Expression of Notch 2 and ABCC8 genes in patients with type 2 diabetes mellitus and their association with diabetic kidney disease

Background. The incidence of type 2 diabetes mellitus (T2DM) has increased over the past years and early identification and management of its complications especially diabetic kidney disease (DKD) is of great importance. T2DM and DKD are of multifactorial etiology with contribution of genetic and environmental factors. We aimed to study the expression of ABCC8 and Notch 2 genes in patients with T2DM and to find their association with DKD. Methods. The present work was carried on 80 patients with T2DM (40 with DKD and 40 without DKD) and 40 healthy subjects as a control group. Real time polymerase chain reaction was used to assess gene expression. Results. Altered expression of ABCC8 and Notch 2 genes were found in patients with T2DM compared to control group. ABCC8 expression had significant positive correlation with HbA1c while Notch 2 expression had significant positive correlation with fasting plasma glucose and HbA1c. Notch 2 expression was significantly higher in patients with DKD compared to those without DKD. Multivariate regression analysis showed that Notch 2 expression had independent relation with increased urinary albumin excretion and reduced estimated glomerular filtration rate. ABCC8 gene expression did not show significant difference between diabetic patients with DKD compared to those without DKD. Conclusion. Increased expression of ABCC8 and Notch 2 genes may play a role in pathogenesis of T2DM. Overexpression of Notch 2 gene may have a role in the development of albuminuria and DKD in patients with T2DM which may represent a possible diagnostic tool and a possible therapeutic target

Neutrophil functions in late preterm neonates with respiratory distress syndrome

Background: Studies that have addressed the effects of respiratory distress syndrome (RDS) on neutrophil function suggested that neutrophil functions other than the generation of the respiratory burst are not impaired. Yet, results have been confusing and in some cases contradictory.Objectives: The aim of this cross-sectional controlled study is to assess neutrophil number and function in late preterm neonates with RDS.Methods: Thirty patients underwent clinical and laboratory evaluation including complete blood counts and tests of neutrophil functions (CD11b, CD62L and Dihydrorhodamine 123 by flowcytometry) in comparison to 15 healthy term controls. RDS was assessed clinically and radiologically (chest x-ray).Results: Fifty percent of patients (12 females and 18 males) had grade II respiratory distress followed by grade III then grade I. DHR, CD 11b and CD62L results were lower among the patients group (mean ± SD: 62.1± 12.23, 63.22 ± 11.41, 15.03 ± 8.7 respectively). There were no significant correlations between neutrophils count, DHR, CD11b and CD62L. Only CD11b was significantly lower with higher grades of RDS.Conclusion: Neonates with RDS show variable affection of neutrophil functions. Further studies are recommended to elucidate the exact mechanisms by which RDS can affect neutrophil functions and whether these effects are associated with increased incidence of infections.Keywords: Neutrophils, function, respiratory distress syndrome, late preterm, innate immunity, infections, adhesion molecule

Unveiling a Biomarker Signature of Meningioma: the Need for a Panel of Genomic, Epigenetic, Proteomic, and RNA Biomarkers to Advance Diagnosis and Prognosis

Meningiomas are the most prevalent primary intracranial tumors. The majority are benign but can undergo dedifferentiation in grades classified from I to III. Meningiomas tremendous variability in tumor behavior and slow growth rates complicate their diagnosis and treatment. A deeper comprehension of the molecular pathways and cellular microenvironment factors implicated in meningioma survival and pathology is needed. This review summarizes the known genetic and epigenetic aberrations involved in meningioma, with a focus on Neurofibromatosis type 2 (NF2) and non-NF2 mutations. Novel potential biomarkers for meningioma diagnosis and prognosis are also discussed, including epigenetic-, RNA-, and protein-based markers. Finally, the landscape of available meningioma-specific animal models is overviewed. Use of these animal models can enable planning of adjuvant treatment, potentially assisting in preoperative and postoperative decision-making. Discovery of novel biomarkers will allow more precise meningioma grading, including meningioma identification, subtype determination, and prediction of metastasis, recurrence, and response to therapy. Moreover, these biomarkers may be exploited in the development of personalized targeted therapies that can distinguish between the 15 diverse meningioma subtypes.This research is funded by a grant from Morehouse School of Medicine to Firas Kobeissy and a grant from Qatar University to Abdullah A. Shaito

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Surgical site infection after gastrointestinal surgery in high-income, middle-income, and low-income countries: a prospective, international, multicentre cohort study

Background: Surgical site infection (SSI) is one of the most common infections associated with health care, but its importance as a global health priority is not fully understood. We quantified the burden of SSI after gastrointestinal surgery in countries in all parts of the world. Methods: This international, prospective, multicentre cohort study included consecutive patients undergoing elective or emergency gastrointestinal resection within 2-week time periods at any health-care facility in any country. Countries with participating centres were stratified into high-income, middle-income, and low-income groups according to the UN's Human Development Index (HDI). Data variables from the GlobalSurg 1 study and other studies that have been found to affect the likelihood of SSI were entered into risk adjustment models. The primary outcome measure was the 30-day SSI incidence (defined by US Centers for Disease Control and Prevention criteria for superficial and deep incisional SSI). Relationships with explanatory variables were examined using Bayesian multilevel logistic regression models. This trial is registered with ClinicalTrials.gov, number NCT02662231. Findings: Between Jan 4, 2016, and July 31, 2016, 13 265 records were submitted for analysis. 12 539 patients from 343 hospitals in 66 countries were included. 7339 (58·5%) patient were from high-HDI countries (193 hospitals in 30 countries), 3918 (31·2%) patients were from middle-HDI countries (82 hospitals in 18 countries), and 1282 (10·2%) patients were from low-HDI countries (68 hospitals in 18 countries). In total, 1538 (12·3%) patients had SSI within 30 days of surgery. The incidence of SSI varied between countries with high (691 [9·4%] of 7339 patients), middle (549 [14·0%] of 3918 patients), and low (298 [23·2%] of 1282) HDI (p < 0·001). The highest SSI incidence in each HDI group was after dirty surgery (102 [17·8%] of 574 patients in high-HDI countries; 74 [31·4%] of 236 patients in middle-HDI countries; 72 [39·8%] of 181 patients in low-HDI countries). Following risk factor adjustment, patients in low-HDI countries were at greatest risk of SSI (adjusted odds ratio 1·60, 95% credible interval 1·05–2·37; p=0·030). 132 (21·6%) of 610 patients with an SSI and a microbiology culture result had an infection that was resistant to the prophylactic antibiotic used. Resistant infections were detected in 49 (16·6%) of 295 patients in high-HDI countries, in 37 (19·8%) of 187 patients in middle-HDI countries, and in 46 (35·9%) of 128 patients in low-HDI countries (p < 0·001). Interpretation: Countries with a low HDI carry a disproportionately greater burden of SSI than countries with a middle or high HDI and might have higher rates of antibiotic resistance. In view of WHO recommendations on SSI prevention that highlight the absence of high-quality interventional research, urgent, pragmatic, randomised trials based in LMICs are needed to assess measures aiming to reduce this preventable complication

Innovative Use of Biodex Balance System to Improve Dynamic Stabilization and Function of Upper Quarter in Recreational Weightlifters: A Randomized Controlled Trial

Background and Objectives: Following an injury, upper-body strength and proprioception training is typically suggested. To our understanding, no prior research has looked into the impact of balance training on upper-body strength and stability. So, this study investigated the effects of Biodex balance training on enhancing the dynamic stability, strength, and function of the upper quarter (UQ) in recreational weightlifters. Materials and Methods: Fifty male weightlifters were randomly assigned into two groups. The experimental group received an upper-extremity Biodex balance training program three times/week for eight weeks, while the control group underwent a regular weightlifting training routine. Pre- and post-test scores of the upper-quarter dynamic stability, strength, and function were measured for both groups using the shoulder active repositioning accuracy test, two-minute push-up test, and the upper-quarter Y-balance test (UQ-YBT) and one-arm hop test, respectively. Results: Post-test values were significantly greater for the normalized UQ-YBT test than pre-test values in both groups (p p p p p p > 0.05). Conclusions: Adding upper-body Biodex balance training to a regular weightlifting training routine was effective in enhancing the upper quarter′s dynamic stability and function

Unveiling a Biomarker Signature of Meningioma: The Need for a Panel of Genomic, Epigenetic, Proteomic, and RNA Biomarkers to Advance Diagnosis and Prognosis

Meningiomas are the most prevalent primary intracranial tumors. The majority are benign but can undergo dedifferentiation into advanced grades classified by World Health Organization (WHO) into Grades 1 to 3. Meningiomas’ tremendous variability in tumor behavior and slow growth rates complicate their diagnosis and treatment. A deeper comprehension of the molecular pathways and cellular microenvironment factors implicated in meningioma survival and pathology is needed. This review summarizes the known genetic and epigenetic aberrations involved in meningiomas, with a focus on neurofibromatosis type 2 (NF2) and non-NF2 mutations. Novel potential biomarkers for meningioma diagnosis and prognosis are also discussed, including epigenetic-, RNA-, metabolomics-, and protein-based markers. Finally, the landscape of available meningioma-specific animal models is overviewed. Use of these animal models can enable planning of adjuvant treatment, potentially assisting in pre-operative and post-operative decision making. Discovery of novel biomarkers will allow, in combination with WHO grading, more precise meningioma grading, including meningioma identification, subtype determination, and prediction of metastasis, recurrence, and response to therapy. Moreover, these biomarkers may be exploited in the development of personalized targeted therapies that can distinguish between the 15 diverse meningioma subtypes