Differentiation signals induce APOBEC3A expression via GRHL3 in squamous epithelia and squamous cell carcinoma.

Two APOBEC (apolipoprotein-B mRNA editing enzyme catalytic polypeptide-like) DNA cytosine deaminase enzymes (APOBEC3A and APOBEC3B) generate somatic mutations in cancer, driving tumour development and drug resistance. Here we used single cell RNA sequencing to study APOBEC3A and APOBEC3B expression in healthy and malignant mucosal epithelia, validating key observations with immunohistochemistry, spatial transcriptomics and functional experiments. Whereas APOBEC3B is expressed in keratinocytes entering mitosis, we show that APOBEC3A expression is confined largely to terminally differentiating cells and requires Grainyhead-like transcription factor 3 (GRHL3). Thus, in normal tissue, neither deaminase appears to be expressed at high levels during DNA replication, the cell cycle stage associated with APOBEC-mediated mutagenesis. In contrast, we show that in squamous cell carcinoma tissues, there is expansion of GRHL3 expression and activity to a subset of cells undergoing DNA replication and concomitant extension of APOBEC3A expression to proliferating cells. These findings indicate a mechanism for acquisition of APOBEC3A mutagenic activity in tumours.

Comparison of Four Protocols for In Vitro Differentiation of Human Embryonic Stem Cells into Trophoblast Lineages by BMP4 and Dual Inhibition of Activin/Nodal and FGF2 Signaling.

Human embryonic stem cells (hESCs) cultured in media containing bone morphogenic protein 4 (BMP4; B) differentiate into trophoblast-like cells. Supplementing media with inhibitors of activin/nodal signaling (A83-01) and of fibroblast growth factor 2 (PD173074) suppresses mesoderm and endoderm formation and improves specification of trophoblast-like lineages, but with variable effectiveness. We compared differentiation in four BMP4-containing media: mTeSR1-BMP4 only, mTeSR1-BAP, basal medium with BAP (basal-BAP), and a newly defined medium, E7-BAP. These media variably drive early differentiation towards trophoblast-like lineages with upregulation of early trophoblast markers CDX2 and KRT7 and downregulation of pluripotency markers (OCT4 and NANOG). As expected, based on differences between media in FGF2 and its inhibitors, downregulation of mesendoderm marker EOMES was variable between media. By day 7, only hESCs grown in E7-BAP or basal-BAP expressed HLA-G protein, indicating the presence of cells with extravillous trophoblast characteristics. Expression of HLA-G and other differentiation markers (hCG, KRT7, and GCM1) was highest in basal-BAP, suggesting a faster differentiation in this medium, but those cultures were more inhomogeneous and still expressed some endodermal and pluripotency markers. In E7-BAP, HLA-G expression increased later and was lower. There was also a low but maintained expression of some C19MC miRNAs, with more CpG hypomethylation of the ELF5 promoter, suggesting that E7-BAP cultures differentiate slower along the trophoblast lineage. We conclude that while all protocols drive differentiation into trophoblast lineages with varying efficiency, they have advantages and disadvantages that must be considered when selecting a protocol for specific experiments.

An Evaluation of the Effectiveness of Repetitive Transcranial Magnetic Stimulation (rTMS) for the Management of Treatment-Resistant Depression with Somatic Attributes: A Hospital-Based Study in Oman.

Depressive illnesses in non-Western societies are often masked by somatic attributes that are sometimes impervious to pharmacological agents. This study explores the effectiveness of repetitive transcranial magnetic stimulation (rTMS) for people experiencing treatment-resistant depression (TRD) accompanied by physical symptoms. Data were obtained from a prospective study conducted among patients with TRD and some somatic manifestations who underwent 20 sessions of rTMS intervention from January to June 2020. The Hamilton Rating Scale for Depression (HAMD) was used for clinical evaluation. Data were analysed using descriptive and inferential techniques (multiple logistic regression) in SPSS. Among the 49 participants (mean age: 42.5 ± 13.3), there was a significant reduction in posttreatment HAMD scores compared to baseline (t = 10.819, p < 0.0001, and 95% CI = 8.574-12.488), indicating a clinical response. Approximately 37% of the patients responded to treatment, with higher response rates among men and those who remained in urban areas, had a history of alcohol use, and were subjected to the standard 10 HZ protocol. After adjusting for all extraneous variables, the rTMS protocol emerged as the only significant predictor of response to the rTMS intervention. To our knowledge, this is the first study to examine the effectiveness of rTMS in the treatment of somatic depression.

Loss of the Maternal Effect Gene Nlrp2 Alters the Transcriptome of Ovulated Mouse Oocytes and Impacts Expression of Histone Demethylase KDM1B.

The subcortical maternal complex (SCMC) is a multiprotein complex in oocytes and preimplantation embryos that is encoded by maternal effect genes. The SCMC is essential for zygote-to-embryo transition, early embryogenesis, and critical zygotic cellular processes, including spindle positioning and symmetric division. Maternal deletion of Nlrp2, which encodes an SCMC protein, results in increased early embryonic loss and abnormal DNA methylation in embryos. We performed RNA sequencing on pools of meiosis II (MII) oocytes from wild-type and Nlrp2-null female mice that were isolated from cumulus-oocyte complexes (COCs) after ovarian stimulation. Using a mouse reference genome-based analysis, we found 231 differentially expressed genes (DEGs) in Nlrp2-null compared to WT oocytes (123 up- and 108 downregulated; adjusted p < 0.05). The upregulated genes include Kdm1b, a H3K4 histone demethylase required during oocyte development for the establishment of DNA methylation marks at CpG islands, including those at imprinted genes. The identified DEGs are enriched for processes involved in neurogenesis, gland morphogenesis, and protein metabolism and for post-translationally methylated proteins. When we compared our RNA sequencing data to an oocyte-specific reference transcriptome that contains many previously unannotated transcripts, we found 228 DEGs, including genes not identified with the first analysis. Interestingly, 68% and 56% of DEGs from the first and second analyses, respectively, overlap with oocyte-specific hyper- and hypomethylated domains. This study shows that there are substantial changes in the transcriptome of mouse MII oocytes from female mice with loss of function of Nlrp2, a maternal effect gene that encodes a member of the SCMC.

Mapping the hepatic immune landscape identifies monocytic macrophages as key drivers of steatohepatitis and cholangiopathy progression.

BACKGROUND AND AIMS: The progression of chronic liver diseases towards liver cirrhosis is accompanied by drastic tissue changes. This study combines elaborate transcriptomic and histological methods aiming at spatially resolving the hepatic immune microenvironment in NAFLD (including NASH, primary sclerosing cholangitis, primary biliary cholangitis, and severe alcoholic hepatitis). APPROACH AND RESULTS: Human liver samples were subjected to RNA-sequencing (n=225) and imaging cytometry (n=99) across 3 independent patient cohorts. Liver samples from alcoholic hepatitis and primary biliary cholangitis patients were used for comparison. Myeloid populations were further characterized in corresponding mouse models. Imaging, clinical, and phenotypical data were combined for multidimensional analysis. NAFLD/NASH and primary sclerosing cholangitis disease stages were associated with loss of parenchymal areas, increased ductular cell accumulation, and infiltration of immune cells. NASH patients predominantly exhibited myeloid cell accumulation, whereas primary sclerosing cholangitis patients additionally had pronounced lymphoid cell responses. Correlating to disease stage, both etiologies displayed intense IBA1 + CD16 low CD163 low macrophage aggregation in nonparenchymal areas, with a distinct spatial proximity to ductular cells. Mouse models revealed that disease-associated IBA1 + hepatic macrophages originated from bone marrow-derived monocytes. Using an unbiased, machine learning-based algorithm, IBA1 in combination with hepatocyte and ductular cell immunostaining-predicted advanced cirrhosis in human NASH, primary sclerosing cholangitis, and alcoholic hepatitis. CONCLUSIONS: Loss of hepatocytes and increased ductular reaction are tightly associated with monocyte-derived macrophage accumulation and represent the most prominent common immunological feature revealing the progression of NAFLD, primary sclerosing cholangitis, primary biliary cholangitis, and alcoholic hepatitis, suggesting IBA1 + CD163 low macrophages are key pathogenic drivers of human liver disease progression across diverse etiologies.

IL-31 levels correlate with pruritus in patients with cholestatic and metabolic liver diseases and is farnesoid X receptor responsive in NASH.

BACKGROUND AND AIMS: Pruritus is associated with multiple liver diseases, particularly those with cholestasis, but the mechanism remains incompletely understood. Our aim was to evaluate serum IL-31 as a putative biomarker of pruritus in clinical trials of an farnesoid X receptor (FXR) agonist, cilofexor, in patients with NASH, primary sclerosing cholangitis (PSC), and primary biliary cholangitis (PBC). APPROACH AND RESULTS: Serum IL-31 was measured in clinical studies of cilofexor in NASH, PSC, and PBC. In patients with PSC or PBC, baseline IL-31 was elevated compared to patients with NASH and healthy volunteers (HVs). IL-31 correlated with serum bile acids among patients with NASH, PBC, and PSC. Baseline IL-31 levels in PSC and PBC were positively correlated with Visual Analog Scale for pruritus and 5-D itch scores. In patients with NASH, cilofexor dose-dependently increased IL-31 from Week (W)1 to W24. In patients with NASH receiving cilofexor 100 mg, IL-31 was higher in those with Grade 2-3 pruritus adverse events (AEs) than those with Grade 0-1 pruritus AEs. IL-31 weakly correlated with C4 at baseline in patients with NASH, and among those receiving cilofexor 100 mg, changes in IL-31 and C4 from baseline to W24 were negatively correlated. IL-31 messenger RNA (mRNA) was elevated in hepatocytes from patients with PSC and NASH compared to HVs. In a humanized liver murine model, obeticholic acid increased IL-31 mRNA expression in human hepatocytes and serum levels of human IL-31. CONCLUSIONS: IL-31 levels correlate with pruritus in patients with cholestatic disease and NASH, with FXR agonist therapy resulting in higher serum levels in the latter group. IL-31 appears to derive in part from increased hepatocyte expression. These findings have therapeutic implications for patients with liver disease and pruritus.

A Comprehensive Neuropsychological Study of Familial Hypercholesterolemia and Its Relationship with Psychosocial Functioning: A Biopsychosocial Approach.

BACKGROUND: Over the past few years, there has been an increasing interest in viewing the diagnosis of familial hypercholesterolemia (FH) through the lens of the biopsychosocial model. However, other than a few epidemiological surveys, there is a dearth of studies from emerging economies that have examined FH using the biological, psychological, and socio-environmental facets of the aforementioned model. AIM. The three aims of the current study were as follows: (i) to examine the psychosocial status among patients with genetically confirmed FH, (ii) to compare their intellectual capacity and cognitive outcomes with a reference group, and (iii) to examine the relationship between health literacy and cognitive functioning. METHOD: Consecutive FH patients referred to the lipid clinic at a tertiary care center for an expert opinion were recruited into this study conducted from September 2019 to March 2020. Information regarding psychosocial functioning, health literacy, quality of life, and affective ranges was surveyed. Indices of current reasoning ability and cognition (attention and concentration, memory, and executive functioning) were compared with a socio-demographically-matched reference group. The current hypothesis also explored the impact of FH on health literacy and cognition. RESULT: A total of 70 participants out of 106 (response rate: 66.0%) initially agreed to participate. However, 18 out of 70 dropped out of the study, yielding a final total of 52 FH patients. With 27 (51.9%) males and 25 (48.1%) females, the mean participant age stood at 37.2 years (SD = 9.2), ranging from 21 to 52 years of age. In the psychosocial data, thirty-two percent (n = 17) of them had anxiety (HADS ≥ 8), and twenty-five percent (n = 13) had depressive symptoms (HADS ≥ 8). The performance of the FH patients was significantly impaired compared to the control group on the indices of current reasoning ability and all domains of cognitive functioning. In the univariate analysis conducted to compare cognitive functioning with health literacy status, only indices of attention and concentration emerged as being significant. CONCLUSION: The current study indicates that the FH population is marked with impediments in biopsychosocial functioning, including indices tapping into the integrity of health literacy, quality of life, affective ranges, and higher functioning such as cognition and current reasoning ability when compared with a socio-demographically-matched reference group. The present results support the hypothesis that chronic diseases vis-à-vis the sequelae of coronary artery disease can potentially impede biopsychosocial functioning.

Combinations of an acetyl CoA carboxylase inhibitor with hepatic lipid modulating agents do not augment antifibrotic efficacy in preclinical models of NASH and fibrosis.

Dysregulated hepatocyte lipid metabolism is a hallmark of hepatic lipotoxicity and contributes to the pathogenesis of nonalcoholic steatohepatitis (NASH). Acetyl CoA carboxylase (ACC) inhibitors decrease hepatocyte lipotoxicity by inhibiting de novo lipogenesis and concomitantly increasing fatty acid oxidation (FAO), and firsocostat, a liver-targeted inhibitor of ACC1/2, is under evaluation clinically in patients with NASH. ACC inhibition is associated with improvements in indices of NASH and reduced liver triglyceride (TG) content, but also increased circulating TG in subjects with NASH and preclinical rodent models. Here we evaluated whether enhancing hepatocyte FAO by combining ACC inhibitors with peroxisomal proliferator-activated receptor (PPAR) or thyroid hormone receptor beta (THRß) agonists could drive greater liver TG reduction and NASH/antifibrotic efficacy, while ameliorating ACC inhibitor-induced hypertriglyceridemia. In high-fat diet-fed dyslipidemic rats, the addition of PPAR agonists fenofibrate (Feno), elafibranor (Ela), lanifibranor (Lani), seladelpar (Sela) or saroglitazar (Saro), or the THRb agonist resmetirom (Res), to an analogue of firsocostat (ACCi) prevented ACCi-induced hypertriglyceridemia. However, only PPARα agonists (Feno and Ela) and Res provided additional liver TG reduction. In the choline-deficient high-fat diet rat model of advanced liver fibrosis, neither PPARα (Feno) nor THRß (Res) agonism augmented the antifibrotic efficacy of ACCi. Conclusion: These data suggest that combination therapies targeting hepatocyte lipid metabolism may have beneficial effects on liver TG reduction; however, they may not be sufficient to drive fibrosis regression.

Prevalence of eating disorders and disordered eating in Western Asia: a systematic review and meta-Analysis.

This study aimed to systematically synthesize and appraise existing literature on the prevalence of eating disorders and disordered eating in Western Asia.A systematic literature search of major English and Arabic databases, i.e., PubMed/Medline, EMBASE, PsychInfo, Web of Science and Scopus (English), Al-Manhal (Arabic) and grey literature was done to obtain the prevalence of disordered eating and eating disorders in Western Asia. The literature search was conducted on June 12th, 2020, and included papers from 1990-2020.Out of the 249 unduplicated original studies reviewed, 27 were included in the final meta-analysis. Data were then categorized according to the tools used to identify the presence of disordered eating or eating disorders. The pooled prevalence of disordered eating as solicited by both the Eating Attitudes Scale 26 and the Eating Attitudes Scale 40 (N = 11841) was 22.07%, the Sick, Control, One stone, Fat, Food Questionnaire (n = 3160) was 22.28% and the Eating Disorder Examination-Questionnaire (n = 425) was 7.95%. The pooled prevalence obtained from those studies using semi-structured interviews for anorexia nervosa (n = 118190) was 1.59%, bulimia nervosa (n = 118513) was 2.41% and the estimated prevalence of Eating Disorder Not Otherwise Specified (EDNOS) (n = 118087) was 3.51%.Although the prevalence rate of eating disorders solicited using semi-structured interviews appeared to parallel the international range, the overall prevalence rate of disordered eating appeared to be slightly higher than the global rates of prevalence. A significant number of the suspected/detected cases of disordered eating appear to fulfill the criteria for EDNOS.This study is classified as evidence obtained from systematic reviews and meta-analyses (i.e. Level 1).

Cognitive Function in Adults with Beta-Thalassemia Major in Oman: A Pilot Study.

OBJECTIVES: Neurocognitive dysfunction has been established in several studies in children with beta-thalassemia major (TM). However, despite its wide occurrence in populations across the Arabian Peninsula, scant attention has been paid to shedding light on neuropsychological functioning among adults with TM. This study aimed to examine the level of neuropsychological functioning among Omani adults with TM regularly followed-up at a tertiary care hospital in Oman. A related aim was to examine the factors associated with neuropsychological performance. METHODS: Standard neuropsychological tests were used to measure attention and concentration, learning and remembering, verbal fluency, and executive functioning. Participants were also gauged on indices of intellectual ability and affective range. As normative data for neuropsychological functioning in Oman is scarce, healthy age- and sex-matched controls underwent the same testing procedure. The log-linear model was used to identify factors associated with TM patients on demographic and neuropsychological performance. RESULTS: This study recruited 28 adult patients with TM (age 30.0±6.5) and 39 healthy controls (age 29.2±6.1). Findings suggested that having a diagnosis of TM was significantly associated with symptoms of depression (p < 0.001) and anxiety (p < 0.001), indices of executive functioning (verbal fluency) (p =0.003), working memory (digit span) (p < 0.001), and verbal and auditory attention scores (California Verbal Learning, p = 0.002). CONCLUSIONS: The data appears to suggest that short-term memory capacity, verbal fluency, and verbal and auditory attention may be impaired in TM compared to controls. Studies on a larger cohort are therefore warranted.

Depressive symptoms among primary healthcare workers during the novel SARS-CoV-2 coronavirus pandemic in the Muscat governorate.

BACKGROUND: With the unprecedented spread of the novel SARS-CoV-2 coronavirus, primary healthcare workers (PHCWs) are having to shoulder the increasing weight of this ongoing pandemic. AIMS: This study explored the rate and covariates of depressive symptoms among PHCWs in the Muscat governorate. METHODS: A cross-sectional online survey was conducted from 10 May to 10 June 2020 among PHCWs working in all primary healthcares across the Muscat governorate. Data on sociodemographic and risk factors of having at least one underlying physical health condition, a psychiatric history, family history of psychiatric disorders, and direct involvement with COVID-19 positive patients were sought. The Patient Health Questionnaire (PHQ-9) was then used to solicit the presence of depressive symptoms. Those with a cutoff point ≥10 were considered as showing depressive symptoms. Logistic regression was used to determine risk factors associated with depressive symptoms in PHCWs after adjusting for all sociodemographic factors. FINDINGS: A total of 432 (72%) out of 600 PHCWs with an average age of 39.2 years (SD = 7.8 years) ranging between 25.0 and 75.0 years responded to the survey. There were more females (n = 281, 65.3%) than males, and more than 45% (n = 195) of them were physicians. Additionally, more than 78% (n = 338) had been in contact with COVID-19 patients. There was a significant association between different age groups and profession (P < .001), having at least one underlying physical health condition (P = 0.001) and depressive symptom status (P = 0.038). A total of 78 out of the 423 subjects (18.1%) were considered to have depressive symptoms. After adjusting for all factors, the logistic regression model showed that an age of 34 years or below (OR = 2.079, P = 0.021) and having at least one underlying physical health condition (OR = 2.216, P = 0.007) were factors contributing significantly to depressive symptoms among the PHCWs.

Post-Stroke Psychiatric and Cognitive Symptoms in West Asia, South Asia and Africa: A Systematic Review and Meta-Analysis.

Recent research has shown that the prevalence of stroke incidents and the number of survivors in developing countries surpass those from developed countries. This study aimed to enumerate the prevalence of post-stroke psychiatric and cognitive symptoms among stroke survivors from West and South Asia and Africa through a systematic review and meta-analysis. Data from each country was systematically acquired from five major databases (PsycINFO, Web of Science, Scopus, PubMed/Medline, and Google Scholar (for any missing articles and grey literature)). Meta-analytic techniques were then used to estimate the prevalence of various post-stoke psychiatric and cognitive symptoms. A total of 36 articles were accrued from 11 countries, of which 25 were evaluated as part of the meta-analysis. The pooled prevalence of post-stroke depression as per the Hospital Anxiety and Depression Scale (HADS), Hamilton Depression Rating Scale, Patient Health Questionnaire, Schedules for Clinical Assessment in Neuropsychiatry (SCAN), Geriatric Depression Scale, and the Montgomery-Asberg Depression Rating Scale ranged from 28.00 to 50.24%. Pooled prevalence of post-stroke anxiety based on the HADS and SCAN was 44.19% and 10.96%, respectively. The pooled prevalence of post-stroke cognitive impairment as per the Mini-Mental Status Examination was 16.76%. This present review has suggested that both psychiatric and cognitive symptoms are common among stroke survivors. Concerted efforts are needed to institute robust studies using culturally sensitive measures to contemplate mechanisms that address the unmet needs of this vulnerable population.

Child and adolescent mental health disorders in the GCC: A systematic review and meta-analysis.

BACKGROUND: The Gulf Cooperation Council (GCC), with a predominant 'youth bulge' among its 54 million people, has witnessed an exponential increase in research pertinent to child and adolescent mental health (CAMH). Aside from a few narrative reviews, to date, no critical appraisal examining the magnitude of CAMH has emerged from this region. AIMS: This study aimed to report the prevalence rates of CAMH disorders in the GCC through a systematic review of the existing literature followed by a meta-analysis. METHODS: A systematic review of the literature from the six GCC countries (Bahrain, Kuwait, Oman, Qatar, Saudi Arabia, and the United Arab Emirates) was conducted. The databases used included Scopus, ProQuest, Pubmed, and a final check was performed on Google Scholar to account for any remaining studies that may have still been under review. Meta analytic techniques were then used to estimate prevalence rates of each specific mental disorder, i.e. ADHD, depression, anxiety, stress, eating disorders, and tobacco use disorder. RESULTS: A total of 33 studies from the six countries were included. The pooled prevalence of ADHD as per the Vanderbilt ADHD Diagnostic Rating Scale (VADHDDRS), clinical judgments, Attention Deficit Disorders Evaluation Scale (ADDES), and the Strengths and Difficulties Questionnaire (SDQ) was found to be 13.125%, 13.38%, 26.135%, and 12.83%, respectively. The pooled prevalence of depressive symptoms solicited by the Patient Health Questionnaire (PHQ-9), Depression, Anxiety, and Stress Scale (DASS), and Mini-International Neuropsychiatric Interview for Children and Adolescents (MINI Kid) was 44.684%, 45.09%, and 26.12%, respectively. The pooled prevalence of anxiety according to the DASS and the MINI Kid was 57.04% and 17.27%, respectively, while the pooled prevalence of stress as per the DASS was found to be 43.15%. The pooled prevalence of disordered eating solicited by the Eating Attitudes Test (EAT-26) was 31.55%. Lastly, the pooled prevalence of tobacco use disorder per the Global Youth Tobacco Survey was 19.39%. DISCUSSION: To date, this is the first systematic review and meta-analysis of its kind from the GCC. The prevalence rate of CAMH disorders appears to be in the upper range of international trends. The higher rates could be attributed to the existing studies using suboptimal methodological approaches and instruments to solicit the presence of CAMH.

Reproductive Outcomes from Maternal Loss of Nlrp2 Are Not Improved by IVF or Embryo Transfer Consistent with Oocyte-Specific Defect.

Nlrp2 encodes a protein of the oocyte subcortical maternal complex (SCMC), required for embryo development. We previously showed that loss of maternal Nlrp2 in mice causes subfertility, smaller litters with birth defects, and growth abnormalities in offspring, indicating that Nlrp2 is a maternal effect gene and that all embryos from Nlrp2-deficient females that were cultured in vitro arrested before the blastocysts stage. Here, we used time-lapse microscopy to examine the development of cultured embryos from superovulated Nlrp2-deficient and wild-type mice after in vivo and in vitro fertilization. Embryos from Nlrp2-deficient females had similar abnormal cleavage and fragmentation and arrested by blastocyst stage, irrespective of fertilization mode. This indicates that in vitro fertilization does not further perturb or improve the development of cultured embryos. We also transferred embryos from superovulated Nlrp2-deficient and wild-type females to wild-type recipients to investigate if the abnormal reproductive outcomes of Nlrp2-deficient females are primarily driven by oocyte dysfunction or if a suboptimal intra-uterine milieu is a necessary factor. Pregnancies with transferred embryos from Nlrp2-deficient females produced smaller litters, stillbirths, and offspring with birth defects and growth abnormalities. This indicates that the reproductive phenotype is oocyte-specific and is not rescued by development in a wild-type uterus. We further found abnormal DNA methylation at two maternally imprinted loci in the kidney of surviving young adult offspring, confirming persistent DNA methylation disturbances in surviving offspring. These findings have implications for fertility treatments for women with mutations in NLRP2 and other genes encoding SCMC proteins.

Impact of vitamin D on neurocognitive function in dementia, depression, schizophrenia and ADHD.

Vitamin D deficiency has been estimated to affect roughly 30% to 50% of the global population and thus labeled as a silent pandemic. In addition to its role in skeletal and calcium homeostasis, vitamin D has been implicated in brain functioning across both preclinical research and human populations studies. These findings have also been extended to various neurodevelopmental and neuropsychiatric conditions. Furthermore, these individuals tend to display diminishing cognition symptoms. In this regard, this review is dedicated to address the relationship between vitamin D and dementia, mood disorders, and the various neuropsychological disorders of psychosis. The review takes both preclinical and clinical studies into consideration. While there are many literature suggesting the critical role of vitamins in cognition on the above said diseases, it is still premature to unequivocally postulate the role of vitamin D on cognitive symptoms. Further research is necessary to establish this association, including the need to increase the ecological validity of animal models, delineating the core cognitive symptoms associated with the disorders, and establishing the optimal source of vitamin D consumption.

Factors associated with mental health outcomes across healthcare settings in Oman during COVID-19: frontline versus non-frontline healthcare workers.

OBJECTIVE: This study aims to assess and compare demographic and psychological factors and sleep status of frontline healthcare workers (HCWs) in relation to non-frontline HCWs. DESIGN, SETTINGS, PARTICIPANTS AND OUTCOMES: This cross-sectional study was conducted from 8 April 2020 to 17 April 2020 using an online survey across varied healthcare settings in Oman accruing 1139 HCWs.The primary and secondary outcomes were mental health status and sociodemographic data, respectively. Mental health status was assessed using the Depression, Anxiety, and Stress Scale (DASS-21), and insomnia was evaluated by the Insomnia Severity Index. Samples were categorised into the frontline and non-frontline groups. χ2 and t-tests were used to compare groups by demographic data. The Mantel-Haenszel OR was used to compare groups by mental health outcomes adjusted by all sociodemographic factors. RESULTS: This study included 1139 HCWs working in Oman. While working during the pandemic period, a total of 368 (32.3%), 388 (34.1%), 271 (23.8%) and 211 (18.5%) respondents were reported to have depression, anxiety, stress and insomnia, respectively. HCWs in the frontline group were 1.5 times more likely to report anxiety (OR=1.557, p=0.004), stress (OR=1.506, p=0.016) and insomnia (OR=1.586, p=0.013) as compared with those in the non-frontline group. No significant differences in depression status were found between the frontline and non-frontline groups (p=0.201). CONCLUSIONS: To our knowledge, this is the first study to explore the differential impacts of the COVID-19 pandemic on different grades of HCWs. This study suggests that frontline HCWs are disproportionally affected compared to non-frontline HCWs, with managing sleep-wake cycles and anxiety symptoms being highly endorsed among frontline HCWs. As psychosocial interventions are likely to be constrained owing to the pandemic, mental healthcare must first be directed to frontline HCWs.

Psychiatric, cognitive functioning and socio-cultural views of menstrual psychosis in Oman: an idiographic approach.

BACKGROUND: Most documented cases of menstrual psychosis have been from Euro-American populations with reports from cross-cultural populations being only a few. A primary aim was to determine whether the cyclical/episodic nature of menstrual psychosis among case series observed at a tertiary care unit in Oman fulfills the diagnostic criteria of the International Classification of Diseases (ICD-10) and diverge into Brockington's sub-types (World Psychiatry. 2005;4(1):9-17). Related aims were to solicit measures of psychometric functioning of those with menstrual psychosis and associated idioms of distress. METHODS: A series of consecutive patients seeking psychiatric consultation from January 2016 to December 2017 were screened via structured interview-Composite-International Diagnostic Interview (CIDI) and Brockington's sub-types. The identified patients (n = 4) also underwent psychometric evaluation including examination of affective functioning, intellectual capacity and neuropsychological functioning (i.e.attention and concentration, learning and remembering, executive function, processing speed and speech and language). The analysis of outcome measures was via an idiographic approach. RESULTS: The spectrum of distress among people with menstrual psychosis does not fit existing psychiatric nosology. Evaluations revealed that a majority of the participants displayed something akin to morbid phenomena relating to manic and psychotic symptoms. In the parlance of traditional Omani society, this would be termed "spirit possession". In terms of classification by timing within the menstrual cycle as expounded by Brockington, the present case series in Oman fulfilled the definition of catamenial psychosis and paramenstrual psychosis. With regard to psychometric function, all participants performed adequately on indices of intellectual functioning but appeared to have impairments in neuropsychological functioning, including the dimensions of processing speed, episodic memory, and executive functioning. Within the given society, the periodicity of mind alteration has been attributed to spirit possession. CONCLUSIONS: This is one of the first case series of its kind in the country elucidating whether the manifestation of menstrual psychosis among individuals in Oman fulfills the subtypes postulated by Brockington. The present case series suggests that menstrual psychosis is marked with neuropsychological impairments that were previously observed in other phasic manic episodes or brief psychotic disorders.

Risk factors underlying depressive symptoms among parents/primary care providers of kids with autism spectrum disorder: A study from Muscat, Oman.

AIM: To explore the prevalence and correlates of depressive symptoms among parents/primary care providers of children with autism spectrum disorder (ASD). DESIGN AND METHODS: A cross-sectional analytical study was conducted among a systematic random sample of parents/caregivers of children with diagnosis of ASD in Muscat, Oman. Depressive symptoms were quantified using the Patient Health Questionnaire-9. FINDINGS: The response rate was at 86% (n = 80) and the prevalence of depressive symptoms, at 71.3% (95% confidence interval, 60.5-80.1). Logistic regression analyses indicated that unemployment and being the sole parent/caregiver in the family were both significant correlates of depressive symptoms. PRACTICE IMPLICATIONS: With an increase in the number of children being diagnosed with ASD, multidimensional preventive and remedial service programs for parents/caregivers will be essential.

The characteristics and patterns of utilization of healthcare services among Omanis with substance use disorders attending therapy for cessation.

BACKGROUND: It is indicated that Oman is witnessing an increase in issues pertinent to alcohol and psychoactive substance use. AIM: The aim of this study was to identify the characteristics of Omanis with substance use disorder attending a specialized hospital in Oman and the pattern of their utilization of healthcare services. A related aim was to ascertain the age group most vulnerable to alcohol and substance use in Oman. METHOD: A cross-sectional study was conducted in a tertiary care center specialized for treatment of those engaging in substance use in Oman. The participants in the study were selected from a convenience sample among patients seeking consultation at the center for alcohol and substance use. A six-part questionnaire was designed to obtain information regarding socio-demographic background, clinical history, healthcare utilization and perceived hurdles to access. Chi-square analyses were used to evaluate the significance of differences among categorical data. Logistic regression modelling was used to obtain measures of association after adjusting for confounding factors. RESULTS: Among the patients (n = 293) seeking cessation therapy, 99% were male and less than 30 years of age. Peer influences on the initiation of substance use were significant. Most patients had a history of polysubstance use, including intravenous substance use. Cannabis and alcohol were the first substances consumed by most patients and Hepatitis C and psychiatric disorders were found to be the most common co-morbidities. The participants that reported use of cannabis and benzodiazepines were more likely to perceive "improvement" upon receiving treatment. CONCLUSION: This study indicated that males below 30 years of age with a history of polysubstance use were likely to attend a hospital specialized in treating substance use disorder in Oman. This study identified information regarding socio-demographic background, risk factors and perceived hurdles to healthcare that could serve as groundwork for further studies conducted on newly emerging issues of substance use in Oman.

Causative Mutations and Mechanism of Androgenetic Hydatidiform Moles.

Androgenetic complete hydatidiform moles are human pregnancies with no embryos and affect 1 in every 1,400 pregnancies. They have mostly androgenetic monospermic genomes with all the chromosomes originating from a haploid sperm and no maternal chromosomes. Androgenetic complete hydatidiform moles were described in 1977, but how they occur has remained an open question. We identified bi-allelic deleterious mutations in MEI1, TOP6BL/C11orf80, and REC114, with roles in meiotic double-strand breaks formation in women with recurrent androgenetic complete hydatidiform moles. We investigated the occurrence of androgenesis in Mei1-deficient female mice and discovered that 8% of their oocytes lose all their chromosomes by extruding them with the spindles into the first polar body. We demonstrate that Mei1-/- oocytes are capable of fertilization and 5% produce androgenetic zygotes. Thus, we uncover a meiotic abnormality in mammals and a mechanism for the genesis of androgenetic zygotes that is the extrusion of all maternal chromosomes and their spindles into the first polar body.