Dementia and competency to stand trial in the United States: A case law review.

OBJECTIVE: Competency to stand trial (CST) is foundational to the U.S. criminal legal system. Dementia is increasingly prevalent in the United States, and older adults are becoming involved with the U.S. criminal legal system at unprecedented rates, which carries significant implications for legal professionals and clinicians involved in CST cases. Unfortunately, CST research to date has largely excluded considerations of dementia and aging. The present study addressed this gap by reviewing U.S. case law related to dementia and CST. HYPOTHESES: The present study had no hypotheses because of its descriptive nature. METHOD: This was a case law review of 118 U.S. court cases involving dementia and CST from 2002 through 2022. Relevant information was coded about the legal case, defendant demographics, clinical evaluation(s), and court determination. RESULTS: Competency was mostly raised by the defense (81%). Similar percentages of defendants were involved in one, two, and three or more evaluations, mostly conducted by experts appointed by courts or retained by the defense. Trends for court determinations were based on the number of evaluations conducted and experts' (dis)agreement about diagnosis and CST recommendation. Ultimately, 45% of defendants were determined incompetent, with trends appearing for dementia diagnosis, cognitive deficits, index offense, and jurisdiction, but not age. Ability to assist was the most cited reason for determinations of incompetence, often in combination with both factual and rational understanding or one of these psycholegal abilities alone. CONCLUSIONS: Dementia and related impairments appear especially relevant to CST among older adults and carry important implications for clinicians, legal professionals, and policymakers. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Adolescents' and Adults' Perceptions of Sensory-Based Interventions: A Qualitative Analysis.

IMPORTANCE: Adolescents and adults report that their sensory integration and processing differences affect their occupational performance and quality of life, thus requiring effective sensory-focused interventions. Researchers have yet to investigate this population's experience of occupational therapy interventions designed to remediate these challenges. OBJECTIVE: To explore the perceived experience of adolescents and adults with respect to (1) response to intervention, (2) strategies offered to manage sensory differences, and (3) need for services on completion of an intervention. DESIGN: Retrospective, qualitative study. SETTING: Zoom or phone call. PARTICIPANTS: Eleven adolescents and adults with sensory integration and processing differences who had previously completed occupational therapy interventions. INTERVENTION: Sensory-based intervention based on the principles of Ayres Sensory Integration® (ASI) and the Sensory Therapies and Research Frame of Reference. OUTCOMES AND MEASURES: A semistructured interview to obtain data, followed by an in-depth analysis using an inductive coding process to group initial open codes into themes and common subthemes Results: Open codes were grouped into three core themes: (1) therapist-related factors (what the therapist did in treatment); (2) client-related factors (what the client experienced); and (3) follow-up (future needs of the clients). Four main subthemes of the client-therapist relationship emerged: (1) therapeutic alliance; (2) education and knowledge; (3) strategies, tools, and resources; and (4) future needs. CONCLUSIONS AND RELEVANCE: This study provides a perspective on the experience of adolescents and adults specific to the impact of a sensory-focused occupational therapy intervention on their daily lives. This will help occupational therapists when designing interventions for current and future clients. What This Article Adds: This study highlights the need for further research addressing effective sensory-based interventions for adolescents and adults. It also captures which components of intervention clients deemed helpful and identifies potential targets for future intervention.

Third reported patient with RAP1B-related syndromic thrombocytopenia and novel clinical findings.

RAP1B is a RAS-superfamily small GTP-binding protein involved in numerous cell processes. Pathogenic gain-of-function variants in this gene have been associated with RAP1B-related syndromic thrombocytopenia, an ultrarare disorder characterized by hematologic abnormalities, neurodevelopmental delays, growth delay, and congenital birth defects including cardiovascular, genitourinary, neurologic, and skeletal systems. We report a 23-year-old male with a novel, de novo RAP1B gain-of-function variant identified on genome sequencing. This is the third reported case which expands the molecular and phenotypic spectrum of RAP1B-related syndromic thrombocytopenia.

MED12-related Hardikar syndrome: Two additional cases and novel phenotypic features.

Hardikar syndrome (HS) is a MED12-related ultra-rare multiple congenital malformation syndrome known to affect the gastrointestinal, cardiac, and genitourinary systems among other features including cleft lip/palate and pigmentary retinopathy. Only 10 patients affected with HS have been previously described in literature, of which seven were molecularly confirmed. We report a 20-year-old and a 13-month-old patient with HS diagnosed by exome sequencing bringing the total number of clinically diagnosed cases to 12 and MED12 associated to 9. We describe previously unreported molecular and clinical findings associated with HS and review all reported cases to permit prompt diagnosis, appropriate management, and genetic counseling of HS patients.

Fasting prevents hypoxia-induced defects of proteostasis in C. elegans.

Low oxygen conditions (hypoxia) can impair essential physiological processes and cause cellular damage and death. We have shown that specific hypoxic conditions disrupt protein homeostasis in C. elegans, leading to protein aggregation and proteotoxicity. Here, we show that nutritional cues regulate this effect of hypoxia on proteostasis. Animals fasted prior to hypoxic exposure develop dramatically fewer polyglutamine protein aggregates compared to their fed counterparts, indicating that the effect of hypoxia is abrogated. Fasting also reduced the hypoxia-induced exaggeration of proteostasis defects in animals that express Aß1-42 and in animals with a temperature-sensitive mutation in dyn-1, suggesting that this effect was not specific to polyglutamine proteins. Our data also demonstrate that the nutritional environment experienced at the onset of hypoxia dictates at least some aspects of the physiological response to hypoxia. We further demonstrate that the insulin/IGF-like signaling pathway plays a role in mediating the protective effects of fasting in hypoxia. Animals with mutations in daf-2, the C. elegans insulin-like receptor, display wild-type levels of hypoxia-induced protein aggregation upon exposure to hypoxia when fed, but are not protected by fasting. DAF-2 acts independently of the FOXO transcription factor, DAF-16, to mediate the protective effects of fasting. These results suggest a non-canonical role for the insulin/IGF-like signaling pathway in coordinating the effects of hypoxia and nutritional state on proteostasis.

Microbial communities in the tropical air ecosystem follow a precise diel cycle.

The atmosphere is vastly underexplored as a habitable ecosystem for microbial organisms. In this study, we investigated 795 time-resolved metagenomes from tropical air, generating 2.27 terabases of data. Despite only 9 to 17% of the generated sequence data currently being assignable to taxa, the air harbored a microbial diversity that rivals the complexity of other planetary ecosystems. The airborne microbial organisms followed a clear diel cycle, possibly driven by environmental factors. Interday taxonomic diversity exceeded day-to-day and month-to-month variation. Environmental time series revealed the existence of a large core of microbial taxa that remained invariable over 13 mo, thereby underlining the long-term robustness of the airborne community structure. Unlike terrestrial or aquatic environments, where prokaryotes are prevalent, the tropical airborne biomass was dominated by DNA from eukaryotic phyla. Specific fungal and bacterial species were strongly correlated with temperature, humidity, and CO2 concentration, making them suitable biomarkers for studying the bioaerosol dynamics of the atmosphere.

Prognostic Role of Cardiopulmonary Exercise Testing in Wild-Type Transthyretin Amyloid Cardiomyopathy Patients Treated With Tafamidis.

BACKGROUND: The prognostic value of cardiopulmonary exercise testing (CPET) in patients with wild-type transthyretin cardiac amyloidosis treated with tafamidis is unknown. METHODS AND RESULTS: This retrospective study included patients with wtATTR who underwent baseline cardiopulmonary exercise testing and were treated with tafamidis from August 31, 2018, until March 31, 2020. Univariate logistic and multivariate cox-regression models were used to predict the occurrence of the primary outcome (composite of mortality, heart transplant, and palliative inotrope initiation). A total of 33 patients were included (median age 82 years, interquartile range [IQR] 79-84 years), 84% were Caucasians and 79% were males). Majority of patients had New York Heart Association functional class III disease at baseline (67%). The baseline median peak oxygen consumption (VO2) and peak circulatory power (CP) were 11.35 mL/kg/min (IQR 8.5-14.2 mL/kg/min) and 1485.8 mm Hg/mL/min (IQR 988-2184 mm Hg/mL/min), respectively, the median ventilatory efficiency was 35.7 (IQR 31-41.2). After 1 year of follow-up, 11 patients experienced a primary end point. Upon multivariate analysis, the low peak VO2 (hazard ratio [HR] 0.43, 95% confidence interval [CI] 0.23-0.79, P = .007], peak CP (HR 0.98, 95% CI 0.98-0.99, P = .02), peak oxygen pulse (HR 0.62, 95% CI 0.39-0.97, P = .03), and exercise duration of less than 5.5 minutes (HR 5.82, 95% CI 1.29-26.2, P = .02) were significantly associated with the primary outcome. CONCLUSIONS: Tafamidis-treated patients with wtATTR who had baseline low peak VO2, peak CP, peak O2 pulse, and exercise duration of less than 5.5 minutes had worse outcomes.

Cobalamin J disease detected on newborn screening: Novel variant and normal neurodevelopmental course.

Cobalamin J disease (CblJ) is an ultra-rare autosomal recessive disorder of intracellular cobalamin metabolism associated with combined methylmalonic acidemia and homocystinuria. It is caused by pathogenic variants in ABCD4, which encodes an ATP-binding cassette (ABC) transporter that affects the lysosomal release of cobalamin (Cbl) into the cytoplasm. Only six cases of CblJ have been reported in the literature. Described clinical features include feeding difficulties, failure to thrive, hypotonia, seizures, developmental delay, and hematological abnormalities. Information on clinical outcomes is extremely limited, and no cases of presymptomatic diagnosis have been reported. We describe a now 17-month-old male with CblJ detected by newborn screening and confirmed by biochemical, molecular, and complementation studies. With early detection and initiation of treatment, this patient has remained asymptomatic with normal growth parameters and neurodevelopmental function. To the best of our knowledge, this report represents the first asymptomatic and neurotypical patient with CblJ.

Health Disparities, Systemic Racism, and Failures of Cultural Competence.

Health disparities are primarily driven by structural inequality including systemic racism. Medical educators, led by the AAMC, have tended to minimize these core drivers of health disparities. Instead, it has adopted a culture-based agenda through the framework of cultural competence to address disparities despite a paucity of supporting data. Cultural competence is ethnocentric in orientation and its content sustains biases that are long-standing in health care. Moreover, Cultural competence is based on a number of flawed assumptions and is not structured around a set of clearly stated ethical values. In this paper, we will demonstrate ways in which Cultural competence reflects embedded ethnocentrism, perpetuates entrenched biases, and fails to recognize the depth and breadth of systemic racism as these relate to the stated goal of Cultural competence-the mitigation of health disparities. In addition, we offer a reframed approach to health disparities in medical education.

Two functionally distinct E2/E3 pairs coordinate sequential ubiquitination of a common substrate in Caenorhabditis elegans development.

Ubiquitination, the crucial posttranslational modification that regulates the eukaryotic proteome, is carried out by a trio of enzymes, known as E1 [ubiquitin (Ub)-activating enzyme], E2 (Ub-conjugating enzyme), and E3 (Ub ligase). Although most E2s can work with any of the three mechanistically distinct classes of E3s, the E2 UBCH7 is unable to function with really interesting new gene (RING)-type E3s, thereby restricting it to homologous to E6AP C-terminus (HECT) and RING-in-between-RING (RBR) E3s. The Caenorhabditis elegans UBCH7 homolog, UBC-18, plays a critical role in developmental processes through its cooperation with the RBR E3 ARI-1 (HHARI in humans). We discovered that another E2, ubc-3, interacts genetically with ubc-18 in an unbiased genome-wide RNAi screen in C. elegans These two E2s have nonoverlapping biochemical activities, and each is dedicated to distinct classes of E3s. UBC-3 is the ortholog of CDC34 that functions specifically with Cullin-RING E3 ligases, such as SCF (Skp1-Cullin-F-box). Our genetic and biochemical studies show that UBCH7 (UBC-18) and the RBR E3 HHARI (ARI-1) coordinate with CDC34 (UBC-3) and an SCF E3 complex to ubiquitinate a common substrate, a SKP1-related protein. We show that UBCH7/HHARI primes the substrate with a single Ub in the presence of CUL-1, and that CDC34 is required to build chains onto the Ub-primed substrate. Our study reveals that the association and coordination of two distinct E2/E3 pairs play essential roles in a developmental pathway and suggests that cooperative action among E3s is a conserved feature from worms to humans.