The effect of caffeine intake and passive smoking on umbilical cord blood unit's quality parameters.

Today cord blood (CB) is a valuable source of hematopoietic stem cells to treat many hematological disorders. One of the limitations of CB utilization is the reduced number of nucleated cells including stem cells. Therefore, CB banks around the world have developed strategies in an attempt to improve donor selection and the quality of the CB inventory. This study aimed to determine the impact of passive smoking and caffeine consumption on CB quality. CBs were obtained from mothers who gave birth at King Abdulaziz Medical City. All mothers gave their informed consent. Personal interviews about the mother's demographics, smoking status and exposure, and caffeine consumption executed, followed by a chart review to analyze maternal and neonatal factors. Laboratory testing was performed on all collected CB units. Using descriptive statistics, maternal and newborn factors were analyzed. T-test or Mann-Whitney U Test, as appropriate, for continuous variables analysis to study the effect of second hand smoking and coffee consumption for the primary outcome. Our study demonstrated a reduction in CB MNC, including lymphocytes, in caffeine consumers among pregnant donors, as well as a reduction in cell potency activities, including total CFU and BFU-E. The effect of passive cigarette smoking on the same cohort was insignificant. Outcome of this study will help in optimizing the quality and quantity of stem cell harvesting from CB to get the maximum benefit and such knowledge will raise the awareness among pregnant women.

Association of KIR gene polymorphisms with COVID-19 disease.

BACKGROUND: Natural killer (NK) cells play an essential role against viruses. NK cells express killer cell immunoglobulin-like receptors (KIRs) which regulate their activity and function. The polymorphisms in KIR haplotypes confer differential viral susceptibility and disease severity caused by infections. We investigated the association between KIR genes and COVID-19 disease severity. METHODS: 424 COVID-19 positive patients were divided according to their disease severity into mild, moderate and severe. KIR genes were genotyped using next generation sequencing (NGS). Association between KIR genes and COVID-19 disease severity was conducted and significant correlations were reported. RESULTS: In the COVID-19 patients, KIR Bx genotype was more common than AA genotype. The Bx genotype was found more frequently in patients with mild disease, while in severe disease the AA genotype was more common than the Bx genotype. The KIR2DS4 gene carried the highest risk for severe COVID-19 infection (OR 8.48, pc= 0.0084) followed by KIR3DL1 (OR 7.61, pc= 0.0192). CONCLUSIONS: Our findings suggest that KIR2DS4 and KIR3DL1 genes carry risk for severe COVID-19 disease.

Inflammatory Response and Phenotyping in Severe Acute Respiratory Infection From the Middle East Respiratory Syndrome Coronavirus and Other Etiologies.

OBJECTIVES: In this study, we evaluated the inflammatory response in patients with severe acute respiratory infection due to the Middle East respiratory syndrome and non-Middle East respiratory syndrome and assessed the presence of distinct inflammatory subphenotypes using latent class analysis. DESIGN: Prospective cohort study. SETTING: A tertiary care ICU in Riyadh, Saudi Arabia. PATIENTS: Consecutive critically ill patients with laboratory-confirmed Middle East respiratory syndrome severe acute respiratory infection and non-Middle East respiratory syndrome severe acute respiratory infection. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: We measured cytokines on days 1, 3, 7, and 14 of ICU stay. We included 116 patients (40 with Middle East respiratory syndrome severe acute respiratory infection and 76 with non-Middle East respiratory syndrome severe acute respiratory infection). On ICU day 1, both patients with Middle East respiratory syndrome severe acute respiratory infection and non-Middle East respiratory syndrome severe acute respiratory infection had higher levels of interleukin-3, interleukin-4, interleukin-6, interleukin-8, interleukin-17A, eotaxin, and epidermal growth factor compared with healthy controls. There were no differences in cytokines over time between patients with Middle East respiratory syndrome severe acute respiratory infection and non-Middle East respiratory syndrome severe acute respiratory infection. Using day 1 cytokine levels, latent class analysis categorized patients into two subphenotypes: subphenotype 1 (n = 74 [64%]) and subphenotype 2 (n = 42 [36%]); the latter had significantly higher levels of interleukin-1ß, interleukin-1ra, interleukin-2, interleukin-6, interleukin-7, interleukin-8, interleukin-10, interleukin-12p70, interleukin-15, interleukin-17A, inducible protein-10, monocyte chemoattractant protein-1, macrophage inflammatory protein-1α, macrophage inflammatory protein-1ß, tumor necrosis factor-α, granulocyte-macrophage colony-stimulating factor, granulocyte-colony stimulating factor, interferon-α, and interferon-γ. Although baseline characteristics were not different between the two subphenotypes, patients in the subphenotype 2 had higher ICU mortality compared with the subphenotype 1 (18/42 [43%] vs 17/74 [23%]; p = 0.03). CONCLUSIONS: One third of critically ill patients with Middle East respiratory syndrome severe acute respiratory infection and non-Middle East respiratory syndrome severe acute respiratory infection demonstrated a subphenotype characterized by increased proinflammatory cytokines, consistent with cytokine storm. Further research is needed to examine whether immunomodulators have differential effects based on inflammatory subphenotypes.

Real-World Issues and Potential Solutions in Hematopoietic Cell Transplantation during the COVID-19 Pandemic: Perspectives from the Worldwide Network for Blood and Marrow Transplantation and Center for International Blood and Marrow Transplant Research Health Services and International Studies Committee.

The current COVID-19 pandemic, caused by SARS-CoV-2, has impacted many facets of hematopoietic cell transplantation (HCT) in both developed and developing countries. Realizing the challenges as a result of this pandemic affecting the daily practice of the HCT centers and the recognition of the variability in practice worldwide, the Worldwide Network for Blood and Marrow Transplantation (WBMT) and the Center for International Blood and Marrow Transplant Research's (CIBMTR) Health Services and International Studies Committee have jointly produced an expert opinion statement as a general guide to deal with certain aspects of HCT, including diagnostics for SARS-CoV-2 in HCT recipient, pre- and post-HCT management, donor issues, medical tourism, and facilities management. During these crucial times, which may last for months or years, the HCT community must reorganize to proceed with transplantation activity in those patients who urgently require it, albeit with extreme caution. This shared knowledge may be of value to the HCT community in the absence of high-quality evidence-based medicine. © 2020 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc.

Screening for pre-leukemia TEL-AML1 chromosomal translocation in banked cord blood units: cord blood bank perspective.

Acute lymphocytic leukemia is the most common leukemia in children. Many studies suggest the existence of two subsequent hits in order for the disease to occur. TEL-AML1 (ETV6-RUNX1) is considered an initial genetic hit that occurs prenatally and generates a pre-leukemia clone. In cord blood (CB) stem cell transplantation, donor cell leukemia (DCL) is one of the complications associated with the presence of the pre-leukemic clone. The aim of this study was to identify the prevalence of ETV6-RUNX1 translocation in CB units and the feasibility in implementing such a screening test, to ensure the safety of the CB units. A total of 424 CB samples were tested from the CB units banked at KAIMRC-CBB. RNA was extracted and cDNA synthesis was performed on 1 ug input RNA using Reverse Transcriptase RT-PCR methodology. Chromosomal translocation ETV6-RUNX1 was tested using real time quantitative PCR methodology. Our study showed undetectable levels of ETV6-RUNX1 in all tested CB samples. The samples were analyzed for the chromosomal translocation ETV6-RUNX1 under controlled conditions, using control and fusion genes with known concentrations. The result of this study does not rule out the importance of this screening test in predicting and/or preventing DCL. Moreover, the outcome strengthens the adopted system in our CBB for mother medical history screening prior to donation. We propose adding this test during the verification testing stage, prior to the release of CB units selected for transplantation rather than at the banking stage.

Factor predicting total nucleated cell counts in cord blood units.

BACKGROUND: Cord blood (CB) stem cells have been used worldwide in transplant medicine to treat various diseases. The efficacy of stem cells in umbilical CB (UCB) can be predicted by the number of total nucleated cells (TNCs). To optimize the clinical use of stem cells in our population, this study addresses several variables affecting the TNC count. STUDY DESIGN AND METHODS: This observational, cross-sectional study was conducted in a single center from 2012 to 2014. In total, 957 CB units (CBUs) were collected from consented mothers. Data analyses of clinically accepted CBUs were correlated with maternal and infant factors. RESULTS: Based on the TNC accepted level of banking, 188 CBUs (19.64%) were rejected. Of the 16 maternal and infant variables evaluated, three factors demonstrated a statistically significant predictive value for the accepted TNC level. CB volume was the best predictive factor (p ≤ 0.0001), followed by newborn birth weight (p = 0.025), and the method of delivery (p = 0.002). CONCLUSIONS: Several maternal, neonatal, and obstetric factors appear to play a major role in predicting an accepted TNC count, which can be used to improve criteria for the donation of stem cells in CBUs.

Improving cord blood unit quantity and quality at King Abdullah International Medical Research Center Cord Blood Bank.

BACKGROUND: Public cord blood banks (CBBs) store cord blood unit (CBU) donations for anyone in need. However, strict regulations need to be followed to build up high-quality bank products that can be used worldwide. We established a public CBB at a tertiary hospital in Saudi Arabia. Here, we investigated the reasons behind rejecting or not collecting CBUs over 2 years (2011-2012) and which steps were implemented to improve the number and quality of storable units. STUDY DESIGN AND METHODS: A total of 2891 mothers were evaluated. Reasons for rejecting donors, not collecting, and rejecting units before or after collection were analyzed and compared for the years 2011 and 2012. RESULTS: A total of 1157 (40%) CBUs were not collected, mainly due to staff availability, and 564 (20%) CBUs were rejected. The main reason for rejecting donations was the mother's or neonate's health. Rejecting CBUs after collection was due to low volume. A total of 1170 (40%) CBUs were successfully collected for potential banking and sent for processing; however, 58% were rejected in the laboratory due to low total nucleated cell counts. Several changes were implemented during the 2 years including physician education and awareness, in utero collection, cesarean collection, and staff recruitment. These changes positively affected the numbers of our collected units. Out of the initially eligible mothers in 2011, only 17% were banked; this was increased to 33% in 2012. CONCLUSIONS: We identified the problems with collecting CBUs for banking and will keep improving our selection process of recruiting more CBUs of high quality.

Screening panel-reactive antibody negative, single-antigen positive: a case report.

Sensitized patients remain a challenge for successful transplant. Virtual crossmatch is used to determine the presence or absence of donor-specific antibodies. A 60-year-old woman with a negative screening for panel-reactive antibodies (PRA) received an A*11, A*68 type kidney with a negative anti-human globulin/complement-dependent cytotoxicity (AHG-CDC) crossmatch. Her transplant course was complicated by delayed graft function, and she required hemodialysis. On day 8 after receiving the transplant, she had a kidney biopsy that showed features of antibody-mediated rejection/severe acute tubular necrosis, which was treated by plasmapheresis for 5 sessions and intravenous immunoglobulin (2 g/kg). Her serum level of creatinine decreased from 6.7 to 3.6 mg/dL (600-320 µmol/L). Panel-reactive antibody by Luminex was repeated and again was negative. Single-antigen detection was tried next. Surprisingly, A*11:02 came up positive with a mean fluorescence intensity of 9500. High-resolution donor HLA type was A*68:01 and A*11:01. A*11:02 is not part of the screening Luminex PRA whereas the 11:01 allele is. Serologically, HLA-A11 has 2 defined splits, A11.1 and A11.2, which encode A*11:01 and A*11:02, respectively. In this case, the A*11:02 antibody does not seem to be responsible for the increasing creatinine level. However, if the donor had been A*11:02, a humeral rejection would have occurred and been missed by a virtual crossmatch. Thus virtual crossmatch may not work at all times. Screening for PRA by single antigens is suggested even in PRA-negative cases, if only virtual crossmatch is to be used.

A need to adopt new strategies for organ donation in Saudi Arabia.

BACKGROUND: HLA matching in kidney transplantation is a major factor in long-term survival of the graft. In Saudi Arabia, most deceased donors are non-Saudi, making it difficult to achieve minimal HLA mismatches between donor and recipient. OBJECTIVE: To analyze HLA types of 200 deceased donors and compare them with the Saudi population's HLA types. MATERIALS AND METHODS: In a retrospective study analyzing HLA types of the last 398 deceased donors processed in a tertiary hospital in Riyadh, Saudi Arabia, HLA types of all donors were compared with HLA types from a control group of healthy Saudi persons. RESULTS: HLA types were significantly different between the deceased donor group and the Saudi population. In all deceased donors, zero mismatches was never achieved. The major differences in HLA types were in HLA-A*02, HLA-B*15, B*40, B*50, HLA-DRB1*14, DRB1*15, and DRB1*04. CONCLUSIONS: As most of our deceased donors are non-Saudis, it is difficult to match for HLA-A, HLA-B, and HLA-DR. HLA matching should be attempted nationwide by adopting different strategies, including typing donors centrally and distributing results to all centers, agreeing on a national point system for allocating organs from deceased donors, and making HLA matching a priority, especially for highly sensitized patients.

Identification of the novel HLA-A*02:829 allele by sequencing-based typing.

The novel HLA-A*02:829 allele is likely generated from the recombination of both HLA-A*02:05:01:01 and HLA-A*32:01:01:01 alleles.

Identification of the novel HLA-B*53:69 allele by sequencing-based typing.

The HLA-B*53:69 allele differs from HLA-B*53:01:01:01 by two nucleotide changes in exon 3.

Characteristics, Outcomes, and Associations of Venous Thromboembolism in Diabetic Patients Infected With COVID-19 in Riyadh, Saudi Arabia.

Background The associations and risk factors for venous thromboembolism (VTE) among hospitalized COVID-19 patients remain ambiguous in the literature, with some conflicting findings, especially in Saudi Arabia. In this study, we aim to elaborate on these data by examining regional patient populations and exploring the incidence, lab findings, and outcomes of VTE among hospitalized COVID-19 patients known to have diabetes mellitus (DM). Methodology This cross-sectional study was conducted at King Abdulaziz Medical City in Riyadh. The BestCare system was used to collect patients' data between September 2020 and February 2022. JMP15 was used for data analysis. Frequencies and percentages were used for categorical data, and median and interquartile ranges were used for quantitative data. The chi-square and Kruskal-Wallis rank-sum tests were used to assess the difference between categorical and quantitative variables, respectively. Nominal logistical regression was used to assess diabetes as a risk factor for developing VTE among COVID-19 patients. Results Data from 153 admitted patients were collected after they satisfied the inclusion criteria. Of these patients, 39 (25.49%) developed VTE. The demographic data included age group, gender, and DM status presented as frequencies and percentages. Through bivariate analysis, patients with longer hospital stays had at least one episode of VTE (p = 0.0072). Using nominal logistic regression analysis, diabetes as a risk factor (odds ratio = 4.11, confidence interval = 0.955-5.05, p = 0.0287) was significantly associated with the development of VTE in COVID-19 patients. Conclusions Based on our study, diabetes proved significant when evaluating the possible factors regarding VTE development in COVID-19 patients. In addition, the length of stay also played a critical role in the severity of VTE in COVID-19 patients. Similar studies should be conducted on a national scale in Saudi Arabia to accomplish two goals: first, to gain further understanding of the impact of the variables investigated in our population, and second, to publish data that are more generalizable to the larger population of Saudi Arabia.

Pubertal characteristics among schoolgirls in Riyadh, Saudi Arabia.

Puberty is the gradual transition period between childhood and adulthood. Many factors may contribute to the onset of puberty. The objective of the study was to determine the age of onset of secondary pubertal characteristics among Saudi Arabian girls. A cross-sectional study was conducted using a cluster sample design. Seven hundred and twenty-five schoolgirls between the ages of 6 and 16 years from diverse socioeconomic levels were included. During physical examinations, the height and weight of the girls were recorded, and the stages of breast and pubic hair development were determined according to Tanner stages; axillary hair development was determined according to modified stages. The median age at Tanner stage 2 for breast and pubic hair development was 10 years. The median age at stage 2 in modified scales for axillary hair development was 12 years. In conclusion, the median age of the onset of breast development at Tanner stage 2 for Saudi girls in Riyadh is lower than what has been reported in some countries in Europe, South Africa, Turkey and India but similar to girls in Hong Kong, China and white girls in the USA, which may support secular trends of an earlier onset of puberty.

Perceptions and Attitudes Regarding Hematopoietic Stem Cell Donation Among Blood Donors in Riyadh, Saudi Arabia.

Introduction In recent years, there has been a growing trend toward using stem cell transplantation for therapeutic purposes, making a positive impact in the medical field. Access to a compatible and willing donor is essential for those therapeutic purposes, yet the current number of registered donors remains inadequate. The present study aimed to investigate the attitude and perception of stem cell donation among blood donors in Saudi Arabia while also exploring their knowledge of hematopoietic stem cells, willingness towards donation, and fear of complications after stem cell donation. Methods A cross-sectional study was implemented to investigate the perception and attitude toward stem cell donation among blood donors in Riyadh, Saudi Arabia, through a validated self-administered questionnaire. The questionnaire comprised 35 questions divided into five sections, namely, demographics, knowledge, attitude, willingness, and fear of stem cell donation. Results The survey was distributed to 400 subjects. Out of the 400 respondents, 98.8% (n=395) were male, and 90.8% (n=363) were Saudi nationals. The majority had a high school level of education (n=259, 64.75%). Only 10.8% (n=43) of the participants were knowledgeable about stem cells. Knowledge of stem cells was highest among females aged 40-49 years, participants knowledgeable of platelet donation, and participants who donated blood more than 10 times (p-value <0.05). Participants with a bachelor's or master's degree had significantly more fear of stem cell donation complications, with a p-value of 0.003. The attitude toward stem cell donation was highly positive. Most participants strongly agreed to donate stem cells to a family member or anyone in need, 94.5% (n=378) and 62% (n=248), respectively. Conclusion Knowledge about stem cell donation among blood donors was scarce, while their willingness to donate after conversing was high. We highly recommend the initiation and establishment of educational programs to increase the knowledge of the public and, specifically, blood donors.

Diagnostic Efficacy of RealStar SARS-CoV-2 Reverse Transcription-Polymerase Chain Reaction (RT-PCR) in Comparison to GeneXpert System for the Detection of COVID-19.

Background and objective The coronavirus disease 2019 (COVID-19) pandemic has become a major health concern due to the rapid transmission of the virus that causes it: severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). To address the growing demand on healthcare systems to control this pandemic, more effective diagnostic methods need to be applied. In this study, we aimed to compare the efficacy of RealStar® SARS-CoV-2 reverse transcription-polymerase chain reaction (RT-PCR) versus the GeneXpert® system. Methods A retrospective cross-sectional study was conducted in the central lab of King Abdulaziz Medical City (KAMC) in Riyadh, Saudi Arabia. Data from all nasopharyngeal swabs (NPS) (150,000) submitted for SARS-CoV-2 analysis from July 2020 to July 2021 were reviewed retrospectively. Furthermore, all NPS (n=384) that were analyzed on both the RealStar® SARS-CoV-2 RT-PCR and GeneXpert® systems for confirmatory purposes were included in the study. Acute respiratory illness (ARI) screening forms of the selected samples were reviewed from the electronic database (BestCare system), and they were analyzed and compared at one point in time; therefore, a cross-sectional study was found to be the best suitable study design. Using the statistical analysis software, the receiver operating characteristic (ROC) curve was obtained to compare the sensitivity (Sn), specificity (Sp), positive predictive value (PPV), and negative predictive value (NPV). The test was considered significant if the area under the curve (AUC) value was >0.5. Results The diagnostic performance of the RealStar® and GeneXpert® assays in detecting SARS-CoV-2 was evaluated using ROC curve analysis, which showed AUCs of 0.597 and 0.637, respectively. In addition, 35% of the total results fell into a substantial agreement of 0.76 (95% CI: 0.6626-0.8732). The majority of the NPS were reported negative by both RealStar® (246, 80.66%) and GeneXpert® (226, 74.10%). Most samples (210, 68.85%) were obtained from asymptomatic patients, scoring less than 4 (ARI <4) based on the ARI screening form. Conclusion Based on the AUC of ROC, there is no significant difference in the performance characteristics between the RealStar® RT-PCR and GeneXpert® in detecting COVID-19.

HLA-based banking of induced pluripotent stem cells in Saudi Arabia.

BACKGROUND: Human iPSCs' derivation and use in clinical studies are transforming medicine. Yet, there is a high cost and long waiting time associated with autologous iPS-based cellular therapy, and the genetic engineering of hypo-immunogenic iPS cell lines is hampered with numerous hurdles. Therefore, it is increasingly interesting to create cell stocks based on HLA haplotype distribution in a given population. This study aimed to assess the potential of HLA-based iPS banking for the Saudi population. METHODS: In this study, we interrogated the HLA database of the Saudi Stem Cell Donor Registry (SSCDR), containing high-resolution HLA genotype data from 64,315 registered Saudi donors at the time of analysis. This database was considered to be a representative sample of the Saudi population. The most frequent HLA haplotypes in the Saudi population were determined, and an in-house developed iterative algorithm was used to identify their HLA matching percentages in the SSCDR database and cumulative coverage. Subsequently, to develop a clinically relevant protocol for iPSCs generation, and to illustrate the applicability of the concept of HLA-based banking for cell therapy purposes, the first HLA-based iPS cell line in Saudi Arabia was generated. Clinically relevant methods were employed to generate the two iPS clones from a homozygous donor for the most prevalent HLA haplotype in the Saudi population. The generated lines were then assessed for pluripotency markers, and their ability to differentiate into all three germ layers, beating cardiomyocytes, and neural progenitors was examined. Additionally, the genetic stability of the HLA-iPS cell lines was verified by comparing the mutational burden in the clones and the original blood sample, using whole-genome sequencing. The standards set by the American College of Medical Genetics and Genomics (ACMG) were used to determine the clinical significance of identified variants. RESULTS: The analysis revealed that the establishment of only 13 iPSC lines would match 30% of the Saudi population, 39 lines would attain 50% coverage, and 596 lines would be necessary for over 90% coverage. The proof-of-concept HLA-iPSCs, which cover 6.1% of the Saudi population, successfully demonstrated pluripotency and the ability to differentiate into various cell types including beating cardiomyocytes and neuronal progenitors. The comprehensive genetic analysis corroborated that all identified variants in the derived iPSCs were inherently present in the original donor sample and were classified as benign according to the standards set by the ACMG. CONCLUSIONS: Our study sets a road map for introducing iPS-based cell therapy in the Kingdom of Saudi Arabia. It underscores the pragmatic approach of HLA-based iPSC banking which circumvents the limitations of autologous iPS-based cellular therapies. The successful generation and validation of iPSC lines based on the most prevalent HLA haplotype in the Saudi population signify a promising step toward broadening the accessibility and applicability of stem cell therapies and regenerative medicine in Saudi Arabia.

Mast cells, histamine, and IL-6 regulate the selective influx of dendritic cell subsets into an inflamed lymph node.

In response to bacterial stimuli, multiple dendritic cell (DC) populations accumulate within the draining lymph node, thus enhancing opportunities for effective T cell-DC interaction. DC subpopulations, such as plasmacytoid, CD8(+), and CD11b(+) subsets, have distinct roles in determining the nature of the immune response. The mechanisms whereby individual DC subpopulations are mobilized and the extent to which these processes are linked to increases in overall lymph node cellularity have not been determined. In the current study, the mechanisms of DC subset mobilization to the draining auricular lymph node were examined after intradermal injection of Staphylococcus aureus-derived peptidoglycan. Using mast cell-deficient mice and local mast cell reconstitution, plasmacytoid and CD8(+) DC responses were shown to be mast cell dependent, whereas the CD11b(+) DC response was not. A histamine H2 receptor-dependent, CXCL9-independent pathway controlled the selective influx of both plasmacytoid and CD11b(+) DC into the lymph node, but not lymph node cellularity. In contrast, IL-6 was important for the mobilization of CD8(+) and CD11b(+) DC. TNF and IL-1 receptor were dispensable for plasmacytoid, CD11b(+), and CD8(+) DC responses. These findings provide novel opportunities for the selective mobilization of specific DC subsets to lymph nodes and demonstrate critical roles for both histamine and IL-6 in this process.

Mesenchymal stem cell therapy: A review of clinical trials for multiple sclerosis.

Multiple sclerosis (MS) is a disease of the central nervous system (CNS) that is the result of the body's own immune cells being auto-reactive to the myelin regions of the body as if these regions were foreign antigens. This demyelination process is damaging to the electrical conductivity of neurons. The current medicines are only capable of fighting off the symptoms of the disease, but not the disease itself. Specialized stem cells, known as mesenchymal stem cells (MSCs), seem to be the candidate therapy to get rid of MS. MSCs can be isolated from multiple sources of the person's body, and even from the umbilical cord (UC) and placenta of a donor. These cells have anti-inflammatory effects so they can target the overactivity and self-antigen attacks by T cells and macrophages; this immune system overactivity is characteristic of MS. MSCs show the ability to locate into brain lesions when injected and thus can compensate for the loss of the brain function by differentiating into neuronal precursor cells and glial cells. The author has listed tables of clinical trials that have utilized MSCs from different sources, along with the years and the phase of study completed for each trial. The consensus is that these cells work on inhibiting CD4+ and CD8+ T cell activation, T regulatory cells (Tregs), and macrophage switch into the auto-immune phenotype. The best source of MSCs seems to be the UC due to the easiness of extraction, the noninvasive method of collection, their higher expansion ability and more powerful immune-modulating properties compared to other locations in the body. Studies showed there was a significant decline of mRNA expression of several cytokines after the administration of MSCs derived from the UC (UCMSCs). Other researchers were able to repair the defects of Tregs in MS patients by co-culturing Tregs from these patients with UCMSCs, which decreased the production of the pro-inflammatory cytokine IFN γ , and also suggested a strong link between Tregs lack of functionality in MS patients with the pathogenesis of the disease.

Correlation between ABO Blood Group Phenotype and the Risk of COVID-19 Infection and Severity of Disease in a Saudi Arabian Cohort.

BACKGROUND: Disease severity among patients infected with SARS-CoV-2 varies remarkably. Preliminary studies reported that the ABO blood group system confers differential viral susceptibility and disease severity caused by SARS-CoV-2. Thus, differences in ABO blood group phenotypes may partly explain the observed heterogeneity in COVID-19 severity patterns, and could help identify individuals at increased risk. Herein, we explored the association between ABO blood group phenotypes and COVID-19 susceptibility and severity in a Saudi Arabian cohort. METHODS: In this retrospective cohort study, we performed ABO typing on a total of 373 Saudi patients infected with SARS-CoV-2 and conducted association analysis between ABO blood group phenotype and COVID-19 infection severity. We then performed gender-stratified analysis by dividing the participating patients into two groups by gender, and classified them according to age. RESULTS: The frequencies of blood group phenotypes A, B, AB and O were 27.3, 23.6, 5.4 and 43.7%, respectively. We found that blood group phenotype O was associated with a lower risk of testing positive for COVID-19 infection (OR 0.76 95% CI 0.62-0.95, p = 0.0113), while blood group phenotype B was associated with higher odds of testing positive (OR 1.51 95% CI 1.17-1.93, p = 0.0009). However, blood group phenotype B was associated with increased risk in the mild and moderate group but not the severe COVID-19 infection group. Blood group phenotype O was protective in all severity groups. CONCLUSION: Our findings provide evidence that blood group phenotype B is a risk for COVID-19 disease while blood group phenotype O is protective from COVID-19 infection. However, further studies are necessary to validate these associations in a larger sample size and among individuals of different ethnic groups.

Impacts of Changing the Curriculum Design on the Examination Results of Anatomy and Physiology Course.

Introduction Innovating strategies have become a compulsion in all fields associated with improved outcomes. Similarly, an innovation was introduced in the curriculum design and content to be tested for the Anatomy and Physiology course at the College of Science and Health Professions (COSHP), King Saud Bin Abdulaziz University for Health Sciences (KSAU-HS), in the spring semester of 2020. Before the COVID-19 pandemic, until the spring semester of 2019, two examinations were conducted as continuous assessments (Midterm I and II), followed by a comprehensive Final examination. In the spring semester of 2020, these examinations were replaced with Block I, II, and III examinations, respectively, with modified content and weightage. The Final examination was comprehensive and included 24 Anatomy, 21 Physiology lectures, and three case-based learning (CBL) sessions, whereas Block III included only eight Anatomy, seven Physiology lectures, and 1 CBL session. Midterm I and II weighed 20% each with a comprehensive examination of 35%, while Block I, II, and III were all 25% each. This study focuses on the impact of the curriculum modifications on the results of written examinations for preprofessional students enrolled at Riyadh, Jeddah, and Al-Ahsa campuses. Methods This retrospective study included data from 2356 male and female students from Riyadh, Jeddah, and Al-Ahsa. Data included Midterm I and II grades and Final examination grades for spring semester 2019 and Block I, II, and III examination grades for spring semester 2021. The results of the spring semester 2021 examinations were compared with the spring semester 2019 examination. The spring semester of 2020 was skipped to avoid the effect of online examinations during the COVID-19 restriction period. Data were analyzed using the statistical software SPSS version 23.0 (IBM Corporation, Armonk, NY, USA). Coefficient of variation (CV) compared spring semester 2019 and spring semester 2021 examination outcomes. The findings were analyzed concerning data related to gender, student groups, and campuses. An independent t-test of proportion was used to compare the CVs for spring 2019 and 2021. Results The overall comparison showed better results in the spring semester of 2021 (p-value < 0.01). Campus-wise, the results were significantly better for Riyadh (p-value < 0.01). The gender-wise study showed better performance from male students (p-value < 0.01). Concerning campus and gender, the results of male and female students of the Riyadh campus came out to be highly significant (p-value < 0.01). Conclusions Changing from Midterms to the Block system significantly improved the Block III examination results in spring semester 2021, particularly at the Riyadh campus. Overall, the changes remained helpful to all students. Further studies are needed to investigate the long-term effect of the curriculum changes.