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1.
Nature ; 630(8015): 206-213, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38778111

RESUMO

Targeted radionuclide therapy, in which radiopharmaceuticals deliver potent radionuclides to tumours for localized irradiation, has addressed unmet clinical needs and improved outcomes for patients with cancer1-4. A therapeutic radiopharmaceutical must achieve both sustainable tumour targeting and fast clearance from healthy tissue, which remains a major challenge5,6. A targeted ligation strategy that selectively fixes the radiopharmaceutical to the target protein in the tumour would be an ideal solution. Here we installed a sulfur (VI) fluoride exchange (SuFEx) chemistry-based linker on radiopharmaceuticals to prevent excessively fast tumour clearance. When the engineered radiopharmaceutical binds to the tumour-specific protein, the system undergoes a binding-to-ligation transition and readily conjugates to the tyrosine residues through the 'click' SuFEx reaction. The application of this strategy to a fibroblast activation protein (FAP) inhibitor (FAPI) triggered more than 80% covalent binding to the protein and almost no dissociation for six days. In mice, SuFEx-engineered FAPI showed 257% greater tumour uptake than did the original FAPI, and increased tumour retention by 13-fold. The uptake in healthy tissues was rapidly cleared. In a pilot imaging study, this strategy identified more tumour lesions in patients with cancer than did other methods. SuFEx-engineered FAPI also successfully achieved targeted ß- and α-radionuclide therapy, causing nearly complete tumour regression in mice. Another SuFEx-engineered radioligand that targets prostate-specific membrane antigen (PSMA) also showed enhanced therapeutic efficacy. Considering the broad scope of proteins that can potentially be ligated to SuFEx warheads, it might be possible to adapt this strategy to other cancer targets.


Assuntos
Terapia de Alvo Molecular , Neoplasias da Próstata , Radioisótopos , Compostos Radiofarmacêuticos , Animais , Humanos , Masculino , Camundongos , Antígenos de Superfície/química , Antígenos de Superfície/metabolismo , Linhagem Celular Tumoral , Fluoretos/química , Fluoretos/metabolismo , Glutamato Carboxipeptidase II/química , Glutamato Carboxipeptidase II/metabolismo , Ligantes , Proteínas de Membrana/metabolismo , Proteínas de Membrana/química , Terapia de Alvo Molecular/métodos , Projetos Piloto , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/radioterapia , Radioisótopos/uso terapêutico , Compostos Radiofarmacêuticos/química , Compostos Radiofarmacêuticos/uso terapêutico , Compostos Radiofarmacêuticos/metabolismo , Compostos Radiofarmacêuticos/farmacocinética , Compostos de Enxofre/química , Compostos de Enxofre/metabolismo , Tirosina/metabolismo , Tirosina/química , Ensaios Antitumorais Modelo de Xenoenxerto
2.
Proc Natl Acad Sci U S A ; 121(19): e2317703121, 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38687792

RESUMO

Fluorescence labeling of chemically fixed specimens, especially immunolabeling, plays a vital role in super-resolution imaging as it offers a convenient way to visualize cellular structures like mitochondria or the distribution of biomolecules with high detail. Despite the development of various distinct probes that enable super-resolved stimulated emission depletion (STED) imaging of mitochondria in live cells, most of these membrane-potential-dependent fluorophores cannot be retained well in mitochondria after chemical fixation. This lack of suitable mitochondrial probes has limited STED imaging of mitochondria to live cell samples. In this study, we introduce a mitochondria-specific probe, PK Mito Orange FX (PKMO FX), which features a fixation-driven cross-linking motif and accumulates in the mitochondrial inner membrane. It exhibits high fluorescence retention after chemical fixation and efficient depletion at 775 nm, enabling nanoscopic imaging both before and after aldehyde fixation. We demonstrate the compatibility of this probe with conventional immunolabeling and other strategies commonly used for fluorescence labeling of fixed samples. Moreover, we show that PKMO FX facilitates correlative super-resolution light and electron microscopy, enabling the correlation of multicolor fluorescence images and transmission EM images via the characteristic mitochondrial pattern. Our probe further expands the mitochondrial toolkit for multimodal microscopy at nanometer resolutions.


Assuntos
Aldeídos , Corantes Fluorescentes , Microscopia de Fluorescência , Mitocôndrias , Mitocôndrias/metabolismo , Humanos , Corantes Fluorescentes/química , Aldeídos/metabolismo , Aldeídos/química , Microscopia de Fluorescência/métodos , Células HeLa , Reagentes de Ligações Cruzadas/química , Animais , Membranas Mitocondriais/metabolismo
3.
J Bone Miner Metab ; 41(5): 693-701, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37351651

RESUMO

INTRODUCTION: The aim here is to examine the association between objectively measured usual walking speed (UWS) and bone status in community-dwelling older Chinese. MATERIALS AND METHODS: This is a cross-sectional study of a population of 1528 adults (817 females, mean age 68.5 ± 5.3; 711 males, mean age 69.1 ± 5.2) aged 60-79, living in communities in Shanghai. Walking speed was assessed using a 4-m walk test at a usual-pace walking speed a walking speed at which the subject felt relaxed-and bone status measured by quantitative ultrasound (QUS). The health-related characteristics of participants include family background, physical activity level, chronic disease, smoking and alcohol consumption, frequency of falls, vitamin intake, and hormone therapy. RESULTS: Multiple linear regression is used to analyses any association between UWS and bone status, adjusting for confounding factors showing a significant association between faster UWS and a higher calcaneal stiffness index (SI) (p < 0.01). Comparing the lowest quartile of the data set with the highest at UWS, a high SI is achieved with 5.34 (95% CI = 3.22, 7.46) (p < 0.01), after adjusting for confounders. An increase of 1 dm/s was associated with a 0.91 (95% CI = 0.53, 1.29) increase in SI. This relationship for most subgroups is consistent. CONCLUSION: Our findings suggest that UWS can be a sensitive indicator of calcaneal bone loss among an older population.


Assuntos
Calcâneo , Velocidade de Caminhada , Masculino , Feminino , Humanos , Idoso , Pessoa de Meia-Idade , Calcâneo/diagnóstico por imagem , Estudos Transversais , China , Estado Nutricional , Caminhada
4.
Can J Anaesth ; 70(6): 963-967, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37165123

RESUMO

PURPOSE: Sociodemographic risks contributing to health inequities are often inadequately captured and reported in critical care studies. To address the lack of standardized terms and definitions, we sought to develop a practical and convenient resource of questions and response options for collecting sociodemographic variables for critical care research. SOURCE: To identify domains and variables that impact health equity, we searched: 1) PubMed for critical care randomized trials (2010 to 2021); 2) high-impact critical care and general medicine journals for special issues relating to equity; and 3) governmental and nongovernmental resources. PRINCIPAL FINDINGS: We identified 23 domains associated with health equity, including pronouns, age, sex, gender identity, sexual orientation, race and ethnicity, visible minorities, language, household income, marital/relationship status, education, disabilities, immigrant and refugee status, employment, primary care access, expanded health insurance, internet access, housing security, food security, dependents, religion, and postal code. For each domain we provided standardized questions and response options; for 13/23 domains, we included more than one version of the question and response categories. CONCLUSION: We developed a standardized, practical, and convenient demographic data collection tool for critical care research studies. Questions and response options can be adapted by researchers for inclusion in individual study questionnaires or case report forms.


RéSUMé: OBJECTIF: Les risques sociodémographiques qui contribuent aux inégalités en matière de santé sont souvent mal saisis et rapportés dans les études de soins intensifs. Pour remédier au manque de termes et de définitions normalisés, nous avons cherché à élaborer une ressource à la fois pratique et utile de questions et d'options de réponse pour le recueil des variables sociodémographiques pour la recherche en soins intensifs. SOURCES: Pour identifier les domaines et les variables qui ont une incidence sur l'équité en santé, nous avons effectué des recherches dans : 1) PubMed, pour en extraire les études randomisées en soins intensifs (2010 à 2021); 2) des revues de soins intensifs et de médecine générale à impact élevé pour identifier les numéros spéciaux liés à l'équité; et 3) les ressources gouvernementales et non gouvernementales. CONSTATATIONS PRINCIPALES: Nous avons identifié 23 domaines associés à l'équité en santé, y compris les pronoms, l'âge, le sexe, l'identité de genre, l'orientation sexuelle, la race et l'origine ethnique, les minorités visibles, la langue, le revenu du ménage, l'état matrimonial / relationnel, l'éducation, les handicaps, le statut d'immigrant·e et de réfugié·e, l'emploi, l'accès aux soins primaires, l'assurance maladie élargie, l'accès à l'internet, la sécurité du logement, la sécurité alimentaire, les personnes à charge, la religion et le code postal. Pour chaque domaine, nous avons fourni des questions et des options de réponse normalisées; pour 13/23 domaines, nous avons inclus plus d'une version des catégories de questions et réponses. CONCLUSION: Nous avons mis au point un outil de collecte de données démographiques normalisé, pratique et utile pour la recherche en soins intensifs. Les options de questions et de réponses peuvent être adaptées par les chercheuses et chercheurs pour être incluses dans des questionnaires d'étude individuels ou des formulaires de présentation de cas.


Assuntos
Identidade de Gênero , Desigualdades de Saúde , Feminino , Humanos , Masculino , Canadá , Coleta de Dados , Atenção à Saúde
5.
BMC Public Health ; 22(1): 2281, 2022 12 06.
Artigo em Inglês | MEDLINE | ID: mdl-36474219

RESUMO

INTRODUCTION: There is a rise in problematic substance use among Canadian youth, which is precipitating a public health crisis. Interventions are needed to empower youth to mitigate substance use risks. Active youth involvement in substance use prevention is urgently needed to increase uptake and ownership of the process and outcome of the intervention. Arts-based interventions are ideal participatory action approaches that can empower young people to be active agents in substance use prevention. These approaches can help promote health, reduce harm, and change behaviours. Scoping reviews are a vital tool that can help the research team identify relevant interventions that can be adapted to a community. METHODS: This scoping review explores various arts-based substance use prevention interventions for youth. The scoping review used the iterative stages of Arksey and O'Malley to search Portal ERIC, Ovid MEDLINE, C.I.N.A.H.L., E.M.B.A.S.E., Web of Science, and A.P.A. PsycInfo and grey literature from Canadian Centre on Substance Use and Addiction and websites suggested by the Canadian Agency for Drugs and Technologies in Health. Inclusion criteria are a) articles utilizing arts-based intervention on substance use prevention; b) studies with a clearly defined intervention; c) intervention targeting the youth (age 12-17) and d) publications written in English. Thematic analysis was used to identify the main themes from the included articles. RESULTS AND DISCUSSION: Themes identified in a thematic synthesis of these studies included a) the intent of the intervention; b) intervention characteristics; and c) the perceived effectiveness of interventions. Art-based interventions increased knowledge and changed attitudes and practices on substance use among youth. Making the interventions aesthetically appealing and engaging, active youth involvement in the development of the intervention and developing youth-centred interventions which attended to the realities they faced were central to the success of these interventions.


Assuntos
Promoção da Saúde , Transtornos Relacionados ao Uso de Substâncias , Humanos , Adolescente , Criança , Canadá , Propriedade , Transtornos Relacionados ao Uso de Substâncias/prevenção & controle
6.
BMC Pediatr ; 22(1): 106, 2022 02 24.
Artigo em Inglês | MEDLINE | ID: mdl-35209870

RESUMO

BACKGROUND: Inhibitory control develops rapidly during the preschool stage, and development of inhibitory control in this period is significant for the healthy growth of the future. However, most studies paid more attention to children and adolescents in recent years, but less focus on preschool children. Therefore, the purpose of this study was to explore the association between the health-related physical fitness and inhibitory control in preschool children. METHODS: This cross-sectional study was based on a baseline data from randomized controlled trial by cluster sampling(including 128 preschoolers, 70 boys, 58girls).The health-related physical fitness T-score (HPFT) was obtained by adding standard scores of six indicators: body mass index, handgrip strength, standing long jump, one-leg balance, 2 × 10 m shuttle run test, and 20 m shuttle run test. Inhibitory control was assessed using the flanker task and reflected by reaction time and accuracy. RESULTS: A total of 120 preschoolers were included in the final statistical analysis. After adjusting the confounders, HPFT was associated with reaction time (ß=-2.49 ms, 95%CI: -4.22, -0.75). Similarly, a negative association was observed between one-leg balance and reaction time (ß=-12.04 ms, 95%CI: -18.94, -5.15), and between 20 m shuttle run test and reaction time (ß=-23.28 ms, 95%CI: -37.00, -9.56). Compared with the participants in the lowest tertile, HPFT (ß=-158.74, 95%CI: -309.63, -7.84), one-leg balance (ß=-267.25 ms, 95%CI: -420.71, -113.79) and 20 m shuttle run test (ß=-215.58 ms, 95%CI: -374.67, -56.49) were all negatively associated with reaction time of those in the highest tertile. CONCLUSIONS: Negative relationships between HPFT and RT of the inhibitory control were observed in preschoolers. To have better inhibitory control, it's suggested that HPFT of preschoolers should be at least 249. These findings are of great significance for the early improvement of HPFT and the development of inhibitory control in preschool children.


Assuntos
Teste de Esforço , Força da Mão , Adolescente , Índice de Massa Corporal , Pré-Escolar , Estudos Transversais , Humanos , Masculino , Aptidão Física
7.
Proc Natl Acad Sci U S A ; 116(25): 12500-12505, 2019 06 18.
Artigo em Inglês | MEDLINE | ID: mdl-31160454

RESUMO

Deficiency in the E3 ubiquitin ligase UBE3A leads to the neurodevelopmental disorder Angelman syndrome (AS), while additional dosage of UBE3A is linked to autism spectrum disorder. The mechanisms underlying the downstream effects of UBE3A gain or loss of function in these neurodevelopmental disorders are still not well understood, and effective treatments are lacking. Here, using stable-isotope labeling of amino acids in mammals and ubiquitination assays, we identify PTPA, an activator of protein phosphatase 2A (PP2A), as a bona fide ubiquitin ligase substrate of UBE3A. Maternal loss of Ube3a (Ube3am-/p+) increased PTPA level, promoted PP2A holoenzyme assembly, and elevated PP2A activity, while maternal 15q11-13 duplication containing Ube3a down-regulated PTPA level and lowered PP2A activity. Reducing PTPA level in vivo restored the defects in dendritic spine maturation in Ube3am-/p+ mice. Moreover, pharmacological inhibition of PP2A activity with the small molecule LB-100 alleviated both reduction in excitatory synaptic transmission and motor impairment in Ube3am-/p+ mice. Together, our results implicate a critical role of UBE3A-PTPA-PP2A signaling in the pathogenesis of UBE3A-related disorders and suggest that PP2A-based drugs could be potential therapeutic candidates for treatment of UBE3A-related disorders.


Assuntos
Espinhas Dendríticas/metabolismo , Peptidilprolil Isomerase/metabolismo , Proteína Fosfatase 2/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , Animais , Transtorno do Espectro Autista/metabolismo , Encéfalo/enzimologia , Ativação Enzimática , Inibidores Enzimáticos/farmacologia , Camundongos , Camundongos Transgênicos , Proteína Fosfatase 2/antagonistas & inibidores , Proteólise , Transmissão Sináptica , Ubiquitina-Proteína Ligases/genética , Ubiquitinação
8.
Epilepsia ; 62(2): 517-528, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33400301

RESUMO

OBJECTIVE: Mutations of the cyclin-dependent kinase-like 5 (CDKL5) gene cause severe neurodevelopmental disorders characterized by intractable epilepsy, intellectual disability, and autism. Multiple mouse models generated for mechanistic studies have exhibited phenotypes similar to some human pathological features, but none of the models has developed one of the major symptoms affecting CDKL5 deficiency disorder (CDD) patients: intractable recurrent seizures. As disrupted neuronal excitation/inhibition balance is closely associated with the activity of glutamatergic and γ-aminobutyric acidergic (GABAergic) neurons, our aim was to study the effect of the loss of CDKL5 in different types of neurons on epilepsy. METHODS: Using the Cre-LoxP system, we generated conditional knockout (cKO) mouse lines allowing CDKL5 deficiency in glutamatergic or GABAergic neurons. We employed noninvasive video recording and in vivo electrophysiological approaches to study seizure activity in these Cdkl5 cKO mice. Furthermore, we conducted Timm staining to confirm a morphological alteration, mossy fiber sprouting, which occurs with limbic epilepsy in both human and mouse brains. Finally, we performed whole-cell patch clamp in dentate granule cells to investigate cell-intrinsic properties and synaptic excitatory activity. RESULTS: We demonstrate that Emx1- or CamK2α-derived Cdkl5 cKO mice manifest high-frequency spontaneous seizure activities recapitulating the epilepsy of CDD patients, which ultimately led to sudden death in mice. However, Cdkl5 deficiency in GABAergic neurons does not generate such seizures. The seizures were accompanied by typical epileptic features including higher amplitude spikes for epileptiform discharges and abnormal hippocampal mossy fiber sprouting. We also found an increase in spontaneous and miniature excitatory postsynaptic current frequencies but no change in amplitudes in the dentate granule cells of Emx1-cKO mice, indicating enhanced excitatory synaptic activity. SIGNIFICANCE: Our study demonstrates that Cdkl5 cKO mice, serving as an animal model to study recurrent spontaneous seizures, have potential value for the pathological study of CDD-related seizures and for therapeutic innovation.


Assuntos
Síndromes Epilépticas/genética , Neurônios GABAérgicos/metabolismo , Ácido Glutâmico/metabolismo , Proteínas Serina-Treonina Quinases/genética , Convulsões/genética , Espasmos Infantis/genética , Animais , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina , Giro Denteado/citologia , Giro Denteado/metabolismo , Modelos Animais de Doenças , Eletroencefalografia , Síndromes Epilépticas/metabolismo , Síndromes Epilépticas/fisiopatologia , Potenciais Pós-Sinápticos Excitadores/fisiologia , Neurônios GABAérgicos/patologia , Proteínas de Homeodomínio , Camundongos , Camundongos Knockout , Fibras Musgosas Hipocampais/patologia , Neurônios/metabolismo , Neurônios/patologia , Técnicas de Patch-Clamp , Prosencéfalo , Convulsões/metabolismo , Convulsões/fisiopatologia , Espasmos Infantis/metabolismo , Espasmos Infantis/fisiopatologia , Fatores de Transcrição
9.
BMC Health Serv Res ; 21(1): 741, 2021 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-34311712

RESUMO

BACKGROUND: Immigrants from culturally, ethnically, and linguistically diverse countries face many challenges during the resettlement phase, which influence their access to healthcare services and health outcomes. The "Healthy Immigrant Effect" or the health advantage that immigrants arrive with is observed to deteriorate with increased length of stay in the host country. METHODS: An exploratory qualitative design, following a community-based research approach, was employed. The research team consisted of health researchers, clinicians, and community members. The objective was to explore the barriers to healthcare access among immigrants with limited English language proficiency. Three focus groups were carried out with 29 women and nine men attending English language classes at a settlement agency in a mid-sized city. Additionally, 17 individual interviews were carried out with healthcare providers and administrative staff caring for immigrants and refugees. RESULTS: A thematic analysis was carried out with transcribed focus groups and healthcare provider interview data. Both the healthcare providers and immigrants indicated that limited language proficiency often delayed access to available healthcare services and interfered with the development of a therapeutic relationship between the client and the healthcare provider. Language barriers also impeded effective communication between healthcare providers and clients, leading to suboptimal care and dissatisfaction with the care received. Language barriers interfered with treatment adherence and the use of preventative and screening services, further delaying access to timely care, causing poor chronic disease management, and ultimately resulting in poor health outcomes. Involving untrained interpreters, family members, or others from the ethnic community was problematic due to misinterpretation and confidentiality issues. CONCLUSIONS: The study emphasises the need to provide language assistance during medical consultations to address language barriers among immigrants. The development of guidelines for recruitment, training, and effective engagement of language interpreters during medical consultation is recommended to ensure high quality, equitable and client-centered care.


Assuntos
Emigrantes e Imigrantes , Idioma , Barreiras de Comunicação , Feminino , Acessibilidade aos Serviços de Saúde , Humanos , Masculino , Pesquisa Qualitativa
10.
Sensors (Basel) ; 20(17)2020 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-32824984

RESUMO

Antibiotic-resistant bacteria have emerged as an imminent global threat. The lack of rapid and sensitive diagnostic techniques leaves health care providers with inadequate resources for guiding therapy and risks the lives of patients. The traditional plate culturing methods for identifying antibiotic-resistant bacteria is laborious and time-consuming. Bulk PCR (Polymerase Chain Reaction) and qPCR are limited by poor detection sensitivity, which is critical for the early-stage detection of bloodstream infections. In this study, we introduce a technique for detecting ß-lactamase-producing bacteria at single-cell sensitivity based on a commercial ß-lactamase sensor (Fluorocillin), droplet microfluidics, and a custom 3D particle counter. Bacteria-containing samples were encapsulated within picoliter-sized droplets at the single-cell level and cultured within water-in-oil droplets containing antibiotics and the Fluorocillin sensor. Then, fluorescent droplets were digitally quantified with the 3D particle counter, which is capable of analyzing milliliter-scale volumes of collected droplets within 10 min. The fluorescence signal from single-colony droplets was detectable in less than 5 h, and the 3D scanning was performed in less than 10 min, which was significantly faster than conventional culture-based methods. In this approach, the limit of detection achieved was about 10 bacterial cells per mL of sample, and the turnaround time from sample to result was less than 6 h. This study demonstrates a promising strategy for the detection of ß-lactamase-producing bacteria using the recently developed IC 3D system.


Assuntos
Bactérias , Sepse , beta-Lactamases , Técnicas Biossensoriais , Humanos , Microfluídica , Reação em Cadeia da Polimerase
11.
Neurobiol Learn Mem ; 123: 168-78, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26070657

RESUMO

Single-session anodal transcranial direct current stimulation (tDCS) can improve the learning-memory function of patients with Alzheimer's disease (AD). After-effects of tDCS can be more significant if the stimulation is repeated regularly in a period. Here the behavioral and the histologic effects of the repetitive anodal tDCS on a rat model of AD were investigated. Sprague-Dawley rats were divided into 6 groups, the sham group, the ß-amyloid (Aß) group, the Aß+20µA tDCS group, the Aß+60µA tDCS group, the Aß+100µA tDCS group and the Aß+200µA tDCS group. Bilateral hippocampus of the rats in the Aß group and the Aß+tDCS groups were lesioned by Aß1-40 to produce AD models. One day after drug injection, repetitive anodal tDCS (10 sessions in two weeks, 20min per session) was applied to the frontal cortex of the rats in the tDCS groups, while sham stimulation was applied to the Aß group and the sham group. The spatial learning and memory capability of the rats were tested by Morris water maze. Bielschowsky's silver staining, Nissl's staining, choline acetyltransferase (ChAT) and glial-fibrillary-acidic protein (GFAP) immunohistochemistry of the hippocampus were conducted for histologic analysis. Results show in the Morris water maze task, rats in the Aß+100µA and the Aß+200µA tDCS groups had shorter escape latency and larger number of crossings on the platform. Significant histologic differences were observed in the Aß+100µA and the Aß+200µA tDCS groups compared to the Aß group. The behavioral and the histological experiments indicate that the proposed repetitive anodal tDCS treatment can protect spatial learning and memory dysfunction of Aß1-40-lesioned AD rats.


Assuntos
Doença de Alzheimer/terapia , Peptídeos beta-Amiloides/farmacologia , Lobo Frontal/fisiopatologia , Aprendizagem em Labirinto/fisiologia , Fragmentos de Peptídeos/farmacologia , Memória Espacial/fisiologia , Estimulação Transcraniana por Corrente Contínua/métodos , Doença de Alzheimer/induzido quimicamente , Doença de Alzheimer/fisiopatologia , Peptídeos beta-Amiloides/administração & dosagem , Animais , Comportamento Animal/fisiologia , Modelos Animais de Doenças , Feminino , Lobo Frontal/patologia , Fragmentos de Peptídeos/administração & dosagem , Desempenho Psicomotor , Ratos , Ratos Sprague-Dawley , Estimulação Transcraniana por Corrente Contínua/efeitos adversos
12.
Disabil Rehabil ; : 1-15, 2024 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-38842140

RESUMO

PURPOSE: Racial minoritized children and youth with acquired brain injury (ABI) often experience multiple forms of discrimination. The purpose of this systematic review was to understand the racial disparities in health care among children and youth with ABI and their caregivers. METHOD: Six international databases (Ovid Medline, Embase, Healthstar, Psychinfo, Scopus, and Web of Science) were systematically searched for peer-reviewed articles. Studies were screened by two researchers who also conducted the data extraction and quality appraisal. A narrative synthesis approach was used to analyze the data. RESULTS: Of the 8081 studies identified in the search, 34 met the inclusion criteria, which involved 838,052 children and youth with brain injuries (or caregivers representing them) across two countries. The following themes were noted in the studies in our review: (1) racial disparities in accessing care (i.e., diagnosis, hospital admission, length of stay, rehabilitation treatment); (2) racial disparities in ABI-related health outcomes (i.e., functional outcomes and mortality rates); and (3) factors affecting racial disparities (i.e., sources in injury, insurance and expenditures, and intersectionality). CONCLUSIONS: Our findings reveal the concerning racial disparities among children and youth with ABI. Further research should explore solutions for addressing such racial disparities and solutions to address them.


Racial minoritized youth with acquired brain injury experience many barriers and inequalities in accessing care and health care leaders should help to address such gaps and disparities in the health system.Clinicians should familiarize themselves with the common factors affecting racial disparities in acquired brain injury outcomes including sources of injury, types of insurance and cultural factors.Additional training in working with patients from racially diverse backgrounds and in providing culturally appropriate care among healthcare providers is needed.More efforts are needed to address racial disparities at the individual and structural levels that continue to exist in rehabilitation services for children and youth with acquired brain injury.

13.
Accid Anal Prev ; 200: 107544, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38493612

RESUMO

Cycling crashes constitute a significant and rising share of traffic accidents. Consequently, exploring factors affecting cycling safety has become a priority for both governmental bodies and scholars. However, most existing studies have neglected the vision factors capable of quantitatively describing the city-level cycling environment. Moreover, they have relied on limited models that lack interpretability and fail to capture the spatial variations in the contribution of factors. To address these gaps, this research proposed a framework that used origin-destination-based cycling flow and vision factors generated from Google Street View images to identify the leading factors. It also employed the comparative Automatic Machine Learning and interpretable SHAP value-based geospatial analysis to explain each factor's contribution to the cycling crash risk, with a particular focus on the spatial variations in the influence of vision factors. The effectiveness of this framework was validated by a case study in Manhattan, which examined the leading risk factors of cycling crash rates at intersections. The results showed that the LightGBM model, with selected subsets of factors, outperformed other models. Through SHAP explanations of global feature importance, the study identified the proportion of road barriers, the proportion of open sky, and the number of visible trucks as the leading visual risk factors. Additionally, using SHAP-based geospatial analysis, the study revealed the local variations in the effects of these three factors and identified eight areas with higher cycling crash rates. Based on these findings, the study provided practical measures for a safer cycling environment in Manhattan.


Assuntos
Acidentes de Trânsito , Ciclismo , Humanos , Acidentes de Trânsito/prevenção & controle , Fatores de Risco , Aprendizado de Máquina , Segurança
14.
Disabil Rehabil ; : 1-20, 2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38864302

RESUMO

PURPOSE: Although the health benefits of early diagnosis and therapeutic approaches for children and youth with autism spectrum disorder (ASD), racial disparities persist. This systematic review explored the experiences of racism and racial disparities in health care among children and youth with ASD and their caregivers. METHODS: We conducted a systematic review, drawing on six international databases. Two reviewers screened titles, abstracts, and full texts. Thirty-seven studies met our inclusion criteria and we applied a narrative synthesis to develop themes. RESULTS: Four themes were identified: (1) experiences and aspects of racism and racial disparities (i.e., language and cultural barriers, poor quality health care interactions, stereotypes and discrimination, family and community stigma, and indirect barriers); (2) racial disparities in health care (i.e., screening and referral, diagnosis, health care services, and care coordination and medication); (3) facilitators to accessing health care services; and (4) recommendations from caregivers. CONCLUSIONS: This review highlights the extensive racial disparities experienced by children with autism. More research is needed to explore youth's perspectives on racism in addition to exploring potential interventions to address racial disparities and improve health equity for youth with ASD.


Racial minoritized youth with autism experience many barriers in accessing health care and there is an urgent need to address the systemic racism within our health care systems.Health care leaders and decision-makers should advocate for policy and systems change to enhance equitable access to health services for all youth with disabilities, especially those who belong to minoritized groups.Health care providers should consider engaging in relevant training to provide culturally safe and appropriate services for racially diverse clients with autism.Health care providers and decision-makers should work together to remove barriers to accessing health care for racial minoritized youth with autism.

15.
Food Chem X ; 21: 101211, 2024 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-38384691

RESUMO

To realize the high-value utilization of Rushan cheese by-product, Rushan cheese whey was used as a raw material to prepare angiotensin-Ⅰ-converting enzyme inhibitory peptides (ACEIPs). After enzymatic hydrolysisn and ultrafiltration, the sequences of peptides were identified by liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS). Two novel ACE inhibitory peptides Phe-Asp-Arg-Pro-Phe-Leu (FDRPFL) and Lys-Trp-Glu-Lys-Pro-Phe (KWEKPF) were identified. Additionally, both of the peptides exhibited good water-solubility and no toxicity according to in-silico prediction. Fourier transform infrared spectroscopy results show that both FDRPFL and KWEKPF were enriched in ß-turn and ß-sheet structures. Lineweaver-Burk plots revealed that FDRPFL and KWEKPF exhibited non-competitive and mixed inhibition patterns, respectively. Molecular docking and MD simulation showed that hydrogen bonds and ionic bonds forces allowed FDRPFL and KWEKPF to form stable and compact complexes with ACE. In conclusion, enzymatic hydrolysis of Rushan cheese by-products yields bioactive peptides, increases the added value of whey and reduces environmental pollution.

16.
PLoS One ; 19(1): e0291228, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38271462

RESUMO

BACKGROUND: Accessible housing is imperative to enabling independent living for many people with disabilities; yet, research consistently shows how people with disabilities often lack appropriate accessible housing and are more likely to experience unaffordable, insecure, and/or poor quality housing. Therefore, the aim of this study was to understand promising practices, policies and interventions regarding accessible independent housing for people with disabilities. METHODS: We conducted a scoping review that involved searching seven international literature databases that identified 4831 studies, 60 of which met our inclusion criteria. RESULTS: The reviewed studies involved 18 countries over a 20-year period. Our review highlighted the following key trends: (1) removing barriers to obtaining accessible housing (e.g., advocacy, builders enhancing housing supply, subsidies and financial incentives); (2) policies influencing accessible housing; (3) interventions to enhance accessible housing (i.e., home modifications, smart homes, mobile applications and other experimental devices); and (4) the impact of accessible independent housing on health and wellbeing. CONCLUSIONS: Our findings emphasize the importance of accessible housing for people with disabilities and the urgent need to advance accessible housing options.


Assuntos
Pessoas com Deficiência , Habitação , Humanos , Políticas , Vida Independente
17.
Disabil Rehabil ; : 1-21, 2024 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-38339994

RESUMO

PURPOSE: Asian children and youth with disabilities often experience multiple barriers and discrimination in education, healthcare, and social settings, which influence their well-being, especially the transition to adulthood. This review aims to explore the types, factors affecting and impact of ableism on Asian children and youth with disabilities and their caregivers. METHODS: We conducted a systematic review and a narrative synthesis whereby we searched the literature from six international databases, including Healthstar, Ovid Medline, Embase, PsycInfo, Scopus, and Web of Science. RESULTS: Twenty-nine studies were included in the review, and three themes were identified that related to ableism: (1) types and rates of ableism (i.e., stigma, bullying and victimization, and discrimination and inequalities); (2) factors affecting ableism (i.e. sociodemographic factors, familial factors, and societal factors); and (3) impacts of ableism (i.e. mental health, family impacts, and societal impacts). CONCLUSIONS: Our review highlights that ableism has various types and can be influenced by multiple factors, influencing social and health outcomes of Asian families with children and youth with disabilities. This review also emphasizes the importance of increasing the public's awareness regarding disabilities to reduce ableism among Asian families with children with disabilities.


Asian children and youth with disabilities often experience bullying and victimization, therefore it is necessary to develop educational materials to raise awareness of disabilities.Healthcare providers should consider developing more educational programs for caregivers to reduce self-stigma and affiliate stigma and promote mental health.  Healthcare service providers should consider creating and implementing more inclusive programs to reduce health disparities and the influence of socio-demographic factors.

18.
Subst Use ; 18: 29768357241244680, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38707894

RESUMO

Introduction: Immigrant youth face heightened risks of substance use due to the stress associated with immigration and acculturation. While parental intervention can have a preventative impact on substance use, parents need to be well-informed about substance use and effective interventions that can prevent substance use among immigrant youth. Such interventions ought to be culturally sensitive, family-based, and targeted at the specific substances that are prevalent in a given context. Identifying and curating interventions that can empower parents in addressing substance use can help mitigate the risks that immigrant youth may face. Methods: This scoping review aimed to identify the types, characteristics, and effectiveness of family-based substance use intervention programs. Based on Arksay and O'Malley's guidelines, interventions included in the review must have met the following criteria: (a) was a family-based intervention aiming to prevent substance use; (b) targeted immigrant teens aged 12 to 17 years old; (c) was published in English; (d) originated from Australia, Canada, New Zealand, or the United States. The pinch table was used to synthesize included articles, after which studies were compared and categorized, and cross-cutting categories were identified. Results: After screening 4551 searched literature, 13 studies that utilized family-based interventions were included in the review. All interventions were face-to-face programs, and most interventions involved parents and youth as participants. Eco-developmental theory and active learning strategies were used by multiple interventions. Given immigrant families were target stakeholders, both deep structure and surface structure cultural adaptations were utilized. Interventions increased parents' knowledge and skills regarding substance use prevention and delayed substance use initiation among youth. Conclusion: From the review, it was evident that parents are an essential element in any program aiming to prevent or reduce children's substance use. Besides information about substance use prevention, the curriculum also involves parenting and communication skills for parents to understand the protective effects of family. Effective family-based interventions for immigrant youth require attention to parenting and immigration stress, while also considering cultural adaptation. Future directions and limitations are also discussed.

19.
PeerJ ; 12: e17606, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38952989

RESUMO

Objective: To investigate the effects of 12-week weight-bearing dance aerobics (WBDA) on muscle morphology, strength and functional fitness in older women. Methods: This controlled study recruited 37 female participants (66.31y ± 3.83) and divided them into intervention and control groups according to willingness. The intervention group received 90-min WBDA thrice a week for 12 weeks, while the control group maintained normal activities. The groups were then compared by measuring muscle thickness, fiber length and pennation angle by ultrasound, muscle strength using an isokinetic multi-joint module and functional fitness, such as 2-min step test, 30-s chair stand, chair sit-and-reach, TUG and single-legged closed-eyed standing test. The morphology, strength, and functional fitness were compared using ANCOVA or Mann-Whitney U test to study the effects of 12 weeks WBDA. Results: Among all recruited participants, 33 completed all tests. After 12 weeks, the thickness of the vastus intermedius (F = 17.85, P < 0.01) and quadriceps (F = 15.62, P < 0.01) was significantly increased in the intervention group compared to the control group, along with a significant increase in the torque/weight of the knee flexor muscles (F = 4.47, P = 0.04). Similarly, the intervention group revealed a significant improvement in the single-legged closed-eyed standing test (z = -2.16, P = 0.03) compared to the control group. Conclusion: The study concluded that compared to the non-exercising control group, 12-week WBDA was shown to thicken vastus intermedius, increase muscle strength, and improve physical function in older women. In addition, this study provides a reference exercise program for older women.


Assuntos
Dança , Força Muscular , Suporte de Carga , Humanos , Feminino , Força Muscular/fisiologia , Idoso , Dança/fisiologia , Suporte de Carga/fisiologia , Aptidão Física/fisiologia , Extremidade Inferior/fisiologia , Extremidade Inferior/diagnóstico por imagem , Pessoa de Meia-Idade , Músculo Esquelético/fisiologia , Músculo Esquelético/anatomia & histologia , Músculo Esquelético/diagnóstico por imagem , Exercício Físico/fisiologia , Músculo Quadríceps/fisiologia , Músculo Quadríceps/diagnóstico por imagem , Músculo Quadríceps/anatomia & histologia
20.
PLoS One ; 19(7): e0307087, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39024322

RESUMO

BACKGROUND: The COVID-19 pandemic has accelerated the transition to remote work, leading to increased attention on presenteeism and absenteeism among remote workers. Understanding the implications of these phenomena on worker health and productivity is crucial for optimizing remote work arrangements and developing policies to improve employee well-being. OBJECTIVES: This scoping review aims to examine the occurrence of presenteeism and absenteeism among remote workers during the COVID-19 pandemic and the interrelated physical and mental health issues during these periods. METHODS: PsycINFO, Medline, Embase, CINAHL, Eric, Business Source Premier, SCOPUS, and sociological abstracts were searched resulting in 1792 articles. Articles were included if the population of interest was 18+ (i.e., working age), engaged in full or part-time work, and the employees shifted from in-person to remote work due to the COVID-19 pandemic. All study designs, geographical areas, and papers written post-onset of the COVID-19 pandemic were included; however, systematic reviews were excluded. Data was charted into Microsoft Excel by 2 independent reviewers. RESULTS: The literature search identified 10 studies (i.e., seven cross-sectional studies, two qualitative studies, and one observational study). Five major overarching themes were identified specifically (1) telework and mental health (2) telework and physical health (3) worker benefits (4) gender dynamics and (5) difficulty navigating the teleworking environment. While remote work offers flexibility in terms of saved commute time and flexible work schedules, it also exacerbates challenges related to presenteeism, absenteeism, and work-life balance. These challenges include experiencing psychological distress, depression, anxiety, stress, sleep deprivation, musculoskeletal pain, difficulties concentrating at work for both women and working parents, struggles disconnecting after hours, and the inability to delineate between the work and home environment. DISCUSSION: The findings suggest that remote work during the COVID-19 pandemic has both positive and negative implications for worker well-being and productivity. However, future research needs to incorporate the potential effects of telework frequency (full time vs. part time) on employee productivity and its role on presenteeism and absenteeism, to gain a more comprehensive understanding on remote work difficulties. Addressing these challenges requires proactive interventions and support mechanisms to promote worker health and productivity in remote settings.


Assuntos
Absenteísmo , COVID-19 , Presenteísmo , Teletrabalho , Humanos , COVID-19/epidemiologia , COVID-19/psicologia , SARS-CoV-2/patogenicidade , Pandemias , Saúde Ocupacional , Saúde Mental , Masculino , Feminino
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