Study of obesity associated proopiomelanocortin gene polymorphism: Relation to metabolic profile and eating habits in a sample of obese Egyptian children and adolescents

AbstractBackgroundMelanocortinergic system represents a known system involved in the central regulation of body weight with the central proopiomelanocortin (POMC) neurons forming a potent anorexigenic network. Polymorphisms in the POMC gene locus are associated with obesity phenotypes.AimTo assess the contribution of the POMC gene 9-bp insertional polymorphism in the susceptibility to obesity and its relation to body mass index (BMI) and adiposity-related co-morbidities in obese children and adolescents; as well as binge eating behavior.Patients and methodsFifty obese children and adolescents with simple obesity were screened for Binge Eating Disorder (BED) by The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), they were compared to 50 age, sex and pubertal stage-matched non obese controls. Anthropometric measurements, blood pressure, abdominal ultrasound for fatty liver, measurement of fasting lipid profile, fasting insulin, fasting blood glucose and assessment of POMC gene 9-bp insertional polymorphism were done.ResultsObese patients had significantly higher anthropometric measurements, blood pressure percentiles, fasting glucose, fasting insulin, homeostasis model assessment for insulin resistance (HOMA-IR) and fasting lipid profiles, and higher frequency of occurrence of non alcoholic fatty liver disease and BED. Allelic frequencies of POMC gene 9bp insertional polymorphism were comparable in patients and controls (p=0.956). Fasting insulin levels were significantly higher in the heterozygous cases having the polymorphism than in wild homozygous cases; whereas no difference was observed among the controls.ConclusionThis polymorphism was associated with higher fasting insulin levels in the obese patients only. These findings support the hypothesis that the melanocortin pathway may modulate glucose metabolism in obese subjects indicating a possible gene-environment interaction. POMC variant may be involved in the natural history of polygenic obesity, contributing to the link between type 2 diabetes and obesity

An overview of the welfare of animals used for scientific and educational purposes in Algeria

This study describes the welfare and animals used for scientific and educational purposes in the field of laboratory animal sciences in Algeria. The aim of this study is to provide an overview of the status of the care and use of animals and to improve implementing plans and animal welfare measures. A literature review was performed using online databases and reference lists of the US National Library of Medicine to assess the prevalence of animal use for research in Algeria between 2013 and 2017. Also a retrospective study was conducted using the Pasteur Institute of Algeria report for 2015 to assess the prevalence of animal use in both teaching and research. The first workshop on animal experimentation was organized in 2013 in collaboration with international animal laboratory organizations (ICLAS and OIE) and involving the participation of universities, research centers, veterinary schools and the Pasteur Institute of Algeria. In addition, after accreditation of the Algerian Association of Experimental Animal Sciences, a number of training workshops and courses relating to laboratory animal sciences were organized. In Algeria the use of laboratory animals in research and education is a subject of debate regarding the need to establish regulations and to propose an appropriate ethical framework for the use of animals. Finally, some actions have been already taken in Algeria to promote the ethical use of animals but many more sustainable actions are needed and require cooperation, harmonization of policies and establishment of regional and international networks for experience exchange

An efficient green ionic liquid for the corrosion inhibition of reinforcement steel in neutral and alkaline highly saline simulated concrete pore solutions

The effect of the green ionic liquid compound, Quaternium-32 (Q-32), on the corrosion inhibition performance of reinforcement steel, in a simulated concrete pore solution, was investigated at different temperatures and pH values, using electrochemical impedance spectroscopy (EIS). The inhibition efficiency was improved as the concentration of Q-32 and pH values were increased. However, it decreased as the temperature was raised. A Q-32 concentration of 20 µmol L–1 exhibited a 94% inhibition efficiency at 20 °C. The adsorption isotherm was evaluated using EIS measurements, and it was found to obey the Langmuir isotherm. The surface topography was examined using an atomic force microscope and scanning electron microscope. The effect of the Q-32 concentration with the highest corrosion efficiency on the mechanical properties of the mortars was also explained by flexure and compression techniques.The authors express their gratitude to the Center for Advanced Materials at Qatar University for technical support. Additionally, the authors are grateful to Qatar University for funding this work through the QUCG-CAM-20/21-2 Grant. The publication of this article was funded by the Qatar National Library

Differential Effects of Low-Dose Erythropoietin in Rat Model of Diabetic Nephropathy: Submitted: Jan 3, 2018 Accepted: Feb 26, 2018 Published online: Mar 3, 2018

Background. Previous reports on the renoprotective effect of erythropoietin (EPO) in the setting of chronic kidney disease (CKD) have yielded conflicting results. The aim of this study is to clarify the effect of low, non-hematopoietic dose of EPO on the evolution of diabetic nephropathy (DN) in rat model. Methods. Low dose of recombinant human EPO (150 U/kg, s.c. three times/week) was given to streptozotocin (STZ)-induced diabetic rats in two schedules; in the first one, EPO was given from day 2 after STZ injection till the end of the study (28 weeks) as prophylactic treatment; and in the other schedule EPO was given after development of DN (last 8 weeks) as therapeutic treatment. Albuminuria, blood pressure, creatinine clearance, renal venous oxygen tension (vPO2), plasma EPO, hematocrit and renal histopathology were assessed. Results. Unexpectedly, 28 weeks administration of EPO to diabetic rats led to aggravation of albuminuria and worsening of histopathological damage in spite of partial correction of renal hypoxia. Contrary to this, terminal 8 weeks EPO therapy of DN reduced albuminuria and demonstrated some favorable effects on biochemical changes and histologic picture. Conclusion. Low dose EPO exerted differential effects in rat model of DN according to treatment duration. In addition, findings of the present study warrants further investigations of the exact renoprotective role of EPO in diabetic patients with CKD who receive EPO therapy for long periods

Ultrasound in managing extrapulmonary tuberculosis: a randomized controlled two-center study

Patients with clinically suspected tuberculosis are often treated empirically, as diagnosis - especially of extrapulmonary tuberculosis - remains challenging. This leads to an overtreatment of tuberculosis and to underdiagnosis of possible differential diagnoses.; This open-label, parallel-group, superiority randomized controlled trial is done in a rural and an urban center in Tanzania. HIV-positive and -negative adults (≥18 years) with clinically suspected extrapulmonary tuberculosis are randomized in a 1:1 ratio to an intervention- or control group, stratified by center and HIV status. The intervention consists of a management algorithm including extended focused assessment of sonography for HIV and tuberculosis (eFASH) in combination with chest X-ray and microbiological tests. Treatment with anti-tuberculosis drugs is started, if eFASH is positive, chest X-ray suggests tuberculosis, or a microbiological result is positive for tuberculosis. Patients in the control group are managed according national guidelines. Treatment is started if microbiology is positive or empirically according to the treating physician. The primary outcome is the proportion of correctly managed patients at 6 months (i.e patients who were treated with anti-tuberculosis treatment and had definite or probable tuberculosis, and patients who were not treated with anti-tuberculosis treatment and did not have tuberculosis). Secondary outcomes are the proportion of symptom-free patients at two and 6 months, and time to death. The sample size is 650 patients.; This study will determine, whether ultrasound in combination with other tests can increase the proportion of correctly managed patients with clinically suspected extrapulmonary tuberculosis, thus reducing overtreatment with anti-tuberculosis drugs.; PACTR, Registration number: PACTR201712002829221, registered December 1st 2017

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P < 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely

AMPA receptor GluA2 subunit defects are a cause of neurodevelopmental disorders.

AMPA receptors (AMPARs) are tetrameric ligand-gated channels made up of combinations of GluA1-4 subunits encoded by GRIA1-4 genes. GluA2 has an especially important role because, following post-transcriptional editing at the Q607 site, it renders heteromultimeric AMPARs Ca2+-impermeable, with a linear relationship between current and trans-membrane voltage. Here, we report heterozygous de novo GRIA2 mutations in 28 unrelated patients with intellectual disability (ID) and neurodevelopmental abnormalities including autism spectrum disorder (ASD), Rett syndrome-like features, and seizures or developmental epileptic encephalopathy (DEE). In functional expression studies, mutations lead to a decrease in agonist-evoked current mediated by mutant subunits compared to wild-type channels. When GluA2 subunits are co-expressed with GluA1, most GRIA2 mutations cause a decreased current amplitude and some also affect voltage rectification. Our results show that de-novo variants in GRIA2 can cause neurodevelopmental disorders, complementing evidence that other genetic causes of ID, ASD and DEE also disrupt glutamatergic synaptic transmission

The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance

INTRODUCTION Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic. RATIONALE We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs). RESULTS Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants. CONCLUSION Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century