RESUMO
Involvement of oxidative stress in the pathophysiology of schizophrenia (SZ) is suggested by studies of peripheral tissue. Nonetheless, it is unclear how such biological changes are linked to relevant, pathological neurochemistry, and brain function. We designed a multi-faceted study by combining biochemistry, neuroimaging, and neuropsychology to test how peripheral changes in a key marker for oxidative stress, glutathione (GSH), may associate with central neurochemicals or neuropsychological performance in health and in SZ. GSH in dorsal anterior cingulate cortex (dACC) was acquired as a secondary 3T 1H-MRS outcome using a MEGA-PRESS sequence. Fifty healthy controls and 46 patients with SZ were studied cross-sectionally, and analyses were adjusted for effects of confounding variables. We observed lower peripheral total GSH in SZ compared to controls in extracellular (plasma) and intracellular (lymphoblast) pools. Total GSH levels in plasma positively correlated with composite neuropsychological performance across the total population and within patients. Total plasma GSH levels were also positively correlated with the levels of Glx in the dACC across the total population, as well as within each individual group (controls, patients). Furthermore, the levels of dACC Glx and dACC GSH positively correlated with composite neuropsychological performance in the patient group. Exploring the relationship between systemic oxidative stress (in particular GSH), central glutamate, and cognition in SZ will benefit further from assessment of patients with more varied neuropsychological performance.
Assuntos
Esquizofrenia , Encéfalo/diagnóstico por imagem , Cognição , Ácido Glutâmico , Glutationa , Giro do Cíngulo , HumanosRESUMO
Lesch-Nyhan disease (LND) is a rare, X-linked recessive neurodevelopmental disorder caused by deficiency of hypoxanthine-guanine phosphoribosyltransferase (HGprt), an enzyme in the purine salvage pathway. HGprt has two functions; it recycles hypoxanthine and guanine. Which of these two functions is more relevant for pathogenesis is unclear because some evidence points to hypoxanthine recycling, but other evidence points to guanine recycling. In this study, we selectively assayed hypoxanthine (Hprt) and guanine (Gprt) recycling in skin fibroblasts from 17 persons with LND, 11 with an attenuated variant of the disease (LNV), and 19 age-, sex-, and race-matched healthy controls (HC). Activity levels of both enzymes differed across groups (p < 0.0001), but only Gprt distinguished patients with LND from those with LNV (p < 0.05). Gprt also showed slightly stronger correlations than Hprt with 13 of 14 measures of the clinical phenotype, including the severity of dystonia, cognitive impairment, and behavioral abnormalities. These findings suggest that loss of guanine recycling might be more closely linked to the LND/LNV phenotype than loss of hypoxanthine recycling.
Assuntos
Guanina/metabolismo , Hipoxantina/metabolismo , Síndrome de Lesch-Nyhan/metabolismo , Adolescente , Adulto , Estudos de Casos e Controles , Fibroblastos/metabolismo , Humanos , Hipoxantina Fosforribosiltransferase/deficiência , Hipoxantina Fosforribosiltransferase/metabolismo , Síndrome de Lesch-Nyhan/genética , Masculino , Fenótipo , Purinas/metabolismo , Pele/metabolismo , Adulto JovemRESUMO
By training nurses and midwives on the basics of obstetric ultrasound, high-risk pregnancies in remote Nepalese villages can be identified and triaged. American radiology residents traveling to Nepal can improve their real-time, hands-on ultrasound scanning skills while learning the intricacies of practicing medicine in a low- and middle-income country. Global outreach work is increasing in popularity among US radiologists, emphasizing the importance of training radiology residents in point-of-care ultrasound.
Assuntos
Sistemas Automatizados de Assistência Junto ao Leito , Ultrassonografia Pré-Natal , Humanos , Feminino , Gravidez , Nepal , Gravidez de Alto Risco , População Rural , Programas de RastreamentoRESUMO
In recent years, advances in ultrasound therapeutics have been implemented into treatment algorithms for the adult population; however, the use of therapeutic ultrasound in the pediatric population still needs to be further elucidated. In order to better characterize the utilization and practicality of sonothrombolysis in the juvenile population, the authors conducted a literature review of current pediatric research in therapeutic ultrasound. The PubMed database was used to search for all clinical and preclinical studies detailing the use and applications of sonothrombolysis, with a focus on the pediatric population. As illustrated by various review articles, case studies, and original research, sonothrombolysis demonstrates efficacy and safety in clot dissolution in vitro and in animal studies, particularly when combined with microbubbles, with potential applications in conditions such as deep venous thrombosis, peripheral vascular disease, ischemic stroke, myocardial infarction, and pulmonary embolism. Although there is limited literature on the use of therapeutic ultrasound in children, mainly due to the lower prevalence of thrombotic events, sonothrombolysis shows potential as a noninvasive thrombolytic treatment. However, more pediatric sonothrombolysis research needs to be conducted to quantify the safety and ethical considerations specific to this vulnerable population.
RESUMO
BACKGROUND: Mobile health (mHealth) systems that support self-management can improve medical, functional, and psychosocial outcomes for individuals with disabilities and chronic conditions. The mHealth systems can potentially be expanded to support community integration. OBJECTIVE: The purposes of this study were to (1) partner with a community-based organization that supports community integration of individuals with disabilities; (2) identify software requirements needed to support community participation; and (3) iteratively refine an existing mHealth application to include new requirements. METHODS: Community Living and Support Services (CLASS), a nonprofit organization that serves individuals with disabilities in Pittsburgh, Pennsylvania, was identified as the focus group for this study. Key stakeholders within the Community Partners Program at CLASS proposed design requirements for an existing mHealth application, Interactive Mobile Health and Rehabilitation (iMHere) 2.0, that has been used to support self-management. RESULTS: We gathered qualitative data from a focus group composed of CLASS members to develop and iteratively revise iMHere 2.0 to include new modules and features to support community integration. A caregiver app was also developed. The new system contains features to support finance, transportation, client and caregiver communication, calendar and checklist management, upcoming medical and nonmedical appointments, social engagement, pain management, and access to a personal profile. Modifications were made to the following existing modules: education, mood, personal health record, goals, medications, and nutrition. CONCLUSIONS: A successful partnership with a community-based organization that supports individuals with disabilities resulted in a newly designed mHealth system with features to support community integration.
RESUMO
BACKGROUND: Imitation, which is impaired in children with autism spectrum disorder (ASD) and critically depends on the integration of visual input with motor output, likely impacts both motor and social skill acquisition in children with ASD; however, it is unclear what brain mechanisms contribute to this impairment. Children with ASD also exhibit what appears to be an ASD-specific bias against using visual feedback during motor learning. Does the temporal congruity of intrinsic activity, or functional connectivity, between motor and visual brain regions contribute to ASD-associated deficits in imitation, motor, and social skills? METHODS: We acquired resting-state functional magnetic resonance imaging scans from 100 8- to 12-year-old children (50 ASD). Group independent component analysis was used to estimate functional connectivity between visual and motor systems. Brain-behavior relationships were assessed by regressing functional connectivity measures with social deficit severity, imitation, and gesture performance scores. RESULTS: We observed increased intrinsic asynchrony between visual and motor systems in children with ASD and replicated this finding in an independent sample from the Autism Brain Imaging Data Exchange. Moreover, children with more out-of-sync intrinsic visual-motor activity displayed more severe autistic traits, while children with greater intrinsic visual-motor synchrony were better imitators. CONCLUSIONS: Our twice replicated findings confirm that visual-motor functional connectivity is disrupted in ASD. Furthermore, the observed temporal incongruity between visual and motor systems, which may reflect diminished integration of visual consequences with motor output, was predictive of the severity of social deficits and may contribute to impaired social-communicative skill development in children with ASD.