Circadian clock gene disruption in white blood cells of patients with celiac disease.

Clock gene disruption has been reported in inflammatory and autoimmune diseases. Specifically, it has been shown that clock gene expression is down-regulated in intestinal tissue and peripheral blood mononuclear cells of patients with inflammatory bowel disease (IBD). We aimed to determine the systemic expression of the circadian clock genes in newly diagnosed untreated, young patients with celiac disease (CeD). We prospectively enrolled patients younger than 20 years old who underwent diagnostic endoscopic procedures either for CeD diagnosis or due to other gastrointestinal complaints, at the pediatric and adult gastroenterology units, the Tel Aviv Sourasky Medical Center from 8/2016-8/2022. Demographic data, anthropometric parameters, and endoscopic macroscopic and microscopic findings were obtained. Blood samples were obtained to determine tissue transglutaminase (tTG) and core clock gene (CLOCK, BMAL1, PER1, PER2, CRY1, CRY2) expression in white blood cells (WBC). Thirty individuals were analyzed (18 with newly diagnosed CeD and 12 controls). Expression of the clock genes CLOCK, BMAL1, CRY2, PER1 and PER2 was significantly reduced in CeD patients compared to controls, while CRY1 did not differ between the groups. In conclusion, newly diagnosed, untreated, young patients with CeD have reduced clock gene expression in WBC compared to controls. These results suggest that, in CeD, the inflammatory response is associated with systemic disruption of clock gene expression, as is manifested in other inflammatory and autoimmune diseases. CLINICALTRIALS.GOV IDENTIFIER: NCT03662646.

Inverse Relationship Between Clock Gene Expression and Inflammatory Markers in Ulcerative Colitis Patients Undergoing Remission.

BACKGROUND: Changes in the expression of clock genes have been reported in inflammatory bowel disease (IBD) patients. AIMS: We aimed to investigate whether reduced inflammation restores clock gene expression to levels of healthy controls. METHODS: This was a prospective study. Participants completed questionnaires providing data on demographics, sleeping habits, and disease activity. Anthropometric parameters, C-reactive protein (CRP), and fecal calprotectin (Fcal) levels were collected. Peripheral blood samples were analyzed for clock gene (CLOCK, BMAL1, CRY1, CRY2, PER1, PER2) expression. Patients with IBD were separated by diagnosis into ulcerative colitis (UC) and Crohn's disease (CD). Each diagnosis was further divided into active disease and disease under remission. RESULTS: Forty-nine patients with IBD and 19 healthy controls completed the study. BMAL1 and PER2 were significantly reduced in active patients with UC compared to patients with UC in remission. BMAL1, PER1, and PER2 were significantly reduced in patients with UC with CRP > 5 mg/dl. PER2, CRY1, and CRY2 were significantly reduced in patients with UC with Fcal > 250 mg/kg. Clock gene expression of patients with UC in remission was comparable to healthy controls. When all patients with IBD were analyzed, an overshoot in CRY1 expression was observed in patients in remission, patients with CRP < 5 mg/dl, and patients with Fcal < 250 mg/kg. CONCLUSION: CRP and Fcal are inversely related to clock gene levels in patients with UC. CRY1 may play a role in counteracting the anti-inflammatory processes when remission is induced in patients with IBD. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03662646.

Enuresis--an unattended comorbidity of childhood obesity.

OBJECTIVE: Obstructive sleep apnea (OSA), attention deficit/hyperactivity disorder (ADHD), type 2 diabetes mellitus and psychopathological problems co-occur at increased rates among both obese and enuretic children. We hypothesized that the prevalence of enuresis will be increased in obese children and adolescents. DESIGN: A cross-sectional study. SUBJECTS: 281 children and adolescents aged 7-18 years, who completed a questionnaire regarding enuresis, medical conditions and sociodemographic parameters; 158 were normal weight, 37 overweight (85thBMI (body mass index)<95th percentiles) and 86 obese (BMI95th percentile). MAIN OUTCOME MEASURE(S): Occurrence of enuresis among obese children and adolescents. RESULTS: Enuresis was reported in 14 (8.8%) normal weight, 6 (16%) overweight and 26 (30%) obese youth. Odds ratio (OR)=6.5, 95% confidence interval (CI)=2.67-15.78 for enuresis among obese compared with normal weight (P<0.0001). Each increment of one BMI-Z score unit was associated with an increased risk of enuresis, OR of 2.14, 95% CI (1.46-3.12), P=0.00008. Male gender (OR 2.84, 95% CI (1.10-5.58), P=0.028), first-degree relative with current/past enuresis (OR 4.24, 95% CI (1.62-11.08), P=0.003), voiding dysfunction symptoms (OR 3.067, 95% CI (1.05-9.00), P=0.041) and ADHD (OR 2.31, 95% CI (0.99-5.34), P=0.051) increased the risk of enuresis. OSA-related symptoms, academic achievements in school, sharing a bedroom, family size relative to number of rooms in home, parental education, family status and religious observance were not found to increase the risk for enuresis. CONCLUSIONS: Obese children are at increased risk for enuresis. Enuresis should be clarified during the primary workup of every obese child and adolescent.

Risk factors for relaparotomy after cesarean section.

OBJECTIVE: To investigate risk factors for relaparotomy after cesarean section (CS). METHODS: A retrospective case-control study comparing all CS that were complicated with relaparotomy to cesarean deliveries without this complication. RESULTS: Relaparotomy complicated 0.23% (n=80) of CS during the study period (n=34,389). Independent risk factors for relaparotomy following CS from a multivariable logistic regression model were post partum hemorrhage, cervical tears, placenta previa, uterine rupture, placental abruption, severe preeclampsia and previous CS. Most women (51.2%) underwent relaparotomy during the first 24 h after CS. The leading causes for relaparotomy was bleeding (70%) and burst abdomen (8.8%). Hysterectomy was performed in 31.3% of the patients. CONCLUSION: Risk factors for relaparotomy after CS are previous CS, severe preeclampsia, placenta previa, uterine rupture, placental abruption, cervical tear and PPH. Experienced obstetricians should be involved in such cases and the possibility for complications including relaparotomy should be emphasized.