Maciasdawson9988

8%). Regarding community-level social capital variables, civic participation was inversely associated with frailty onset (OR=0.94, 95% CI 0.90 to 0.97, p=0.001), after adjusting for individual-level and community-level covariates. The potential intermediate factors of individual social relationships and health behaviours did not largely change the results. This association was found regardless of individual socioeconomic status.

Living in a community with rich civic participation, such as engagement in social activities, was associated with lower frailty onset among older adults. Community development that fosters social participation is essential for frailty prevention.

Living in a community with rich civic participation, such as engagement in social activities, was associated with lower frailty onset among older adults. Community development that fosters social participation is essential for frailty prevention.In the United States, criminal proceedings must be halted or suspended if a defendant is determined to be incompetent to stand trial. Competency to stand trial (CST) is one of the most notable intersections between psychiatry and criminal law, and evaluating defendants for CST is a key role for many forensic psychiatrists and other mental health professionals. Despite the significance of CST evaluations in U.S. criminal justice, the number of CST evaluations conducted across the country each year remains largely unknown. National estimates dating back to the 1970s have ranged from approximately 19,000 to 94,000 CST evaluations each year, but these numbers vary considerably and often stem from imprecise calculations. This article examines estimates of annual numbers of CST evaluations across the United States, the need to develop more accurate statistics, and ways to implement systems for tracking the numbers of CST evaluations across the country.Unlawful behaviors have been reported in association with Huntington's disease (HD), although their overall prevalence and clinical significance remain unknown. Recognition of problematic behavior is limited by stigma and lack of routine clinical assessment, as well as the absence of validated screening measures. We performed a retrospective chart review of 289 patients treated for HD at Vanderbilt University Medical Center from 2006 to 2020 to assess the frequency of illegal activity in our HD population. We identified 31 patients with HD who have a documented history of unlawful behavior, comprising 11 percent of the charts reviewed. Physical violence was the most common behavior reported, followed by reckless driving, substance abuse, illegal financial activity, and inappropriate sexual behavior. Mean age at the time of the first offense was 37 years. Patients with criminal offenses were more likely to be male and in the early stages of disease with associated psychiatric symptoms. Our results emphasize that illegal activities are a significant clinical problem in individuals with HD, particularly young adult males with comorbid psychiatric symptoms. These findings highlight the need for improved screening measures to detect high-risk behaviors in individuals with HD, as well as evidence-based protocols to guide triage and management of patients engaging in potentially detrimental activities.Prior research suggests a greater degree of suicidality and self-harm behavior in those involved with criminal justice and forensic mental health systems. Such individuals also evidence increased exposure to early childhood adversity, which is often associated with suicide risk. Other significant predictors of suicidality have been noted within forensic populations, however, including indicators of specific psychopathology and situational and demographic factors. These populations present with overlapping risk factors that remain underexamined. In the current study, 182 persons residing in secure forensic psychiatric care following incidents of illegal and aggressive behavior were evaluated. Adverse childhood experiences and other empirically derived potential predictors of suicide attempts and self-harm were examined via binomial logistic regression. Findings indicate frequent experiences of early adversity across participants, and that a combination of race, individual adverse childhood experiences, number of biological children, and diagnoses of either posttraumatic stress disorder or borderline personality disorder were significant predictors of suicide attempts, self-harm behavior, and first hospitalization resulting from a suicide attempt. Clinical and research implications are discussed.Medications for opioid use disorder, also known as medication-assisted treatment (MAT), are critical in the treatment of opioid use disorder. Historically, inmates with opioid use disorder in U.S. jails and prisons have had difficulty accessing these medications, particularly methadone and buprenorphine. IGF-1R inhibitor A series of recent legal cases, however, have set an evolving precedent for prisoners' rights to medications for opioid use disorder during incarceration based on the Eighth Amendment and the Americans with Disabilities Act. In addition to reviewing these cases, this article evaluates the recent clinical and research landscape in which these cases arose and highlights the need for further study into the role of medications in reducing in-prison morbidity and mortality from opioid use disorder.

Traumatic and non-traumatic spinal cord injury produce neurodegeneration across the entire neuraxis. However, the spatiotemporal dynamics of spinal cord grey and white matter neurodegeneration above and below the injury is understudied.

We acquired longitudinal data from 13 traumatic and 3 non-traumatic spinal cord injury patients (8-8 cervical and thoracic cord injuries) within 1.5 years after injury and 10 healthy controls over the same period. The protocol encompassed structural and diffusion-weighted MRI rostral (C2/C3) and caudal (lumbar enlargement) to the injury level to track tissue-specific neurodegeneration. Regression models assessed group differences in the temporal evolution of tissue-specific changes and associations with clinical outcomes.

At 2 months post-injury, white matter area was decreased by 8.5% and grey matter by 15.9% in the lumbar enlargement, while at C2/C3 only white matter was decreased (-9.7%). Patients had decreased cervical fractional anisotropy (FA -11.3%) and increased progressed in parallel. Tracking trajectories of tissue-specific neurodegeneration provides valuable assessment tools for monitoring recovery and treatment effects.

SARS-CoV-2 seroconversion rate after COVID-19 may be influenced by disease-modifying therapies (DMTs) in patients with multiple sclerosis (MS) or neuromyelitis optica spectrum disorders (NMO-SD).

To investigate the seroprevalence and the quantity of SARS-CoV-2 antibodies in a cohort of patients with MS or NMO-SD.

Blood samples were collected in patients diagnosed with COVID-19 between 19 February 2020 and 26 February 2021. SARS-CoV-2 antibody positivity rates and Ig levels (anti-S IgG titre, anti-S IgA index, anti-N IgG index) were compared between DMTs groups. Multivariate logistic and linear regression models were used to estimate the influence of DMTs and other confounding variables on SARS-CoV-2 serological outcomes.

119 patients (115 MS, 4 NMO, mean age 43.0 years) were analysed. Overall, seroconversion rate was 80.6% within 5.0 (SD 3.4) months after infection. 20/21 (95.2%) patients without DMT and 66/77 (85.7%) patients on DMTs other than anti-CD20 had at least one SARS-CoV-2 Ig positivity, while this rate decreased to only 10/21 (47.6%) for patients on anti-CD20 (p<0.001). Being on anti-CD20 was associated with a decreased odd of positive serology (OR, 0.07 (95% CI 0.01 to 0.69), p=0.02) independently from time to COVID-19, total IgG level, age, sex and COVID-19 severity. Time between last anti-CD20 infusion and COVID-19 was longer (mean (SD), 3.7 (2.0) months) in seropositive patients compared with seronegative patients (mean (SD), 1.9 (1.5) months, p=0.04).

SARS-CoV-2 antibody response was decreased in patients with MS or NMO-SD treated with anti-CD20 therapies. Monitoring long-term risk of reinfection and specific vaccination strategies in this population may be warranted.

NCT04568707.

NCT04568707.Wilson's disease is an autosomal-recessive disorder of copper metabolism caused by mutations in ATP7B and associated with neurological, psychiatric, ophthalmological and hepatic manifestations. Decoppering treatments are used to prevent disease progression and reduce symptoms, but neurological outcomes remain mixed. In this article, we review the current understanding of pathogenesis, biomarkers and treatments for Wilson's disease from the neurological perspective, with a focus on recent advances. The genetic and molecular mechanisms associated with ATP7B dysfunction have been well characterised, but despite extensive efforts to identify genotype-phenotype correlations, the reason why only some patients develop neurological or psychiatric features remains unclear. We discuss pathological processes through which copper accumulation leads to neurodegeneration, such as mitochondrial dysfunction, the role of brain iron metabolism and the broader concept of selective neuronal vulnerability in Wilson's disease. Delayed diagnoses continue to be a major problem for patients with neurological presentations. We highlight limitations in our current approach to making a diagnosis and novel diagnostic biomarkers, including the potential for newborn screening programmes. We describe recent progress in developing imaging and wet (fluid) biomarkers for neurological involvement, including findings from quantitative MRI and other neuroimaging studies, and the development of a semiquantitative scoring system for assessing radiological severity. Finally, we cover the use of established and novel chelating agents, paradoxical neurological worsening, and progress developing targeted molecular and gene therapy for Wilson's disease, before discussing future directions for translational research.

Intratumoral injection of cyclic dinucleotide (CDN) agonists of the stimulator of interferon genes (STING) pathway engages innate immune activation and priming of adaptive immune effectors to foster local and distal tumor clearance. Despite proven therapeutic efficacy in preclinical models, a thorough understanding of how CDNs reprogram suppressive myeloid stroma in mouse and man is lacking.

Here, we perform deep transcript-level and protein-level profiling of myeloid-derived suppressor cells and M2 macrophages following stimulation with CDNs of ascending potency. Additionally, we leverage orthotopic

(KPC) derived models of pancreatic adenocarcinoma (PDAC) to determine the capacity for locally administered CDNs to sensitize PDAC to immune checkpoint blockade. We use bioluminescent in vivo imaging and 30-parameter flow cytometry to profile growth kinetics and remodeling of the tumor stroma post-therapy.

Highly potent synthetic STING agonists repolarize suppressive myeloid populations of human and muriltifocal model of PDAC.

This study defines the molecular basis of STING-mediated myeloid reprogramming, revealing previously unappreciated and qualitatively unique pathways engaged by CDNs of ascending potency during functional repolarization. Furthermore, we demonstrate the potential for high potency CDNs to overcome immunotherapy resistance in an orthotopic, multifocal model of PDAC.