Knowledge and Awareness About Risk Factors, Clinical Manifestations, and Prevention of Thyroid Disorders in the Era of COVID-19 and Their Association With Socioeconomic Status Among the General Population in Riyadh, Saudi Arabia.

Background Thyroid dysfunction represents the most commonly observed endocrine illness within the population of Saudi Arabia. Thyroid cancer has been recognized as the second most commonly occurring malignant neoplasm among women in Saudi Arabia. Furthermore, there is evidence suggesting that COVID-19 and, to a certain degree, immunization may have an impact on thyroid function. The aim of this study was to evaluate the level of public knowledge, awareness, and attitudes pertaining to the manifestations and risk factors of thyroid disease. Additionally, the study sought to examine the potential role of COVID-19 as a risk factor and explore preventive measures in the context of Riyadh, Saudi Arabia. Methods A cross-sectional online survey was conducted targeting the Saudi population living in Riyadh aged 18 years and older. A self-administered questionnaire constructed on Google Forms was distributed to the general population using an online platform. The questionnaire consisted of five sections: demographic data, risk factors for thyroid disorders, clinical manifestations, prevention, and history of thyroid disease. Binary logistic regression analysis was used to identify predictors of better knowledge of thyroid diseases.  Results Among the 693 participants enrolled, 57.7% were female, and 31.7% were aged between 18 and 25 years. The overall mean knowledge score was 12.2 (SD = 6.57) out of 23 points. Poor knowledge of the risk factors, clinical manifestations, and prevention was observed in 50.4% of the participants. A total of 27.6% had moderate knowledge, and 22.1% had good knowledge levels. Furthermore, only 33.9% of the participants believed that COVID-19 infection was a risk factor. The results of the binary logistic regression analysis revealed that individuals within the age range of 36-45 years, females, and students had a significantly higher level of knowledge compared to other participants (p<0.05). Conclusion This study revealed that the general population of Riyadh, Saudi Arabia, lacked adequate knowledge, awareness, and attitudes regarding the risk factors, clinical symptoms, and prevention of thyroid problems. However, middle-aged individuals, females, and those who were enrolled as students showed a higher level of knowledge. Regarding the pathogenesis of COVID-19, it was observed that all participants had a limited understanding and a lack of awareness. Insufficient public awareness may result in misunderstandings, insufficient identification, and potential oversight of COVID-19-infected patients with thyroid dysfunction. Therefore, it is imperative that healthcare authorities intensify their efforts to broaden the dissemination of information throughout the population.

The Immunomodulatory Role of Microbiota in Rheumatic Heart Disease: What Do We Know and What Can We Learn from Other Rheumatic Diseases?

Rheumatic heart disease (RHD) represents a serious cardiac sequela of acute rheumatic fever, occurring in 30-45% of patients. RHD is multifactorial, with a strong familial predisposition and known environmental risk factors that drive loss of immunological tolerance. The gut and oral microbiome have recently been implicated in the pathogenesis of RHD. Disruption of the delicate balance of the microbiome, or dysbiosis, is thought to lead to autoimmune responses through several different mechanisms including molecular mimicry, epitope spreading, and bystander activation. However, data on the microbiomes of RHD patients are scarce. Therefore, in this comprehensive review, we explore the various dimensions of the intricate relationship between the microbiome and the immune system in RHD and other rheumatic diseases to explore the potential effect of microbiota on RHD and opportunities for diagnosis and treatment.

Knowledge, Attitude, and Practice Toward Diabetes Mellitus and Their Association With Socioeconomic Status Among Patients With Type 2 Diabetes Mellitus in Saudi Arabia.

OBJECTIVES:  The objective is to assess knowledge, attitude, and practice toward diabetes mellitus (T2DM) and its association with socioeconomic status among adult patients with T2DM. METHODS:  This cross-sectional study used the validated "Diabetes Knowledge Test (DKT)" questionnaire obtained from the Michigan Diabetes Research Center. A translated copy into Arabic has been validated and used in another study. The questionnaire was created on Google Forms and distributed through digital platforms to collect data from patients with T2DM in Saudi Arabia. RESULTS:  In this study, the majority were female (63.4%), and Saudi Arabians (96.5%), among them 23.7% lived in Riyadh, and 42.8% were from the central region. As for marital status, 60.5% were married, 28.4% were single, and 11.1% were divorced or widowed. 58.9% had college/higher degrees, and 45.8% were unemployed. Furthermore, the majority (47.1%) reported having a salary of less than 5,000 Saudi Riyals per month. 55.1% of participants lived in villas, while 46.6% had 6-10 people living in their household. Generalized linear model (GLM) findings showed that age, marital status, level of education, monthly income, and accommodation are significantly correlated with the level of knowledge. CONCLUSION:  Findings indicated a high level of knowledge, positive behavior, and good adherence to practice among patients with T2DM. GLM findings showed that age, marital status, level of education, monthly income, and accommodation are significantly correlated with the level of knowledge. Researchers suggest that effective health education interventions are needed to improve diabetes knowledge, behavior, and practices, particularly regarding lifestyle modifications and dietary management.

Quality of Sleep in the Saudi Population During the Holy Month of Ramadan.

Background The holy month of Ramadan carries a massive change in a Muslim's lifestyle. During these 30 days of all-day fasting, people in Saudi Arabia prefer staying up all night and sleeping in the daytime, thus highly impacting their regular sleeping schedule, with a sizable effect on the quality of sleep. This study aimed to measure the quality of sleep and sleep hygiene practices in the Saudi population. Methodology This cross-sectional study was conducted among the Saudi population during the holy month of Ramadan. A self-administered questionnaire was sent to the targeted population using social media platforms. Our questionnaire included demographic data, the Sleep Quality Scale (SQS) to measure sleep quality, and the Sleep Hygiene Index (SHI) to measure sleep hygiene practices. Results Of the 386 participants, 71.2% were females, and 64.5% were single. The total mean SQS score was 35.8 (SD = 10.9) out of 84 points, while the total mean SHI score was 19.8 (SD = 8.61) out of 52 points. Overall, 63.5% of the respondents had poor sleep hygiene practices. Significant factors for increased SHI included being unmarried, a student, not the main provider in the family, not a parent, and earning less than 5,000 SAR per month while having more than six individuals in the family was a significant factor for increased SQS. Conclusions During the month of Ramadan, poor sleep quality and inadequate sleep hygiene practices were common among the Saudi population. A significant risk factor for poor sleep quality was having more than six individuals at home while being unmarried, a student, not being the family's main provider, and earning less than 5,000 SAR per month were the significant risk factors for poor sleep hygiene practices. Further research is needed to establish the effect of poor sleep quality and inadequate sleep hygiene practices during Ramadan fasting in our region.

Knowledge and Attitude of General People Towards Symptoms of Heart Attack and the Impact of Delay Time in Riyadh, Saudi Arabia.

BACKGROUND: Cardiovascular disease is prevalent worldwide. The goal of this research is to evaluate the knowledge of Riyadh, Saudi Arabia, population about heart attack symptoms and risk factors. METHODOLOGY: A one-year cross-sectional study was carried out. The study was conducted on 385 individuals in Riyadh, Saudi Arabia. We used the Acute Coronary Syndrome Response Index, with additional questions added, such as risk factors of heart attack and physical activity time. An anonymous self-administered online questionnaire was used to collect the data. RESULTS: We collected data from 440 participants, but only 385 were included in the analysis. Males represented 41.4% of the participants. In terms of participant knowledge of heart attack symptoms, we found that chest pain or pressure was the most common (80.5%), followed by shortness of breath (77%) and weakness and fatigue (72.0%). In addition, 90.2% and 90.7% of the participants knew that smoking and obesity were risk factors for heart attacks. Furthermore, 46% of participants said they "would not be at all certain" of identifying the symptoms and indicators of a heart attack in another person and 45.7% "in themselves." We found that males were more likely than females to have low knowledge (RR: 1.84, 95% CI: 1.24:2.72, P = 0.002). CONCLUSION: Our findings suggest that there is a lack of awareness of the heart attack warning signs and symptoms. We propose that future local campaigns focus on increasing awareness and recognition of heart attack symptoms.

Cytokine Profiling among Children with Multisystem Inflammatory Syndrome versus Simple COVID-19 Infection: A Study from Northwest Saudi Arabia.

BACKGROUND: Multisystem Inflammatory Syndrome in Children (MIS-C) is a novel syndrome associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection with varying clinical features. This study aimed to analyze the expression profiles of cytokines in blood, report the important clinical characteristics, and correlate these with the short- and mid-term outcomes. METHODS: This cross-sectional study was conducted on hospitalized children with MIS-C from March 2021 to May 2022. Phenotypes were classified into two groups (A,B) according to the severity of the disease and the need for invasive respiratory support. Clinical features, laboratory parameters, and outcomes were reported. RESULTS: We identified 60 children with MIS-C (mean age of 7.4 ± 3.8 years) compared to 30 age- and sex-matched controls with simple COVID-19. The clinical manifestations of MIS-C patients were fever (100%), respiratory (83.3%), GIT (80%), and conjunctivitis (80%). Twenty-seven MIS-C children (45%) required PICU admission due to shock and needed mechanical ventilation. Anemia, lymphopenia, and elevated levels of inflammatory and tissue injury markers were observed in the MIS-C groups (mainly B). High cytokine levels (IL-1ß, IL-6, IFN-α, GM-CSF, and HMGB1) were observed acutely in the MIS-C children, and a persistent elevation of some cytokines were reported at midterm follow-up, especially in Group B. CONCLUSION: Robust inflammatory response to COVID-19 disease with elevated IL-1ß, IL-6, and GM-CSF levels might explain the severity and outcome of the clinical syndrome.

The Polymorphism at the microRNA-155 Binding Site in the AGTR1 Gene is not Significantly Associated with Rheumatic Heart Disease in Saudi Arabia Population.

BACKGROUND: Rheumatic Heart Disease (RHD) remains a major cause of cardiovascular diseases and the most devastating effects are shown on children and young adults. RHD is caused due to the interaction between microbial, environmental, immunologic, and genetic factors. The Renin- Angiotensin Aldosterone System (RAAS) has been strongly implicated as the susceptibility pathway in the pathogenesis of the cardiovascular disease. OBJECTIVE: The present study investigated the modulating effect of Angiotensin II type 1 receptor (AGTR1) 1166A>C polymorphism on the RHD and its clinical features in Saudi Arabia. METHODS: AGTR1 1166A>C polymorphism was genotyped in 96 echocardiographically confirmed RHD patients and 142 ethnically matched controls by the TaqMan allelic discrimination method. RESULTS: Genotype distribution of the AGTR1 1166A>C polymorphism was not significantly different between RHD and control groups. Furthermore, AGTR1 1166A>C genotypes are not associated with the clinical features of RHD. These data support that there was no evidence for an association between AGTR1 1166A>C polymorphism and RHD in Saudi Arabia. CONCLUSION: To the best of our knowledge, this is the first study that has investigated the possible association between AGTR1 1166A>C polymorphism and susceptibility to RHD and its clinical features. Even though the AGTR1 gene, 1166A>C (rs5186), was reported to be associated with hypertension, left ventricular hypertrophy and coronary heart disease. The present study did not find any association between AGTR1 1166A>C polymorphism and RHD in Saudi Arabia. Further studies are needed to confirm our findings.

Digenic Inheritance of LAMA4 and MYH7 Mutations in Patient with Infantile Dilated Cardiomyopathy.

Background and objectives: Dilated cardiomyopathy (DCM) is a rare cardiac disease characterised by left ventricular enlargement, reduced left ventricular contractility, and impaired systolic function. Childhood DCM is clinically and genetically heterogenous and associated with mutations in over 100 genes. The aim of this study was to identify novel variations associated with infantile DCM. Materials and Methods: Targeted next generation sequencing (NGS) of 181 cardiomyopathy-related genes was performed in three unrelated consanguineous families from Saudi Arabia. Variants were confirmed and their frequency established in 50 known DCM cases and 80 clinically annotated healthy controls. Results: The three index cases presented between 7 and 10 months of age with severe DCM. In Family A, there was digenic inheritance of two heterozygous variants: a novel variant in LAMA4 (c.3925G > A, p.Asp1309Asn) and a known DCM mutation in MYH7 (c.2770G > A; p.Glu924Lys). The LAMA4 p.Asp1309Asn variant was predicted to be likely pathogenic according to international guidelines. The other two families had no identifiable potentially deleterious variants. Conclusions: Inheritance of two genetic variants may have a synergistic or dose effect to cause severe DCM. We report of a novel p.Asp1309Asn variation associated with DCM. Targeted NGS is useful in the molecular diagnosis of DCM and to guide whole-family management and counselling.

A novel splice-site mutation in the ASPM gene underlies autosomal recessive primary microcephaly.

BACKGROUND: Autosomal recessive primary microcephaly (MCPH) is a clinically and genetically heterogeneous disorder. Patients with MCPH exhibit reduced occipito-frontal head circumference and non-progressive intellectual disability. To date, 17 genes have been known as an underlying cause of MCPH in humans. ASPM (abnormal spindle-like, microcephaly associated) is the most commonly mutated MCPH gene. OBJECTIVE: Identify the genetic defect underlying MCPH in a Saudi family. DESIGN: A cross-sectional clinical genetic study of a Saudi family. SETTING: Madinah Maternity and Children Hospital and Centre for Genetics and Inherited Diseases, Taibah University. PATIENTS AND METHODS: A molecular analysis was carried out on DNA samples from 10 individuals of a Saudi family segregating MCPH. DNA was isolated from the peripheral blood of 10 individuals, including 2 patients, and whole exome sequencing was performed using the Nextera Rapid Capture kit and NextSeq500 instrument. VariantStudio was used to filter and prioritize variants. MAIN OUTCOME MEASURE(S): Detection of mutation in the ASPM gene in a family segregating autoso- mal recessive primary microcephaly. RESULTS: A novel homozygous splice-site variant (c.3742-1G > C) in the ASPM gene was identified. The variant is predicted to have an effect on splicing. Human Splice Finder, an in silico tool, predicted skipping of exon 16 due to this variant. CONCLUSION: Skipping of exon 16 may change the order and number of IQ motifs in the ASPM protein leading to typical MCPH phenotype. LIMITATIONS: Single family study.

LGMD2D syndrome: the importance of clinical and molecular genetics in patient and family management. Case Report.

We report the case of a seven-year-old female from a consanguineous Saudi family with autosomal recessive limb girdle muscular dystrophy type 2D (LGMD2D) most likely caused by a rare SGCA mutation. Histopathological and molecular investigations resulted in the discovery of a homozygous mutation (c.226 C>T (p.L76 F)) in exon 3 of SGCA in the patient. The parents and one sibling were heterozygous carriers, but the mutation was not otherwise detected in 80 ethnic controls from the same geographic area. In silico analysis revealed that the mutation resulted in a functional leucine to phenylalanine alteration that was deleterious to the protein structure. This is only the second reported case of the p.L76F mutation in LGMD, and highlights that molecular genetics analysis is essential to deliver the most appropriate management to the patient and offer the family genetic counseling.

CIT, a gene involved in neurogenic cytokinesis, is mutated in human primary microcephaly.

Autosomal recessive primary microcephaly (MCPH) is a static neurodevelopmental disorder characterized by congenital small head circumference and non-progressive intellectual disability without additional severe brain malformations. MCPH is a genetically heterogeneous disorder. Sixteen genes (MCPH1-MCPH16) have been discovered so far, mutations thereof lead to autosomal recessive primary microcephaly. In a family, segregating MCPH in an autosomal recessive manner, genome-wide homozygosity mapping mapped a disease locus to 16.9-Mb region on chromosome 12q24.11-q24.32. Following this, exome sequencing in three affected individuals of the family discovered a splice site variant (c.753+3A>T) in citron kinase (CIT) gene, segregating with the disorder in the family. CIT co-localizes to the midbody ring during cytokinesis, and its loss of expression results in defects in neurogenic cytokinesis in both humans and mice. Splice site variant in CIT, identified in this study, is predicted to abolish splice donor site. cDNA sequence of an affected individual showed retention of an intron next to the splice donor site. The study, presented here, revealed the first variant in the CIT causing MCPH in the family.

Impact of MIF Gene Promoter Variations on Risk of Rheumatic Heart Disease and Its Age of Onset in Saudi Arabian Patients.

Although macrophage migration inhibitory factor (MIF) has consistently been shown to be an important immune modulator, data on the association between MIF promoter variations and the risk of developing rheumatic heart disease (RHD) remain inconclusive. RHD is an important complication of streptococcal infections in the Middle East, not least in Saudi Arabia, and identifying risk markers is an important priority. Therefore, we investigated the association between two functional MIF promoter variations and RHD susceptibility and severity in Saudi patients: the MIF-173G > C substitution (rs755622) and the MIF-794 CATT5-8 tetranucleotide repeat (rs5844572). Three hundred twenty-six individuals (124 RHD patients and 202 age-, sex-, and ethnically matched healthy controls) were genotyped using allelic discrimination and fragment analysis. Data were analyzed with respect to disease susceptibility, severity, sex, and age of onset. There was a significantly lower frequency of 173C allele carriage in RHD patients compared to controls [odds ratio (OR) = 0.47; 95% confidence intervals (CIs) = 0.28-0.77; p = 0.003]. Interestingly, the 173C allele was associated with late disease onset (p = 0.001). The 794 5-repeat allele was associated with decreased RHD risk (OR = 0.56; 95% CIs = 0.38-0.82; p = 0.003). In contrast, the 794 6-repeat allele was associated with increased risk of RHD (OR = 1.7; 95% CIs = 1.2-2.5; p = 0.002). MIF promoter variations appear to have a dual role in RHD, with 173C allele non-carriers at higher risk of developing RHD at a younger age. These results require further validation in larger multi-ethnic cohorts, and functional studies are necessary to understand the underlying molecular mechanisms driving the at-risk phenotype.

IL10 Promoter Polymorphisms are Associated with Rheumatic Heart Disease in Saudi Arabian Patients.

Rheumatic heart disease (RHD) is an inflammatory disease that develops following streptococcal infections. IL10 helps to balance immune responses to pathogens. IL10 polymorphisms have been associated with RHD, although results remain inconclusive. Our aim was to investigate the association between IL10 polymorphisms and RHD in Saudi Arabian patients. IL10 promoter polymorphisms (-1082A/G, -829C/T, and -592C/A) were genotyped in 118 RHD patients and 200 matched controls using the TaqMan allelic discrimination assay. There was a significant difference in IL10-1082 genotype frequency between patients and controls (p = 0.01). -1082G allele carriage (GG+GA vs AA) and the (-1082, -819, -592) GCC haplotype carriage were associated with an increased risk of RHD (p = 0.004, OR 2.1, 95% CIs 1.7-3.4 and p = 0.004, OR 2, 95% CIs 1.3-3.4, respectively). The ACC haplotype was associated with a decrease in RHD risk (p = 0.015, OR 0.6, 95% CIs 0.4-0.9). IL10 promoter polymorphisms may play an important role in the development of RHD and provide an opportunity for therapeutic stratification.

Angiotensin-converting enzyme gene insertion/deletion polymorphism in Saudi patients with rheumatic heart disease.

OBJECTIVES: To investigate the association between angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphism and rheumatic heart disease (RHD) in Saudi patients. METHODS: A case-control study was conducted in Saudi RHD patients. Genomic DNA was isolated from 99 RHD patients attending the Pediatric Cardiology Clinic at the Maternity and Children Hospital, Al-Madinah, Saudi Arabia from March 2013 to June 2014, and from 145 age- and gender-matched controls. Patient clinical records were reviewed to report major and minor modified Jones' criteria for diagnosis. The diagnosis was confirmed by echocardiography. The ACE I/D polymorphism was identified by polymerase chain reaction. RESULTS: A significant difference in ACE D allele carriage (DD+ID) distribution between RHD cases and controls was identified (p=0.02, odds ratio = 3.6, 95% confidence interval: 1.2-10.8). The D allele carriage was significantly associated with development of mitral valve lesions alone (p=0.03). CONCLUSION: The ACE I/D polymorphism is associated with an increased risk of RHD in the Saudi population. Further studies are needed to confirm our findings and to understand the molecular mechanisms underlying this association.

Kawasaki disease in Western Saudi Arabia.

OBJECTIVE: To describe our experience on Kawasaki disease in the Madinah region, Kingdom of Saudi Arabia (KSA). METHODS: This is a retrospective hospital based study. The study was conducted in Maternity and Children Hospital, Madinah, Kingdom of Saudi Arabia during January 2007 to January 2010. The study included 51 patients' records as suspected cases of Kawasaki disease. The study was approved by the Ethical Committee. RESULTS: Twenty-four patients were proven to have Kawasaki disease in this study. The mean age of the patients at diagnosis was 3.1+/-2.4 years. Most patients were younger than 5 years (83.3%). The male to female ratio was 1.7:1. Diagnosis was made 8.1+/-3.3 days after start of fever with a range from 4-15 days. All patients received intravenous immunoglobulin (IVIG) with 2 requiring another dose of IVIG. Echocardiography was performed 10.1+/-3.9 days from onset of fever with a range of 4-20 days. The duration of hospital stay was 7.9+/-5.8 days with a range from 3-25 days. Three patients had coronary artery abnormalities and still have coronary artery dilatation at last follow-up appointment. CONCLUSION: A high index of suspicion is mandatory for early diagnosis of Kawasaki disease as delayed diagnosis may lead to coronary lesions. A national awareness program on Kawasaki disease is recommended.