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Background: In the wake of the warning by WHO that the prevalence of dementia may have a rise of 125% in the Middle East by 2050, identification of the genetic risk factors in Arab populations is urgent. Objective: To investigate the association of Single Nucleotide Polymorphisms (SNPs) in apolipoprotein E (ApoE), clusterin (CLU), tumor necrotic factor- α (TNF-α) and interleukin-6 (IL-6) genes, with risk of Alzheimer’s disease (AD) in Saudi Arabian participants. Method: A total of 42 Saudi AD patients and 23 age-matched control participants were genotyped for eight SNPs: rs429358, rs7412 (ApoE); rs11136000, rs1532278 (CLU); rs1800629, rs1799724 (TNF-α) and rs1800796, rs1800795(IL-6), by RT-PCR using the TaqMan assay. Serum concentrations of amyloid beta peptide 1–40(Aβ1-40), amyloid beta peptide 1–42(Aβ1- 42), CLU and some other biochemical markers were measured. Results: A significant increase (p=0.004) in the serum CLU level was detected in the AD group (340.4 ± 74.6) compared with control group (265.0 ± 80.9). For rs1532278 (CLU), genotype GA was significantly higher in AD patients (57.1%) than in the control participants (26.1%), [p=0.024, OR = 4.00, 95% CI (1.20-13.28)]. For the ApoE SNP rs7412, 40.4% of patients carried a TT genotype, whereas it was completely absent in the controls [p = 0.020, OR = 30.53, 95% CI (1.73 – 540.05)].For rs429358 (ApoE), patients showed a significantly increased frequency of the TC genotype [p = 0.006, OR = 9.33, 95% CI (1.89–46.19)] and TT [p = 0.045, OR = 19.76, 95% CI (1.07–366.0)] genotype than controls. AD patients with CC genotype for ApoE rs429358 had significantly lower levels of Aβ1-40 (p=0.04) in AD patients than controls. Carriers of genotype GG for rs1800629 (TNF-α) showed significantly higher levels of serum IL-6 (p = 0.04) in AD patients. Conclusion: Genetic variants in ApoE and CLU may influence susceptibility to AD among Saudi Arabian participants.

Post-menopausal osteoporosis (PMO) is a multifactorial bone disorder in elderly women. Various vitamin D receptor (VDR) gene variants have been studied and associated with osteoporosis in other populations, but not in a homogenous Arab ethnic group. Herein, the current study explores the association between VDR polymorphisms and susceptibility to osteoporosis in Saudi postmenopausal women. In total, 600 Saudi postmenopausal women (N = 300 osteoporosis, N = 300 control) were genotyped for VDR gene variants (rs7975232, rs1544410, rs731236) using TaqMan® SNP genotyping assays. Bone mineral density (BMD) for the lumbar spine and femur was assessed using dual-energy X-ray absorptiometry (DEXA). The heterozygous frequency distributions AC of rs7975232, CT of rs1544410, and AG of rs731236 were significantly higher in the osteoporosis group than controls (p &lt, 0.05). Heterozygous AC of rs7975232 (1.6, 95% CI 1.1–2.3, p &lt, 0.023), CT of rs1544410 (1.6, 95% CI 1.1–2.4, 0.022), and AG of rs731236 (1.6, 0.024) were significantly associated with increased risk of osteoporosis, independent of age and BMI. In conclusion, VDR gene variants rs7975232, rs1544410, rs731236 had a significant effect on BMD and were associated with osteoporosis risk in Saudi postmenopausal women.

© The Author(s) 2022 Open Access This article is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License, which permits any non-commercial use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc/4.0/., Knee osteoarthritis (OA) is one of the most common and disabling medical conditions. In the case of moderate to severe pain, a single intervention may not be sufficient to allay symptoms and improve quality of life. Examples include first-line, background therapy with symptomatic slow-acting drugs for OA (SYSADOAs) or non-steroidal anti-inflammatory drugs (NSAIDs). Therefore, the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO) performed a review of a multimodal/multicomponent approach for knee OA therapy. This strategy is a particularly appropriate solution for the management of patients affected by knee OA, including those with pain and dysfunction reaching various thresholds at the different joints. The multimodal/multicomponent approach should be based, firstly, on different combinations of non-pharmacological and pharmacological interventions. Potential pharmacological combinations include SYSADOAs and NSAIDs, NSAIDs and weak opioids, and intra-articular treatments with SYSADOAs/NSAIDs. Based on the available evidence, most combined treatments provide benefit beyond single agents for the improvement of pain and other symptoms typical of knee OA, although further high-quality studies are required. In this work, we have therefore provided new, patient-centered perspectives for the management of knee OA, based on the concept that a multimodal, multicomponent, multidisciplinary approach, applied not only to non-pharmacological treatments but also to a combination of the currently available pharmacological options, will better meet the needs and expectations of patients with knee OA, who may present with various phenotypes and trajectories.

Purpose Primary hyperparathyroidism (PHPT) is a common cause of hypercalcemia and remains understudied within the Arabian population. The present study, the largest of its kind within the Gulf Cooperation Council (GCC) countries, aims to determine the demographics and clinical presentation of PHPT in Saudi Arabia. Methods In this multi-center retrospective study involving three tertiary hospitals in different geographic locations of Saudi Arabia namely, Riyadh, Al Ahsa and Jeddah, a total of 205 out of 243 confirmed PHPT cases aged 16 to 93 years old were included (N = 96 from Riyadh; N = 59 from Al Ahsa and N = 50 from Jeddah). Demographics, clinical manifestations and surgical outcomes were recorded as well as laboratory and radiologic investigations including serum parathyroid hormone (PTH), 25(OH)D, adjusted calcium, estimated glomerular filtration rate (eGFR) and nuclear scan outcome. Results PHPT cases appeared to increase over time when compared to other local studies published so far, with 12.8 cases per 100,000 hospital population. Females outnumber males (3:1) with 86% seen as out-patients. The average age was 59.8 ± 15.5 years. Abnormal PTH scan was seen in 171 patients (83.4%). Kidney stones was the most common renal manifestation (32 cases, 15.6%) and osteoporosis was the most common skeletal manifestation (67 cases, 32.7%). Al Ahsa had the highest prevalence of multiple comorbidities at 54% and the highest prevalence of obesity as a single comorbidity (17%) compared to other regions (p p Conclusion Comparison of present data with previous local studies suggest an increasing trend in PHPT cases in Saudi Arabia. Regional variations in the clinical presentation of PHPT were observed and warrant further investigation.

Background and objective: There is limited information as to the association of several key bone markers with bone mineral density (BMD) in understudied ethnic groups. This study investigated the relationship between circulating levels of osteoprotegerin (OPG) and receptor activator of nuclear factor kappa-Β ligand (RANKL) with BMD in Arab postmenopausal women. Materials and methods: In this cross-sectional study, a total of 617 Saudi postmenopausal women from the Osteoporosis Registry of the Chair for Biomarkers of Chronic Diseases were included. Anthropometric data, BMD, and biochemical data were retrieved from the registry. Participants were stratified into three groups based on T-score; n = 169 with osteoporosis, n = 282 with osteopenia, and n = 166 normal. Analysis of bone markers including RANKL, OPG, osteocalcin, and N-terminal telopeptide (NTx) was completed using commercially available bioassays. Results: The results suggested that OPG was significantly and positively correlated with age in the osteoporosis group (r = 0.29, p < 0.05), while it was inversely correlated with BMD femoral neck left (r = −0.56, p < 0.001) and BMD femoral neck right (r = −0.37, p < 0.05) in the same group. Moreover, RANKL showed a significant inverse correlation with NTx in the osteopenia group (r = −0.37, p < 0.05). Furthermore, the RANKL/OPG ratio had a positive and significant correlation with BMI (r = 0.34, p < 0.05), BMD femoral neck left (r = 0.36, p < 0.05) and BMD femoral neck right (r = 0.35, p < 0.05) in the osteopenia group. By contrast, it showed a significant inverse correlation with waist to hip ratio in the osteoporosis group (r = −0.38, p < 0.05). Multiple regression analysis showed that OPG contributes to BMD variations in the osteopenia group (p = 0.03). Conclusions: In conclusion, changes in circulating levels of RANKL and OPG might be a protective mechanism contrary to the increased bone loss in postmenopausal women.

Background This study aimed to assess the telomere length and plasma telomere repeat-binding factor 2 (TRF2) levels in addition to other inflammatory markers in children with sickle cell disease (SCD). Methods We enrolled 106 children (90 SCD and 26 controls) aged 1–15 years from the Hematology unit of King Fahad Medical City (KFMC), Saudi Arabia. Genomic DNA extracted from blood and leukocyte TL was determined using quantitative reverse transcription PCR, whereas TRF2, C-reactive protein, interleukin-6, and DNA oxidative damage were determined by using respective commercially available assays. Results Leukocyte TL was inversely correlated with age in the SCD patients (r = −0.24, P = 0.02) and the controls (r = −0.68, P P = 0.003) than controls (8.28 ± 0.73 kb). In contrast, no significant difference in TL among the SCD genotypes (HbSS and HbSβ0) has been observed. A modest, positive correlation was seen between TL and reticulocyte % (r = 0.21; P = 0.06). There were no significant differences in the TL and TRF2 concentrations between subjects with HbSS and HbSβ0 genotypes. Conclusions Short leukocyte TL was significantly associated with SCD. An inverse association was observed between TL and hemoglobin. Hydroxyurea treatment revealed no impact on TL. Impact This study explored the TL and plasma TRF2 in Saudi children with SCD. This is the first documentation that SCD children have shorter TL than their healthy counterparts, and no association between TL and TRF2 has been observed. Hydroxyurea treatment showed no impact on TL in children with SCD. This study is the first of its kind in children with SCD. It will pave the way for another study with a larger sample size in a diverse population to scrutinize these findings better.

Purpose As the world continues to cautiously navigate its way through the coronavirus disease 2019 (COVID-19) pandemic, several breakthroughs in therapies and vaccines are currently being developed and scrutinized. Consequently, alternative therapies for severe acute respiratory coronavirus 2 (SARS-CoV-2) prevention, such as vitamin D supplementation, while hypothetically promising, require substantial evidence from countries affected by COVID-19. The present retrospective case–control study aims to identify differences in vitamin D status and clinical characteristics of hospitalized patients screened for SARS-CoV-2, and determine associations of vitamin D levels with increased COVID-19 risk and mortality. Methods A total of 222 [SARS-CoV-2 (+) N = 150 (97 males; 53 females); SARS-CoV-2 (−) N = 72 (38 males, 34 females)] out of 550 hospitalized adult patients screened for SARS-CoV-2 and admitted at King Saud University Medical City-King Khalid University Hospital (KSUMC-KKUH) in Riyadh, Saudi Arabia from May–July 2020 were included. Clinical, radiologic and serologic data, including 25(OH)D levels were analyzed. Results Vitamin D deficiency (25(OH)D 60 years and pre-existing conditions (p

Objective. To examine differences in maternal serum levels of adipokines (adiponectin, leptin, and resistin) and inflammatory markers (tumor necrosis factor-alpha (TNF-α) and interlukin-6 (IL-6)) from early to midpregnancy among Arab women with or without gestational diabetes mellitus (GDM), along with their links to GDM risk. Methods. This is a multicenter prospective study involving 232 Saudi women attending obstetric care. Both circulating adipokine and markers of inflammation were observed at the first (eight to 12 weeks) and second trimesters (24 to 28 weeks). GDM was screened at 24 to 28 weeks using the International Association of the Diabetes and Pregnancy Study Groups (IADPSG) criteria. Results. Age and body mass index- (BMI-) matched circulating TNF-α was significantly higher in women with GDM in comparison to non-GDM women ( p = 0.01 ). Adiponectin and resistin significantly decreased from the first to second trimester in women without GDM ( p = 0.002 and 0.026, respectively). Leptin presented a significant rise from the first to second trimester in both groups, with a higher increase in women with GDM ( p = 0.013 ). Multivariate logistic regression analysis revealed that TNF-α was significantly correlated with GDM ( p = 0.03 ). However, significance was lost after adjustments for maternal and lifestyle risk factors (OR 23.58 (0.50 to 1119.98), p = 0.11 ). Conclusion. Inflammatory and adipocytokine profiles are altered in Arab women with GDM, TNF-α in particular. Further studies are needed to establish whether maternal inflammatory and adipocytokine profile influence fetal levels in the same manner.

Background Information on the clinical characteristics and outcomes of hospitalized Covid-19 patients with or without diabetes mellitus (DM) is limited in the Arab region. This study aims to fill this gap. Methods In this single-center retrospective study, medical records of hospitalized adults with confirmed Covid-19 [RT-PCR positive for SARS-CoV2] at King Saud University Medical City (KSUMC)-King Khaled University Hospital (KKUH), Riyadh, Saudi Arabia from May to July 2020 were analyzed. Clinical, radiological and serological information, as well as outcomes were recorded and analyzed. Results A total of 439 patients were included (median age 55 years; 68.3% men). The most prevalent comorbidities were vitamin D deficiency (74.7%), DM (68.3%), hypertension (42.6%) and obesity (42.2%). During hospitalization, 77 out of the 439 patients (17.5%) died. DM patients have a significantly higher death rate (20.5% versus 12.3%; p = 0.04) and lower survival time (p = 0.016) than non-DM. Multivariate cox proportional hazards regression model revealed that age [Hazards ratio, HR 3.0 (95% confidence interval, CI 1.7–5.3); p 90 µmol/l [adjusted HR 2.1 (CI 1.3–3.5); p = 0.004] and 25(OH)D 7.5, creatinine > 90 µmol/l and alanine aminotransferase > 65U/l. Conclusion The prevalence of DM is high among hospitalized Covid-19 patients in Riyadh, Saudi Arabia. While DM patients have a higher mortality rate than their non-DM counterparts, other factors such as old age, congestive heart failure, smoking, β-blocker use, presence of bilateral lung infiltrates, elevated creatinine and severe vitamin D deficiency, appear to be more significant predictors of fatal outcome. Patients with acute metabolic dysfunctions, including hyperglycemia on admission are more likely to receive intensive care.

Sarcopenia is the loss of skeletal muscle mass, and is most common in older people. The present multi-center cross-sectional study aimed to determine the prevalence of sarcopenia and possible risk factors among Arab elderly females. A total of 131 ambulatory Saudi elderly females aged 60–85 years (mean age 65.9 ± 5.5 years) were recruited to participate. A general questionnaire with questions related to sociodemographic factors, medical history, diet, physical activity, and lifestyle was administered. Anthropometrics and muscle assessments were done. Fasting blood glucose and lipids were measured routinely. Circulating 25(OH)D and irisin levels were measured using commercially available assays. Sarcopenia was assessed using the criteria of the Asian Working Group for Sarcopenia (AWGS). Over-all prevalence of sarcopenia was 19.8% (26 out of 131 participants). Novel measures such as abdominal volume index (AVI), dietary fiber, and irisin were found to be significantly lower in the sarcopenia group than those without sarcopenia, independent of age. No associations were found with physical activity or dietary and lifestyle habits. In conclusion, sarcopenia is relatively common among Arab elderly females. Longitudinal studies are needed to determine whether lifestyle modifications can decrease the incidence of sarcopenia in this population. Irisin maybe a promising biomarker for sarcopenia but needs to be confirmed using larger sample sizes.

ObjectiveWe aimed to evaluate and compare the impact of COVID-19 lockdown on lifestyle changes and other common related effects of the lockdown in Saudi adults with diabetes mellitus (DM), both type 1 (T1D) and type 2 diabetes (T2D).Methods265 T1D and 285 T2D individuals were included in this cross-sectional survey during lockdown using an online questionnaire and compared with 297 participants without DM. Variables included demographics, treatment changes, use of supplements, change in sleeping habits and physical activity, dietary changes, social and mental health, and education and awareness during COVID-19 lockdown.ResultsThe COVID-19 lockdown was associated with more treatment doses in people with T1D but not in those with T2D (p = 0.003). More participants with T1D and T2D than the control group reported that they felt symptoms of depression during lockdown (ORs of 1.83, p = 0.008 and 2.2, p = 0.001, respectively) and that lockdown affected them psychologically (ORs of 1.64, p = 0.019 and 1.85, p = 0.005, respectively). More participants with T1D than controls reported that their physical activity decreased during lockdown (OR of 2.70, p = 0.024). Furthermore, significantly lesser participants in both DM groups than controls agreed that the health education regarding COVID-19 covered everything (ORs of 0.41, p < 0.001 and 0.56, p < 0.001, respectively for T1D and T2D groups). Regarding dietary habits, the DM groups reported more changes in either the number of daily meals, meal content, or mealtimes than the control group.ConclusionsCOVID-19 lockdown-associated lifestyle changes were more prevalent in individuals with T1D and T2D compared to control. Findings may assist public health authorities in outlining their responses in pandemics and promote healthy lifestyle adaptations in this high-risk cohort to limit adverse effects in future lockdowns.

This 12-month school-based intervention study investigated the effects of hybrid educational lifestyle modifications on glycemic control among Saudi youth with different glycemic statuses. A total of 2600 Arab adolescents aged 12–18 years were recruited from 60 randomly selected schools. Anthropometrics, blood glucose, and HbA1c were measured pre- and post-intervention. Participants were grouped according to baseline HbA1c into normal, prediabetes, and diabetes groups. All participants received lifestyle education at base line and at every 3-month interval to improve diet and exercise behavior. Diabetic and prediabetic participants received a tailored lifestyle intervention. Post-intervention, 643 participants were analyzed as follows: 20 participants from the diabetes group, 39 from prediabetes, and 584 from the normal group. A modest but significant improvement in the glycemic status of diabetic and prediabetic participants was observed, but not in the normal group. In the diabetes group, 11 (55%) participants achieved normal HbA1c levels, 5 had prediabetes levels, and only 4 remained within diabetes HbA1c levels. In the prediabetes group, 34 (87.2%) participants achieved normal HbA1c levels, while 2 (5.1%) participants remained prediabetic and 3 (7.7%) had diabetes HbA1c levels (p < 0.001). This hybrid lifestyle intervention program modestly reduces the risk of T2DM among youth with elevated HbA1c levels. The challenge of sustaining interest in adopting lifestyle changes for a longer duration should be addressed in further studies in this population.

Background The increase in soft drink (SD) consumption is emerging as a serious health issue. Our aim is to explore the prevalence and awareness regarding SD consumption among Saudi students. Methods This cross-sectional study included 1000 apparently healthy Saudi students (527 males, 473 females) aged 16–23 years. A designed questionnaire including various sections was used to obtain the required information. Results The BMI and frequency of SD consumption were significantly higher in males (P Conclusions Arab students exhibited a high prevalence of SD consumption especially in males. Although females showed more awareness and knowledge about SD, various misconceptions were notable in both sexes. New policies, health promotion campaigns must be organized to raise awareness among children and parents. Parents and health educators should motivate and encourage the children to consume more water in the context of a healthy balanced diet.

The incidence of osteoporosis and cardiovascular disease increases with age, and there are potentially shared mechanistic associations between the two conditions. It is therefore highly relevant to understand the cardiovascular implications of osteoporosis medications. These are presented in this narrative review. Calcium supplementation could theoretically cause atheroma formation via calcium deposition, and in one study was found to be associated with myocardial infarction, but this has not been replicated. Vitamin D supplementation has been extensively investigated for cardiac benefit, but no consistent effect has been found. Despite findings in the early 21st century that menopausal hormone therapy was associated with coronary artery disease and venous thromboembolism (VTE), this therapy is now thought to be potentially safe (from a cardiac perspective) if started within the first 10 years of the menopause. Selective estrogen receptor modulators (SERMs) are associated with increased risk of VTE and may be related to fatal strokes (a subset of total strokes). Bisphosphonates could theoretically provide protection against atheroma. However, data from randomised trials and observational studies have neither robustly supported this nor consistently demonstrated the potential association with atrial fibrillation. Denosumab does not appear to be associated with cardiovascular disease and, although parathyroid hormone analogues are associated with palpitations and dizziness, no association with a defined cardiovascular pathology has been demonstrated. Finally, romosozumab has been shown to have a possible cardiovascular signal, and therefore post-market surveillance of this therapy will be vital., SCOPUS: re.j, info:eu-repo/semantics/published

Background In 2016, an expert working group was convened under the auspices of the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO) and formulated consensus recommendations for the conduct of clinical trials for drugs to prevent or treat sarcopenia. Aims The objective of the current paper is to provide a 2020 update of the previous recommendations in accordance with the evidence that has become available since our original recommendations. Methods This paper is based on literature reviews performed by members of the ESCEO working group and followed up with face to face meetings organized for the whole group to make amendments and discuss further recommendations. Results The randomized placebo-controlled double-blind parallel-arm drug clinical trials should be the design of choice for both phase II and III trials. Treatment and follow-up should run at least 6 months for phase II and 12 months for phase III trials. Overall physical activity, nutrition, co-prescriptions and comorbidity should be recorded. Participants in these trials should be at least 70-years-old and present with a combination of low muscle strength and low physical performance. Severely malnourished individuals, as well as bedridden patients, patients with extremely limited mobility or individuals with physical limitations clearly attributable to the direct effect of a specific disease, should be excluded. Multiple outcomes are proposed for phase II trials, including, as example, physical performance, muscle strength and mass, muscle metabolism and muscle-bone interaction. For phase III trials, we recommend a co-primary endpoint of a measure of functional performance and a Patient Reported Outcome Measure. Conclusion The working group has formulated consensus recommendations on specific aspects of trial design, and in doing so hopes to contribute to an improvement of the methodological robustness and comparability of clinical trials. Standardization of designs and outcomes would advance the field by allowing better comparison across studies, including performing individual patient-data meta-analyses, and different pro-myogenic therapies.

Osteoarthritis (OA) is the most common joint condition and, with a burgeoning ageing population, is due to increase in prevalence. Beyond conventional medical and surgical interventions, there are an increasing number of ‘alternative’ therapies. These alternative therapies may have a limited evidence base and, for this reason, are often only afforded brief reference (or completely excluded) from current OA guidelines. Thus, the aim of this review was to synthesize the current evidence regarding autologous chondrocyte implantation (ACI), mesenchymal stem cell (MSC) therapy, platelet-rich plasma (PRP), vitamin D and other alternative therapies. The majority of studies were in knee OA or chondral defects. Matrix-assisted ACI has demonstrated exceedingly limited, symptomatic improvements in the treatment of cartilage defects of the knee and is not supported for the treatment of knee OA. There is some evidence to suggest symptomatic improvement with MSC injection in knee OA, with the suggestion of minimal structural improvement demonstrated on MRI and there are positive signals that PRP may also lead to symptomatic improvement, though variation in preparation makes inter-study comparison difficult. There is variability in findings with vitamin D supplementation in OA, and the only recommendation which can be made, at this time, is for replacement when vitamin D is deplete. Other alternative therapies reviewed have some evidence (though from small, poor-quality studies) to support improvement in symptoms and again there is often a wide variation in dosage and regimens. For all these therapeutic modalities, although controlled studies have been undertaken to evaluate effectiveness in OA, these have often been of small size, limited statistical power, uncertain blindness and using various methodologies. These deficiencies must leave the question as to whether they have been validated as effective therapies in OA (or chondral defects). The conclusions of this review are that all alternative interventions definitely require clinical trials with robust methodology, to assess their efficacy and safety in the treatment of OA beyond contextual and placebo effects. Electronic supplementary material The online version of this article (10.1007/s40520-020-01515-1) contains supplementary material, which is available to authorized users.

Vitamin D is endowed with a number of biological properties, including down-regulation of inflammation, and might contribute to the pathogenesis of autism spectrum disorders (ASD). Vitamin D binds to the vitamin D Receptor (VDR); the biological activity of the ensuing complex depends on VDR FokI, BsmI, ApaI, and TaqI gene polymorphisms. We evaluated such Single Nucletoide Polymorphismsm (SNPs) in a cohort of 100 Italian families with ASD children. FokI genotype distribution was skewed in ASD children compared with their healthy sibs (Pc = 0.03 2 df) and to a group of 170 Italian healthy women (HC) (Pc = 0.04 2 df). FokI genotype and allelic distribution skewing were also observed in mothers of ASD children compared to HC (Pc = 0.04 2 df). Both Transmission Disequilibrium Test for single loci and haplotype analysis distribution revealed a major FokI (C) allele-mediated protective effect, which was more frequently transmitted (73%) than not transmitted to healthy sibs (P = 0.02). A protective FokI-, BsmI-, ApaI-, and TaqI (CCAG) haplotype was more frequently carried by healthy sibs than by ASD children (P = 1 × 10-4 ; OR: 0.1, 95% CI: 0.03-0.4) too. Finally, a strong gene-dose association of FokI (T) allele with both higher Childhood Autism Rating Scale score (Pc = 0.01) and, particularly, with hyperactivity behavior (Pc = 0.006) emerged in ASD children. Because the protein produced by the FokI (T) allele is transcriptionally less active than that produced by the FokI (C) allele, the reduced biological activity of the vitamin D/VDR complex prevalent in ASD could favor ASD- and maternal immune activation- associated inflammation. Vitamin D supplementation might be useful in preventative and rehabilitation protocols for ASD. Autism Res 2020, 13: 680-690. © 2020 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: Vitamin D deficiency and Vitamin D receptor (VDR) polymorphisms are associated with structural and functional brain abnormalities and behavioral disorders. We analyzed the association of VDR gene polymorphisms in a cohort of 100 Italian families with ASD children. A strong correlation between one of the VDR polymorphisms and hyperactivity behavior was evidenced in ASD children. In healthy mothers, the same VDR polymorphism was also correlated with an increased risk of giving birth to children with ASD.

Metabolic syndrome (MetS) is a serious health condition that is becoming extremely threatening in Saudi Arabia. The link between vitamin D receptor (VDR) gene polymorphisms and maternal MetS has been observed in several ethnic groups, but is yet to be clarified in the Arabian population. This study aims to investigate the relationship between the FokI VDR genotype and the risk of MetS and its components in pregnant Saudi women. A cross-sectional study was conducted using 368 pregnant Saudi women on first trimester screened for MetS (44 with MetS and 324 without MetS). Measurements included anthropometrics, glycemic and lipid profile and 25(OH)D. TaqMan genotyping assay was used to determine Fokl VDR genotype of participants. Vitamin D deficiency (25(OH)D FokI VDR genotyping frequencies for FF, Ff, and ff genotypes were 50%, 36.4% and 13.6%, respectively. In controls, the frequencies were 62.7%, 31.4% and 5.9%, respectively. No significant association between the individual MetS components and FokI VDR genotypes were observed. Nevertheless, carriers of the ff allele had a significant risk for full maternal MetS [Odds Ratio 4.2 (95% Confidence Interval 1.4-12.2; adjusted p=0.009). The study suggests that the ff FokI VDR genotype is a genetic marker of maternal MetS in pregnant Arabian women. Prospective studies that include neonatal outcomes may confirm present findings.

Recent literature suggests that sarcopenia, often represented by low lower limbs muscle mass and strength, can be considered a potential risk factor for knee osteoarthritis (OA), but the available literature is still limited. We therefore aimed to investigate whether sarcopenia is associated with a higher risk of radiographic (ROA) and symptomatic knee OA (SxOA) in a large cohort of North American people in the context of the OA initiative. Sarcopenia at baseline was diagnosed in case of low skeletal muscle mass (i.e., lower skeletal mass index) and poor performance in the chair stands test. The outcomes of interest for this study included ROA (radiographical osteoarthritis) if a knee developed a Kellgren and Lawrence (KL) grade ≥2 at follow-up, and SxOA (symptomatic osteoarthritis) defined as new onset of a combination of painful knee OA. Altogether, 2,492 older participants (mean age: 68.4 years, 61.4% females) were included. At baseline, sarcopenia was present in 6.1% of the population. No significant difference in ROA prevalence was observed between those with and without sarcopenia (p=0.76), whilst people with sarcopenia reported a significant higher prevalence of SxOA (p

Premature aging, as denoted by a reduced telomere length (TL), has been observed in several chronic inflammatory diseases, such as obesity and type 2 diabetes mellitus (T2DM). However, no study to date has addressed the potential inflammatory influence of the gut-derived Gram-negative bacterial fragments lipopolysaccharide, also referred to as endotoxin, and its influence on TL in low-grade inflammatory states such as type 2 diabetes mellitus (T2DM). The current study therefore investigated the influence of endotoxin and inflammatory factors on telomere length (TL) in adults with (T2DM: n = 387) and without (non-diabetic (ND) controls: n = 417) obesity and T2DM. Anthropometric characteristics were taken, and fasted blood samples were used to measure biomarkers, TL, and endotoxin. The findings from this study highlighted across all participants that circulating endotoxin (r = −0.17, p = 0.01) was inversely associated with TL, noting that endotoxin and triglycerides predicted 18% of the variance perceived in TL (p &lt, 0.001). Further stratification of the participants according to T2DM status and sex highlighted that endotoxin significantly predicted 19% of the variance denoted in TL among male T2DM participants (p = 0.007), where TL was notably influenced. The influence on TL was not observed to be impacted by anti-T2DM medications, statins, or anti-hypertensive therapies. Taken together, these results show that TL attrition was inversely associated with circulating endotoxin levels independent of the presence of T2DM and other cardiometabolic factors, suggesting that low-grade chronic inflammation may trigger premature biological aging. The findings further highlight the clinical relevance of mitigating the levels of circulating endotoxin (e.g., manipulation of gut microbiome) not only for the prevention of chronic diseases but also to promote healthy aging.

This study aims to investigate the association of vitamin D (VD) knowledge, behavior, and attitude with BMI status among Saudi adults. This cross-sectional online survey included a total of 774 participants (M/F: 239/535). Knowledge about the overall sources of VD was highest in OB participants in correctly identifying sunlight (95.1%; p < 0.001) while significantly more OW participants answered food (83.1%; p = 0.04) and fortified food (66.5%; p = 0.02). However, 18.9% of OB participants also wrongly identified air as a VD source and this was significantly higher than in other groups (p = 0.03). OW participants were 50% less likely to identify salmon and fish oil (odds ratio, OR 0.5 (95% Confidence interval, CI 0.4–0.7); p < 0.01) and 40% more likely to identify chicken (OR 1.4 (1.0–1.9); p < 0.05) as dietary sources of VD than controls. On the other hand, OB participants were almost three times more likely to know that sunlight exposure is the main source of VD than controls (OR 2.65 (1.2–6.0); p < 0.05). In conclusion, while VD knowledge overall was apparently high in Saudi adults regardless of BMI status, the quality of knowledge among OB and OW individuals appear inconsistent, particularly in terms of identifying the right VD sources. Public health awareness campaigns should include the correction of VD misconceptions so that high-risk populations are able to make well-informed decisions in achieving optimal VD levels.

Lipocalin (Lcn2) acts as a mediator of several inflammatory processes. However, evidence on the role of Lcn2 in regulating adiposity and type 2 diabetes mellitus (T2DM) is scarce. Therefore, our study aimed to evaluate the associations between Lcn2 and cardiometabolic parameters among Arab adults with varying degrees of adiposity and insulin resistance. A total of 819 adult Saudi participants (307 males and 512 females) with and without T2DM were included. Anthropometrics, metabolic profile and circulating Lcn2 were assessed. Circulating Lcn2 was significantly highest in the obese group independent of age and sex (p = 0.004), but this significance was lost after stratification to T2DM status. Comparison within age groups revealed that among T2DM participants aged 60-70 years, Lcn2 levels were significantly lower than their younger counterparts in both non-obese and obese groups (unadjusted p = 0.04 and 0.001, respectively). Lcn2 was inversely associated with diastolic blood pressure (R = -0.25, p = 0.01) and triglycerides (R = 0.23; p = 0.04) as well as positively associated with adiponectin (R = 0.27; p = 0.005) among non-obese, non-T2DM participants. In the T2DM/obese group (N = 328), Lcn2 was inversely associated with age (R = -0.15; p = 0.008) and positively associated with HDL-cholesterol (R = 0.12; p = 0.04) and adiponectin (R = 0.17; p = 0.002). Our study suggests that circulating Lcn2 maybe protective against obesity and T2DM, but prospective studies are needed to confirm findings.

Epidemiological studies suggest that the Zinc-α-2-glycoprotein (ZAG) plays significant physiological roles. In this study we investigate whether ZAG could be considered as a clinical biomarker in the diagnosis and prognosis of metabolic syndrome (MetS) in Saudi population. As such insights urgently required for management of MetS. Thus, we have determined serum levels of ZAG in patients with MetS and normal individuals. We have also assessed the correlation between ZAG and different components of MetS. In this case–control study, clinical information of 200 Saudi male and female subjects (age range 30–65) with MetS (n = 100) and healthy controls (n = 100) were extracted from the database of the Chair of Biomarkers of Chronic Disease (CBCD) in King Saud University (KSU), Riyadh, Saudi Arabia. MetS was screened according to NCEP ATP III criteria (National Cholesterol Education Program Adult Treatment Panel III). Fasting glucose and lipid profile levels were measured using Konelab. Serum TNF-α, IL- 6, CRP and ZAG levels were measured using commercially available assays. There was an age-dependent significant increase in ZAG level among MetS subjects than controls (43.8 ± 19.5 vs 48.1 ± 14.8; P = 0.04). A significant inverse correlation between ZAG and serum HDL-cholesterol (r = − 0.20, P P P P

The parathyroid hormone 1 receptor (PTHR1) plays a crucial role in calcium homeostasis and bone metabolism. However, its genetic role in regulating bone turnover markers (BTMs) in postmenopausal osteoporosis (PMO) remains unclear. Herein, we explored parathyroid hormone (PTH) and PTHR gene variant susceptibility to osteoporosis and their association with various circulating BTM and inflammatory markers in postmenopausal women of Arab ethnicity. In total, 600 postmenopausal Arab women (300-PMO and 300-control) were genotyped for selected SNPs in PTH (rs1459015, rs307253, rs6054, rs307247, rs10500783 and rs10500784), PTHR1 (rs6442037, rs1138518, and rs724449 SNPs) and PTHR2 (rs9288393, rs10497900, and rs897083). Anthropometrics, BTMs, and inflammatory markers were measured. Bone mineral density (BMD) was measured at the lumbar spine L1–L4 and the femoral neck using dual-energy X-ray absorptiometry (DXA). PTHR1 rs1138518 genotype C/T was found to be a significant risk factor for PMO ( OR = 1.49 , 95% CI 1.0-2.1, P = 0.03 ). The genotypes C/T and T/T of PTHR1 rs1138518 were associated with 25-hydroxy-vitamin D (25(OH)D) regulation. In the PMO group, carriers of the C/T genotype had significantly lower 25(OH)D levels than carriers of the same genotypes in the control group (59.9 (36.7-92.4) nmol/l and 66.4 (43.5-87.8) nmol/l, respectively; P = 0.048 ]. Our study concludes that the PTHR1 rs1138518 genotype could be a potential risk factor for osteoporosis and 25(OH)D regulation in Arab women with PMO.

Assessment and treatment pathways based on age-specific intervention thresholds in Saudi Arabi can be used to identify patients at high risk of fracture and avoid unnecessary treatment in those at low fracture risk.Intervention thresholds for the treatment of osteoporosis have historically been based on the measurement of bone mineral density. The aim of the present study was to explore treatment paths and characteristics of women eligible for treatment in Saudi Arabia based on fracture probabilities derived from FRAX®.The approach to the setting of intervention and assessment thresholds used the methodology adopted by the National Osteoporosis Guideline Group for FRAX-based guidelines in the UK but based on the epidemiology of fracture and death in Saudi Arabia. The methodology was applied to women age 40 years or more drawn from a tertiary referral population for skeletal assessment. Missing data for the calculation of FRAX was simulated using data from the referral and FRAX derivation cohorts.Intervention thresholds expressed as a 10-year probability of a major osteoporotic fracture ranged from 2.0% at the age of 50 years increasing to 7.6% at the age of 70 years. A total of 163 of 1365 women (11.9%) had a prior fragility fracture and would be eligible for treatment for this reason. An additional 5 women were eligible for treatment in that MOF probabilities lay above the upper assessment threshold. A BMD test would be recommended for 593 women (43.4%) so that FRAX could be recalculated with the inclusion of femoral neck BMD. Of these, 220 individuals would be eligible for treatment after a BMD test and 373 women categorised at low risk after a BMD test.Probability-based assessment of fracture risk using age-specific intervention thresholds was developed for Saudi Arabia to help guide decisions about treatment.

Objective: Vitamin D deficiency has been associated with an increased risk of COVID-19 severity. This multi-center randomized clinical trial aims to determine the effects of 5000 IU versus 1000 IU daily oral vitamin D3 supplementation in the recovery of symptoms and other clinical parameters among mild to moderate COVID-19 patients with sub-optimal vitamin D status. Study Design and Setting: A total of 69 reverse transcriptase polymerase chain reaction (RT-PCR) SARS-CoV-2 positive adults who were hospitalized for mild to moderate COVID-19 disease were allocated to receive once daily for 2 weeks either 5000 IU oral vitamin D3 (n = 36, 21 males, 15 females) or 1000 IU oral vitamin D3 (standard control) (n = 33, 13 males, 20 females). Anthropometrics were measured and blood samples were taken pre- and post-supplementation. Fasting blood glucose, lipids, serum 25(OH)D, and inflammatory markers were measured. COVID-19 symptoms were noted on admission and monitored until full recovery. Results: Vitamin D supplementation for 2 weeks caused a significant increase in serum 25(OH)D levels in the 5000 IU group only (adjusted p = 0.003). Within-group comparisons also showed a significant decrease in BMI and IL-6 levels overtime in both groups (p-values &lt, 0.05) but was not clinically significant in between-group comparisons. Kaplan–Meier survival analysis revealed that the 5000 IU group had a significantly shorter time to recovery (days) than the 1000 IU group in resolving cough, even after adjusting for age, sex, baseline BMI, and D-dimer (6.2 ± 0.8 versus 9.1 ± 0.8, p = 0.039), and ageusia (loss of taste) (11.4 ± 1.0 versus 16.9 ± 1.7, p = 0.035). Conclusion: A 5000 IU daily oral vitamin D3 supplementation for 2 weeks reduces the time to recovery for cough and gustatory sensory loss among patients with sub-optimal vitamin D status and mild to moderate COVID-19 symptoms. The use of 5000 IU vitamin D3 as an adjuvant therapy for COVID-19 patients with suboptimal vitamin D status, even for a short duration, is recommended.

Hip fracture is the most clinically devastating and economically important complication of osteoporosis. Pain, suffering, loss of mobility and independence are some of the devastating consequences of hip fractures. The present study aimed to determine the main characteristics and outcomes of patients with osteoporotic hip fracture and treatment gaps at King Abdulaziz Medical City (KAMC), Riyadh, Saudi Arabia. This is a single-center, retrospective cohort study analyzing charts of patients > 45 years who were admitted for hip fracture secondary to low-grade trauma from 2008 to 2012. A total of 264 patients (50.4% males and 49.6% females) were included. The most common fracture types were trochanter (49%) and femoral neck (46%). History of falls was documented in 115 (43.6%) patients. Bone mineral density (BMD) was assessed in only 41 (15.5%) patients. Majority underwent surgery (92%). Surgical complications occurred in 15 (5.7%) patients and medical complications in 21 (7.9%) patients. Vitamin D and calcium were the most common medications, but given only to 45 (17%) patients. Bone mineral density (BMD) assessment was significantly more frequent post-surgery than pre-surgery (p = 0.03). Very few patients received osteoporosis-specific therapy. F ollow-up revealed that 62 (23.5%) patients died 1 year after surgery. These present findings warrant urgent reassessment of clinical care and treatments provided to patients with osteoporotic hip fractures to prevent recurrent fractures. The introduction of Fracture Liaison Service (FLS) in institutions caring for patients with hip fractures as internationally recommended will definitely change the current status of care.

Summary Objective The aim of this trial was to characterize the beneficial effects of probiotics on decreasing endotoxin levels and other cardiometabolic parameters in Arab patients with type 2 diabetes mellitus (T2DM). Methods Saudi adults with naive T2DM (n = 30; 12 males and 18 females) were randomly allocated to receive twice daily placebo or 2.5 × 109 cfu/g of Ecologic®Barrier (multi-strain probiotics; n = 31; 14 males and 17 females) in a double-blind manner over a 6 month period, respectively. Anthropometrics were measured and fasting blood samples were collected to analyze endotoxin, glycemic parameters [glucose, insulin, c-peptide and homeostasis model assessment for insulin resistance (HOMA-IR)], lipids [triglycerides, total cholesterol, low and high-density lipoprotein (LDL and HDL, respectively) cholesterol and total/HDL-cholesterol ratio], inflammatory markers [tumor-necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and C-reactive protein (CRP)] and adipocytokines [leptin, adiponectin and resistin] at baseline and after 3 and 6 months of intervention. Results Multi-strain probiotics supplementation for 6 months caused a significant decrease in circulating levels of endotoxin by almost 70% over 6 months, as well as glucose (38%), insulin (38%), HOMA-IR (64%), triglycerides (48%), total cholesterol (19%), total/HDL-cholesterol ratio (19%), TNF-α (67%), IL-6 (77%), CRP (53%), resistin (53%), and a significant increase in adiponectin (72%) as compared with baseline. Only HOMA-IR had a clinically significant reduction (−3.4, 64.2%) in the probiotics group as compared to placebo group at all time points. No other clinically significant changes were observed between the probiotic or placebo group at 3 and 6 months in other markers. Conclusion Multi-strain probiotic supplementation over 6 months as a monotherapy significantly decreased HOMA-IR in T2DM patients, with the probiotic treatment group highlighting reduced inflammation and improved cardiometabolic profile. As such, multi-strain probiotics is a promising adjuvant anti-diabetes therapy. Trial registration ClinicalTrials.gov Identifier: NCT01765517 .

There is increasing emphasis on patient-centred research to support the development, approval and reimbursement of health interventions that best meet patients' needs. However, there is currently little guidance on how meaningful patient engagement may be achieved. An expert working group, representing a wide range of stakeholders and disciplines, was convened by the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO) and the World Health Organization (WHO). Through a structured, collaborative process the group generated practical guidance to facilitate optimal patient engagement in clinical development and regulatory decisions. Patient engagement is a relational process. The principles outlined in this report were based on lessons learned through applied experience and on an extensive dialogue among the expert participants. This practice guidance forms a starting point from which tailoring of the approach to suit different chronic diseases may be undertaken.

Prospective studies indicate that the exposure to organochlorine pesticides (OCPs) during fetal life, infancy, and early childhood may be associated with features of neurodevelopmental disorders in children. However, few studies have investigated the concentrations of serum OCPs in children with categorically diagnosed neurodevelopmental disorders. The aim of this study was to assess the concentrations and detection rates of dichlorodiphenyltrichloroethane (DDT) metabolites, hexachlorocyclohexane (HCH) isomers, cyclodienes, and methoxychlor in serum samples of children with autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD), and specific learning disorder (SLD), all of normal intelligence, compared to typically developing controls (TD). In total, 114 schoolchildren, aged 6-13 years old, were assessed and distributed into four groups: ASD (n = 39), ADHD (n = 21), SLD (n = 32), and TD (n = 18). Each clinical group was compared to the TD group. Concentrations of serum OCPs were determined by gas chromatography and are presented as ng/g lipid. Concentrations of β-HCH, the sum of HCH isomers, and o,p'-DDD were significantly higher in ASD children: ASD vs. TD (mean ± SD): 10.5 ± 7.7 vs. 6.1 ± 4.0, (p = 0.049); 12.0 ± 10.3 vs. 6.6 ± 4.0, (p = 0.025); 7.4 ± 6.5 vs. 2.8 ± 2.3, (p = 0.0019), respectively. The detection rates of p,p'-DDT, at least one substance from DDTs detected, and the cyclodiene heptachlor epoxide, were significantly lower in the ASD group: ASD vs. TD: 12.8% vs. 38.9%, (p = 0.037); 69.2% vs. 94.4%, (p = 0.044); 10.3% vs. 38.9%, (p = 0.026), respectively. No significant differences between the ADHD or SLD groups and the TD group were observed. We demonstrated higher serum concentrations and lower detection rates of selected OCPs in ASD than TD children. Our results add to potential neurodevelopmental concerns surrounding OCPs and provide evidence of specificity in the relations between HCHs and ASD.

It is well recognized that poor muscle function and poor physical performance are strong predictors of clinically relevant adverse events in older people. Given the large number of approaches to measure muscle function and physical performance, clinicians often struggle to choose a tool that is appropriate and validated for the population of older people they deal with. In this paper, an overview of different methods available and applicable in clinical settings is proposed. This paper is based on literature reviews performed by members of the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO) working group on frailty and sarcopenia. Face-to-face meetings were organized afterwards where the whole group could amend and discuss the recommendations further. Several characteristics should be considered when choosing a tool: (1) purpose of the assessment (intervention, screening, diagnosis); (2) patient characteristics (population, settings, functional ability, etc.); (3) psychometric properties of the tool (test–retest reliability, inter-rater reliability, responsiveness, floor and ceiling effects, etc.); (4) applicability of the tool in clinical settings (overall cost, time required for the examination, level of training, equipment, patient acceptance, etc.); (5) prognostic reliability for relevant clinical outcomes. Based on these criteria and the available evidence, the expert group advises the use of grip strength to measure muscle strength and the use of 4-m gait speed or the Short Physical Performance Battery test to measure physical performance in daily practice. The tools proposed are relevant for the assessment of muscle weakness and physical performance. Subjects with low values should receive additional diagnostic workups to achieve a full diagnosis of the underlying condition responsible (sarcopenia, frailty or other).

Neck circumference (NC) is a relatively unused index of upper body adiposity. The present study aims to analyze the associations of NC with anthropometric measures of obesity, as well as cardiovascular and metabolic risks in Arab women. This cross-sectional study included 623 women (aged 18–70 years) recruited from different primary care centers in Riyadh, Saudi Arabia. NC, waist circumference (WC), body mass index (BMI), blood pressure, and metabolic and serological markers were measured in all participants. Covariance and regression analyses were used to evaluate the associations between NC and cardiometabolic risk factors. The correlation coefficients of NC and WC with the clinical indices were highly significant (p

RON receptor tyrosine kinase is a transmembrane protein directly involved in suppression of inflammation and its aberrant expression linked to cancers and metastasis. Efforts to block deregulated RON signaling in tumors using small molecule kinase inhibitors or antibodies have been complicated by the presence of unknown number/types of isoforms of RON, which, despite being structurally similar, localize differently and mediate varied functions. Current study was designed to identify the splice variants of RON transcripts formed by skipping of sequences between exons 9 and 14 for better understanding of isoform specific RON signaling in cancers. PCR amplification and bi-directional sequencing of a 901 bp cDNA sequence located between exons 9 to 14 of RON from lung cancer cell lines revealed the presence of two splicing variants formed by skipping of exons 11 and 11-13. Each of these transcripts was found in more than one cell line. Expressed sequence tag (EST) database search indicated that the splicing variant lacking exons 11-13 was a novel one. Here we conclude that the splice variants of RON lacking exon 11 and exons 11-13 were detected in several lung cancer cell lines. Novel variant formed by skipping exons 11-13, the sequence of which code for transmembrane region, is predicted to code for a truncated isoform that may be secreted out. Tumors may antagonize the ligand dependent anti-inflammatory function of wild-type RON by secreting out the ligand binding isoforms.

Studies have explored how vitamin B12 status affects sleep among elders and children, but this remains to be investigated among young adults. We used the Pittsburgh Sleep Quality Index (PSQI) to assess the association between serum vitamin B12 and sleep among female college students in Saudi Arabia. In this cross-sectional study, we enrolled 355 participants (age (years), 20.7 ± 1.5, body mass index, 23.6 kg/m2 ± 5.2) at King Saud University, Riyadh, Saudi Arabia. Fasting blood samples were analyzed regarding the serum vitamin B12 and blood lipids. Anthropometric, socio-demographic, clinical history, stress, physical activity, and dietary data were collected. We assessed the sleep statuses of the participants using the PSQI. Around 72% of the participants were “poor” sleepers (PSQI &gt, 5). Subgroup analysis within the tertiles showed that participants with higher vitamin B12 in the second and third tertiles reported better scores for sleep quality (B ± SE = −12.7 ± 5.6, p = 0.03, B ± SE = −32.7 ± 16.4, p = 0.05, respectively) and also reported a lower use of sleep medication (B ± SE = −21.2 ± 9.9, p = 0.03, in the second tertile only), after adjusting for the waist–hip ratio and stress. However, sleep was not found to be directly associated with either serum vitamin B12 or dietary vitamin B12. In conclusion, the serum vitamin B12 results show that the participants with higher vitamin B12 in the second and third tertiles reported better scores on the sleep quality scale and a lower use of sleep medication. However, no such associations were observed with the overall PSQI. More studies with larger sample sizes are needed to establish a direct relationship between sleep and vitamin B12.

The study aimed to explore the influence of the COVID-19 lockdown on the mental status and dietary intake of residents in Saudi Arabia. In this cross-sectional study, an online survey was conducted from 11 May to 6 June 2020 corresponding to almost two weeks during and after Ramadan (23 April–23 May 2020). The Patient Health Questionnaire was used to assess anxiety, depression, and insomnia. Logistic regression analysis was used to identify predictors of anxiety, depression, and insomnia. The prevalence of anxiety, depression, and insomnia among the participants was 25.4%, 27.7%, and 19.6%, respectively. Participants aged ≥50 years with high income (≥8000 SAR) were at a lower risk of developing depression, whereas participants of the same age group with income 5000–7000 SAR were at high risk of developing anxiety. Students and master-educated participants suffer from median elevated depression and are required to take more multivitamins and vitamin D than others. Anxiety and depression were more common among married participants with low income. There is a wide range of Saudi residents who are at a higher risk of mental illness during the COVID-19 pandemic. Policymakers and mental healthcare providers are advised to provide continuous monitoring of the psychological consequences during this pandemic and provide mental support.

Aims/Introduction This 6‐month interventional study aimed to investigate the effectiveness of different educational programs among Saudi women with prediabetes referred by primary care. Materials and Methods A total of 253 (100 group education program [GEP], 84 WhatsApp education program [WEP] and 69 control group [CG]) eligible participants were invited to take part in the study, out of whom 120 received intervention (40 GEP, 43 WEP and 37 CG). GEP participants received focused, individualized lifestyle modification advice with bimonthly support sessions, WEP participants received the same intervention, but delivered through social media (WhatsApp). The CG received standard care. Anthropometrics, biochemical profiles and macronutrient intake were measured at baseline, and 3 and 6 months. The primary end‐points were glycated hemoglobin and weight, with lipids and dietary changes as secondary outcomes. Results Glycated hemoglobin significantly improved in all groups post‐intervention (GEP baseline 6.0 ± 0.2 vs 6 months 5.5 ± 0.54; P, Education programs whether delivered through a focused educational group, social media or standard care, are equally efficacious in improving HbA1c levels among Saudi women with prediabetes. This may have been due to reduced energy intakes and favourable increases in physical activity. Digital platforms may offer a more accessible and less resource intensive option that is equally effective.

This retrospective study aimed to characterize comorbidities and associated with mortality among hospitalized adults with Covid-19 managed as perthe Saudi Ministry of Health protocol in a specialized tertiary hospital in Riyadh, Saudi Arabia. Medical records of 300 adult patients with PCR-confirmed SARS-CoV2 infection and admitted in King Salman Hospital (KSH) from May 1 to July 31, 2020 were included. Medical history, management and outcomes were noted. Males significantly outnumber females (259 versus 41). South Asians comprise 41% of all admitted patients. Mortality rate was 10% and highest among Saudi males (28.9%). Type 2 diabetes mellitus (T2DM) was the most common comorbidity (45.7%). Almost all patients (99%) had pneumonia. Patients 50 years were three times more likely to die (confidence interval, CI 1.3-6.9; p = 0.01) from Covid-19. Congestive heart failure (odds ratio OR 19.4, CI-1.5-260.0; p = 0.02) and acute kidney injury (OR 11.7, CI-4.7-28.6; p 0.001) were significantly associated with higher mortality. Dexamethasone use significantly improved the final outcome based on net reclassification improvement (NRI) and integrated discrimination improvement (IDI) (p 0.05). In this single-center study, T2DM was very common among hospitalized Covid-19 patients. Patients 50 years, those with congestive heart failure and acute kidney injury are at higher risk for worse Covid-19 outcome.

Objectives Vitamin D status in patients with COVID-19 is an on-going controversial issue. This study aims to determine differences in the serum 25(OH)D concentrations of Arab Gulf adult residents screened for SARS-CoV-2 and its association with risk of COVID-19 infection together with other comorbidities. Methods In this multi-center, case–control study, a total of 220 male and female adults presenting with none to mild symptoms were screened for COVID-19 (n = 138 RT-PCR-confirmed SARS-CoV-2 positive and 82 negative controls). Medical history was noted. Anthropometrics were measured and non-fasting blood samples were collected for the assessment of glucose, lipids, inflammatory markers and serum 25(OH)D concentrations. Results Serum 25(OH)D levels were significantly lower in the SARS-CoV-2 positive group compared to the negative group after adjustment for age and BMI (52.8 nmol/l ± 11.0 versus 64.5 nmol/l ± 11.1; p = 0.009). Being elderly (> 60 years) [Odds ratio 6 (95% Confidence Interval, CI 2–18; p = 0.001) as well as having type 2 diabetes (T2D) [OR 6 (95% CI 3–14); p Conclusions Among Arab Gulf residents screened for SARS-CoV-2, serum 25(OH) D levels were observed to be lower in those who tested positive than negative individuals, but it was the presence of old age, diabetes mellitus and low-HDL-c that were significantly associated with risk of COVID-19 infection. Large population-based randomized controlled trials should be conducted to assess the protective effects of vitamin D supplementation against COVID-19.

Objective. The role of lipid metabolism disorders in the pathogenesis of T2DM has been recognized. Lipid droplets (LDs) are dynamic organelles that store lipids. Perilipin 3 (PLIN3) is one of the five LD coat proteins that is relatively understudied as compared to other LDs. This study is aimed at determining levels of PLIN3 among adults with varying levels of obesity and insulin resistance to determine metabolic associations of PLIN3. Methodology. A total of 280 Saudi adults ( n = 127 males ; n = 153 females ) were randomly recruited and divided into three groups according to their body mass index (BMI) and fasting glucose levels: healthy and lean (HL), obese and T2DM (OD), or obese and nondiabetic (OND). Lipid profiles, fasting glucose levels, insulin, and perilipin 3 levels were measured. Results. Circulating PLIN3 was significantly lower in the OD group [8.3 ng/mL (1.2–22.5; p < 0.001 )] than the HL group [23.1 ng/mL (6.2–39.1; p < 0.001 )]. Triglycerides, total cholesterol, glucose, and insulin levels were inversely correlated with PLIN3 in all subjects. Lastly, glucose, insulin, and total cholesterol cumulatively predict circulating levels of PLIN3 by as much as 11% of the variances perceived ( p < 0.001 ). Conclusion. Circulating PLIN3 is significantly associated with insulin resistance markers and maybe a promising candidate as a protective biomarker for T2DM.

NLRP3 inflammasome is one of the multimeric protein complexes of the nucleotide-binding domain, leucine-rich repeat (NLR)-containing pyrin and HIN domain family (PYHIN). When activated, NLRP3 inflammasome triggers the release of pro-inflammatory interleukins (IL)-1β and IL-18, an essential step in innate immune response; however, defective checkpoints in inflammasome activation may lead to autoimmune, autoinflammatory, and metabolic disorders. Among the consequences of NLRP3 inflammasome activation is systemic chronic low-grade inflammation, a cardinal feature of obesity and insulin resistance. Understanding the mechanisms involved in the regulation of NLRP3 inflammasome in adipose tissue may help in the development of specific inhibitors for the treatment and prevention of obesity-mediated metabolic diseases. In this narrative review, the current understanding of NLRP3 inflammasome activation and regulation is highlighted, including its putative roles in adipose tissue dysfunction and insulin resistance. Specific inhibitors of NLRP3 inflammasome activation which can potentially be used to treat metabolic disorders are also discussed.

In this narrative review, the role of vitamin D deficiency in the pathophysiology, healing of fragility fractures, and rehabilitation is discussed. Vitamin D status can be assessed by measuring serum 25(OH)-vitamin D level with standardized assays. There is a high prevalence of vitamin D insufficiency (25(OH)D < 50 nmol/l (i.e., 20 ng/mL)) or deficiency (25(OH)D < 25 nmol/l (i.e., 10 ng/mL)) in patients with fragility fractures and especially in those with a hip fracture. The evidence on the effects of vitamin D deficiency and/or vitamin D supplementation on fracture healing and material osseointegration is still limited. However, it appears that vitamin D have a rather positive influence on these processes. The fracture liaison service (FLS) model can help to inform orthopedic surgeons, all caregivers, and fractured patients about the importance of optimal vitamin D status in the management of patients with fragility fractures. Therefore, vitamin D status should be included in Capture the Fracture (R) program as an outcome of FLS in addition to dual-energy X-ray absorptiometry (DXA) and specific antiosteoporosis medication. Vitamin D plays a significant role in the pathophysiology and healing of fragility fractures and in rehabilitation after fracture. Correction of vitamin D deficiency should be one of the main outcomes in fracture liaison services.

Widespread vitamin D deficiency (serum 25-hydroxyvitamin D 50 nmol/L) in Saudi Arabia (SA) has been documented, yet a time trend is needed to establish where the prevalence is headed. This study aims to fill this gap.This cross-sectional series (N = 7360) were conducted in the central region of SA from 2008 to 2017. Participants of all ages were taken from multiple cohorts that included the Biomarker Screening in Riyadh (2008-2010; N = 1460), the Osteoporosis Registry (2014-2017; N = 1225), Gestational Diabetes Mellitus cohort (2014-2017, N = 281), Vitamin D School Project (2011-2017; N = 3039) and Prediabetes cohort (2012-2017; N = 1355) master databases.Vitamin D deficiency in SA has a 10-year prevalence of 73.2 %. Between 2008-2017, the prevalence of vitamin D deficiency decreased from 87.1% to 64.7% for participants aged 18-40 years (p-trend0.001), and from 86.2% to 45.7% in participants aged40 years (p-trend0.001). During this period, vitamin D deficiency in females decreased from 80.1% to 69.6% (p-trend0.001), whereas in males, it decreased from 93.2% to 49.3% (p-trend0.001). Serum 25(OH)D was observed to have an overall increase of 2.2 ± 0.1 nmol/l (p 0.001) along with the seasonally adjusted annual increase of 1.3 ± 0.2 nmol/l from 2008 to 2017 (p 0.001).The decreasing trend in vitamin D deficiency in SA across all demographics suggests successful public health campaigns over time. It will be interesting to investigate further whether the general improvement in the vitamin D status at the community level also translated in lesser incidences of vitamin d-related diseases over time.

Dietary intake influences gut microbiota activity. Nevertheless, there is a lack of evidence available that illustrates the acute effects of high glucose meal on metabolic endotoxemia. The present study assessed the acute impact of high glucose meal on endotoxemia and other clinical parameters in Saudi females with varying degrees of glycemia.\ud \ud The subjects were 64 consenting pre-menopausal women, grouped into 3: control [n = 14 lean, non-T2DM, BMI = 22.2 ± 2.2 kg/m2]; overweight [n = 16, non-T2DM, BMI = 28.5 ± 1.5 kg/m2] and T2DM [n = 34, BMI = 35.2 ± 7.7 kg/m2]. After an overnight fast, all subjects were given a standardized high-glucose (75 g) meal. Anthropometrics were taken and blood samples were withdrawn at baseline and postprandial (0, 2 and 4-hours), serum glucose, endotoxin and lipid profile were quantified.\ud \ud At baseline, total cholesterol, LDL-cholesterol, triglycerides and serum glucose levels were significantly higher (P values

Vitamin D (VD) has been observed to have anti-inflammatory properties. However, the effects of VD supplementation on the serum amyloid P component (SAP) has not been established. This study aimed to investigate the effect of VD supplementation on serum SAP levels in Arab adults. A total of 155 VD-deficient adult Saudis (56 males and 99 females) were recruited in this non-randomized, 6-month, single-arm trial. The intervention was as follows, cholecalciferol 50,000 international units (IU) every week for the first 2 months, followed by 50,000 twice a month for the next two months, and for the last two months, 1000 IU daily. Serum 25(OH)D, SAP, C-reactive protein (CRP), lipid profile, and glucose were assessed at baseline and post-intervention. At post-intervention, VD levels were significantly increased, while SAP levels significantly decreased in all study participants. Remarkably, this reduction in SAP was more significant in males than females after stratification. SAP was inversely correlated with VD overall (r = &minus, 0.17, p &lt, 0.05), and only in males (r = &minus, 0.27, p &lt, 0.05) after stratification according to sex after 6 months of VD supplementation. Such a relationship was not observed at baseline. VD supplementation can favorably modulate serum SAP concentrations in Arab adults, particularly in males.

Public health endorsements during the present COVID-19 pandemic has led the governments of largely affected countries to imply policies that restrict social mobility to slow COVID-19 spread. The study aimed to explore the effects of COVID-19 home quarantine on lifestyle and health behavior of Saudi residents. An online survey in Saudi Arabia was launched from May 11 to June 6, 2020. The survey was designed by multidisciplinary scientists and academics uploaded and shared through the Google platform in Arabic and English languages. Questions presented related to responses “before” and “during” COVID-19 home quarantine. A total of 1965 respondents participated and were included in the analysis [921 (47.0%) males and 1044 (53.0%) females]. Non-Saudis were more likely to increase their physical activity during quarantine [odds ratio (95% confidence interval 1.41 (1.11–1.79); p p p p = 0.019). The lockdown imposed in Saudi Arabia modestly but significantly impacted physical activity and dietary behaviors of several citizens and residents in an unhealthy way. Interventions to alleviate these acute adverse lifestyle behaviors during pandemic should be formulated.

An abnormal lipid profile is an independent risk factor for cardiovascular diseases. The relationship between vitamin B12 deficiency and lipid profile is inconclusive, with most studies conducted in unhealthy populations. In this study, we aimed to assess the relationship between serum vitamin B12 levels and lipid profiles in a cross-sectional study that included 341 apparently healthy Saudi women, aged 19&ndash, 30 years, from different colleges at King Saud University, Saudi Arabia. Sociodemographic, anthropometric, biochemical, and lifestyle data were collected, including diet and physical activity. Serum vitamin B12 deficiency was defined as serum B12 level of &lt, 148 pmol/L. The prevalence of vitamin B12 deficiency was approximately 0.6%. Using multivariable linear regression models, serum vitamin B12 levels were found to be inversely associated with total cholesterol (B = &minus, 0.26, p &lt, 0.001), low-density lipoprotein cholesterol levels (B = &minus, 0.30, 0.001), and triglyceride (B = &minus, 0.16, 0.01) after adjusting for potential confounders, while obesity indices of body mass index, central obesity, and fat percentage showed no association. Therefore, we conclude that low serum vitamin B12 levels are independently associated with abnormal lipid profiles in healthy young Saudi women. Further interventional studies are needed to determine whether improving serum vitamin B12 levels in a healthy population can improve lipid profiles.

A consensus platform is provided by the experts of the Gulf Cooperation Council (GCC) countries’ respective osteoporosis societies, on which specific guidelines can be developed further for regional use on the assessment and treatment of postmenopausal women at risk from fractures due to osteoporosis. Guidance is provided in a Gulf Cooperation Council (GCC) country setting on the assessment and treatment of postmenopausal women at risk from fractures due to osteoporosis, which is an adaptation of the European guidance by Kanis et al., jointly published by the International Osteoporosis Foundation and the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO). The respective osteoporosis societies of the Gulf Cooperation Council (GCC) countries assembled for a unifying consensus on the diagnosis and management of osteoporosis in postmenopausal women for the region. The Chair for Biomarkers of Chronic Diseases (CBCD) in King Saud University (KSU), Riyadh, Kingdom of Saudi Arabia (KSA), in cooperation with the Saudi Osteoporosis Society (SOS), hosted regional experts and respective leaders from different GCC osteoporosis societies, together with an adviser from the ESCEO. An assembly of experts representing the different osteoporosis societies from Saudi Arabia, the UAE, Bahrain, Oman, and Kuwait gathered on February 15–16, 2019 in Riyadh, KSA for the formulation of a general osteoporosis consensus for the region. The following areas were covered: diagnosis of osteoporosis and assessment of fracture risk; general and pharmacological management of osteoporosis; and hip fractures, vitamin D, recommendation on which FRAX tool to follow, and the importance of country-specific FRAX® and fracture liaison services for secondary fracture prevention. A platform is provided on which specific guidelines can be developed for regional use in GCC.

The objective of this study was to examine the awareness, knowledge, and habits regarding dietary fiber intake and to analyze its relationship with self-reported health status among Saudi adults. A survey-based study using face-to-face interview was designed, and 1363 apparently healthy adult Saudi males and females participated. Most participants were females (81.2%), aged 25 and above (87.2%), and were educated at least up to the secondary level of education (80.8%). The majority of the participants were aware of the role of fiber-rich foods in health conditions such as obesity (70.5%), cardiovascular diseases (68.9%), and regulation of blood sugar (68.9%), with females significantly having higher nutrition knowledge than males. A disconnect in translating this nutrition knowledge was observed particularly in food choices when eating out, where preferences for white bread (84.4%), fried potatoes (69.9%) and peeled fruits (60.6%) were significantly higher than preferences for cooked vegetables (29.6%) and brown bread (18.1%). The most common reason for this disconnect was due to perception that foods rich in dietary fibers were expensive (72.1%), have less health benefits (56.5%), were not readily available (51.6%), and participants&rsquo, disliking of the taste (52.8%). Participants in the highest quartile (Q4) for dietary fiber consumption reported a lower prevalence of constipation (odds ratio, 95% confidence interval of 0.40, 0.28&ndash, 0.57, p &lt, 0.01), high cholesterol (0.43, 0.27&ndash, 0.68, p &lt, 0.01) and obesity (0.67, 0.44&ndash, 0.98, p = 0.03) than participants in the lowest quartile (Q1). Dietary fiber intake appears to be protective against constipation, high cholesterol and obesity in Saudi adults. However, a disparity observed between knowledge and attitude towards intake of dietary fibers could limit its health benefits. Further studies including adolescents should be conducted to impart knowledge on the emotional, cognitive and sensory factors related to food choices in order to minimize the gap between nutrition knowledge and the consumption of healthy high-fiber diets.

A summary of recommendations is given within the Gulf Cooperation Council (GCC) setting on the assessment and management of vitamin D deficiency in the region. An assembly of 11 regional experts gathered to formulate an all-inclusive approach to vitamin D deficiency within GCC. Several gaps were identified before regional guidelines could be developed. These include adequacy and standardization of vitamin D testing, frequency of repeated testing and reference ranges, distinguishing prevention from the treatment of vitamin D deficiency, quality assurance of vitamin D products sold within GCC including contents and origins of products, and cut-points for vitamin D levels in local populations. A platform is created that can be further developed for overall regional implementation.