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1.
Proc Natl Acad Sci U S A ; 118(16)2021 04 20.
Artigo em Inglês | MEDLINE | ID: mdl-33859044

RESUMO

Age-related macular degeneration (AMD) is a leading cause of blindness among the elderly. Canonical disease models suggest that defective interactions between complement factor H (CFH) and cell surface heparan sulfate (HS) result in increased alternative complement pathway activity, cytolytic damage, and tissue inflammation in the retina. Although these factors are thought to contribute to increased disease risk, multiple studies indicate that noncanonical mechanisms that result from defective CFH and HS interaction may contribute to the progression of AMD as well. A total of 60 ciliated sensory neurons in the nematode Caenorhabditis elegans detect chemical, olfactory, mechanical, and thermal cues in the environment. Here, we find that a C. elegans CFH homolog localizes on CEP mechanosensory neuron cilia where it has noncanonical roles in maintaining inversin/NPHP-2 within its namesake proximal compartment and preventing inversin/NPHP-2 accumulation in distal cilia compartments in aging adults. CFH localization and maintenance of inversin/NPHP-2 compartment integrity depend on the HS 3-O sulfotransferase HST-3.1 and the transmembrane proteoglycan syndecan/SDN-1. Defective inversin/NPHP-2 localization in mouse and human photoreceptors with CFH mutations indicates that these functions and interactions may be conserved in vertebrate sensory neurons, suggesting that previously unappreciated defects in cilia structure may contribute to the progressive photoreceptor dysfunction associated with CFH loss-of-function mutations in some AMD patients.


Assuntos
Fator H do Complemento/metabolismo , Heparitina Sulfato/metabolismo , Retina/metabolismo , Animais , Caenorhabditis elegans/metabolismo , Proteínas de Caenorhabditis elegans/metabolismo , Cílios/metabolismo , Fator H do Complemento/fisiologia , Heparitina Sulfato/fisiologia , Degeneração Macular/metabolismo , Degeneração Macular/fisiopatologia , Neurônios/metabolismo , Fatores de Transcrição/metabolismo
2.
Fam Community Health ; 46(Suppl 1): S41-S51, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37696015

RESUMO

Community power represents the ability of communities to develop, sustain, and grow the capacity to participate in and advance systems change that addresses health inequities but is difficult to assess because of its multifaceted, longitudinal nature. Using California's school-based Local Control Funding Formula (LCFF) as an example, this article examines the interconnectedness of longitudinal policy and systems changes as one approach to understanding and visualizing evolving community power. Data on policy and systems changes were collected during the 10-year, place-based Building Healthy Communities initiative and coded using thematic analysis. Related changes within sites and between community and state levels were linked to show how changes built and overlapped over time. Around 45% of changes were interconnected and cascaded to build momentum within sites; in addition, a substantial proportion of statewide changes (68%) overlapped with community ones. The state-level LCFF policy led to multiple community-based changes over time, involving ongoing engagement from various community groups across communities. Local implementation of the LCFF policy change was used to illustrate the usefulness of connecting community-driven policy and systems changes over time to explore the dynamics of community power and address some of the limitations of that approach.


Assuntos
Nível de Saúde , Políticas , Humanos
3.
Eval Program Plann ; 102: 102381, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-37839214

RESUMO

Community organizing and base building groups operate as part of a larger ecosystem of organizations, each with complementary capacities necessary to build power and achieve social change. Analytic approaches to assessing power in organizational networks can generate data to inform strategy, identify gaps, and help nurture organizational ecosystems that support communities in building and exercising power. This article uses a network of 43 justice-focused organizations in the Bay Area, California and their 267 reported connections as a case study to assess the feasibility of measuring power building capacities using social network analyses. We evaluated network capacity for different power-building capacities and explored the relationships between organizations' positions in the network and their access to capacity. We found that justice-focused organizations were more likely than their connections to have mature capacity for creating alliances and coalitions and for research/legal strategies, whereas their connections were more likely to report mature capacity for community organizing. Most participants in the network were connected within one degree to an organization that was mature in organizing and base building. These results highlight the potential to assess community power building capacities within networks of organizations to identify ecosystem strengths and weaknesses and opportunities for strategic development.


Assuntos
Fortalecimento Institucional , Ecossistema , Humanos , Avaliação de Programas e Projetos de Saúde
4.
BMJ Open ; 14(10): e089884, 2024 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-39448212

RESUMO

BACKGROUND: Population-based genetic screening and testing programmes have substantial potential to improve cancer-related outcomes through early detection and cancer prevention. Yet, genetic testing for cancer risk remains largely underused. This study aimed to describe barriers and facilitators to patient engagement at each stage of a California-based genetic screening programme, from completing the electronic screener to receiving the test and to identify potential improvements that could support precision medicine-based approaches to patient care. METHODS: We conducted 26 semistructured interviews among programme participants who did not complete the screener (n=9), those who did not receive the recommended test (n=7) and those who received a genetic test (n=10). Interviewees were selected from patients who recently received a mammogram through one of the participating Southern California clinics. Interviews were transcribed and coded using Atlas.ti. The study used a qualitative descriptive approach to identify similar and contrasting themes among the participant groups. RESULTS: This study found that barriers and facilitators to engagement were largely the same regardless of how far participants had moved through the process towards getting a genetic test. We identified four overarching themes: participants wanted clear communication of personal benefits at each stage; participants needed additional information and knowledge to navigate genetic screening and testing; a trusted provider could be instrumental in participants following a recommendation; and repetition and timing strongly impacted participants' likelihood to engage. CONCLUSIONS: Providing education about the benefits of genetic screening and testing to patients and their families, as well as clear communication about what each step entails may help patients engage with similar programmes. Strategies aimed at increasing coordination among a patient's healthcare team can also help ensure information reaches patients in multiple ways, from multiple providers, to increase the likelihood that recommendations for testing come from trusted sources, which supports the uptake of genetic testing.


Assuntos
Neoplasias da Mama , Detecção Precoce de Câncer , Testes Genéticos , Mamografia , Pesquisa Qualitativa , Humanos , Feminino , Neoplasias da Mama/genética , Neoplasias da Mama/diagnóstico , Pessoa de Meia-Idade , California , Idoso , Adulto , Entrevistas como Assunto , Participação do Paciente , Aceitação pelo Paciente de Cuidados de Saúde
5.
Artigo em Inglês | MEDLINE | ID: mdl-36078291

RESUMO

Adverse childhood experiences (ACEs) increase the risk of poor health and wellbeing in adulthood. In this study, we tested whether experiences in early adulthood-intimate partner violence (IPV), substance use, social isolation, and work instability-mediate the relationship between ACEs and poor physical health in later adulthood. Using data from a large-scale survey of Medicaid enrollees in the Portland metropolitan area, four separate mediation models were constructed to assess the indirect effects of each early adulthood experience and the proportion of the total effect on physical health accounted for by the pathway. Experiencing four or more ACEs increased the risk of poor adult physical health by 50% (RR 1.50). Considered in separate models, mediation by IPV accounted for 14.4% of the total effect; substance use mediated a similar proportion (14.0%). Social isolation was a less substantial mediator (7.6%). Work instability did not mediate the relationship between ACEs and adult physical health in our population. These findings provide evidence that IPV, substance use, and social isolation in early adulthood are part of the pathway between high ACEs and poor adult physical health. Intervening to prevent negative early adult experiences may mitigate some of the long-term effects of childhood trauma on health.


Assuntos
Experiências Adversas da Infância , Violência por Parceiro Íntimo , Transtornos Relacionados ao Uso de Substâncias , Adulto , Humanos , Pobreza , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Inquéritos e Questionários
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