Peri-adolescent drinking of ethanol and/or nicotine modulates astroglial glutamate transporters and metabotropic glutamate receptor-1 in female alcohol-preferring rats

Impairment in glutamate neurotransmission mediates the development of dependence upon nicotine (NIC) and ethanol (EtOH). Previous work indicates that continuous access to EtOH or phasic exposure to NIC reduces expression of the glutamate transporter-1 (GLT-1) and cystine/glutamate antiporter (xCT) but not the glutamate/aspartate transporter (GLAST). Additionally, metabotropic glutamate receptors (mGluRs) expression was affected following exposure to EtOH or NIC. However, little is known about the effects of EtOH and NIC co-consumption on GLT-1, xCT, GLAST, and mGluR1 expression. In this study, peri-adolescent female alcohol preferring (P) rats were given binge-like access to water, sucrose (SUC), SUC-NIC, EtOH, or EtOH-NIC for four weeks. The present study determined the effects of these reinforcers on GLT-1, xCT, GLAST, and mGluR1 expression in the nucleus accumbens (NAc), hippocampus (HIP) and prefrontal cortex (PFC). GLT-1 and xCT expression were decreased in the NAc following both SUC-NIC and EtOH-NIC. In addition, only xCT expression was downregulated in the HIP in both of these latter groups. Also, glutathione peroxidase (GPx) activity in the HIP was reduced following SUC, SUC-NIC, EtOH, and EtOH-NIC consumption. Similar to previous work, GLAST expression was not altered in any brain region by any of the reinforcers. However, mGluR1 expression was increased in the NAc in the SUC-NIC, EtOH, and EtOH-NIC groups. These results indicate that peri-adolescent binge-like drinking of EtOH or SUC with or without NIC may exert differential effects on astroglial glutamate transporters and receptors. Our data further parallel some of the previous findings observed in adult rats

Automatic alignment of surgical videos using kinematic data

Over the past one hundred years, the classic teaching methodology of "see one, do one, teach one" has governed the surgical education systems worldwide. With the advent of Operation Room 2.0, recording video, kinematic and many other types of data during the surgery became an easy task, thus allowing artificial intelligence systems to be deployed and used in surgical and medical practice. Recently, surgical videos has been shown to provide a structure for peer coaching enabling novice trainees to learn from experienced surgeons by replaying those videos. However, the high inter-operator variability in surgical gesture duration and execution renders learning from comparing novice to expert surgical videos a very difficult task. In this paper, we propose a novel technique to align multiple videos based on the alignment of their corresponding kinematic multivariate time series data. By leveraging the Dynamic Time Warping measure, our algorithm synchronizes a set of videos in order to show the same gesture being performed at different speed. We believe that the proposed approach is a valuable addition to the existing learning tools for surgery.Comment: Accepted at AIME 201

Time trends of cigarette and waterpipe smoking among a cohort of school children in Irbid, Jordan, 2008–11

Background: Coordinated high-impact interventions and community-level changes in smoking behaviour norms effectively reduced prevalence of smoking among youth in many developed countries. Smoking trends among Jordanian adolescents are likely different than their Western counterparts and must be understood in the context of their daily lives to tailor interventions specifically for adolescents in this setting. Methods: Between 2008 and 2011, a school-based longitudinal study was conducted in Irbid, Jordan. All seventh-grade students in 19 randomly selected schools (of 60) were surveyed annually for 4 years. Outcomes of interest were time trends in smoking behaviour, age at initiation and change in frequency of smoking. Results: Among 1781 participants, baseline prevalence of current smoking (cigarettes or waterpipe) for boys was 22.9% and 8.7% for girls. Prevalence of ever-smoking and current any smoking, cigarette smoking, waterpipe smoking and dual cigarette/waterpipe smoking was significantly higher in boys than girls each year (P \u3c 0.001). Smoking prevalence increased every year after year 2 for current smoking (P \u3c 0.05) across all methods (any, cigarette, waterpipe and dual). At all time points for both boys and girls, prevalence of waterpipe smoking was higher than that of cigarette smoking (P \u3c 0.001). Conclusion: This study shows intensive smoking patterns at early ages among Jordanian youth in Irbid, characterized by a predominance of waterpipe smoking and steeper age-related increase in cigarette smoking. It also points to the possibility of waterpipe being the favourite method for introducing youth to tobacco, as well as being a vehicle for tobacco dependence and cigarette smoking

The initial pharmaceutical development of an artesunate/amodiaquine oral formulation for the treatment of malaria: a public-private partnership

<p>Abstract</p> <p>Background</p> <p>Artemisinin-based combination therapy is currently recommended worldwide for the treatment of uncomplicated malaria. Fixed-dose combinations are preferred as they favour compliance. This paper reports on the initial phases of the pharmaceutical development of an artesunate-amodiaquine (ASAQ) bilayer co-formulation tablet, undertaken following pre-formulation studies by a network of scientists and industrials from institutions of both industrialized and low income countries.</p> <p>Methods</p> <p>Pharmaceutical development was performed by a research laboratory at the University Bordeaux Segalen, School of Pharmacy, for feasibility and early stability studies of various drug formulations, further transferred to a company specialized in pharmaceutical development, and then provided to another company for clinical batch manufacturing. The work was conducted by a regional public-private not-for-profit network (TropiVal) within a larger Public Private partnership (the FACT project), set up by WHO/TDR, Médecins Sans Frontières and the Drugs for Neglected Disease initiative (DND<it>i</it>).</p> <p>Results</p> <p>The main pharmaceutical goal was to combine in a solid oral form two incompatible active principles while preventing artesunate degradation under tropical conditions. Several options were attempted and failed to provide satisfactory stability results: incorporating artesunate in the external phase of the tablets, adding a pH regulator, alcoholic wet granulation, dry granulation, addition of an hydrophobic agent, tablet manufacturing in controlled conditions. However, long-term stability could be achieved, in experimental batches under GMP conditions, by physical separation of artesunate and amodiaquine in a bilayer co-formulation tablet in alu-alu blisters. Conduction of the workplan was monitored by DND<it>i</it>.</p> <p>Conclusions</p> <p>Collaborations between research and industrial groups greatly accelerated the process of development of the bi-layered ASAQ tablet. Lack of public funding was the main obstacle hampering the development process, and no intellectual property right was claimed. This approach resulted in a rapid technology transfer to the drug company Sanofi-Aventis, finalizing the process of development, registration and WHO pre-qualification of the fixed-dose co-formulation together with DND<it>i</it>. The bi-layered tablet is made available under the names of Coarsucam^®and Artesunate amodiaquine Winthrop^®, Sanofi-Aventis. The issue related to the difficulty of public institutions to valorise their participation in such initiative by lack of priority and funding of applied research is discussed.</p

Baseline characteristics and treatment pattern of type 2 diabetes patients in Jordan: analysis from the DISCOVER patient population

Introduction: Jordan has limited published data on T2DM and its treatment patterns. This analysis of the DISCOVER study, focusing on Jordan, is aimed at describing the characteristics of patients and treatment patterns according to the real-world setting in T2DM patients initiating a second-line antidiabetic treatment Methods: The DISCOVER study is an ongoing, multi-country, multicenter, observational, prospective, and longitudinal cohort study. The baseline data of patients’ characteristics, clinical and laboratory variables, micro- and macro-complications, and treatment choices were captured on a standardized case report form. Results: Two hundred and seventy-one patients were enrolled from 13 different clinical sites in Jordan. Sixty percent of the patients were male. The participants overall mean age was 53.8 ± 11.3 years with a mean BMI 30.8 ± 5.0 kg/m 2. The mean duration of T2DM was almost 6 years and the mean documented HbA1c and fasting plasma glucose were e 8.4% ± 1.6 and 180.9 ± 63.7 mg/dL, respectively, at the initiation of second-line antidiabetic treatment. Almost 25% of the participants were reported to be either current smokers or ex-smokers. More than 40% of patients had comorbidities such as hypertension or dyslipidemia. Diabetes related microvascular and macrovascular complications were documented in 10.3% and 12.5% of patients, respectively. Metformin (MET) alone was used as a first-line therapy in almost one-half of the patients and in combination with sulfonylurea (SU) in approximately one-third of the patients. The most commonly used second-line therapy was the combination of MET and dipeptidyl peptidase-4 inhibitors (DPP-4i) with 29.9% followed by the triple therapy of MET, SU, and DPP-4i with 28%. Conclusion: A substantial number of patients were young with uncontrolled diabetes and at high risk for micro- and macrovascular complications. Therefore, a comprehensive management with early treatment intensification and risk factors modifications are required to achieve target goals

Ampicillin/Sulbactam Treatment Modulates NMDA Receptor NR2B Subunit and Attenuates Neuroinflammation and Alcohol Intake in Male High Alcohol Drinking Rats

Exposure to ethanol commonly manifests neuroinflammation. Beta (β)-lactam antibiotics attenuate ethanol drinking through upregulation of astroglial glutamate transporters, especially glutamate transporter-1 (GLT-1), in the mesocorticolimbic brain regions, including the nucleus accumbens (Acb). However, the effect of β-lactam antibiotics on neuroinflammation in animals chronically exposed to ethanol has not been fully investigated. In this study, we evaluated the effects of ampicillin/sulbactam (AMP/SUL, 100 and 200 mg/kg, i.p.) on ethanol consumption in high alcohol drinking (HAD1) rats. Additionally, we investigated the effects of AMP/SUL on GLT-1 and N-methyl-d-aspartate (NMDA) receptor subtypes (NR2A and NR2B) in the Acb core (AcbCo) and Acb shell (AcbSh). We found that AMP/SUL at both doses attenuated ethanol consumption and restored ethanol-decreased GLT-1 and NR2B expression in the AcbSh and AcbCo, respectively. Moreover, AMP/SUL (200 mg/kg, i.p.) reduced ethanol-increased high mobility group box 1 (HMGB1) and receptor for advanced glycation end-products (RAGE) expression in the AcbSh. Moreover, both doses of AMP/SUL attenuated ethanol-elevated tumor necrosis factor-alpha (TNF-α) in the AcbSh. Our results suggest that AMP/SUL attenuates ethanol drinking and modulates NMDA receptor NR2B subunits and HMGB1-associated pathways

Bile-acid-mediated decrease in endoplasmic reticulum stress: a potential contributor to the metabolic benefits of ileal interposition surgery in UCD-T2DM rats

Post-operative increases in circulating bile acids have been suggested to contribute to the metabolic benefits of bariatric surgery; however, their mechanistic contributions remain undefined. We have previously reported that ileal interposition (IT) surgery delays the onset of type 2 diabetes in UCD-T2DM rats and increases circulating bile acids, independently of effects on energy intake or body weight. Therefore, we investigated potential mechanisms by which post-operative increases in circulating bile acids improve glucose homeostasis after IT surgery. IT, sham or no surgery was performed on 2-month-old weight-matched male UCD-T2DM rats. Animals underwent an oral fat tolerance test (OFTT) and serial oral glucose tolerance tests (OGTT). Tissues were collected at 1.5 and 4.5 months after surgery. Cell culture models were used to investigate interactions between bile acids and ER stress. IT-operated animals exhibited marked improvements in glucose and lipid metabolism, with concurrent increases in postprandial glucagon-like peptide-1 (GLP-1) secretion during the OFTT and OGTTs, independently of food intake and body weight. Measurement of circulating bile acid profiles revealed increases in circulating total bile acids in IT-operated animals, with a preferential increase in circulating cholic acid concentrations. Gut microbial populations were assessed as potential contributors to the increases in circulating bile acid concentrations, which revealed proportional increases in Gammaproteobacteria in IT-operated animals. Furthermore, IT surgery decreased all three sub-arms of ER stress signaling in liver, adipose and pancreas tissues. Amelioration of ER stress coincided with improved insulin signaling and preservation of β-cell mass in IT-operated animals. Incubation of hepatocyte, adipocyte and β-cell lines with cholic acid decreased ER stress. These results suggest that postoperative increases in circulating cholic acid concentration contribute to improvements in glucose homeostasis after IT surgery by ameliorating ER stress

Bile-acid-mediated decrease in endoplasmic reticulum stress: a potential contributor to the metabolic benefits of ileal interposition surgery in UCD-T2DM rats

Post-operative increases in circulating bile acids have been suggested to contribute to the metabolic benefits of bariatric surgery; however, their mechanistic contributions remain undefined. We have previously reported that ileal interposition (IT) surgery delays the onset of type 2 diabetes in UCD-T2DM rats and increases circulating bile acids, independently of effects on energy intake or body weight. Therefore, we investigated potential mechanisms by which post-operative increases in circulating bile acids improve glucose homeostasis after IT surgery. IT, sham or no surgery was performed on 2-month-old weight-matched male UCD-T2DM rats. Animals underwent an oral fat tolerance test (OFTT) and serial oral glucose tolerance tests (OGTT). Tissues were collected at 1.5 and 4.5 months after surgery. Cell culture models were used to investigate interactions between bile acids and ER stress. IT-operated animals exhibited marked improvements in glucose and lipid metabolism, with concurrent increases in postprandial glucagon-like peptide-1 (GLP-1) secretion during the OFTT and OGTTs, independently of food intake and body weight. Measurement of circulating bile acid profiles revealed increases in circulating total bile acids in IT-operated animals, with a preferential increase in circulating cholic acid concentrations. Gut microbial populations were assessed as potential contributors to the increases in circulating bile acid concentrations, which revealed proportional increases in Gammaproteobacteria in IT-operated animals. Furthermore, IT surgery decreased all three sub-arms of ER stress signaling in liver, adipose and pancreas tissues. Amelioration of ER stress coincided with improved insulin signaling and preservation of β-cell mass in IT-operated animals. Incubation of hepatocyte, adipocyte and β-cell lines with cholic acid decreased ER stress. These results suggest that postoperative increases in circulating cholic acid concentration contribute to improvements in glucose homeostasis after IT surgery by ameliorating ER stress

A Comparison of Machine Learning Methods for Cross-Domain Few-Shot Learning

We present an empirical evaluation of machine learning algorithms in cross-domain few-shot learning based on a fixed pre-trained feature extractor. Experiments were performed in five target domains (CropDisease, EuroSAT, Food101, ISIC and ChestX) and using two feature extractors: a ResNet10 model trained on a subset of ImageNet known as miniImageNet and a ResNet152 model trained on the ILSVRC 2012 subset of ImageNet. Commonly used machine learning algorithms including logistic regression, support vector machines, random forests, nearest neighbour classification, naïve Bayes, and linear and quadratic discriminant analysis were evaluated on the extracted feature vectors. We also evaluated classification accuracy when subjecting the feature vectors to normalisation using p-norms. Algorithms originally developed for the classification of gene expression data—the nearest shrunken centroid algorithm and LDA ensembles obtained with random projections—were also included in the experiments, in addition to a cosine similarity classifier that has recently proved popular in few-shot learning. The results enable us to identify algorithms, normalisation methods and pre-trained feature extractors that perform well in cross-domain few-shot learning. We show that the cosine similarity classifier and ℓ² -regularised 1-vs-rest logistic regression are generally the best-performing algorithms. We also show that algorithms such as LDA yield consistently higher accuracy when applied to ℓ² -normalised feature vectors. In addition, all classifiers generally perform better when extracting feature vectors using the ResNet152 model instead of the ResNet10 model

Experimental validation of daylighting simulation methods for complex fenestration systems

The objective of this paper is to assess the capability of existing lighting simulation methods to predict the performance of complex fenestration systems, which are becoming a commonly used component in buildings construction domain. A specific experimental protocol was conducted to collect reliable reference data based on illuminance measurements inside a black box with (and without) one complex glazing sample facing a measured external luminance distribution. Two types of simulation methods were tested and compared: The first is based on modeling the glazing sample in a ray-tracing simulation program and the second is based on use of the samples' BTDF data. The BTDF data sets were combined with the external luminance distribution to predict the flux distribution inside the room and the resulting illuminance values at the reference points. The comparison between the experimental reference data and the simulation results showed that the influence of the CFS could be predicted with good accuracy