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Background Inherited blood disorders (IBDs) are a major health concern in the Kingdom of Saudi Arabia (KSA), largely due to the high prevalence of consanguineous marriages. Objectives This review is aimed at summarizing gene mutations and variants associated with IBDs in the Saudi population to enhance diagnosis and personalized care. Methods Published studies on IBD‐related genetic mutations in Saudis were systematically retrieved from PubMed, Web of Science, Google Scholar, and EGEMS database using keywords “gene,” “Saudi,” “polymorphism,” and “the different inherited blood disorders.” A total of 118 studies published between 2015 and 2024 met the inclusion criteria. Results The β‐globin (HBB) gene showed the greatest mutational diversity, with over 60 β‐thalassemia variants identified. The α‐globin genes (HBA1, HBA2, and the unique HBA12) were frequently involved in α‐thalassemia, with the –α3.7 deletion predominating. In sickle cell disease, the HbS mutation (c.20A>T) is the most common, primarily linked to the Arab–Indian haplotype, whereas polymorphisms in BCL11A, HBS1L-MYB, and ANTXR1 influenced fetal hemoglobin levels. Frequent thrombophilia‐related variants occurred in F5, SERPINC1, MTHFR, and FII, and inherited thrombocytopenias were linked to MPL, ANKRD26, THPO, DIAPH1, and ADAMTS13. Rare disorders such as Wiskott–Aldrich syndrome (WAS) and coagulation factor deficiencies (e.g., FX, F7, and F8) were also reported. Conclusion The Saudi population exhibits a distinct and diverse spectrum of IBD‐related mutations. Understanding these genetic patterns can enhance diagnostic precision, guide genetic counseling, and advance personalized medicine initiatives across the Kingdom.

Two-component systems (TCSs) are an essential way that bacteria sense and respond to their environment. These systems are usually composed of a membrane-bound histidine kinase that phosphorylates a cytoplasmic response regulator. Staphylococcus aureus is a ubiquitous Gram-positive bacterium and an opportunistic human pathogen. S. aureus pathogenesis relies on a complex network of regulatory factors that adjust gene expression. Two important factors in this network are CodY, a repressor protein responsive to nutrient availability, and the SaeRS two-component system (TCS), which responds to neutrophil-produced factors. Our previous work revealed that CodY regulates the secretion of many toxins indirectly via Sae through an unknown mechanism. We report that disruption of codY results in increased levels of phosphorylated SaeR (SaeR~P) and that codY mutant cell membranes contain a higher percentage of branched-chain fatty acids (BCFAs) than do wild-type membranes, prompting us to hypothesize that changes to membrane composition modulate the activity of the SaeS sensor kinase. Disrupting the lpdA gene encoding dihydrolipoyl dehydrogenase, which is critical for BCFA synthesis, significantly reduced the abundance of SaeR, phosphorylated SaeR, and BCFAs in the membrane, resulting in reduced toxin production and attenuated virulence. Lower SaeR levels could be explained in part by reduced stability. Sae activity in the lpdA mutant could be complemented genetically and chemically with exogenous short- or full-length BCFAs. Intriguingly, lack of lpdA also alters the activity of other TCSs, suggesting a specific BCFA requirement managing the basal activity of multiple TCSs. These results reveal a novel method of posttranscriptional virulence regulation via BCFA synthesis, potentially linking CodY activity to multiple virulence regulators in S. aureus . IMPORTANCE Two-component systems (TCSs) are an essential way that bacteria sense and respond to their environment. These systems are usually composed of a membrane-bound histidine kinase that phosphorylates a cytoplasmic response regulator. Because most of the histidine kinases are embedded in the membrane, lipids can allosterically regulate the activity of these sensors. In this study, we reveal that branched-chain fatty acids (BCFAs) are required for the activation of multiple TCSs in Staphylococcus aureus . Using both genetic and biochemical data, we show that the activity of the virulence activator SaeS and the phosphorylation of its response regulator SaeR are reduced in a branched-chain keto-acid dehydrogenase complex mutant and that defects in BCFA synthesis have far-reaching consequences for exotoxin secretion and virulence. Finally, we show that mutation of the global nutritional regulator CodY alters BCFA content in the membrane, revealing a potential mechanism of posttranscriptional regulation of the Sae system by CodY.

Objectives: To examine the colonoscopy referrals in an open-access system and determine the outcome and factors associated with appropriate referral. Methods: A retrospective study of colonoscopy referrals used patients' medical records at King Khalid University Hospital, Riyadh, Saudi Arabia, during 2020-2022. Fisher's exact or Pearson's Chi-squared test were used for data analysis. Results: Out of 365 patients, 95.1% were referred from family medicine clinics with a mean age of 56.2[+ or -]15.7 years. Men account for 53.2% of patients. The most common symptoms were change in bowel habits (35.6%), abdominal pain (30.4%), and anemia (20.1%). A family history of colorectal cancer was positive in 12.1%, while a personal history was positive in 4.4%. Most referrals (86.0%) were appropriate based on the American Society for Gastrointestinal Endoscopy (ASGE) guidelines. However, approximately 89.1% of patients aged [greater than or equal to]45 years had neoplasia and 40.0% had inflammatory bowel disease (p=0.019). The rank of the physicians (p=0.558) or the gender of the patients (p=0.665) did not influence the appropriateness. The inappropriate referrals were lower in patients with neoplasia (1.6%) than in patients with other lesions (p=0.002). Conclusion: The colonoscopy referrals were appropriate. The incidence of neoplasia was higher among those aged [greater than or equal to]45. Low inappropriate referrals and a high neoplasia detection were found based on ASGE guidelines. Future research should involve prospective multicenter referrals from family physicians outside hospitals and investigate patients' hesitancy to proceed with colonoscopy and cost-effectiveness. Keywords: colonoscopy, referrals, outcomes, colorectal cancer [phrase omitted]

This narrative review compares the peri-implant soft tissue responses around zirconia and titanium abutments in the aesthetic zone, emphasizing their mechanical, biological, and aesthetic properties. Titanium abutments, known for their excellent mechanical strength and fatigue resistance, have traditionally been the standard in dental restorations but face challenges in aesthetic integration due to their metallic appearance and potential for higher inflammatory responses. Zirconia abutments, emerging as a promising alternative, offer superior aesthetic outcomes, reduced plaque accumulation, and lower inflammatory responses, making them ideal for use in visible areas with thin soft tissue biotypes. However, zirconia's mechanical properties, such as lower fracture resistance, necessitate careful clinical application. The review also highlights rare instances of titanium allergies, underscoring the importance of individualized treatment planning and regular monitoring to ensure the longevity and success of implant restorations.

Staphylococcus aureus is a ubiquitous Gram-positive bacterium that colonizes up to 30% of the human population. As an opportunistic human pathogen, the bacterium is a leading cause of skin and soft tissue infections, endocarditis, and bacteremia. Drug resistance compounds the problem, and the lack of an efficacious vaccine emphasizes the need for new therapies to combat staphylococcal infections. One exciting approach is to target the regulation of virulence genes. Virulence genes are often regulated by multiple factors that respond to different environmental cues. Some of the factors act directly on virulence genes; others control virulence indirectly by controlling the expression or activity of other regulators. My dissertation research focuses on CodY, an amino acid- and GTP-responsive global transcriptional regulator of many metabolic pathways, and the mechanism by which it funnels nutrient depletion signals through a major regulator of virulence-the SaeR/S two-component system. Previous work by others and I in the Brinsmade lab and elsewhere showed that overexpressing the sensor kinase gene saeS and the response regulator gene saeR does not increase the expression of the Sae regulon genes. To explain this surprising result, my thesis provides experimental support for the hypothesis that CodY controls the cellular fraction of activated SaeR (SaeR~P) to adjust the expression of virulence factor genes. In Chapter II, I show that transcriptional regulation of the sae locus is dispensable for CodY-dependent upregulation of the Sae regulon. Moreover, CodY-deficient S. aureus strains have higher SaeS kinase activity, correlating with increased membrane branch-chain fatty acids derived from isoleucine. In chapter III, I show that CodY regulates SaeS kinase activity during periods of nutrient sufficiency by repressing the genes that code for enzymes and proteins that catalyze branched-chain fatty acid synthesis. Additional work herein focuses on the molecular mechanism by which the branched-chain fatty acids alter the SaeS signaling complex. My work contributes to the elucidation of a novel method of post-transcriptional virulence regulation by branched-chain fatty acids. Understanding the molecular basis of this regulation is an important first step in characterizing potentially new anti-virulence targets with therapeutic potential.

Globally, breast cancer management is associated with a heavy economic burden, but its impact in Saudi Arabia has not been fully quantified. The aim of this study was to estimate the economic burden of breast cancer management at various disease stages, in Saudi Arabia, from a payer perspective. We conducted a retrospective, multicenter cost of illness study in two governmental healthcare centers from January to December 2018, using the data of 300 patients at different breast cancer stages. A micro-costing, bottom-up method was used, and descriptive and inferential statistics were analyzed. The total estimated cost for treating breast cancer during the study period was$13.345 million USD, with the average cost per patient ranging from $ 14,249 USD in stage I to $81,489 USD in stage IV (p < 0.001). Medication cost was the main driver of total healthcare spending, followed by hospitalization and diagnostic tests. The cost of targeted therapy drugs represented 67% of the total medication costs, mostly driven by trastuzumab-based regimens. The economic burden of breast cancer management in Saudi Arabia is substantial and increases significantly with disease advancement. Early detection screening programs, evaluating the value of highly expensive interventions, and considering biosimilars, may contribute toward cost savings.

Objectives: To determine the influence of metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) and hepatic fibrosis on the pattern and management of patients who had acute coronary syndrome (ACS). Methods: Retrospective records of patients with ACS included demographic, electrocardiographic, and laboratory data of platelets count, glycated hemoglobin, lipogram, liver and cardiac enzymes. Ultrasound was used to evaluate fatty liver. Coronary angiography data included the number, site and percentage of the coronary arteries occluded. The type and outcome of treatment of ACS were recorded. Laboratory markers were measured to evaluate fibrosis. Results: The study recruited 259 patients, and the majority were males. MASLD was detected in 123 (47.5%). The ST segment-elevation myocardial infarction (STEMI) was reported in 42.9% and non-STEMI (NSTEMI) in 30.1%. MASLD patients had frequent STEMI (38.2%) and NSTEMI (31.7%) with more involvement of left main coronary artery (10.6%). Patients with MASLD and higher fibrosis showed involvement of multiple coronary arteries and needed revascularization but without significant difference from non-MASLD. Left anterior descending and right coronary arteries were significantly involved in higher fibrosis. Conclusion: STEMI and NSTEMI were frequent in MASLD. People with MASLD and hepatic fibrosis had more incidence of occlusion of multiple coronary arteries and needed cardiac intervention. Keywords: MASLD, Steatosis, Coronary artery, Myocardial infarction, Acute coronary syndrome, Angiography, Fatty liver, Hepatic fibrosis