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Background: Pesticide poisoning remains a major global health concern contributing to an estimated 371,594 deaths annually. Both accidental and deliberate pesticide exposure, particularly in developing countries, pose challenges to public health systems. In KSA, pesticide poisoning is prevalent, and insecticides such as carbamates and organophosphates are the primary culprits., Case Presentation: Four cases of acute poisoning caused by the ingestion of contaminated shawarma sandwiches containing carbofuran and bifenthrin, a carbamate and pyrethroid mixture, respectively, are described. The affected individuals, all siblings, exhibited varying degrees of cholinergic symptoms, including muscle fasciculations, excessive secretions, and respiratory distress. Despite their severe symptoms, three patients had normal or low-normal acetylcholinesterase levels, probably because of individual variability, delayed testing, or improper sample handling. One patient exhibited diminished acetylcholinesterase activity, thus suggesting severe inhibition; pancreatitis was a further complication that contributed to delayed recovery. Early clinical management included atropine, pralidoxime, and botulinum antitoxin, because of initial suspicion for botulism. Toxicological analysis confirmed carbofuran poisoning, and food safety investigations identified improper pesticide use in food preparation areas., Conclusion: The reported cases underscore the importance of timely toxicological consultation, proper testing, and appropriate sample handling to guide treatment of pesticide-related poisoning. These findings highlight the crucial need for adherence to WHO regulations and monitoring of pesticide use, as well as strict food safety practices to prevent future outbreaks. The successful multidisciplinary approach to managing these cases demonstrates the critical role of coordinated efforts between clinical teams and public health authorities in addressing such public health threats., (© 2024 The Authors.)

Abu Marawat area in the Central Eastern Desert of Egypt is a very promising mineralization district located in the Golden Triangle area. The current study provides an integrated approach from multisource datasets including; remote sensing, airborne geophysical spectrometry and magnetic data supported by field studies and spectroscopic analyses for delineating potential mineralization localities. Several remote sensing techniques were adopted including; Band Ratios, Relative Band Depth, Mineralogical Indices, Spectral Angle Mapper, and Constrained Energy Minimization. These techniques showed that the alteration mineral assemblage is mainly, kaolinite, sericite, and iron oxides, with less abundant chlorite, epidote, and carbonates. In addition, the radiometry data were processed to map the localities with the highest possibility of potassic alteration abundance by integrating the potassium distribution, K/eTh ratio, and the F-parameter maps. The surface and subsurface linear structural features were also mapped using Digital Elevation Model (DEM) and aeromagnetic data, respectively. The surface linear structures were found exhibiting E-W and NE-SW trends, while, the subsurface structures showed dominant NW-SE trend. All the depicted fault trends match well with the local and regional geological and tectonic setting of the study area suggesting structural control on the mineralization in this area. Integration between the results obtained from both the remote sensing and the geophysical data was conducted by a GIS weighted overlay model. The obtained mineralization potentiality map highlights eight potential localities for mineralization. The accuracy of the adopted methodology was demonstrated through fieldwork and spectral analyses; several alteration indicators were observed, including quartz veins, iron oxides, kaolinite, malachite, montmorillonite, chlorite, talc, and sericite alteration indicator minerals. The adopted remote sensing-geophysical approach showed being very effective for mapping the hydrothermal gold-related alteration zones, and is recommended for other similar investigations., (© 2024. The Author(s).)

There are limited data regarding the burden and trend of cardiovascular diseases (CVD) in psoriatic arthritis (PsA). We analyzed the National Inpatient Sample database from January 2005 to December 2018 to examine the hospitalization trends amongst adults with PsA primarily for heart failure (HF), acute myocardial infarction (AMI), and stroke. The primary outcomes of interest included in-hospital mortality, length of stay (LOS), and inflation-adjusted cost. The age-adjusted percentage of HF hospitalizations among PsA patients decreased from 2.5% (2005/06) to 1.4% (2011/12; P-trend 0.013) and subsequently increased to 2.0% (2017/18; P-trend 0.044). The age-adjusted percentage of AMI hospitalizations among PsA patients showed a non-statistically significant decreasing trend from 2.1% (2005/06) to 1.7% (2011/12; P-trend 0.248) and showed a non-statistically significant increase to 2.3% (2017/18; P-trend 0.056). The age-adjusted stroke hospitalizations increased from 1.1% (2005/06) to 1.3% (2017/18; P-trend 0.036). Apart from a decrease in adjusted inflation-adjusted cost among heart failure hospitalizations, there was no significant change in inpatient mortality, length of stay or hospital cost, during the study period. We found an increasing trend of cardiovascular hospitalizations in patients with PsA. These findings will raise awareness and inform further research and clinical practice for PSA patients with CVD., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Inflammatory processes are increasingly attributed to macrophage polarization. Proinflammatory macrophages promote T helper (Th) 1 response, tissue repair, and Th2 responses. Detection of macrophages in tissue sections is facilitated by CD68. Our study is focused on the expression of CD68 and the estimation of proinflammatory cytokines in children's patients with chronic tonsillitis secondary to vitamin D supplementation. This hospital-based Randomized prospective case-control study was conducted on 80 children with chronic tonsillitis associated with vitamin D deficiency where (40 received vitamin D 50,000 IU weekly for 3-6 months and 40 received 5 ml distilled water as placebo). The serum 25-hydroxyvitamin D [25(OH)D] was measured using an Enzyme-linked immunosorbent assay on all included children. Different histological and immunohistochemical studies for the detection of CD68 were done. There was a significantly lower serum level of 25(OH)D in the placebo group versus the vitamin D group (P < 0.001). The levels of pro-inflammatory cytokines, TNFα, and IL-2 significantly increased in the placebo group as compared to the vitamin D group (P < 0.001). The increased level of IL-4 and IL-10 in the placebo group as compared to the vitamin D group was insignificant (P = 0.32, 0.82) respectively. Vitamin D supplementation alleviated the deleterious effect of chronic tonsillitis on the histological structure of the tonsil. Tonsillar tissues of the children in the control and vitamin D groups demonstrated a highly statistically significantly lower number of CD68 immunoexpressing cells compared with those in the placebo group (P < 0.001). Low vitamin D may play a role in chronic tonsillitis. Vitamin D supplementation could help reduce the occurrence of chronic tonsillitis in susceptible children., (© 2023. The Author(s).)

Background: White matter hyperintensities (WMH) are the result of cerebral small vessel disease and may increase the risk of cognitive impairment (CI), recurrent stroke, and depression. We aimed to explore the association between selected cerebrovascular risk factors (CVRF) and WMH load as well as the effect of increased WMH burden on recurrent vascular events, CI, and depression in first-ever ischemic stroke patients., Methods: 431 from the PROSpective Cohort with Incident Stroke (PROSCIS) were included; Age-Related White Matter Changes (ARWMC) score was used to assess WMH burden on FLAIR. The presence of CVRF (defined via blood pressure, body-mass-index, and serological markers of kidney dysfunction, diabetes mellitus, and hyperlipoproteinemia) was categorized into normal, borderline, and pathological profiles based on commonly used clinical definitions. The primary outcomes included recurrent vascular events (combined endpoint of recurrent stroke, myocardial infarction and/or death), CI 3 years post-stroke, and depression 1-year post-stroke., Results: There was no clear association between CVRF profiles and WMH burden. High WMH lesion load (ARWMC score ≥ 10) was found to be associated with CI (adjusted OR 1.05 [95% CI 1.00-1.11]; p < 0.02) in a mixed-model analysis. Kaplan-Meier survival analysis showed a visible increase in the risk of recurrent vascular events following stroke; however, after adjustment, the risk was non-significant (HR 1.5 [95% CI 0.76-3]; p = 0.18). WMH burden was not associated with depression 1-year post stroke (adjusted OR 0.72 [95% CI 0.31-1.64]; p = 0.44)., Conclusion: Higher WMH burden was associated with a significant decline in cognition 3 years post-stroke in this cohort of first-ever stroke patients., (© 2022. The Author(s).)

Background: Accurate prediction of clinical outcomes in individual patients following acute stroke is vital for healthcare providers to optimize treatment strategies and plan further patient care. Here, we use advanced machine learning (ML) techniques to systematically compare the prediction of functional recovery, cognitive function, depression, and mortality of first-ever ischemic stroke patients and to identify the leading prognostic factors., Methods: We predicted clinical outcomes for 307 patients (151 females, 156 males; 68 ± 14 years) from the PROSpective Cohort with Incident Stroke Berlin study using 43 baseline features. Outcomes included modified Rankin Scale (mRS), Barthel Index (BI), Mini-Mental State Examination (MMSE), Modified Telephone Interview for Cognitive Status (TICS-M), Center for Epidemiologic Studies Depression Scale (CES-D) and survival. The ML models included a Support Vector Machine with a linear kernel and a radial basis function kernel as well as a Gradient Boosting Classifier based on repeated 5-fold nested cross-validation. The leading prognostic features were identified using Shapley additive explanations., Results: The ML models achieved significant prediction performance for mRS at patient discharge and after 1 year, BI and MMSE at patient discharge, TICS-M after 1 and 3 years and CES-D after 1 year. Additionally, we showed that National Institutes of Health Stroke Scale (NIHSS) was the top predictor for most functional recovery outcomes as well as education for cognitive function and depression., Conclusion: Our machine learning analysis successfully demonstrated the ability to predict clinical outcomes after first-ever ischemic stroke and identified the leading prognostic factors that contribute to this prediction., Competing Interests: ME reports grants from Bayer and fees paid to the Charité from Abbot, Amgen, AstraZeneca, Bayer, 296 Boehringer Ingelheim, BMS, Daiishi Sankyo, Sanofi, Novartis, Pfizer, all outside the submitted work. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Fast, Temuulen, Villringer, Kufner, Ali, Siebert, Huo, Piper, Sperber, Liman, Endres and Ritter.)

Objective: To determine the nutritional knowledge and clinical practices of physicians regarding nutrition in cirrhosis patients., Methods: This multi-centre cross-sectional knowledge and practice study was conducted at Pak Emirates Military Hospital, Rawalpindi, Bahria Town International Hospital, Rawalpindi, and District Headquarter Hospital, Mandi Bahauddin, Pakistan, from January to March 2020, and comprised physicians working in wards, out-patient and emergency departments. Data was collected through interviews using a self-generated structured questionnaire. Correct responses were scored 1 and incorrect ones as 0, with a maximum possible score of 13. Data was analysed using SPSS 16., Results: Of the 92 participants, 52(56.5%) were males, while the overall mean age was 28.3±4years and mean years in service 3.7±3 years. The mean score obtained was 5.8±2.1. Of the total, 33(35.9%) physicians had received formal nutritional training, 27(29.3%) were giving regular nutritional counselling and 48(52.2%) wrongly believed in the implementation of restricted diets. A large number of participants incorrectly considered salt 61(66.3%), water 49(53.2%) and lipids/oils 24(26%) to be avoided in ascites. Mean knowledge scores varied significantly for physicians dealing with cirrhosis patients on a daily basis (p<0.001) and those who had received formal training (p=0.003)., Conclusions: The nutritional knowledge of physicians regarding cirrhosis was found to be sub-optimal.

Background: The smoking-paradox of a better outcome in ischemic stroke patients who smoke may be due to increased efficacy of thrombolysis. We investigated the effect of smoking on outcome following endovascular therapy (EVT) with mechanical thrombectomy alone versus in combination with intra-arterial (IA-) thrombolysis., Methods: The primary endpoint was defined by three-month modified Rankin Scale (mRS). We performed a generalized linear model and reported relative risks (RR) for smoking (adjustment for age, sex, hypertension, atrial fibrillation, stroke severity, time to EVT) in patient data stemming from the Virtual International Stroke Trials Archive-Endovascular database., Results: Among 1,497 patients, 740(49.4%) were randomized to EVT; among EVT patients, 524(35.0%) received mechanical thrombectomy alone and 216(14.4%) received it in combination with IA-thrombolysis. Smokers (N = 396) had lower mRS scores (mean 2.9 vs. 3.2; p = 0.02) and mortality rates (10% vs. 17.3%; p<0.001) in univariate analysis. In all patients and in patients treated with mechanical thrombectomy alone, smoking had no effect on outcome in regression analyses. In patients who received IA-thrombolysis (N = 216;14%), smoking had an adjusted RR of 1.65 for an mRS≤1 (95%CI 0.77-3.55). Treatment with IA-thrombolysis itself led to reduced RR for favorable outcome (adjusted RR 0.30); interaction analysis of IA-thrombolysis and smoking revealed that non-smokers with IA-thrombolysis had mRS≤2 in 47 cases (30%, adjusted RR 0.53 [0.41-0.69]) while smokers with IA-thrombolysis had mRS≤2 in 23 cases (38%, adjusted RR 0.61 [0.42-0.87])., Conclusions: Smokers had no clear clinical benefit from EVT that incorporates IA-thrombolysis., Competing Interests: The authors have read the journal’s policy and the authors of this manuscript have the following competing interests: JBF reports consulting and advisory board fees from Abbvie, AC Immune, Artemida, BioClinica, Biogen, BMS, Brainomix, Cerevast, Daiichi-Sankyo, EISAI, Guerbet, Ionis Pharmaceuticals, Julius Clinical, jung diagnostics, Eli Lilly, Merck, and Tau Rx, all outside of the submitted work. M. Endres reports grants from Bayer and fees paid to the Charité from Bayer, Boehringer Ingelheim, BMS/Pfizer, Daiichi Sankyo, Amgen, GSK, Sanofi, Covidien, and Novartis, all outside of the submitted work. DSL reports research funding as an imaging core lab from Cerenovus, Genentech, Medtronic and Stryker. There are no patents, products in development or marketed products to declare. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Microbial pathogens drive tumorigenesis in 20% of cancer cases, so the present study is aimed to evaluate the carcinogenic activities, sperm abnormalities and other dangerous effects of the subcutaneous injection of extracts obtained from various clinical Gram-negative bacteria derived from cancer patients using albino rats. We isolated, identified and extracted of their secondary metabolites of carbapenem resistant Gram-negative bacteria derived from cancer patients. Various methods have been used to determine hepatotoxicity, nephrotoxicity, tumorigenesis, inflammatory and sperm abnormalities in the albino rats injected with extracts. In comparison with the normal animals group, all extracts induced hepatotoxicity which was evidenced by the significant elevation in the activity of the serum alanine aminotransferase, aspartate aminotransferase, gamma-glutamyltransferase and alkaline phosphatase; also, nephrotoxicity that was indicated through the marked increase in the serum urea and creatinine levels; tumorigenesis was achieved from the sharp elevation in serum levels of alpha fetoprotein, carcinoembryonic antigen and lactate dehydrogenase values as tumor markers; as well as severe inflammatory characteristics were monitored from the marked raise of tumor necrosis factor alpha and interleukin-1beta. Furthermore, the proportion of micronuclei in polychromatic erythrocytes and sperm abnormalities were statistically significant in all groups compared to control group. Various kinds of head abnormalities and coiled tail were noted. Histopathological examination of hepatic tissue came in line with the biochemical and cytological findings. It could conclude that the extracts of Serratia sp. Esraa 1, Stenotrophomonas sp. Esraa 2, Acinetobacter sp. Esraa 3, Escherichia sp. Esraa 4 and Pseudomonas sp. Esraa 5 were able to initiate cytotoxicity and tumorigenesis in rats.

Psoriasis vulgaris (PsV) is an immune-mediated inflammatory disorder with devastating psychosocial consequences. Expression of immunoregulator molecules on leukocytes in PsV remains unclear. Leukocyte-associated Ig-like receptor-1 (LAIR-1) and complement receptor-1 (CR-1) are immunoregulator receptors reported to bind complement component 1q involved in phagocytosis. We aimed to explore if altered leukocyte expression of LAIR-1 and CR-1 is associated with PsV. This case-control study included 36 PsV patients and 36 healthy controls. Neutrophils, monocytes and B and T cells were examined by flow cytometry for LAIR-1 and CR-1 mean fluorescence intensity (MFI) and positive cell percentage. Comparison between both groups revealed a significant decrease in LAIR-1 MFI on neutrophils and T cells ( P  < 0.001 and P  = 0.003, respectively). CR-1 MFI on neutrophils, monocytes and T cells also showed a significant decrease in patients ( P  = 0.033, P  = 0.001 and P  = 0.040, respectively). There was a significant positive correlation of LAIR-1 MFI on neutrophils with CR-1 MFI on neutrophils ( r  = 0.503; P  = 0.002) and LAIR-1 MFI on monocytes with CR-1 MFI on monocytes ( r  = 0.371; P  = 0.026). Receiver operating characteristic curves revealed that CR-1 MFI on monocytes had the highest discrimination power to differentiate patients from controls, with 86.1% specificity and 75% sensitivity ( P  = 0.001). In conclusion, altered leukocytes expression of LAIR-1 and CR-1 is associated with PsV. Down-regulated CR-1 MFI on monocytes is a promising diagnostic biomarker for PsV.

Objective: Inhibition of dipeptidyl peptidase IV (DPP-4) is currently one of the most valuable and potential chemotherapeutic regimes for the medication of Type 2 Diabetes Mellitus (T2DM)., Method: Based on linagliptin, this study discusses the design, synthesis and biological evaluation of spiro cyclohexane-1,2'-quinazoline scaffold hybridized with various heterocyclic ring systems through different atomic spacers as a highly potent DPP-4 inhibitors. DPP-4 enzyme assay represented that most of the target compounds are 102-103 folds more active than the reference drug linagliptin (IC50: 0.0005-0.0089 nM vs 0.77 nM; respectively). Moreover, in vivo oral hypoglycemic activity assay revealed that most of the tested candidates were more potent than the reference drug, sitagliptin, producing rapid onset with long duration of activity that extends to 24 h. Interestingly, the derivatives 11, 16, 18a and 23 showed evidence of mild cytochrome P450 3A4 (CYP3A4) inhibition (IC50; > 210 µM) and their acute toxicity (LD50) was more than 1.9 gm/kg. Molecular simulation study of the new quinazoline derivatives explained the obtained biological results., Conclusion: Finally, we conclude that our target compounds could be highly beneficial for diabetic patients in the clinic., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Type 2 diabetes (T2D) is a severe disease and it is one of the most raising problems worldwide. This study deals with design, synthesis and in vivo determination of a new set of tetralin-sulfonamide derivatives as anti-diabetic and dipeptidyl peptidase-IV (DPP-4) inhibiting agents. Most of the new compounds exhibited significant hypoglycemic effect alongside with DPP-4 suppression potency considering sitagliptin as a reference drug. The most promising compounds 4, 15 showed 2.80 nM DPP-4 IC 50 with 20-40 folds selectivity over DPP-8 and DPP-9. 2D and 3D QSAR models were performed using auto QSAR of Schrödinger, QuaSAR of MOE and 3D Field-based QSAR of Schrödinger, respectively. The experimental results revealed that the alignment-independent descriptors, electrostatic and steric field descriptors were significantly correlated with the antidiabetic activity of the new derivatives. In addition, the new compounds were docked in the active site of DPP-4 in reference to sitagliptin to rationalize the binding modes of the compounds with the amino acid residues of the enzyme. Furthermore, 131 I-compound 4 complex was selected to evaluate the pharmacokinetic behavioral profile of compound 4 and its body organs uptakes alongside its elimination pathway as a representative example for the rest of the analogues. The bio distribution pattern of the tracer proved the selective accumulation of 131 I-substrate in the pancreas and rapid clearance from most of the body organs., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Many surgeons practice prophylactic drainage after cholecystectomy without reliable evidence. This study was conducted to answer the question whether to drain or not to drain after cholecystectomy for acute calculous cholecystitis. A retrospective review of all patients who had cholecystectomy for acute cholecystitis in Aseer Central Hospital, Abha, Saudi Arabia, was conducted from April 2010 to April 2012. Data were extracted from hospital case files. Preoperative data included clinical presentation, routine investigations and liver function tests. Operative data included excessive adhesions, bleeding, bile leak, and drain insertion. Complicated cases such as pericholecystic collections, mucocele and empyema were also reported. Patients who needed therapeutic drainage were excluded. Postoperative data included hospital stay, volume of drained fluid, time of drain removal, and drain site problems. The study included 103 patients allocated into two groups; group A (n  =  38) for patients with operative drain insertion and group B (n  =  65) for patients without drain insertion. The number of patients with preoperative diagnosis of acute non-complicated cholecystitis was significantly greater in group B (80%) than group A (36.8%) (P < 0.001). Operative time was significantly longer in group A. All patients who were converted from laparoscopic to open cholecystectomy were in group A. Multivariate analysis revealed that hospital stay was significantly (P < 0.001) longer in patients with preoperative complications. There was no added benefit for prophylactic drain insertion after cholecystectomy for acute calculous cholecystitis in non-complicated or in complicated cases.

The effects of both garlic (Allium sativum) and onion (Allium cepa) on some biochemical parameters in Schistosoma mansoni infected mice individually and mixed either with or without the currently used drug, praziquantel (PZQ) were investigated. These involved some immunological parameters, namely IgM, IgG, interleukins 2 and 6 (IL-2 and 6) and tumor necrosis factor (TNF-α), some antioxidant enzymes [catalase, superoxide dismutase (SOD) and glutathione peroxidase (GPX)]. In addition, parasitological and histopathological investigations were performed. No changes were observed in the normal control mice treated with dry extract of onion or garlic, individually or mixed, with or without PZQ, compared to the normal healthy control group. Infection with S. mansoni showed an increase in IgG, IgM, IL-2, IL-6, TNF-α and catalase enzyme, accompanied with a decrease in GPX and SOD antioxidant enzyme activities. Remarkable amelioration was noticed in the levels of all the measured parameters in S. mansoni infected mice after administration of the studied extracts. Moreover a significant reduction in worm burden, hepatic and intestinal eggs and oogram count was noticed which was reflected in normalization of liver architecture.

The study of protective immune mechanisms effective against filarial nematodes has been hampered by the inability of these important human pathogens to infect laboratory mice. Recently, Litomosoides sigmodontis, a natural parasite of rats, has been developed as a valuable model for the study of filarial infection. BALB/c mice are fully susceptible to infection with L. sigmodontis third-stage larvae and develop patent infection. In contrast, mice on the C57BL background are resistant, and parasites undergo only a single molt and do not mature to adulthood. We used interleukin-5 (IL-5)-deficient mice on the C57BL/6 background to address the role of IL-5 and eosinophils in the innate resistance of C57BL/6 mice. We found no differences in parasite survival between IL-5-deficient and C57BL/6 mice. However, when these mice were used for the analysis of vaccine-mediated immunity, a critical role for IL-5 was elucidated. Mice genetically deficient in IL-5 were unable to generate a protective immune response when vaccinated with irradiated larvae, whereas C57BL/6 mice were fully protected from challenge infection. These studies help to clarify the highly controversial role of eosinophils in filarial infection.