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.

Hepcidin, soluble transferrin receptor and IL-6 levels in obese children and adolescents with and without type 2 diabetes mellitus/impaired glucose tolerance and their association with obstructive sleep apnea.

PURPOSE: Obesity, type 2 diabetes mellitus (T2DM), and obstructive sleep apnea (OSA) are associated with chronic low-grade inflammation. Iron metabolism is linked with insulin-resistant states and with OSA in adults. The association of body iron status with T2DM in children remains undefined. We aimed to evaluate plasma interleukin-6 (IL-6), hepcidin, and soluble transferrin receptor (sTfR) levels in obese patients with T2DM or impaired glucose tolerance (IGT) and in those without, and the contribution of OSA to their levels. METHODS: In this cross-sectional study, obese children and adolescents with and without T2DM/IGT underwent overnight polysomnography. Fasting plasma concentrations of IL-6, hepcidin, and sTfR were measured and evaluated according to glycemic status (T2DM/IGT and normal glucose tolerance) and the presence of OSA. RESULTS: Ten patients with T2DM (age 15.9 ± 3.6 years), 8 with IGT (age 13.1 ± 2.5 years) and 20 subjects with normal glucose tolerance matched for body mass index standard deviation score (age 12.6 ± 3.3 years) were studied. Sleep measures or IL-6, hepcidin, and sTfR levels were not significantly different between the group with T2DM/IGT vs. the control group. No significant differences were found in hepcidin or sTfR levels between patients with OSA and those without. However, patients with OSA showed higher plasma IL-6 values compared with those without (4.56 ± 2.92 vs. 2.83 ± 1.54 pg/ml, P = 0.025), and the highest values were evident in patients affected by both T2DM/IGT and OSA. CONCLUSIONS: Higher IL-6 levels were associated with both glycemic status and OSA. No differences in body iron regulator levels were found in obese patients with T2DM/IGT compared to those without or in those with OSA compared to those without. Further longitudinal studies in larger population samples are warranted.

Sensory profile in infants and toddlers with behavioral insomnia and/or feeding disorders.

BACKGROUND: Sleep and feeding difficulties are two common disorders in early childhood. It has been shown that feeding difficulties are more common among children with sleep disorders and vice versa. Since a child's characteristics play a substantial role in these two conditions, we aimed to investigate the sensory profile of infants and toddlers with behavioral insomnia (BI) or feeding disorders (FDs) in comparison with healthy age-matched controls. METHODS: Children aged 7-36 months with BI or FD were recruited from the sleep and feeding disorders clinics. Healthy controls were recruited from well-baby clinics. Parents completed a questionnaire which included demographics and socioeconomic status, as well as a sensory profile evaluation using the Infant/Toddler Sensory Profile (ITSP). RESULTS: Twenty-five children with BI, 28 with FDs and 32 controls were recruited. Oral processing scores were significantly lower in both BI and FD groups vs the controls (p = 0.015 and 0.001, respectively). Auditory processing scores were lower in the FD group vs the controls (p = 0.028). The scores of three out of the four ITSP sensory quadrants (Low Registration, Sensory Sensitivity, and Sensation Avoiding) were significantly lower in the FD group vs the controls (p = 0.027, 0.025, and 0.001, respectively), and in one quadrant (Sensation Avoiding) in the BI group vs the controls (p = 0.037). CONCLUSIONS: There were considerable differences in sensory processing, as reported by parents between children with BI and those with FDs compared to healthy controls, most often in the direction of the 'hypersensitive' profile. These differences may underlie the development and partially explain the coexistence of the two disorders. Sensory profile may be a target of intervention as part of the management of sleep and feeding disorders in early childhood.

Parental sleep quality and continuous glucose monitoring system use in children with type 1 diabetes.

To compare sleep quality and sleep-wake patterns in parents of children with type 1 diabetes before routine use of the continuous glucose monitoring system (CGMS) and while using it. Thirteen parents completed the Pittsburg Sleep Quality Index (PSQI), a 7-day sleep diary, and wore an actigraph (a wristwatch-size motion detector) during the night for 1 week before pediatric use of CGMS and 4-8 weeks after initiating routine use of the CGMS. Mean age of parents (ten mothers, three fathers) was 39 (range 32-47) years; mean age of children was 9.3 years (range 5.5-16.5 years); mean disease duration was 3.4 (range 0.6-11.2) years. PSQI total score demonstrated similar quality of sleep with and without use of the CGMS (4.6 and 4.9, respectively, p = 0.45). Six of the 13 parents reported severe sleep problems (PSQI ≥ 5) with and without the CGMS. The sleep diary indicated a greater number of awakening episodes during CGMS use than without the CGMS (1.6 and 1, respectively, p = 0.03), and actigraphy documented an increase in the number of wake bouts (22.9 and 19.7, p = 0.03) as well as in total wake time (48.3 and 42.2 min, p = 0.03) during CGMS use as compared with the period prior to CGMS use. Although self-perception of sleep quality remained unchanged, CGMS use appeared to affect actual parental sleep continuity somewhat negatively. This should be made clear to parents who may hold expectations of improvement in sleep quality following initiation of CGMS use.

Effect of religious observance on infants' sleep position in the Jewish population.

OBJECTIVES: To describe the effect of the level of religiousness on infants' sleep position in the Jewish population. METHODS: A longitudinal telephone survey of randomly selected 608 2-month-old Jewish infants repeated at 4 and 6 months. Results were analyzed versus the four levels of Jewish religion observance. RESULTS: A significant correlation was found between the level of religious practice and sleep position (P < or = 0.002). 56.8% (50/88) of ultra-orthodox parents put their babies to sleep in the non-prone position, compared with 79% (411/520) in the other three groups (P < 0.001). Non-prone sleeping decreased when infants grew. Higher parity correlated with the level of religiousness and with prone sleeping in religious families (OR = 1.15, 95% CI 1.00-1.33, P < 0.001). CONCLUSIONS: Jews and especially the ultra-orthodox families comply significantly less with recommendations to avoid prone sleeping. Specific measures may be required in this population that rely more on personal experience and belief than on health care provider advice.

Melatonin production in healthy infants: evidence for seasonal variations.

The objective of this study was to determine the normal range of nocturnal urinary excretion of the major melatonin metabolite, 6-sulfatoxymelatonin (6SMT) in a large sample of healthy full-term infants (8 and 16 wk old) and assess whether the endogenous production of melatonin changes with season. 6SMT was assessed in urine samples extracted from disposable diapers removed from full-term, 8- (n = 317) and 16-wk-old (n = 93) infants over the nocturnal period (19:00-08:00 h). In addition, 6SMT was assessed in 8-wk-old (n = 35) healthy infants over the entire 24-h period. 6SMT was determined by an ELISA assay. 6SMT excretion at 8 wk of age exhibited diurnal variations with (mean +/- SD) 61 +/- 18% of the daily production excreted during the nocturnal period regardless of season. The nocturnal 6SMT values in the entire cohort (at 8 as well as 16 wk of age) were found to significantly depart from normal distribution (Kolmogorov-Smirnov test). A normal distribution was obtained using a natural base logarithmic (ln) transformation of the data. The normal range (2.5-97.5 percentile of the ln 6SMT excretion per night) was thus defined as 4.66-8.64 (106-5646 ng/night) for 8-wk-old and 5.19-9.67 (180-15,820 ng/night) for 16-wk-old infants. A significant effect of the month of birth on 6SMT production at the age of 8 wk was found (ANOVA, p < 0.002) with maximal levels produced by infants born in June (summer solstice) and minimal excretion in infants born in December (winter solstice). Short-photoperiod-born infants excreted on average about threefold less 6SMT compared with long-photoperiod-born infants (t test, p = 0. 01). The seasonal variations were no longer present at 16 wk of age. No effect of breast-feeding at the time of sampling on seasonality of 6SMT was found. Normal ranges for the nocturnal urinary excretion of 6SMT in full-term infants at 8 and 16 wk of age are defined. This enables the evaluation of nocturnal 6SMT excretion as a prognostic and diagnostic factor for child development. The strong effect of season on the normal excretion of nocturnal 6SMT at 8 but not 16 wk of age suggests prenatal influence of the photoperiod on the ontogeny of melatonin.

[Neurosurgical aspects in achondroplasia: evaluation and treatment].

Achondroplasia is the most common genetic disorder associated with bone dysplasia. The mode of inheritance is autosomal dominance, while most cases appear to represent a new mutation. Achondroplastic patients suffer from dwarfism, and from typical features of the head and limbs (rhizomelia, macrocephaly, frontal bossing and kyphosis). Half of the patients show various neurological complications. The most serious complication of achondroplasia is respiratory impairment, apnea and sudden infant death, resulting from compression of the medulla oblongata. This study describes the neurosurgical sequels in 10 achondroplastic patients, who underwent 12 surgical procedures. The average age was 14 years (ages ranged from 3 months to 40 years). The patients suffered from back pain, muscle weakness, incontinence, hypotonia, psychomotor delay, apnea and respiratory arrest. Four patients were diagnosed as suffering from obstructive sleep apnea. Craniocervical MRI showed: narrowing of the foramen magnum, fusion of C1, spinal stenosis, and severe cervicomedullary or spinal cord compression. In 5 patients the MRI also showed ventriculomegaly of the lateral and third ventricles. Seven patients underwent foramen magnum decompression and C1 laminectomy. Three patients with severe spinal cord compression underwent laminectomy of the involved spines (T12-L5). Two of the patients required more then one operation due to the recurrence of their neurological symptoms. There was no need for duraplasty or shunt procedures. The average hospital stay was 6 days. Eight patients showed improvement or resolution of symptoms, with an average follow-up period of 13.5 months after the last operation (ranged 6-24 months). We conclude that early neurological and MRI evaluations are required in achondroplasia patients, in order to prevent the high morbidity and mortality during infancy and childhood. In adults, MRI evaluation is needed if the patient has neurological symptoms. Early identification and immediate cervicomedulary decompression procedure can prevent the serious complications occurring in achondroplasia, including respiratory failure, apnea and sudden death.

Duration of home monitoring for infants discharged with apnea of prematurity.

Sixty-four preterm infants with apnea of prematurity (AOP) discharged with cardiorespiratory home monitoring (HM) were prospectively followed. For each monitor alarm the parents recorded the occurrence of apnea, bradycardia or color change, and the type of assistance provided. The mean gestational age at birth was 28.8 (26-34) weeks, and the mean birth weight was 1,180 (730-2,390) g. The parents of 61/64 infants (95%) reported a total of 185 true AOPs with a mean of 3 (1-12) events/infant. The mean postconceptional age (PCA) at the last apnea was 41.0 (37-44) weeks. In 80%, AOP terminated between 40 and 44 weeks PCA. There was no correlation between the degree of prematurity and the PCA of the last apnea. We conclude that in preterm infants with AOP discharged with HM, HM may be discontinued at 45 weeks PCA.