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This study evaluated the effects of Pediococcus pentosaceus GT001 on Salmonella typhimurium (S. typhimurium)-challenged broiler chickens. Two hundred Ross 708 broiler day-old chicks with comparable weight were distributed at random into four treatments with five replicates and ten chicks per replicate. The following were the treatment groups: (B) basal diet (control); (B + S) basal diet and birds were challenged with S. typhimurium at 1.0 × 107 cfu/g; (B + P) basal diet + Pediococcus pentosaceus GT001 at 4.0 × 108 cfu/g; (B + P + S) basal diet + P. pentosaceus GT001 at 4.0 × 108 cfu/g and birds were challenged with S. typhimurium at 1.0 × 107 cfu/g. There was a significant reduction (p < 0.05) in the body weight of the Salmonella-infected birds compared to the other treatment groups. However, the FCRs of the broilers were comparable among the different treatment groups (p > 0.05). The lipid profile and liver function indices measured were significantly enhanced in the P. pentosaceus GT001-supplemented groups (B + P and B + P + S) compared to the group that was Salmonella-challenged (p < 0.05) but were similar to those in the control group. The serum antioxidant activities, such as the T-AOC, SOD, CAT, GHS-Px and MDA, were significantly improved in the P. pentosaceus GT001-supplemented groups (B + P and B + P + S) (p < 0.05). The MDA was similar in the B + P and B + P + S groups, but both were significantly lower than the control and the Salmonella groups. The administration of P. pentosaceus GT001 enhanced the lipase and amylase levels in both the serum and intestine of the broilers (p < 0.05). The immunoglobin (IgA, IgG, IgM) and cytokine (IL-10 and IL-6) levels in the serum were significantly higher in the B, B + P and B + P + S treatment groups (p < 0.05). The immune-related organs (bursa and spleen) were significantly influenced in the birds fed with P. pentosaceus GT001. No significant variation was noted among all the dietary treatments in terms of the measured meat quality indices. The small intestinal digesta content of the Salmonella load was below a detectable range after 14 days of infection (p < 0.05). No significant differences were observed among the different treatment groups in terms of the breast pH, drip loss and meat color (p > 0.05). The inclusion of P. pentosaceus GT001 also modified the community structure in the cecum. This indicates that it has health benefits and could be incorporated in the broiler diet.

The coronavirus disease 2019 (COVID-19) pandemic caused an abrupt transition from face-to-face to online anatomy teaching, learning, and assessment. Although online education has ensured the continuity of anatomy education during the pandemic, its implementation has been challenging, and its effectiveness has been questioned. Therefore, literature pertinent to online anatomy education during the pandemic is crucial to explain COVID-19's disruptions to this field. Accordingly, this scoping review explored changes, disruptions, and gaps in anatomy teaching and assessment during COVID-19 using an enhanced version of Arksey and O'Malley's six-stage protocol. Five online databases were searched for articles that described changes and disruptions in anatomy education. Three independent researchers were involved in titles, abstracts, and full texts screening, while another four researchers were independently involved in data extraction, charting, and synthesis. This review revealed six themes: immediate strategic plans and actions, teaching and learning changes, online assessment practice, students' and educators' receptivity and adaptability, online learning and assessment effects, and future directions. It also revealed four gaps: non-future-ready curricula, learning obstacles, administrative and teaching challenges, and online education ethical issues. The results were reported in tabular and narrative forms, following the PRISMA Extension for Scoping Reviews (PRISMA-ScR guidelines). Understanding the evolution and gaps in anatomy education during the COVID-19 pandemic will help anatomists design future-ready, adaptable curricula.

Introduction: The structural and dynamic determinants that confer highly selective RET kinase inhibition are poorly understood. Objectives: To explore the druggability landscape of the RET active site in order to uncover structural and dynamic vulnerabilities that can be therapeutically exploited. Methods: We apply an integrated structural, computational and biochemical approach in order to explore the druggability landscape of the RET active site. Results: We demonstrate that the that the druggability landscape of the RET active site is determined by the conformational setting of the ATP-binding (P-) loop and its coordination with the αC helix. Open and intermediate P-loop structures display additional druggable vulnerabilities within the active site that were not exploited by first generation RET inhibitors. We identify a cryptic pocket adjacent to the catalytic lysine formed by K758, L760, E768 and L772, that we name the post-lysine pocket, with higher druggability potential than the adenine-binding site and with important implications in the regulation of the phospho-tyrosine kinase activity. Crystal structure and simulation data show that the binding mode of highly-selective RET kinase inhibitors LOXO-292 and BLU-667 is controlled by a synchronous open P-loop and αC-in configuration that allows accessibility to the post-lysine pocket. Molecular dynamics simulations show that these inhibitors efficiently occupy the post-lysine pocket with high stability through the simulation time-scale (300 ns), with both inhibitors forming hydrophobic contacts further stabilized by pi-cation interactions with the catalytic K758. Engineered mutants targeting the post-lysine pocket impact on inhibitor binding and sensitivity, as well as RET tyrosine kinase activity. Conclusions: The identification of the post-lysine pocket as a new druggable vulnerability in the RET kinase and its exploitation by second generation RET inhibitors have important implications for future drug design and the development of personalized therapies for patients with RET-driven cancers.

Abstract Cytosine deaminase (CDA) is a prodrug mediating enzyme converting 5-flurocytosine into 5-flurouracil with profound broad-range anticancer activity towards various cell lines. Availability, molecular stability, and catalytic efficiency are the main limiting factors halting the clinical applications of this enzyme on prodrug and gene therapies, thus, screening for CDA with unique biochemical and catalytic properties was the objective. Thermotolerant/ thermophilic fungi could be a distinctive repertoire for enzymes with affordable stability and catalytic efficiency. Among the recovered thermotolerant isolates, Aspergillus niger with optimal growth at 45 °C had the highest CDA productivity. The enzyme was purified, with purification 15.4 folds, molecular mass 48 kDa and 98 kDa, under denaturing and native PAGE, respectively. The purified CDA was covalently conjugated with dextran with the highest immobilization yield of 75%. The free and CDA-dextran conjugates have the same optimum pH 7.4, reaction temperature 37 °C, and pI 4.5, and similar response to the inhibitors and amino acids suicide analogues, ensuring the lack of effect of dextran conjugation on the CDA conformational structure. CDA-Dextran conjugates had more resistance to proteolysis in response to proteinase K and trypsin by 2.9 and 1.5 folds, respectively. CDA-Dextran conjugates displayed a dramatic structural and thermal stability than the free enzyme, authenticating the acquired structural and catalytic stability upon dextran conjugation. The thermal stability of CDA was increased by about 1.5 folds, upon dextran conjugation, as revealed from the half-life time (T 1/2 ). The affinity of CDA-conjugates (K m 0.15 mM) and free CDA (K m 0.22 mM) to deaminate 5-fluorocytosine was increased by 1.5 folds. Upon dextran conjugation, the antiproliferative activity of the CDA towards the different cell lines “MDA-MB, HepG-2, and PC-3” was significantly increased by mediating the prodrug 5-FC. The CDA-dextran conjugates strongly reduce the tumor size and weight of the Ehrlich cells (EAC), dramatically increase the titers of Caspase-independent apoptotic markers PARP-1 and AIF, with no cellular cytotoxic activity, as revealed from the hematological and biochemical parameters.

Abstract Background Available data collected from patients of different types of acute cerebrovascular strokes can detect risk factors, clinical data (including semiology of seizures), EEG findings and functional outcome of these patients. Stroke, both ischemic and hemorrhagic, has been considered an essential cause of epilepsy, especially in the elderly. Complications of acute stroke during the early days after the insult determine the ultimate outcome of events. The aim of this study is to determine the clinical and neurophysiological characteristics of stroke patients with or without clinical evident fits for early detection and better management. Results The brain imaging of the cases group who developed seizures showed that 50% of the cases have arterial ischemic infarction, 30% venous infarction, 6.67% ischemic infarction with haemorrhagic transformation, 6.67% intracerebral haemorrhage and 6.67% have subarachnoid haemorrhage. Based on the 2017 ILAE criteria, 43.33% of the patients developed focal to bilateral tonic clonic seizures, 33.33% developed focal aware seizures, 16.67% of the patients developed generalized tonic clonic seizures and 6.67% of the patient developed status epilepticus. EEG findings of the group of patients who developed seizures showed, focal slowing in 46.67%, focal epileptiform activity in 13.33%, focal activity with secondary generalization in 10%, PLEDS in 6.67%, generalized epileptiform activity in 6.67%, generalized slowing in 6.67% and normal EEG in 10% of the patients. Non convulsive status was found in 2 patients (6.67%) of the group with altered mental status. There was no PLEDS in EEG of group of patients without clinical seizures. This study did not find age and sex differences in patients with and without seizures. In addition, it was found that there was no statistically significant difference between the three groups as regard history of diabetes mellitus, hypertension, heart diseases, atrial fibrillation, carotid stenosis and collagen diseases. There was no significant relationship between seizures and early treatment with Rtpa and thrombectomy. Conclusions Focal to bilateral tonic clonic and focal aware seizures were the most prevalent type of early onset seizures after stroke, followed by generalized tonic clonic seizures and status epilepticus. Most EEG findings in this study were focal slowing, focal epileptiform activities, generalized epileptiform activities and PLEDS.

The purpose of this study is to construct and evaluate diagnostic battery tests of verbal and non-verbal learning disabilities for students in the Arabic schools. 612 students were in the 3rd, 4th and 5th grades of primary school were involved, mostly from Egypt and Saudi Arabia. Their ages ranged from 7.94-10.98 with mean age = 9.62 and SD = ±0.93. The Diagnostic Battery Tests (DBT) of VLD and NVLD for the primary school students was developed in accordance with the Arabic environment. The Battery includes seven subtests divided into two fields; the verbal learning disabilities and the non-verbal learning disabilities. The tests are developed in accordance with the ages of students and their academic grades. With the help of results, it has been found that DBT of VLD and NVLD have shown good reliability and validity indictors. Additionally, DBT showed the ability to distinguish between neurotypical students and those with learning difficulties. With increasing grades from three to five, the increase in performance level, decrease in performance time and standard deviations were noticeable, which can be attributed to the improvement in learning, experience, maturity and cognitive growth level with the progress of grades.

Abstract Background The use of Khat (Catha edulis) causes health, psychological, and socioeconomic burdens, and many scientific studies have been conducted on this abused plant. A careful review using bibliometric methods is required to increase the usefulness of this research and contribute to curbing the Khat problem. The main objective of this study is to evaluate the intellectual structure, diffusion of knowledge, emerging literature, and impact of collaboration in Khat research using bibliometric analysis. Main body The Scopus database was used to extract scientific papers published from 1961 to 2021 and search for titles and abstracts published in English. The VOSviewer software and MS Excel were used for citation, co-citation, and co-authorship analyses. Bibliographic coupling was calculated using the fractional counting method. There were 996 papers published in 60 years, 159 researchers, and 80 countries that met the criteria for inclusion. The top publishing countries, in order, are Ethiopia, the USA, Saudi Arabia, the UK, and Yemen. The USA provided the most prominent financial support for Khat’s research. 32.1% of research is in the medical field, with eleven more diverse research fields. The top-publishing researcher with the highest total link strength is Mustafa al’Absi from Minnesota Medical School, USA. A bibliometric mapping of citations revealed 113 articles with more than 50 citations, diffused across various research areas. The Journal of Ethnopharmacology is the top-cited source. Ethiopia is the most collaborative country. Molecular mechanisms of Khat toxicity on gene and protein levels are emerging. A network visualization map of terms' occurrence in titles and abstracts resulted in four research themes. Conclusion The current study encourages researchers from various fields to inaugurate new platforms and direct the research toward evidence-based cessation programs.

Helicobacter pylori is a microaerophile Gram-negative bacillus, resistant to the activity of gastric juice. The bacteria may take the vegetative form (spiral shape) or sporulation form .Liver cirrhosis and H.Pylori infection are two common diseases in our population and reducing the incidence of complications in cirrhotic subjects is an important step in current gastroenterology practice. The aim of the present study is to determine incidence of H. Pylori infection among patients with liver cirrhosis secondary to HCV infection and study the correlation between esophageal varices degree and H. Pylori infection. This study involved 50 patients with liver cirrhosis secondary to Hepatitis C Virus infection were selected from gastroenterology and internal medicine clinics at Beni-Suef general hospital and Beni-Suef university hospital. Our results illustrate that the percent of H. pylori infection among studied patients was 68%, our results illustrate that there is statistically significant association between the grade of varices and the detection of H. pylori; p value is less than 0.001.