Seasonal variation and sleep patterns in a hot climate Arab Region.

PURPOSE: To describe the effect of seasonal variations on sleep patterns in a hot climate Arab region. METHODS: This is a cross-sectional study that included healthy Omani subjects of both genders between ages 18 and 59 years. Data for sleep pattern identification in summer and winter were collected from participants using an actigraphy wristband. RESULTS: Among 321 participants, in summer seasons, a polyphasic sleep pattern (40%) prevailed over other sleep patterns (P < 0.001). While in the winter season, monophasic sleep (31%) was the dominant pattern (P < 0.001). Subjects slept longer during the winter seasons with total hours of sleep during the day 48 min longer than in the summer, though the difference was not statistically significant (P > 0.05), while siesta duration in the summer was significantly longer (13 min, P < 0.01). In summer, the sleep quality was good (PSQI ≤ 5); however, it was poor (PSQI > 5) in winter (P < 0.05). Night sleep duration, daytime sleepiness, and sleep latency were not statistically different between the summer and winter seasons. CONCLUSION: Sleep patterns may be influenced by seasonal changes. A polyphasic sleep pattern prevailed in summer while a monophasic pattern was the predominant sleep pattern in winter. In summer, the sleep quality was good and the siesta duration was longer compared to the winter.

Agreement analysis of sleep patterns between self-reported questionnaires and actigraphy in adults.

PURPOSE: To investigate the agreement in sleep pattern recording by self-reported sleep questionnaires and actigraphy in adults. METHODS: This is a cross-sectional study. Men and women who met inclusion criteria were recruited for this study. The inclusion criteria were apparently healthy Omani nationals ages 19 to 50 years. Sleep questionnaires were randomly distributed in Muscat either directly or via electronic and paper announcements. Data were collected from the participants using the self-reported questionnaires with four piloted questions for sleep pattern identification and through the actigraphy wristband given to subjects to wear for a week. Cohen's kappa test was performed for agreement analysis. RESULTS: A total of 964 Omani subjects between ages 18 and 59 years of both genders were recruited and completed the questionnaires successfully. Out of these, only 321 subjects wore the actigraphy wristband for 1 week (response rate = 33%). Agreement analysis reported a mild level of agreement for the monophasic (41%), moderate level for biphasic (59%), and good level for polyphasic (70%) sleep patterns. The overall agreement level of sleep patterns between the two methods was 57%. There is a low specificity of self-reported assessment in reporting sleep pattern. CONCLUSION: The average agreement level of subjective versus objective assessments of sleep patterns was moderate at 57% and self-reported sleep pattern is not specific. The study recommends the use of actigraphy along with sleep questionnaires for accurate assessment of sleep patterns in cohort studies.

Deletion of SOCS2 Reduces Post-Colitis Fibrosis via Alteration of the TGFß Pathway.

Inflammatory bowel disease (IBD) is an immunologically mediated chronic intestinal disorder. Growth hormone (GH) administration enhances mucosal repair and decreases intestinal fibrosis in patients with IBD. In the present study, we investigated the effect of cellular sensitivity to GH via suppressor of cytokine signaling 2 (SOCS2) deletion on colitis and recovery. To induce colitis, wild type and SOCS2 knockout (SOCS2-/-) mice were treated with 3% dextran sodium sulphate (DSS), followed by a recovery period. SOCS2-/- mice showed higher disease activity during colitis with increased mRNA expression of the pro-inflammatory cytokines nitric oxide synthase 2 (NOS2) and interleukin 1 ß (IL1-ß). At recovery time point, SOCS2-/- showed better recovery with less fibrosis measured by levels of α-SMA and collagen deposition. Protein and mRNA expressions of transforming growth factor beta ß1 (TGF-ß1) receptors were significantly lower in SOCS2-/- mice compared to wild-type littermates. Using an in vivo bromodeoxyuridine (BrdU) proliferation assay, SOCS2-/- mice showed higher intestinal epithelial proliferation compared to wild-type mice. Our results demonstrated that deletion of the SOCS2 protein results in higher growth hormone sensitivity associated with higher pro-inflammatory signaling; however, it resulted in less tissue damage with less fibrotic lesions and higher epithelial proliferation, which are markers of GH-protective effects in IBD. This suggests a pleiotropic effect of SOCS2 and multiple cellular targets. Further study is required to study role of SOCS2 in regulation of TGFß-mothers against the decapentaplegic homolog (Smad) pathway.

Tuberous Sclerosis Complex Axis Controls Renal Extracellular Vesicle Production and Protein Content.

The tuberous sclerosis complex (Tsc) proteins regulate the conserved mTORC1 growth regulation pathway. We identified that loss of the Tsc2 gene in mouse inner medullary collecting duct (mIMCD) cells induced a greater than two-fold increase in extracellular vesicle (EV) production compared to the same cells having an intact Tsc axis. We optimized EV isolation using a well-established size exclusion chromatography method to produce high purity EVs. Electron microscopy confirmed the purity and spherical shape of EVs. Both tunable resistive pulse sensing (TRPS) and dynamic light scattering (DLS) demonstrated that the isolated EVs possessed a heterogenous size distribution. Approximately 90% of the EVs were in the 100-250 nm size range, while approximately 10% had a size greater than 250 nm. Western blot analysis using proteins isolated from the EVs revealed the cellular proteins Alix and TSG101, the transmembrane proteins CD63, CD81, and CD9, and the primary cilia Hedgehog signaling-related protein Arl13b. Proteomic analysis of EVs identified a significant difference between the Tsc2-intact and Tsc2-deleted cell that correlated well with the increased production. The EVs may be involved in tissue homeostasis and cause disease by overproduction and altered protein content. The EVs released by renal cyst epithelia in TSC complex may serve as a tool to discover the mechanism of TSC cystogenesis and in developing potential therapeutic strategies.

Homozygosity for FARSB mutation leads to Phe-tRNA synthetase-related disease of growth restriction, brain calcification, and interstitial lung disease.

Aminoacyl-tRNA synthetases (ARSs) canonical function is to conjugate specific amino acids to cognate tRNA that are required for the first step of protein synthesis. Genetic mutations that cause dysfunction or absence of ARSs result in various neurodevelopmental disorders. The human phenylalanine-tRNA synthetase (PheRS) is a tetrameric protein made of two subunits coded by FARSA gene and two subunits coded by FARSB gene. We describe eight affected individuals from an extended family with a multisystemic recessive disease manifest as a significant growth restriction, brain calcifications, and interstitial lung disease. Genome-wide linkage analysis and whole exome sequencing identified homozygosity for a FARSB mutation (NM_005687.4:c.853G > A:p.Glu285Lys) that co-segregate with the disease and likely cause loss-of-function. This study further implicates FARSB mutations in a multisystem, recessive, neurodevelopmental phenotype that share clinical features with the previously known aminoacyl-tRNA synthetase-related diseases.

Reanalysis of exome sequencing data of intellectual disability samples: Yields and benefits.

Recently, with the advancement in next generation sequencing (NGS) along with the improvement of bioinformatics tools, whole exome sequencing (WES) has become the most efficient diagnostic test for patients with intellectual disability (ID). This study aims to estimate the yield of a reanalysis of ID negative exome cases after data reannotation. Total of 50 data files of exome sequencing, representing 50 samples were collected. The inclusion criteria include ID phenotype, and previous analysis indicated a negative result (no abnormality detected). These files were pre-processed and reannotated using ANNOVAR tool. Prioritized variants in the 50 cases studied were classified into three groups, (1) disease-causative variants (2) possible disease-causing variants and (3) variants in novel genes. Reanalysis resulted in the identification of pathogenic/likely pathogenic variants in six cases (12%). Thirteen cases (26%) were classified as having possible disease-causing variants. Candidate genes requiring future functional studies were detected in seven cases (14%). Improvement in bioinformatics tools, update in the genetic databases and literature, and patients' clinical phenotype update were the main reasons for identification of these variants in this study.

Genetic diversity and prevalence of CCR2-CCR5 gene polymorphisms in the Omani population.

Polymorphisms in the regulatory region of the CCR5 gene affect protein expression and modulate the progress of HIV-1 disease. Because of this prominent role, variations in this gene have been under differential pressure and their frequencies vary among human populations. The CCR2V64I mutation is tightly linked to certain polymorphisms in the CCR5 gene. The current Omani population is genetically diverse, a reflection of their history as traders who ruled extensive regions around the Indian Ocean. In this study, we examined the CCR2-CCR5 haplotypes in Omanis and compared the patterns of genetic diversity with those of other populations. Blood samples were collected from 115 Omani adults and genomic DNA was screened to identify the polymorphic sites in the CCR5 gene and the CCR2V64I mutation. Four minor alleles were common: CCR5-2554T and CCR5-2086G showed frequencies of 49% and 46%, respectively, whereas CCR5-2459A and CCR5-2135C both had a frequency of 36%. These alleles showed moderate levels of heterozygosity, indicating that they were under balancing selection. However, the well-known allele CCR5Δ32 was relatively rare. Eleven haplotypes were identified, four of which were common: HHC (46%), HHE (20%), HHA (14%) and HHF*2 (12%).

Elevated oxidative stress biomarkers in adults with segmented sleep patterns.

STUDY OBJECTIVES: We investigated the association between different sleep patterns and inflammatory and oxidative stress biomarkers in adults. METHODS: A total of 321 consented adults who fulfilled the inclusion criteria were recruited in this cross-sectional study. The inclusion criteria were mainly based on apparently healthy adults aged 18-59 years. To identify sleep patterns, participants were requested to wear the actigraph for 1 week for 24 hours a day. Fasting blood was collected from each participant at day 8. The blood serum was analyzed for inflammatory and oxidative stress biomarkers. Sleep patterns were defined as monophasic (1 episode of night sleep) biphasic (2 episodes of sleep; night and aternoon siesta), and polyphasic sleep pattern (3 or more sleep episodes). RESULTS: There was no correlation between night sleep duration, total sleep in 24 hours, and napping among inflammatory and oxidative stress biomarkers: high-sensitivity C-reactive protein, malondialdehyde, total glutathione, and basal oxidizability status. Actigraphy reports showed 3 sleep patterns in this cohort, monophasic (24.3%), biphasic-napping (45.2%) and polyphasic (30.5%). Individuals with segmented sleep patterns were significantly associated with oxidative stress biomarkers. A polyphasic sleep pattern was significantly associated with higher basal oxidizability status (P = .023), whereas a biphasic sleep pattern showed higher malondialdehyde (P = .036) as compared to a monophasic sleep pattern. Total glutathione was significantly higher in monophasic sleepers (P = .046). There was no difference in serum high-sensitivity C-reactive protein among all sleep patterns. CONCLUSIONS: Segmented sleep in polyphasic and biphasic sleep patterns is associated with higher serum malondialdehyde and basal oxidizability status in particular. Further studies are recommended on the cardiometabolic impact of oxidative stress biomarkers in individuals with segmented sleep. CITATION: Al Lawati I, Zadjali F, Al-Abri MA. Elevated oxidative stress biomarkers in adults with segmented sleep patterns. J Clin Sleep Med. 2024;20(6):959-966.

Revisiting Exome Data Identified Missed Splice Site Variant of the Asparagine Synthetase ( ASNS ) Gene.

Next-generation sequencing, such as whole-exome sequencing (WES), is increasingly used in the study of Mendelian disorders, yet many are reported as "negative." Inappropriate variant annotation and filtering steps are reasons for missing the molecular diagnosis. Noncoding variants, including splicing mutations, are examples of variants that can be overlooked. Herein, we report a family of four affected newborns, and all presented with severe congenital microcephaly. Initial research WES analysis identified a damaging homozygous variant in NME1 gene as a possible cause of primary microcephaly phenotype in these patients. However, reanalysis of the exome data uncovered a biallelic splice site variant in asparagine synthetase gene which seems to be the possible cause of the phenotype in these patients. This study highlights the importance of revisiting the exome data and the issue of "negative" exome and the afterward approaches to identify and prove new candidate genes.

Suppressor of cytokine signaling 6 (SOCS6) negatively regulates Flt3 signal transduction through direct binding to phosphorylated tyrosines 591 and 919 of Flt3.

The receptor tyrosine kinase Flt3 is an important growth factor receptor in hematopoiesis, and gain-of-function mutations of the receptor contribute to the transformation of acute myeloid leukemia. SOCS6 (suppressor of cytokine signaling 6) is a member of the SOCS family of E3 ubiquitin ligases that can regulate receptor tyrosine kinase signal transduction. In this study, we analyzed the role of SOCS6 in Flt3 signal transduction. The results show that ligand stimulation of Flt3 can induce association of SOCS6 and Flt3 and tyrosine phosphorylation of SOCS6. Phosphopeptide fishing indicated that SOCS6 binds directly to phosphotyrosines 591 and 919 of Flt3. By using stably transfected Ba/F3 cells with Flt3 and/or SOCS6, we show that the presence of SOCS6 can enhance ubiquitination of Flt3, as well as internalization and degradation of the receptor. The presence of SOCS6 also induces weaker activation of Erk1/2, but not Akt, in transfected Ba/F3 and UT-7 cells and in OCI-AML-5 cells. The absence of SOCS6 promotes Ba/F3 and UT-7 cell proliferation induced by oncogenic internal tandem duplications of Flt3. Taken together, these results suggest that SOCS6 negatively regulates Flt3 activation, the downstream Erk signaling pathway, and cell proliferation.

SOCS2 deletion protects against hepatic steatosis but worsens insulin resistance in high-fat-diet-fed mice.

Hepatic steatosis is a prominent feature in patients with growth hormone (GH) deficiency. The ubiquitin ligase SOCS2 attenuates hepatic GH signaling by inhibiting the Janus kinase 2 (JAK2)-signal transducer and activator of transcription 5b (STAT5b) axis. Here, we investigated the role of SOCS2 in the development of diet-induced hepatic steatosis and insulin resistance. SOCS2-knockout (SOCS2(-/-)) mice and wild-type littermates were fed for 4 mo with control or high-fat diet, followed by assessment of insulin sensitivity, hepatic lipid content, and expression of inflammatory cytokines. SOCS2(-/-) mice exhibited increased hepatic TG secretion by 77.6% (P<0.001) as compared with wild-type control mice and were protected from high-fat-diet (HFD)-induced hepatic steatosis, showing 49.3% (P<0.01) reduction in liver TG levels compared to HFD-fed wild-type littermates. In contrast, we found that HFD-triggered attenuation of systemic insulin sensitivity was more marked in SOCS2(-/-) mice. Livers from the HFD-fed SOCS2(-/-) mice showed increased NF-κB activity as well as elevated expression of genes for the inflammatory cytokines IFN-γ and IL-6. An inhibitory role of SOCS2 on Toll-like receptor 4 signaling was demonstrated in macrophages obtained from the SOCS2(-/-) and wild-type mice. This study identified SOCS2 as an important regulator of hepatic homeostasis under conditions of high-fat dietary stress.

Reference Ranges of Serum Anti-Müllerian Hormone in Healthy Reproductive-aged Omani Women.

Objectives: Anti-Müllerian hormone (AMH), a glycoprotein that belongs to the transforming growth factor-beta superfamily, is important for women's health. We aimed to determine the age-specific reference range of serum AMH in healthy Omani women from reproductive ages to menopause. Methods: This cross-sectional cohort study was conducted among a group of healthy 20-50 years old Omani women. The participants were required to have body mass index < 32 kg/m2, regular periods, no history of chronic illness, polycystic ovary syndrome, or gynecological operation. They were also required to not be using any hormonal contraceptive. Serum concentrations of AMH, follicle-stimulating hormone, luteinizing hormone, progesterone, and hemoglobin A1c were measured. AMH-age nomogram and AMH levels were compared between the six selected age groups. Results: The subjects were 319 Omani women aged 20-50 years. Serum AMH concentrations were found to decrease progressively with increasing age. An exponential model defined as √AMH = 479.02 × 0.91age was selected to explain the reduction in AMH with age (R2 = 0.298). The median AMH levels were 26.61 pmol/L for those aged 20-25 years, 20.89 pmol/L for 26-30 years, 19.92 pmol/L for 31-35 years, 13.71 pmol/L for 36-40 years, 9.24 pmol/L for 41-45 years, and 0.68 pmol/L for 46-50 years. The recommended 2.5th to 97.5th percentiles of AMH level, as reference ranges for various age groups, were found to be: 10.63-55.64 pmol/L (20-25 years), 3.74-61.88 pmol/L (26-30 years), 5.49-47.56 pmol/L (31-35 years), 2.15-48.91 pmol/L (36-40 years), 0.92-41.26 pmol/L (41-45 years), and 0.14-5.10 pmol/L (46-50 years). Conclusions: This study (the first in Oman) determined the age-specific reference ranges of serum AMH in healthy Omani women in the age range of 20-50 years.

Base of the tongue hyalinizing clear cell carcinoma: Case report and literature review.

Hyalinizing clear cell carcinoma is an uncommon neoplasm arising in minor salivary glands. We present a rare case of hyalinizing clear cell carcinoma in the base of the tongue. We report a case of a 38-year-old female presented with a progressive history of hemoptysis and dysphagia over the course of 4 years. Examination revealed a mass originating from the base of the tongue with a biopsy confirmed as hyalinizing clear cell carcinoma . An Ovid MEDLINE and PubMed literature review was conducted due to the rarity of this type of tumor. The patient underwent surgical excision with immediate reconstruction with radial forearm free flap followed with adjuvant radiotherapy and was disease free at her most recent follow-up (12 months). Our review included a total of 13 new cases, including our case. The majority of the cases presented with dysphagia. Surgical excision is the mainstay of treatment, and overall these patients have a good prognosis. Our case highlights a rare presentation of hyalinizing clear cell carcinoma of the base of the tongue, successfully treated with surgical excision, free tissue reconstruction and adjuvant radiotherapy.

Gender-specific Reference Range for Serum Leptin in Omani Population.

Objectives: Leptin is a hormone that contributes to glucose homeostasis and food intake regulation via its action on the hypothalamus. Leptin level increases with obesity and overfeeding and decreases with energy deficiency. Serum leptin levels vary between different ethnic groups with no reports of its reference range in the Arabic population. We sought to determine gender-specific reference ranges for serum leptin in a cohort of the Arabic population and identify the cut-off value for different metabolic derangements. Methods: The study data were obtained from the records of 1198 subjects included in the Oman Family Study. The percentile method was used in the estimation reference range and the receiver operating characteristic to identify cut-off points for multiple metabolic derangements. Results: The reference range of serum leptin was 0.5-90.6 ng/mL, and it was not correlated with the age of the subjects. Higher leptin was observed in females compared to males (p < 0.001), and the reference range for serum leptin in females was 4.9-96.3 ng/mL compared to 0.25-48.8 ng/mL in males. The optimum cut-off value for leptin ranged between 24.1-28.9 ng/mL for metabolic syndrome, obesity, central obesity, and type 2 diabetes. Conclusions: We identified gender-specific reference ranges for serum leptin in a large cohort of Arabs. The optimum cut-off value for serum leptin to determine metabolic derangement with the highest sensitivity and specificity was 24.1-28.9 ng/mL. Future studies are needed to study the relative risk of higher serum leptin using prospective studies.

Cytotoxicity, mutagenicity and genotoxicity of electronic cigarettes emission aerosols compared to cigarette smoke: the REPLICA project.

Concerns have recently increased that the integrity of some scientific research is questionable due to the inability to reproduce the claimed results of some experiments and thereby confirm that the original researcher's conclusions were justified. This phenomenon has been described as 'reproducibility crisis' and affects various fields from medicine to basic applied sciences. In this context, the REPLICA project aims to replicate previously conducted in vitro studies on the toxicity of cigarette smoke and e-cigarette aerosol, sometimes adding experiments or conditions where necessary, in order to verify the robustness and replicability of the data. In this work the REPLICA Team replicated biological and toxicological assessment published by Rudd and colleagues in 2020. As in the original paper, we performed Neutral Red Uptake (NRU) assay for the evaluation of cytotoxicity, Ames test for the evaluation of mutagenesis and In Vitro Micronuclei (IVMN) assay for the evaluation of genotoxicity on cells treated with cigarette smoke or e-cigarette aerosol. The results showed high cytotoxicity, mutagenicity and genotoxicity induced by cigarette smoke, but slight or no cytotoxic, mutagenic and genotoxic effects induced by the e-cigarette aerosol. Although the two studies presented some methodological differences, the findings supported those previously presented by Rudd and colleagues.

Structural basis for c-KIT inhibition by the suppressor of cytokine signaling 6 (SOCS6) ubiquitin ligase.

The c-KIT receptor tyrosine kinase mediates the cellular response to stem cell factor (SCF). Whereas c-KIT activity is important for the proliferation of hematopoietic cells, melanocytes and germ cells, uncontrolled c-KIT activity contributes to the growth of diverse human tumors. Suppressor of cytokine signaling 6 (SOCS6) is a member of the SOCS family of E3 ubiquitin ligases that can interact with c-KIT and suppress c-KIT-dependent pathways. Here, we analyzed the molecular mechanisms that determine SOCS6 substrate recognition. Our results show that the SH2 domain of SOCS6 is essential for its interaction with c-KIT pY568. The 1.45-Å crystal structure of SOCS6 SH2 domain bound to the c-KIT substrate peptide (c-KIT residues 564-574) revealed a highly complementary and specific interface giving rise to a high affinity interaction (K(d) = 0.3 µm). Interestingly, the SH2 binding pocket extends to substrate residue position pY+6 and envelopes the c-KIT phosphopeptide with a large BG loop insertion that contributes significantly to substrate interaction. We demonstrate that SOCS6 has ubiquitin ligase activity toward c-KIT and regulates c-KIT protein turnover in cells. Our data support a role of SOCS6 as a feedback inhibitor of SCF-dependent signaling and provides molecular data to account for target specificity within the SOCS family of ubiquitin ligases.

Association of elevated glycated hemoglobin and obesity with afternoon napping for more than 1 h in young and middle-aged healthy adults.

Introduction: Sleep has different patterns followed worldwide and can be influenced by social, cultural, and environmental factors. Daytime napping is commonly practiced in different parts of the world with controversial results of its effect on glucose metabolism. The current study aims to examine the association of afternoon napping and night sleep duration with metabolic derangements. Methods: This is a cross-sectional study involving young adults and middle-aged subjects. Anthropometric measurements were taken for height and weight and hip and waist ratio. Consented subjects were asked to wear actigraphy for 1 week and run their usual daily activities. Home sleep apnea testing was performed to exclude obstructive sleep apnea. Subjects had been asked to come fasting on day seven for blood collection to test for fasting glucose, glycated hemoglobin, lipid profile, and insulin. Results: A total of 405 subjects were involved to complete the study (52% male, 48% female). The mean age of participants was 32.8 ± 11.5 years. The study indicated that the duration of afternoon napping was significantly associated with abnormal glycated hemoglobin (HbA1c > 5.7%) (p = 0.01) and body mass index (p = 0.046) independent of age, gender, and nocturnal sleep duration. Nocturnal sleep duration was associated with increased insulin level (p = 0.04). Conclusion: Afternoon napping is associated with an increased level of glycated hemoglobin and obesity and that may predispose to the development of type 2 diabetes mellitus.

The Parental and Children Report of the Prevalence of Depressive Symptoms in Children and Adolescents Amid the COVID-19 Pandemic: A Cross-Sectional Study From Oman.

Objective: Studies from the past decades have shown that mood disorders are common during childhood and adolescence. This study aimed to estimate the point prevalence of depression in Omani children and adolescents during social distancing and lockdown and identify the risk factors for developing depressive symptoms during the COVID-19 pandemic. Methods: This is an analytical cross-sectional study conducted in May 2020, in which all young Omani people attending a mainstream school aged 8-18 years old were eligible to participate. Parents were asked to complete the online survey, which consisted of the parent version of the Mood and Feelings Questionnaire (MFQ-Parent). In addition, the option of a self-reported version (MFQ-Self) was provided in cases where children preferred to fill out the survey themselves. Logistic regression was used to identify the contributing socio-demographic variables associated with depressive symptoms. Results: A total of 445 participants completed the MFQ, out of which 72.1% were parents, and 27.9% were children, adolescents and young people. 13.9% of children and adolescents exhibited depressive symptoms during the COVID-19 pandemic in Oman. The presence of depressive symptoms was associated with increased food intake (OR 1.81, 95% CI 1.00-3.29, p-value <0.05), longer use of smartphones (OR 2.72, 95% CI 1.56-4.73, p-value <0.001), whereas additional entertainment activities during lockdown were protective against depression (OR 0.35 95% CI 0.19-0.64, p-value <0.001). Conclusion: This study from Oman concurs with recent reports of depression being common during the COVID-19 pandemic. Concerted efforts are needed to mitigate this trend and identify high-risk groups during the lockdown period.

Single Gene Mutations in Pkd1 or Tsc2 Alter Extracellular Vesicle Production and Trafficking.

Patients with autosomal dominant polycystic kidney disease (ADPKD) and tuberous sclerosis complex (TSC) are born with normal or near-normal kidneys that later develop cysts and prematurely lose function. Both renal cystic diseases appear to be mediated, at least in part, by disease-promoting extracellular vesicles (EVs) that induce genetically intact cells to participate in the renal disease process. We used centrifugation and size exclusion chromatography to isolate the EVs for study. We characterized the EVs using tunable resistive pulse sensing, dynamic light scattering, transmission electron microscopy, and Western blot analysis. We performed EV trafficking studies using a dye approach in both tissue culture and in vivo studies. We have previously reported that loss of the Tsc2 gene significantly increased EV production and here demonstrate that the loss of the Pkd1 gene also significantly increases EV production. Using a cell culture system, we also show that loss of either the Tsc2 or Pkd1 gene results in EVs that exhibit an enhanced uptake by renal epithelial cells and a prolonged half-life. Loss of the primary cilia significantly reduces EV production in renal collecting duct cells. Cells that have a disrupted Pkd1 gene produce EVs that have altered kinetics and a prolonged half-life, possibly impacting the duration of the EV cargo effect on the recipient cell. These results demonstrate the interplay between primary cilia and EVs and support a role for EVs in polycystic kidney disease pathogenesis.

Socio-Demographic and Clinical Profiles of Adult Attention Deficit Hyperactivity Disorder Patients in a University Hospital in Oman.

Objectives: Although attention deficit hyperactivity disorder (ADHD) is typically considered a condition affecting children, there is evidence that children diagnosed with ADHD continue to suffer from this condition after the age of 18. This study aimed to describe the socio-demographic and clinical characteristics of adult ADHD patients in Oman and evaluate their association with the disorder's different subtypes. Methods: This retrospective study included adult patients with ADHD from the outpatient clinic at Sultan Qaboos University Hospital, Muscat, Oman. Data from medical records from January 2018 to April 2020 were collected. Socio-demographic characteristics, clinical profiles and psychiatric comorbidities were examined. Results: This study included 100 adults who fulfilled the standard diagnosis of ADHD, with 54.0% (n = 54) and 46.0% (n = 46) from the inattentive and combined subtypes, respectively. It was found that ADHD was more prevalent among males (64.0%) than females (36.0%), with the inattentive subtype being more predominant among females. The ADHD patients with the inattentive subtype were associated with comorbid substance use disorders (odds ratio [OR] = 11.29; P = 0.049), personality disorders (OR = 7.96; P = 0.017) and major depressive disorder (OR = 15.94; P = 0.002) compared to patients predominantly with the combined subtype. Conclusion: This study echoes the findings from the current literature that adult patients with ADHD commonly have comorbid psychiatric disorders, leading to significant functional impairment. Psychiatric comorbidities must be identified and urgently treated for better clinical and functional outcomes in adult patients with ADHD.