No Evidence of Early Developmental Delay in Juvenile-Onset Huntington's Disease Patients.

Background: Previous studies suggest that early developmental delay is a common feature of Juvenile-Onset Huntington's disease (JOHD), with highest incidence in those with very high CAG repeats (> 80). However, all reports of developmental delay in JOHD are exclusively based on retrospective review of medical charts. Comprehensive assessment of birth history metrics may provide better insight into the question of early life development in JOHD.

β-Blocker Use and Delayed Onset and Progression of Huntington Disease.

Importance: Huntington disease (HD) is characterized by motor, cognitive, and psychiatric decline. β-Blockers may play a therapeutic role by decreasing enhanced sympathetic tone in HD.

Objective: To evaluate the impact of β-blockers on the timing of motor diagnosis onset and progression of HD symptoms.

Shear stress-stimulated AMPK couples endothelial cell mechanics, metabolism and vasodilation.

Endothelial cells respond to mechanical force by stimulating cellular signaling, but how these pathways are linked to elevations in cell metabolism and whether metabolism supports the mechanical response remains poorly understood. Here, we show that the application of force to endothelial cells stimulates VE-cadherin to activate liver kinase B1 (LKB1; also known as STK11) and AMP-activated protein kinase (AMPK), a master regulator of energy homeostasis. VE-cadherin-stimulated AMPK increases eNOS (also known as NOS3) activity and localization to the plasma membrane, reinforcement of the actin cytoskeleton and cadherin adhesion complex, and glucose uptake.

Mutant Huntingtin Drives Development of an Advantageous Brain Early in Life: Evidence in Support of Antagonistic Pleiotropy.

Objective: Huntington's disease (HD) is a neurodegenerative disease caused by a triplet repeat expansion within the gene huntingtin (HTT). Antagonistic pleiotropy is a theory of aging that posits that some genes, facilitating individual fitness early in life through adaptive evolutionary changes, also augment detrimental aging-related processes. Antagonistic pleiotropy theory may explain a positive evolutionary pressure toward functionally advantageous brain development that is vulnerable to rapid degeneration.

Mechanical activation of VE-cadherin stimulates AMPK to increase endothelial cell metabolism and vasodilation.

Endothelia cells respond to mechanical force by stimulating cellular signaling, but how these pathways are linked to elevations in cell metabolism and whether metabolism supports the mechanical response remains poorly understood. Here, we show that application of force to VE-cadherin stimulates liver kinase B1 (LKB1) to activate AMP-activated protein kinase (AMPK), a master regulator of energy homeostasis. VE-cadherin stimulated AMPK increases eNOS activity and localization to the plasma membrane as well as reinforcement of the actin cytoskeleton and cadherin adhesion complex, and glucose uptake.

Global incidence of adverse clinical events in non-alcoholic fatty liver disease: A systematic review and meta-analysis.

Background/aims: Nonalcoholic fatty liver disease (NAFLD) is associated with a multitude of adverse outcomes. We aimed to estimate the pooled incidence of NAFLD-related adverse events.

Methods: We performed a systematic review and meta-analysis of cohort studies of adults with NAFLD to evaluate the pooled incidence of adverse events.

Evaluating motor progression of juvenile-onset Huntington's Disease: An Enroll-HD analysis.

Introduction: Juvenile-onset Huntington's disease (JOHD) is characterized by a unique motor phenotype relative to patients with adult-onset Huntington's Disease (AOHD). This study characterized motor progression of JOHD to propose improved outcome measures for this group.

Methods: We used linear mixed effect regression models to compare progression of the Unified Huntington's Disease Rating Scale (UHDRS) Total Motor Score (TMS) and the chorea score between patients with JOHD and AOHD.

Dementia: Helping Caregivers and Family Members Cope.

Physicians who care for patients with dementia also must provide support for patient caregivers and family members. Caregiver burden requires attention from the health care team because most caregivers of patients with dementia report high levels of emotional stress. This burden is more severe when patients have comorbid conditions, behavioral and psychological symptoms of dementia, and more severe functional impairments.

Dementia: Dementia Types.

Dementia, also called major neurocognitive disorder, is characterized by a chronic progressive loss of cognitive function in the absence of fluctuating consciousness. It represents a primarily geriatric syndrome that may be caused by one of several underlying conditions. There is insufficient evidence to support universal screening for cognitive impairment in older adults; however, clinicians should be alert to patient and caregiver concerns about cognitive changes and investigate such concerns with validated cognitive assessment tools.

Unravelling the role of huntingtin: from neurodevelopment to neurodegeneration.

This scientific commentary refers to ‘Genetic topography and cortical cell loss in Huntington’s disease link development and neurodegeneration’ by Estevez-Fraga (https://doi.org/10.1093/brain/awad275).

Malaria and Pregnancy.

Recent identification of local mosquito-borne transmission of malaria in Florida, Texas, and Maryland and increasing travel to malaria-endemic countries raise the likelihood that U.S. obstetricians might encounter a pregnant patient with malaria.

Impact of prior COVID-19 infection on perceptions about the benefit and safety of COVID-19 vaccines.

In this online survey of 1,733 US adults in December 2021, respondents believed COVID-19 vaccines are less beneficial and less safe for someone who had already had COVID-19. Those who experienced COVID-19 after being vaccinated believed that the vaccines are less beneficial and less safe than those who had not. Findings highlight the need to better communicate evolving evidence of COVID-19 vaccine benefit and safety and to tailor communications to peoples' COVID-19 history and vaccination status.

Memantine Use and Cognitive Decline in Huntington's Disease: An Enroll-HD Study.

Background: Memantine is an -methyl--aspartate (NMDA) receptor antagonist that is used to treat moderate to severe Alzheimer's Dementia (AD) and has been speculated to provide clinical benefits in Huntington's disease (HD).

Objective: To assess the effectiveness of memantine on the trajectory of cognitive decline in individuals with manifest HD.

Methods: Using participants from the Enroll-HD study, the primary analysis compared trajectories in cognition over a 5-year period using linear mixed effect models of prevalent and incident memantine users who were propensity-score-matched with non-users on measures of disease progression and demographics.

Care coordination across healthcare systems: development of a research agenda, implications for practice, and recommendations for policy based on a modified Delphi panel.

Objective: For large, integrated healthcare delivery systems, coordinating patient care across delivery systems with providers external to the system presents challenges. We explored the domains and requirements for care coordination by professionals across healthcare systems and developed an agenda for research, practice and policy.

Design: The modified Delphi approach convened a 2-day stakeholder panel with moderated virtual discussions, preceded and followed by online surveys.

Longitudinal Clinical and Biological Characteristics in Juvenile-Onset Huntington's Disease.

Background: Juvenile-onset Huntington's disease (JOHD) is a rare form of Huntington's disease (HD) characterized by symptom onset before the age of 21 years. Observational data in this cohort is lacking.

Objectives: Quantify measures of disease progression for use in clinical trials of patients with JOHD.

The effects of antidepressants on depressive symptoms in manifest Huntington's disease.

Objective: Currently there is little evidence to guide the treatment of depression in Huntington's disease (HD). The primary objective was to determine the effectiveness of antidepressant medications on lowering depressive symptom scores in patients with manifest HD. The secondary objective was to determine the effect of antidepressant use on measures of disease progression.

Genotype-phenotype correlations in valosin-containing protein disease: a retrospective muticentre study.

Background: Valosin-containing protein (VCP) disease, caused by mutations in the gene, results in myopathy, Paget's disease of bone (PBD) and frontotemporal dementia (FTD). Natural history and genotype-phenotype correlation data are limited. This study characterises patients with mutations in gene and investigates genotype-phenotype correlations.

Neurofilament Light Protein as a Potential Blood Biomarker for Huntington's Disease in Children.

Background: Juvenile-onset Huntington's disease (JOHD) is a rare and particularly devastating form of Huntington's disease (HD) for which clinical diagnosis is challenging and robust outcome measures are lacking. Neurofilament light protein (NfL) in plasma has emerged as a prognostic biomarker for adult-onset HD.

Methods: We performed a retrospective analysis of samples and data collected between 2009 and 2020 from the Kids-HD and Kids-JHD studies.

Latino Invisibility in the Pandemic.

Devastating effects of COVID-19 among Latinos have not been adequately emphasized or addressed by media, public health experts, researchers, or government officials. Moreover, the underreporting of the crisis' effect on Latinos and the undercounting of cases continues even as programs, initiatives, and policies are designed and implemented to mitigate the spread of the virus; to allocate resources to lessen the economic, educational, housing, and nutritional consequences of COVID; and to direct recovery planning. The invisibility and systematic neglect of the Latino population has contributed to Latino individuals' disproportionately high rates of infection, hospitalization, and death.

Dietary Guidelines for Americans, 2020-2025: Understanding the Scientific Process, Guidelines, and Key Recommendations.

The was issued jointly by the US Departments of Agriculture and of Health and Human Services in December 2020. It is the ninth edition of the and is the first to provide recommendations by life stage, from birth to older adulthood. The is grounded in the current body of scientific evidence on diet and health outcomes and aims to promote health and prevent chronic diseases.

Association of CAG Repeat Length in the Huntington Gene With Cognitive Performance in Young Adults.

Objective: To investigate the relationships between CAG repeat length in the huntingtin gene and cognitive performance in participants above and below the disease threshold for Huntington disease (HD), we performed a cross-sectional analysis of the Enroll-HD database.

Methods: We analyzed data from young, developing adults (≤30 years of age) without a history of depression, apathy, or cognitive deficits. We included participants with and without the gene expansion (CAG ≥36) for HD.

Autonomic dysregulation as an early pathologic feature of Huntington Disease.

Objective: Autonomic nervous system (ANS) dysfunction has been described in adults with motor-manifest Huntington's Disease (HD) or those who are near their predicted motor onset. It is unclear if ANS dysfunction is present years prior to the onset of motor symptoms of HD. To bridge this gap in knowledge, we compared crude markers of ANS function between children with the gene-expansion that causes HD (GE group) who were decades from their predicted motor onset and gene-non-expanded children (GNE group).

Melatonin may slow disease progression in amyotrophic lateral sclerosis: Findings from the Pooled Resource Open-Access ALS Clinic Trials database.

Introduction: We utilized the Pooled Resource Open-Access Clinical Trials (PRO-ACT) database to investigate whether melatonin use among patients with amyotrophic lateral sclerosis (ALS) was associated with slower disease progression and prolonged survival.

Methods: This retrospective analysis of the PRO-ACT database addresses the impact of melatonin on progression and overall survival of ALS. A Cox proportional hazards ratio model was performed to investigate the effect that melatonin had on time to death.