Differential potency of vitamin D3, folic acid and memantine in protecting against neurobehavioral alterations of scopolamine induced Alzheimer’s model in rats

Background: Alzheimer disease is the cause of 60% to 70% of cases of dementia in elderly people, it is a chronic neurodegenerative disease that usually starts slowly and worsens over time. AD is characterized by the presence of senile plaques enriched with insoluble aggregate of beta-amyloid, neurofibrillary tangles and cholinergic neuronal degeneration in the brain tissue, leading to neural dysfunction, neuroinflammation, and critical pathological perturbations.Methods: Thirty-six males were classified into control group, Alzheimer-induced model (scopolamine 2.5 mg/kg IP once daily for 21 days). Folic acid-treated group (4 mg/kg, IP) once daily for 21 days with scopolamine. Vitamin D3-treated group (42 IU/kg, SC) once daily for 21 days with scopolamine. Vitamin D3 and folic acid-treated group (vitamin D3; 42 IU/kg, SC and folic acid; 4 mg/kg, IP) once daily with scopolamine for 21 days. Memantine-treated group (20 mg/kg IP) once daily with scopolamine for 21 days.Results: Induction of Alzheimer’s showed significant decrease in brain tissue levels of BDNF, Ach, glutathione reductase and significant increase in amyloid peptide 1-42 level with significant memory impairment, significant increase of initial acquisition latency, firstt retention latency and second retention latency. While administration of folic acid, vitamin D3, memantine separately or in combination resulted insignificant increase of brain tissue levels of BDNF, Ach, glutathione reductase with significant reduction of amyloid peptide 1-42 level with significant memory improvement (significant decrease IAL, first RL and second RL). Also showed improvement of histopathological changes occurred in the brain.Conclusions: Data obtained in the present study revealed that treatment of experimentally induced alzheimer rats with folic acid or vitamin D3 or memantine separately or combined group (folic acid+vitamin D3) resulted in significant increase of brain tissue levels of BDNF, acetyl choline, glutathione reductase with significant reduction of amyloid peptide 1-42 level with significant decrease of IAL, first RL and second RL to reach the platform with improvement of histopathological changes occurred in the brain. But combined and memantine-treated groups resulted in more significant improvement than other treated groups

Tempol improves optic nerve histopathology and ultrastructures in cisplatin-induced optic neuropathy in rats by targeting oxidative stress—Endoplasmic reticulum stress—Autophagy signaling pathways

IntroductionOptic neuropathy is an affection of the optic neurons, which ends with blindness and occurs either primarily due to direct affection of the optic nerve or secondarily as a complication of chronic diseases and/or adverse effects of their therapy. The search for novel therapeutic tools is crucial in addressing the limited therapeutic approaches for optic neuropathy. Therefore, the present study was developed to investigate the possible ameliorative effect of tempol against cisplatin-induced optic neuropathy and its underlying mechanism.MethodsForty-eight adult male albino Wistar rats were divided into four equal groups—control, tempol (TEM), cisplatin (CIS), and tempol and cisplatin combined (TEM+CIS). Optic nerve oxidative stress (MDA, SOD, and GPx), gene expression of endoplasmic reticulum stress (ATF-6, XBP-1, BIP, CHOP, and JNK), autophagy 6 (LC3, Beclin-1, and p62) markers, nerve growth factor-1, immunohistochemical expression of (LC3 and p62), histopathological, and electron microscopic examination were performed.ResultsHistopathological and ultrastructure examination validated that cisplatin caused optic neuropathy by inducing oxidative stress, upregulating ER stress markers, and downregulating autophagy markers, and NGF-1 expression. TEM + CIS showed improvement in optic nerve structure and ultrastructure along with oxidative stress, ER stress mRNA, autophagy (immunohistochemical proteins and mRNA) markers, and nerve growth factor mRNA expression.ConclusionsBased on previous findings, tempol represents a valid aid in cisplatin-induced optic neuropathy by implicating new molecular drug targets (ER stress and autophagy) for optic neuropathy therapy

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

Burnout among surgeons before and during the SARS-CoV-2 pandemic: an international survey

Background: SARS-CoV-2 pandemic has had many significant impacts within the surgical realm, and surgeons have been obligated to reconsider almost every aspect of daily clinical practice. Methods: This is a cross-sectional study reported in compliance with the CHERRIES guidelines and conducted through an online platform from June 14th to July 15th, 2020. The primary outcome was the burden of burnout during the pandemic indicated by the validated Shirom-Melamed Burnout Measure. Results: Nine hundred fifty-four surgeons completed the survey. The median length of practice was 10&nbsp;years; 78.2% included were male with a median age of 37&nbsp;years old, 39.5% were consultants, 68.9% were general surgeons, and 55.7% were affiliated with an academic institution. Overall, there was a significant increase in the mean burnout score during the pandemic; longer years of practice and older age were significantly associated with less burnout. There were significant reductions in the median number of outpatient visits, operated cases, on-call hours, emergency visits, and research work, so, 48.2% of respondents felt that the training resources were insufficient. The majority (81.3%) of respondents reported that their hospitals were included in the management of COVID-19, 66.5% felt their roles had been minimized; 41% were asked to assist in non-surgical medical practices, and 37.6% of respondents were included in COVID-19 management. Conclusions: There was a significant burnout among trainees. Almost all aspects of clinical and research activities were affected with a significant reduction in the volume of research, outpatient clinic visits, surgical procedures, on-call hours, and emergency cases hindering the training. Trial registration: The study was registered on clicaltrials.gov "NCT04433286" on 16/06/2020

Improving the nutritive value of olive pomace by solid state fermentation of Kluyveromyces marxianus with simultaneous production of gallic acid

Abstract Purpose Olive oil industry is a growing industrial sector in Mediterranean countries. Unfortunately, about 30–35% of total olive weight is discarded as olive pomace (OP), a highly environmental-polluting solid waste. OP is mostly used for composting and production of animal feed; nevertheless, the high oil content, phenolic compounds and fiber contents in addition to its low protein content represent major obstacles for both applications. So, the present study was conducted to evaluate the role of solid state fermentation (SSF) in OP using Kluyveromyces marxianus NRRL Y-8281 yeast on the chemical composition and tannin content of OP in a trial for its bioconversion into a value-added animal feed. Methods Chemical composition, nutritive and energetic values, tannin and gallic acid contents of unfermented and fermented olive pomace were investigated. Results The fermentation altered the chemical composition of OP, so that crude fiber was decreased by 8.56%, while crude protein, fat and carbohydrate contents were increased by 2.74, 2.63 and 3.57%, respectively. Moreover, the effect of fermentation on cell wall constituents, gross energy, digestible energy, total digestible nutrients and digestible crude protein was evaluated. Furthermore, HPLC analysis revealed that K. marxianus mediated fermentation of OP resulted in a sharp decrease in tannin content by 96.75% with 2.8 times increase in gallic acid concentration. Conclusion SSF of OP by K. marxianus does not only eliminate the environmental pollution resulting from its accumulation, but also presents a new eco-friendly valorization technique which leaves OP with an altered chemical composition allowing its use as animal feed or compost

LC–MS/MS based-comparative study of (S)-nicotine metabolism by microorganisms, mushroom and plant cultures: Parallels to its mammalian metabolic fate

The metabolic fate of nicotine using the cell cultures of microorganisms, mushroom and plants was explored using LC–MS/MS analysis. The study demonstrated parallels to phase I mammalian metabolism of nicotine and reported that nicotine was biotransformed into its N-oxide by Streptomyces fradiae culture. Moreover, it was metabolized in Pleurotus ostreatus culture into nornicotine, norcotinine and β-nicotyrine; whereas, cotinine and its 3′-hydroxylated derivative were the identified nicotine metabolic products in Pimpinella anisum cell culture. However, the microbial culture of Agaricus bisporus bioconverted nicotine into one of its derived-carcinogenic nitrosamines which is “4-(methylnitrosamino)-4-(3-pyridyl)butanal”. Mushroom and plant cell cultures were thus proven to be competent to microbial cultures in bioconverting nicotine into many of its previously reported metabolites. Convincingly, the obtained results highlighted the prospect of utilizing other species which are intrinsically-endowed with unique biocatalytic systems, such as mushrooms and plants, in the drug metabolic studies

Diaphragmatic dysfunction in hemodialysis patients: risk factors and effect of incentive spirometry training

Abstract Background Diaphragmatic dysfunction (DD) in hemodialysis patients is a scarcely studied issue. Incentive spirometry (IS) is a commonly prescribed maneuver used to prevent or manage pulmonary complications. The present study aimed to identify the prevalence and risk factors of DD in 100 HD patients. Moreover, we assessed the role of IS in management of DD in those patients. Methods The present study followed a hybrid design with two phases. In the first cross-sectional phase, 100 consecutive maintenance HD patients for at least 3 years were evaluated for the presence of DD using ultrasound. In the second interventional phase, patients with DD (n = 43) were randomly assigned to receive IS (n = 22) or standard care (n = 21) for management of DD. Results Comparison between patients with DD and patients without regarding clinical and laboratory data revealed that the former group had significantly higher frequency of males [29 (67.4%)/14 (32.6%) vs. 26 (45.6%)/31 (54.4%), p = 0.03] with lower BMI [23.8 ± 3.8 vs. 26.3 ± 3.5 kg/m2, p < 0.001] and longer HD duration (82.2 ± 42.1 vs. 64.8 ± 36.9 months, p = 0.031). Moreover, it was noted that DD group had significantly higher frequency of patients with moderate/severe malnutrition (81.4% vs. 45.6%, p = 0.005), lower Hb levels (9.6 ± 1.5 vs. 10.3 ± 1.4 gm/dL, p = 0.011), lower albumin levels (3.4 ± 0.4 vs. 4.1 ± 0.5 gm/dL, p < 0.001) and higher hsCRP levels [median (IQR) 113.6 (90.9–130.4) vs. 91.1 (50.9–105.6) mg/dL, p < 0.001] as compared to patients without DD. While no significant differences were found between patients receiving study interventions at baseline, patients submitted to IS training showed significant improvement of diaphragmatic excursion measurements as compared to the standard care group. Conclusions In conclusion, DD is commonly encountered in HD patients. Probable risk factors include longer HD duration and low albumin levels. Use of IS can improve diaphragmatic excursion in affected patients

Potential Effect of Biochar on Soil Properties, Microbial Activity and <i>Vicia faba</i> Properties Affected by Microplastics Contamination

Microplastics (MPs) contamination is an emerging issue globally; however, adverse impacts of MPs on soil, plants and microbial activity have not been intensively studied. In this study, the potential effect of different levels of MPs (1.5, 7.5, 15%) has been investigated on soil properties, plant properties (Vicia Faba) and microbial activities through a pot experiment. The effect of biochar (BC: 2%) to mitigate the adverse effects of MP has also been examined. Soil properties (pH, EC, OM, CaCO3 and some elements) have significantly differed due to contamination of soil by MPs as well as by adding BC to the soil. The pH and CaCO3 were significantly increased more than in the control, while EC, TDS, available P, Mn and Fe were significantly decreased lower than the control, which implies adsorption on microplastic. Plant properties, such as enzymes, chlorophyll and fresh and dry weight in roots, were adversely affected by MPs contamination; however, BC mitigated this effect, especially with low contamination levels of MPs. The fresh and dry weight of the shoot was not significantly affected by MPs. The cytogenetic analysis showed that the mitotic index was significantly reduced compared to the control (9.39%), while BC increased the mitotic index at 1.5% MPs (7.11%) although it was less than the control. The percentage of abnormalities of V. faba root tip cells under different levels of MPs was significantly increased more than the control; however, BC mitigated this effect, especially at 7.5% MPs. The total count of bacteria and fungi even in soil or in the rhizosphere area did not follow a clear trend; however, the effect of BC was clear in increasing their activities. Microbial biomass carbon and nitrogen were also significantly affected by MPs and BC. In this study, the BC level was low, however, it mitigated some adverse effects of MPs, especially at 1.5 and 7.5% of MPs. Thus, the BC could be promising in mitigating the negative impacts of MPs when applied with suitable levels that need more future studies