Disruptive Mood Dysregulation Disorder in a Community Mental Health Clinic: Prevalence, Comorbidity and Correlates

Objective: The revision of the Diagnostic and Statistical Manual of Mental Disorders, 5th ed. (DSM-5) added a new diagnosis of disruptive mood dysregulation disorder (DMDD) to depressive disorders. This study examines the prevalence, comorbidity, and correlates of the new disorder, with a particular focus on its overlap with oppositional defiant disorder (ODD), with which DMDD shares core symptoms

TPN‐associated intestinal epithelial cell atrophy is modulated by TLR4/EGF signaling pathways

Recent studies suggest a close interaction between epidermal growth factor (EGF) and TLR signaling in the modulation of intestinal epithelial cell (IEC) proliferation; however, how these signaling pathways adjust IEC proliferation is poorly understood. We utilized a model of total parenteral nutrition (TPN), or enteral nutrient deprivation, to study this interaction as TPN results in mucosal atrophy due to decreased IEC proliferation and increased apoptosis. We identified the novel finding of decreased mucosal atrophy in TLR4 knockout (TLR4KO) mice receiving TPN. We hypothesized that EGF signaling is preserved in TLR4KO‐TPN mice and prevents mucosal atrophy. C57B1/6 and strain‐matched TLR4KO mice were provided either enteral feeding or TPN. IEC proliferation and apoptosis were measured. Cytokine and growth factor abundances were detected in both groups. To examine interdependence of these pathways, ErbB1 pharmacologic blockade was used. The marked decline in IEC proliferation with TPN was nearly prevented in TLR4KO mice, and intestinal length was partially preserved. EGF was significantly increased, and TNF‐α decreased in TLR4KO‐TPN versus wild‐type (WT)‐TPN mice. Apoptotic positive crypt cells were 15‐fold higher in WT‐TPN versus TLR4KO‐TPN mice. Bcl‐2 was significantly increased in TLR4KOTPN mice, while Bax decreased 10‐fold. ErbB1 blockade prevented this otherwise protective effect in TLR4KO‐sTPN mice. TLR4 blockade significantly prevented TPN‐associated atrophy by preserving proliferation and preventing apoptosis. This is driven by a reduction in TNF‐α abundance and increased EGF. Potential manipulation of this regulatory pathway may have significant clinical potential to prevent TPN‐associated atrophy.—Freeman, J. J., Feng, Y., Demehri, F. R., Dempsey, P. J., Teitelbaum, D. H. TPN‐associated intestinal epithelial cell atrophy is modulated by TLR4/EGF signaling pathways. FASEB J. 29, 2943‐2958 (2015). www.fasebj.orgPeer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/154328/1/fsb2fj14269480.pd

Gene expression profiling of mammary gland development reveals putative roles for death receptors and immune mediators in post-lactational regression

INTRODUCTION: In order to gain a better understanding of the molecular processes that underlie apoptosis and tissue regression in mammary gland, we undertook a large-scale analysis of transcriptional changes during the mouse mammary pregnancy cycle, with emphasis on the transition from lactation to involution. METHOD: Affymetrix microarrays, representing 8618 genes, were used to compare mammary tissue from 12 time points (one virgin, three gestation, three lactation and five involution stages). Six animals were used for each time point. Common patterns of gene expression across all time points were identified and related to biological function. RESULTS: The majority of significantly induced genes in involution were also differentially regulated at earlier stages in the pregnancy cycle. This included a marked increase in inflammatory mediators during involution and at parturition, which correlated with leukaemia inhibitory factor–Stat3 (signal transducer and activator of signalling-3) signalling. Before involution, expected increases in cell proliferation, biosynthesis and metabolism-related genes were observed. During involution, the first 24 hours after weaning was characterized by a transient increase in expression of components of the death receptor pathways of apoptosis, inflammatory cytokines and acute phase response genes. After 24 hours, regulators of intrinsic apoptosis were induced in conjunction with markers of phagocyte activity, matrix proteases, suppressors of neutrophils and soluble components of specific and innate immunity. CONCLUSION: We provide a resource of mouse mammary gene expression data for download or online analysis. Here we highlight the sequential induction of distinct apoptosis pathways in involution and the stimulation of immunomodulatory signals, which probably suppress the potentially damaging effects of a cellular inflammatory response while maintaining an appropriate antimicrobial and phagocytic environment

Dietary supplementation with Bifidobacterium longum subsp. infantis (B. infantis) in healthy breastfed infants: study protocol for a randomised controlled trial.

BackgroundThe development of probiotics as therapies to cure or prevent disease lags far behind that of other investigational medications. Rigorously designed phase I clinical trials are nearly non-existent in the field of probiotic research, which is a contributing factor to this disparity. As a consequence, how to appropriately dose probiotics to study their efficacy is unknown. Herein we propose a novel phase I ascending dose trial of Bifidobacterium longum subsp. infantis (B. infantis) to identify the dose required to produce predominant gut colonisation in healthy breastfed infants at 6 weeks of age.Methods/designThis is a parallel-group, placebo-controlled, randomised, double-blind ascending dose phase I clinical trial of dietary supplementation with B. infantis in healthy breastfed infants. The objective is to determine the pharmacologically effective dose (ED) of B. infantis required to produce predominant (>50 %) gut colonisation in breastfed infants at 6 weeks of age. Successively enrolled infant groups will be randomised to receive two doses of either B. infantis or placebo on days 7 and 14 of life. Stool samples will be used to characterise the gut microbiota at increasing doses of B. infantis.DiscussionProbiotic supplementation has shown promising results for the treatment of a variety of ailments, but evidence-based dosing regimes are currently lacking. The ultimate goal of this trial is to establish a recommended starting dose of B. infantis for further efficacy-testing phase II trials designed to evaluate B. infantis for the prevention of atopic dermatitis and food allergies in at-risk children.Trial registrationClinicaltrials.gov # NCT02286999 , date of trial registration 23 October 2014

A summary of water-quality and salt marsh monitoring, Humboldt Bay, California

This report summarizes data-collection activities associated with the U.S. Geological Survey Humboldt Bay Water-Quality and Salt Marsh Monitoring Project. This work was undertaken to gain a comprehensive understanding ofwater-quality conditions, salt marsh accretion processes, marsh-edge erosion, and soil-carbon storage in Humboldt Bay, California. Multiparameter sondes recorded water temperature, specific conductance, and turbidity at a 15-minute timestep at two U.S. Geological Survey water-quality stations: Mad River Slough near Arcata, California (U.S. Geological Survey station 405219124085601) and (2) Hookton Slough near Loleta, California (U.S. Geological Survey station 404038124131801). At each station, discrete water samples were collected to develop surrogate regression models that were used to compute a continuous time seriesof suspended-sediment concentration from continuously measured turbidity. Data loggers recorded water depth at a 6-minute timestep in the primary tidal channels (Mad River Slough and Hookton Slough) in two adjacent marshes (Mad River marsh and Hookton marsh). The marsh monitoring network included five study marshes. Three marshes (Mad River, Manila, and Jacoby) are in the northern embayment of Humboldt Bay and two marshes (White and Hookton) are in the southern embayment. Surface deposition and elevation change were measured using deep rod surface elevation tables and feldspar marker horizons. Sediment characteristics and soil-carbon storage were measured using a total of 10 shallow cores, distributed across 5 study marshes, collected using an Eijkelkamp peat sampler. Rates of marsh edge erosion (2010–19) were quantified in four marshes (Mad River, Manila, Jacoby, and White) by estimating changes in the areal extent of the vegetated marsh plain using repeat aerial imagery and light detection and ranging (LiDAR)-derived elevation data. During the monitoring period (2016–19), the mean suspended-sediment concentration computed for Hookton Slough (50±20 milligrams per liter [mg/L]) was higher than Mad River Slough (18±7 mg/L). Uncertainty in mean suspended-sediment concentration values is reported using a 90-percent confidence interval. Across the five study marshes, elevation change (+1.8±0.6 millimeters per year[mm/yr]) and surface deposition (+2.5±0.5 mm/yr) were lower than published values of local sea-level rise (4.9±0.8 mm/yr), and mean carbon density was 0.029±0.005 grams of carbon per cubic centimeter. From 2010 to 2019, marsh edge erosion and soil carbon loss were greatest in low-elevation marshes with the marsh edge characterized by a gentle transition from mudflat to vegetated marsh (herein, ramped edge morphology) and larger wind-wave exposure. Jacoby Creek marsh experienced the greatest edge erosion. In total, marsh edge erosion was responsible for 62.3 metric tons of estuarine soil carbon storage loss across four study marshes. Salt marshes are an important component of coastal carbon, which is frequently referred to as “blue carbon.” The monitoring data presented in this report provide fundamental information needed to manage blue carbon stocks, assess marsh vulnerability, inform sea-level rise adaptation planning, and build coastal resiliency to climate change

Web-based physiotherapy for people affected by multiple sclerosis: a single blind, randomized controlled feasibility study

Objective: To examine the feasibility of a trial to evaluate web-based physiotherapy compared to a standard home exercise programme in people with multiple sclerosis. Design: Multi-centre, randomized controlled, feasibility study. Setting: Three multiple sclerosis out-patient centres. Participants: A total of 90 people with multiple sclerosis (Expanded Disability Status Scale 4–6.5). Interventions: Participants were randomized to a six-month individualized, home exercise programme delivered via web-based physiotherapy (n = 45; intervention) or a sheet of exercises (n = 45; active comparator). Outcome measures: Outcome measures (0, three, six and nine months) included adherence, two-minute walk test, 25 foot walk, Berg Balance Scale, physical activity and healthcare resource use. Interviews were undertaken with 24 participants and 3 physiotherapists. Results: Almost 25% of people approached agreed to take part. No intervention-related adverse events were recorded. Adherence was 40%–63% and 53%–71% in the intervention and comparator groups. There was no difference in the two-minute walk test between groups at baseline (Intervention-80.4(33.91)m, Comparator-70.6(31.20)m) and no change over time (at six-month Intervention-81.6(32.75)m, Comparator-74.8(36.16)m. There were no significant changes over time in other outcome measures except the EuroQol-5 Dimension at six months which decreased in the active comparator group. For a difference of 8(17.4)m in two-minute walk test between groups, 76 participants/group would be required (80% power, P > 0.05) for a future randomized controlled trial. Conclusion: No changes were found in the majority of outcome measures over time. This study was acceptable and feasible by participants and physiotherapists. An adequately powered study needs 160 participants

Is Caregiver-Adolescent Disagreement Due to Differences in Thresholds for Reporting Manic Symptoms?

Cross-informant disagreement is common and results in different interpretations of a youth's behavior. Theoretical explanations for discrepancies typically rely on scale level analyses. This article explores whether caregivers and adolescents differ in when they notice and report symptoms of youth mania depending on the severity of overall manic disturbance