Therapeutic effect of autophagy induced by rapamycin versus intermittent fasting in animal model of fatty liver

Introduction. High-fructose, high-fat diet consumption (HFHF) is one of the primary causes of non-alcoholic fatty liver disease (NAFLD), which is due to impaired beta-oxidation or apolipoprotein secretion by hepatocytes. Activation of autophagy in hepatocytes could be a therapeutic method against hepatic complications. This study was designed to compare effects of rapamycin and intermittent fasting-inducing autophagy in rats with experimentally induced nonalcoholic fatty liver. Material and methods. Male rats were divided into five groups: C (control, n = 6), the experimental group (EX) subdivided, EXIa (HFHF, n = 6), EXIb (recovery, n = 6), EXII (rapamycin, n = 6) and EXIII (intermittent fasting, n = 6). All rats in the experimental group received HFHF diet for 8 weeks to induce nonalcoholic-fatty liver and obesity. Then, for the next 8 weeks the animals received either a daily oral dose of rapamycin (EXII group) or to intermittent fasting (IF) for 16 hours daily (EXIII group). Blood samples were drawn, and serum TG concentration as well as ALT and AST activities were determined. Hepatic sections were examined by light and electron microscopy. LC3B immunohistochemical staining, morphometric and statistical studies were performed. Results. Subgroups EXIa (HFHF subgroup) and EXIb (Recovery subgroup) showed marked increase in TG, ALT, and AST levels associated with loss of normal hepatic architecture, cytoplasmic vacuolations and faint LC3B immunoreactivity. Ultrathin sections exhibited many autophagosomes in hepatocytes. On the other hand, rapamycin (EXII) and IF (EXIII) showed significant improvement to a variable extent in comparison to EXI. Conclusions. It could be concluded that rapamycin and intermittent fasting significantly improved NAFLD-induced changes of liver structure and function by inducing autophagy in hepatocytes

Factors Affecting Outcomes of COVID-19 Infection among Older Adults with Type 2 Diabetes: A Single Center, Cross-Sectional Study

Objective: COVID-19 infection and the factors affecting it are major concerns worldwide. This retrospective study aimed to investigate clinical, laboratory and radiological characteristics associated with disease severity and hospitalization among older adults with type 2 diabetes mellitus (T2D) with COVID-19. Materials and methods: A retrospective case series study was conducted to review the records of older adults with T2D infected with COVID-19. Sociodemographic, COVID-19-related data, laboratory tests at the time of COVID-19 diagnosis and CT findings were collected. Bivariate and multivariate regression analysis were done to determine the predictors of the studied outcome, either hospitalization or complete recovery. Results: A total of 343 patients’ records were reviewed, with a mean age of 73.6 ± 6.4 years. Most of patients had fever and cough at the time of diagnosis and ground glass opacities was found on CT in 62.1% of patients. Hospitalized patients had higher duration of diabetes, suffered more from dyspnea, body aches and chest pain, had higher HbA1c, CRP and ferritin and lower lymphocytes and hemoglobin. Fasting plasma glucose and HbA1c positively affected the duration from onset of symptoms till resolution, while hemoglobin level negatively affected it. Logistic regression analysis revealed that duration of diabetes, HbA1c, ferritin and dyspnea were significant predictors of hospitalization. Conclusions: Among older adults with T2D infected with COVID-19, poor glycemic control is associated with higher risk of hospitalization and longer duration till recovery of symptoms. Longer duration of diabetes, high serum ferritin and the presence of dyspnea are associated with higher risk for hospitalization among these patients

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

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 &lt; 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

Influence of photobiomodulation and vitamin D on osteoblastic differentiation of human periodontal ligament stem cells and bone-like tissue formation through enzymatic activity and gene expression

Human periodontal ligament stem cells (HPDLSCs) are a unique population of mesenchymal stem cells (MSCs). Recently, the positive effects of photobiomodulation on the regulation of MSCs proliferation and osteogenic differentiation have gained significant attention. This study aimed to assess the effects of photobiomodulation and vitamin D (as an anabolic factor) on HPDLSCs for bone regeneration

Potential use of GAPDH m-RNA in estimating PMI in brain tissue of albino rats at different environmental conditions

Abstract Background Estimation of the postmortem interval (PMI) is a critical issue in forensic science. Various approaches have been used to determine the PMI including physical, biochemical and entomological methods. Most of these methods have practical limitations or provide insufficient results in certain conditions. Postmortem degradation of RNA may be a useful tool for PMI estimation if there is a correlation between the quantity of residual RNA and the elapsed time. This study aimed to evaluate the use of GAPDH mRNA quantity in the brain as a possible indicator for PMI in different environmental conditions. Methods Seventy-eight adult female albino rats were sacrificed by cervical dislocation. Rats were divided into five groups, the control group and 4 studied groups left after sacrificing in different conditions (ambient air at 30 °C and at 6 °C, buried in sand and submerged under water). Brain samples were obtained at different intervals (0, 24, 48 and 96 h postmortem). The mRNA of GAPDH gene of rats’ brain was quantitatively detected by qRT-PCR. Results The decrease of GAPDH mRNA levels with increasing PMI were observed in all study groups. There were significant negative correlations between brain GAPDH mRNA and Time intervals in rats left in air at 30 °C, buried in sand and recovered from the water. Conclusion GAPDH mRNA in rat ’s brain could be a useful marker for PMI estimation in several environmental conditions

Estimation of the postmortem interval using GAPDH mRNA in skin and heart tissues of albino rats at different environmental conditions

Abstract Background and objectives Post-mortem interval (PMI) estimation is an important topic in forensic sciences. Several methods have been used to determine the PMI, but most of these provide inaccurate results under certain conditions. The degradation of RNA after death has been reported to be a useful tool for PMI estimation. This study aimed to evaluate the potential use of skin and heart GAPDH mRNA levels for determining the PMI under different environmental conditions. Methods Seventy-eight adult female albino rats were sacrificed by cervical dislocation. Then, rats divided into the control group and four experimental groups left under different conditions (in ambient air at 30 °C and at 6 °C, buried in sand and submerged under water at an air temperature of 30 °C). The skin and heart samples were obtained at different time points (0, 24, 48, and 96 h post-mortem), and the GAPDH mRNA level in each sample was detected by qRT-PCR. Results The GAPDH mRNA levels decreased with increasing PMI in all study groups. There were significant negative correlations between the heart GAPDH mRNA level and the time interval in all studied groups, while the skin GAPDH mRNA level only showed negative correlations under certain conditions. Conclusion The GAPDH mRNA level in rat heart and skin could be a useful marker for PMI estimation under various environmental conditions

Investigation of Antibacterial Efficiency of Various Lytic Bacteriophages Isolated from Chickens Against Characterized Multidrug-resistant Pathogenic Bacterial Strains

This study targeted isolation and characterization of potential bacteriophages (phages) infecting MDR pathogenic bacteria recovered from chickens and analyzed their efficacy as bio-control agents. A total of 45 different bacterial isolates (18 E. coli, 16 Salmonellae spp., 5 Staphylococcus spp., 2 Pseudomonas spp., 1 Proteus mirbalis, 1 Citrobacter spp., 1 Enterobacter aerogenes and 1 Klebsiella pneumonia) were obtained from chickens in the current study and previous studies. The identified isolates were investigated for the presence of virulence genes and MDR using PCR and disc diffusion method, respectively. Nine purified phages classified morphologically into 3 families (Myoviridae, Siphoviridae and Podoviridae) using Transmission Electron Microscope were recovered from chicken intestinal contents and showed viability at wide pH range, resistance to organic solvents and thermostability at high temperatures (up to 80ºC). The potential phages exhibited various bacterial host ranges using the spot test and the efficiency of plating (EOP) assay. The results revealed the prevalent of pathogenic E. coli and salmonella serovars among the recovered isolates with different virulence and genotypic patterns. The lytic phages were highly stable and have the capacity to infect different pathogenic MDR bacterial strains. This study demonstrated that these promising phages of avian origin could be used to control the pathogenic MDR E. coli and Salmonella serovars which possess public concerns on human health and poultry industry