Binding selectivity analysis of new delhi metallo-beta-lactamase-1 inhibitors using molecular dynamics simulations: Exploring possibilities for decoding antimicrobial drug resistance.

BACKGROUND: New Delhi metallo-beta-lactamase-1 (NDM1) confers resistance to several bacterial species against a broad range of beta-lactam antibiotics and turning them into superbugs that pose a significant threat to healthcare systems worldwide. As such, it is a potentially relevant biological target for counteracting bacterial infections. Given the lack of effective treatment options against NDM1 producing bacteria, finding a reliable inhibitor for the NDM1 enzyme is crucial. METHODS: Using molecular dynamics simulations, the binding selectivities and affinities of three ligands, viz. PNK, 3S0, and N1G were investigated against NDM1. RESULTS: The results indicate that N1G binds with more affinity to NDM1 than PNK and 3S0. The binding energy decomposition analysis revealed that residues I35, W93, H189, K211, and N220 showed significant binding energies with PNK, 3S0, and N1G, and hence are crucially involved in the binding of the ligands to NDM1. Molecular dynamics trajectory analysis further elicited that the ligands influence dynamic flexibility of NDM1 morphology, which contributes to the partial selectivities of PNK, 3S0, and N1G. CONCLUSIONS: This in silico study offers a vital information for developing potential NDM1 inhibitors with high selectivity. Nevertheless, in vitro and in vivo experimental validation is mandated to extend the possible applications of these ligands as NDM1 inhibitors that succor in combating antimicrobial resistance.

Seroprevalence of brucellosis among high-risk individuals in Madinah, Saudi Arabia.

Background and Aim: Brucellosis is a highly contagious, neglected zoonotic disease of major importance worldwide. The disease is endemic in many countries, burdening healthcare systems and the livestock industry and representing a persistent public health concern in these countries. Brucellosis is considered an important occupational hazard for livestock workers. Limited studies have investigated human brucellosis in Saudi Arabia. Therefore, this study aimed to estimate the prevalence of brucellosis among employees of high-risk brucellosis professions, including veterinarians, animal herders, and abattoir workers in Madinah, Saudi Arabia, and to determine the associated risk factors. Materials and Methods: A cross-sectional study was conducted in Madinah, Saudi Arabia, during the period of January-March 2023. Ninety blood samples were collected from individuals occupationally at risk of exposure to Brucella infections. Serum samples were examined for immunoglobulins (Ig)M and IgG antibodies against Brucella using an indirect enzyme-linked immunosorbent assay. Before sample collection, a predesigned online questionnaire was used to collect the participants' sociodemographic characteristics and the probable risk factors for human brucellosis. A Chi-square test was used to compare the differences among groups; p < 0.05 were considered statistically significant. Results: Among the 90 participants among the high-risk individuals, Brucella IgM and IgG seropositivity were found in 8 (8.8%) and 11 (12.12%) cases, respectively. IgM mono antibody positivity was observed in 4 (4.44%) and 7 (7.77%) of the study population who tested positive for IgG only. Dual positivity for IgM and IgG antibodies was observed in 4 (4.44%) participants. No significant association was determined between seropositivity and age, urbanicity, education, occupation, and duration of exposure (p > 0.05). Conclusion: Brucellosis is a high-risk occupational disease among workers with close contact with livestock. This study demonstrates that the seroprevalence of brucellosis among occupationally high-risk individuals in Madinah, Saudi Arabia, is relatively low compared to other countries in the region. Nevertheless, educational programs should be implemented to improve knowledge regarding brucellosis, particularly among high-risk individuals.

Merkel Cell Polyomavirus and their Association with the Pathogenesis of Cervical Squamous Cell Carcinomas and Adenocarcinomas: A Review Article.

Background: This review aims to determine the potential role of Merkel Cell Polyomavirus (MCPyV) in the pathogenesis of cervical squamous cell carcinomas and adenocarcinomas. Methods: A PRISMA systematic search appraisal was conducted. The Scopus, Web of Science, PubMed, EMBASE, Google Scholar, and MEDLINE databases for publications in English were searched up to September 2022 for all relevant articles. All articles that have outlined the contributions of the MCPyV to cervical squamous cell carcinomas and adenocarcinomas were included. Results: The six databases produced 6806 articles. Only six articles met the inclusion criteria and were included. The protocol of this review was submitted and registered with the PROSPERO (Code no. CRD42022369197). The total sample size across the articles was 1135; the age of the participants ranged between 18 and 75 years. In addition, the included articles were conducted between 2012 to 2016. All included articles have a cross-sectional design.Furthermore, different kinds of samples were collected in the reviewed articles, namely cervical tissue biopsies, cervical smears, formalin-fixed paraffin-embedded resection specimens, and cervical adenocarcinomas. Moreover, five articles showed no statistically significant association between the MCPyV and cervical squamous cell carcinomas and adenocarcinomas. In contrast, one article revealed a positive association between MCPyV and cervical squamous cell carcinomas and adenocarcinomas. Conclusions: MCPyV could not be associated with the pathogenesis of cervical squamous cell carcinomas and adenocarcinomas. Further attention should be given to examining this association, and further studies with a large sample size are recommended to confirm these findings.

Artificial intelligence in healthcare: combining deep learning and Bayesian optimization to forecast COVID-19 confirmed cases.

Healthcare is a topic of significant concern within the academic and business sectors. The COVID-19 pandemic has had a considerable effect on the health of people worldwide. The rapid increase in cases adversely affects a nation's economy, public health, and residents' social and personal well-being. Improving the precision of COVID-19 infection forecasts can aid in making informed decisions regarding interventions, given the pandemic's harmful impact on numerous aspects of human life, such as health and the economy. This study aims to predict the number of confirmed COVID-19 cases in Saudi Arabia using Bayesian optimization (BOA) and deep learning (DL) methods. Two methods were assessed for their efficacy in predicting the occurrence of positive cases of COVID-19. The research employed data from confirmed COVID-19 cases in Saudi Arabia (SA), the United Kingdom (UK), and Tunisia (TU) from 2020 to 2021. The findings from the BOA model indicate that accurately predicting the number of COVID-19 positive cases is difficult due to the BOA projections needing to align with the assumptions. Thus, a DL approach was utilized to enhance the precision of COVID-19 positive case prediction in South Africa. The DQN model performed better than the BOA model when assessing RMSE and MAPE values. The model operates on a local server infrastructure, where the trained policy is transmitted solely to DQN. DQN formulated a reward function to amplify the efficiency of the DQN algorithm. By examining the rate of change and duration of sleep in the test data, this function can enhance the DQN model's training. Based on simulation findings, it can decrease the DQN work cycle by roughly 28% and diminish data overhead by more than 50% on average.

Epidemiological Characteristics and Outcomes Predictors for Intensive Care Unit COVID-19 Patients in Al-Madinah, Saudi Arabia. Retrospective Cohort Study.

Introduction: The global pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) increased the demand for intensive care unit (ICU) services. Mortality and morbidity rates among ICU COVID-19 patients are affected by several factors, such as severity, comorbidities, and coinfections. In this study, we describe the demographic characteristics of COVID-19 patients admitted to an ICU in Saudi Arabia, and we determined the predictors for mortality and prolonged ICU length of stay. Additionally, we determined the prevalence of bacterial coinfection and its effect on the outcomes for ICU COVID-19 patients. Methods: We retrospectively studied the medical records of 142 COVID-19 patients admitted to the ICU at a tertiary hospital in Madinah, Saudi Arabia. Data on demographics, medical history, mortality, length of stay, and presence of coinfection were collected for each patient. Results: Neutrophil-to-Lymphocyte ratio (NLR) and intubation were reliable predictors of mortality and ICU length of stay among these ICU COVID-19 patients. Moreover, bacterial coinfections were detected in 23.2% of the patients and significantly (p < 0.001) prolonged their ICU length of stay, explaining the 10% increase in the length of stay for these patients. Furthermore, mortality reached 70% among the coinfected patients, and 60.8% of the isolated coinfecting pathogens were multidrug-resistant (MDR) strains of Klebsiella pneumoniae, Acinetobacter baumannii, and Staphylococcus aureus. Conclusion: Increased NLR and intubation are predictors of mortality and prolonged length of stay in COVID-19 patients admitted to the ICU. Coinfection with MDR bacterial strains potentially results in complications and is a high-risk factor for prolonged ICU length of stay.

Evaluation of the Most Visible Symptoms Associated with COVID-19 Vaccines Among the Residents of Makkah, Saudi Arabia: An Observational, Cross-Sectional Study.

Background: This research evaluated the most visible symptoms associated with coronavirus (COVID-19) vaccines among residents in Makkah of Saudi Arabia. Methods: A cross-sectional study was conducted in 2021 among a representative sample of residents receiving COVID-19 vaccination at King Abdullah Medical City, Al Ukayshiyyah, and Umm Al-Qura University vaccination centers. A total of 805 participants selected by a census sampling method were included. Data regarding characteristics, medical history, and post-vaccination symptoms were obtained with an interview-based questionnaire. Results: The participants' mean age was 25.20 ± 15.5 years. Of them, 61.7% and 38.3% received one and two doses of the COVID-19 vaccine, respectively. 2.2% have an allergic reaction to the COVID-19 vaccine. 25.3% were infected with COVID-19, 23% were infected before the first dose, and only 1.6% were infected after the first dose. Significant statistical associations were found between males and females in smoking status, age, body mass index, history of diabetes mellitus, and types of COVID-19 vaccines (P-value < 0.05). After adjustment for confounding variables, male participants had lower odds of having swelling, redness, or pain at the injection site, muscle or joint pain, headache, dizziness, and nausea compared to female participants [OR = 0.596, 95% CI = (0.388-0.916)], [OR = 0.272, 95% CI = (0.149-0.495)], [OR = 0.529, 95% CI = (0.338-0.828)], [OR = 0.263, 95% CI = (0.125-0.554)], and [OR = 0.145, 95% CI = (0.31-0.679), P < 0.05 for all], respectively. Conclusion: The female participants may have a higher risk of post-COVID-19 vaccination symptoms than males among Makkah residents of Saudi Arabia.

Low prevalence of community-acquired influenza coinfections among COVID-19 patients in Al-Madinah, Saudi Arabia: A retrospective cohort study.

BACKGROUND: Coinfections with respiratory viruses among SARS CoV-2 patients have been reported by several studies during the current COVID-19 pandemic. Most of these studies designated these coinfections as being hospital-acquired infections; however, there is inadequate knowledge about community-acquired respiratory coinfections among SARS CoV-2 patients. METHODS: In this retrospective cohort study, we investigated the seroprevalence of influenza A, influenza B, and parainfluenza-2 among newly hospitalized patients with confirmed COVID-19 infections (n = 163). The study was conducted during the early phase of the COVID-19 pandemic in Saudi Arabia (from April to October 2020). The patients' serum samples were subjected to commercial immunoglobulin M (IgM) antibody tests against the three aforementioned viruses. RESULTS: Seropositivity for influenza A and B and parainfluenza-2 occurred only in 4.2% (7/163) of COVID-19 patients, indicating simultaneous acute infections of these three viruses with SARS CoV-2 infection. All coinfection cases were mild and misdiagnosed during the care period in the hospital. CONCLUSION: This study highlights the low prevalence of community-acquired respiratory infections among COVID-19 patients in the current pandemic and we discussed the possible factors for this finding. During newly emerging epidemics or pandemics, considering other respiratory viruses circulating in the community is essential to avoid their misdiagnosis and account for their possible negative effects on pandemic disease management and prognosis.

Knowledge of HIV/AIDS transmission modes and attitudes toward HIV/AIDS infected people and the level of HIV/AIDS awareness among the general population in the kingdom of Saudi Arabia: A cross-sectional study.

Introduction: The human immunodeficiency virus (HIV) and acquired immunodeficiency syndrome (HIV/AIDS) are worldwide public health issues. Since Saudi Arabia is growing more accessible to the outside world, it is critical to analyze the general population's knowledge of HIV/AIDS transmission modes and attitudes toward HIV/AIDS infected people, and the level of HIV/AIDS awareness. Therefore, this study aimed to assess the knowledge of HIV/AIDS transmission modes and attitudes toward HIV/AIDS infected people, as well as the level of HIV/AIDS awareness among the general population in the Kingdom of Saudi Arabia. Methods: The current online community-based cross-sectional descriptive study was conducted among the general population of the Kingdom of Saudi Arabia using a self-administrated electronic questionnaire between October 2017 and February 2018. A score <3 was considered a negative response. In contrast, scores of 3 and 4 were considered positive responses. The sum score of each outcome was evaluated according to Bloom's cutoff point. The scores for knowledge and attitude were transformed into mean percentage scores by dividing the sum scores obtained by the respondents by the number of items multiplied by 100. Consequently, the overall mean percentage of scores for each category of knowledge and attitude at 60% and above was considered a good level, whereas <60% was deemed a poor level. Results: A total of 2,081 subjects residing in the Kingdom of Saudi Arabia participated in this survey. The mean score of the participant's responses to knowledge items on HIV/AIDS transmission modes was 84.2 ± 15.8%. The mean score of the participant's responses to attitude items toward HIV/AIDS infected people was 50.1 ± 49.9%. The mean score of the participant's responses to attitude items toward the level of HIV/AIDS awareness in Saudi Arabia was 55.7 ± 3.6%. Many socio-demographic variables were significantly associated with mean scores of knowledge of HIV/AIDS transmission modes, mean scores of attitude toward HIV/AIDS infected people, and mean scores of attitude toward the level of HIV/AIDS awareness (P-value ≤ 0.05). The Spearman rank correlation explained significant negative linear correlations between knowledge of HIV/AIDS transmission modes-attitudes toward HIV/AIDS infected people and knowledge of HIV/AIDS transmission modes-attitudes toward the level of HIV/AIDS awareness of r = -0.040 and r = -0.070, respectively (P-value ≤ 0.05). Otherwise, there was a positive linear correlation between attitudes toward HIV/AIDS infected people-attitudes toward the level of HIV/AIDS awareness (r = 0.080, P-value = 0.072). Conclusions: The study showed that a high percentage of the respondents had good knowledge of HIV/AIDS transmission modes. However, a low rate of the study respondents had positive attitudes toward HIV/AIDS infected people and the level of HIV/AIDS awareness among the general population in Saudi Arabia. Therefore, there is a dire need for advocacy campaigns and policies to help reduce HIV stigmatization levels.

Acute Helicobacter pylori Infection Prevalence Among Renal Failure Patients and Its Potential Roles with Other Chronic Diseases: A Retrospective Cohort Study.

Background: Helicobacter pylori (H. pylori) infection is relevant to several chronic human diseases, from digestive diseases to renal, metabolic, and cancer diseases. H. pylori infections and chronic kidney diseases are in increasing, global records; if not well controlled in a specific population, these diseases might lead to more clinical complications. Methods: In this retrospective study, we investigated the prevalence of acute H. pylori infections among 127 dialysis patients via subjecting their serums to the enzyme-linked immunosorbent assay (ELISA) to detect the human Immunoglobulin M (IgM) against H. pylori infections. Samples were from dialysis patients in a single hemodialysis center in Medina, Saudi Arabia, from January to August 2021. Results: Our results indicated the significant prevalence of H. pylori acute infections among 33.1% of renal failure patients recruited in this study, chi-squared: 14.559, p-value: 0.0001. In addition, no significant occurrence of acute H. pylori infection among males and females, chi-squared: 1.823, p-value: 0.177. Furthermore, the prevalence of acute H. pylori infection was not significant in different age groups of renal failure patients. Chi-squared: 6.803, p-value: 0.147, despite H. pylori-infected cases predominantly represented in patients above 51 years. Moreover, we noticed that hypertension, followed by diabetes, was the most prevalent underlying medical condition among acute infected H. pylori and renal failure patients. Conclusion: We documented the significant prevalence of acute H. pylori infection among renal failure patients. We also highlighted and discussed the possible potential roles of H. pylori in renal failure and other chronic diseases. Routine screening and treatment for acute H. pylori infection for chronic kidney diseases, hypertension, and diabetes patients would positively reduce the bacterium's progressive effects on them. They might even improve the control of these diseases.

Effect of the COVID-19 Vaccine on the Menstrual Cycle among Females in Saudi Arabia.

Background: The number of reports of menstrual changes after COVID-19 vaccination in the Saudi population is still unknown. Therefore, this study aimed to assess the effect of the COVID-19 vaccine(Pfizer, AstraZeneca, and Moderna) on the menstrual cycle among females in Saudi Arabia. Methods: This descriptive cross-sectional study was conducted in Saudi Arabia at Umm Al-Qura University (UQU) from August 2021 to February 2022. Data was collected through a previously validated online questionnaire. Results: A total of 2338 participants who received the first dose of the COVID-19 vaccine participated in this study; 1606 (68.7%) of them received the second dose in addition to the first. The mean age of the study participants was 35.4±9.5 years. No significant associations were found between the type of COVID-19 vaccine and the impact on the menstrual cycle, either for the first or second dose (P-values > 0.05). A significant association was found only between the first dose vaccination day and the impact on the menstrual cycle in the second question of "After receiving the COVID-19 vaccine, your next period was" (P-value ≤ 0.05). Significant associations were found between the second dose vaccination day and the impact on the menstrual cycle in the first and second questions of "After receiving the COVID-19 vaccine, your next period was", and "After receiving the first dose, your next period was," respectively (P-values ≤ 0.05). Conclusion: The study found a potential association between the COVID-19 vaccine and menstrual cycle irregularities, which could impact females' quality of life.

Seroprevalence of community-acquired atypical bacterial pneumonia among adult COVID-19 patients from a single center in Al Madinah Al Munawarah, Saudi Arabia: A retrospective cohort study.

OBJECTIVES: To investigate the seroprevalence of the community-acquired bacterial that causes atypical pneumonia among confirmed severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) patients. METHODS: In this cohort study, we retrospectively investigated the seroprevalence of Chlamydia pneumoniae, Mycoplasma pneumoniae, and Legionella pneumophila among randomly selected 189 confirmed COVID-19 patients at their time of hospital presentation via commercial immunoglobulin M (IgM) antibodies against these bacteria. We also carried out quantitative measurements of procalcitonin in patients' serum. RESULTS: The seropositivity for L. pneumophila was 12.6%, with significant distribution among patientsolder than 50 years (χ2 test, p=0.009), while those of M. pneumoniae was 6.3% and C. pneumoniae was 2.1%, indicating an overall co-infection rate of 21% among COVID-19 patients. No significant difference (χ2 test, p=0.628) in the distribution of bacterial co-infections existed between male and female patients. Procalcitonin positivity was confirmed amongst 5% of co-infected patients. CONCLUSION: Our study documented the seroprevalence of community-acquired bacteria co-infection among COVID-19 patients. In this study, procalcitonin was an inconclusive biomarker for non-severe bacterial co-infections among COVID-19 patients. Consideration and proper detection of community-acquired bacterial co-infection may minimize misdiagnosis during the current pandemic and positively reflect disease management and prognosis.