Decorin (DCN) Downregulation Activates Breast Stromal Fibroblasts and Promotes Their Pro-Carcinogenic Effects through the IL-6/STAT3/AUF1 Signaling.

Decorin (DCN), a member of the small leucine-rich proteoglycan gene family, is secreted from stromal fibroblasts with non-cell-autonomous anti-breast-cancer effects. Therefore, in the present study, we sought to elucidate the function of decorin in breast stromal fibroblasts (BSFs). We first showed DCN downregulation in active cancer-associated fibroblasts (CAFs) compared to their adjacent tumor counterpart fibroblasts at both the mRNA and protein levels. Interestingly, breast cancer cells and the recombinant IL-6 protein, both known to activate fibroblasts in vitro, downregulated DCN in BSFs. Moreover, specific DCN knockdown in breast fibroblasts modulated the expression/secretion of several CAF biomarkers and cancer-promoting proteins (α-SMA, FAP- α, SDF-1 and IL-6) and enhanced the invasion/proliferation abilities of these cells through activation of the STAT3/AUF1 signaling. Furthermore, DCN-deficient fibroblasts promoted the epithelial-to-mesenchymal transition and stemness processes in BC cells in a paracrine manner, which increased their resistance to cisplatin. These DCN-deficient fibroblasts also enhanced angiogenesis and orthotopic tumor growth in mice in a paracrine manner. On the other hand, ectopic expression of DCN in CAFs suppressed their active features and their paracrine pro-carcinogenic effects. Together, the present findings indicate that endogenous DCN suppresses the pro-carcinogenic and pro-metastatic effects of breast stromal fibroblasts.

Single nucleotide polymorphisms in cytokine genes and their association with primary Sjögren's syndrome in Saudi patients: A cross-sectional study.

OBJECTIVES: To determine the allelic frequencies and effects of genotypic variations in cytokine gene polymorphisms in a Saudi Arabian population. METHODS: This cross-sectional study involved 41 patients with Primary Sjögren's syndrome (pSS) and 71 healthy controls between October 2018 and May 2019. Single nucleotide polymorphisms genotyping was performed using the SEQUENOM MassARRAY® System, targeting nine polymorphisms in different cytokine genes. Chi-square tests were used to compare the patients and controls. RESULTS: The interleukin-1 beta (IL-1ß) rs1143627 CT (control, 52.7%; patients, 21.2%) and TT + CT (p= 0.003; p=0.033) genotypes were less frequent in patients with pSS than in healthy controls. The C allele in rs10488631 in the interferon regulatory factor 5 (IRF5) gene and the A allele in rs12583006 in the B-cell activating factor (BAFF) gene were associated with an increased risk of pSS development in the patient group. CONCLUSION: The CT genotype at -31 (rs1143627) in the IL-1ß gene was not associated with a high risk of pSS development in the Saudi population, in contrast to what has been verified in other ethnicities. However, the C allele in rs10488631 in IRF-5 and the A allele in rs12583006 in BAFF were associated.

Association of Inflammatory Cytokine Levels with Extra Glandular Manifestations, Fatigue, and Disease Activity in Primary Sjögren's Syndrome in Saudi Patients: A Cross-Sectional Study.

BACKGROUND: Primary Sjögren's syndrome (pSS) is an autoimmune disease that can cause fatigue and extraglandular manifestations (EGMs). pSS is associated with cytokine network dysregulation, which may be related to the immune-mediated destruction of exocrine glands. OBJECTIVE: We determined cytokine levels and their relationship to EGMs, the European League Against Rheumatism (EULAR) Sjögren's syndrome disease activity index (ESSDAI), and fatigue in Saudi patients with pSS. METHODS: This study was a cross-sectional, single-center study. We included forty-one patients and 71 controls. Serum samples were collected from random healthy people and pSS patients who were followed in the rheumatology and pulmonary clinics of King Saud University Medical City in Riyadh, Saudi Arabia. Levels of the frequently studied cytokines were measured using Luminex xMAP technology. Each ESSDAI score and EGM were recorded, and the Arabic version of the fatigue severity scale (FSS) was applied to assess fatigue. The main outcome measures were cytokine levels in pSS Saudi patients using/not using immune-suppressive medications (ISMs). RESULTS: Thirty-six (87.8%) patients had one or more EGMs, and the mean ESSDAI score was 9.95 ± 7.73. There was a significant decrease in TNFα and IL-21 levels in the pSS group compared to those in the control group (p = 0.034 and p < 0.001, respectively), whereas IL-12 levels were significantly elevated in the pSS group (p = 0.002). Cytokine levels in patients who used ISMs were the same as those in patients who did not use medications. Decreased IL-1ß (p = 0.014), IL-2 (p = 0.035), IL-6 (p = 0.014), and IL-35 (p = 0.010) levels were observed in patients who had EGMs. Patients who had low disease activity exhibited low IL-10 (p = 0.018) and high IFN-α (p = 0.049), IFN-ß (p = 0.049), IL-1ß (p = 0.006), and IL-35 (p = 0.032) levels compared to patients with high disease activity. A negative association between a positive fatigue score and IL-1ß (p = 0.010), IL-2 (p = 0.037), IFN-α (p = 0.025), TNFα (p = 0.030), IL-17 (p = 0.029), IL-12 (p = 0.046), and IL-21 (p = 0.005) levels was found. CONCLUSIONS: Cytokine profiles correlate with EGMs, ESSDAI, and fatigue. Patients with controlled disease activity have a normal cytokine profile that is similar to that of controls.

The Fidelity of Rheumatoid Arthritis Multivariate Diagnostic Biomarkers Using Discriminant Analysis and Binary Logistic Regression.

Rheumatoid arthritis (RA) is an autoimmune inflammatory disease that causes multi-articular synovitis. The illness is characterized by worsening inflammatory synovitis, which causes joint swelling and pain. Synovitis erodes articular cartilage and marginal bone, resulting in joint deterioration. This bone injury is expected to be permanent. Cytokines play a prominent role in the etiology of RA and could be useful as early diagnostic biomarkers. This research was carried out at Riyadh's King Khalid University Hospital (KKUH). Patients were enrolled from the Rheumatology unit. Seventy-eight RA patients were recruited (67 (85.9%) females and 11 (14.1%) males). Patients were selected for participation by convenience sampling. Demographic data were collected, and disease activity measurements at 28 joints were recorded using the disease activity score (DAS-28). Age- and sex-matched controls from the general population were included in the study. A panel of 27 cytokines, chemokines, and growth factors was determined in patient and control sera. Binary logistic regression (BLR) and discriminant analysis (DA) were used to analyze the data. We show that multiple cytokine biomarker profiles successfully distinguished RA patients from healthy controls. IL-17, IL-4, and RANTES were among the most predictive variables and were the only biomarkers incorporated into both BLR and DA predictive models for pooled participants (men and women). In the women-only models, the significant cytokines incorporated in the model were IL-4, IL-17, MIP-1b, and RANTES for the BLR model and IL-4, IL-1Ra, GM-CSF, IL-17, and eotaxin for the DA model. The BLR and DA men-only models contained one cytokine each, eotaxin for BLR and platelet-derived growth factor-bb (PDGF-BB) for DA. We show that BLR has a higher fidelity in identifying RA patients than DA. We also found that the use of gender-specific models marginally improves detection fidelity, indicating a possible benefit in clinical diagnosis. More research is needed to determine whether this conclusion will hold true in various and larger patient populations.

Single Nucleotide Polymorphisms Associated with Rheumatoid Arthritis in Saudi Patients.

Rheumatoid arthritis (RA) is a complex, multifactorial disorder with an autoimmune etiology. RA is highly heritable and is associated with both human leucocyte antigen (HLA) and non-HLA genes. We investigated the associations of 33 single nucleotide polymorphisms (SNPs) with RA in the Saudi population. METHODS: This study included 105 patients with RA and an equal number of age- and sex-matched controls. The patients with RA attended outpatient clinics at King Khalid University Hospital in Riyadh, Saudi Arabia. Blood samples were collected, and DNA was extracted using Qiagen kits. Primers were designed for the 33 selected SNPs using the MassEXTEND primers program, and samples were genotyped on the Sequenom MassARRAY iPLEX platform. The allele frequencies and genotypes were determined for each SNP, and the results obtained for the patients were compared to those for the controls. RESULTS: The allele and genotype frequencies of six SNPs were significantly associated with RA: rs1188934, rs10919563, rs3087243, rs1980422, rs10499194, and rs629326. The minor alleles of rs1188934, rs10919563, rs10499194, and rs629326 were protective, with odds ratios of 0.542, 0.597, 0.589, and 0.625, and p-values of 0.002, 0.023, 0.013 and 0.036, respectively. In addition, the heterozygote frequencies of two SNPs (rs6859219 and rs11586238) were significantly higher in the controls than in the patients. CONCLUSIONS: There is considerable heterogeneity in the genetics of RA in different populations, and the SNPs that are associated with RA in some populations are not in others. We studied 33 SNPs and only eight were associated with RA. The remaining SNPs showed no allelic or genotypic associations with RA.

CYP2D6 genetic polymorphisms in Saudi systemic lupus erythematosus patients: A cross-sectional study.

OBJECTIVES: To determine the prevalence of selected single nucleotide polymorphisms (rs1080985, rs28624811, rs1065852, rs28371725, and rs1135840) in cytochrome P450 2D6 (CYP2D6) gene among Saudi systemic lupus erythematosus (SLE) patients and to investigate the association between the genetic variants and clinical features of SLE. METHODS: This cross-sectional study was carried out on adult Saudi patients at King Khalid University Hospital, Riyadh, Saudi Arabia. Patients with confirmed SLE based on the 2012 Systemic Lupus International Collaborating Clinics classification criteria were included in the study. Peripheral blood was collected for genomic deoxyribonucleic acid extraction and TaqMan® technologies were used for target genotyping. For statistical analysis, differences in genotype frequencies were determined using the Chi-square test, and the association between the variant genotypes and SLE features was evaluated using logistical regression models. RESULTS: There were 107 participants included in this study. Overall, the most predominant (23.4%) recessive genotype was AA in rs28624811, and the least prevalent (1.9%) recessive genotype was TT in rs28371725. Moreover, the variant rs1080985 genotypes (GC or CC) were significantly associated with the presence of serositis manifestation (OR=3.15, p=0.03), even after adjusting for age and gender. However, the dominant rs28624811 genotype (GG) was associated with renal involvement (OR=2.56, p=0.03). CONCLUSION: Systemic lupus erythematosus patients carrying CYP2D6 variants might be considered at risk for certain manifestations of SLE. Further studies are needed to investigate the implication of these genetic variations in clinical outcomes and drug response.

SHQ1-associated neurodevelopmental disorder: Report of the first homozygous variant in unrelated patients and review of the literature.

Compound heterozygous mutations in SHQ1 have been associated with a rare and severe neurological disorder characterized by global developmental delay (GDD), cerebellar degeneration coupled with seizures, and early-onset dystonia. Currently, only five affected individuals have been documented in the literature. Here, we report three children from two unrelated families harboring a homozygous variant in the gene but with a milder phenotype than previously described. The patients had GDD and seizures. Magnetic resonance imaging analyses revealed diffuse white matter hypomyelination. Sanger sequencing confirmed the whole-exome sequencing results and revealed full segregation of the missense variant (SHQ1:c.833 T > C; p.I278T) in both families. We performed a comprehensive in silico analysis using different prediction classifiers and structural modeling of the variant. Our findings demonstrate that this novel homozygous variant in SHQ1 is likely to be pathogenic and leads to the clinical features observed in our patients.

Global Transcriptional Profiling of Granulosa Cells from Polycystic Ovary Syndrome Patients: Comparative Analyses of Patients with or without History of Ovarian Hyperstimulation Syndrome Reveals Distinct Biomarkers and Pathways.

Ovarian hyperstimulation syndrome (OHSS) is often a complication of polycystic ovarian syndrome (PCOS), the most frequent disorder of the endocrine system, which affects women in their reproductive years. The etiology of OHSS is multifactorial, though the factors involved are not apparent. In an attempt to unveil the molecular basis of OHSS, we conducted transcriptome analysis of total RNA extracted from granulosa cells from PCOS patients with a history of OHSS (n = 6) and compared them to those with no history of OHSS (n = 18). We identified 59 significantly dysregulated genes (48 down-regulated, 11 up-regulated) in the PCOS with OHSS group compared to the PCOS without OHSS group (p-value < 0.01, fold change >1.5). Functional, pathway and network analyses revealed genes involved in cellular development, inflammatory and immune response, cellular growth and proliferation (including DCN, VIM, LIFR, GRN, IL33, INSR, KLF2, FOXO1, VEGF, RDX, PLCL1, PAPPA, and ZFP36), and significant alterations in the PPAR, IL6, IL10, JAK/STAT and NF-κB signaling pathways. Array findings were validated using quantitative RT-PCR. To the best of our knowledge, this is the largest cohort of Saudi PCOS cases (with or without OHSS) to date that was analyzed using a transcriptomic approach. Our data demonstrate alterations in various gene networks and pathways that may be involved in the pathophysiology of OHSS. Further studies are warranted to confirm the findings.

Gut Microbiota Dynamics in Relation to Long-COVID-19 Syndrome: Role of Probiotics to Combat Psychiatric Complications.

Increasing numbers of patients who recover from COVID-19 report lasting symptoms, such as fatigue, muscle weakness, dementia, and insomnia, known collectively as post-acute COVID syndrome or long COVID. These lasting symptoms have been examined in different studies and found to influence multiple organs, sometimes resulting in life-threating conditions. In this review, these symptoms are discussed in connection to the COVID-19 and long-COVID-19 immune changes, highlighting oral and psychiatric health, as this work focuses on the gut microbiota's link to long-COVID-19 manifestations in the liver, heart, kidney, brain, and spleen. A model of this is presented to show the biological and clinical implications of gut microbiota in SARS-CoV-2 infection and how they could possibly affect the therapeutic aspects of the disease. Probiotics can support the body's systems in fighting viral infections. This review focuses on current knowledge about the use of probiotics as adjuvant therapies for COVID-19 patients that might help to prevent long-COVID-19 complications.

Functional and psychosocial impact of COVID-19 pandemic on rheumatic patients' quality of life in Saudi Arabia.

PURPOSE: The COVID-19 pandemic might add to the stressors experienced by people living with rheumatic diseases. This study aimed to examine rheumatic patients' functional and psychosocial states during the pandemic and assess its impact on their quality of life. METHODS: Our time-series study included a patient-centered electronic survey, sampling adult rheumatic patients living in Saudi Arabia at different time points from March to August 2020. Patient-reported outcomes included physical function, anxiety, depression, fatigue, sleep disturbance, ability to participate in social roles, and pain interference domains were measured using the Patient-Reported Outcomes Measurement Information System (PROMIS-29 Profile v2.1). RESULTS: A total of 1278 respondents were enrolled. Results showed significant variation in patients' experiences. Our analyses revealed that the physical well-being of rheumatic patients was significantly impacted, and such effect was persistent over time irrespective of public health measures to control the COVID-19 outbreak. CONCLUSION: Our findings consistently demonstrated the need for psychological and social consideration to improve rheumatic patients' quality of life. Nevertheless, there is still a lot to be learned about the extent of COVID-19 impact on rheumatic patients and the implications it has on long-term disease outcomes.

Venom of the desert black snake Walterinnesia aegyptia enhances anti-tumor immunity via its beneficial modulatory effects on pro- and anti-tumorigenic inflammatory mediators in cultured colon cancer cells.

The role of inflammation in colon cancer is understood as a well-accepted factor that has the tendency to release multiple pro- and anti-tumorigenic inflammatory mediators. Inflammation-induced increased expression of anti-tumorigenic inflammatory mediators and decreased expression of pro-tumorigenic inflammatory mediators encourage beneficial inflammatory effects in terms of powerful anti-tumor immunity. The present study aims to screen the beneficial inflammatory effects of Walterinnesia aegyptia venom via determining its modulatory tendency on the expression of 40 pro- and anti-tumorigenic inflammatory mediators (cytokines/growth factors/chemokines) in LoVo human colon cancer cell line. LoVo-cells were treated with varying doses of crude venom of W. aegyptia. Cell viability was checked utilizing flow cytometry, and IC50 of venom was determined. Venom-induced inflammatory effects were evaluated on the expression of 40 different inflammatory mediators (12 anti-tumorigenic cytokines, 11 pro-tumorigenic cytokines, 7 pro-tumorigenic growth factors, 9 pro-tumorigenic chemokines and 1 anti-tumorigenic chemokine) in treated LoVo-cells [utilizing enzyme-linked immunosorbent assay (ELISA)] and compared with controls. Treatment of venom induced significant cytotoxic effects on inflamed LoVo-cells. IC50 treatment of venom caused significant modulations on the expression of 22 inflammatory mediators in treated LoVo-cells. The beneficial modulatory effects of venom were screened via its capability to significantly increase the expression of five powerful anti-tumorigenic mediators (IL-9, IL-12p40, IL-15, IL-1RA and Fractalkine) and decrease the expression of four major pro-tumorigenic mediators (IL-1ß, VEGF, MCP-1 and MCP-3). Walterinnesia aegyptia venom-induced beneficial modulations on the expression of nine crucial pro/anti-tumorigenic inflammatory mediators can be effectively used to enhance powerful anti-tumor immunity against colon cancer.

National systemic lupus erythematosus prospective cohort in Saudi Arabia: A study protocol.

ABSTRACT: Systemic Lupus erythematosus (SLE) is a chronic multisystem, multifactorial inflammatory autoimmune disease. The SLE patients have 3 times increased risk of mortality based on international data with ethnicity playing an important impact on patients' morbidity and mortality. Descriptive studies from Saudi Arabia showed variation in clinical features from one region to another. Moreover, reliable inference from these studies is limited by study methodology and lack of translational data using biological samples to understand clinical phenotypes of Saudi SLE patients.The aim of this report is to describe the prospective study protocol of the National Systemic Lupus Erythematosus Cohort in Saudi Arabia. The purpose of this cohort study is multifold: first, to examine clinical characteristics and molecular phenotypes of Saudi SLE patients in relation to local environment and practices/lifestyles; second, to assess long-term outcomes of SLE in Saudi population and factors that influence favorable outcomes; third, to compare the effectiveness of various treatment regimens in Saudi SLE population.This study is a longitudinal prospective cohort study of adult, Saudi SLE patients using open cohort study design. Primary outcomes include disease-related outcomes (activity, improvement, and organ damage) and patient-reported outcomes (quality of life). Secondary outcomes include physiological and molecular modifications associated with changes in disease activity states.Results and analysis are in on-going study.This study provides a source of reliable data for clinical and translational research. This will allow us to have a holistic approach to SLE pathogenesis especially in Saudi population and may take us a step further toward much more personalized medicine.This protocol has been registered in NIH ClinicalTrial.gov (ClinicalTrial.gov identifier: NCT04604990) on October 27, 2020.

Adverse Effects of Selected Markers on the Metabolic and Endocrine Profiles of Obese Women With and Without PCOS.

The aim of the present study, is to investigate the influence of obesity, with and without polycystic ovarian syndrome (PCOS), on the levels of kisspeptin, vitamin D (Vit D), and vascular endothelial growth factor (VEGF) and to explore the relationship between these parameters and endocrine and metabolic variables. The study group included 126 obese Saudi females. Of these 63 were suffering from PCOS while the rest were normo-ovulatory obese women (non-PCOS obese). In the obese PCOS, VEGF was almost four times as high as in the non-PCOS obese, while kisspeptin and Vit D did not differ. A highly significant elevation was recorded in the waist/hip (WHR), cholesterol, LDL-C, fasting glucose, LH, LH/FSH ratio, estradiol (E2), and testosterone, while hip circumference, leptin, progesterone, and sex hormone binding globulin (SHBG) were lower in the obese PCOS subjects. BMI, HDL-C, ghrelin, insulin, and FSH levels did not differ significantly between the two groups. The obese PCOS had the same level of insulin resistance as the non-PCOS group, as judged by QUICK Index. Correlation studies showed a significant negative correlation between kisspeptin and glucose and LH levels, and a positive correlation with LH/FSH ratio in obese PCOS while in the non-PCOS obese, the kisspeptin correlated positively with glucose, and there was no correlation with LH or LH/FSH. VEGF negatively correlated with FSH and positively with LH/FSH ratio in the non-PCOS obese but this was lost in the obese PCOS. PCOS had no effect on the correlation between Vit D and all studied parameters. Multiple regression analysis showed triglyceride as predictor variable for kisspeptin as a dependent variable, while, leptin is a predictor variable for VEGF as a dependent variable. ROC studies showed the highest sensitivity and specificity for VEGF (AOC=1.00), followed by LH/FSH ratio (AOC=0.979). In conclusion, our study shows that PCOS results in significant elevation of VEGF in obese females, while kisspeptin and Vit D levels are not affected. It also leads to elevation in several of the lipid and hormonal abnormalities in the obese females. In addition, PCOS influences relationship between Kisspeptin and VEGF and some parameters such as glucose, LH or FSH and LH/FSH ratio in obese females, but does not affect Vit D relationship with other parameter.

Disease phenotype and diagnostic delay in Saudi patients with primary Sjögren's syndrome: An exploratory cross-sectional study.

OBJECTIVES: To describe primary Sjögren's syndrome (pSS) cohort in Saudi Arabiain view in of clinical/serological/histopathological phentotype, and, diagnostic delay. METHODS: A cross-sectional study conducted between October 2018 and May 2019. Diagnostic delay was calculated from symptoms onset to clinical diagnosis. The European League Against Rheumatism (EULAR) Sjögren's Syndrome Disease Activity Index (ESSDAI) and EULAR Sjogren's Syndrome Patient Reported Index (ESSPRI) were calculated. RESULTS: Forty-one patients were included in the study. There were predominantly females (78%) with a mean (±SD) age of 58.76±12.7 and disease duration of 4.6±2.28 years. The mean diagnostic delay was 2.2±2.4 (range 1-11) years. Minor salivary gland biopsy was performed on 38 (92.7%) patients with a mean focus score of 2.3± 1.2 points. Interstitial lung disease and arthritis were the most common extra-glandular manifestations (EGM) affecting 27 (65.9%) patients for both. The mean ESSDAI was 9.95±7.73 and ESSPRI was 5.17±2.4. CONCLUSION: Saudi primary Sjogren's syndrome patients have a high prevalence of EGM predominantly arthritis and ILD. The diagnostic delay is variable in our cohort.

Influence of b2 adrenergic receptor polymorphism (rs1042713 and rs1042714) on anthropometric, hormonal and lipid profiles in polycystic ovarian syndrome.

BACKGROUND: Polycystic ovarian syndrome (PCOS) is a frequently encountered disorder. This study aimed to identify polymorphisms in ADRB2 in Saudi PCOS development and to study its influence on lipids, hormones, and anthropometric parameters. METHODS: Saudi females (100) suffering from PCOS and healthy controls (100) were investigated. The estimation of cholesterol, triglycerides, high-density lipoprotein (HDL-C), low-density lipoprotein (LDL-C), plasma glucose, leptin Insulin, and ghrelin were carried out. The DNA was extracted, and ADRB2 fragment carrying the exon 1 was amplified and sequenced. RESULTS: The waist, W/H ratio, lipids, glucose, and insulin were significantly higher in the obese PCOS compared to the normal weight group. The leptin and ghrelin were not different. Two single nucleotide polymorphisms (SNPs): rs1042713 (Arg16Gly; A>G) and rs1042714 (Gln27Glu; C>G) were identified. The genotype and allele frequency of rs1042713 did not differ in the total PCOS and normal weight, and obese PCOS compare to the controls. However, rs1042714 was significantly associated with PCOS development, where the minor G allele was protective against PCOS development. CONCLUSIONS: The rs1042714 polymorphism of the ADRB associates with PCOS development in Saudis, while rs1042713 does not. However, the GG genotype of rs1042713 associates significantly with elevated BMI, waist, hip, W/H, and leptin, and decreased ghrelin. On the other hand, rs1042714 genotypes do not associate with any abnormality except the homozygous GG have higher triglycerides and lower HDL-C. Interestingly, glucose showed different correlation patterns in individuals carrying different genotypes of the two studied SNP, indicating clearly that the metabolic responses to a normal nutrient are significantly influenced by the genotypes of the SNPs in ADRB2.

Hematological findings associated with tubulin-folding cofactors D-related encephalopathy: Expanding the phenotype.

The dysfunction of microtubules (α/ß-tubulin polymers) underlies a wide range of nervous system genetic abnormalities. Defects in TBCD, a tubulin-folding cofactor, cause diseases highlighted with early-onset encephalopathy with or without neurodegeneration, intellectual disability, seizures, microcephaly and tetraparaperesis. Utilizing various molecular methods, we describe nine patients from four unrelated families with two novel exon 18 variants in TBCD exhibiting the typical neurological phenotype of the disease. Interestingly, all the investigated patients had previously unreported hematological findings in the form of neutropenia and mild degree of anemia and thrombocytopenia. In addition to delineating the neurological phenotype in several patients with TBCD variants, our study stresses on the new association of neutropenia, in particular, with the disease.

Fatigue in Saudi Patients with Primary Sjögren's Syndrome and Its Correlation with Disease Characteristics and Outcome Measures: A Cross-Sectional Study.

BACKGROUND: Fatigue is a prevalent symptom affecting primary Sjögren's syndrome (pSS) patients. The purpose of this study is to determine the prevalence of fatigue in Saudi pSS patients and its correlation with disease features and outcome measures using a validated tool. METHODS: This is a cross-sectional study evaluating fatigue in pSS using the Arabic version of the fatigue severity scale (FSS). The EULAR Sjögren's syndrome disease activity index (ESSDAI) and EULAR Sjögren's syndrome patient reported index (ESSPRI) were calculated. RESULTS: Forty-one patients met the sample criteria and were involved in the final report. There were predominantly females (78%) with a mean (±SD) age and disease duration of 58.76±12.7 and 4.6±2.28 years, respectively. Based on the FSS, 18 (43.9%) patients had a positive test with a mean score of 5.43±0.76. The mean ESSDAI was 9.95±7.73, while the mean EESPRI was 5.17±2.4 with individual component scores were dryness (5.23±2.62), fatigue (5.4±2.88), and pain (4.88±3.31). The FSS had a significant correlation with PGA (r=0.559; p<0.001), PhGA (r=0.671; p<0.001), ESSDAI (r=0.402; p=0.01), ESSPRI fatigue component (r=0.0.621; p<0.001), ESSPRI pain component (r=0.558; p<0.001), and missed significance for the ESSPRI dryness component (r=0.289; p=0.071). There was no correlation between the total ESSPRI score and presence of fatigue (r=-0.261; p=0.104) nor the FSS score (r=-0.136; p=0.409). CONCLUSION: Fatigue is prevalent in Saudi pSS patients. FSS correlated with ESSDAI and ESSPRI components but not its total score signaling other unmeasured factors contributing to fatigue development.

RS1799817 in INSR associates with susceptibility to polycystic ovary syndrome.

BACKGROUND: Insulin and its receptor (INSR) have been implicated in the etiology of the polycystic ovarian syndrome (PCOS). Here, we investigate the association between INSR rs1799817 polymorphism and PCOS in Saudi Arabian women. METHODS: Study group included 126 PCOS women and 118 normo-ovulatory matched controls. The demographic data was recorded, and the plasma levels of glucose, lipids, leptin, E2, LH, FSH, T, SHBG, and insulin were determined. The genotypic and allele frequencies of rs1799817 were evaluated in both PCOS and control group. Polymerase chain reaction (PCR) was used to amplify Exon 17 of the INSR gene, and the amplified products were analyzed by direct sequencing. A single-nucleotide polymorphism (C to T) was found at locus 10923 (His1058) of rs1799817. RESULTS: In the PCOS group, the mutant allele T occurs at a significantly higher frequency (0.306) compared to the control group (0.174) (p<0.001). It shows a dominant effect and elevates the relative risk of PCOS even in the heterozygotes (RR=2.82). After stratification of the participants by body mass index, the frequency of T allele was significantly higher in the lean patients with PCOS compared to the lean control. The obese PCOS also had a higher frequency than the obese control, but the difference was not statistically significant. Several parameter values were affected by the INSR genotype, particularly W/H ratio, lipid, insulin and glucose levels and insulin resistance in PCOS patients. CONCLUSIONS: The INSR gene polymorphism rs1799817 is a susceptibility locus associated with PCOS in Saudis and associated metabolic and hormonal changes, particularly, in the lean PCOS females.

Impact of COVID-19 outbreak on rheumatic patients' perceptions and behaviors: A cross-sectional study.

AIM: The dynamics of coronavirus disease 2019 (COVID-19) pandemic has become of special concern to the rheumatology community. Rheumatic patients are required to engage in effective health management but their behavior is often influenced by intrinsic and extrinsic factors. This cross-sectional study aims to examine patients' experiences during the current pandemic and its implication on their health perception and behavior. METHOD: A patient-centered electronic survey was used, randomly sampling rheumatic patients in Saudi Arabia during March and April 2020. Questions included patients' socio-demographics, diseases, medications, COVID-19 knowledge, source of information, fear level, disease activity perception, health care utilization, medication accessibility, and therapeutic compliance (measured using a modified version of Medication Adherence Reporting Scale). Correlation and regression coefficients were used to evaluate associations among the aforementioned variables. RESULTS: A total of 637 respondents were included. The majority were rheumatoid arthritis patients (42.7%). Patients' knowledge about COVID-19 was correlated with social media use (P = .012). Fear of COVID-19 infection correlated with healthcare facility for follow-up visits (P = .024) and fear of disease deterioration if contracting the infection correlated with patients' levels of knowledge (P = .035). Both types of fear did not correlate with patients' perceptions of disease activity. However, patients' perceptions of worsened disease activity were correlated with unplanned healthcare visits (P < .001), medication non-adherence, and difficulty accessing medication (P = .010 and .006, respectively). CONCLUSION: The COVID-19 pandemic and surrounding public health measures could affect rheumatic patients' health management which might contribute to disease flare-up and subsequently taxing healthcare systems even further.

Influence of KISS1 gene polymorphisms on the risk of polycystic ovary syndrome and its associated variables, in Saudi women.

BACKGROUND: Polycystic ovary syndrome (PCOS) is a complex multifactorial disorder, affecting millions of women worldwide. The role of genetic polymorphisms of the KISS1 gene on the development of PCOS is still obscure. This study was designed to investigate the probable influence of KISS1 gene polymorphisms on PCOS and its associated variables: BMI, waist-hip ratio, kisspeptin, LH, FSH, and LH-FSH ratio. METHODS: The study comprised 104 PCOS women and 109 controls, with age ranging from 19 to 36 years. BMI, waist-hip ratio, and circulating levels of kisspeptin, LH, and FSH were measured. DNA was extracted, and genotyping of the KISS1 gene was carried out by nucleotide sequencing. The PCOS-associated variables were analyzed in different genotypes of single nucleotide polymorphisms (SNPs) of the KISS1 gene. RESULTS: The values of waist-hip ratio (WHR), LH, and LH-FSH ratio were significantly higher in PCOS women than controls. BMI, kisspeptin, and FSH levels exhibited no significant difference between the groups. Six novel SNPs of KISS1 gene were identified. Three: rs372790354G > A, rs12998G > A, and rs35431622A > T were investigated. Among these SNPs, the genotype and allele frequencies of rs372790354 showed significant association with PCOS (GA: p = 0.018, AA: p = 0.022, mutant allele-A: p = 0.021) and the G allele was protective. The values of LH, kisspeptin, and WHR of PCOS women were significantly influenced (p < 0.05) by the AA genotype of rs372790354. The other two SNPs rs12998G > A and rs35431622A > T revealed no significant influence on PCOS and associated variables. Haplotypes were constructed, but there was no significant difference between the patients and controls. CONCLUSION: In conclusion, this is the first study, which reports a significant influence of KISS1 gene polymorphism (rs372790354G > A) on PCOS and its associated variables. However, more extensive research is necessary to confirm these findings.