miRNome of Child A hepatocellular carcinoma in Egyptian patients

IntroductionHepatocellular carcinoma (HCC) has different etiologies that contribute to its heterogeneity. In regards to the number of HCC patients, Egypt ranks third in Africa and fifteenth worldwide. Despite significant advancements in HCC diagnosis and treatment, the precise biology of the tumor is still not fully understood, which has a negative impact on patient outcomes.MethodsAdvances in next-generation sequencing (NGS) have increased our knowledge of the molecular complexity of HCC.Results & discussionIn this research, 16 HCC and 6 tumor adjacent tissues (control) of Child A Egyptian patients were successfully profiled for the expression profile of miRNAs by NGS. Forty-one differentially expressed miRNAs (DEMs) were found by differential expression analysis, with 31 being upregulated and 10 being downregulated. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis was then conducted on these differentially expressed miRNAs revealing that Sensitivity and specificity analysis showed that hsa-miR-4488, hsa-miR-3178, and hsa-miR-3182 were unique miRNAs as they are expressed in HCC tissues only. These miRNAs were all highly involved in AMPK signaling pathways. However, hsa-miR-214-3p was expressed in control tissues about eight times higher than in cancer tissues and was most abundant in “pathways in cancer and PI3K-Akt signaling pathway” KEGG terms. As promising HCC diagnostic markers, we here suggest hsa-miR-4488, hsa-miR-3178, hsa-miR-3182, and hsa-miR-214-3p. We further urge future research to confirm these markers' diagnostic and prognostic potential as well as their roles in the pathophysiology of HCC

Copper nanoparticles encapsulated in zeolitic imidazolate framework-8 as a stable and selective CO2 hydrogenation catalyst

Metal–organic frameworks have drawn attention as potential catalysts owing to their unique tunable surface chemistry and accessibility. However, their application in thermal catalysis has been limited because of their instability under harsh temperatures and pressures, such as the hydrogenation of CO2 to methanol. Herein, we use a controlled two-step method to synthesize finely dispersed Cu on a zeolitic imidazolate framework-8 (ZIF-8). This catalyst suffers a series of transformations during the CO2 hydrogenation to methanol, leading to ~14 nm Cu nanoparticles encapsulated on the Zn-based MOF that are highly active (2-fold higher methanol productivity than the commercial Cu–Zn–Al catalyst), very selective (>90%), and remarkably stable for over 150 h. In situ spectroscopy, density functional theory calculations, and kinetic results reveal the preferential adsorption sites, the preferential reaction pathways, and the reverse water gas shift reaction suppression over this catalyst. The developed material is robust, easy to synthesize, and active for CO2 utilization.King Abdullah University of Science and Technology (KAUST) funded this work: BAS/1/1403. The authors acknowledge the KAUST Supercomputing Laboratory for providing high-performance computational resources and support from the KAUST Core Labs

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

Reinforcing effect of tramadol in the rat

International audienceTramadol is one of the most commonly prescribed analgesic opioids in various pharmacopeias. Tramadol has been linked to abuse in recent clinical investigations. However, the behavioral effects and neural substrates of the drug have not been well characterized in preclinical studies. As a result, the present study investigated the effects of tramadol on behavioral sensitizations in rats. Its impacts on cellular and molecular alterations in the brain were also investigated. In conditioned place preference (CPP) paradigm, tramadol induced behavioral as well as motor sensitizations. These effects were dramatically reduced by intraperitoneal administration of naltrexone, an opioid receptor antagonist. Tramadol caused changes in several molecular markers (pERK1/2, Δ-FosB, PKCγ, PKMζ GAD67) in the anterior cingulate cortex, which could indicate an increase in excitation within this structure. Tramadol is demonstrated in the present study to be a reinforcing drug in rats, as it increased both behavioral and motor sensitizations. Tramadol’s effects are most likely due to the high levels of excitation it causes in the brain, which is mostly caused by the activation of opioid receptors

Metabolomics of lean/overweight insulin resistant females reveals alterations in steroids and fatty acids.

The global diabetes epidemic is largely attributed to obesity-triggered metabolic syndrome. However, the impact of insulin resistance (IR) prior to obesity on the high prevalence of diabetes and the molecular mediators remain largely unknown. This study aims to compare the metabolic profiling of apparently healthy lean/overweight participants with IR and insulin sensitivity (IS), and identify the metabolic pathways underlying IR. In this cross-sectional study, clinical and metabolic data for 200 seemingly healthy young females (100 IR and 100 IS) was collected from Qatar Biobank. Orthogonal partial least square analysis was performed to assess the extent of separation between individuals from the two groups based on measured metabolites. Classical linear models were used to identify the metabolic signature of IR, followed by elastic-net-regularized generalized linear model (GLMNET) and Receiver Operating Characteristic (ROC) analysis to determine top metabolites associated with IR. Compared to lean/overweight participants with IS, those with IR showed increased androgenic steroids, including androsterone glucuronide, in addition to various microbiota byproducts, such as the phenylalanine-derivative carboxyethylphenylalanine. On the other hand, participant with IS had elevated levels of long chain fatty acids. A ROC analysis suggested a better discriminatory performance using 20 metabolites selected by GLMNET in comparison to the classical clinical traits (area under curve: 0.93 vs 0.73, respectively). Our data confirm the multifactorial mechanism of IR with diverse spectrum of emerging potential biomarkers, including steroids, long chain fatty acids and microbiota metabolites. Further studies are warranted to validate these markers for diagnostic and therapeutic applications

Role of Fetal Cardiac ECHO and Fetal Cardiac MRI in Prediction of Post Natal Hemodynamic Maladaptation in Fetuses of Diabetic Mothers

Background: Maternal diabetes mellitus (DM) is defined as a degree of glucose intolerance with recognition during pregnancy (pregestational or gestational, type 1 or type 2), and it is estimated to be 15% in pregnant females in 2019. The current study aimed to study the role of fetal echocardiography and fetal cardiac magnetic resonance imaging (MRI) in anticipation and diagnosis of hemodynamic maladaptation changes in fetuses of diabetic mothers as predictors for (closure of Patent ductus arteriosus (PDA), persistent pulmonary hypertension and diastolic dysfunction) which were confirmed with post-natal echocardiographic and clinical assessment. Methods: This study was an observational follow-up study that included 80 pregnant diabetic females who were following in the specialized clinics of Ain Shams University Hospitals during the period starting from August 2020 till December 2022. Results: Diabetes affected left ventricle (LV) diastolic function and global cardiac function but did not affect LV systolic function (p-value=0.000). Interventricular septum (IVS) thickness had a significant positive correlation with LV- Myocardial performance index (MPI) and indices of DM such as HbA1c. Diastolic dysfunction was the most affected cardiac parameter in infants of diabetic mothers (p-value=0.002). The hemoglobin A1c (HbA1c) was the most significant predictor for IVS thickness in diabetic mothers' fetuses, especially with a long duration of DM (p-value=0.012). Conclusion: Fetal echocardiography in diabetic mothers is essential and the gold standard modality not only for diagnosing structural abnormalities but also for evaluating the cardiac function of the fetuses. Fetal cardiac MRI could be considered a complementary imaging modality that uses no ionizing radiation, good tissue contrast, and a larger field of view