Pulse Shape Analysis Studies in Si(Li) Detector

This work presents developments in the nuclear radiation detection, which take advantage of fast digital electronics. Numerical algorithms, which analyze detector pulse shape, were tested. A method to discriminate between electrons and gamma radiation using pulse shape analysis was demonstrated. The analysis was done on the data taken with 207Bi source using a semiconductor Si(Li) detector. An algorithm to improve the timing resolution of the detection system was implemented. Software code to simulate the pulse shape generation process, for electrons and gamma radiation, in a Si(Li) detector was developed. Advantages of the applications of digital electronics in nuclear spectroscopy are discussed

Emergency peripartum hysterectomy: a 7-year review at tertiary hospital

Emergency peripartum hysterectomy (EPH) is a major obstetric procedure, usually performed as a life-saving measure in cases of intractable obstetric hemorrhage. The aim of this study was to determine the incidence, indications and the risk factors and complications of emergency peripartum hysterectomy (EPH). The medical records of 13 patients who had undergone EPH, between January 2012 and December 2018, were reviewed retrospectively. All necessary data was obtained by record review. The mean age of pregnant women was 30 year. There were 13 EPHs out of 15768 deliveries, a rate of 0.82 per 1,000 deliveries. Out of 13 women who underwent EPHs, 8 hysterectomies were performed after cesarean delivery and 5 after vaginal delivery. The most common indication for hysterectomy was abnormal placentation (7/13), followed by atony (4/13), rupture of scared uterus (1/13) and rupture of unscared uterus (1/13). There were two cases of intra-operative bladder injury, we had 1/13 maternal death because of EPH. There were no cases of neonatal mortality. In our series, abnormal placentation was the most common of indication for EPH. The risk factors for EPH were previous CS for abnormal placentation and placental abruption for uterine atony and peripartum hemorrhage. Limiting the number of CS deliveries would bring a significant impact on decreasing the risk of EPH

Design and Evaluation of a Novel Gas Formation-Based Multiple-Unit Gastro-Retentive Floating Drug Delivery System for Quetiapine Fumarate

Purpose: To develop a gastro-retentive formulation of quetiapine fumarate in the form of floating minitablets.Methods: The system consisted of core units prepared by direct  compression process, which were coated with three successive layers, namely, an inner seal coat, effervescent layer and an outer polymeric layer of polymethacrylates.Results: Mini-tablets coated with Eudragit RS 30D (5, 7.5 and 10%)  released . 85% of the drug after 12 h, while those coated with Eudragit RL 30D (5, 7.5 and 10%) released . 85% drug within the same period. Drug release kinetic studies showed that drug diffusion fitted best to zero order and Higuchi models, indicating that drug release was anomalous  non-Fickian transport. In vivo gastric residence time results indicate that the units remained in the stomach for about 6 h (n = 3). There was nosignificant change in dissolution profiles before and after storage at 40‹C and 75% RH for 6 months.Conclusion: The developed floating mini-tablets of quetiapine fumarate exhibit prolonged release for .12 h, and thus may improve bioavailability and minimize fluctuations in plasma drug concentrations. Keywords: Mini-tablets; Floating delivery system; Effervescence, Polymeric membrane, Controlled release, Quetiapine fumarat

Necrotic debris and STING exert therapeutically relevant effects on tumor cholesterol homeostasis.

Malignant tumors commonly display necrosis, which invariably triggers an inflammatory response that supports tumor growth. However, the effect on tumor cells of necrotic debris, or damage-associated molecular patterns (DAMPs) released by dying cells is unknown. Here, we addressed the effect of DAMPs on primary Ewing sarcoma (EwS) cells and cell lines grown in 3D (spheroids) and 2D culture. We show that DAMPs promote the growth of EwS spheroids but not 2D cultures and that the underlying mechanism implicates an increase in cholesterol load in spheroids. In contrast, stimulation of the nucleic acid sensor signaling platform STING by its ligand cyclic GMP-AMP decreases the tumor cell cholesterol load and reduces their tumor initiating ability. Overexpression of STING or stimulation with cyclic GMP-AMP opposes the growth stimulatory effect of DAMPs and synergizes with the cholesterol synthesis inhibitor simvastatin to inhibit tumor growth. Our observations show that modulation of cholesterol homeostasis is a major effect of necrotic cell debris and STING and suggest that combining STING agonists with statins may help control tumor growth

Fabrication and in vitro evaluation of subgingival strips of calcium alginate for controlled delivery of ofloxacin and metronidazole

Objetivos: Elaborar y evaluar tiras subgingivales combinadas compuestas por Ofloxacino y metronidazol in vitro con alginato de calcio biodegradable.Métodos: las tiras se prepararon utilizando el método de evaporación del disolvente. Se usó una concentración del 10% de CaCl2 para la gelificación.de las tiras.Resultados: el grosor de las tiras se encuentra dentro de las recomendaciones (>320 μm). In vitro, la liberación de la droga siguió una cinética bifásica que fue suficiente para alcanzar la CMI e inhibir el crecimiento de microorganismos durante 5 días. La “tasa de liberación de la droga” es inversamente proporcional a la concentración de polímero de la formulación. La liberación de la “droga” fue por difusión y en segunda fase por disolución.Discusión: Las preparaciones OM1 y OM2 que contienen un 90 y un 75% de polímero respectivamente, podrían ser empleadas en liberación controlada durante cinco días en infecciones sublinguales. Siendo el alginato cálcico biodegradable una buena elección como polímero retardanteAim: Subgingival strips of combined ofloxacin (OFX) and metronidazole (MET) were fabricated and evaluated in vitro using biodegradable calcium alginate.Methods: Strips of drug:polymer (10:90, 25:75, 50:50 and 75:25) were prepared using solvent casting method. A 10%w/v CaCl2 solution was used for gelation of the strips.Results: The thickness of strips were at par of recommended thickness (<320 μm). In vitro release of drugs followed a biphasic kinetics which was sufficient to maintain the minimum inhibitory concentrations (MIC) to inhibit the growth of the microorganisms for 5 days. The rate of drug release was inversely proportional to polymer concentration in the formulations. The drug release was by diffusion in second phase of dissolution.Conclusions: The formulations OM1 and OM2 which contain 90 and 75%w/w of polymer could be employed for controlled delivery of combined OFX and MET for 5 days in subgingival infections. Calcium alginate, being a biodegradable is a good choice as drug retarding polymer

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

Male mice lacking the androgen receptor (AR) in pancreatic β cells exhibit blunted glucose-stimulated insulin secretion (GSIS), leading to hyperglycemia. Testosterone activates an extranuclear AR in β 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 β 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 β cells

Computerised interpretation of fetal heart rate during labour (INFANT): a randomised controlled trial

Background. Continuous electronic fetal heart-rate monitoring is widely used during labour, and computerised interpretation could increase its usefulness. We aimed to establish whether the addition of decision-support software to assist in the interpretation of cardiotocographs affected the number of poor neonatal outcomes. Methods. In this unmasked randomised controlled trial, we recruited women in labour aged 16 years or older having continuous electronic fetal monitoring, with a singleton or twin pregnancy, and at 35 weeks’ gestation or more at 24 maternity units in the UK and Ireland. They were randomly assigned (1:1) to decision support with the INFANT system or no decision support via a computer-generated stratified block randomisation schedule. The primary outcomes were poor neonatal outcome (intrapartum stillbirth or early neonatal death excluding lethal congenital anomalies, or neonatal encephalopathy, admission to the neonatal unit within 24 h for ≥48 h with evidence of feeding difficulties, respiratory illness, or encephalopathy with evidence of compromise at birth), and developmental assessment at age 2 years in a subset of surviving children. Analyses were done by intention to treat. This trial is completed and is registered with the ISRCTN Registry, number 98680152. Findings. Between Jan 6, 2010, and Aug 31, 2013, 47062 women were randomly assigned (23515 in the decision-support group and 23547 in the no-decision-support group) and 46042 were analysed (22987 in the decision-support group and 23055 in the no-decision-support group). We noted no difference in the incidence of poor neonatal outcome between the groups—172 (0·7%) babies in the decision-support group compared with 171 (0·7%) babies in the no-decision-support group (adjusted risk ratio 1·01, 95% CI 0·82–1·25). At 2 years, no significant differences were noted in terms of developmental assessment. Interpretation. Use of computerised interpretation of cardiotocographs in women who have continuous electronic fetal monitoring in labour does not improve clinical outcomes for mothers or babies

Role of Neural NO Synthase (nNOS) Uncoupling in the Dysfunctional Nitrergic Vasorelaxation of Penile Arteries from Insulin-Resistant Obese Zucker Rats

Objective: Erectile dysfunction (ED) is considered as an early sign of vascular disease due to its high prevalence in patients with cardiovascular risk factors. Endothelial and neural dysfunction involving nitric oxide (NO) are usually implicated in the pathophysiology of the diabetic ED, but the underlying mechanisms are unclear. The present study assessed the role of oxidative stress in the dysfunctional neural vasodilator responses of penile arteries in the obese Zucker rat (OZR), an experimental model of metabolic syndrome/prediabetes. Methods and Results: Electrical field stimulation (EFS) under non-adrenergic non-cholinergic (NANC) conditions evoked relaxations that were significantly reduced in penile arteries of OZR compared with those of lean Zucker rats (LZR). Blockade of NO synthase (NOS) inhibited neural relaxations in both LZR and OZR, while saturating concentrations of the NOS substrate L-arginine reversed the inhibition and restored relaxations in OZR to levels in arteries from LZR. nNOS expression was unchanged in arteries from OZR compared to LZR and nNOS selective inhibition decreased the EFS relaxations in LZR but not in OZR, while endothelium removal did not alter these responses in either strain. Superoxide anion production and nitro-tyrosine immunostaining were elevated in the erectile tissue from OZR. Treatment with the NADPH oxidase inhibitor apocynin or acute incubation with the NOS cofactor tetrahydrobiopterin (BH4) restored neural relaxations in OZR to levels in control arteries, while inhibition of the enzyme of BH4 synthesis GTP-cyclohydrolase (GCH) reduced neural relaxations i

Architecture of Androgen Receptor Pathways Amplifying Glucagon-Like Peptide-1 Insulinotropic Action in Male Pancreatic β Cells

Male mice lacking the androgen receptor (AR) in pancreatic β cells exhibit blunted glucose-stimulated insulin secretion (GSIS), leading to hyperglycemia. Testosterone activates an extranuclear AR in β 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 β cells. Testosterone cooperates with GLP-1 to enhance cAMP production at the plasma membrane and endosomes via: (1) increased mitochondrial production of C