Association of iron deficiency anaemia with the hospitalization and mortality rate of patients with COVID­19.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) illness led to the coronavirus disease 2019 (COVID-19) pandemic, which has caused enormous health and financial losses, as well as challenges to global health. Iron deficiency anaemia (IDA) has been linked to adverse outcomes in patients infected with SARS-COV-2. The present study aimed to assess the association between IDA and the severity of COVID-19 in hospitalized patients. For this purpose, a retrospective data analysis of 100 patients with COVID-19 was conducted. Data of patients hospitalized with SARS-COV-2 infection confirmed by RT-PCR were collected between June, 2021 and March, 2022. The collected data included patient demographics, comorbidities, clinical signs, symptoms and IDA medical laboratory findings, including complete blood count and iron profiles. The results revealed that patients with COVID-19 admitted to the isolation unit represented 61.0% of the study sample, whereas 39.0% were admitted to the intensive care unit (ICU). No patients had stage I IDA, whereas 4 patients (4%) had stage II IDA. Furthermore, 19 patients (19.0%) had stage III IDA. A significantly higher proportion of patients with IDA (69.6%) were admitted to the ICU compared with those without IDA (29.9%, P<0.001). Additionally, patients with IDA had a higher proportion of a history of stroke compared with those without IDA (17.4 vs. 2.6%, respectively, P=0.024). The most common comorbidities identified were hypertension (29%), diabetes (23%) and heart problems (17%). On the whole, the present study demonstrates significant associations between IDA and a longer hospitalization period. A greater incidence of complications was observed in the hospitalized patients who were SARS-COV-2-positive. Although further studies with larger sample sizes are required to confirm these findings, the results presented herein may provide insight for physicians as regards the prevention and treatment of patients with IDA who are infected with coronavirus.

Association of Genetic and Allelic Variants of Von Willebrand Factor (VWF), Glutathione S-Transferase and Tumor Necrosis Factor Alpha with Ischemic Stroke Susceptibility and Progression in the Saudi Population.

Stroke is a key cerebrovascular disease and important cause of death and disability worldwide, including in the kingdom of Saudi Arabia (KSA). It has a large economic burden and serious socioeconomic impacts on patients, their families and the community. The incidence of ischemic stroke is probably increased by the interaction of GSTT1 and GSTM1 null genotypes with high blood pressure, diabetes and cigarette smoking. The roles of VWF, GSTs and TNF-alpha gene variations in the induction of stroke are still uncertain and require further examination. In the current study, we studied the associations of SNPs in the genes VWF, GSTs and TNF-alpha with stroke in the Saudi population. Genotyping was performed using the ARMS -PCR for TNF-alpha, AS-PCR for VWF and multiplex PCR for GSTs. The study included 210 study subjects: 100 stroke cases and 110 healthy controls. We obtained significant distributions of VWF rs61748511 T > C, TNF-alpha rs1800629 G > A and GST rs4025935 and rs71748309 genotypes between stroke cases and the healthy controls (p < 0.05). The results also indicated that the TNF-alpha A allele was associated with risk of stroke with odd ratio (OR) = 2.22 and risk ratio = RR 2.47, p < 0.05. Similarly, the VWF-TC genotype and C allele were strongly linked with stroke with OR = 8.12 and RR 4.7, p < 0.05. In addition, GSTT1 and GSTT1 null genotype was strongly associated with stroke predisposition with OR = 8.30 and RR = 2.25, p < 0.0001. We conclude that there is a possible strong association between the VWF-T > C, TNF-alpha G > A, GSTT1 gene variants and ischemic stroke susceptibility in the Saudi population. However, future well-designed and large-scale case-control studies on protein-protein interactions and protein functional studies are required to verify these findings and examine the effects of these SNPs on these proteins.

Antiapoptotic Gene Genotype and Allele Variations and the Risk of Lymphoma.

BACKGROUND: The findings of earlier investigations of antiapoptotic gene genotypes and allele variants on lymphoma risk are ambiguous. This study aimed to examine the relationship between the mutation in the antiapoptotic genes and lymphoma risk among Saudi patients. METHODS: This case-control study included 205 patients, 100 of whom had lymphoma (cases) and 105 who were healthy volunteers (controls). We used tetra amplification refractory mutation polymerase chain reaction (PCR) to identify antiapoptotic genes such as B-cell lymphoma-2 (BCL2-938 C > A), MCL1-rs9803935 T > G, and survivin (BIRC5-rs17882312 G > C and BIRC5-rs9904341 G > C). Allelic-specific PCR was used to identify alleles such as BIRC5-C, MCL1-G, and BIRC5-G. RESULTS: The dominant inheritance model among cases showed that mutations in all four antiapoptotic genes were more likely to be associated with the risk of lymphoma by the odds of 2.0-, 1.98-, 3.90-, and 3.29-fold, respectively, compared to controls. Apart from the BCL-2-A allele, all three specified alleles were more likely to be associated with lymphoma by the odds of 2.04-, 1.65-, and 2.11-fold, respectively. CONCLUSION: Unlike healthy individuals, lymphoma patients are more likely to have antiapoptotic gene genotypes and allele variants, apart from BCL-2-A alterations. In the future, these findings could be used to classify and identify patients at risk of lymphoma.

Vasorelaxant and Antihypertensive Effects of Bergenin on Isolated Rat Aorta and High Salt-Induced Hypertensive Rats.

Bergenin is a phenolic glycoside that has been reported to be present in some medicinal plants which are traditionally used for their antihypertensive actions. So, bergenin was investigated for antihypertensive and vasorelaxant experiments in a rat model. Bergenin produced a significant fall in the mean arterial pressure (MAP) of rats. To explore the involvement of NO and muscarinic receptors, rats were pretreated with L-NAME and atropine in-vivo. The L-NAME did not change significantly the effect of bergenin on MAP excluding the involvement of NO. Unlike the L-NAME, atropine pretreatment reduced the effect of bergenin on MAP, indicating the role of muscarinic receptors. In in-vitro study, the bergenin produced endothelium-dependent (at lower concentrations) and independent (at higher concentrations) vasorelaxation, which was attenuated significantly in the presence of atropine and indomethacin but not with L-NAME. While a partial response was observed against K+-induced contractions. This was further confirmed when bergenin partly shifted the CaCl2-CRCs toward right. Bergenin also suppressed the PE peak formation, indicating the antagonist effect against the release of Ca2+. Moreover, the bergenin-induced vasorelaxant response was not markedly attenuated with TEA, while significantly ablated with 4-AP and BaCl2. In conclusion, the antihypertensive effects of bergenin are due to Ca2+ channel blockade, K+ channels activation, and muscarinic receptor-linked vasodilation.

Melatonin ameliorates the adrenal and pancreatic alterations in streptozotocin-induced diabetic rats: Clinical, biochemical, and descriptive histopathological studies.

Previous studies have demonstrated the beneficial effects of melatonin in diabetic rats. However, limited studies have been conducted on the potential effects of melatonin on the descriptive histopathological and morphometric findings in different compartments of the adrenal glands in diabetic animal models. In this study, using a streptozotocin (STZ)-induced diabetic rat model, we sought to examine histological alterations in the pancreas and adrenal glands and observe the effect of the administration of melatonin on the histopathology and morphology of the pancreas and the adrenal gland cortex and medulla that are altered by STZ-induced hyperglycemia. Rats were randomly assigned to four different groups: Group I, normal control; Group II, melatonin group (MT) (10 mg/kg/day); Group III, (diabetic STZ group), and Group IV, diabetic (STZ) + melatonin group (MT). Throughout the experiment, the animals' fasting blood sugar levels were measured. Blood was obtained to determine the animals' cumulative blood sugar levels after sacrification. For histological and morphometrical evaluations, the pancreatic and adrenal gland tissues were dissected and processed. Our results showed that diabetic rats receiving melatonin significantly (P < 0.05) improved their fasting blood sugar and cumulative blood sugar levels compared to the diabetic group not receiving melatonin. Furthermore, histopathological examinations of the pancreatic and adrenal tissues of the diabetic rats indicated the occurrence of severe histopathological and morphometric changes. Morphometric analysis of the adrenals indicated a significant increase (P < 0.05) in the thickness of the cortex zones [zona glomerulosa (ZG), zona fasciculata (ZF), and zona reticularis (ZR)] for the diabetic STZ group compared with other groups, and a significant decrease (P < 0.05) in the diameter of the in adrenal gland medullas in the diabetic STZ rats compared to the other groups. Furthermore, treatment with melatonin restored these changes in both the pancreatic and adrenal gland tissues and produced a significant (P < 0.05) improvement in the cortex and medulla thickness compared to the untreated diabetic rats. Overall, melatonin significantly reduced the hyperglycemic levels of glucose in diabetic rats and reversed the majority of histopathological alterations in the tissues of the pancreas and adrenals, demonstrating its anti-diabetic activity.

Genetic Determinants of Cardiovascular Disease: The Endothelial Nitric Oxide Synthase 3 (eNOS3), Krüppel-Like Factor-14 (KLF-14), Methylenetetrahydrofolate Reductase (MTHFR), MiRNAs27a and Their Association with the Predisposition and Susceptibility to Coronary Artery Disease.

Coronary artery disease (CAD) is an important cause of death worldwide. CAD is caused by genetic and other factors including hypertension, hyperlipidemia, obesity, stress, unhealthy diet, physical inactively, smoking and Type 2 diabetes (T2D). The genome wide association studies (GWASs) have revealed the association of many loci with risk to diseases such as cancers, T2D and CAD. Nitric oxide (NO) is a potent vasodilator and is required for normal vascular health. It is produced in the endothelial cells in a reaction catalyzed by the endothelial NO synthase (eNOS). Methylenetetrahydrofolate reductase (MTHFR) is a very important enzyme involved in metabolism of folate and homocysteine, and its reduced function leads to cardiovascular disease. The Krüppel-like factor-14 (KLF-14) is an important transcriptional regulator that has been implicated in metabolic syndrome. MicroRNA (MiRNAs) are short non-coding RNAs that regulate the gene expression of proteins involved in important physiological processes including cell cycle and metabolism. In the present study, we have investigated the potential impact of germline pathogenic variants of endothelial eNOS, KLF-14, MTHFR, MiRNA-27a and their association with risk to CAD in the Saudi population. Methods: Amplification Refractory Mutation System (ARMS) PCR was used to detect MTHFR, KLF-14, miRNA-27a and eNOS3 genotyping in CAD patients and healthy controls. About 125 CAD cases and 125 controls were enrolled in this study and statistical associations were calculated including p-value, risk ratio (RR), and odds ratio (OD). Results: There were statistically significant differences (p < 0.05) in genotype distributions of MTHFR 677 C>T, KLF-14 rs972283 G>A, miRNAs27a rs895819 A>G and eNOS3 rs1799983 G>T between CAD patients and controls. In addition, our results indicated that the MTHFR-TT genotype was associated with increased CAD susceptibility with an OR 2.75 (95%) and p < 0.049, and the KLF14-AA genotype was also associated with increased CAD susceptibility with an OR of 2.24 (95%) and p < 0.024. Moreover, the miRNAs27a-GG genotype protects from CAD risk with an OR = 0.31 (0.016), p = 0.016. Our results also indicated that eNOS3 -GT genotype is associated with CAD susceptibility with an OR = 2.65, and p < 0.0003. Conclusion: The MTHFR 677C>T, KLF14 rs972283 G>A, miRNAs27a A>G, and eNOS3 rs1799983 G>T genotypes were associated with CAD susceptibility (p < 0.05). These findings require verification in future large-scale population based studies before these loci are used for the prediction and identification of individuals at risk to CAD. Weight control, physical activity, and smoking cessation are very influential recommendations given by clinicians to the at risk individuals to reduce or delay the development of CAD.

Prevalence of Transfusion-Transmitted Infections (HCV, HIV, Syphilis and Malaria) in Blood Donors: A Large-Scale Cross-Sectional Study.

Blood plays a major role in transmitting infectious diseases such as hepatitis C virus (HCV), human immunodeficiency virus (HIV), hepatitis B virus (HBV), syphilis, malaria, and many others. Thus, this study sought to evaluate the distribution of HCV, HIV, syphilis, and malaria among blood donors in Yemen. This is a cross-sectional study, conducted on blood donors at the national center in Yemen. Blood donors' specimens were serologically tested for the presence of anti-HCV and anti-HIV antibodies, as well as anti-Treponema pallidum, anti-Plasmodium falciparum, and anti-Plasmodium vivax. A total of 16,367 donors were included in this study. Based on the donor's occupation, the study showed that the relative seroprevalence of anti-HCV Ab among the donors was statistically significant, and relatively high prevalence was found among military donors (2.8%). Positive HIV antibody tests were only reported in 33 male donors (0.2%), who were mostly manual workers. A remarkably high prevalence of anti-Treponema pallidum was observed among manual workers (3.1%). There was a statistically significant difference in the distribution of anti-malaria Ab based on residency and age groups. This study revealed that the prevalence of HCV, HIV, syphilis, and malaria among donors was 2.0%, 0.2%, 2.4%, and 0.7%, respectively. Further genotyping studies are necessary to provide a complete picture of the prevalence of transfusion-transmitted infections (TTIs).

Prevalence and Association of Transfusion Transmitted Infections with ABO and Rh Blood Groups among Blood Donors in the Western Region of Saudi Arabia: A 7-Year Retrospective Analysis.

This study was aimed at determining the prevalence estimate and association of transfusion-transmitted infections (TTIs) with ABO and Rh blood groups among blood donors at the King Faisal Specialist Hospital and Research Center (KFSH & RC) in the western region of Saudi Arabia. A retrospective study was conducted at the blood bank center of KFSH and RC from 1 January 2013 to 31 December 2019. Data on ABO and Rh blood group testing, serological testing, molecular investigations, serological assays, nucleic acid testing (NATs), and socio-demographic information were gathered. During the study period, there were 959,431 blood donors at the KFSH and RC. The overall 7-year cumulative prevalence estimate of blood transfusion-transmitted infections among blood donors was low at 7.93%, with an average prevalence estimate of 0.66%. Donors with the O blood group, the O RhD +ve blood group, in particular, were more at risk of developing TTIs, whereas donors with the AB blood group, the AB RhD -ve blood group, in particular, were at the lowest risk of developing TTIs. In total, 96.9% of the blood donors were males (n = 916,567). Almost half of the blood donors belong to the O blood group (49.4%). A total of 861,279 (91.0%) donors were found to be RhD positive. The percentages of TTIs were found to be higher in RhD +ve donors compared with RhD -ve donors. The prevalence estimate of the hemoglobin C (HbC) infection was the most common TTI among the blood donors being 3.97%, followed by malaria being 2.21%. The least prevalence estimate of TTI in the present study was for NAT HIV being 0.02%. Significant associations were observed between RhD +ve and RhD -ve among the malaria-infected donors (A: χ2 = 26.618, p = 0.001; AB: χ2 = 23.540, p = 0.001; B: χ2 = 5.419, p = 0.020; O: χ2 = 68.701, p = 0.001). The current 7-year retrospective study showed a low level of TTIs among blood donors. However, we urge that more research encompassing the entire country be conducted in order to obtain more representative results in terms of the prevalence estimate and association of transfusion-transmitted infections with ABO and Rh blood groups in communities.

Outcome Prediction of Hematologic Malignancy in Critically Sick People.

People with hematologic malignancies (HM) frequently postulate intensive care unit (ICU) hospitalization due to organ damage caused by the disease process or treatment-related consequences. This study is aimed at looking at mortality and sign factors in adult patients with hematologic malignancy (HM) who have been hospitalized in the ICU. Death was one quality indicator; researchers used a machine learning approach to find determinants of death. As per the study, there have been 206 patients hospitalized in the ICU (mean age: 51.3 ± 13.6 years; 60% male). The average length of stay was three days, with 14.1% requiring extended ICU commitment. ICU death was 45.6% at 30 days, 62.6% at sixty days, and 74.3% at twelve months, rising to 59.2% at thirty days, 62.6% at sixty days, and 74.3% at twelve months. Ventilation systems and vasodilating medication were linked to higher ICU death, but admission to the ICU surgically and experiencing malignancies are linked with lower death rates. Patients with HM who are hospitalized in the ICU have a high mortality rate (45.6%), which rises to 74.3% after a year. Serious illness, postsurgical hospitalization, and malignancy were revealed as determinants of patient outcomes in multivariate analyses.

Receptor binding domain of SARS-CoV-2 from Wuhan strain to Omicron B.1.1.529 attributes increased affinity to variable structures of human ACE2.

BACKGROUND: COVID-19 is an infectious disease declared as a global pandemic caused by SARS-CoV-2 virus. Genomic changes in the receptor binding domain (RBD) region of SARS-CoV-2 led to an increased, infectivity in humans through interaction with the angiotensin-converting enzyme2 (ACE2) receptor. Simultaneously, the genetic variants in ACE2 provide an opportunity for SARS-CoV-2 infection and severity. We demonstrate the binding efficiencies of RBDs of SARS-CoV-2 strain with ACE2 variants of the human host. METHODOLOGY: A Total of 615 SARS-CoV-2 genomes were retrieved from repository. Eighteen variations were identified contributing to structural changes in RBD that are distributed in 615 isolates. An analyses of 285 single nucleotide variances at the coding region of the ACE2 receptor showed 34 to be pathogenic. Homology models of 34 ACE2 and 18 RBD structures were constructed with 34 and 18 structural variants, respectively. Protein docking of 612 (34 *18) ACE2-RBD complexes showed variable affinities compared to wildtype Wuhan's and other SARS-CoV-2 RBDs, including Omicron B.1.1.529. Finally, molecular dynamic simulation was performed to determine the stability of the complexes. RESULTS: Among 612, the top 3 complexes showing least binding energy were selected. The ACE2 with rs961360700 variant showed the least binding energy (-895.2 Kcal/mol) on binding with the RBD of Phe160Ser variant compared to Wuhan's RBD complex. Interestingly, the binding energy of RBD of Omicron B.1.1.529 with ACE2 (rs961360700) structure showed least binding energy of -1010 Kcal/mol. Additionally, molecular dynamics showed structure stability for all the analysed complexes with the RMSD (0.22-0.26 nm), RMSF (0.11-0.13 nm), and Rg (2.53-2.56 nm). CONCLUSION: In conclusion, our investigation highlights the clinical variants contributing to structural variants in ACE2 receptors that lead to efficient binding of SARS-CoV-2. Therefore, screening of these ACE2 polymorphisms will help detect COVID-19 risk population so as to provide additional care and for safe management.