Novel mutation in alpha-spectrin gene in Saudi patients with hereditary spherocytosis.

Hereditary spherocytosis (HS) is the most common hereditary hemolytic disorder induced by red blood cell (RBC) membrane defect. This study was undertaken to determine mutations in genes associated with RBC membrane defect in patients with HS such as α-spectrin gene (SPTA1), ß-spectrin gene (SPTB), ankyrin gene (ANK1), band 3 anion transport gene (SLC4A1) and erythrocyte membrane protein band 4.1 gene (EPB41). Blood samples were collected from 23 unrelated patients with HS. Patients were diagnosed according to the guidelines from the British Society for Hematology. All hematological examinations for the determination of RBC abnormalities and osmotic fragility tests were conducted. Genomic DNA were extracted from peripheral blood cells and coding exons of known genes for hereditary spherocytosis were enriched using Roche/KAPA sequence capture technology and sequenced on an Illumina system via next-generation sequencing (NGS). The data showed that most of the HS patients confirmed splenomegaly and showed elevated reticulocytes and abnormal bilirubin values. NGS analysis identified the heterozygous variant c.5501G > A in the exon 39 of SPTA1 gene, resulted in a Trp1834*, which leads to a premature stop codon and subsequent mRNA degradation (nonsense- mediated decay) or truncation in α spectrin. Moreover, our data also revealed conventional mutations in genes SPTB, ANK, SLC4A1 and EBP41 in severe patients of HS. In short, this is the first report that determined a novel mutation c.5501G > A in SPTA1 gene in the Saudi population. To the best of our knowledge, this variant c.5501G > A has not been described in global literature so far. This novel mutation in SPTA1 gene is unique in the Saudi population.

Mucormycosis co-infection in COVID-19 patients: An update.

Mucormycosis (MCM) is a rare fungal disorder that has recently been increased in parallel with novel COVID-19 infection. MCM with COVID-19 is extremely lethal, particularly in immunocompromised individuals. The collection of available scientific information helps in the management of this co-infection, but still, the main question on COVID-19, whether it is occasional, participatory, concurrent, or coincidental needs to be addressed. Several case reports of these co-infections have been explained as causal associations, but the direct contribution in immunocompromised individuals remains to be explored completely. This review aims to provide an update that serves as a guide for the diagnosis and treatment of MCM patients' co-infection with COVID-19. The initial report has suggested that COVID-19 patients might be susceptible to developing invasive fungal infections by different species, including MCM as a co-infection. In spite of this, co-infection has been explored only in severe cases with common triangles: diabetes, diabetes ketoacidosis, and corticosteroids. Pathogenic mechanisms in the aggressiveness of MCM infection involves the reduction of phagocytic activity, attainable quantities of ferritin attributed with transferrin in diabetic ketoacidosis, and fungal heme oxygenase, which enhances iron absorption for its metabolism. Therefore, severe COVID-19 cases are associated with increased risk factors of invasive fungal co-infections. In addition, COVID-19 infection leads to reduction in cluster of differentiation, especially CD4+ and CD8+ T cell counts, which may be highly implicated in fungal co-infections. Thus, the progress in MCM management is dependent on a different strategy, including reduction or stopping of implicit predisposing factors, early intake of active antifungal drugs at appropriate doses, and complete elimination via surgical debridement of infected tissues.

Impact of COVID-19 pandemic quarantine on physical, nutritional, psychosocial life and work aspects in the Kingdom of Saudi Arabia.

Background: The coronavirus disease-2019 (COVID-19) is a global public health disaster imposing a nationwide lockdown. This study was undertaken to determine the impact of COVID-19 quarantine on physical, nutritional, psychosocial life, and work aspects on the population of Saudi Arabia. Methods: Data collection was based on the fear of COVID-19 Scale (FCV-19S) and was analyzed by the Likert-type scale. A total of 2828 individuals participated during their COVID-19 quarantine. The data were collected during June 10-17, 2020 using the psychosocial FCV-19S. Results: COVID-19 quarantine was negatively correlated with the physical, nutritional, psychosocial life and work aspects of the Saudi Arabia's population (P < 0.05). As a result of the correlation analysis, gender, sociodemographic status and having a family member dying of COVID-19, marital status (single), monthly income (<3000) and occupation (student), and lost a job or businesses were significantly associated with fear of COVID-19 (P < 0.05). Furthermore, the participants reported a reduction in their physical activity by 59%, whereas 26.5% of participants showed an increase of body weight. Moreover, 23% of participants lost their jobs during the pandemic. Conclusions: The lockdown period was associated with an increase in the COVID-19 fear score. The degree FCV-19S was varied in different categories in several aspects. Low levels of physical activity and weight gained were observed during the lockdown period.

Association of genetic polymorphisms in DNA repair genes ERCC2 Asp312Asn (rs1799793), ERCC2 Lys 751 Gln (rs13181), XRCC1 Arg399 Gln (rs25487) and XRCC3 Thr 241Met (rs861539) with the susceptibility of lung cancer in Saudi population.

This study demonstrated the association of polymorphisms in ERCC2 (Asp312Asn) rs1799793, ERCC2 (Lys751Gln) rs13181, XRCC1 (Arg399Gln) rs25487 and XRCC3(Thr241Met) rs861539 polymorphisms with a susceptibility of lung cancer (LC) onset in the Saudi population. The study was performed on 134 LC patients and 270 controls. The data revealed that there was no significant association of LC with subtype squamous cell carcinoma (SCC), small cell lung cancer (SCLC) and adenocarcinoma with the ERCC2 rs1799793 polymorphism. The data showed that the CC genotype for ERCC2 rs13181, the AA genotype for XRCC1 rs25487, and the genotype TT for XRCC3 rs861539 were significantly associated with SCC susceptibility (p < 0.05). Similarly, the CC genotype for ERCC2 rs13181 and the AA genotype for XRCC1 rs25487 were significantly associated with adenocarcinoma susceptibility (p < 0.05). Whereas, the TT genotype for XRCC3 rs861539 was significantly associated with SCLC susceptibility (p = 0.005). In total, significant association of LC susceptibility was found in the following combination models of recessive genotypes: AC heterozygous for ERCC2 rs13181 + AA homozygous for XRCC1 rs25487, CC homozygous for ERCC2 rs13181 + GA heterozygous for rs25487, CC homozygous for rs13181 + AA homozygous for XRCC1 rs25487, CC homozygous for ERCC2 rs13181 + TT homozygous for XRCC3 rs861539, GA heterozygous for XRCC1 rs25487 + CT heterozygous for XRCC3 rs861539, GA heterozygous for XRCC1 rs25487 + TT homozygous for XRCC3 rs861539, AA homozygous for XRCC1 rs25487 + CT heterozygous for XRCC3 rs861539, AA homozygous for XRCC1 rs25487+ TT homozygous for XRCC3 rs861539. These data clearly demonstrated that the combination of recessive genotypes may be associated with susceptibility of LC onset (p < 0.05). In short, the data indicated that DNA repair genes increase LC risk via gene-gene interaction rather than independent variants.

Modulation of mice immune responses against Schistosoma mansoni infection with anti-schistosomiasis drugs: Role of interleukin-4 and interferon-gamma.

Objective: Schistosoma mansoni (S. mansoni) is endemic in Africa, the Middle East, South America, and the Caribbean. This study investigated the modulation of immune response against S. mansoni through estimation of interleukin-4 (IL-4) (Th2 cytokine) and interferon-gamma (INF-γ) (Th1 cytokine) under the effect of anti-schistosomal drugs. Methods: Laboratory bred female albino mice (n = 120) were divided into the following groups: untreated mice, S. mansoni infected mice, S. mansoni infected mice treated with artemisinin (ART), arachidonic acid (ARA), nifedipine or praziquantel (PZQ). Levels of IL-4 and INF-γ cytokines in the serum samples of treated and untreated mice were determined by enzyme-linked immunosorbent assay and the results were further validated by measuring the mRNA levels IL-4 and INF-γ using quantitative real-time polymerase chain reaction. Results: Anti-schistosomiasis drugs ART and ARA increased the levels of Th2 cytokine IL-4 (P < 0.05), whereas PZQ drug decreased the response of IL-4 (P < 0.05). However, nifedipine was found to be ineffective in modulating the response of IL-4 (P > 0.05). As far as Th-1 cytokine IFN γ was concerned, only PZQ increased its levels (P < 0.05), whereas other tested anti-schistosomiasis drugs; ART, ARA, and nifedipine were found to be infective (P > 0.05). Conclusions: These findings indicated that anti-schistosomiasis drugs ART, ARA, and PZQ play a role in the modulation of expression of Th2 cytokines. Whereas, only PZQ may play a role in the modulation of Th1 cytokines. These findings provide a scope for the formulation of novel anti-schistosomal drugs as well as in the therapeutic management of patients infected with S. mansoni.

COVID-19: Post-recovery long-term symptoms among patients in Saudi Arabia.

BACKGROUND: After recovery from acute infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), many patients experience long-term symptoms in different body systems. The aim of the present study was to identify these symptoms, their severity, and their duration as a first step in building a system to classify post-recovery long-term symptoms of coronavirus disease 2019 (COVID-19). METHODS: An online-based cross-sectional survey was administered between September and October 2020. Data regarding the severity of post-recovery symptoms and their duration were collected using an Arabic questionnaire divided into six categories encompassing the 20 most prevalent symptoms. RESULTS: A total of 979 patients recovered from COVID-19 in Saudi Arabia in the study period, of whom 53% were male and 47% were female. The most common symptoms included general fatigue and weakness (73% each), with moderate severity of neurological symptoms including mood changes (41%) and insomnia (39%). Among the special senses, loss of smell and taste of marked severity were reported by 64% and 55% among respiratory symptoms, cough of mild severity (47%), and dyspnea of moderate severity (43%). Loss of appetite of moderate severity was reported in 42%, and diarrhea, abdominal pain, and nausea of mild severity were reported by 53%, 50%, and 44% of respondents, respectively. CONCLUSIONS: Long-term symptoms after recovery from COVID-19 warrant patient follow-up. The authors propose a classification system as a starting point to guide the identification and follow-up of long-term symptoms post-recovery, and recommend larger-scale studies to broaden the definition of recovery from COVID-19, which appears to have two phases, acute and chronic.

Physicians based emergency medical services for the management of burn injuries in trauma centers of the center region of Saudi Arabia: evaluation of physicians' knowledge and experience.

BACKGROUND: Medical services at trauma centers regularly encounter severe burn patients but prehospital care of these patients in Saudi Arabia is comparatively unexplored. This study evaluates the knowledge and experience of physicians working in trauma centers of Qassim province of Saudi Arabia for the management of patients with burn injuries. METHODS: This is a cross sectional study performed on 204 physicians working in the trauma centers of Qassim province. Physicians' knowledge and experience were assessed via administration of validated questionnaires and the data were analyzed using SPSS software. RESULTS: Among total studied physicians, only 35.3% and 24.0% gave the right answer to the question on the diagnosis of burn skin in depth/extent for adults and pediatric patients, respectively. Importantly, 93.6% physicians responded correctly for first aid treatment. For the parkland concept, 62.2% responded correctly, however, only 22.5% understand the colloid fluid concept. The 74% physicians knew the methods of fluid revival for mass burn injuries and about half of studied physicians showed right knowledge for intubation for breathing for mass burn injuries. Only 47.5% physicians understand the concept of electrolyte disorder. CONCLUSIONS: This is the first study from the central region of Saudi Arabia that analyzed the knowledge and experience of physicians working in trauma centers for the management of patients with burn injuries. Overall data showed that ~60% physicians working in trauma centers have knowledge for handling the patients with burn injuries but the rest needed counseling, therefore proper training sessions for them are needed for management of burn patients.

Early prediction keys for COVID-19 cases progression: A meta-analysis.

BACKGROUNDː: Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), within few months of being declared as a global pandemic by WHO, the number of confirmed cases has been over 75 million and over 1.6 million deaths since the start of the Pandemic and still counting, there is no consensus on factors that predict COVID-19 case progression despite the diversity of studies that reported sporadic laboratory predictive values predicting severe progression. We review different biomarkers to systematically analyzed these values to evaluate whether are they are correlated with the severity of COVID-19 disease and so their ability to be a predictor for progression. METHODS: The current meta-analysis was carried out to identify relevant articles using eight different databases regarding the values of biomarkers and risk factors of significance that predict progression of mild or moderate cases into severe and critical cases. We defined the eligibility criteria using a PICO model. RESULTS: Twenty-two relevant articles were selected for meta-analysis the following biomarkers C-reactive protein, interleukin-6, LDH, neutrophil, %PD-1 expression, D-dimer, creatinine, AST and Cortisol all recorded high cut-off values linked to severe and critical cases while low lymphocyte count, and low Albumin level were recorded. Also, we meta- analyzed age and comorbidities as a risk factors of progression as hypertension, Diabetes and chronic obstructive lung diseases which significantly correlated with cases progression (p < 0.05). CONCLUSIONS: ː The current meta-analysis is the first step for analysing and getting cut-off references values of significance for prediction COVID-19 case progression. More studies are needed on patients infected with SARS-CoV-2 and on a larger scale to establish clearer threshold values that predict progression from mild to severe cases. In addition, more biomarkers testing also help in building a scoring system for the prediction and guiding for proper timely treatment.