Anticoagulation dosage strategy therapy, length of stay, and all-cause mortality in critically ill COVID-19 patients admitted to the intensive care unit.

Few studies examined several anticoagulation (AC) dosage strategy therapies for various outcomes among coronavirus disease-2019 (COVID-19) patients. However, this AC dosage strategy therapy has not been investigated to assess the length of stay (LOS) and all-cause mortality among critically ill COVID-19 patients admitted to the intensive care unit (ICU), especially in the eastern province of Saudi Arabia. Thus, this study aimed to examine the association of AC dosage strategy therapy with the LOS and all-cause mortality among critically ill COVID-19 patients admitted to the ICU. We enrolled 170 patients aged 18 years or older, had a confirmed COVID-19, and were hospitalized in a tertiary care facility in the eastern province of Saudi Arabia between March 1, 2020, and January 31, 2021. Patients (n = 56) who received Enoxaparin at a dose of less than or equal to 5000 units of unfractionated heparin thrice daily were categorized as receiving a "prophylaxis" dose. Patients (n = 114) who received a therapeutic dose but not a prophylaxis dose were categorized as receiving a "therapeutic dose." The 30-day ICU LOS was the main outcome, while all-cause mortality was the secondary outcome. The covariate-adjusted logistic regression analysis revealed that the therapeutic dose was significantly associated with a 1.74-fold longer ICU LOS and 6.60-fold greater mortality risk than the prophylaxis dose. Critically ill COVID-19 patients who received the therapeutic dose had a longer ICU LOS and higher mortality than those who received the prophylaxis dose.

Toll-like Receptor 9 Gene in the Development of Type 2 Diabetes Mellitus in the Saudi Arabian Population.

Diabetes mellitus is a complex disease with a wide range of manifestations. Diabetes, notably type 2 diabetes mellitus (T2DM), is becoming more common in Saudi Arabia as a result of obesity and an aging population. T2DM is classified as a noncommunicable disease, and its incidence in the Saudi population continues to grow as a consequence of socioeconomic changes. Toll-like receptors (TLRs) are innate immune receptors that mediate the inflammatory response in diabetes mellitus. Previous studies have documented the relationship between different SNPs in the TLR9 gene in different forms of diabetes. As a result, the purpose of this study was to investigate the relationship between rs187084, rs352140, and rs5743836 SNPs in the TLR9 gene among T2DM patients in the Saudi population. This was a case-control study that included 100 T2DM cases and 100 control subjects. The three SNPs were identified in the study population (n = 200) using polymerase chain reaction (PCR), restriction enzymes for rs352140, and Sanger sequencing for rs187084 and rs5783836. Next, statistical analyses were performed using various software to determine the association between the SNPs and T2DM. rs187084 and rs5743836 were associated with an increased risk of T2DM development. rs187084 and rs5743836 allelic frequencies were associated with a 3.2 times increased risk of T2DM development (p < 0.05). DBP was associated with T2DM (p = 0.02). rs187084 was associated with TC and HDLc; rs352140 was associated with DBP, HbA1c, and HDLc; rs5743836 was associated with waist (p < 0.05). The CGT haplotype was strongly associated with T2DM (p < 0.003). Gene-gene interaction, graphical presentation, and dendrogram showed the strong association with T2DM patients (p < 0.05). This study concluded that rs187084 and rs5743836 were strongly associated with T2DM in Saudi Arabian patients. This study provides further evidence that SNPs in the TLR9 gene play a significant role in T2DM development in a Saudi community.

Alginate Beads as a Promising Tool for Successful Production of Viable and Pluripotent Human-Induced Pluripotent Stem Cells in a 3D Culture System.

Purpose: Two-dimensional (2D)-based cell culture systems, limited by their inherent heterogeneity and scalability, are a bottleneck in the production of high-quality cells for downstream biomedical applications. Finding the optimal conditions for large-scale stem cell culture while maintaining good cellular status is challenging. The aim of this study was to assess the effects of three-dimensional (3D) culture on the viability, proliferation, self-renewal, and differentiation of human induced pluripotent stem cells (IPSCs). Patients and Methods: Various culture conditions were evaluated to determine the optimal conditions to maintain the viability and proliferation of human IPSCs in a 3D environment: static versus dynamic culture, type of adhesion protein added to alginate (Matrigel™ versus gelatin), and the addition of Y-27632t on long-term 3D culture. The proliferation ability of the cells was evaluated via the MTS proliferation assay; the expression levels of the pluripotency markers Nanog and Oct3/4, PAX6 as an ectoderm marker, and laminin-5 and fibronectin as markers of extracellular matrix synthesis were assessed; and HIF1α and HIF2α levels were measured using quantitative reverse transcription polymerase chain reaction. Results: Using a high-aspect-ratio vessel bioreactor with a gentle, low-sheer, and low-turbulence environment with sufficient oxygenation and effective mass transfer of nutrients and waste, we verified its ability to promote cell proliferation and self-renewal. The findings showed that human IPSCs have the ability to maintain pluripotency in a feeder-free system and by inhibiting ROCK signaling and using hypoxia to improve single-cell viability in 3D culture. Furthermore, these cells demonstrated increased self-renewal and proliferation when inoculated as single cells in 3D alginate beads by adding RI during the culture period. Conclusion: Dynamic 3D culture is desirable for the large-scale expansion of undifferentiated human IPSCs.

Relevance of Serum Levels and Functional Genetic Variants in Vitamin D Receptor Gene among Saudi Women with Gestational Diabetes Mellitus.

Background: This study explored the association between ApaI-TaqI Single Nucleotide Polymorphisms (SNPs) in a Vitamin D receptor (VDR) and the risk of Gestational Diabetes Mellitus (GDM) in Saudi women, along with the serum levels of vitamin D. Methods: Ninety women with GDM and 90 non-GDM women were enrolled, based on the inclusion and exclusion criteria for pregnant women enrolled in a single-center study. Blood samples were retrieved from 180 pregnant women using ethylenediaminetetraacetic acid (EDTA) tubes. Serum samples were used to measure the vitamin D, 25-hydroxyvitamin D (25(OH)D or calcidiol), and lipid profiles. Blood was used to measure the hemoglobin A1c levels and to isolate the DNA. The polymerase chain reaction (PCR) was performed for the ApaI (rs79785232), BsmI (rs1544410), FokI (rs2228570), and TaqI (rs731236) SNPs in the VDR gene using restriction fragment length polymorphism analysis. Validation was performed using Sanger sequencing. Statistical analyses were performed between the patients with and without GDM using various statistical software packages. Results: The Hardy-Weinberg equilibrium analysis was statistically significant (p > 0.05). The ApaI, BsmI, and TaqI SNPs were associated with alleles, genotypes, and different genetic models (p < 0.05). Vitamin D levels were associated with deficient levels (p = 0.0002), as well as with a normal and overweight body mass index (p = 0.0004). When vitamin D levels were measured with GDM covariates, the fasting plasma glucose (FPG) (p = 0.0001), postprandial blood glucose (PPBG) (p < 0.0001), oral glucose tolerance test (OGTT)-1 h (p = 0.005), high-density lipoprotein (p = 0.022), and low-density lipoprotein cholesterol (LDLc) (p = 0.001) levels were significantly different. When similar vitamin D levels were measured for each genotype, we confirmed that the ApaI SNP was associated with sufficient levels (p < 0.0001), whereas the BsmI, FokI, and TaqI (p < 0.05) were associated with insufficient levels. The logistic regression model confirmed that the first hour of the OGTT (p = 0.005) was strongly associated with GDM, whereas the analysis of variance confirmed that FPG and PPBG (p < 0.05) were strongly associated with all the SNPs evaluated in the VDR gene. Additionally, the second hour of the OGTT (p = 0.048) and LDLc (p = 0.049) were associated with the ApaI and FokI SNP. Moreover, the first hour OGTT (p = 0.045) and lipid profile parameters (p < 0.05) were associated. Haplotype analysis revealed positive associations among the examined SNPs, which seemed compatible with the hypothesis that variants and combinations of multiple SNP genotypes enhance the risk of GDM in women. Haplotype analysis revealed that different combinations of alleles, such as AGCC, CATT, CGTC, AGTC, and CATT (p < 0.05), were strongly associated. The linkage disequilibrium (LD) analysis showed a strong association with all combinations (p < 0.05). Among the gene-gene interactions, all possible combinations showed a positive association (p < 0.05). Conclusions: Low vitamin D levels were observed in women with GDM. The ApaI, BsmI, and TaqI SNPs were associated with genotype and allele frequencies (p < 0.05). Vitamin D and the SNPs in the VDR gene were associated, according to the ANOVA, logistic regression, haplotype analysis, LD analysis, and the generalized multifactor dimensionality reduction model (p < 0.05).

Molecular Effect of Variants in Toll-like Receptor 4 Gene in Saudi Patients with Type 2 Diabetes Mellitus.

Single-nucleotide polymorphisms (SNPs) in the Toll-like receptor 4 (TLR4) gene have been documented in type 2 diabetes mellitus (T2DM) and other diseases in the Saudi population. We investigated the relationship between rs11536889, rs4986790, and rs4986791 SNPs in the TLR4 gene and T2DM in the Saudi population; 105 patients with T2DM and 105 healthy controls were analyzed. The TLR4 gene was amplified through PCR, followed by restriction fragment length polymorphism analysis for rs4986791 and Sanger sequencing for rs11536889 and rs4986790 SNPs. The clinical and biochemical characteristics were associated with T2DM (p < 0.05). The rs11536889, rs4986790, and rs4986791 SNPs in control subjects followed the Hardy-Weinberg equilibrium (p > 0.05). Alleles were associated with rs11536889, rs4986791, heterozygous codominant, and dominant models (p < 0.05). However, the rs4986790 SNP was not associated with T2DM (p > 0.05). Logistic regression analysis showed that high-density lipoprotein cholesterol (HDLc) levels were associated with T2DM (p < 0.001). Analysis of variance showed that waist (p = 0.0005) and hip circumferences (p = 0.002) in rs4986790 and rs4986791 SNPs, in SBP (p = 0.001), DBP (p = 0.002), and HDLc levels (p = 0.003), were associated with T2DM subjects. T2DM was also associated with the haplotype (p < 0.001) but not with linkage disequilibrium. The gene-gene interaction was associated with the three SNPs studied in patients with T2DM according to the generalized multifactor dimensionality reduction model (p < 0.0001). Dendrogram and graphical depletion analysis revealed a moderate association in patients with T2DM. The results suggest that rs11536889 and rs4986790 SNPs are genotypically and allelically associated with T2DM in Saudi patients. Future functional studies are recommended to validate the genetic roles of these SNPs in the pathogenesis and progression of diseases.

Immune cell ratio and coagulation markers in assessing prognosis of asthma: a cross-sectional study from Saudi Arabia.

Asthma affects a significant number of individuals in Saudi Arabia, with increasing prevalence worldwide, leading to a considerable impact on their quality of life and frequent hospitalizations. In this study, we aimed to explore the relationship between the immune cell ratio and coagulation markers, specifically to identify the occurrence of coagulation abnormalities associated with asthma. To achieve this, we assessed asthma history and severity using a questionnaire while analyzing coagulation biomarkers through venous blood samples. The biomarkers examined included d-dimer, prothrombin time (PT), partial thromboplastin time (PTT), and the international normalized ratio (INR). In addition, we evaluated various hematological parameters such as blood cell counts and hemoglobin (HGB) levels. Our findings revealed compelling evidence, showing significantly elevated levels of d-dimer and the eosinophil-to-neutrophil (ENR) ratio in asthma cases compared to the controls. Moreover, we observed a positive correlation between d-dimer levels and the ENR, with each unit increase in d-dimer associated with a 0.0006 increase in the ENR among asthma cases. These results highlight the potential of assessing ENR and d-dimer levels as predictive indicators for disease prognosis and the development of coagulation abnormalities in individuals with asthma. By shedding light on the relationship between immune cell ratios and coagulation markers in the context of asthma, our study contributes to a better understanding of disease progression and the associated complications. These insights can potentially lead to improved management strategies and better outcomes for asthma patients.

Predictors of disease severity in patients hospitalized with coronavirus disease 2019.

BACKGROUND: Coronavirus disease 2019 (COVID-19), caused by a novel coronavirus, manifests as a respiratory illness primarily and symptoms range from asymptomatic to severe respiratory syndrome and even death. During the pandemic, due to overcrowding of medical facilities, clinical assessment to triage patients for home care or in-hospital treatment was an essential element of management. OBJECTIVES: Study the demographic features, comorbidities and bio-markers that predict severe illness and mortality from COVID-19 infection. DESIGN: Retrospective observational SETTING: Single tertiary care center PATIENTS AND METHODS: The study included all patients admitted with a positive PCR test for COVID-19 during the period from March 2020 to September 2020 (7 months). Data on demographics, clinical data and laboratory parameters was collected from medical records every 3 days during hospital stay or up until transfer to ICU. MAIN OUTCOME MEASURES: Demographic, comorbidities and biochemical features that might predict severe COVID-19 disease. SAMPLE SIZE: 372 RESULTS: Of the 372 patients, 72 (19.4%) had severe disease requiring admission to intensive care unit (ICU); 6 (1.6%) died. Individuals over 62 years were more likely to be admitted to the ICU (P=.0001, while a BMI of 40 and higher increased the odds of severe disease (P=.032). Male gender (P=.042), hypertension (P=.006) and diabetes (P=.001) conferred a statistically significant increased risk of admission to ICU, while coexisting COPD, and ischemic heart disease did not. Laboratory features related to severe COVID-19 infection were: leukocytosis (P=.015), thrombocytopenia (P=.001), high levels of C-reactive protein (P=.0001), lactic dehydrogenase (P=.0001), D-dimer (P=.0001) and ferritin (P=.001). With the multivariate analysis, diabetes, high lac-tate dehydrogenase, C-reactive protein and thrombocytopenia were associated with severity of illness. CONCLUSIONS: Particular demographic and clinical parameters may predict severe illness and need for ICU care. LIMITATIONS: Single referral center, several cases of severe COVID-19 could not be included due to lack of consent and or data. CONFLICT OF INTEREST: None.

Strategy for immunological analysis of pro-inflammatory cytokine marker studies with chronic hepatitis B virus in Southwestern region of Saudi Arabia.

BACKGROUND: Hepatitis B Virus (HBV) is one of the leading causes of infectious disease in the global population, and its prevalence has been increasing globally. Human HBV infection is complex, involving both innate and adaptive immune systems. Cytokines play a role in both physiologic and pathologic processes in the liver. This study was designed to screen serum levels using an enzyme linked immunosorbent assay (ELISA) and genetic variants in the TNF-α and IL6 genes using polymerase chain reactions (PCR). The aim of this study was to screen the serum levels and genotype levels with TNF-α (C-308 T/G-308A) and IL-6 (G-174 C) genes in HBV patients and control subjects. METHODS: In this study, we have selected 50 HBV patients and 40 control subjects from Saudi Population. Patient serum samples was used for measuring the serum levels and PCR analysis using RFLP analysis. Prior to this, HBV patients were confirmed with PCR analysis followed by Sanger sequencing analysis. RESULTS: The current study results confirmed positive association in serum levels (p < 0.05) and negative association with both genotype and allele frequencies in TNF-α (C-308 T) and IL-6 (G-174 C) genes among HBV patients and controls (p > 0.05). Positive associations between blood levels of TNF-α and IL-6 were confirmed, while negative associations were found between PCR investigations involving the TNF-α (G-308A) and IL-6 (G-174 C) genes with the HBV prevalence in the Saudi population. CONCLUSION: This study confirmed serum levels are strongly associated with HBV patients in the Saudi population. However, PCR studies showed the negative association with the couple of variants selected for this study.

A study on the immunological vitality of an inflammatory biomarker explored with rs5743708 polymorphism in TLR2 gene among Saudi women confirmed with polycystic ovarian syndrome.

Introduction: Polycystic ovary syndrome (PCOS) is an ovarian health condition as well as a long-term endocrine dysfunction that affects reproductive-aged women. Toll-like receptor 2 (TLR2) gene was linked to PCOS and chronic inflammation, and the prevalence of obesity was rising in Saudi women. Previous studies on rs5743708 polymorphism were documented in the obesity as well as in PCOS women. Aim: In this study, we investigated the molecular role of rs5743708 polymorphism in TLR2 gene among Saudi women diagnosed with PCOS using the Rotterdam criteria. Methods: Blood samples were collected from 220 Saudi women in this hospital-based case-control study; 110 were PCOS women and remaining 110 were non-PCOS (control women). Biochemical analysis was performed on serum samples, and molecular analysis was performed on EDTA blood. Genotyping for rs5743708 polymorphism was performed with polymerase chain reaction-restriction fragment length polymorphism analysis. Results: In both groups, clinical data was calculated using t-test, which revealed both positive (p < 0.05) and negative (p > 0.05) associations. HWE analysis supported the rs5743708 polymorphism (p < 0.05). In the rs5743708 polymorphism, none of the genotypes, genetic models, or allele frequencies were found to be associated with PCOS and non-PCOS women. However, both ANOVA and regression analyses revealed a positive relationship in PCOS with weight and BMI (p < 0.0001). Conclusion: The rs5743708 polymorphism was not associated to PCOS in Saudi women. One of the predictions could be that 42.7% of PCOS and 73.6% of non-PCOS women were obese, and the rs5743708 polymorphism has been linked to both obesity and PCOS in the previous studies. This study suggests screening for additional polymorphisms with a large sample size.

Molecular Role of Asn680Ser and Asp37Glu Missense Variants in Saudi Women with Female Infertility and Polycystic Ovarian Syndrome.

Female infertility (FI) is a global health issue. Polycystic ovary syndrome (PCOS) is a common cause of FI. The renalase gene (RNLS) is associated with FI and other human diseases. Based on the documented missense variants, rs6166 and rs2296545 single-nucleotide polymorphisms (SNPs) were not identified in Saudi women with FI and PCOS. This study aimed to investigate the molecular role of the two SNPs in Saudi women with FI and PCOS. In this cross-sectional study, 96 healthy controls, 96 women with FI, and 96 women with PCOS were recruited. DNA was isolated, and polymerase chain reactions and Sanger sequencing analysis were performed using rs6166 and rs2296545 SNPs. The data obtained from the three groups were used to perform statistical analyses based on genotype, allele frequencies, regression models, and ANOVA analysis. Both rs6166 and rs2296545 had no role in FI or PCOS in Saudi women. A predicted reason for non-association in Saudi women could be the role of elderly women in the controls compared with women with FI and PCOS. Moreover, age, weight, and body mass index were higher in the control group than the FI and PCOS groups. In conclusion, rs6166 and rs2296545 SNPs were not associated with FI or PCOS in Saudi women.

A conceptual model of factors associated with health-related quality of life in men and women with knee osteoarthritis in Riyadh, Saudi Arabia: A multicenter cross-sectional study.

This study used a conceptual model to examine the factors influencing physical, mental, and overall health-related quality of life (HRQoL) in women and men aged 45 and older with knee osteoarthritis (KOA) in Saudi Arabia. In this multicenter cross-sectional study, we randomly included 356 individuals aged 45 years or above with doctor-confirmed KOA from the orthopedic and physiotherapy departments of the 5 tertiary hospitals in Riyadh, Saudi Arabia, between March 2016 and March 2017. We split all participants into men (n = 146) and women (n = 210) based on gender. A conceptual model was developed using the HRQoL influential potential factors, such as age, sex, education, occupation, and way of eating (sociodemographic), and clinical factors, such as osteoarthritis knee and its severity, duration, pain, and body mass index. The 36-item short form health survey and its subscales of the physical composite scale and mental composite scale were used to evaluate overall HRQoL, physical, and mental health, respectively. We used unadjusted multiple linear regression analyses to investigate the associations between gender-specific potential factors and HRQoL outcomes. Women and men aged between 60 and 64 years were more strongly associated significantly with less physical composite scale score by -3.17, (standard error [SE] = 1.71, P = .021) and -3.18 (SE = 1.69, P = .023) respectively, followed by the primary school or less education by -3.40 (SE = 1.27, P = .0002), severe KOA of -8.94 (SE = 0.99, P < .001), eating on the floor bending the knee of -3.93 (SE = 1.63, P = .042), and pain of -2.39 (SE = 0.26, P < .0001). Women and men with primary school or less education significantly had low mental composite scale and 36-item short form health survey scores of -3.07 (SE = 1.22, P = .041) and -3.23 (SE = 0.99, P = .018), respectively, followed by severe KOA of -4.07 (SE = 1.22, P = .001) and -6.50 (SE = 0.83, P < .0001) and eating on the floor, extending the knee at -3.35 (SE = 1.74, P = .043). Risk factors like age, education, pain, body mass index, and severe KOA are linked to poor physical, mental, and overall HRQoL among women and men in Saudi Arabia.

Differentiation of human induced pluripotent stem cells into functional lung alveolar epithelial cells in 3D dynamic culture.

Introduction: Understanding lung epithelium cell development from human induced pluripotent stem cells (IPSCs) in vitro can lead to an individualized model for lung engineering, therapy, and drug testing. Method: We developed a protocol to produce lung mature type I pneumocytes using encapsulation of human IPSCs in 1.1% (w/v) alginate solution within a rotating wall bioreactor system in only 20 days without using feeder cells. The aim was to reduce exposure to animal products and laborious interventions in the future. Results: The three-dimensional (3D) bioprocess allowed cell derivation into endoderm, and subsequently into type II alveolar epithelial cells within a very short period. Cells successfully expressed surfactant proteins C and B associated with type II alveolar epithelial cells, and the key structure of lamellar bodies and microvilli was shown by transmission electron microscopy. The survival rate was the highest under dynamic conditions, which reveal the possibility of adapting this integration for large-scale cell production of alveolar epithelial cells from human IPSCs. Discussion: We were able to develop a strategy for the culture and differentiation of human IPSCs into alveolar type II cells using an in vitro system that mimics the in vivo environment. Hydrogel beads would offer a suitable matrix for 3D cultures and that the high-aspect-ratio vessel bioreactor can be used to increase the differentiation of human IPSCs relative to the results obtained with traditional monolayer cultures.

Dissecting the Molecular Role of ADIPOQ SNPs in Saudi Women Diagnosed with Gestational Diabetes Mellitus.

The traditional definition of gestational diabetes mellitus (GDM) is the leading cause of carbohydrate intolerance in hyperglycemia of varying severity, with onset or initial detection during pregnancy. Previous studies have reported a relationship among obesity, adiponectin (ADIPOQ), and diabetes in Saudi Arabia. ADIPOQ is an adipokine that is produced and secreted by adipose tissue involved in the regulation of carbohydrate and fatty acid metabolism. This study investigated the molecular association between rs1501299, rs17846866, and rs2241766 single-nucleotide polymorphisms (SNPs) in ADIPOQ and GDM in Saudi Arabia. Patients with GDM and control patients were selected, and serum and molecular analyses were performed. Statistical analyses were performed on clinical data, Hardy Weinberg Equilibrium, genotype and allele frequencies, multiple logistic regression, ANOVA, haplotype, linkage disequilibrium, as well as MDR and GMDR analyses. The clinical data showed significant differences in various parameters between the GDM and non-GDM groups (p < 0.05). In GDM women with alleles, genotypes, and different genetic models, the rs1501299 and rs2241766 SNPs showed a strong association (p < 0.05). Multiple logistic regression analysis revealed a negative correlation (p > 0.05). This study concluded that rs1501299 and rs2241766 SNPs were strongly associated with GDM in women in Saudi Arabia.

The risk of venous thromboembolism and blood hyperlactatemia is associated with increased mortality among critically ill patients with Covid-19.

INTRODUCTION: Coronavirus disease 2019 (Covid-19) following venous thromboembolism (VTE) and blood hyperlactatemia are associated with higher mortality. However, reliable biomarkers for this association remain to be elucidated. This study investigated the associations of VTE risk and blood hyperlactatemia with mortality among critically ill Covid-19 patients admitted to the intensive care unit (ICU). METHODS: In this single-centre retrospective study, we included 171 patients aged ≥18 years with confirmed Covid-19 admitted to the ICU at a tertiary healthcare clinic in the Eastern region of Saudi Arabia between 1 March 2020 and 31 January 2021. Patients were divided into two groups: survivor and non-survivor. The survivors have been identified as the patients discharged from the ICU alive. The VTE risk was defined using a Padua prediction score (PPS) >4. The blood lactate concentration (BLC) cut-off value >2 mmol/L was used to determine the blood hyperlactatemia. RESULTS: Multi-factor Cox analysis showed that PPS >4 and BLC >2 mmol/L were more likely to be significantly associated with higher odds of ICU mortality in critically ill Covid-19 patients (hazard ratio [HR] = 2.80, 95% confidence interval [CI] = 1.00-8.08, p = 0.050; HR = 3.87, 95% CI = 1.12-13.45, p = 0.033, respectively). The Area under the Curve for VTE and blood hyperlactatemia were 0.62 and 0.85, respectively. CONCLUSION: VTE risk and blood hyperlactatemia have been associated with a higher mortality risk in critically ill Covid-19 patients who are hospitalized in the ICU in Saudi Arabia. According to our findings, these people needed more effective VTE prevention strategies based on a personalized assessment of their risk of bleeding. Moreover, persons without diabetes and other groups with a high risk of dying from COVID-19 may be recognized by measuring glucose as having elevated glucose and lactate jointly.

Evidence from genetic studies among rs2107538 variant in the CCL5 gene and Saudi patients diagnosed with type 2 diabetes mellitus.

Type 2 diabetes mellitus (T2DM) is a chronic and metabolic disorder that affects the adult population. Chemokines are proinflammatory cytokines that play a role in the development of chronic diseases such as obesity, gestational diabetes, and T2DM. The C-C Motif Chemokine Ligand 5 (CCL5) gene plays a role in antiviral immunity, tumor development, obesity, impaired glucose tolerance, and T2DM. This study aimed to investigate the genetic role of the rs2107538 variant in the CCL5 gene in Saudi patients with T2DM. Sixty subjects with T2DM patients and 60 healthy controls participated in this prospective case-control study. Prior to Sanger sequencing, genomic DNA was extracted and amplified with Polymerase chain reaction (PCR), after which the PCR products were purified. The collected data were used to conduct various statistical analyses to determine the relationship between T2DM and control subjects. The findings of the current study revealed a positive association for most parameters between T2DM and control subjects (p < 0.05). The frequency of genotypes (p = 0.002, AA vs.GG: p = 0.008, GA + AA vs. GG: p = 0.0002) and alleles (A vs. G: p = 0.0007) revealed a strong risk association. Multiple logistic regression with individual effects revealed a link between SBP and HDLc levels (p = 0.03). In patients with T2DM, waist (p = 0.001), TG (p = 0.0007), and LDLc (p = 0.0004) levels were all associated with the ANOVA. Finally, the rs2107538 variant was linked to an increased risk of T2DM in the Saudi Population. The GA and AA genotypes were strongly connected to the T2DM subjects. In order to rule out disease-causing variants in the global population, future research should use a large sample size.

Evaluation of CAT Variants A-89T, C389T, and C419T in Patients with Vitiligo in the Saudi Population.

Background and Objectives: Vitiligo is a chronic autoimmune and depigmentation disorder in humans that manifests as whitening lesions. Reactive oxygen species (ROS) are involved in cell damage. Catalase (CAT) is a well-known oxidative stress regulator and is primarily responsible for the catalytic decomposition of hydrogen peroxide into water and oxygen. Based on previous case-control and meta-analysis studies, we assessed the prevalence of three single-nucleotide polymorphisms (SNPs) of the CAT genes A-89T (rs7943316), C389T (rs769217) and C419T (rs11032709) in participants with vitiligo and healthy controls in the Saudi population. Materials and Methods: We recruited 152 participants with vitiligo and 159 healthy controls for A-89T, C389T, and C419T SNP genotyping studies using PCR and RFLP analysis. Additionally, we performed linkage disequilibrium and haplotype analyses between vitiligo cases and controls. Results: The rs7943316 and rs11032709 SNPs of the CAT genes showed a positive association with vitiligo for both heterozygous genotypes and dominant genetic models (TT + AT vs. AA in A-89T and TT + CT vs. CC in C389T), in the CAT gene. Linkage disequilibrium analysis revealed a moderate linkage between rs7943316 and rs11032709 SNPs in vitiligo cases and controls. Haplotype frequency estimation revealed a significant association (p = 0.003) among the three SNP alleles. Conclusions: The rs7943316 and rs11032709 SNPs of the CAT genes were strongly associated with susceptibility to vitiligo.

Saudi Community-Based Screening Study on Genetic Variants in ß-Cell Dysfunction and Its Role in Women with Gestational Diabetes Mellitus.

BACKGROUND: Diabetes (hyperglycemia) is defined as a multifactorial metabolic disorder in which insulin resistance and defects in pancreatic ß-cell dysfunction are two major pathophysiologic abnormalities that underpin towards gestational diabetes mellitus (GDM). TCF7L2, KCNQ1, and KCNJ11 genes are connected to the mechanism of ß-cell dysfunction. The purpose of this study was to investigate the genes associated with ß-cell dysfunction and their genetic roles in the rs7903146, rs2237892, and rs5219 variants in Saudi women diagnosed with type 2 diabetes mellitus and GDM. MATERIALS AND METHODS: In this case-control study, 100 women with GDM and 100 healthy volunteers (non-GDM) were recruited. Genotyping was performed using polymerase chain reaction (PCR), followed by restriction fragment length analysis. Validation was performed using Sanger sequencing. Statistical analyses were performed using multiple software packages. RESULTS: Clinical studies showed a ß-cell dysfunction positive association in women with GDM when compared to non-GDM women (p < 0.05). Both rs7903146 (CT vs. CC: OR-2.12 [95%CI: 1.13-3.96]; p = 0.01 & T vs. C: (OR-2.03 [95%CI: 1.32-3.11]; p = 0.001) and rs5219 SNPs (AG vs. AA: OR-3.37 [95%CI: 1.63-6.95]; p = 0.0006 & G vs. A: OR-3.03 [95%CI: 1.66-5.52]; p = 0.0001) showed a positive association with genotype and allele frequencies in women with GDM. ANOVA analysis confirmed that weight (p = 0.02), BMI (p = 0.01), and PPBG (p = 0.003) were associated with rs7903146 and BMI (p = 0.03) was associated with rs2237892 SNPs. CONCLUSIONS: This study confirms that the SNPs rs7903146 (TCF7L2) and rs5219 (KCNJ11) are strongly associated with GDM in the Saudi population. Future studies should address the limitations of this study.

Molecular role of non-exonic variants in CALPAIN 10 gene in polycystic ovarian syndrome in Saudi women.

Introduction: Non-diabetic women with polycystic ovarian syndrome (PCOS) often have abnormal insulin regulation. Calpain 10 (CALP10) is a biomarker of type 2 diabetes mellitus, with some of its single-nucleotide polymorphisms (SNPs) influencing PCOS development. Methods: In this case-control study on 90 women each with and without PCOS, we explored the molecular role of five CALP10 SNPs using biochemical parameters and Sanger sequencing analyses. Results: Different genetic models, genotypes, and allele frequencies were significantly associated with UCSNP-19 (rs3842570; p=0.01), UCSNP-44 (rs2975760; p=0.009), UCSNP-56 (rs2975762; p<0.0001), and UCSNP-63 (rs5030952; p=0.0003) in women with PCOS. The multiple logistic regression model showed a strong association of CALP10 SNPs with fasting blood glucose (p<0.001). ANOVA showed significant associations with various biochemical parameters such as FSH (p=0.0001) in UCSNP-19 (rs3842570), FI (p=0.002), TG (p=0.01) in UCSNP-56 (rs2975762) and FBG (p=0.001), FI (p=0.004), FSH (p=0.02) & LDLc (p=0.04) in UCSNP-63 (rs5030952) SNPs. Haplotype analysis also revealed significant associations between different combinations of alleles in the studied 5 SNPs in women with PCOS (p<0.05). Generalized multifactor dimensionality reduction analysis showed the best gene-gene interactions among the five SNPs in CALP10I (p<0.05). However, dendrogram and graphical depletion models found no strong association in women with PCOS. Conclusion: In conclusion, this study confirms rs3842570, rs2975760, rs2975767, and rs5030952 SNPs in CALP10 gene is associated in diagnosed PCOS women in the Saudi Arabia.

Clinical Assessment of Cytokine Profiles and Haematological Parameters in Patients with Systemic Lupus Erythematosus: A Cross-Sectional Study from Saudi Arabia.

BACKGROUND: Systemic lupus erythematosus (SLE)-related hematological disorders have different pathogenic mechanisms involving immune dysregulation as well as microangiopathy. The current study aimed to assess the relationship between pro- and anti-inflammatory cytokines and SLE-related hematological abnormalities for Saudi Patients. METHODS: The current cross-sectional study including 140 participants was performed at the Prince Mohammad bin Abdulaziz Hospital (PMAH), Riyadh, Saudi Arabia. Two blood samples were collected from each of the study participants for evaluation of the haematological indices including complete blood count (CBC), erythrocyte sedimentation rate (ESR), and cytokine profile (i.e., tumour necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and interleukin-10 (IL-10)). Statistical analyses were performed using the Statistical Package of Social Sciences (SPSS) software, v25. RESULTS: Haematological abnormalities were documented in 63% of SLE patients, and anaemia was the highest at 52%. Haemoglobin levels were found to be significantly lower among SLE patients compared to the controls (p < 0.001). In the cytokine profiles, the levels of TNF-α (p < 0.001), IL-6 (p < 0.001), and IL-10 (p = 0.009) were significantly higher among SLE patients compared to the controls. A positive correlation was also identified between TNF-α, platelet count, red cell distribution width (RDW), and ESR. CONCLUSIONS: Haematological abnormalities were found to be the most common among SLE patients. Further, the correlation between cytokine profile and haematological indices indicates the influence of cytokines in the development of haematological abnormalities. Understanding hematological abnormalities and cytokines' role in the pathogenesis of these abnormalities may aid in the early diagnosis and development of more specific SLE disease therapies.

T-Cell Subsets and Interleukin-10 Levels Are Predictors of Severity and Mortality in COVID-19: A Systematic Review and Meta-Analysis.

Background: Many COVID-19 patients reveal a marked decrease in their lymphocyte counts, a condition that translates clinically into immunodepression and is common among these patients. Outcomes for infected patients vary depending on their lymphocytopenia status, especially their T-cell counts. Patients are more likely to recover when lymphocytopenia is resolved. When lymphocytopenia persists, severe complications can develop and often lead to death. Similarly, IL-10 concentration is elevated in severe COVID-19 cases and may be associated with the depression observed in T-cell counts. Accordingly, this systematic review and meta-analysis aims to analyze T-cell subsets and IL-10 levels among COVID-19 patients. Understanding the underlying mechanisms of the immunodepression observed in COVID-19, and its consequences, may enable early identification of disease severity and reduction of overall morbidity and mortality. Methods: A systematic search was conducted covering PubMed MEDLINE, Scopus, Web of Science, and EBSCO databases for journal articles published from December 1, 2019 to March 14, 2021. In addition, we reviewed bibliographies of relevant reviews and the medRxiv preprint server for eligible studies. Our search covered published studies reporting laboratory parameters for T-cell subsets (CD4/CD8) and IL-10 among confirmed COVID-19 patients. Six authors carried out the process of data screening, extraction, and quality assessment independently. The DerSimonian-Laird random-effect model was performed for this meta-analysis, and the standardized mean difference (SMD) and 95% confidence interval (CI) were calculated for each parameter. Results: A total of 52 studies from 11 countries across 3 continents were included in this study. Compared with mild and survivor COVID-19 cases, severe and non-survivor cases had lower counts of CD4/CD8 T-cells and higher levels of IL-10. Conclusion: Our findings reveal that the level of CD4/CD8 T-cells and IL-10 are reliable predictors of severity and mortality in COVID-19 patients. The study protocol is registered with the International Prospective Register of Systematic Reviews (PROSPERO); registration number CRD42020218918. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020218918, identifier: CRD42020218918.