Multiple Intravenous Administrations of Human Umbilical Cord Blood Cells Benefit in a Mouse Model of ALS

Background: A promising therapeutic strategy for amyotrophic lateral sclerosis (ALS) is the use of cell-based therapies that can protect motor neurons and thereby retard disease progression. We recently showed that a single large dose (25x10(6) cells) of mononuclear cells from human umbilical cord blood (MNC hUCB) administered intravenously to pre-symptomatic G93A SOD1 mice is optimal in delaying disease progression and increasing lifespan. However, this single high cell dose is impractical for clinical use. The aim of the present pre-clinical translation study was therefore to evaluate the effects of multiple low dose systemic injections of MNC hUCB cell into G93A SOD1 mice at different disease stages. Methodology/Principal Findings: Mice received weekly intravenous injections of MNC hUCB or media. Symptomatic mice received 10(6) or 2.5x10(6) cells from 13 weeks of age. A third, pre-symptomatic, group received 10(6) cells from 9 weeks of age. Control groups were media-injected G93A and mice carrying the normal hSOD1 gene. Motor function tests and various assays determined cell effects. Administered cell distribution, motor neuron counts, and glial cell densities were analyzed in mouse spinal cords. Results showed that mice receiving 10(6) cells pre-symptomatically or 2.5x10(6) cells symptomatically significantly delayed functional deterioration, increased lifespan and had higher motor neuron counts than media mice. Astrocytes and microglia were significantly reduced in all cell-treated groups. Conclusions/Significance: These results demonstrate that multiple injections of MNC hUCB cells, even beginning at the symptomatic disease stage, could benefit disease outcomes by protecting motor neurons from inflammatory effectors. This multiple cell infusion approach may promote future clinical studies

Neural underpinnings of threat bias in relation to loss-of-control eating behaviors among adolescent girls with high weight

IntroductionLoss-of-control (LOC) eating, a key feature of binge-eating disorder, may relate attentional bias (AB) to highly salient interpersonal stimuli. The current pilot study used magnetoencephalography (MEG) to explore neural features of AB to socially threatening cues in adolescent girls with and without LOC-eating.MethodsGirls (12–17 years old) with overweight or obesity (BMI >85th percentile) completed an AB measure on an affective dot-probe AB task during MEG and evoked neural responses to angry or happy (vs. neutral) face cues were captured. A laboratory test meal paradigm measured energy intake and macronutrient consumption patterns.ResultsGirls (N = 34; Mage = 15.5 ± 1.5 years; BMI-z = 1.7 ± 0.4) showed a blunted evoked response to the presentation of angry face compared with neutral face cues in the left dorsolateral prefrontal cortex, a neural region implicated in executive control and regulation processes, during attention deployment (p < 0.01). Compared with those without LOC-eating (N = 21), girls with LOC-eating (N = 13) demonstrated a stronger evoked response to angry faces in the visual cortex during attention deployment (p < 0.001). Visual and cognitive control ROIs had trends suggesting interaction with test meal intake patterns among girls with LOC-eating (ps = 0.01).DiscussionThese findings suggest that girls with overweight or obesity may fail to adaptively engage neural regions implicated in higher-order executive processes. This difficulty may relate to disinhibited eating patterns that could lead to excess weight gain

Deep Phenotyping of Post-infectious Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

Post-infectious myalgic encephalomyelitis/chronic fatigue syndrome (PI-ME/CFS) is a disabling disorder, yet the clinical phenotype is poorly defined, the pathophysiology is unknown, and no disease-modifying treatments are available. We used rigorous criteria to recruit PI-ME/CFS participants with matched controls to conduct deep phenotyping. Among the many physical and cognitive complaints, one defining feature of PI-ME/CFS was an alteration of effort preference, rather than physical or central fatigue, due to dysfunction of integrative brain regions potentially associated with central catechol pathway dysregulation, with consequences on autonomic functioning and physical conditioning. Immune profiling suggested chronic antigenic stimulation with increase in naïve and decrease in switched memory B-cells. Alterations in gene expression profiles of peripheral blood mononuclear cells and metabolic pathways were consistent with cellular phenotypic studies and demonstrated differences according to sex. Together these clinical abnormalities and biomarker differences provide unique insight into the underlying pathophysiology of PI-ME/CFS, which may guide future intervention

A Crisis of Consciousness

(Statement of Responsibility) by Shanna Turner(Thesis) Thesis (B.A.) -- New College of Florida, 2010(Electronic Access) RESTRICTED TO NCF STUDENTS, STAFF, FACULTY, AND ON-CAMPUS USE(Bibliography) Includes bibliographical references.(Source of Description) This bibliographic record is available under the Creative Commons CC0 public domain dedication. The New College of Florida, as creator of this bibliographic record, has waived all rights to it worldwide under copyright law, including all related and neighboring rights, to the extent allowed by law.(Local) Faculty Sponsor: Harvey, Davi

Examining more inclusive approaches to social work, physical disability, and sexuality

People with disabilities often experience the idea that those with disabilities are not, or should not be, sexual beings. This article examines how people with physical disabilities define sexual activity, their levels of sexual satisfaction, group differences in how people define different acts as sexual activities, and the differences in levels of sexual satisfaction. Additionally, this study (N = 450) looks at the correlations between levels of independence in multiple contexts. Levels of independence are also assessed in relationship to severity of disability and sexual satisfaction. Implications for social work and social service practice, education, and policy are discussed

COVID-19 related stress, quality of life, and intrinsic religiosity among college students during the global pandemic: A cross-sectional study

AbstractThe purpose of this correlational, cross-sectional design study was to examine the relationships between COVID-19-related stress, quality of life (QOL), and intrinsic religiosity of university students during the pandemic. Data were collected using the Psychological General Well-being Index, Impact of Events Scale-Revised, and Duke University Religiosity Index and analyzed using bivariate and hierarchical regression analyses, and hierarchical regression analysis. For the sample of 422 participants, COVID-19-related stress was negatively associated with QOL, while religiosity was positively associated with participants’ QOL. Religiosity, however, did not moderate the relationship between stress and QOL. Institutions of higher education should consider providing additional mental health support and self-care initiatives to improve student stress responses. Understanding the effects of religiosity on student stress responses and QOL would allow faculty and institutions to prioritize holistic care, including spiritual care in conjunction with religiosity

A randomized feasibility trial of medium chain triglyceride-supplemented ketogenic diet in people with Parkinson's disease

Abstract Background A ketogenic diet (KD) may benefit people with neurodegenerative disorders marked by mitochondrial depolarization/insufficiency, including Parkinson’s disease (PD). Objective Evaluate whether a KD supplemented by medium chain triglyceride (MCT-KD) oil is feasible and acceptable for PD patients. Furthermore, we explored the effects of MCT-KD on blood ketone levels, metabolic parameters, levodopa absorption, mobility, nonmotor symptoms, simple motor and cognitive tests, autonomic function, and resting-state electroencephalography (rsEEG). Methods A one-week in-hospital, double-blind, randomized, placebo-controlled diet (MCT-KD vs. standard diet (SD)), followed by an at-home two-week open-label extension. The primary outcome was KD feasibility and acceptability. The secondary outcome was the change in Timed Up & Go (TUG) on day 7 of the diet intervention. Additional exploratory outcomes included the N-Back task, Unified Parkinson’s Disease Rating Scale, Non-Motor Symptom Scale, and rsEEG connectivity. Results A total of 15/16 subjects completed the study. The mean acceptability was 2.3/3, indicating willingness to continue the KD. Day 7 TUG time was not significantly different between the SD and KD groups. The nonmotor symptom severity score was reduced at the week 3 visit and to a greater extent in the KD group. UPDRS, 3-back, and rsEEG measures were not significantly different between groups. Blood ketosis was attained by day 4 in the KD group and to a greater extent at week 3 than in the SD group. The plasma levodopa metabolites DOPAC and dopamine both showed nonsignificant increasing trends over 3 days in the KD vs. SD groups. Conclusions An MCT-supplemented KD is feasible and acceptable to PD patients but requires further study to understand its effects on symptoms and disease. Trial Registration Trial Registration Number NCT04584346, registration dates were Oct 14, 2020 – Sept 13, 2022

Heart Rate Variability and Laboratory-Based Loss-of-Control Eating in Children and Adolescents

Among youth, greater heart rate (HR) and lesser HR variability (HRV) are precursors to loss-of-control (LOC) eating episodes in the natural environment. However, there are limited data examining whether pre-meal HR and HRV are associated with greater LOC-eating in the laboratory setting. We therefore examined temporal relationships between pre-meal HR, frequency- and time-based metrics of pre-meal HRV, perceived LOC-eating, and energy intake during a meal designed to simulate a LOC-eating episode. Among 209 participants (54.5% female, 12.58 ± 2.72 years, 0.52 ± 1.02 BMIz), 19 reported LOC-eating in the prior month. Perceived LOC-eating during the laboratory meal was not significantly linked to pre-meal HR (p = 0.37), but was positively related to pre-meal HRV (ps = 0.02–0.04). This finding was driven by youth with recent LOC-eating, as these associations were not significant when analyses were run only among participants without recent reported LOC-eating (p = 0.15–0.99). Pre-meal HR and HRV were not significantly related to total energy intake (ps = 0.27–0.81). Additional research is required to determine whether early-stage pediatric LOC-eating is preceded by a healthy pre-meal stress response. Longitudinal studies could help clarify whether this pattern becomes less functional over time among youth who develop recurrent LOC-eating episodes