Assessment and Validation of Globodera pallida as a Novel In Vivo Model for Studying Alzheimer’s Disease

Publication history: Accepted - 11 September 2021; Published online - 19 September 2021.Background: Whole transgenic or non-transgenic organism model systems allow the screening of pharmacological compounds for protective actions in Alzheimer’s disease (AD). Aim: In this study, a plant parasitic nematode, Globodera pallida, which assimilates intact peptides from the external environment, was investigated as a new potential non-transgenic model system of AD. Methods: Fresh second-stage juveniles of G. pallida were used to measure their chemosensory, perform immunocytochemistry on their neurological structures, evaluate their survival rate, measure reactive oxygen species, and determine total oxidized glutathione to reduced glutathione ratio (GSSG/GSH) levels, before and after treatment with 100 µM of various amyloid beta (Aβ) peptides (1–40, 1–42, 17–42, 17–40, 1–28, or 1–16). Wild-type N2 C. elegans (strain N2) was cultured on Nematode Growth Medium and directly used, as control, for chemosensory assays. Results: We demonstrated that: (i) G. pallida (unlike Caenorhabditis elegans) assimilates amyloid-β (Aβ) peptides which co-localise with its neurological structures; (ii) pre-treatment with various Aβ isoforms (1–40, 1–42, 17–42, 17–40, 1–28, or 1–16) impairs G. pallida’s chemotaxis to differing extents; (iii) Aβ peptides reduced survival, increased the production of ROS, and increased GSSG/GSH levels in this model; (iv) this unique model can distinguish differences between different treatment concentrations, durations, and modalities, displaying good sensitivity; (v) clinically approved neuroprotective agents were effective in protecting G. pallida from Aβ (1–42) exposure. Taken together, the data indicate that G. pallida is an interesting in vivo model with strong potential for discovery of novel bioactive compounds with anti-AD activity.N.A.A. received a PhD studentship from Shaqra University, KSA and the Saudi Cultural Bureau in London (UKSACB). B.D.G.’s laboratory has received support for AD research from Alzheimer’s Research UK (ARUK-NC2019-NI), the Medical Research Council (MRC) (CIC-CD1718- CIC25), US-Ireland Health and Social Care NI (HSC R&DST/5460/2018) and InvestNI (RD101427 11-01-17-008). This work was also supported by Shaqra University, Saudi Arabi

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 years; 78.2% included were male with a median age of 37 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

THE ROLE OF MAGNETIC RESONANCE SPECTROSCOPY FOR PROSTATE CANCER DIAGNOSIS

Prostate cancer (PC) is the most common malignancy among men and is the fifth leading cause of cancer-related death in men worldwide. The present study aims to systematically review the ability of magnetic resonance spectroscopy (MRS) to differentiate between benign and malignant prostate lesions. According to the 06-PRISMA guideline, we searched in five English databases, including Scopus, PubMed, Web of Science, EMBASE, and Google Scholar without time limitation for publications related to the role of magnetic resonance spectroscopy for prostate cancer diagnosis. The searched words and terms were: “prostate cancer”, “prostatitis”, “magnetic resonance spectroscopy”, “benign prostate hyperplasia”, “malignant prostate hyperplasia”, “comparison”. Totally 1927 papers were identified by database searching. Out of these papers, 261 papers were discarded because of duplication. Of the remaining 1666 papers, 1604 papers were discarded because of the inadequate information and the ones in which the abstract was submitted in congresses as preceding papers, conferences, and editorials without full text. Out of the remaining 62 papers which were studied for eligibility, 52 papers were removed for a number of reasons including inconsistency between methods with results, incorrect interpretation of the results, poor methodology, etc. Finally, 10 papers were included in this present study. In general, based on the results of the review of articles, MRS has optimal sensitivity, specificity and accuracy in diagnosing prostate cancer and differentiating it from benign prostate hyperplasia in comparison with other diagnostic and pathological methods. Due to the small number of studies related to the sensitivity and specificity of MRS, further checking was not possible to confirm these results. Therefore, further studies in this regard are recommended

The The predicting factors of clinical outcomes in patients with COVID-19 in the Kingdom of Saudi Arabia [KSA]: A multi-center cohort study

Background: On March 2020, the first case of coronavirus disease-19 was registered in the Kingdom of Saudi Arabia and subsequently the first mortality case. The predicting factors for patients' outcomes are essential to triage patients with COVID-19. This may provide low-cost facilities that help in the fight against the existing global pandemic.    Objectives: This study aimed to predict hospitalization and death outcomes of COVID-19 patients using the simplest facilities. Method: The electronic medical records of 280 COVID-19 patients between March 2020 and May 2021 were retrieved from a multi-centre of healthcare facilities across Kingdom of Saudi Arabian cites. All demographic and clinical information were examined to determine predictors and outcomes. Results: Of the 280 COVID -19 patients enrolled in our study, 14.3% were aged ≥ 66 years and 62.5% were female. The elderly (≥ 66 years, P= 0.000) and male patients (P= 0.001) were significantly hospitalized by COVID -19 than others. Patients with symptoms were hospitalized significantly more than patients without symptoms (P= 0.001). Patients with chronic conditions were hospitalized more frequently (P= 0.001). Hospitalization status also did not differ by smoking. Fever occurred significantly more frequently in patients with one or more chronic diseases (P = 0.000). Elderly (≥ 66 years, P= 0.000) and male patients of COVID -19 (P= 0.022) had significant evidence of association with death outcome than others. Hospitalization status was associated with death (P = 0.000). Conclusion: This study reported that male gender and advanced age COVID-19 patients are independent predictors for both hospital admission and death outcomes more than others. The COVID-19 patients who complain from symptoms are at risk for hospitalization as well. Additionally, having chronic clinical conditions are predictor factor for hospital admission outcome. Finally, the hospitalized patients of COVID-19 infection are at risk for death outcome

Anti-Tumor Effects of Queen Bee Acid (10-Hydroxy-2-Decenoic Acid) Alone and in Combination with Cyclophosphamide and Its Cellular Mechanisms against Ehrlich Solid Tumor in Mice

Queen bee acid or 10-hydroxy-2-decenoic acid (10-HDA) is one of the main and unique lipid components (fatty acids) in royal jelly. Previous studies have demonstrated that 10-HDA has various pharmacological and biological activities. The present study aims to evaluate the anti-tumor effects of 10-HDA alone and combined with cyclophosphamide (CP), as an alkylating agent which widely used for the treatment of neoplastic cancers, against the Ehrlich solid tumors (EST) in mice. Methods: A total of 72 female Swiss albino mice were divided into eight groups. EST mice were treated with 10-HDA (2.5 and 5 mg/kg) alone and combined with CP (25 mg/kg) orally once a day for 2 weeks. Tumor growth inhibition, body weight, the serum level of alpha-fetoprotein (AFP) and carcinoembryonic antigen tumor (CAE), liver and kidney enzymes, tumor lipid peroxidation (LPO) and nitric oxide (NO), antioxidant enzymes (e.g. glutathione reductase (GR), glutathione peroxidase (GPx), catalase enzyme (CAT)), tumor necrosis factor alpha level (TNF-α), and the apoptosis-regulatory genes expression were assessed in tested mice. Results: the findings exhibited that treatment of EST-suffering mice with 10-HDA at the doses of 2.5 and 5 mg/kg especially in combination with CP significantly (p p Conclusions: According to the results of the present investigations, 10-HDA at the doses of 2.5 and 5 mg/kg especially in combination with CP showed promising antitumor effects against EST in mice and can be recommended as a new or alternative anticancer agent against tumor; nevertheless, further investigations, particularly in clinical setting, are required to confirm these results

Green Silver Nanoparticles Synthesized from Taverniera couneifolia Elicits Effective Anti-Diabetic Effect in Alloxan-Induced Diabetic Wistar Rats

Background: Using a variety of chemical compounds and biomolecules, researchers have been working on new antidiabetic drugs for many years. Anti-diabetic research is increasingly using nanomaterials because of their unique qualities, such as their tiny size, biocompatibility, and ability to penetrate cell membranes for drug delivery. Using extract of T. couneifolia coated with silver nanoparticles as a model for diabetes mellitus research was one of the goals of this work. Methods: Uv-Vis spectroscopy was used to measure the TAgNPs surface plasmon resonance. FTIR spectroscopy confirmed the attached functional groups, XRD analysis confirmed the size and crystallinity, scanning electron microscopy revealed that the majority of the particles were spherical, and EDX performed the elemental analysis. For 21 days, alloxan-induced diabetic Wistar rats (N = 25, n = 5/group) were administered 10 mg/kg body weight of photosynthesized AgNPs as a standard animal model, while those in the untreated normal control group C, received distilled water as a control, diabetics who were treated with 0.5 mg/kg of body weight of glibenclamide, 10 mg/kg of methanolic T. couneifolia extract, and diabetics who were given 10 mg/kg of body weight of synthetic AgNPs derived from T. couneifolia in the DAgNPs group. At the conclusion of the treatment, lipid, liver and kidney profiles were re-examined to determine whether or not the treatment had been effective (day 21). Oral glucose doses of 2 g/kg of body weight were administered to each group, and blood glucose levels were measured at various intervals (day 21). Fasting glucose levels were measured using a glucometer. Each animal’s urine was tested for leukocytes, nitrites, and bilirubin using lab-made prepared assay kits. One-way ANOVA and Dunnett’s test were used for statistical analysis. Results: The surface plasmon resonance effect was examined with UV-vis, it showed a sharp peak at 412 nm. X-ray diffraction measurements indicated that the produced nanoparticles were between 15 to 31.44 nm in size. Alloxan-induced diabetic rats were fed AgNPs derived from phytosynthesized AgNPs, compared to diabetic control rats, diabetic rats treated with AgNPs showed a considerable improvement in their dyslipidemia status. Over the course of the days, it also lowered blood glucose levels. A reduction in blood glucose levels, a rise in body weight, and significant improvements in the lipid, liver, and renal profiles were also seen. Conclusions: The present findings revealed that plant mediated silver nanoparticles significantly improved the alloxan induced diabetic changes in various treated rats and might be used for the treatment of diabetes

Ethnomedicinal plants with protective effects against beta-amyloid peptide (Aβ)1-42 indicate therapeutic potential in a new in vivo model of alzheimer’s disease

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder with unmet medical need. This investigation consisted of testing a range of ethanolic ethnomedicinal plant extracts (n = 18) traditionally used in the treatment of disorders such as anxiety, delirium, and memory loss. They were then screened for in vitro inhibitory activity against acetylcholinesterase (AChE), butylcholinesterase (BuChE), beta-secretase 1/beta-site amyloid precursor protein (APP) cleaving enzyme 1 (BACE1), and antioxidant activities. Plants with potent activities were further characterised using a recently developed in vivo model of AD, Globodera pallida. The ability of phytoextracts to protect this organism against amyloid-beta Aβ (1-42) exposure was assessed by measuring chemosensing, survival rate, production of reactive oxygen species (ROS), and antioxidant responses. Extracts (n = 5) from Juglans regia (leaves), Ellettaria cardamomum (seeds), Cinnamomum zeylanicum (bark), Salvia officinalis (leaves/flowers), and Hypericum perforatum (flowers) exerted concentration-dependent inhibitory activities against AChE and BuChE. Three of these plant extracts (i.e., J. regia, E. cardamomum, and S. officinalis) possessed strong concentration-dependent inhibitory activity against BACE1. Furthermore, the five selected medicinal plant extracts not only enhanced significantly (p < 0.05) the nematode’s chemosensing, survival rate, and antioxidant responses (i.e., anti-ROS production, mitochondrial reductase activity, oxidized glutathione (GSSG) to reduced glutathione (GSH) ratio), but also greatly restored (p < 0.05) in a concentration-dependent manner the Aβ (1-42)-induced deleterious changes in these same parameters. In brief, this investigation highlights plant extracts with strong anti-AD activities which could be trialled as novel therapeutic supplements or undergo further biodiscovery research

Physicochemical Characterizations and Pharmacokinetic Evaluation of Pentazocine Solid Lipid Nanoparticles against Inflammatory Pain Model

Pentazocine (PTZ), a narcotic-antagonist analgesic, has been extensively used in the treatment of initial carcinogenic or postoperative pain. Hepatic first-pass metabolism results in low oral bioavailability and high dose wastage. Herein, 10 mg (-)-Pentazocine (HPLC-grade) was incorporated to solid lipid nanoparticles (SLNs) using a double water-oil-water (w/o/w) emulsion by solvent emulsification–evaporation technique, followed by high shear homogenization to augment its oral bioavailability, considering the lymphatic uptake. The resulting SLNs were characterized for zeta potential (ZP), particle size (PS), and polydispersity index (PDI) using a zetasizer. The entrapment efficiency (EE) and loading capacity (LC) were calculated. Chemical interactions, through the identification of active functional groups, were assessed by Fourier-transformed infrared (FTIR) spectroscopy. The nature (crystallinity) of the SLNs was determined by X-ray diffractometry (XRD). The surface morphology was depicted by transmission electron microscopy (TEM). In vitro (in Caco-2 cells) and in vivo (in male Wistar rats) investigations were carried out to evaluate the PTZ release behavior and stability, as well as the cellular permeation, cytotoxicity, systemic pharmacokinetics, antinociceptive, anti-inflammatory, and antioxidative activities of PTZ-loaded SLNs, mainly compared to free PTZ (marketed conventional dosage form). The optimized PTZ-loaded SLN2 showed significantly higher in vitro cellular permeation and negligible cytotoxicity. The in vivo bioavailability and pharmacokinetics parameters (t1/2, Cmax) of the PTZ-loaded SLNs were also significantly improved, and the nociception and inflammation, following carrageenan-induced inflammatory pain, were markedly reduced. Concordantly, PTZ-loaded SLNs showed drastic reduction in the oxidative stress (e.g., malonaldehyde (MDA)) and proinflammatory cytokines (e.g., Interleukin (IL)-1β, -6, and TNF-α). The histological features of the paw tissue following, carrageenan-induced inflammation, were significantly improved. Taken together, the results demonstrated that PTZ-loaded SLNs can improve the bioavailability of PTZ by bypassing the hepatic metabolism via the lymphatic uptake, for controlled and sustained drug delivery

SARS-CoV-2 vaccination modelling for safe surgery to save lives: data from an international prospective cohort study

Background: Preoperative SARS-CoV-2 vaccination could support safer elective surgery. Vaccine numbers are limited so this study aimed to inform their prioritization by modelling. Methods: The primary outcome was the number needed to vaccinate (NNV) to prevent one COVID-19-related death in 1 year. NNVs were based on postoperative SARS-CoV-2 rates and mortality in an international cohort study (surgical patients), and community SARS-CoV-2 incidence and case fatality data (general population). NNV estimates were stratified by age (18-49, 50-69, 70 or more years) and type of surgery. Best- and worst-case scenarios were used to describe uncertainty. Results: NNVs were more favourable in surgical patients than the general population. The most favourable NNVs were in patients aged 70 years or more needing cancer surgery (351; best case 196, worst case 816) or non-cancer surgery (733; best case 407, worst case 1664). Both exceeded the NNV in the general population (1840; best case 1196, worst case 3066). NNVs for surgical patients remained favourable at a range of SARS-CoV-2 incidence rates in sensitivity analysis modelling. Globally, prioritizing preoperative vaccination of patients needing elective surgery ahead of the general population could prevent an additional 58 687 (best case 115 007, worst case 20 177) COVID-19-related deaths in 1 year. Conclusion: As global roll out of SARS-CoV-2 vaccination proceeds, patients needing elective surgery should be prioritized ahead of the general population