Results from a Double-Blind, Randomized, Placebo-Controlled, Single-Dose, Crossover Trial of Lovastatin or Minocycline in Fragile X Syndrome.

Treatment studies in knockout rodent models have found that minocycline and lovastatin each improve synaptic, neurological, and behavioral functioning, and open-label chronic dosing studies in human patients with fragile X syndrome (FXS) have demonstrated modest clinical improvements. Findings from blinded studies are mixed, and there is a limited understanding of electrophysiological target engagement that would facilitate cross-species translational studies. Smaller-scale, acute (e.

Parent-Reported Outcome Measures for Individuals with Fragile X Syndrome: Clinically Meaningful Change Thresholds.

Estimating meaningful change thresholds (MCT) on clinical outcome assessments is an important consideration when evaluating treatments. In fragile X syndrome (FXS) research, there has been no consensus on how to define MCT's on several commonly used outcome measures. The purpose of the current study was to determine clinically relevant MCT's of caregiver-rated assessments using data from a phase 3 clinical trials of arbaclofen (Berry-Kravis et al.

Telehealth regulating together pilot trial: emotion regulation intervention for autistic children and adolescents.

Introduction: Autistic children and adolescents frequently experience emotion dysregulation, or difficulties with appropriately modifying their emotional reactions. Caregivers of autistic teens frequently seek psychotherapy support for navigating challenges associated with emotion dysregulation. During the COVID-19 pandemic, access to clinical services became limited, with interventions halted or transitioned into a telehealth format.

A near normal distribution of IQ in Fragile X Syndrome.

Fragile X Syndrome (FXS) is an X-linked disorder leading to the loss of expression of FMR1-protein product, FMRP. The absence or deficiency of FMRP is thought to result in the characteristic FXS phenotypes, including intellectual disability. Identifying the relationship between FMRP levels and IQ may be critical to better understand underlying mechanisms and advance treatment development and planning.

A Randomised Phase II Trial of Hippocampal Sparing Versus Conventional Whole Brain Radiotherapy After Surgical Resection or Radiosurgery in Favourable Prognosis Patients With 1-10 Brain Metastases.

Aims: To assess in patients with 1-10 brain metastases, each of which has been treated by neurosurgery or stereotactic radiosurgery, whether hippocampal sparing whole brain radiotherapy (HS-WBRT) better spares neurocognitive function (NCF) than standard WBRT. Further, to assess whether a phase III randomised trial of HS-WBRT would be feasible in the UK.

Materials And Methods: A multicentre, randomised, open label phase II trial was undertaken, randomising patients to 30Gy in 10 fractions of WBRT or HS-WBRT.

Examining the feasibility and utility of heart rate variability on intervention outcomes targeting emotion regulation in autism: a brief report.

Autistic youth experience several behavioral and emotional characteristics that can predispose them to emotion dysregulation (ED). Current literature examining ED in autism spectrum disorder (ASD) is limited to parent- and self-reported measures, indicating a need for biological or physiological methods to better assess emotion regulation in ASD. Utilizing the autonomic nervous system, specifically heart rate variability (HRV), may be a promising method to objectively measure ED in ASD, given it is one of the body's primary means of regulating physiological arousal.

Frontal Cortex Hyperactivation and Gamma Desynchrony in Fragile X Syndrome: Correlates of Auditory Hypersensitivity.

Fragile X syndrome (FXS) is an X-linked disorder that often leads to intellectual disability, anxiety, and sensory hypersensitivity. While sound sensitivity (hyperacusis) is a distressing symptom in FXS, its neural basis is not well understood. It is postulated that hyperacusis may stem from temporal lobe hyperexcitability or dysregulation in top-down modulation.

Provider perspectives on the impact of COVID-19 on treatment of substance use and opioid use disorders among American Indian and Alaska Native adults.

Introduction: American Indian/Alaska Native (AI/AN) communities are more likely to suffer negative consequences related to substance misuse. The COVID-19 pandemic exacerbated the opioid poisoning crisis, in combination with ongoing treatment barriers resulting from settler-colonialism, systemic oppression and racial discrimination. AI/AN adults are at greatest risk of COVID-19 related serious illness and death.

Reliability of resting-state electrophysiology in fragile X syndrome.

Objective: Fragile X Syndrome (FXS) is the leading monogenic cause of intellectual disability and autism spectrum disorder. Currently, there are no established biomarkers for predicting and monitoring drug effects in FXS, and no approved therapies are available. Previous studies have shown electrophysiological changes in the brain using electroencephalography (EEG) in individuals with FXS and animal models.

Effects of genetically predicted posttraumatic stress disorder on autoimmune phenotypes.

Observational studies suggest that posttraumatic stress disorder (PTSD) increases risk for various autoimmune diseases. Insights into shared biology and causal relationships between these diseases may inform intervention approaches to PTSD and co-morbid autoimmune conditions. We investigated the shared genetic contributions and causal relationships between PTSD, 18 autoimmune diseases, and 3 immune/inflammatory biomarkers.

Traffic-related air pollution and dementia incidence in the Adult Changes in Thought Study.

Background: While epidemiologic evidence links higher levels of exposure to fine particulate matter (PM) to decreased cognitive function, fewer studies have investigated links with traffic-related air pollution (TRAP), and none have examined ultrafine particles (UFP, ≤100 nm) and late-life dementia incidence.

Objective: To evaluate associations between TRAP exposures (UFP, black carbon [BC], and nitrogen dioxide [NO]) and late-life dementia incidence.

Methods: We ascertained dementia incidence in the Seattle-based Adult Changes in Thought (ACT) prospective cohort study (beginning in 1994) and assessed ten-year average TRAP exposures for each participant based on prediction models derived from an extensive mobile monitoring campaign.

Brief Report: A Double-Blind, Placebo-Controlled, Crossover, Proof-of-Concept Study of Minocycline in Autism Spectrum Disorder.

Neuroinflammatory mechanisms have been implicated in the pathophysiology of autism spectrum disorder (ASD). Minocycline is a matrix metalloproteinase inhibitor 9 (MMP9) inhibitor tetracycline antibiotic with known anti-inflammatory properties. In preclinical animal models of ASD, minocycline has demonstrated potential positive effects on phenotypes that may have relevance to ASD.

Health Related Quality of Life in Autistic Youth and Their Families.

Purpose: The construct Quality of Life (QoL) involves a range of factors related to one's well-being. Individuals on the autism spectrum have been previously reported to have lower QoL. The purpose of the present study is to examine QoL in autistic individuals and their families and to evaluate associations between QoL and measures of functioning using the PedsQL 4.

Comparison of Trihalomethane exposure assessment metrics in epidemiologic analyses of reproductive and developmental outcomes.

Background: Researchers have developed exposure assessment metrics for disinfection by-products (DBPs) utilizing drinking water monitoring data and accounting for spatial and temporal variability, water consumption, and showering and bathing time with an expectation of decreasing exposure misclassification compared to the use of measured concentrations at public water supply (PWS) monitoring locations alone.

Objective: We used exposure data collected for a previous study of DBPs to evaluate how different sources of information impact trihalomethane (THM) exposure estimates.

Methods: We compared gestational exposure estimates to THMs based on water utility monitoring data alone, statistical imputation of daily concentrations to incorporate temporal variability, and personal water consumption and use (bathing and showering).

A Paradigm Shifting View of Intellectual Disability: A Near Normal Distribution of IQ in Fragile X Syndrome.

Fragile X Syndrome (FXS) is an X-linked disorder leading to the loss of expression of -protein product, FMRP. The absence or deficiency of FMRP is thought to result in the characteristic FXS phenotypes, including intellectual disability. Identifying the relationship between FMRP levels and IQ may be critical to better understand underlying mechanisms and advance treatment development and planning.

Empirical Frequency Bound Derivation Reveals Prominent Mid-Frontal Alpha Associated with Neurosensory Dysfunction in Fragile X Syndrome.

The FMR1 gene is inactive in Fragile X syndrome (FXS), resulting in low levels of FMRP and consequent neurochemical, synaptic, and local circuit neurophysiological alterations in the fmr1 KO mouse. In FXS patients, electrophysiological studies have demonstrated a marked reduction in global alpha activity and regional increases in gamma oscillations associated with intellectual disability and sensory hypersensitivity. Since alpha activity is associated with a thalamocortical function with widely distributed modulatory effects on neocortical excitability, insight into alpha physiology may provide insight into systems-level disease mechanisms.

Developing improved outcome measures in FXS: Key stakeholder feedback.

Background: There is a critical need for the development of improved outcome measures in Fragile X Syndrome (FXS). Because the majority of respondents of behavior outcome measures are caregivers or individuals with FXS, it is important to consider stakeholders' firsthand experiences when designing a caregiver- or self-report measure.

Aims: The current research study aimed to understand experiences of completing commonly used caregiver-/self-report measures of behavior in FXS via focus groups.

Behavioral inflexibility in fragile X syndrome: Accounts from caregivers and self-advocates.

Introduction: Behavioral difficulties in individuals with fragile X Syndrome (FXS) are one of the primary reasons families seek medical and psychological support. Among these, behavioral inflexibility is very common, and when left untreated, can negatively impact quality of life for the individuals with FXS and their families. Behavioral inflexibility refers to the difficulty in changing one's behaviors based on environmental demands or social contexts, thus impeding daily functioning, opportunities for learning, and social interactions.

Comparative susceptibility of children and adults to neurological effects of inhaled manganese: A review of the published literature.

Background: Manganese (Mn) is neurotoxic in adults and children. Current assessments are based on the more extensive adult epidemiological data, but the potential for greater childhood susceptibility remains a concern. To better understand potential lifestage-based variations, we compared susceptibilities to neurotoxicity in children and adults using Mn biomarker data.

Lymphocytic Extracellular Signal-Regulated Kinase Dysregulation in Autism Spectrum Disorder.

Objective: Extracellular signal-regulated kinase (ERK1/2) is a conserved central intracellular signaling cascade involved in many aspects of neuronal development and plasticity. Converging evidence support investigation of ERK1/2 activity in autism spectrum disorder (ASD). We previously reported enhanced baseline lymphocytic ERK1/2 activation in autism, and now we extend our work to investigate the early phase kinetics of lymphocytic ERK1/2 activation in idiopathic ASD.