The Gut-Brain Axis.

Preclinical evidence has firmly established bidirectional interactions among the brain, the gut, and the gut microbiome. Candidate signaling molecules and at least three communication channels have been identified. Communication within this system is nonlinear, is bidirectional with multiple feedback loops, and likely involves interactions between different channels. Alterations in gut-brain-microbiome interactions have been identified in rodent models of several digestive, psychiatric, and neurological disorders. While alterations in gut-brain interactions have clearly been established in irritable bowel syndrome, a causative role of the microbiome in irritable bowel syndrome remains to be determined. In the absence of specific microbial targets for more effective therapies, current approaches are limited to dietary interventions and centrally targeted pharmacological and behavioral approaches. A more comprehensive understanding of causative influences within the gut-brain-microbiome system and well-designed randomized controlled trials are needed to translate these exciting preclinical findings into effective therapies.

Assessment of Sleep Disturbances and Exhaustion in Mothers of Children With Atopic Dermatitis.

Importance: The well-being and development of children is strongly influenced by parents' physical and psychosocial health. Data from small, clinic-based studies suggest that sleep loss may be common in parents of children with atopic dermatitis (AD), but longitudinal population-based studies are lacking. Objectives: To compare sleep disturbances over time between mothers of children with and without AD and to determine whether these disturbances are associated with the child's disease severity and the child's sleep disturbances. Design, Setting, and Participants: In the ongoing Avon Longitudinal Study of Parents and Children, all pregnant women residing in Avon, United Kingdom, with an expected delivery date between April 1, 1991, and December 31, 1992, were recruited. Analyses for this study, a secondary analysis of this cohort, were performed from September 2017 to September 2018. Mother-child pairs were followed up with a time-varying measure of child AD activity and severity and self-reported maternal sleep measures repeated at multiple time points between child ages 6 months and 11 years. Main Outcomes and Measures: Time-varying binary measures of maternal sleep duration (<6 vs ≥6 hours per night), difficulty falling asleep, early morning awakening, subjectively insufficient sleep, and daytime exhaustion. Results: The study followed up 13 988 mother-child pairs from birth for a median duration of 11 (interquartile range, 7-11) years. Among the cohort, 11 585 of 13 972 mothers (82.9%) were aged 21 to 34 years and 12 001 of 12 324 (97.4%) were of white race/ethnicity; 7220 of 13 978 children (51.7%) were male. Sleep duration (adjusted odds ratio [AOR], 1.09; 95% CI, 0.90-1.32) and early morning awakenings (AOR, 1.16; 95% CI, 0.93-1.46) were similar between mothers of children with and without AD. In contrast, mothers of children with AD were more likely to report difficulty falling asleep (AOR, 1.36; 95% CI, 1.01-1.83), subjectively insufficient sleep (AOR, 1.43; 95% CI, 1.24-1.66), and daytime exhaustion (AOR, 1.41; 95% CI, 1.12-1.78) independent of the child's comorbid asthma and/or allergic rhinitis. For all measures, worse child AD severity was associated with worse maternal sleep outcomes. The magnitude and significance of the associations were largely unchanged after adjustment for child sleep disturbances. Conclusions and Relevance: Mothers of children with AD reported difficulty falling asleep, subjectively insufficient sleep, and daytime exhaustion throughout the first 11 years of childhood. However, child sleep disturbances did not fully explain maternal sleep disturbances, and future research should investigate other mechanisms. In caring for children with AD, clinicians should consider maternal sleep disturbances and caregiver fatigue.

Association of Atopic Dermatitis With Sleep Quality in Children.

Importance: Pruritus, a hallmark of atopic dermatitis (AD), is thought to disrupt sleep, yet little is known about how variations in disease activity and severity of this common childhood condition may be associated with sleep patterns over time. Objective: To determine whether children with active AD have impaired sleep duration and quality at multiple time points throughout childhood and whether disease severity affects sleep outcomes. Design, Setting, and Participants: This longitudinal cohort study used data of children enrolled in the Avon Longitudinal Study of Parents and Children, a population-based birth cohort in Avon, United Kingdom. Participants were children (N = 13 988) alive at 1 year and followed up with repeated measures of self-reported AD and sleep through 16 years of age. This study was based on data collected from 1990 to 2008. Data analysis was performed from September 2017 to September 2018. Main Outcomes and Measures: Standardized measure of sleep duration and composite measure of sleep quality, including nighttime awakenings, early morning awakenings, difficulty falling asleep, and nightmares, were repeated at multiple time points between 2 and 16 years of age. Results: The study sample comprised 13 988 children (7220 male [51.6%]) followed up for a median (interquartile range [IQR]) duration of 11 (5-14) years. Of this total, 4938 children (35.3%) met the definition of having atopic dermatitis between 2 and 16 years of age. Total sleep duration was similar between children with active AD and without AD at all ages, and the average estimated difference across childhood was a clinically negligible difference of 2 minutes less per day for children with AD (95% CI, -4 to 0 minutes). In contrast, children with active AD were more likely to report worse sleep quality at all time points, with a nearly 50% higher odds of experiencing more sleep-quality disturbances (adjusted odds ratio [aOR], 1.48; 95% CI, 1.33 to 1.66). Children with more severe active disease (quite bad or very bad AD: aOR, 1.68; 95% CI, 1.42 to 1.98) and with comorbid asthma or allergic rhinitis (aOR, 1.79; 95% CI, 1.54 to 2.09) had worse sleep quality. However, even children with mild AD (OR, 1.40; 95% CI, 1.27 to 1.54) or inactive AD (OR, 1.41; 95% CI, 1.28 to 1.55) had statistically significantly increased odds of impaired sleep quality. Conclusions and Relevance: Atopic dermatitis appeared to be associated with impaired sleep quality throughout childhood; thus, it is suggested that clinicians should consider sleep quality among all children with AD, especially those with comorbid asthma or allergic rhinitis and severe disease, and that interventions to improve sleep quality are needed.

Diacylglycerol Kinases in T Cell Tolerance and Effector Function.

Diacylglycerol kinases (DGKs) are a family of enzymes that regulate the relative levels of diacylglycerol (DAG) and phosphatidic acid (PA) in cells by phosphorylating DAG to produce PA. Both DAG and PA are important second messengers cascading T cell receptor (TCR) signal by recruiting multiple effector molecules, such as RasGRP1, PKCθ, and mTOR. Studies have revealed important physiological functions of DGKs in the regulation of receptor signaling and the development and activation of immune cells. In this review, we will focus on recent progresses in our understanding of two DGK isoforms, α and ζ, in CD8 T effector and memory cell differentiation, regulatory T cell development and function, and invariant NKT cell development and effector lineage differentiation.

Promoting personal safety of building service workers: issues and challenges.

This exploratory, descriptive study conducted at a large western Canadian university solicited perceptions of personal safety among building service workers who perform night shift work alone. Ten semi-structured interviews were conducted at approximately 10:00 p.m. or 7:00 a.m with a convenience sample of night building service workers in private or semi-private locations on the university campus. Transcribed interview data were subjected to inductive content analysis using descriptive, interpretive, and pattern coding (Miles & Huberman, 1994). Results suggest that building service night shift workers are exposed to personal safety hazards in their physical and psychosocial work environments. In addition, culturally and linguistically appropriate delivery of safety training and education about policies and procedures is required for culturally diverse building service workers. Promotion of personal safety in this heterogeneous worker population requires due diligence, assessment, and advocacy.