Derivation of two iPSC lines (KAIMRCi004-A, KAIMRCi004-B) from a Saudi patient with Biotin-Thiamine-responsive Basal Ganglia Disease (BTBGD) carrying homozygous pathogenic missense variant in the SCL19A3 gene.

The neurometabolic disorder known as biotin-thiamine-responsive basal ganglia disease (BTBGD) is a rare autosomal recessive condition linked to bi-allelic pathogenic mutations in the SLC19A3 gene. BTBGD is characterized by progressive encephalopathy, confusion, seizures, dysarthria, dystonia, and severe disabilities. Diagnosis is difficult due to the disease's rare nature and diverse clinical characteristics. The primary treatment for BTBGD at this time is thiamine and biotin supplementation, while its long-term effectiveness is still being investigated. In this study, we have generated two clones of induced pluripotent stem cells (iPSCs) from a 10-year-old female BTBGD patient carrying a homozygous mutation for the pathogenic variant in exon 5 of the SLC19A3 gene, c.1264A > G (p.Thr422Ala). We have confirmed the pluripotency of the generated iPS lines and successfully differentiated them to neural progenitors. Because our understanding of genotype-phenotype correlations in BTBGD is limited, the establishment of BTBGD-iPSC lines with a homozygous SLC19A3 mutation provides a valuable cellular model to explore the molecular mechanisms underlying SLC19A3-associated cellular dysfunction. This model holds potential for advancing the development of novel therapeutic strategies.

Generation of iPSC lines (KAIMRCi003A, KAIMRCi003B) from a Saudi patient with Dravet syndrome carrying homozygous mutation in the CPLX1 gene and heterozygous mutation in SCN9A.

The most prevalent form of epileptic encephalopathy is Dravet syndrome (DRVT), which is triggered by the pathogenic variant SCN1A in 80% of cases. iPSCs with different SCN1A mutations have been constructed by several groups to model DRVT syndrome. However, no studies involving DRVT-iPSCs with rare genetic variants have been conducted. Here, we established two DRVT-iPSC lines harboring a homozygous mutation in the CPLX1 gene and heterozygous mutation in SCN9A gene. Therefore, the derivation of these iPSC lines provides a unique cellular platform to dissect the molecular mechanisms underlying the cellular dysfunctions consequent to CPLX1 and SCN9A mutations.

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.

The Gulf Achievement of Cholesterol Targets in Out-Patients Study (GULF ACTION): Design, Rationale, and Preliminary Results.

AIM: To assess the current dyslipidemia management in the Arabian Gulf region by describing the demographics, study design, and preliminary results of out-patients who achieved low-density lipoprotein cholesterol (LDL-C) goals at the time of the survey. BACKGROUND: The Arabian Gulf population is at high risk for atherosclerotic cardiovascular disease at younger ages. There is no up-to-date study regarding dyslipidemia management in this region, especially given the recent guideline-recommended LDL-C targets. OBJECTIVE: Up-to-date comprehensive assessment of the current dyslipidemia management in the Arabian Gulf region, particularly in view of the recent evidence of the additive beneficial effects of ezetimibe and proprotein convertase subtilisin/kexin-9 (PCSK-9) inhibitors on LDL-C levels and cardiovascular outcomes. METHODS: The Gulf Achievement of Cholesterol Targets in Out-Patients (GULF ACTION) is an ongoing national observational longitudinal registry of 3000 patients. In this study, adults ≥18 years on lipidlowering drugs for over three months from out-patients of five Gulf countries were enrolled between January 2020 and May 2022 with planned six-month and one-year follow-ups. RESULTS: Of the 1015 patients enrolled, 71% were male, aged 57.9±12 years. In addition, 68% had atherosclerotic cardiovascular disease (ASCVD), 25% of these patients achieved the LDL-C target, and 26% of the cohort were treated using combined lipid-lowering drugs, including statins. CONCLUSION: The preliminary results of this cohort revealed that only one-fourth of ASCVD patients achieved LDL-C targets. Therefore, GULF ACTION shall improve our understanding of current dyslipidemia management and "guideline gaps" in the Arabian Gulf region.

Generation of myoglobin (MB)-knockout human embryonic stem cell (hESC) line (KAIMRCe002-A-1S) using CRISPR/Cas9 technology.

Myoglobin (MB) is a cytoplasmic hemoprotein that is predominantly expressed in the heart and oxidative myofibers of skeletal muscle. It has been demonstrated that MB binds to oxygen and promotes its diffusion for energy production in the mitochondria. Recently, MB was found to be expressed in different forms of malignant tumors and cancer cell lines. Further studies using gene disruption technology will enhance the understanding of MB's role in human cardiovascular biology and cancers. Here, we describe the generation of a homozygous MB knockout in human embryonic stem cells (hESC-MB-/-) via CRISPR/Cas9 to study MB function in human biology and diseases.

Bacillus thuringiensis CHGP12 uses a multifaceted approach for the suppression of Fusarium oxysporum f. sp. ciceris and to enhance the biomass of chickpea plants.

BACKGROUND: Bacillus species synthesize antifungal lipopeptides (LPs) making them a sustainable and eco-friendly management option to combat Fusarium wilt of chickpea. RESULTS: In this study, 18 endophytic Bacillus strains were assessed for their antifungal activity against Fusarium oxysporum f. sp. ciceris (FOC) associated with Fusarium wilt of chickpea. Among them, 13 strains produced significant inhibition zones in a direct antifungal assay while five strains failed to produce the inhibition of FOC. Bacillus thuringiensis CHGP12 exhibited the highest inhibition 3.45 cm of FOC. The LPs extracted from CHGP12 showed significant inhibition of the pathogen. Liquid chromatography-mass spectrometry (LC-MS) analysis confirmed that CHGP12 possessed the ability to produce fengycin, surfactin, iturin, bacillaene, bacillibactin, plantazolicin, and bacilysin. In an in vitro qualitative assay CHGP12 exhibited the ability to produce lipase, amylase, cellulase, protease, siderophores, and indole 3-acetic acid (IAA). IAA and gibberellic acid (GA) were quantified using ultra-performance liquid chromatography (UPLC) with 370 and 770 ng mL-1 concentrations of IAA and GA respectively. Furthermore, the disease severity showed a 40% decrease over control in CHGP12 treated plants compared to the control in a glasshouse experiment. Moreover, CHGP12 also exhibited a significant increase in total biomass of the plants namely, root and shoot growth parameters, stomatal conductance, and photosynthesis rate. CONCLUSION: In conclusion, our findings suggest that B. thuringiensis CHGP12 is a promising strain with high antagonistic and growth-promoting potential against Fusarium wilt of chickpea. © 2022 Society of Chemical Industry.

Saudi Heart Association Guidelines on Best Practices in the Management of Chronic Coronary Syndromes.

Background: The prevalence of both chronic coronary syndrome (CCS) and its risk factors is alarming in Saudi Arabia and only a minority of patients achieve optimal medical management. Context-specific CCS guidelines outlining best clinical practices are therefore needed to address local gaps and challenges. Consensus panel: A panel of experts representing the Saudi Heart Association (SHA) reviewed existing evidence and formulated guidance relevant to local clinical practice considering the characteristics of the Saudi population, the Saudi healthcare system, its resources and medical expertise. They were reviewed by external experts to ensure scientific and medical accuracy. Consensus findings: Recommendations are provided on the clinical assessment and management of CCS, along with supporting evidence. Risk reduction through non-pharmacological therapy (lifestyle modifications) remains at the core of CCS management. Great emphasis should be placed on the use of available pharmacological options (anti-anginal therapy and event prevention) only as appropriate and necessary. Lifestyle counseling and pharmacological strategy must be optimized before considering revascularization, unless otherwise indicated. Revascularization strategies should be carefully considered by the Heart Team to ensure the appropriate choice is made in accordance to current guidelines and patient preference. Conclusion: Conscientious, multidisciplinary, and personalized clinical management is necessary to navigate the complex landscape of CCS in Saudi Arabia considering its population and resource differences. The reconciliation of international evidence and local characteristics is critical for the improvement of healthcare outcomes among CCS patients in Saudi Arabia.

Acute Inferior ST-Elevation Myocardial Infarction Due to Wraparound Left Anterior Descending Artery.

Most of the inferior ST-elevation myocardial infarctions (STEMIs) are due to the occlusion of the dominant right coronary artery, but there are few exceptions. In order to diagnose the actual life-threatening STEMI, we should be aware of the exceptional causes. Here, we present a case of a 69-year-old female with the first diagnostic electrocardiogram report interpreted as inferior STEMI, but the culprit occlusion was later found to be by left anterior descending artery in coronary angiography. All these observed circumstances are reported accordingly.

Generation of induced pluripotent stem cell Line KAIMRCi001-A by reprogramming erythroid progenitors from peripheral blood of a healthy Saudi donor.

In this study we isolated and enriched erythroid progenitor cells (EPCs) from a 10 ml peripheral blood sample from a 37-year old healthy Saudi donor. After expansion, these EPCs were reprogrammed using episomal plasmids to generate an induced pluripotent stem (iPS) cell line, KAIMRCi001-A. The pluripotency of this line was confirmed by measuring the expression of typical pluripotency markers and assessing differentiation potential in vitro.

Repatriation to referral hospital after reperfusion of STEMI patients transferred for primary percutaneous coronary intervention: Insights of a Canadian regional STEMI care system.

BACKGROUND: In regional systems of ST-segment elevation myocardial infarction (STEMI) care, patients presenting to hospitals without percutaneous coronary intervention (PCI) are transferred to PCI-capable hospitals for primary PCI. Repatriation, a practice whereby such patients are transferred back to non-PCI referral hospitals after reperfusion is prevalent in many jurisdictions, yet little is known of this practice and its safety. METHODS: We studied 979 consecutive STEMI patients transported from the emergency department and catchment area of two non-PCI hospitals in Ontario, Canada to a regional PCI-hospital for primary PCI between January 2008 and June 2014. Logistic regression modeling was performed to determine factors associated with delayed repatriation beyond 24 hours and to evaluate the association between repatriation and index-admission mortality. RESULTS: Eight hundred and fifteen (83.2%) patients were repatriated with 524 (65.2%) patients repatriated within 24 hours. Factors independently associated with delayed repatriation included systolic blood pressure (OR 1.03 per 5 mmHg decrease, 95% CI 1.01-1.06, P= .04), requirement for mechanical ventilation (OR 24.9, 95% CI 5.4-115.3, P< .0001), ventricular arrhythmia (OR 3.0, 95% CI 1.3-6.6, P= .01), infarct-related artery (P= .03), final TIMI flow grade (P= .01) and access-site complications (OR 2.36, 95% CI 1.04-5.4, P= .04). After repatriation, 9 (1.3%) patients returned to the PCI-hospital for urgent care, and 16 (2.0%) died during index-admission. After adjustment, repatriation was not associated with increase in index-admission mortality (adjusted OR 0.46, 95% CI 0.16-1.32, P= .15). CONCLUSIONS: In a regional STEMI care system in Ontario, Canada, patients are routinely repatriated to non-PCI hospitals after primary PCI. This practice was associated with very low and acceptable rate of return to the PCI-hospital during index-admission without an adverse impact on short-term outcomes.

A matter of degrees: the introduction of clinical doctorates to the Saudi higher education system and a comparative prospective from the American model.

Recent unprecedented growth in Saudi population challenged its infrastructure and intensified demand for higher education and healthcare. In response, both the government and the private sector founded numerous colleges and universities, increasing the overall number from 8 to 49 institutions of higher education. A significant portion of the expansion has been in the health professions higher education, which also included the establishment of new teaching hospitals and other medical training facilities. As part of this growth, practice (clinical) doctorates have conspicuously made their presence felt in Saudi Arabia. The doctor of pharmacy is the first clinical doctorate that has been formally adopted as the terminal professional degree in the field. Others are in the works. Results are presented using descriptive methods. Data were collected from reviews of the literature and individual institutional websites of Saudi colleges, universities and salient governmental regulatory and national accrediting agencies. This article will introduce clinical doctorates, their status and state of implementation in the American health professions higher education system as a possible model. The article will review the current status of clinical doctorates' implementation in Saudi Arabia. It will conclude with a recommendation for concerned stake holders, including policy makers, educators, and practitioners.

The need for national medical licensing examination in Saudi Arabia.

BACKGROUND: Medical education in Saudi Arabia is facing multiple challenges, including the rapid increase in the number of medical schools over a short period of time, the influx of foreign medical graduates to work in Saudi Arabia, the award of scholarships to hundreds of students to study medicine in various countries, and the absence of published national guidelines for minimal acceptable competencies of a medical graduate. DISCUSSION: We are arguing for the need for a Saudi national medical licensing examination that consists of two parts: Part I (Written) which tests the basic science and clinical knowledge and Part II (Objective Structured Clinical Examination) which tests the clinical skills and attitudes. We propose this examination to be mandated as a licensure requirement for practicing medicine in Saudi Arabia. CONCLUSION: The driving and hindering forces as well as the strengths and weaknesses of implementing the licensing examination are discussed in details in this debate.

Drainage of pancreatic pseudocysts. The importance of cyst wall biopsy in the recent era.

OBJECTIVE: While open internal drainage has been the standard treatment for pancreatic pseudocysts, less invasive techniques which pay little attention to cyst wall biopsy, are becoming popular. The aim of this study is to report on our experience in draining pancreatic pseudocysts and probe the necessity or otherwise of obtaining a wall biopsy at drainage. METHODS: Operation theatre registry, operation log books and medical records at Aseer Central Hospital, Abha, Kingdom of Saudi Arabia, were reviewed to retrieve the clinical details of patients with pancreatic pseudocyst who required a drainage procedure in a 13 years period from August 1989 to November 2002. RESULTS: Sixteen patients were identified. Cyst wall biopsy was obtained in 10 cases, in 8 of them the diagnosis was confirmed, while a true cyst was found in the remaining 2 excluding them from further analysis. In the remaining 14 cases (8 males, 6 females, mean age 38 years, range 4-60), pain was the main presenting feature. Open internal drainage was offered to 12 cases while one patient received external drainage under ultrasound guidance and the other received open external drainage. The type of operation was cystogastrostomy in 9 patients and cystojejunostomy in 3 patients. The recurrence rate after internal drainage was 16.7%, while after external drainage was 100%. There was no mortality in this series. A procedure-related complication occurred in 3 (21.4%) patients. CONCLUSION: The mortality, morbidity and recurrence rates in this series are compared favorably with other reports. The final diagnosis of a presumed pancreatic pseudocyst should rest on the histopathologic examination of the cyst wall.

Current issues in medical education.

Medical education has witnessed recently an accelerated and worldwide trend of change. The race is on for curricula that are relevant, appropriate and accountable. One of the consequences of this is the need for a drastic reassessment of how we devise curricula, and of what models, approaches, and strategies to adopt. Outcomes-based education is currently offered as an alternative to the content-based approach, which has been criticized by many educational experts in the past. Although this new approach has its detractors, it holds some promise of being able to improve on a current situation that is in deadlock with itself. There has been a great deal of interest in educational strategies in the last decade. This has been associated with the development of new concepts such as "problem-based learning", "student-centered learning", and "integrated teaching". Each school has to assess each of these strategies and adopt what ever will serve the aims of the curriculum. Similarly, the considerable progress that has taken place in the design and development of instructional materials and instructional technology should be appreciated. This includes, development in computer assisted learning, virtual reality, the use of simulated subjects, e learning, and the new concept of Reusable Learning Objects (RLO's). Finally, it was realized, with the rapid development in medical education that medical education requires professional training. The assumption that any good medical practitioner has the ability to teach no longer holds and professional training is required.

Prevention of herniation at the site of cannula insertion after laparoscopic cholecystectomy.

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