Overuse Ordering Serum Vitamin B12: A Call for Appropriate Ordering Guidelines Based on a Single Institutional Experience.

OBJECTIVE: Vitamin B12 is an essential nutrient for numerous functions in the human body. As such, many clinical scenarios justify assaying serum B12; however, there are no evidence-based guidelines available for determining when to order B12 tests. Here we investigate B12 assay ordering patterns to identify methods of enhancing efficiency and minimizing inappropriate requests. METHODS: All serum B12 requests within the year spanning July 2018 to June 2019 were reviewed using the hospital's health information system. These amounted to 3,400 requests, of which data from the first 1,000 were evaluated. Patient demographics, hematological data, serum folate, and ferritin were extracted from the electronic requests. Physician identity and request reason were retrieved where available. RESULTS: Of the 877 B12 requests for which patient age was available, the majority (80.3%) were for young and middle-aged patients. Interestingly, serum B12 was low in only a quarter of the 1,000 reviewed requests; the remaining three quarters had normal levels. Folate, which can be ordered with vitamin B12, was tested in 82 cases, of which only two (2.4%) had folate deficiency. CONCLUSION: This study highlights a high occurrence of improper ordering of vitamin B12 assays, indicating a need for revised guidelines to promote optimal test ordering.

Association of ABO, Rh-D and Kell blood groups with transfusion transmitted infections among blood donors from the Asir Region, Saudi Arabia: A retrospective observational study.

OBJECTIVES: To evaluate the association between transfusion-transmitted infections (TTIs) and ABO, Rh-D, and Kell blood systems among blood donors. METHODS: This was a retrospective study of 10,095 donors who visited the Blood Bank at Asir Hospital, Abha, Saudi Arabia. Data including demographic information, ABO, Rh-D, and Kell blood groups, and serological and molecular test results of TTIs (the TTIs were obtained from each donor's records). Chi-squared and Fisher's exact tests were employed to establish possible associations between blood groups and TTIs. RESULTS: The prevalence rate of TTIs among donors was 6.3%, with HBcAb (70%) being the most prevalent biomarker among positive donors. Donors with the O blood group were at a higher risk of contracting TTIs. Significant associations were observed between HIV and blood group A (χ2=6.30, p=0.01), HBsAg and group AB (χ2=17.3193, p=0.00003), malaria and group A (χ2=5.0567, p=0.02), and HBV-DNA and group AB (χ2=12.3163, p=0.0004). Also, Kell blood group was significantly associated with HIV (χ2=14.5, p=0.0001), HBcAb (χ2=78.51, p<0.0001), and syphilis (χ2=25.225, p<0.00001). CONCLUSION: ABO and Kell blood groups are associated with TTI markers. These findings highlight the need for improved strategies and approaches in screening and managing blood donations to minimize the risk of TTIs.

Idiopathic Thrombocytosis in Alpha Thalassemia Trait Patient.

Platelet count increases are typically a reactionary response to one of a variety of pathophysiological events. We present here a case of microcytic hypochromic red blood cells and thrombocytosis in an adolescent female that we have monitored for three years. The patient was positive for alpha thalassemia trait; negative for mutation in Janus kinase 2, calreticulin, or myeloproliferative leukemia virus oncogene; and negative for reactive causes of thrombocytosis. Noticeably, a variant in atypical chemokine receptor 1 (ACKR1) (c.-67T>C, rs2814778) was found to be homozygous. Accordingly, the case was diagnosed as idiopathic thrombocytosis, and treatment was given to restore platelet levels to normal. Our findings highlight the possibility of an unknown association between alpha thalassemia trait and idiopathic thrombocytosis in the presence of ACKR1 mutation, which could be implicated in disease pathogenesis.

Hematological malignancies: Prevalence and hematological characteristics in a single center in southern Saudi Arabia.

OBJECTIVES: To determine the prevalence of leukemia in the Aseer region of Saudi Arabia and the importance of hematological, biochemical and coagulation profiles for leukemic patients in the context of disease management. METHODS: This retrospective study comprised 210 patients between 2012 and 2022 who had been diagnosed with leukemia at different ages. The multiple unpaired t-test was used to compare leukemic patients with control samples, which consisted of healthy individuals, and p<0.05 was taken as significant. The data was compiled from Aseer Central Hospital in the Aseer region and collected through peripheral blood smear and bone marrow biopsy (2012-2017) or by flow cytometry (2018-2022), according to the hospital information system and registry data. RESULTS: Of the total 210 leukemic patients (61.4% males and 38.6% females), 104 cases (2012-2017) were diagnosed based on peripheral blood smear and bone marrow biopsy, and 106 cases (2018-2022) based on flow cytometry. Fifteen subtypes of leukemia were identified, with chronic myeloid leukemia being the most common (34.2%), followed by acute myeloid leukemia (17.6%), chronic lymphoblastic leukemia (11.9%), and B-cell acute lymphoid leukemia (9.5%). Other rare cases were also found. CONCLUSION: Of the 210 leukemia cases diagnosed in the Aseer region between 2012-2022, the most common subtype was chronic myeloid leukemia, followed by acute myeloid leukemia. In all leukemia subtypes, distinctive significant changes were observed in hematological parameters, biochemical parameters, and coagulation profiles.

C-5401331 identified as a novel T-cell immunoglobulin and mucin domain-containing protein 3 (Tim-3) inhibitor to control acute myeloid leukemia (AML) cell proliferation.

T-cell immunoglobulin and mucin domain-containing protein 3 (Tim-3) is a checkpoint protein expressed in exhausted T-cells during cancer scenarios. This exhaustion may end in T-cell effector dysfunction, resulting in suboptimal control of cancers like acute myeloid leukemia (AML). Use of immune checkpoint inhibitors (ICIs) to block checkpoint receptors such as Tim-3 is an emerging, revolutionary concept in the immuno-oncology therapeutic arena; however, ICIs are not effective on myeloid malignancies. Here, a multifaceted approach is utilized to identify novel compounds that target and inhibit Tim-3 with improved efficacy. High-throughput virtual screening of the ChemBridge small molecule library and molecular dynamics simulation yielded a lead molecule C-5401331 predicted to bind with high affinity and inhibit the activity of Tim-3. In vitro evaluations demonstrated the compound to have anti-proliferative effects on Tim-3-positive populations of THP-1 and HC-5401331 AML cells, inducing early and late phase apoptosis. With further development, the lead molecule identified in this work has potential to aid the natural "gatekeeper" functions of the body in immunocompromised AML cancer patients by successfully hampering the binding of Tim-3 to T-cells.

Subtractive sequence-mediated therapeutic targets from the conserved gene clusters of Campylobacter hyointestinalis and computational inhibition assessment.

Campylobacter hyointestinalis is a causative agent of enteritis, proctitis, human gastroenteritis, and diarrhea. Reported transmission is from pigs to humans. Link with gastrointestinal carcinoma has also been established in non-Helicobacter pylori patients carrying this strain. The genome size of the strain LMG9260 is 1.8 MB with 1785 chromosomal and seven plasmid proteins. No therapeutic targets have been identified and reported in this bacterium. Therefore, subtractive computational screening of its genome was carried out for the purpose. In total, 31 such targets were mined and riboflavin synthase was utilized for screening natural product inhibitors against it. Among more than 30,000 screened natural compounds from the NPASS library, three (NPC472060, NPC33653, and NPC313886) were prioritized to have the potential to be developed into new antimicrobial drugs. Dynamics simulation assay along with other relevant parameters like absorption, toxicity, and distribution of the inhibiting compounds were also predicted and NPC33653 was identified as having the best drug-like properties among the prioritized compounds. Thus, it has potential to be pursued further for the inhibition of riboflavin synthesis in C. hyointestinalis for subsequent obstruction of its growth and survival.Communicated by Ramaswamy H. Sarma.

Saudi Arabian women's knowledge and attitudes towards premarital screening of genetic disorders.

This study assessed the knowledge and attitudes of Saudi women regarding the premarital screening program (PMS) using a tailored questionnaire survey. Of the 185 participants, 176 (95.1%) were familiar with PMS, and 117 (63.2%) were aware of the diseases that the screening tests aim to detect. The majority of participants supported also including screenings for drug use and mental illness. When considering the situation of compatible partners with one being a carrier, a considerable proportion of respondents indicated they would not proceed with matrimony. Overall, the level of awareness and attitudes concerning the critical significance of PMS were deemed satisfactory. To mitigate the impact of diseases, it is imperative to continue disseminating information concerning the program, its importance, and the necessity of making well-informed decisions after the evaluations.

Cette étude a évalué les connaissances et les attitudes des femmes saoudiennes concernant le programme de dépistage prénuptial (PMS) à l'aide d'un questionnaire personnalisé. Sur les 185 participants, 176 (95,1 %) connaissaient le syndrome prémenstruel et 117 (63,2 %) connaissaient les maladies que les tests de dépistage visent à détecter. La majorité des participants étaient également favorables à l'inclusion de dépistages de la consommation de drogues et de la maladie mentale. Lorsqu'on considère la situation des partenaires compatibles, dont l'un est porteur, une proportion considérable de personnes interrogées ont indiqué qu'elles ne procéderaient pas au mariage. Dans l'ensemble, le niveau de sensibilisation et les attitudes concernant l'importance critique du syndrome prémenstruel ont été jugés satisfaisants. Pour atténuer l'impact des maladies, il est impératif de continuer à diffuser des informations concernant le programme, son importance et la nécessité de prendre des décisions éclairées après les évaluations.

Prevalence, Risk Factors, and Management of Irritable Bowel Syndrome in Saudi Arabia: A Systematic Review.

The prevalence and associated risk factors of irritable bowel syndrome (IBS) have been a significant area of focus in several studies conducted in Saudi Arabia. These studies have looked at varied populations, including school teachers, university students, and the general populace. The reported prevalence rates for IBS vary substantially across studies, ranging from 7.9% to an astounding 49.3%. The average prevalence noted across these studies is about 24%. The aim of this review is to collate, compare, and analyze data from these studies, hoping to shed light on the key risk factors and demographic trends associated with IBS in Saudi Arabia. This review encompasses data from 20 studies, aggregating information from 17,018 participants. The research methodologies adopted by each of these studies have been analyzed, especially focusing on their sample sizes, which vary significantly. Furthermore, the review incorporates details on the socio-demographic attributes of the participants, including age specifics, gender representation, and geographical distribution within Saudi Arabia. The results demonstrate a wide variability in IBS prevalence among different groups. The overall prevalence of IBS in Saudi Arabia based on the provided data is approximately 24%. Gender-based breakdown in some studies indicated varying prevalence among males and females, which indicated that females are more prone to the disease. The same for certain age groups, specifically between 51 and 60 years, which showed slightly higher rates. Factors such as educational discipline, living conditions, mental health, dietary habits, family history of IBS, and certain comorbidities such as diabetes mellitus were found to influence the occurrence of IBS in different cohorts. Moreover, lifestyle factors such as low water intake, lack of dietary fiber, stress, and even caffeine intake were associated with IBS. Socioeconomic aspects, including family income levels and academic performance, were also hinted to have a potential link with IBS prevalence. In light of the presented data, it is evident that IBS prevalence in Saudi Arabia is influenced by a multitude of factors, ranging from genetic and dietary to psychological and socioeconomic. The substantial variations in prevalence across different cohorts suggest the need for a more nuanced understanding of this condition, specifically tailored to the unique demographics and cultural contexts of Saudi Arabia. Early diagnosis and tailored interventions, considering these multifaceted determinants, are crucial for the effective management of IBS in the region.

Identification by molecular dynamic simulation and in vitro validation of SISB-A1, N-[1-(4-bromophenyl)-3-methyl-1H-pyrazol-5-yl]-2-[(2-oxo-4-phenyl-2H-chromen-7-yl) oxy], as an inhibitor of the AblT315I mutant kinase to combat imatinib resistance in chronic myeloid leukemia.

The discovery of imatinib, a specific inhibitor of Abl kinase, revolutionized the therapeutic approach to chronic myeloid leukemia (CML); however, its efficacy can be impeded by the emergence of novel mutations within the kinase domain, particularly AblT315I, that lead to the development of drug resistance. It therefore remains necessary to identify specific inhibitors that can effectively target imatinib-resistant CML harboring the AblT315I mutation. A natural product library sourced from the ZINC database was screened against the experimental structure of AblT315I kinase to identify compounds that selectively target the mutated kinase. The top-scoring compound was empirically tested for inhibition of AblT315I kinase using a luminescence-based kit and for impact on cellular proliferation using the BaF3-BCR-ABL-T315I stable cell line. Computational docking and molecular dynamic simulations identified the compound SISB-A1, N-[1-(4-bromophenyl)-3-methyl-1H-pyrazol-5-yl]-2-[(2-oxo-4-phenyl-2H-chromen-7-yl)oxy] acetamide, to effectively bind the catalytic domain of the mutant AblT315I kinase. Moreover, SISB-A1 exhibited greater preference than imatinib for amino acid residues of the mutant kinase's active site, including isoleucine 315. MMPBSA-based Gibbs binding free energy estimation predicted SISB-A1 to have a free energy of -51.5 versus -65.0 kcal/mol for the conventional AblT315I inhibitor ponatinib. Cell proliferation assays showed SISB-A1 to have a GI50 of 164.0 nM against the ABL-T315I stable cell line, whereas imatinib had a GI50 of 5035 nM. The IC50 value obtained for SISB-A1 against the AblT315I kinase was 197.9 nM. The results indicate SISB-A1 to have a notable ability to bind the catalytic domain of the AblT315I mutant kinase and effectively suppress its activity, thereby surpassing the associated resistance to imatinib. Continued advancement of this lead compound has the potential to yield innovative therapeutics for imatinib-resistant CML.

Predictive value of ferritin, glucose, urea, and creatinine for COVID-19 severity and mortality in patients from Asir, Saudi Arabia.

OBJECTIVES: To correlate demographics, blood groupings, and laboratory characteristics of hospitalized COVID-19 patients with disease severity and outcomes. METHODS: This study included 294 COVID-19 patients. Data on patient age, gender, laboratory results, clinical severity, mortality, comorbidities, and blood group were obtained from medical records retrospectively. RESULTS: High levels of ferritin (p<0.01), urea (p<0.0001), and creatinine (p<0.05) were detected in intensive care unit (ICU)-admitted patients. Ferritin (p<0.05), glucose (p<0.0001), urea (p<0.0001), and creatinine (p<0.0001) were significantly higher in non-survivor compared to survivor COVID-19 patients. Predictors for ICU admission among patients were ferritin (odd ratio [OR]=0.999, p=0.0055) and urea (OR=0.991, p=0.0001). Predictors for mortality were: age (OR=0.963, p=0.0001), ferritin (OR=0.999, p=0.0149), glucose (OR=0.993, p=0.0001), urea (OR=0.976, p=0.0001), and creatinine (OR=0.556, p=0.0001). The most reliable laboratory parameters in predicting mortality were: age (area under the curve [AUC]=0.685, p<0.0001), ferritin (AUC=0.610, p<0.05), glucose (AUC=0.681, p<0.0001), urea (AUC=0.856, p<0.0001), and creatinine (AUC=0.823, p<0.0001). CONCLUSION: High ferritin, glucose, urea, and creatinine levels may predict poor outcomes in COVID-19 patients. These findings could help predict admissions to the ICU and mortality among such patients.

Unveiling the multitargeted repurposing potential of taxifolin (dihydroquercetin) in cervical cancer: an extensive MM\GBSA-based screening, and MD simulation study.

Cervical cancer is a significant cause of morbidity and mortality in women worldwide. Despite the availability of effective therapies, the development of drug resistance and adverse side effects remain significant challenges in cervical cancer treatment. Thus, repurposing existing drugs as multitargeted therapies for cervical cancer is an attractive approach. In this study, we extensively screened the complete prepared FDA-approved drugs and identified the repurposing potential of taxifolin, a flavonoid with known antioxidant and anti-inflammatory properties, as a multitargeted therapy for cervical cancer. We performed a computational analysis using molecular docking with various sampling algorithms, namely HTVS, SP, and XP algorithms, for robust sampling pose and filtered with MM/GBSA analysis to determine the binding affinity of taxifolin with potential targets involved in cervical cancer, such as Symmetric Mad2 Dimer, replication initiation factor MCM10-ID, TPX2, DNA polymerase epsilon B-subunit, human TBK1, and alpha-v beta-8. We then conducted MD simulations to investigate the stability and conformational changes of the complex formed between taxifolin and the mentioned proteins. Our results suggest that taxifolin has a high binding affinity ranging from - 6.094 to - 9.558 kcal/mol, indicating its potential as a multitargeted therapy for cervical cancer. Furthermore, interaction fingerprints, pharmacokinetics and MD simulations revealed that the Taxifolin-target complexes remained stable over the simulation period, indicating that taxifolin may bind to the targets for an extended period. Our study suggests that taxifolin has the potential as a multitargeted therapy for cervical cancer, and further experimental studies are necessary to validate our findings.

Estimating the prevalence of pediatric hematological malignancies in Al-Madinah Al-Munawwarah, Saudi Arabia.

OBJECTIVES: To provide an updated estimate to the prevalence of pediatric hematological malignancies (HMs) in the Al-Madinah Al-Munawwara, Saudi Arabia. METHODS: This is a retrospective study that was carried out between 2016 and 2022. The study population was comprised of 171 children under 16 who had been diagnosed with HMs. The data was compiled from King Salman Medical City's Maternity and Children's Hospital, Al-Madinah Al-Munawwarah, Saudi Arabia. RESULTS: Among the 171 HM patients (64% males and 36% females), 13 subtypes were identified, with B-cell acute lymphoblastic leukemia having the highest incidence (70.3%). Acute myelomonocytic leukemia (8.7%), T-cell acute lymphoblastic leukemia (4.7%), and acute promyelocytic leukemia (3.5%) were the next most common types of HMs. Other rare cases were also found. CONCLUSION: Prevalence rate can be utilized to monitor the progression of disease incidence. Here, HMs demonstrated a pattern of increasing incidence in males over a 7-year period, with a higher rate in early childhood. There were 13 types of HMs diagnosed, with B-acute lymphocytic leukemia having the highest incidence. Although juvenile cancer is rare, it is nonetheless a significant cause of mortality in children. A successful prognosis requires prompt and accurate diagnosis and treatment.

Prevalence, hematological parameters, and coagulation profiles: Cardiovascular diseases statistics in the Asir region, Saudi Arabia.

OBJECTIVES: To determine the prevalence of cardiovascular disease (CVD) types in the Asir region of Saudi Arabia and the importance of hematological testing for CVD patients in the context of disease management. METHODS: This retrospective study comprised 416 CVD patients, and samples were divided based the type of CVD. The Mann Whitney U test was used to compare patients' hematological markers and coagulation profiles to those of healthy controls. RESULTS: The rate of ischemic heart disease (IHD) was 80.7% that of other CVDs, and the rate of ST-elevation myocardial infarction (STEMI) was 37.3% the rate of CVD. Significant differences were observed in the hematological and coagulation parameters of CVD patients compared to the control group. White blood cells (WBC) were significantly higher in STEMI, non-ST-elevation myocardial infarction (NSTEMI), unstable angina (UA), and heart failure (HF) groups. Red blood cells (RBC) were significantly lower in STEMI, NSTEMI, UA, chronic coronary syndrome (CCS), HF, dilated cardiomyopathy (DCM), and ischemic cardiomyopathy (ICM). Red distribution width (RDW) was significantly greater in the HF, DCM, and ICM groups. Prothrombin time (PT) was significantly higher in the STEMI, HF, and DCM groups. CONCLUSION: ST-elevation myocardial infarction has a higher prevalence rate among CVD patients in the Asir region. Both coagulation and hematological indicators have high potential utility as CVD diagnostic and prognostic markers.

Prediction Model of Adverse Effects on Liver Functions of COVID-19 ICU Patients.

SARS-CoV-2 is a recently discovered virus that poses an urgent threat to global health. The disease caused by this virus is termed COVID-19. Death tolls in different countries remain to rise, leading to continuous social distancing and lockdowns. Patients of different ages are susceptible to severe disease, in particular those who have been admitted to an ICU. Machine learning (ML) predictive models based on medical data patterns are an emerging topic in areas such as the prediction of liver diseases. Prediction models that combine several variables or features to estimate the risk of people being infected or experiencing a poor outcome from infection could assist medical staff in the treatment of patients, especially those that develop organ failure such as that of the liver. In this paper, we propose a model called the detecting model for liver damage (DMLD) that predicts the risk of liver damage in COVID-19 ICU patients. The DMLD model applies machine learning algorithms in order to assess the risk of liver failure based on patient data. To assess the DMLD model, collected data were preprocessed and used as input for several classifiers. SVM, decision tree (DT), Naïve Bayes (NB), KNN, and ANN classifiers were tested for performance. SVM and DT performed the best in terms of predicting illness severity based on laboratory testing.

Assessment of renal function among covid-19 patients admitted to the intensive care unit.

Severe acute respiratory viral infections are frequently associated with multiple organ failure, including acute kidney damage. The present study aimed to investigate the associated influence of COVID-19 on renal function in patients admitted to the intensive care unit in Asir region, Saudi Arabia. Thirty patients infected with COVID-19 who were referred to the intensive care unit during November and October 2020 at Asir central hospital, Asir region, Saudi Arabia were recruited. The age of patients ranged between 30 and 90 years old. Renal function tests exhibited dramatic changes in the renal biomarkers in patients with COVID-19. Blood urea levels in COVID-19 patients were significantly higher than in the control group. In addition, significantly lower albumin levels with abnormally decreased total protein levels were found in COVID-19 patients. Among the different electrolytes analyzed, a significantly lower calcium level was observed in COVID-19 patients' groups than in the controls. Renal function tests for COVID-19-infected ICU patients revealed significant changes, indicating the major impact of COVID-19 on kidney function. Monitoring renal function tests may assist in the early prognosis of COVID-19 patients. It is, therefore, crucial to increase the understanding of renal function tests in COVID-19 patients who were admitted to the hospital before their condition deteriorated.

Radiologic technologists in Saudi Arabia: Does long-term exposure to radiation increase the risk of hematological disorders?

OBJECTIVES: To determine the influence of prolonged exposure to radiation based on dosimeter readings on hematological parameters among radiologic technologists (RTs) in Saudi Arabia. METHODS: The study was specifically conducted on selected RTs with experience of more than 10 years and the highest thermoluminescent dosimeter (TLD) readings among all RTs in the Radiological Department, Sabya General Hospital, Ministry of Health, Saudi Arabia from August to October 2020. The RTs group was compared with a control group of non-irradiated participants. Blood samples were collected for hematological and coagulation profile evaluation. RESULTS: The acquired radiation dose analysis revealed that the average accumulated dose in 10 years is 7.6 mSv. The medians of prothrombin time (PT) and activated partial thromboplastin time (APTT) of the RTs group were significantly lower when compared to the control group. In addition, RTs group exhibited a significant reduction in neutrophil count and an elevation in lymphocyte count. CONCLUSION: Chronic exposure to radiation revealed a significant change in blood tests and may reflect an effect on RTs tissues, leading to serious health problems. However, further investigation in a large cohort to study the association between alteration in hematological parameters and chronic radiation exposure is required.

Hemoglobinopathies: An update on the prevalence trends in Southern Saudi Arabia.

OBJECTIVES: To investigate trends in hemoglobinopathies following the establishment of a mandatory premarital screening program (MPMSP) in the southern region of Saudi Arabia, where they are considered highly predominant. METHODS: A retrospective analysis was performed on data from 32,130 high-performance liquid chromatography (HPLC) tests between November 2017 and October 2020. The data was obtained from the Hematology section, Laboratory Department, Armed Forces Hospital, Southern Region. RESULTS: Despite the establishment of the MPMSP, our data showed that sickle cell disease remains a predominant hemoglobinopathy accounting for more than 7% of total tests in Southern Saudi Arabia. Observed HPLC hemoglobin fractions among the tested population showed a reduction in Hb A mean indicating a high rate of hemoglobin abnormalities. In addition, the prevalence of hemoglobin variants, including sickle cell and thalassemia, was higher in the younger population born after the MPMSP than in older subjects. CONCLUSION: Even with the implementation of the MPMSP, hemoglobin abnormalities remain prevalent in southern Saudi Arabia. A longer time frame is recommended to verify the validity of the program.

Synergistic efficacies of thymoquinone and standard antibiotics against multi-drug resistant isolates.

OBJECTIVES: To explore the antibacterial activity of thymoquinone (TQ), a quinone extracted from Nigella sativa. METHODS: This study was conducted from May 2019 to March 2020 at the Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Khalid University, Abha, Saudi Arabia. The antimicrobial activity, minimum inhibitory concentration (MIC), and minimum bactericidal concentration (MBC) of TQ were determined using an agar well diffusion method and broth microdilution assays, and the synergistic effect was evaluated using antibiotics in parallel. The disruptive effect of TQ on bacterial cell membranes was determined using scanning electron microscopy. The antivirulence properties of TQ, which include adherence and biofilm formation, were also investigated using adherence and biofilm formation assays, respectively. RESULTS: Thymoquinone demonstrated bactericidal efficacy against 4/14 bacterial strains, with MIC range of 1.04-8.3 µg/mL and and MBC range of 10.41-66.66 µg/mL. Thymoquinone showed synergism against Klebsiella pneumoniae, Staphylococcus epidermidis (American Type Culture Collection 12228), Staphylococcus aureus, and Staphylococcus epidermidis in combination with the tested antibiotics. Thymoquinone inhibited bacterial adhesion by 39%-54%, 48%-68%, and 61%-81% at 0.5 × MIC, 1 × MIC, and 2 × MIC, respectively. The tested bacterial strains significantly inhibited biofilm formation after treatment with various concentrations of TQ for 24 and 48 hours. CONCLUSION: The combinatory effect of TQ with antimicrobials should be considered when developing new antimicrobial therapy regimens to overcome multidrug-resistant.

Computational and in vitro characterization of ICY-5: A potential candidate promoting mitochondrial apoptosis via the c-MET and STAT3 pathways.

Targeted chemotherapy remains the primary choice in controlling various forms of breast cancer (BC) due to its heterogenous gene expressions in various subtypes. In silico and in vitro evaluation of ICY-5, a novel arylidene analogue against c-MET, was performed. ICY-5 exhibited a docking score of -9.6 kcal/mol in inactive conformation and, - 8.6 kcal/mol in active conformation for c-MET. ICY-5 inhibited c-MET enzyme with an IC50 of 34.34 nM. The compound effectively inhibited MDA-MB 231 and MCF-7 cell proliferation, with GI50 values of 62.61 and 75.31 nM, respectively, and hepatocyte growth factor (HGF)/R c-MET phosphorylation with IC50 s of 71.41 and 83.77 nM, respectively. ICY-5 dose-dependently inhibited HGF-induced transmigration, cell scattering, invasion and altered cell cycle. An increase in apoptotic populations of these cells, with a dose-dependent decease in phosphorylation of STAT3 protein was observed. Furthermore, ICY-5 upregulated the caspase-3, caspase-9, Bcl-2-associated X and survivin, and downregulated Bcl-2, vascular endothelial growth factor, matrix metalloproteinase-2 (MMP-2), and MMP-9 in both BC cell lines. In summary, ICY-5 exhibited excellent efficacy in BC cells, targeting c-MET/SAT-3-mediated mitochondrial apoptosis. Further research will be required to ascertain ICY-5 suitability as a targeted chemotherapeutic against multiple forms of BC.

Body Mass Index and Its Association with Genetically Transmitted Traits.

BACKGROUND: Body mass index (BMI) is a metric widely used to measure the healthy weight of an individual and to predict a person's risk of developing serious illnesses. Study the statistical association between genetically transmitted traits and BMI might be of interest. OBJECTIVES: The present study designed to extend the inadequate evidence concerning the influence of some genetically transmitted traits including ABO blood type, Rh factor, eye color, and hair color on BMI variation. METHODS: A total of 142 undergraduate female students of the Department of Clinical Laboratory Sciences, Faculty of Applied Medical Sciences, King Khalid University, Abha, Saudi Arabia, were participated to investigate the possible linkage between genetic traits and BMI variations. Height and weight are collected from participants for BMI measurement. ABO blood type and Rh factor were determined by antisera. RESULTS: Out of 142 female students, 48 were categorized in the first tertile (T1: less than 19.8 kg/m2), 50 were categorized in the second tertile (T2: between 19.8 and 23.7 kg/m2), and 44 were categorized in the third tertile (T3: greater than 23.7 kg/m2). Chi-square analysis shows that there were no associations of genetic traits including hair color, eye color, ABO blood type, and Rh blood type with BMI. However, a significant association between hair color and BMI was observed using multinomial logistic regression analysis. CONCLUSIONS: Our data provides a more robust prediction of the relative influence of genetic effects such as hair color on BMI. Future studies may contribute to identifying more association between genes involved in hair pigmentation and BMI variation.