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1.
J Anxiety Disord ; 103: 102856, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38554604

ABSTRACT

AIMS: There is ongoing debate about the extent to which the epidemiology of OCD is similar across the world, given the lack of nationally representative data from key regions like the Middle East and North Africa. Using the nationally representative dataset from the Saudi National Mental Health Survey (SNMHS), we aimed to delineate the epidemiological profile of OCD in the Saudi population. METHODS: A subsample of 1981 participants from the SNMHS was assessed. Prevalence estimates and correlates of OCD were determined using logistic regressions and cross tabulations. RESULTS: The lifetime, 12-month, and 30-day prevalence estimates for OCD were 4.2%, 1.8%, and 1.6%, respectively, with hoarding being the most common symptom dimension. The mean age-of-onset of OCD was 16.8 years. In over two-thirds of respondents with lifetime (72.2%) or 12-month (71.2%), OCD was accompanied by comorbid mental disorder, particularly impulse control, anxiety, and mood disorders. Among individuals with 12-month OCD, 77.5% reported severe impairment, and only 9.2% received treatment. CONCLUSIONS: In Saudi Arabia, OCD is a prevalent and persistent condition, characterized by early onset, high odds of mental comorbidity, and significant associated impairment. These findings emphasize the universality of OCD epidemiology and the need for improved diagnosis and treatment globally.


Subject(s)
Obsessive-Compulsive Disorder , Humans , Adolescent , Saudi Arabia/epidemiology , Obsessive-Compulsive Disorder/diagnosis , Obsessive-Compulsive Disorder/epidemiology , Obsessive-Compulsive Disorder/psychology , Anxiety Disorders/psychology , Comorbidity , Surveys and Questionnaires , Prevalence , Health Surveys
2.
J Affect Disord ; 352: 429-436, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38382818

ABSTRACT

OBJECTIVE: Suicidal thoughts and behaviors (STB) constitute an escalating public health concern globally. Despite the growing burden of suicidal ideation, plan, and attempts, national information on the trends of STB is lacking in the Kingdom of Saudi Arabia (KSA). Therefore, we aim to report on the prevalence, correlates, and treatment-seeking behaviors associated with STB in the country using nationally representative information from The Saudi National Mental Health Survey (SNMHS). METHODS: The SNMHS is a national household survey of Saudi citizens aged 15-65 (n = 4004). The adapted Composite International Diagnostic Interview (CIDI) 3.0 was administered to produce lifetime and 12-month prevalence and treatment estimates of STB in the KSA. Associated correlates were calculated using cross tabulations and logistic regressions. RESULTS: Suicidal ideation, plan, and attempt had respective lifetime prevalence rates of 4.90 %, 1.78 %, and 1.46 %; 12-month prevalence rates of 1.82 %, 0.89 %, and 0.63 %. Significant correlates of STB include younger age, female gender, low education, urban rearing, and singe marital status. STB were also significantly associated with the presence of prior mental disorders, childhood adversities, and low treatment-seeking. CONCLUSIONS: High unmet need and significant sociocultural and psychological risk factors have been identified in association with STB in the KSA. Given the community-based nature of the SNMHS and the limited national data on STB in the Middle East and North Africa region, our findings can extend to inform the necessary healthcare policies, treatment plans, and prevention strategies needed to alleviate the burdens of STB in the region.


Subject(s)
Mental Disorders , Suicidal Ideation , Humans , Female , Child , Suicide, Attempted/psychology , Saudi Arabia/epidemiology , Mental Disorders/psychology , Surveys and Questionnaires , Prevalence , Risk Factors
3.
Int J Soc Psychiatry ; 70(1): 166-181, 2024 Feb.
Article in English | MEDLINE | ID: mdl-37740657

ABSTRACT

INTRODUCTION: Social determinants of health (SDH) influence and modify the risk for mental health disorders. To our knowledge, no study has explored SDH in the context of mental health in Saudi Arabia (SA) using population-based data. This study investigated the association between several SDH and anxiety and mood disorders in SA. METHODS: We utilized data from the nationally-representative Saudi National Mental Health Survey (SNMHS) conducted in 2014 to 2016. This study examined associations between personal-level, socioeconomic, physical health, and family environment characteristics and anxiety and mood disorders. Participants were classified as having anxiety-only disorders, mood-only disorders, or comorbidity of both disorders. Multinomial logistic regression models were employed to examine the associations between SDH and anxiety and/or mood disorders, comparing them to participants who had not experienced these disorders. RESULTS: A total of 4,004 participants were included in this analysis; the lifetime prevalence of disorders was: anxiety only (18%), mood only (3.8%), and comorbidity of both (5.3%). Regression models indicated that females, young adults (26-35 years), individuals with a higher level of education, and those who were separated or widowed had higher odds of experiencing anxiety and/or mood disorders. Furthermore, there was a significant and direct association between having physical chronic conditions and all three categories of anxiety and mood disorders. Experiencing Adverse Childhood Events (ACEs) was also associated with a significant risk of developing anxiety and/or mood disorders, with the highest risk associated with physical or sexual abuse, followed by violence and neglect. CONCLUSION: This study underscores the correlation between several personal-level, socioeconomic, and environmental SDH and anxiety and mood disorders in SA. These findings provide a foundation for future analyses examining the intricate interplay between upstream and downstream SDH in SA. Such research can enhance local scientific knowledge, aid in planning for social services, and inform policy decisions and treatment strategies.


Subject(s)
Mental Disorders , Mood Disorders , Female , Young Adult , Humans , Child , Mood Disorders/epidemiology , Mood Disorders/psychology , Social Determinants of Health , Saudi Arabia/epidemiology , Mental Disorders/epidemiology , Mental Disorders/psychology , Anxiety , Health Surveys
4.
Front Public Health ; 11: 1238326, 2023.
Article in English | MEDLINE | ID: mdl-38089017

ABSTRACT

Introduction: Comorbidities of mental disorders and chronic physical conditions are a common medical burden reported among Western countries. National estimates of such comorbidities among the general population of Arab countries like Saudi Arabia are unknown. This study examined the prevalence of lifetime chronic physical conditions among the Saudi general population with DSM-IV 12-month mental disorders, and the associations with disability in the Kingdom of Saudi Arabia (KSA). Methods: The Saudi National Mental Health Survey, a cross-sectional household study - part of the World Mental Health (WMH) Survey Consortium - was conducted between 2013-2016 in the KSA, with 4,001 Saudi citizens aged 15-65 (response rate 61%). The World Health Organization Composite International Diagnostic Interview 3.0 was used to assess prevalence of lifetime chronic physical conditions and 12-month mental disorders; disability was measured in terms of days out of role. Results: The prevalence of any comorbid 12-month mental disorder among those with chronic physical conditions was 24%. Major depressive disorder, social phobia, and adult separation anxiety disorder were the most common comorbid mental disorders across all chronic physical conditions. Gender, education, income, urbanicity, region, and employment were associated with the presence of any chronic physical condition. Respondents with mental / physical comorbidities had 2.97 days out of role (on average) in the last 30 days. Conclusion: Comorbidities of mental disorders and chronic physical conditions are common among Saudis. National efforts are needed to increase awareness of such comorbidities among the general population, and develop prevention and treatment services tailored to the needs of individuals at-risk for comorbidities.


Subject(s)
Depressive Disorder, Major , Mental Disorders , Adult , Humans , Depressive Disorder, Major/epidemiology , Saudi Arabia/epidemiology , Cross-Sectional Studies , Mental Disorders/epidemiology , Mental Disorders/therapy , Surveys and Questionnaires , Chronic Disease , Health Surveys
5.
BMJ Open ; 13(10): e072115, 2023 10 06.
Article in English | MEDLINE | ID: mdl-37802615

ABSTRACT

OBJECTIVE: To assess prevalence and correlation of factors of family burden associated with mental and physical disorders in the general population of Saudi Arabia. SETTING AND PARTICIPANTS: A secondary analysis of data from the Saudi National Mental Health Survey (SNMHS). OUTCOME MEASURES: Mental and physical health disorders of first-degree relatives and objective (time, financial) and subjective (distress, embarrassment) family burden. RESULTS: We found significant caregiver burden for family members with mental health disorders. Around one-third of the sample was providing care for a family member with a health issue. Within this group, 40% had a mental health diagnosis. 73% of the study population reported experiencing some form of burden as a result of the care they are obligated to provide for their family members. We found the highest burden on male caregivers, in providing care for family members with serious memory disorders, mental retardation, schizophrenia or psychosis, followed by, alcohol and drug disorders, anxiety, depression or manic depression. CONCLUSION: Our findings for family burden were statistically significant, indicating potential negative impact on caregiver coping ability with the demands of caring for family members with health issues. A comprehensive review of national mental health policies is required to integrate aspects of community mental health promotion, scale-up prevention, screening interventions and social support to protect against the difficulties of mental illness and reduce the burden on caregivers, the family, society, health system and the economy.


Subject(s)
Mental Disorders , Psychotic Disorders , Schizophrenia , Humans , Male , Saudi Arabia/epidemiology , Mental Disorders/epidemiology , Adaptation, Psychological , Caregivers/psychology , Family/psychology , Health Surveys
6.
Sci Rep ; 13(1): 6186, 2023 04 15.
Article in English | MEDLINE | ID: mdl-37061556

ABSTRACT

Previous global and regional studies indicate that adolescents and young adults (i.e., youth) are affected by various mental disorders with lifelong consequences. However, there are no national estimates of mental disorders prevalent among Saudi youth. Using data from the Saudi National Mental Health Survey (SNMHS), we examined the lifetime prevalence, treatment, and socio-demographic correlates of mental disorders among Saudi youth (aged 15-30). A total of 4004 interviews were conducted using the adapted Composite International Diagnostic Interview (CIDI 3.0). Cross tabulations and logistic regression were used to generate estimates for the SNMHS youth sample (n = 1881). The prevalence of a mental disorder among Saudi youth was 40.10%, where anxiety disorders affected 26.84% of the sample, followed by disruptive behavior disorders (15.44%), mood disorders (9.67%), substance use disorders (4%) and eating disorders (7.06%). Sex, education, parental education, income, marital status, region, and family history of disorders were significant correlates of various classes of mental disorders. Only 14.47% of Saudi youth with any mental disorder received treatment for a lifetime disorder. Age, parental education, and family history of disorders emerged as significant correlates of mental health treatment. Lifetime mental disorders are highly prevalent among Saudi youth. There is an unmet need for culturally sensitive and age-appropriate treatment of lifetime mental disorders among youth in Saudi Arabia.


Subject(s)
Mental Disorders , Young Adult , Humans , Adolescent , Prevalence , Saudi Arabia/epidemiology , Mental Disorders/epidemiology , Mental Disorders/therapy , Mental Disorders/psychology , Mood Disorders/diagnosis , Anxiety Disorders/epidemiology , Anxiety Disorders/therapy , Anxiety Disorders/diagnosis , Health Surveys , Diagnostic and Statistical Manual of Mental Disorders
7.
Int J Soc Psychiatry ; 69(5): 1121-1133, 2023 08.
Article in English | MEDLINE | ID: mdl-36825615

ABSTRACT

BACKGROUND: While global studies demonstrated that features of urban living are associated with the risk of developing mental disorders, there remains a significant knowledge gap surrounding this topic in the Middle East and North Africa region. AIMS: This study aims to assess the prevalence, severity, correlates, and treatment of mental disorders in Riyadh City by examining certain aspects of urban living such as exposure to traumatic events, early exposure to urbanization, and seeking treatment. METHODS: The Saudi National Mental Health Survey is a community epidemiological survey in a nationally representative sample of citizens aged 15 to 65 in KSA. The World Health Organization Composite International Diagnostic Interview (CIDI 3·0) was used to estimate the 12-month prevalence of common mental disorders. RESULTS: The prevalence of any mental disorder in Riyadh City was 29.2%. The most common disorders were anxiety disorders and mood disorders. Female, young, and previously married respondents were at higher risk for developing mental disorders. Exposure to traumatic events was associated with all types of mental disorders. Only 2.9% of those with any mental disorder sought mental health treatments. CONCLUSIONS: We found a high prevalence of mental disorders in Riyadh City that could be attributed to certain features of urban living. These results may point to potential interventions in urban areas that can mitigate the adverse consequences of urban living and promote the salutogenic aspects of cities.


Subject(s)
Mental Disorders , Mental Health , Humans , Female , Saudi Arabia/epidemiology , Cities , Urbanization , Mental Disorders/epidemiology , Mental Disorders/therapy , Anxiety Disorders/epidemiology , Prevalence , Health Surveys
8.
Int J Eat Disord ; 55(11): 1541-1552, 2022 11.
Article in English | MEDLINE | ID: mdl-35932093

ABSTRACT

OBJECTIVE: Limited studies have been conducted in the Kingdom of Saudi Arabia on eating disorders (EDs). This study presents national epidemiological survey data on the prevalence and correlates of anorexia nervosa (AN), bulimia nervosa (BN), and binge-eating disorder (BED) and their association with other mental health disorders, impairment in role functioning, and individual help-seeking behaviors in the Saudi National Mental Health Survey (SNMHS). METHOD: A face-to-face survey was conducted in a nationally representative household sample of Saudi citizens aged 15-65 (n = 4004). The Composite International Diagnostic Interview (CIDI 3.0) was used to produce estimates of lifetime and 12-month prevalence and treatment of common DSM-IV mental disorders. RESULTS: Twelve-month prevalence of any of the three EDs was 3.2%; the overall lifetime prevalence was 6.1%. Education and marital status were significantly associated with both 12-month and lifetime EDs prevalence. Significant mental health comorbidities associated with 12-month EDs were anxiety, mood, and impulse-control disorders, while lifetime EDs were significantly related to all disorders. A similar percentage of respondents that reported having ED-related treatment at some point in their lifetime utilized healthcare and nonhealthcare sector. There was a significant relationship between body mass index category, and lifetime BED and BN. DISCUSSION: The 12-month prevalence of EDs in the Saudi population was higher than the EDs rates reported worldwide. These findings can help healthcare experts, and policymakers in the implementation of initiatives for raising awareness of EDs among the Saudi population, and the development of a country-wide plan for the prevention of EDs. PUBLIC SIGNIFICANCE STATEMENT: The study presents data on the prevalence, correlates, and help-seeking behaviors of AN, BN, and BED, in the Saudi National Mental Health Survey (SNMHS). Obtaining information on this underrepresented region is essential due to the large differences in cross-national data in addition to cultural beliefs about mental illness and treatment seeking to exert an important influence on eating disorders. Such knowledge could provide a better understand of mechanisms underlying the development of eating disorders and thereby improve prediction, prevention, and treatment.


Subject(s)
Anorexia Nervosa , Binge-Eating Disorder , Bulimia Nervosa , Feeding and Eating Disorders , Humans , Bulimia Nervosa/diagnosis , Binge-Eating Disorder/diagnosis , Anorexia Nervosa/complications , Prevalence , Saudi Arabia/epidemiology , Feeding and Eating Disorders/complications , Surveys and Questionnaires , Health Surveys
9.
BMC Public Health ; 22(1): 289, 2022 02 12.
Article in English | MEDLINE | ID: mdl-35151288

ABSTRACT

BACKGROUND: A major component of illness burden is role impairment. As part of the recently-completed Saudi National Mental Health Survey (SNMHS), we compare the number of days out of role in the Saudi population associated with ten core mental disorders assessed in the survey to those associated with ten commonly occurring chronic physical disorders. METHODS: The SNMHS was a household survey that assessed prevalence of ten common anxiety, mood, disruptive behavior, and eating disorders in a nationally representative sample of n = 1981 citizens of the Kingdom of Saudi Arabia (KSA) ages 15-65. Comparison information was obtained on prevalence of ten common chronic physical disorders and number of health-related days out of role (DOR) in the 30 days before interview. Generalized linear models were used to examine univariate and multivariable associations of disorders with DOR and to calculate population attributable risk (PAR) separately and overall for the disorders controlling for socio-demographics. RESULTS: 19.9% of respondents had one or more of the selected mental disorders and 47.1% had one or more of the selected physical disorders. Nine mental disorders and two physical disorders were associated with increased DOR. PAR was 32.9% for mental disorders, 27.0% for physical disorders, and 59.9% for both combined. CONCLUSIONS: Mental disorders are associated with a substantial proportion of all health-related DOR in the Kingdom of Saudi Arabia. Programs to detect and treat mental disorders might lead to substantially decreased role impairment in the Kingdom.


Subject(s)
Mental Disorders , Adolescent , Adult , Aged , Anxiety Disorders/epidemiology , Health Surveys , Humans , Mental Disorders/therapy , Middle Aged , Prevalence , Saudi Arabia/epidemiology , Surveys and Questionnaires , Young Adult
10.
Crit Rev Food Sci Nutr ; 62(11): 3116-3123, 2022.
Article in English | MEDLINE | ID: mdl-33356450

ABSTRACT

BACKGROUND: Inconsistencies exist with regard to the influence of omega-3 supplementation on 25-hydroxyvitamin D (25(OH)D) levels, which could be attributed to many factors, such as the duration and dose of omega-3 supplementation, and individuals' baseline 25(OH)D levels. Therefore, to address the inconsistencies, we conducted a systematic review and dose-response meta-analysis to accurately determine the effect of omega-3 supplementation on 25(OH)D levels in humans. METHODS: We performed a comprehensive literature search in Web of Science, PubMed/Medline, Scopus, and Embase databases from inception up to January 2020. We included only randomized controlled trials (RCTs). We used weighted mean difference (WMD) with 95% confidence interval (CI) to assess the influence of omega-3 supplementation on serum 25(OH)D levels using the random-effects model. RESULTS: Our pooled results of 10 RCTs demonstrated an overall significant increase in 25(OH)D levels following omega-3 intake (WMD = 3.77 ng/ml, 95% CI: 1.29, 6.25). In addition, 25(OH)D levels were significantly increased when the intervention duration lasted >8 weeks and when the baseline serum 25(OH)D level was ˂20 ng/ml. Moreover, omega-3 intake ≤1000 mg/day resulted in higher 25(OH)D levels compared to omega-3 intake >1000 mg/day. CONCLUSION: In conclusion, omega-3 supplementation increased 25(OH)D concentrations, particularly with dosages ≤1000 mg/day and intervention durations >8 weeks.


Subject(s)
Dietary Supplements , Vitamin D , Humans , Randomized Controlled Trials as Topic , Vitamins
11.
Crit Rev Food Sci Nutr ; 62(12): 3389-3402, 2022.
Article in English | MEDLINE | ID: mdl-33350317

ABSTRACT

Cardiovascular disease (CVD) is the greatest cause of premature death and disability globally. Numerous therapeutic strategies have been developed to improve and prevent the adverse cardiovascular events, including nutritional approaches. This systematic review and meta-analysis summarized the evidence on orange juice consumption on CVD risk factors. Four databases were searched up to September 2020. Ten randomized controlled trials were included in the final analysis. Pooled results demonstrated a significant effect of orange juice on glucose (WMD: -2.92 mg/dl, 95% CI: -5.327, -0.530, p = 0.017), insulin (WMD: -1.229 µU/ml, 95% CI: -2.083, -0.374, p = 0.005), HOMA-IR (WMD: -0.464, 95% CI: -0.747, -0.181, p = 0.001), total cholesterol (WMD: -9.84 mg/dl, 95% CI: -15.43, -4.24, p = 0.001), LDL-C (WMD: -9.14 mg/dl, 95% CI: -15.79, -2.49, p = 0.007), and CRP (WMD: -0.467 mg/l, 95% CI: -0.815, -0.120, p = 0.008) compared to control group. However, the effect of orange juice on body composition factors and other CVD risk factors was not significant compared to control group. These lowering effects of glucose, HOMA-IR, total cholesterol, and LDL-C were robust in subgroups with orange juice consumption ≥500 ml/day. This meta-analysis suggests that orange juice may be beneficial in improving several CVD risk factors.


Subject(s)
Cardiovascular Diseases , Citrus sinensis , Cardiovascular Diseases/prevention & control , Cholesterol, LDL , Dietary Supplements , Glucose , Humans , Lipids , Randomized Controlled Trials as Topic
12.
Clin Res Hepatol Gastroenterol ; 46(1): 101782, 2022 01.
Article in English | MEDLINE | ID: mdl-34339872

ABSTRACT

PURPOSE: The standard of care for treatment of celiac disease (CD) is a stringent lifetime gluten-free diet (GFD). Larazotide acetate (AT-1001) is an anti-zonulin which functions as a gut permeability regulator for treatment of CD. We endeavored to conduct a systematic review and meta-analysis of all randomized controlled trials (RCTs) which studied the efficacy and safety of AT-1001 in patients with CD. METHODS: We examined four databases from inception to 20-August-2020. We pooled continuous outcomes as mean difference and dichotomous outcomes as risk ratio with 95% confidence interval under the fixed-effects meta-analysis model. RESULTS: Four RCTs met our eligibility criteria, comprising 626 patients (AT-1001, n=465, placebo, n=161). Three and two RCTs reported outcomes of patients undergoing gluten challenge (intake of 2.4-2.7 grams of gluten/day) and GFD, respectively. For change in lactulose-to-mannitol ratio, the endpoint did not significantly differ between AT-1001 and placebo groups, irrespective of the gluten status. Subgroup analysis of patients undergoing gluten challenge showed AT-1001 treatment (compared with placebo) significantly correlated with better symptomatic improvement in the two endpoints of change in total gastrointestinal symptom rating scale (total GSRS) and CD-specific GSRS (CD-GSRS). However, no significant difference was noted among patients undergoing GFD for the abovementioned two efficacy endpoints. Compared with placebo, AT-1001 favorably reduced the adverse event (AE) of gluten-related diarrhea in patients who underwent gluten challenge. Other AEs were comparable between both AT-1001 and placebo groups. CONCLUSIONS: AT-1001 is largely well-endured and seems somehow superior to placebo in alleviating gastrointestinal symptoms among CD patients undergoing gluten challenge. Nevertheless, additional RCTs are warranted to validate these findings.


Subject(s)
Celiac Disease , Celiac Disease/diagnosis , Diet, Gluten-Free , Double-Blind Method , Glutens/adverse effects , Humans , Oligopeptides/therapeutic use , Randomized Controlled Trials as Topic
13.
Respir Res ; 22(1): 323, 2021 Dec 28.
Article in English | MEDLINE | ID: mdl-34963461

ABSTRACT

BACKGROUND: Pulmonary fibrosis is thought to be driven by recurrent alveolar epithelial injury which leads to the differentiation of fibroblasts into α-smooth muscle actin (α-SMA)-expressing myofibroblasts and subsequent deposition of extracellular matrix (ECM). Transforming growth factor beta-1 (TGF-ß1) plays a key role in fibroblast differentiation, which we have recently shown involves human antigen R (HuR). HuR is an RNA binding protein that also increases the translation of hypoxia inducible factor (HIF-1α) mRNA, a transcription factor critical for inducing a metabolic shift from oxidative phosphorylation towards glycolysis. This metabolic shift may cause fibroblast differentiation. We hypothesized that under hypoxic conditions, HuR controls myofibroblast differentiation and glycolytic reprogramming in human lung fibroblasts (HLFs). METHODS: Primary HLFs were cultured in the presence (or absence) of TGF-ß1 (5 ng/ml) under hypoxic (1% O2) or normoxic (21% O2) conditions. Evaluation included mRNA and protein expression of glycolytic and myofibroblast/ECM markers by qRT-PCR and western blot. Metabolic profiling was done by proton nuclear magnetic resonance (1H- NMR). Separate experiments were conducted to evaluate the effect of HuR on metabolic reprogramming using siRNA-mediated knock-down. RESULTS: Hypoxia alone had no significant effect on fibroblast differentiation or metabolic reprogramming. While hypoxia- together with TGFß1- increased mRNA levels of differentiation and glycolysis genes, such as ACTA2, LDHA, and HK2, protein levels of α-SMA and collagen 1 were significantly reduced. Hypoxia induced cytoplasmic translocation of HuR. Knockdown of HuR reduced features of fibroblast differentiation in response to TGF-ß1 with and without hypoxia, including α-SMA and the ECM marker collagen I, but had no effect on lactate secretion. CONCLUSIONS: Hypoxia reduced myofibroblasts differentiation and lactate secretion in conjunction with TGF-ß. HuR is an important protein in the regulation of myofibroblast differentiation but does not control glycolysis in HLFs in response to hypoxia. More research is needed to understand the functional implications of HuR in IPF pathogenesis.


Subject(s)
Cell Differentiation/physiology , Cell Hypoxia/physiology , Cellular Reprogramming/physiology , ELAV-Like Protein 1/metabolism , Lung/metabolism , Transforming Growth Factor beta/pharmacology , Cell Differentiation/drug effects , Cell Hypoxia/drug effects , Cells, Cultured , Cellular Reprogramming/drug effects , Dose-Response Relationship, Drug , ELAV-Like Protein 1/genetics , Fibroblasts/drug effects , Fibroblasts/metabolism , Humans , Lung/cytology , Lung/drug effects
14.
Commun Biol ; 4(1): 884, 2021 07 16.
Article in English | MEDLINE | ID: mdl-34272480

ABSTRACT

Endoplasmic reticulum (ER) stress induction of cell death is implicated in cardiovascular diseases. Sustained activation of ER-stress induces the unfolded protein response (UPR) pathways, which in turn activate three major effector proteins. We previously reported a missense homozygous mutation in FBXO32 (MAFbx, Atrogin-1) causing advanced heart failure by impairing autophagy. In the present study, we performed transcriptional profiling and biochemical assays, which unexpectedly revealed a reduced activation of UPR effectors in patient mutant hearts, while a strong up-regulation of the CHOP transcription factor and of its target genes are observed. Expression of mutant FBXO32 in cells is sufficient to induce CHOP-associated apoptosis, to increase the ATF2 transcription factor and to impair ATF2 ubiquitination. ATF2 protein interacts with FBXO32 in the human heart and its expression is especially high in FBXO32 mutant hearts. These findings provide a new underlying mechanism for FBXO32-mediated cardiomyopathy, implicating abnormal activation of CHOP. These results suggest alternative non-canonical pathways of CHOP activation that could be considered to develop new therapeutic targets for the treatment of FBXO32-associated DCM.


Subject(s)
Apoptosis , Cardiomyopathy, Dilated/genetics , Endoplasmic Reticulum Stress/genetics , Muscle Proteins/genetics , Mutation, Missense , SKP Cullin F-Box Protein Ligases/genetics , Up-Regulation , Apoptosis/genetics , Muscle Proteins/metabolism , SKP Cullin F-Box Protein Ligases/metabolism
15.
J Cell Physiol ; 236(10): 6836-6851, 2021 10.
Article in English | MEDLINE | ID: mdl-33855709

ABSTRACT

Idiopathic pulmonary fibrosis (IPF) is a disease of progressive scarring caused by excessive extracellular matrix (ECM) deposition and activation of α-SMA-expressing myofibroblasts. Human antigen R (HuR) is an RNA binding protein that promotes protein translation. Upon translocation from the nucleus to the cytoplasm, HuR functions to stabilize messenger RNA (mRNA) to increase protein levels. However, the role of HuR in promoting ECM production, myofibroblast differentiation, and lung fibrosis is unknown. Human lung fibroblasts (HLFs) treated with transforming growth factor ß1 (TGF-ß1) showed a significant increase in translocation of HuR from the nucleus to the cytoplasm. TGF-ß-treated HLFs that were transfected with HuR small interfering RNA had a significant reduction in α-SMA protein as well as the ECM proteins COL1A1, COL3A, and FN1. HuR was also bound to mRNA for ACTA2, COL1A1, COL3A1, and FN. HuR knockdown affected the mRNA stability of ACTA2 but not that of the ECM genes COL1A1, COL3A1, or FN. In mouse models of pulmonary fibrosis, there was higher cytoplasmic HuR in lung structural cells compared to control mice. In human IPF lungs, there was also more cytoplasmic HuR. This study is the first to show that HuR in lung fibroblasts controls their differentiation to myofibroblasts and consequent ECM production. Further research on HuR could assist in establishing the basis for the development of new target therapy for fibrotic diseases, such as IPF.


Subject(s)
Cell Transdifferentiation , ELAV-Like Protein 1/metabolism , Extracellular Matrix/metabolism , Fibroblasts/metabolism , Idiopathic Pulmonary Fibrosis/metabolism , Lung/metabolism , Myofibroblasts/metabolism , Actins/genetics , Actins/metabolism , Animals , Cell Transdifferentiation/drug effects , Cells, Cultured , Disease Models, Animal , ELAV-Like Protein 1/genetics , Extracellular Matrix/drug effects , Extracellular Matrix/pathology , Extracellular Matrix Proteins/genetics , Extracellular Matrix Proteins/metabolism , Fibroblasts/drug effects , Fibroblasts/pathology , Gene Expression Regulation , Humans , Idiopathic Pulmonary Fibrosis/genetics , Idiopathic Pulmonary Fibrosis/pathology , Lung/drug effects , Lung/pathology , Mice , Myofibroblasts/pathology , Transforming Growth Factor beta1/pharmacology
16.
Nutrients ; 13(2)2021 Jan 31.
Article in English | MEDLINE | ID: mdl-33572661

ABSTRACT

We are currently facing an obesity pandemic, with worldwide obesity rates having tripled since 1975. Obesity is one of the main risk factors for the development of non-communicable diseases, which are now the leading cause of death worldwide. This calls for urgent action towards understanding the underlying mechanisms behind the development of obesity as well as developing more effective treatments and interventions. Appetite is carefully regulated in humans via the interaction between the central nervous system and peripheral hormones. This involves a delicate balance in external stimuli, circulating satiating and appetite stimulating hormones, and correct functioning of neuronal signals. Any changes in this equilibrium can lead to an imbalance in energy intake versus expenditure, which often leads to overeating, and potentially weight gain resulting in overweight or obesity. Several lines of research have shown imbalances in gut hormones are found in those who are overweight or obese, which may be contributing to their condition. Therefore, this review examines the evidence for targeting gut hormones in the treatment of obesity by discussing how their dysregulation influences food intake, the potential possibility of altering the circulating levels of these hormones for treating obesity, as well as the role of short chain fatty acids and protein as novel treatments.


Subject(s)
Appetite Regulation/physiology , Fatty Acids, Volatile/therapeutic use , Gastrointestinal Hormones/metabolism , Obesity/therapy , Acetic Acid/therapeutic use , Animals , Appetite/physiology , Butyrates/therapeutic use , Central Nervous System/physiology , Cholecystokinin/metabolism , Dipeptides/metabolism , Dipeptides/therapeutic use , Energy Intake/physiology , Energy Metabolism/physiology , Gastrointestinal Hormones/blood , Gastrointestinal Tract/physiology , Ghrelin/metabolism , Glucagon-Like Peptide 1/agonists , Glucagon-Like Peptide 1/metabolism , Glucagon-Like Peptide 1/therapeutic use , Humans , Hyperphagia/etiology , Mice , Neuropeptide Y/metabolism , Obesity/etiology , Obesity/metabolism , Overweight/etiology , Overweight/metabolism , Oxyntomodulin/metabolism , Oxyntomodulin/therapeutic use , Pancreatic Polypeptide/metabolism , Propionates/therapeutic use , Satiation/physiology
17.
Eat Weight Disord ; 26(7): 2117-2125, 2021 Oct.
Article in English | MEDLINE | ID: mdl-33423153

ABSTRACT

BACKGROUND AND OBJECTIVE: Very few studies have investigated the relationship between body mass index (BMI) and risk of urinary tract infection (UTI), and conclusions from these available studies have been inconsistent. To resolve this inconsistency, we performed a systematic review and meta-analysis to precisely examine the association between BMI and UTI. METHODS: This meta-analysis was performed based on the PRISMA recommendations. PubMed, Web of Science, Scopus, Embase, and Google Scholar databases were searched for all published observational studies that reported the risk of UTI based on BMI categories up to March 2020. RESULTS: Fourteen (n = 14) articles comprising 19 studies in different populations met our inclusion criteria. The overall analysis showed a significant increased risk of UTI in subjects affected by obesity vs. individuals without obesity (RR = 1.45; 95% CI: 1.28 - 1.63; I2 = 94%), and a non-significant increased risk of UTI in subjects who were overweight (RR = 1.03; 95% CI: 0.98 - 1.10; I2 = 49.6%) and underweight (RR = 0.99; 95% CI: 0.81 - 21; I2 = 0.0%) when compared to subjects who had normal weight. In the stratified analysis, we showed that obesity increased the risk of UTI in females (RR = 1.63; 95% CI: 1.38 - 1.93) and in subjects below 60 years old (RR = 1.53; 95% CI: 1.33 - 1.75). CONCLUSION: This systematic review and meta-analysis recognized a significant relationship between BMI and incidence of UTI in obese vs. non-obese subjects, as well as in females and in individuals below 60 years old.


Subject(s)
Overweight , Urinary Tract Infections , Body Mass Index , Cohort Studies , Female , Humans , Middle Aged , Obesity/complications , Observational Studies as Topic , Urinary Tract Infections/complications
18.
Pharmacol Res ; 165: 105456, 2021 03.
Article in English | MEDLINE | ID: mdl-33515709

ABSTRACT

Formulation of insulin analogs and its delivery are developed in over recent years but glycemic control in most patients with type-1 diabetes mellitus (DM) is not adequate yet. The aim of this meta-analysis is to evaluate the efficacy of dapagliflozin in patients with type-1 DM. The MEDLINE/PubMed, Scopus, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), and Web of Science databases were searched up to Aug 2020 to identify the potential literature. Random-effects model (DerSimonian and Laird method) was used to estimate the pooled effect size as weighted mean difference (WMD) with 95 % confidence interval (CI). Five randomized placebo-controlled trials with 11 arms were included in the quantitative analysis. The pooled results suggested a significant reduction in glycated hemoglobin A1C (HbA1C; WMD: -0.36 %, 95 % CI: -0.55, -0.18), body weight (WMD: -4.02 kg, 95 % CI: -4.78, -3.25), and total daily insulin dose (TDID; WMD: -10.36 %, 95 % CI: -13.42, -7.29), as well as an increase in 24-h urinary glucose excretion (24-h UGE; WMD: 90.02 g/24-h, 95 % CI: 72.96, 107.09) in dapagliflozin group compared to control group. Dose of dapagliflozin had a significant effect on body weight reduction (Coef = -3.7, p = 0.01) and 24-h UGE (coef = 0.85, p = 0.005). Pooled results of this meta-analysis identified a significant reduction in HbA1c levels, body weight, and TDID, and a substantial increase in 24-h UGE in patients who received dapagliflozin versus placebo.


Subject(s)
Benzhydryl Compounds/therapeutic use , Diabetes Mellitus, Type 1/blood , Diabetes Mellitus, Type 1/drug therapy , Glucosides/therapeutic use , Sodium-Glucose Transporter 2 Inhibitors/therapeutic use , Animals , Benzhydryl Compounds/pharmacology , Clinical Trials as Topic/methods , Glucosides/pharmacology , Glycated Hemoglobin/antagonists & inhibitors , Glycated Hemoglobin/metabolism , Humans , Insulin/blood , Sodium-Glucose Transporter 2 Inhibitors/pharmacology , Treatment Outcome
19.
Int J Methods Psychiatr Res ; 29(3): e1830, 2020 09.
Article in English | MEDLINE | ID: mdl-33245571

ABSTRACT

OBJECTIVES: To present an overview of the survey and field procedures developed for the Saudi National Mental Health Survey (SNMHS). METHODS: The SNMHS is a face-to-face community epidemiological survey of DSM-IV mental disorders in a nationally representative sample of the household population in the Kingdom of Saudi Arabia (KSA) (n = 4,004). The SNMHS was implemented as part of the WHO World Mental Health (WMH) Survey Initiative. WMH carries out coordinated psychiatric epidemiological surveys in countries throughout the world using standardized procedures designed to provide valid cross-national comparative data on prevalence and correlates of common mental disorders. However, these procedures need to be adapted to the unique experiences in each country. We focus here on the adaptations made for the SNMHS. RESULTS: Modifications were needed to several interview sections and expansions were needed to address issues of special policy importance in KSA. Several special field implementation challenges also had to be addressed because of the need for female interviewers to travel with male escorts and for respondents to be interviewed by interviewers of the same gender. CONCLUSIONS: Thoughtful revisions led to a high-quality field implementation in the SNMHS.


Subject(s)
Mental Disorders , Mental Health , Diagnostic and Statistical Manual of Mental Disorders , Female , Health Surveys , Humans , Male , Mental Disorders/epidemiology , Saudi Arabia/epidemiology , Surveys and Questionnaires
20.
Int J Methods Psychiatr Res ; 29(3): e1836, 2020 09.
Article in English | MEDLINE | ID: mdl-33245595

ABSTRACT

OBJECTIVES: To estimate lifetime prevalence of mental disorders in the Saudi National Mental Health Survey (SNMHS). METHODS: The SNMHS is a face-to-face community epidemiological survey in a nationally representative household sample of citizens ages 15-65 in the Kingdom of Saudi Arabia (KSA) (n = 4,004). The World Health Organization (WHO) Composite International Diagnostic Interview (CIDI) was used to estimate lifetime prevalence of common DSM-IV mental disorders. RESULTS: Estimated lifetime prevalence of any DSM-IV/CIDI disorder is 34.2% and lifetime morbid risk is 38.0%. Anxiety disorders are by far the most prevalent (23.2%) followed by disruptive behavior (11.2%), mood (9.3%), eating (6.1%), and substance use (4.0%) disorders. Synthetic estimates of cohort effects suggest that prevalence of many disorders has increased in recent cohorts. Onsets typically occur in childhood for a number of anxiety and disruptive behavior disorders and in adolescence or early adulthood for most other disorders, although age-of-onset distributions for drug abuse is much later (median age of 31) than in CIDI surveys carried out in other high-income countries. CONCLUSIONS: Lifetime mental disorders are highly prevalent in Saudi Arabia and typically have early ages-of-onset.


Subject(s)
Mental Disorders , Adolescent , Adult , Aged , Diagnostic and Statistical Manual of Mental Disorders , Health Surveys , Humans , Mental Disorders/epidemiology , Middle Aged , Prevalence , Saudi Arabia/epidemiology , Young Adult
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