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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. The current study investigated antagonistic pleiotropy in HD using a years‐to‐onset paradigm in a unique sample of children and young adults at risk for HD. Methods: Cognitive, behavioral, motor, and brain structural measures from premanifest gene‐expanded (n = 79) and gene nonexpanded (n = 112) participants (6–21 years) in the Kids‐HD study were examined. All measures in the gene‐expanded group were modeled using a mixed‐effects regression approach to assess years‐to‐onset‐based changes while controlling for normal growth. Simultaneously, structure–function associations were also examined. Results: Decades from motor onset, gene‐expanded participants showed significantly better cognitive, behavioral, and motor scores versus gene nonexpanded controls, along with larger cerebral volumes and cortical features. After this initial peak, a prolonged deterioration was observed in both functional and structural measures. Far from onset, brain measures were positively correlated with functional measures, supporting the view that functional advantages were mediated by structural differences. Interpretation: Mutant HTT may drive the development of a larger than normal brain that subserves superior early‐life function. These findings support the antagonistic pleiotropy theory of HTT in HD, where this gene drives early advantage followed by accelerated aging processes. ANN NEUROL 2024;96:1006–1019 [ABSTRACT FROM AUTHOR]

Parkinson's disease (PD) is a common neurodegenerative disease that lacks therapies to prevent progressive neurodegeneration. Impaired energy metabolism and reduced ATP levels are common features of PD. Previous studies revealed that terazosin (TZ) enhances the activity of phosphoglycerate kinase 1 (PGK1), thereby stimulating glycolysis and increasing cellular ATP levels. Therefore, we asked whether enhancement of PGK1 activity would change the course of PD. In toxin-induced and genetic PD models in mice, rats, flies, and induced pluripotent stem cells, TZ increased brain ATP levels and slowed or prevented neuron loss. The drug increased dopamine levels and partially restored motor function. Because TZ is prescribed clinically, we also interrogated 2 distinct human databases. We found slower disease progression, decreased PD-related complications, and a reduced frequency of PD diagnoses in individuals taking TZ and related drugs. These findings suggest that enhancing PGK1 activity and increasing glycolysis may slow neurodegeneration in PD., Introduction Parkinson's disease (PD) is the second most common neurodegenerativo disease. It is estimated to affect approximately 6 million people worldwide, and its prevalence will increase further as populations age [...]

Background: Use of the National Healthcare Safety Network (NHSN) has been essential to the success of the Massachusetts Hemovigilance Program and has allowed for the timely identification of signals and trends over a defined population that correlate with national and international hemovigilance (HV) data. Here, we outline how the NHSN system is used for monitoring HV data in Massachusetts and encourage adoption of NHSN for nationwide HV surveillance. Study Design and Methods: A collaboration that grew over time between local HV stakeholders and the Massachusetts Department of Public Health (MDPH) resulted in the change from a paper‐based method of reporting adverse reactions and monthly transfusion activity for compliance with state requirements to replacement with statewide adoption of reporting via NHSN. Results: Over 1.5 million blood products were transfused in Massachusetts between 2017 and 2021, with 3000 adverse reactions among 10 defined types reported. Using NHSN, MDPH has been able to produce numerous reports, publications, and presentations that have made previously non‐obtainable HV and blood utilization data available. Discussion: Although limitations to these self‐reported data exist, such as lack of external validation, successful statewide implementation of NHSN for hospital blood bank reporting is possible and has benefits beyond those for regulatory oversight. It results in standardized, actionable data at both the hospital and state level, enabling inter‐facility comparisons, benchmarking, and opportunities for practice improvement. [ABSTRACT FROM AUTHOR]

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. Methods: Participants who received a motor diagnosis of HD before the age of 21 were included in the Kids‐JOHD study. The comparator group consisted of children and young adults who were at‐risk for inheriting the genetic mutation that causes HD, but who were found to have a CAG repeat in the non‐expanded range (gene non‐expanded [GNE]). Results: Data were obtained between March 17, 2006, and February 13, 2020. There were 26 JOHD participants and 78 GNE participants who were comparable on age (16.03 vs. 14.43, respectively) and sex (53.8% female vs. 57.7% female, respectively). The mean annualized decrease in striatal volume in the JOHD group was −3.99% compared to −0.06% in the GNE (mean difference [MD], −3.93%; 95% confidence intervals [CI], [−4.98 to −2.80], FDR < 0.0001). The mean increase in the Unified Huntington's Disease Rating Scale Total Motor Score per year in the JOHD group was 7.29 points compared to a mean decrease of −0.21 point in the GNE (MD, 7.5; 95% CI, [5.71–9.28], FDR < 0·0001). Conclusions: These findings demonstrate that structural brain imaging and clinical measures in JOHD may be potential biomarkers of disease progression for use in clinical trials. Collaborative efforts are required to validate these results in a larger cohort of patients with JOHD. © 2022 International Parkinson and Movement Disorder Society. [ABSTRACT FROM AUTHOR]

On May 17, 2022, the Massachusetts Department of Public Health (MDPH) Laboratory Response Network (LRN) laboratory confirmed the presence of orthopoxvirus DNA via real-time polymerase chain reaction (PCR) from lesion swabs obtained from a Massachusetts resident. Orthopoxviruses include Monkeypox virus, the causative agent of monkeypox. Subsequent real-time PCR testing at CDC on May 18 confirmed that the patient was infected with the West African clade of Monkeypox virus. Since then, confirmed cases* have been reported by nine states. In addition, 28 countries and territories,† none of which has endemic monkeypox, have reported laboratory-confirmed cases. On May 17, CDC, in coordination with state and local jurisdictions, initiated an emergency response to identify, monitor, and investigate additional monkeypox cases in the United States. This response has included releasing a Health Alert Network (HAN) Health Advisory, developing interim public health and clinical recommendations, releasing guidance for LRN testing, hosting clinician and public health partner outreach calls, disseminating health communication messages to the public, developing protocols for use and release of medical countermeasures, and facilitating delivery of vaccine postexposure prophylaxis (PEP) and antivirals that have been stockpiled by the U.S. government for preparedness and response purposes. On May 19, a call center was established to provide guidance to states for the evaluation of possible cases of monkeypox, including recommendations for clinical diagnosis and orthopoxvirus testing. The call center also gathers information about possible cases to identify interjurisdictional linkages. As of May 31, this investigation has identified 17§ cases in the United States; most cases (16) were diagnosed in persons who identify as gay, bisexual, or men who have sex with men (MSM). Ongoing investigation suggests person-to-person community transmission, and CDC urges health departments, clinicians, and the public to remain vigilant, institute appropriate infection prevention and control measures, and notify public health authorities of suspected cases to reduce disease spread. Public health authorities are identifying cases and conducting investigations to determine possible sources and prevent further spread. This activity was reviewed by CDC and conducted consistent with applicable federal law and CDC policy.¶. [ABSTRACT FROM AUTHOR]