Assessment of Knowledge, Attitude, and Preventive Behavior Regarding Toxoplasmosis among Females in Riyadh, Saudi Arabia: A Cross-Sectional Study.

Toxoplasmosis, a prevalent parasitic zoonotic disease, is influenced by various factors such as the climate, dietary habits, and hygiene practices. This study aimed to evaluate the knowledge, attitudes, and preventive behaviors regarding toxoplasmosis among females in Riyadh, Saudi Arabia. Utilizing a bilingual Google form, a cross-sectional online survey was distributed in both Arabic and English, and it was conducted between 11 January 2024 and 4 March 2024. Statistical analysis was conducted using SPSS Version 27, with a p-value ≤ 0.05 indicating significant qualitative data. The data were analyzed using descriptive statistics and the chi-square test. A total of 533 participants were included in the study. Participants aged 18-25 years old constituted the largest group (70.4%), with those aged 26-40 years old accounting for 14.4% and ages 41-60 years old comprising 15.2%. Among the participants, 76.4% were unmarried, and 21.4% were pregnant. Notably, 79.2% of participants reported being unaware of toxoplasmosis, with only 9.0% gaining awareness from doctors and a mere 3.6% from awareness campaigns. Any understanding of the disease's severity and causative factors was limited to 15.9%. Despite a generally positive attitude towards preventive measures, significant correlations were found between toxoplasmosis and age (p-value 0.093), as well as the consumption of medium-cooked meat (p-value 0.008). Other variables, such as social status, cat ownership, handwashing before meals, and washing fruits and vegetables did not show significant correlations. Diet and hygiene practices notably impact toxoplasmosis transmission. In Riyadh, 79% of participants did not own cats, and 67.7% avoided undercooked meat. However, 6.7% used unfiltered water, and 8.4% did not wash their hands after handling raw meat and vegetables. The study concludes that there is insufficient knowledge regarding toxoplasmosis among females in Riyadh. Despite low knowledge, there is a neutral to slightly positive attitude and a willingness to learn and adopt preventive measures when informed. With better education, attitudes towards toxoplasmosis could improve due to a desire to learn and act. While general hygiene practices were favorable, specific preventive behaviors for toxoplasmosis need enhancement to reduce infection risks.

A cross-sectional study on adult lifestyle habits during the COVID-19 pandemic.

COVID-19 has spread and developed into a pandemic disease, forcing countries to impose challenging protocols and lockdowns. This study assessed shopping, food consumption behavior, and feelings in Jordan and several Arab countries during the COVID-19 pandemic. A cross-sectional web-based survey among the Middle East population was conducted using an online questionnaire between July and September 2022. Participants were requested to answer a standardized and validated structured questionnaire. Demographic information, shopping behavior information, and mental health data were requested. A total of 542 respondents were included in the study. During COVID-19 quarantine, participants (68.6%) reported decreased shopping frequency and buying more food than usual (37.5%). Cereals and legumes were the primary food types stored by participants (76.9%). Multiple logistic regression revealed the age of the participant as a significant factor affecting storing of food (being ≤ 25 years old (OR = 0.456, p value = 0.038)). 75.7% of female participants eat less frequently in restaurants than usual. In contrast, among males, 48.5% reported that they eat at restaurants less frequently than usual. The country of residency and gender were the significant factors affecting negative feelings and emotions. Participants in countries other than Jordan had a higher negative feeling score (Beta = 0.086, p value = 0.042). Furthermore, females had a higher negative feeling score (Beta = -0.128, p value = 0.003) as the negative feelings score for females was 3.58 (SD = 5.443). On the other hand, it was 2.10 (SD = 5.091) for males. The COVID-19 pandemic has altered Jordanians' attitudes, shopping, and food consumption habits. Although positive behaviors have improved, such as shopping less frequently, eating home-cooked meals, and dining with family, frequent snacking and food storage have increased. Finally, public awareness of shopping and food consumption habits should be promoted.

Contributions of Hyperactive Mutations in Mpro from SARS-CoV-2 to Drug Resistance.

The appearance and spread of mutations that cause drug resistance in rapidly evolving diseases, including infections by the SARS-CoV-2 virus, are major concerns for human health. Many drugs target enzymes, and resistance-conferring mutations impact inhibitor binding or enzyme activity. Nirmatrelvir, the most widely used inhibitor currently used to treat SARS-CoV-2 infections, targets the main protease (Mpro) preventing it from processing the viral polyprotein into active subunits. Our previous work systematically analyzed resistance mutations in Mpro that reduce binding to inhibitors; here, we investigate mutations that affect enzyme function. Hyperactive mutations that increase Mpro activity can contribute to drug resistance but have not been thoroughly studied. To explore how hyperactive mutations contribute to resistance, we comprehensively assessed how all possible individual mutations in Mpro affect enzyme function using a mutational scanning approach with a fluorescence resonance energy transfer (FRET)-based yeast readout. We identified hundreds of mutations that significantly increased the Mpro activity. Hyperactive mutations occurred both proximal and distal to the active site, consistent with protein stability and/or dynamics impacting activity. Hyperactive mutations were observed 3 times more than mutations which reduced apparent binding to nirmatrelvir in recent studies of laboratory-grown viruses selected for drug resistance. Hyperactive mutations were also about three times more prevalent than nirmatrelvir binding mutations in sequenced isolates from circulating SARS-CoV-2. Our findings indicate that hyperactive mutations are likely to contribute to the natural evolution of drug resistance in Mpro and provide a comprehensive list for future surveillance efforts.

The role of TAOK3 in cancer progression and development as a prognostic marker: A pan-cancer analysis study.

The protein kinase TAOK3, belongs to the MAP kinase family, is one of three closely related members, namely TAOK1, TAOK2, and TAOK3. We performed a pan-cancer investigation of TAOK3 across different cancer types, including uterine carcinosarcoma, adenocarcinoma of the stomach and pancreas, and endometrial carcinoma of the uterus, to better understand TAOK3's role in cancer. In at least 16 types of cancer, our findings indicate that TAOK3 expression levels differ considerably between normal and tumor tissues. In addition, our study is the first to identify the oncogenic role of TAOK3 locus S331 and S471 in renal clear cell carcinoma, Glioblastoma Multiforme, hepatocellular carcinoma, Lung adenocarcinoma, and Pancreatic adenocarcinoma, indicating their involvement in cancer progression. In addition, our data analysis indicates that copy number variation is the most prevalent form of mutation in the TAOK3 gene, and that there is a negative correlation between TAOK3 mRNA and DNA promoter methylation. Moreover, our analysis suggests that TAOK3 may serve as a prognostic marker for several kinds of cancer, including Colon adenocarcinoma, renal clear cell carcinoma, Lower Grade Glioma, Lung adenocarcinoma, Mesothelioma, and hepatocellular carcinoma. In addition, our research on signature cancer genes has uncovered a positive association between TAOK3 and SMAD2, SMAD4, and RNF168 in most of the malignancies we have examined. TAOK3 is also correlated with the frequency of mutations and microsatellite instability in four types of cancer. Numerous immune-related genes are closely associated with TAOK3 levels in numerous malignancies. TAOK3 expression is positively correlated with immune infiltrates, which include activated CD4 T cells, CD8 T cells, and type 2T helper cells. Our pan-cancer analysis of TAOK3 provides vital insight into its potential role across a variety of cancer types.

Protective influence of supplementary betaine against heat stress by regulating intestinal oxidative status and microbiota composition in broiler chickens.

To assess the impact of supplementing betaine (BT) under heat stress (HS) conditions on broiler performance and intestinal health from 21 to 42 days of age, a total of 150 male Ross 308 broilers were indiscriminately allotted to 3 treatments with 10 replications of 5 birds each. The control (CON) group was given a basal ration and accommodated at a thermoneutral condition (22 ± 1 °C), whereas the HS and HS + BT groups were raised under cyclic HS (33 ± 1 °C for 8 h and 22 ± 1 °C for 16 h per day) and received the basal ration without or with 1000 mg/kg BT, respectively. The HS reduced average daily gain (ADG); average daily feed intake; villus height (VH); VH to crypt depth (CD) ratio (VCR); activities of trypsin, lipase, glutathione peroxidase (GPX), and catalase; and enumeration of Lactobacillus and Bifidobacterium (P < 0.05) and augmented feed conversion ratio (FCR), CD, malondialdehyde (MDA) accumulation, and enumeration of Escherichia coli, Clostridium, and coliforms (P < 0.05). Conversely, BT supplementation heightened ADG, VH, VCR, trypsin activity, GPX activity, and populations of Lactobacillus and Bifidobacterium (P < 0.05) and lowered FCR, MDA accumulation, and Clostridium population (P < 0.05). Furthermore, the FCR value, trypsin and GPX activities, MDA content, and Bifidobacterium and Clostridium populations in the HS + BT group were nearly equivalent to those in the CON group. To conclude, feeding BT under HS conditions could improve broiler performance through improving intestinal health by specifically mitigating oxidative damage and enhancing the colonization of beneficial bacteria.

Anemia and Hypoxia Impact on Chronic Kidney Disease Onset and Progression: Review and Updates.

Chronic kidney disease (CKD) is caused by hypoxia in the renal tissue, leading to inflammation and increased migration of pathogenic cells. Studies showed that leukocytes directly sense hypoxia and respond by initiating gene transcription, encoding the 2-integrin adhesion molecules. Moreover, other mechanisms participate in hypoxia, including anemia. CKD-associated anemia is common, which induces and worsens hypoxia, contributing to CKD progression. Anemia correction can slow CKD progression, but it should be cautiously approached. In this comprehensive review, the underlying pathophysiology mechanisms and the impact of renal tissue hypoxia and anemia in CKD onset and progression will be reviewed and discussed in detail. Searching for the latest updates in PubMed Central, Medline, PubMed database, Google Scholar, and Google search engines were conducted for original studies, including cross-sectional studies, cohort studies, clinical trials, and review articles using different keywords, phrases, and texts such as "CKD progression, anemia in CKD, CKD, anemia effect on CKD progression, anemia effect on CKD progression, and hypoxia and CKD progression". Kidney tissue hypoxia and anemia have an impact on CKD onset and progression. Hypoxia causes nephron cell death, enhancing fibrosis by increasing interstitium protein deposition, inflammatory cell activation, and apoptosis. Severe anemia correction improves life quality and may delay CKD progression. Detection and avoidance of the risk factors of hypoxia prevent recurrent acute kidney injury (AKI) and reduce the CKD rate. A better understanding of kidney hypoxia would prevent AKI and CKD and lead to new therapeutic strategies.

Systematic Analyses of the Resistance Potential of Drugs Targeting SARS-CoV-2 Main Protease.

Drugs that target the main protease (Mpro) of SARS-CoV-2 are effective therapeutics that have entered clinical use. Wide-scale use of these drugs will apply selection pressure for the evolution of resistance mutations. To understand resistance potential in Mpro, we performed comprehensive surveys of amino acid changes that can cause resistance to nirmatrelvir (Pfizer), and ensitrelvir (Xocova) in a yeast screen. We identified 142 resistance mutations for nirmatrelvir and 177 for ensitrelvir, many of which have not been previously reported. Ninety-nine mutations caused apparent resistance to both inhibitors, suggesting likelihood for the evolution of cross-resistance. The mutation with the strongest drug resistance score against nirmatrelvir in our study (E166V) was the most impactful resistance mutation recently reported in multiple viral passaging studies. Many mutations that exhibited inhibitor-specific resistance were consistent with the distinct interactions of each inhibitor in the substrate binding site. In addition, mutants with strong drug resistance scores tended to have reduced function. Our results indicate that strong pressure from nirmatrelvir or ensitrelvir will select for multiple distinct-resistant lineages that will include both primary resistance mutations that weaken interactions with drug while decreasing enzyme function and compensatory mutations that increase enzyme activity. The comprehensive identification of resistance mutations enables the design of inhibitors with reduced potential of developing resistance and aids in the surveillance of drug resistance in circulating viral populations.

Antibiotic-Lysobacter enzymogenes proteases combination as a novel virulence attenuating therapy.

Minimizing antibiotic resistance is a key motivation strategy in designing and developing new and combination therapy. In this study, a combination of the antibiotics (cefixime, levofloxacin and gentamicin) with Lysobacter enzymogenes (L. enzymogenes) bioactive proteases present in the cell- free supernatant (CFS) have been investigated against the Gram-positive methicillin-sensitive Staphylococcus aureus (MSSA), methicillin-resistant Staphylococcus aureus (MRSA) and the Gram-negative Escherichia coli (E. coli O157:H7). Results indicated that L. enzymogenes CFS had maximum proteolytic activity after 11 days of incubation and higher growth inhibitory properties against MSSA and MRSA compared to E. coli (O157:H7). The combination of L. enzymogenes CFS with cefixime, gentamicin and levofloxacin at sub-MIC levels, has potentiated their bacterial inhibition capacity. Interestingly, combining cefixime with L. enzymogenes CFS restored its antibacterial activity against MRSA. The MTT assay revealed that L. enzymogenes CFS has no significant reduction in human normal skin fibroblast (CCD-1064SK) cell viability. In conclusion, L. enzymogenes bioactive proteases are natural potentiators for antimicrobials with different bacterial targets including cefixime, gentamicin and levofloxacin representing the beginning of a modern and efficient era in the battle against multidrug-resistant pathogens.

Crystal Structures of Inhibitor-Bound Main Protease from Delta- and Gamma-Coronaviruses.

With the spread of SARS-CoV-2 throughout the globe causing the COVID-19 pandemic, the threat of zoonotic transmissions of coronaviruses (CoV) has become even more evident. As human infections have been caused by alpha- and beta-CoVs, structural characterization and inhibitor design mostly focused on these two genera. However, viruses from the delta and gamma genera also infect mammals and pose a potential zoonotic transmission threat. Here, we determined the inhibitor-bound crystal structures of the main protease (Mpro) from the delta-CoV porcine HKU15 and gamma-CoV SW1 from the beluga whale. A comparison with the apo structure of SW1 Mpro, which is also presented here, enabled the identification of structural arrangements upon inhibitor binding at the active site. The cocrystal structures reveal binding modes and interactions of two covalent inhibitors, PF-00835231 (active form of lufotrelvir) bound to HKU15, and GC376 bound to SW1 Mpro. These structures may be leveraged to target diverse coronaviruses and toward the structure-based design of pan-CoV inhibitors.

Allosteric quinoxaline-based inhibitors of the flavivirus NS2B/NS3 protease.

Viruses from the Flavivirus genus infect millions of people worldwide and cause severe diseases, including recent epidemics of dengue virus (DENV), and Zika virus (ZIKV). There is currently no antiviral treatment against flavivirus infections, despite considerable efforts to develop inhibitors against essential viral enzymes including NS2B/NS3 protease. Targeting the flavivirus NS2B/NS3 protease proved to be challenging because of the conformational dynamics, topology, and electrostatic properties of the active site. Here, we report the identification of quinoxaline-based allosteric inhibitors by fragment-based drug discovery approach as a promising new drug-like scaffold to target the NS2B/NS3 protease. Enzymatic assays and mutational analysis of the allosteric site in ZIKV NS2B/NS3 protease support noncompetitive inhibition mechanism as well as engineered DENV protease construct indicating the compounds likely compete with the NS2B cofactor for binding to the protease domain. Furthermore, antiviral activity confirmed the therapeutic potential of this new inhibitor scaffold.

The Relationship Between Menstrual Cycle Irregularities and COVID-19 Vaccination.

Background After COVID-19 vaccination, females reported irregularities and changes in their menstrual cycle. We aimed to explore the menstrual irregularities following COVID-19 vaccination in Saudi women of childbearing age. Methodology The study was a cross-sectional study conducted among women in Riyadh, Saudi Arabia, who had no history of menstrual irregularities before receiving the first dose of the COVID-19 vaccine. The participants filled out an online self-administered questionnaire via Google Form about any menstrual irregularities they experienced after receiving the COVID-19 vaccine. Results A total of 535 participants completed the survey. The study found that 41.7% (223) of women experienced menstrual changes after the first dose of the COVID-19 vaccine, increasing to 44.1% (236) after the second dose. The incidence of these changes varied between the first and second doses. For example, the incidence of changes in period duration decreased from 51.6% to 48.3% after the first and second doses, respectively. Similarly, the incidence of delayed periods decreased from 48.4% to 47.9%, while dysmenorrhea increased slightly from 30.9% to 32.2% after the two doses. The incidence of heavier menstrual flow increased from 26.9% to 30.5%, while the incidence of lighter menstrual flow decreased from 26.9% to 24.6% after the first and second doses, respectively. Conclusions There is an increased incidence of changes in menstrual cycle after COVID-19 vaccination, particularly in menstrual cycle length, menstrual pain, and the flow of menstruation. Future studies are needed to investigate the potential underlying biological mechanisms.

Anticancer, Immunomodulatory, and Phytochemical Screening of Carthamus oxyacantha M.Bieb Growing in the North of Iraq.

Carthamus oxyacantha M.Bieb is a promising repository of active phytochemicals. These bioactive compounds work synergistically to promote the plant's antioxidant, anticancer, and immunomodulatory capabilities. The present study aimed to discover the potential immunomodulatory and cytotoxicity of different extracts of Carthamus oxycantha roots. Aqueous ethanol (70%), aqueous methanol (90%), ethyl acetate, and n-hexane extracts were tested against five cell lines (T47D, MDA-MB231, Caco-2, EMT6/P, and Vero). Among these extracts, ethyl acetate and n-hexane extracts showed significant activity in inhibiting the proliferation of cancerous cells because of the presence of several phytochemical compounds, including flavonoids, phenolics, and alkaloids. The n-hexane extract was the most potent extract against T47D and Caco-2 cell lines and had IC50 values of 0.067 mg/mL and 0.067 mg/mL, respectively. In comparison, ethyl acetate extract was active against T47D and MDAMB231, and IC50 values were 0.0179 mg/mL and 0.03 mg/mL, respectively. Both n-hexane and ethyl acetate extracts reduced tumor size (by 49.981% and 51.028%, respectively). Remarkably, Carthamus oxyacantha extracts decreased the average weight of the tumor cells in the in vivo model. The plant induced significant apoptotic activity by the activation of caspase-3, immunomodulation of macrophages, and triggering of pinocytosis. The implications of these intriguing findings demand additional research to broaden the scope of the understanding of this field, opening the doors to the possibilities of using Carthamus oxyacantha M.Bieb as an effective cancer treatment adjuvant in the future.

Knowledge, practice and attitude associated with SARS-CoV-2 Delta Variant among adults in Jordan.

COVID-19 infection is a global pandemic health emergency. This contagious disease was caused by the Severe Acute Respiratory Syndrome Coronavirus­2 (SARS­CoV-2) which is mutating over time. In 2021, the Delta variant became the most dominant transmissible form. During the crisis, human practice and knowledge were critical in the overall efforts to encompass the outbreak. A cross-sectional, web-based approach was conducted among adults in Jordan to quantify knowledge, attitude, and practices towards SARS-CoV-2 (Delta variant). This research was carried out between 15th April and 15th of May 2021. The study questionnaire consisted of four sections including the participant's demographics, knowledge, practices and attitude. Comparative evaluation of responses was accomplished using a scoring system. Respondents who scored above the mean score (60%) on the item measured were categorized as knowledgeable, having a positive attitude, and good practices. Participants were allocated to one of the three groups; medical, non-medical and others (unemployed and housewives). Data collected was analyzed using Statistical Package for Social Sciences (SPSS) version 23.0 software. A variance test to assess the statistical difference between groups was used. Pearson's chi-squared test was applied to compare the variables and identify significant predictors. Of the participants, 308 (66%) were in the age group of 18-25yrs, 392 (84.1%) females, 120 (25.8%) employed and 346 (74.2%) unemployed. The principle source of knowledge was social media (291, 62.4%). Interestingly, participants had adequate overall knowledge. The mean knowledge score was 22.6 (± 0.19), 20.6 (± 0.19), and 21.3 (± 0.18) for the medical, the non-medical and the others group, respectively. Also, participants showed a positive attitude and good practices towards SARS-CoV-2 (Delta variant). The mean practice score for medical, the non-medical and the others groups was 7.35 (± 0.25), 7.38 (± 0.24), 7.35 (± 0.24) and the mean attitude score was 10.8 (± 0.16), 9.4 (± 0.21), 9.5 (± 0.22), respectively. The studied groups generally had good knowledge, positive attitudes and good practices about SARS-CoV-2 (Delta variant). This was expected due to the authorities' successful management of the pandemic and the high educational level of the Jordanian society, bearing in mind the economic and social impact of COVID-19 disease.

MULTISYSTEM INFLAMMATORY SYNDROME IN CHILDREN COURSE AMID COVID-19 PANDEMIC IN THE REBUBLIC OF BELARUS

ResumeIn first two years of COVID-19 pandemic, children usually had a mild or asymptomatic form of the disease. However, in rare cases, after suffering COVID-19, children had clinical manifestations similar to incomplete Kawasaki Disease (CD) or toxic shock syndrome. This condition is known as multisystem inflammatory syndrome in children (MIS-C). The purposeof this research was to study clinical and laboratory features and outcomes of multisystem inflammatory syndrome in children who were hospitalized during COVID-19 pandemic. Materials and methodsIn 19 months (May 2020 - December 2021) 63 patients with a diagnosis of "Multisystem inflammatory syndrome in children" (MIS-C) associated with COVID-19 were observed in the departments of Anesthesiology and Intensive Care of the Healthcare Institution "City Childrens Infectious Clinical Hospital" in Minsk, Republic of Belarus. MIS-C was diagnosed on criteria of CDC/WHO, 2020. All calculations were carried out in the statistical package R, version 4.1. The results of the analysis were considered statistically significant with p<0,05. The results of the studyAll of 63 children with MIS-C didnt have an acute coronavirus infection. Therefore, it was impossible to determine which strain of SARS-CoV-2 patient exactly had. However, we formed 3 groups of patients based on circulation of the dominant strain of SARS-CoV-2 in Belarus at different times. The 1st group included 40 patients (63,5%) received treatment from 05.25.2020 to 02.21.2021 ("wuhan strains"); the 2nd group - 9 children (14,3%) from 02.23.2021 to 06.13.2021 ("alpha"); the 3rd group - 14 children (22,2%) from 07.01.2021 to 11.19.2021 ("delta"). 47 (74,6%) patients had complete and incomplete Kawasaki Disease phenotype of MIS-C. Nonspecific phenotype was observed in 16 (25,4%) children. It manifested as signs of shock. The mean age didnt differ in study groups. It was 7{+/-}2,5; 9,4{+/-}4,2; 7,9{+/-}5 years respectively. All children had hyperthermic syndrome. Fever reached febrile numbers 3-4 times a day. Average fever duration was 3,2 [1-15] days. The course of MIS-C in children also didnt depend on the circulating strain of the virus. For instance, gastrointestinal dysfunction was observed in all three groups with equal frequency (73%, 78% and 57%, respectively). The only a statistically significant increase was in the number of children with cheilitis. In the 2nd group 8 children (89%) and the 3rd group 13 children (93%) had cheilitis, respectively, p=0,002. Neurological disorders such as headache, hyperesthesia, hallucinations, photophobia were more often observed in the 1st group of children - 19 (48%) cases and less frequently in the 2nd and 3rd group (in 11% and 14% of cases), p=0,022. Pathological blood flow regurgitation was the most common disorder (68-71%). Several biochemical markers of inflammation levels, such as C-reactive protein (CRP) and procalcitonin (PCT), were high. CRP levels were 162 mg/l [130; 245]; 130 mg/l [90; 160]; 130 mg/l [106; 149] in 3 study groups, respectively. In children of the 1st group CRP level was significantly higher, p=0.052. PCT level was higher in patients of the 3rd group (4.2 ng/ml [2,4; 8,8]; 3.9 ng/ml [3,2; 11,9]; 8.7 ng/ml [3,4; 14,1], p=0.625). ConclusionAs a result of the research there wasnt found notable connection between clinical or laboratory features of MIS-C and the dominant circulating strain of SARS-CoV-2 in given time periods. During the circulation of "alpha" and "delta" strains, the only significant differences were decrease of the number of patients with neurological disorders and increase in the frequency of cheilitis, p=0,002. The remaining indicators of organ dysfunction were similar in three groups of children. There was 1 (1,6%) fatal outcome in our study.

Hepatitis Virus C-associated Nephropathy: A Review and Update.

Hepatitis C virus (HCV) infection causes hepatic and extrahepatic organ involvement. Chronic kidney disease (CKD) is a prevalent non-communicable disorder, accounting for significant morbidity and mortality worldwide. Acute kidney injury and CKD are not uncommon sequels of acute or chronic HCV infection. The pathogenesis of HCV-associated kidney injuries is not well explored. Excess cryoglobulin production occurs in HCV infection. The cryoglobulin may initiate immune complex-mediated vasculitis, inducing vascular thrombosis and inflammation due to cryoglobulin deposits. Furthermore, direct damage to nephron parts also occurs in HCV patients. Other contributory causes such as hypertension, diabetes, and genetic polymorphism enhance the risk of kidney damage in HCV-infected individuals. Implementing CKD prevention, regular evaluation, and therapy may improve the HCV burden of kidney damage and its related outcomes. Therefore, in this review, we discuss and update the possible mechanism(s) of kidney injury pathogenesis with HCV infection. We searched for related published articles in EMBASE, Google Scholar, Google, PubMed, and Scopus. We used various texts and phrases, including hepatitis virus and kidney, HCV and CKD, kidney pathology in viral hepatitis, kidney transplantation in HCV-infected patients, kidney allograft survival in viral hepatitis patients, mechanism of kidney pathology in viral hepatitis, dialysis and viral hepatitis, HCV infection and kidney injuries, and viral hepatitis and CKD progression, etc. to identify relevant articles.

Defining the substrate envelope of SARS-CoV-2 main protease to predict and avoid drug resistance.

Coronaviruses can evolve and spread rapidly to cause severe disease morbidity and mortality, as exemplified by SARS-CoV-2 variants of the COVID-19 pandemic. Although currently available vaccines remain mostly effective against SARS-CoV-2 variants, additional treatment strategies are needed. Inhibitors that target essential viral enzymes, such as proteases and polymerases, represent key classes of antivirals. However, clinical use of antiviral therapies inevitably leads to emergence of drug resistance. In this study we implemented a strategy to pre-emptively address drug resistance to protease inhibitors targeting the main protease (Mpro) of SARS-CoV-2, an essential enzyme that promotes viral maturation. We solved nine high-resolution cocrystal structures of SARS-CoV-2 Mpro bound to substrate peptides and six structures with cleavage products. These structures enabled us to define the substrate envelope of Mpro, map the critical recognition elements, and identify evolutionarily vulnerable sites that may be susceptible to resistance mutations that would compromise binding of the newly developed Mpro inhibitors. Our results suggest strategies for developing robust inhibitors against SARS-CoV-2 that will retain longer-lasting efficacy against this evolving viral pathogen.

Isolated tectal cavernomas: A comprehensive literature review with a case presentation.

Intracranial cavernous angiomas or cavernomas (ICCs) are abnormal blood-filled vasculatures made of mono-endothelial layer and characterized by their bubble-like caverns. Brainstem cavernomas (BSCs) is a critical form of ICCs since slight changes in the lesion can result in devastating or life-threatening outcomes. We hereby present a rare case of BSC developed in the mesencephalic tectum with intraventricular bleeding and Parinaud's Syndrome. Our patient was managed by complete surgical resection of the lesion through an infra-tentorial supracerebellar approach. Additionally, we reviewed and analyzed the hitherto reported cases of isolated tectal cavernomas (TCs) in the literature, including our case, to elucidate the main factors associated with the management outcomes of TCs. There have been 25 cases of isolated TC reported until now. Most of the patients were adults between 18-77 y of age, except for two children (7 and 13 y). There was no sex predominance. Symptomatic patients presented with headache 56%, altered level of consciousness 24%, and/or double vision 20%. Most cases (64%) had hemorrhagic lesions at presentation, and 60% of all cases experienced recurrent hemorrhages. Parinaud's Syndrome was recorded in five cases, including the current one. All cases affected with Parinaud's were males. Lesion size was a determinant of the outcome as larger lesions were more likely to result in persistent deficits. Surgical resection of the lesion was an effective management modality with ∼79% (15/19) of patients who underwent surgery ended up with complete recovery.

Association of Academic Performance With Obesity and Unhealthy Lifestyle Among Female University Students.

Aim This study aims to examine the relationship between obesity and academic performance and to investigate the relevance between an unhealthy lifestyle and academic performance, which may exist among obese and non-obese female students in the College of Science and College of Medicine of Imam Mohammad Ibn Saud Islamic University. Method The study is observational, descriptive, and cross-sectional in nature and covers a sample of 328 female students aged 19 to 23 years. They were randomly selected from the College of Science and College of Medicine. Sample collection was conducted from December 12, 2020 to June 15, 2021. Results The result indicates that obesity did not influence academic performance. The association between obesity and academic performance was non-significant (p = 0.335). In the College of Science, grades in physics and math were analyzed, which reflected a weak association with obesity (p = 0.893 and p = 0.872, respectively). Various factors exerted a positive impact on academic performance, such as eating yogurt at least 1-5 times per week (p < 0.05) and spending less than 4 hours on social media or watching TV (p < 0.05). Conclusion Academic performance is influenced by many factors. Eating yogurt more frequently and watching TV and less time for social media are the factors with the largest influence on academic performance. However, obesity does not influence academic performance. In summary, physical activity and a healthy diet exerted no direct effect on academic performance.

Current epidemiological situation of COVID-19 in the Republic of Belarus: characteristics of the epidemic process, sanitary and anti-epidemic measures

This is an analysis of the features of the COVID-19 pandemic the population of the Republic of Belarus from February 2020 to January 2022, the characteristics of sanitary and anti-epidemic measures carried out in the country, assessment of study the safety (tolerance) of the vaccines used the epidemiological efficacy of the vaccination. A retrospective analysis of COVID-19 cases in the Republic of Belarus from the beginning of registration (February 28, 2020) to January, 3, 2022 was performed. Vaccine safety (tolerance) and efficacy were assessed in an observational study. Safety (tolerance) was assessed by presence/absence of adverse reactions: general (fever, malaise, headache, muscle pain, runny nose, nausea, vomiting, sore throat, etc) and local ones (redness, swelling, soreness at the injection place). The COVID-19 pandemic in the Republic of Belarus is characterized by successive development stages: from no cases in early 2020 to detected cases where most individuals had no history of contact with COVID-19 patients; periods of rising and falling incidence Vaccines against COVID-19 (Gam-COVID-Vac (Russia), inactivated vaccine against SARS-CoV-2 (Vero Cell) Sinopharm / BIBP (China) demonstrated a high safety profile in mass vaccination of the population of the Republic of Belarus.

Defining the Substrate Envelope of SARS-CoV-2 Main Protease to Predict and Avoid Drug Resistance

Coronaviruses, as exemplified by SARS-CoV-2, can evolve and spread rapidly to cause severe disease morbidity and mortality. Direct acting antivirals (DAAs) are highly effective in decreasing disease burden especially when they target essential viral enzymes, such as proteases and polymerases, as demonstrated in HIV-1 and HCV and most recently SARS-CoV-2. Optimization of these DAAs through iterative structure-based drug design has been shown to be critical. Particularly, the evolutionarily conserved molecular mechanisms underlying viral replication can be leveraged to develop robust antivirals against rapidly evolving viral targets. The main protease (Mpro) of SARS-CoV-2, which is evolutionarily constrained to recognize and cleave 11 specific sites to promote viral maturation, exemplifies one such target. In this study we define the substrate envelope of Mpro by determining the molecular basis of substrate recognition, through nine high-resolution cocrystal structures of SARS-CoV-2 Mpro with the viral cleavage sites. These structures enable identification of evolutionarily vulnerable sites beyond the substrate envelope that may be susceptible to drug resistance and compromise binding of the newly developed Mpro inhibitors.