A peptide-binding domain shared with an Antarctic bacterium facilitates Vibrio cholerae human cell binding and intestinal colonization.

Vibrio cholerae, the causative agent of the disease cholera, is responsible for multiple pandemics. V. cholerae binds to and colonizes the gastrointestinal tract within the human host, as well as various surfaces in the marine environment (e.g., zooplankton) during interepidemic periods. A large adhesin, the Flagellar Regulated Hemagglutinin A (FrhA), enhances binding to erythrocytes and epithelial cells and enhances intestinal colonization. We identified a peptide-binding domain (PBD) within FrhA that mediates hemagglutination, binding to epithelial cells, intestinal colonization, and facilitates biofilm formation. Intriguingly, this domain is also found in the ice-binding protein of the Antarctic bacterium Marinomonas primoryensis, where it mediates binding to diatoms. Peptide inhibitors of the M. primoryensis PBD inhibit V. cholerae binding to human cells as well as to diatoms and inhibit biofilm formation. Moreover, the M. primoryensis PBD inserted into FrhA allows V. cholerae to bind human cells and colonize the intestine and also enhances biofilm formation, demonstrating the interchangeability of the PBD from these bacteria. Importantly, peptide inhibitors of PBD reduce V. cholerae intestinal colonization in infant mice. These studies demonstrate how V. cholerae uses a PBD shared with a diatom-binding Antarctic bacterium to facilitate intestinal colonization in humans and biofilm formation in the environment.

Total Hip Arthroplasty Versus Education and Exercise: A Propensity-Matched Analysis of 266 Patients Who Have Hip Osteoarthritis.

BACKGROUND: Total hip arthroplasty (THA) for osteoarthritis (OA) is a major health system cost. Education and exercise (Edu + Ex) programs may reduce the number of THAs needed, but supporting data are limited. This study aimed to estimate the treatment effect of THA versus Edu + Ex on pain, function, and quality of life outcomes 3 and 12 months after treatment initiation for hip OA. METHODS: Patients who had hip OA who underwent THA or an Edu + Ex program were included in this propensity-matched study. In 778 patients (Edu + Ex, n = 303; THA, n = 475), propensity scores were based on pretreatment characteristics, and patients were matched on a 1:1 ratio. Between-group treatment effects (pain, function, and quality of life) were estimated as the mean difference (MD) in change from pretreatment to 3-month and 12-month follow-up using linear mixed models. RESULTS: The matched sample consisted of 266 patients (Edu + Ex, n = 133; THA, n = 133) who were balanced on all pretreatment characteristics except opioid use. At 12-month follow-up, THA resulted in significantly greater improvements in pain (MD 35.4; 95% confidence interval [CI] 31.4 to 39.4), function (MD 30.5; 95% CI 26.3 to 34.7), and quality of life (MD 33.6; 95% CI 28.8 to 38.4). Between 17% and 30% of patients receiving Edu + Ex experienced a surgical threshold for clinically meaningful improvement in outcomes, compared to 84% and 90% of THA patients. CONCLUSIONS: A THA provides greater improvements in pain, function, and quality of life. A notable proportion of Edu + Ex patients had clinically meaningful improvements, suggesting Edu + Ex may result in THA deferral in some patients, but confirmatory trials are needed.

Effects of Mediterranean diets and nutrigenomics on cardiovascular health.

The field of nutrigenomics studies the interaction between nutrition and genetics, and how certain dietary patterns can impact gene expression and overall health. The Mediterranean diet (MedDiet), characterized by a high intake of fruits, vegetables, whole grains, and healthy fats, has been linked to better cardiovascular health (CVH) outcomes. This review summarizes the current state of research on the effects of nutrigenomics and MedDiet on cardiovascular health. Results suggest that MedDiet, through its impact on gene expression, can positively influence CVH markers such as blood pressure, lipid profile, and inflammation. However, more research is needed to fully understand the complex interactions between genetics, nutrition, and CVH, and to determine the optimal dietary patterns for individualized care. The aim of this scientific review is to evaluate the current evidence on the effects of nutrigenomics and MedDiet on cardiovascular health. The review summarizes the available studies that have investigated the relationship between nutrition, genetics, and cardiovascular health, and explores the mechanisms by which certain dietary patterns can impact CVH outcomes. The review focuses on the effects of MedDiet, a dietary pattern that is rich in whole foods and healthy fats, and its potential to positively influence CVH through its impact on gene expression. The review highlights the limitations of current research and the need for further studies to fully understand the complex interplay between nutrition, genetics, and cardiovascular health.

Hospital spending and length of stay attributable to perioperative adverse events for inpatient hip, knee, and spine surgery: a retrospective cohort study.

BACKGROUND: The incremental hospital cost and length of stay (LOS) associated with adverse events (AEs) has not been well characterized for planned and unplanned inpatient spine, hip, and knee surgeries. METHODS: Retrospective cohort study of hip, knee, and spine surgeries at an academic hospital in 2011-2012. Adverse events were prospectively collected for 3,063 inpatient cases using the Orthopaedic Surgical AdVerse Event Severity (OrthoSAVES) reporting tool. Case costs were retrospectively obtained and inflated to equivalent 2021 CAD values. Propensity score methodology was used to assess the cost and LOS attributable to AEs, controlling for a variety of patient and procedure factors. RESULTS: The sample was 55% female and average age was 64; 79% of admissions were planned. 30% of cases had one or more AEs (82% had low-severity AEs at worst). The incremental cost and LOS attributable to AEs were $8,500 (95% confidence interval [CI]: 5100-11,800) and 4.7 days (95% CI: 3.4-5.9) per admission. This corresponded to a cumulative $7.8 M (14% of total cohort cost) and 4,290 bed-days (19% of cohort bed-days) attributable to AEs. Incremental estimates varied substantially by (1) admission type (planned: $4,700/2.4 days; unplanned: $20,700/11.5 days), (2) AE severity (low: $4,000/3.1 days; high: $29,500/11.9 days), and (3) anatomical region (spine: $19,800/9 days; hip: $4,900/3.8 days; knee: $1,900/1.5 days). Despite only 21% of admissions being unplanned, adverse events in these admissions cumulatively accounted for 59% of costs and 62% of bed-days attributable to AEs. CONCLUSIONS: This study comprehensively demonstrates the considerable cost and LOS attributable to AEs in orthopaedic and spine admissions. In particular, the incremental cost and LOS attributable to AEs per admission were almost five times as high among unplanned admissions compared to planned admissions. Mitigation strategies focused on unplanned surgeries may result in significant quality improvement and cost savings in the healthcare system.

Bovine serum albumin functionalized blue emitting Ti3 C2 MXene quantum dots as a sensitive fluorescence probe for Fe3+ ion detection and its toxicity analysis.

In the present work, an improved class of protein functionalized fluorescent 2D Ti3 C2 MXene quantum dots (MXene QDs) was prepared using a hydrothermal method. Exfoliated 2D Ti3 C2 sheets were used as the starting precursor and transport protein bovine serum albumin (BSA) was used to functionalize the MXene QDs. BSA-functionalized MXene QDs exhibited excellent photophysical property and stability at various physiological parameters. High-resolution transmission electron microscopy analysis showed that the BSA@MXene QDs were quasispherical in shape with a size of ~2 nm. The fluorescence intensity of BSA@MXene QDs was selectively quenched in the presence of Fe3+ ions. The mechanism of fluorescence quenching was further substantiated using time-resolved fluorescence and Stern-Volmer analysis. The sensing assay showed a linear response within the concentration range 0-150 µM of Fe3+ ions with excellent limit of detection. BSA@MXene QDs probe showed good selectivity toward ferric ions even in the presence of other potential interferences. The practical applicability of BSA@MXene QDs was further tested in real samples for Fe3+ ion quantification and the sensor had good recovery rates. The cytotoxicity studies of the BSA@MXene QDs toward the human glioblastoma cells revealed that BSA@MXene QDs are biocompatible at lower doses and showed significant cytotoxicity at higher dosages.

Review on the Recent Advances on Typhoid Vaccine Development and Challenges Ahead.

Control of Salmonella enterica serovar typhi (S. typhi), the agent of typhoid fever, continues to be a challenge in many low- and middle-income countries. The major transmission route of S. typhi is fecal-oral, through contaminated food and water; thus, the ultimate measures for typhoid fever prevention and control include the provision of safe water, improved sanitation, and hygiene. Considering the increasing evidence of the global burden of typhoid, particularly among young children, and the long-term horizon for sustained, effective water and sanitation improvements in low-income settings, a growing consensus is to emphasize preventive vaccination. This review provides an overview of the licensed typhoid vaccines and vaccine candidates under development, and the challenges ahead for introduction.

New Classification System for Cleft Alveolus: A Computed Tomography-based Appraisal.

AIM: The present study proposed a new classification system based on computed tomography (CT) scan appraisal; this enables the surgeon to identify the extent of the defect and helps to execute the proper treatment plan. BACKGROUND: Various terminologies and classifications were proposed to understand developmental defects. But none of the existing classifications/nomenclatures used the preoperative radiographic evaluation (i.e., computed tomography scan-CT scan) in the management and prognosis. Various treatments were advocated and practiced successfully for the surgical correction of lip and palate. MATERIALS AND METHODS: The available CT scans from archives of the Department of Radiology and Oral and Dental Surgery were evaluated (retrospectively) for cleft alveolus and its morphology as per the proposal. The English language literature was searched in the MEDLINE database without date restriction to revise existing literature on numerous classification systems/nomenclatures using MeSH keywords related to cleft lip, palate, alveolus, developmental disturbance, facial clefts, and classification. Existing classification systems were revisited with a note on the drawbacks. After careful examination of morphological patterns of all clefts, the new CT scan-based alveolar cleft classification is proposed depending on the extent of cleft. RESULTS: The literature revealed a total of twenty-nine classifications of cleft lip and palate starting from the year 1922 to the year 2015, but none exclusively classified the cleft alveolus based on CT scan observations. The observation of three thousand CT scans showed five types of cleft alveolus, depending on the extent of involvement. CONCLUSION: The CT scan-based classification is essential to the surgeon for successful surgical planning of cleft alveolus. The proposed classification is clinically relevant in this digital era for relating surgical outcomes. The three-dimensional viewing of a defect is essential for the surgeon for virtual planning. This paper provides a CT scan-based classification for universal acceptance in this era of digital technology, and CT scan aids in achieving these goals. CLINICAL SIGNIFICANCE: The new proposal is based on preoperative evaluation of cleft using a CT scan. CT scan imaging provides a clear picture of the cleft in three dimensions for the operating surgeon. Advanced technology-enhanced surgical management modalities like CAD/CAM guided templates to support graft for successful management. The classification system will help the medical and surgical fraternity in various aspects. The three-dimensional modeling of defect and printing of a defect model using additive manufacturing technology helps the surgeon for presurgical visualization and virtual planning in a better way. This strategy of defect classification using a CT scan will help obtain better clinical outcomes and patient satisfaction.

Risk factors for mortality among inpatients with smear positive pulmonary tuberculosis.

OBJECTIVE: To evaluate risk factors having significant effect on mortality of smear positive Pulmonary Tuberculosis (PTB) inpatients. METHODS: A descriptive cross-sectional study was conducted at Ojha Institute of Chest Diseases, Dow University Hospital Ojha Campus, Karachi. One hundred and seventy (170) inpatients of smear positive PTB confirmed by Acid Fast Bacilli (AFB) smear, aged between 13-80 years were enrolled by using consecutive sampling technique while patients with drug resistant Tuberculosis (TB) and extra pulmonary TB were excluded from the study. Selected patients were interviewed for collecting demographic data and risk factor data by using a standard questionnaire. RESULTS: Out of 170 PTB inpatients, mortality was observed in 23 (13.5%) patients among which male patients were 12 (52.2%), and female were 11 (47.8%). Mortality was significantly associated with increasing age (p=0.003), socioeconomic status (p=0.019), anemia (p=0.03), Chronic Liver Disease (CLD) (p=0.005), Diabetes Mellitus (DM) (p=0.001), Human Immunodeficiency Virus (HIV) (p=0.007), Hypertension (HTN) (p=0.006), recurrent TB (p=0.001), and smoking (p=0.001). CONCLUSION: Increasing age, poverty, smoking history, and presence of comorbidities like DM, CLD, HIV, hypertension, and anemia are associated with higher mortality in smear positive PTB cases.

Design and synthesis of indolopyridone hybrids as new antituberculosis agents.

Tuberculosis continues to be the most dangerous infectious disease globally and need for development of new therapies is of utmost importance. In this study we describe the rationale design for synthesis using molecular hybridization and subsequent in-vitro antimycobacterial activity of various indolo-pyridone hybrid molecules against Mycobacterium tuberculosis H37Rv. A total of 16 indolo-pyridone hybrid molecules were synthesized with 85-90% yields and characterized by various spectroscopic techniques. Four compounds were ineffective with MIC >256 µg/ml (highest concentration tested), six exhibited poor activity with MIC > 100 µg/ml, four showed moderate activity with MIC > 50 µg/ml and two had notable anti-TB activity with MIC values 32 µg/ml. Interestingly the last two compounds were observed equally effective against drug susceptible and various drug resistant strains including multidrug-resistant (MDR) strains, thereby clearly demonstrating their potential against MDR-TB. Our results showed that un-substituted aryl rings posses better antituberculosis activity than those having any kind of substitution and derivatives with small sized electron withdrawing groups in aryl ring exhibited activity while bigger groups lead to considerable loss in activity. The results of this study open up a new door for further SAR guided synthesis on one hand and on the other hand provide a promising opportunity that may lead to the discovery of a new class of antituberculosis agents.

Yield of closed pleural biopsy and cytology in exudative pleural effusion.

OBJECTIVE: To determine diagnostic yield of Closed Pleural Biopsy (CPB) and Cytology in Exudative Pleural Effusion (PE). METHODS: This prospective comparative study was conducted at Chest Unit-II & Medical Unit-IV of Dow University of Health Sciences, Karachi Pakistan from January 2011 till December 2014. RESULTS: Ninety-four patients with exudative PE were finally included. The mean age (SD) was 44.0 (13.8) years. Overall Specific Diagnosis was reached in 76/94 patients; 46 Tuberculosis PE (TPE) & 30 Malignant PE (MPE). CPB diagnosed all TPE patients alone and 28/30 of MPE. Cytology diagnosed only 10/30 patients of MPE with 8 patients having both CPB & Cytology positive for malignancy whereas in the remaining two cases only Cytology positive. The sensitivity of CPB in detecting TPE and MPE was 93.9% and 82.4% respectively whereas specificity for both was 100%. The diagnostic yield of cytology in detecting MPE is only (33.3%). The diagnostic yield of CPB for TPE and MPE is 100% and 93.3% respectively. The overall specific diagnostic yield of CPB is 78.7%. CONCLUSION: CPB is better than pleural fluid cytology alone with the later adding little to diagnostic yield when both combined in distinguishing TPE from MPE, the two main differential of exudative PE in a TB-Endemic country.

Zinc mediated activation of terminal alkynes: stereoselective synthesis of alkynyl glycosides.

Zinc mediated alkynylation reaction was studied for the preparation of C-glycosides from unactivated alkynes. Different glycosyl donors such as glycals and anomeric acetates were tested towards an alkynyl zinc reagent obtained from alkynes using zinc dust and ethyl bromoacetate as an additive. The method provides simple, mild and stereoselective access to alkynyl glycosides both from aromatic and aliphatic acetylenes.

The impact of diabetes status on pain and physical function following total joint arthroplasty for hip and knee osteoarthritis: variation by sex and body mass index.

Few studies have examined diabetes impact on total joint arthroplasty (TJA) outcomes, with variable findings. We investigated the association between diabetes and post-TJA physical function and pain, examining whether diabetes impact differs by sex and BMI. Patient sample completed questionnaires within 3 months prior to hip or knee TJA for osteoarthritis (OA) and 1-year post-surgery. Surgical 'non-response' was defined as < 30% improvement in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain and physical function at 1-year. Two adjusted logistic regression models were estimated: (1) excluding, (2) including an interaction between diabetes, sex and BMI. The sample (626 hip, 754 knee) was 54.9% female, had mean BMI of 30.1, 13.0% reported diabetes. In adjusted models excluding an interaction, diabetes was not associated with non-response. However, a significant 3-way interaction (physical function: p = 0.003; pain: p = 0.006) between diabetes, sex, and BMI was found and was associated with non-response: non-response probability increased with increasing BMI in men with diabetes, but decreased with increasing BMI in women in diabetes. Findings suggest uncertainty in diabetes impact may be due to differential impacts by sex and BMI. A simple consideration of diabetes as present vs. absent may not be sufficient, with implications for the large TJA population.

Advancements in biosensors for cancer detection: revolutionizing diagnostics.

Cancer stands as the reigning champion of life-threatening diseases, casting a shadow with the highest global mortality rate. Unleashing the power of early cancer treatment is a vital weapon in the battle for efficient and positive outcomes. Yet, conventional screening procedures wield limitations of exorbitant costs, time-consuming endeavors, and impracticality for repeated testing. Enter bio-marker-based cancer diagnostics, which emerge as a formidable force in the realm of early detection, disease progression assessment, and ultimate cancer therapy. These remarkable devices boast a reputation for their exceptional sensitivity, streamlined setup requirements, and lightning fast response times. In this study, we embark on a captivating exploration of the most recent advancements and enhancements in the field of electrochemical marvels, targeting the detection of numerous cancer biomarkers. With each breakthrough, we inch closer to a future where cancer's grip on humanity weakens, guided by the promise of personalized treatment and improved patient outcomes. Together, we unravel the mysteries that cancer conceals and illuminate a path toward triumph against this daunting adversary. This study celebrates the relentless pursuit of progress, where electrochemical innovations take center stage in the quest for a world free from the clutches of carcinoma.

Optimum Working Hours for College of Physicians and Surgeons Pakistan Fellowship Residents of General Medicine and General Surgery Disciplines.

OBJECTIVE: To determine the optimum working hours per week for CPSP trainees of Fellowship Programmes in the disciplines of General Surgery and General Medicine. STUDY DESIGN: Mixed-methods, explanatory study. Place and Duration of the Study: Department of General Medicine and Department of General Surgery, Abbasi Shaheed Hospital, Karachi, from February to August 2023. METHODOLOGY: The total number of subjects included were 33 residents, 7 supervisors (4 from General Medicine and 3 from Geneneral Surgery), and 3 hospital managers (from private sector), constituting a representative sample. Postgraduate trainees (PGTs) of third-and fourth-year FCPS training programme who showed willingness to participate were included as were all supervisors and hospital managers involved in the training programme. FCPS residents, who were not willing, on leave, and on rotation to other departments were excluded, as were PGTs enrolled in university and other programmes. For quantitative analysis, survey forms were distributed to the selected participants. For qualitative analysis, one-to-one interviews were conducted in-person and through video-link. Data collection procedure included distribution by hand and via email. SPSS was used for the data analysis. RESULTS: All residents recorded that duty stress, fatigue, and burnout resulted in poor quality of family and social life. All the stakeholders were convinced that acquisition of skills, learning outcomes, and patient safety with optimum care is compromised. The duration of emergency calls varied from 30 to 36 hours. There were 19 out of 33 residents (57.5%) who recommended 24 hours of rest after each emergency call. All the supervisors recommended six to eight daily duty hours and 66 to 90 weekly working hours. Four out of seven supervisors (57.1%) suggested emergency duty of 30 hours with post-call rest of 24 hours at every 3rd  day. CONCLUSION: There is a need for a comprehensive approach that caters to the patient care as well as learning outcomes and residents' well-being when devising the duty schedules. KEY WORDS: Training hours, Fellowship programme, Fatigue, Learning outcomes.

The impact of diabetes on physical and mental health status and patient satisfaction after total hip and knee arthroplasty.

OBJECTIVE: To assess the impact of diabetes on physical and mental health status, as well as patient satisfaction, one-year following knee and hip total joint arthroplasty (TJA) for osteoarthritis (OA). METHODS: Participants were 626 hip and 754 knee TJA patients. Pre-surgery data were collected on socio-demographics and health status. The 12-item Short Form Health Survey (SF-12) was collected pre- and one year post-surgery, and physical (PCS) and mental component (MCS) summary scores computed. One-year patient satisfaction was also recorded. Four regression models tested the effect of diabetes on: 1) PCS change score; 2) MCS change score; 3) achieving minimal clinically important improvement (MCII) on PCS; and 4) patient satisfaction ('Somewhat or Very Satisfied' vs. 'Somewhat or Very Dissatisfied'). An interaction between surgical joint and diabetes was tested in each model. RESULTS: Self-reported diabetes prevalence was 13.0% (95% CI: 11.2%-14.7%) and was more common in knee 16.1% (95% CI: 13.4%-18.7%) than hip 9.3% (95% CI: 7.0%-11.5%) patients. In adjusted analyses, change scores were 2.3 units less on the PCS for those with diabetes compared to those without (p = 0.005). Patients with diabetes were about half as likely to achieve MCII as patients without diabetes (p = 0.004). Diabetes was not significantly associated with satisfaction or changes in MCS scores. Diabetes effects did not differ by surgical joint. CONCLUSIONS: Findings support that diabetes has a negative impact on improvements in physical health after TJA. Considering the growing prevalence of OA and diabetes in the population, our findings support the importance of perioperative screening and management of diabetes in patients undergoing TJA.

Total Knee Arthroplasty Versus Education and Exercise for Knee Osteoarthritis: A Propensity-Matched Analysis.

OBJECTIVE: We estimate the treatment effect of total knee arthroplasty (TKA) versus an education and exercise (Edu+Ex) program on pain, function, and quality of life outcomes 3 and 12 months after treatment initiation for knee osteoarthritis (OA). METHODS: Patients with knee OA who had undergone TKA were matched on a 1:1 ratio with participants in an Edu+Ex program based on a propensity score fitted to a range of pretreatment covariates. After matching, between-group differences in improvement (the treatment effect) in Knee Injury and Osteoarthritis Outcome Score 12-item version (0, worst to 100, best) pain, function, and quality of life from baseline to 3 and 12 months were estimated using linear mixed models, adjusting for unbalanced covariates, if any, after matching. RESULTS: The matched sample consisted of 522 patients (Edu+Ex, n = 261; TKA, n = 261) who were balanced on all pretreatment characteristics. At 12-month follow-up, TKA resulted in significantly greater improvements in pain (mean difference [MD] 22.8; 95% confidence interval [95% CI] 19.7-25.8), function (MD 21.2; 95% CI 17.7-24.4), and quality of life (MD 18.3; 15.0-21.6). Even so, at least one-third of patients receiving Edu+Ex had a clinically meaningful improvement in outcomes at 12 months compared with 75% of patients with TKA. CONCLUSION: TKA is associated with greater improvements in pain, function, and quality of life, but these findings also suggest that Edu+Ex may be a viable alternative to TKA in a meaningful proportion of patients, which may reduce overall TKA need. Confirmatory trials are needed.

Mind Matters: Exploring the Intersection of Psychological Factors and Cognitive Abilities of University Students by Using ANN Model.

Purpose: While previous studies have suggested close association of psychological variables of students withtheir higher-order cognitive abilities, such studies have largely been lacking for third world countries like India, with their unique socio-economic-cultural set of challenges. We aimed to investigate the relationship between psychological variables (depression, anxiety and stress) and cognitive functions among Indian students, and to predict cognitive performance as a function of these variables. Patients and Methods: Four hundred and thirteen university students were systematically selected using purposive sampling. Widely used and validated offline questionnaires were used to assess their psychological and cognitive statuses. Correlational analyses were conducted to examine the associations between these variables. An Artificial Neural Network (ANN) model was applied to predict cognitive levels based on the scores of psychological variables. Results: Correlational analyses revealed negative correlations between emotional distress and cognitive functioning. Principal Component Analysis (PCA) reduced the dimensionality of the input data, effectively capturing the variance with fewer features. The feature weight analysis indicated a balanced contribution of each mental health symptom, with particular emphasis on one of the symptoms. The ANN model demonstrated moderate predictive performance, explaining a portion of the variance in cognitive levels based on the psychological variables. Conclusion: The study confirms significant associations between emotional statuses of university students with their cognitive abilities. Specifically, we provide evidence for the first time that in Indian students, self-reported higher levels of stress, anxiety, and depression are linked to lower performance in cognitive tests. The application of PCA and feature weight analysis provided deeper insights into the structure of the predictive model. Notably, use of the ANN model provided insights into predicting these cognitive domains as a function of the emotional attributes. Our results emphasize the importance of addressing mental health concerns and implementing interventions for the enhancement of cognitive functions in university students.

Whole-Exome Sequencing Detecting a Recurrent Pathogenic Mutation, HFE p.His63Asp (H63D) in COVID-19 Patients and Its Effect on Mortality.

BACKGROUND: In recent years, various coronaviruses have caused severe respiratory illnesses worldwide. For example the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infections of COVID-19 outbreak in 2019 in Wuhan, China. Genome-wide association studies (GWAS) have significantly expanded our comprehension of how specific genetic variations are linked to diseases. Research has demonstrated the existence of genetic factors influencing susceptibility to coronaviruses. The objective of this study was to examine the association of certain loci with the COVID-19 in Saudi population. METHODS: In the present study we have examined the link between the COVID-19 disease and certain genetic variants in hospitalized COVID-19 patients (n = 16) in Tabuk and Bisha, Kingdom Saudi Arabia. We used the genome Analysis Toolkit (GATK) and Comprehensive variant annotation was performed different databases and tools such as Search Tool for the Retrieval of Interacting Genes (STRING), PanelApp and PolyPhen-2. RESULTS: The study showed that the genetic variants associated with genes such as Homeostatic Iron Regulator (HFE) (found in 7 patients, representing 44%), complement factor H (CFH) (6 patients, 38%), cadherin 23 (CDH23) (4 patients, 25%), cytotoxic T-lymphocyte associated protein 4 (CTLA-4) (3 patients, 19%), Transforming Growth Factor Beta 1 (TGFB1) (3 patients, 19%), CREB-binding protein (CREBBP) (2 patients, 13%), E1A Binding Protein P300 (EP300) (2 patients, 13%), hemoglobin subunit beta (HBB) (2 patients, 13%), interferon regulatory factor 7 (IRF7) (2 patients, 13%), and unc-119 lipid binding chaperone (UNC119) (2 patients, 13%) might be associated with susceptibility to coronavirus. We also identified mutations in the COVID-19 patient that are pathogenic or likely pathogenic. CONCLUSION: A recurrent pathogenic mutation, HFE p.His63Asp (H63D), was identified in 7 patients, suggesting its potential contribution to disease severity. Additionally, a likely pathogenic variant, HBB p.Glu7Val (E7V), was present in 2 patients, highlighting its potential role in disease susceptibility. Our results shed light on the key genetic mechanisms of COVID-19 pathogenesis and help to identify and stratify the individuals or populations that are at risk to corona virus infection. The identification of susceptible individuals or populations assist in prevention and/or in treatment programs.

Regioselective monochloro substitution in carbohydrates and non-sugar alcohols via Mitsunobu reaction: applications in the synthesis of reboxetine.

A regioselective high yielding monochloro substitution (chlorohydrin formation) via Mitsunobu reaction is reported. In carbohydrates and sterically hindered non-sugars, only the primary hydroxyl group is chlorinated, whereas in the non-sugar 1,2- and 1,3-alcohols, predominantly the secondary chloride substitution occurs. The versatile methodology provides indirect access to epoxides with the retention of configuration, as against conventional Mitsunobu reaction which generates epoxides with inversion. The methodology was successfully used as a key step in the synthesis of optically active diastereoisomers of the antidepressant drug reboxetine from (R)-2,3-O-cyclohexylidene-d-glyceraldehyde in ∼43% overall yields.

Changes in femoral cortical porosity after reaming and intramedullary canal preparation in a canine model.

This study examined changes in femoral cortical porosity resulting from femoral canal preparation during cemented total hip arthroplasty (THA). Twenty-four canines were randomly assigned to 3 groups: (1) reaming only, (2) cementing without pressurization, and (3) cementing with pressurization. Femoral cortical porosity was measured from histologic samples of the femurs at 7 positions. Reaming during canal preparation significantly increased cortical porosity. Cementing further increased cortical porosity, whereas pressurization of cement helped to counteract the increase in cortical porosity caused by cementing alone. Cortical porosity was considered to be a marker for bone mineral density (BMD) during the early phase of peri-implant healing around cemented stems. To maximize bone mineral density after cemented total hip arthroplasty, we suggest using implants that do not require reaming and pressurizing cement appropriately.