty-five compounds in smokeless tobacco which have cancer causing activity. Use of smokeless tobacco has been linked with risk of oral cancer. Smokeless tobacco contains tobacco-specific nitrosamines (TSNAs), polonium, formaldehyde, cadmium, lead, and benzo[a]pyrene, which are carcinogenic agents. Although there is presence of some compounds, carotenoids and phenolic compounds, that have cancer inhibiting properties, they are in low concentrations. Dry snuff use is linked with higher relative risks, while the use of other smokeless tobacco is of intermediate risk. Moist snuff and chewing tobacco have a very low risk for oral cancer. Therefore, from this review article, it was concluded that smokeless tobacco has risk for oral cancer - either low, medium or high depending on the balance between cancer causing agents and cancer inhibiting agents.

Zinc: Role in the management of diarrhea and cholera.

Diarrhea and cholera are major health problems. Vibrio cholera, the causative agent of cholera, infects the small intestine, resulting in vomiting, massive watery diarrhea and dehydration. Reduced water and electrolyte absorption is also due to zinc deficiency. Zinc has an important role in recovery from the disease. The combination of zinc with cholera vaccine and oral rehydration solutions has a positive impact on cholera and diarrhea. It has led to a decrease in the mortality and morbidity associated with diarrhea.

Comparative pharmacokinetics of levofloxacin in healthy volunteers and in patients suffering from typhoid Fever.

The aim of this study was to characterize the effect of typhoid fever on pharmacokinetic parameters of levofloxacin (LF) and compare the pharmacokinetic parameters of the said antibiotic in healthy human volunteers and patients with typhoid fever. Total of 12 subjects were divided into two groups "A" (healthy volunteers) and "B" (typhoid patients). Single oral dose of LF 500 mg was given and 5 mL of blood was collected from each subject at 0, 0.25, 0.5, 1, 2, 3, 6, 12, 24, 36 and 72 h. Plasma concentrations of LF were measured by HPLC. Pharmacokinetic parameters were calculated from plasma concentration-time data by using MW/PHARM pharmacological analysis. In healthy volunteers, the average pharmacokinetic parameters were as Cmax (6.79 µg/mL), Tmax (1.84 h), T(½) (10.03 h), Ka (2.23 h(-1)), AUC (110.09 µgh/mL), Vd (85.84 L), Cl (4.57 L/h) and in typhoid patients were Cmax (6.90 µg/mL), Tmax (1.82 h), T(½) (9.42 h), Ka (2.21 h(-1)), AUC (105.55 µgh/mL), Vd (64.31 L), Cl (4.75 L/h). The difference between pharmacokinetic parameters of LF in healthy human volunteers and typhoid patients was calculated by using unpaired t-test. As the p-value in case of all pharmacokinetic parameters was more than 0.05, the difference between pharmacokinetic parameters in both healthy human volunteers and typhoid patients was insignificant. It is concluded that there is no need to adjust the dose of LF in typhoid patients.

Spasmolytic, bronchodilator and vasorelaxant activity of methanolic extract of Tephrosia purpurea.

The methanolic extract of the whole plant of Tephrosia pupurea, Linn. was subjected to find out its possible therapeutic utility to validate its folkloric use in native systems of medicine. The extract on application to spontaneous contractions in isolated rabbit jejunum preparations exerted a concentration dependent (0.003-3.0 mg/mL) relaxant effect. The extract also caused concentration dependent relaxation of K+(80 mM)-induced spastic contractions. These findings were further supported by the observations that the extract caused a concentration dependent right ward shift of the Ca2+ response curves in manner similar to that of verapamil. The extract exhibited a relaxant effect on carbachol and high K+ (80 mM)-induced contractions of isolated rabbit tracheal preparations in a manner similar to verapamil. The observed non-specific bronchodilator response is possibly mediated through Ca2+ channel blockade. Moreover, the extract also exhibited a dose dependent relaxant effect on phenylephrine (1 microM) and K+(80 mM)-induced contractions in a manner similar to verapamil. On the basis of the above-mentioned findings, it can be concluded that the use of Tephrosia purpurea, in gastrointestinal spasm, asthma and hypertension is likely to be mediated through calcium channel blockage.