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1.
Proc Natl Acad Sci U S A ; 119(27): e2118529119, 2022 07 05.
Artigo em Inglês | MEDLINE | ID: mdl-35767640

RESUMO

During normal T cell development in mouse and human, a low-frequency population of immature CD4-CD8- double-negative (DN) thymocytes expresses early, mature αß T cell antigen receptor (TCR). We report that these early αß TCR+ DN (EADN) cells are DN3b-DN4 stage and require CD3δ but not major histocompatibility complex (MHC) for their generation/detection. When MHC - is present, however, EADN cells can respond to it, displaying a degree of coreceptor-independent MHC reactivity not typical of mature, conventional αß T cells. We found these data to be connected with observations that EADN cells were susceptible to T cell acute lymphoblastic leukemia (T-ALL) transformation in both humans and mice. Using the OT-1 TCR transgenic system to model EADN-stage αß TCR expression, we found that EADN leukemogenesis required MHC to induce development of T-ALL bearing NOTCH1 mutations. This leukemia-driving MHC requirement could be lost, however, upon passaging the tumors in vivo, even when matching MHC was continuously present in recipient animals and on the tumor cells themselves. These data demonstrate that MHC:TCR signaling can be required to initiate a cancer phenotype from an understudied developmental state that appears to be represented in the mouse and human disease spectrum.


Assuntos
Linfócitos T CD8-Positivos , Leucemia-Linfoma Linfoblástico de Células T Precursoras , Receptor Notch1 , Receptores de Antígenos de Linfócitos T alfa-beta , Animais , Linfócitos T CD8-Positivos/metabolismo , Diferenciação Celular , Antígenos de Histocompatibilidade/metabolismo , Humanos , Complexo Principal de Histocompatibilidade , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Mutação , Leucemia-Linfoma Linfoblástico de Células T Precursoras/genética , Receptor Notch1/genética , Receptores de Antígenos de Linfócitos T/genética , Receptores de Antígenos de Linfócitos T/metabolismo , Receptores de Antígenos de Linfócitos T alfa-beta/metabolismo , Timo/metabolismo
2.
Kidney Int ; 105(5): 898-911, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38642985

RESUMO

Research teams are increasingly interested in using cluster randomized trial (CRT) designs to generate practice-guiding evidence for in-center maintenance hemodialysis. However, CRTs raise complex ethical issues. The Ottawa Statement on the Ethical Design and Conduct of Cluster Randomized Trials, published in 2012, provides 15 recommendations to address ethical issues arising within 7 domains: justifying the CRT design, research ethics committee review, identifying research participants, obtaining informed consent, gatekeepers, assessing benefits and harms, and protecting vulnerable participants. But applying the Ottawa Statement recommendations to CRTs in the hemodialysis setting is complicated by the unique features of the setting and population. Here, with the help of content experts and patient partners, we co-developed this implementation guidance document to provide research teams, research ethics committees, and other stakeholders with detailed guidance on how to apply the Ottawa Statement recommendations to CRTs in the hemodialysis setting, the result of a 4-year research project. Thus, our work demonstrates how the voices of patients, caregivers, and all stakeholders may be included in the development of research ethics guidance.


Assuntos
Consentimento Livre e Esclarecido , Projetos de Pesquisa , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Diálise Renal , Ética em Pesquisa
3.
J Gen Intern Med ; 2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-38937366

RESUMO

BACKGROUND: The effectiveness of hospital-based transitional opioid programs (TOPs), which aim to connect patients with substance use disorders (SUD) to ongoing treatment in the community following initiation of medication for opioid use disorder (MOUD) treatment in the hospital, hinges on successful patient transitions. These transitions are enabled by strong partnerships between hospitals and community-based organizations (CBOs). However, no prior study has specifically examined barriers and facilitators to establishing SUD care transition partnerships between hospitals and CBOs. OBJECTIVE: To identify barriers and facilitators to developing partnerships between hospitals and CBOs to facilitate care transitions for patients with SUDs. DESIGN: Qualitative study using semi structured interviews conducted between November 2022-August 2023. PARTICIPANTS: Staff and providers from hospitals affiliated with four safety-net health systems (n=21), and leaders and staff from the CBOs with which they had established partnerships (n=5). APPROACH: Interview questions focused on barriers and facilitators to implementing TOPs, developing partnerships with CBOs, and successfully transitioning SUD patients from hospital settings to CBOs. KEY RESULTS: We identified four key barriers to establishing transition partnerships: policy and philosophical differences between organizations, ineffective communication, limited trust, and a lack of connectivity between data systems. We also identified three facilitators to partnership development: strategies focused on building partnership quality, strategic staffing, and organizing partnership processes. CONCLUSIONS: Our findings demonstrate that while multiple barriers to developing hospital-CBO partnerships exist, stakeholders can adopt implementation strategies that mitigate these challenges such as using mediators, cross-hiring, and focusing on mutually beneficial services, even within resource-limited safety-net settings. Policymakers and health system leaders who wish to optimize TOPs in their facilities should focus on adopting implementation strategies to support transition partnerships such as inadequate data collection and sharing systems.

4.
J Hered ; 115(2): 166-172, 2024 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-37952226

RESUMO

The illegal poaching of lions for their body parts poses a severe threat to lion populations across Africa. Poaching accounts for 35% of all human-caused lion deaths, with 51% attributed to retaliatory killings following livestock predation. In nearly half of the retaliatory killings, lion body parts are removed, suggesting that high demand for lion body parts may fuel killings attributed to human-lion conflict. Trafficked items are often confiscated in transit or destination countries far from their country of origin. DNA from lion parts may in some cases be the only available means for examining their geographic origins. In this paper, we present the Lion Localizer, a full-stack software tool that houses a comprehensive database of lion mitochondrial DNA (mtDNA) sequences sourced from previously published studies. The database covers 146 localities from across the African continent and India, providing information on the potential provenance of seized lion body parts. Lion mtDNA sequences of 350 or 1,140 bp corresponding to the cytochrome b region can be generated from lion products and queried against the Lion Localizer database. Using the query sequence, the Lion Localizer generates a listing of exact or partial matches, which are displayed on an interactive map of Africa. This allows for the rapid identification of potential regions and localities where lions have been or are presently being targeted by poachers. By examining the potential provenance of lion samples, the Lion Localizer serves as a valuable resource in the fight against lion poaching. The software is available at https://lionlocalizer.org.


Assuntos
DNA Mitocondrial , Leões , Animais , Humanos , DNA Mitocondrial/genética , Leões/genética , África , Software
5.
Health Care Manage Rev ; 49(3): 229-238, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38775754

RESUMO

BACKGROUND: Nonprofit hospitals are required to conduct community health needs assessments (CHNA) every 3 years and develop corresponding implementation plans. Implemented strategies must address the identified community needs and be evaluated for impact. PURPOSE: Using the Community Health Implementation Evaluation Framework (CHIEF), we assessed whether and how nonprofit hospitals are evaluating the impact of their CHNA-informed community benefit initiatives. METHODOLOGY: We conducted a content analysis of 83 hospital CHNAs that reported evaluation outcomes drawn from a previously identified 20% random sample ( n = 613) of nonprofit hospitals in the United States. Through qualitative review guided by the CHIEF, we identified and categorized the most common evaluation outcomes reported. RESULTS: A total of 485 strategies were identified from the 83 hospitals' CHNAs. Evaluated strategies most frequently targeted behavioral health ( n = 124, 26%), access ( n = 83, 17%), and obesity/nutrition/inactivity ( n = 68, 14%). The most common type of evaluation outcomes reported by CHIEF category included system utilization ( n = 342, 71%), system implementation ( n = 170, 35%), project management ( n = 164, 34%), and social outcomes ( n = 163, 34%). PRACTICE IMPLICATIONS: CHNA evaluation strategies focus on utilization (the number of individuals served), with few focusing on social or health outcomes. This represents a missed opportunity to (a) assess the social and health impacts across individual strategies and (b) provide insight that can be used to inform the allocation of limited resources to maximize the impact of community benefit strategies.


Assuntos
Avaliação das Necessidades , Humanos , Estados Unidos , Avaliação de Programas e Projetos de Saúde , Serviços de Saúde Comunitária , Hospitais Filantrópicos
6.
FASEB J ; 36(7): e22381, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35661421

RESUMO

Exposure to organic dust in animal and agricultural farms and the ensuing lung inflammation are linked to the development of respiratory diseases. We found previously that elevated production of reactive oxygen species (ROS) by aqueous poultry organic dust extract (hereafter referred to as dust extract) mediates induction of proinflammatory mediators in airway epithelial cells. In the present study, we investigated whether ROS generated by NADPH oxidases (NOX) and xanthine oxidase (XO) controls induction of inflammatory mediators by dust extract and the underlying mechanisms in bronchial epithelial cells. Using chemical inhibitors and siRNA targeted knockdown, we found that NOX1, NOX2, NOX4, and XO-derived ROS regulates induction of proinflammatory mediator levels. Like airway epithelial cells in vitro, NOX inhibitor VAS2870 reduced keratinocyte chemoattractant (KC), IL-6, and TNF-α production and 4-hydroxynonenal (4-HNE) staining induced by dust extract in mouse lungs. VAS2870 inhibition of proinflammatory mediators was associated with reduced NFκB and Stat3 activation indicating that NOX generated ROS activates NFκB and Stat3 to induce proinflammatory gene expression. Dust extract increased the membrane association of p47phox in airway epithelial cells indicating NOX2 activation but had no effect on NOX2 protein levels. In summary, our studies have shown that NOX and XO generated ROS control organic dust induction of proinflammatory mediators in airway epithelial cells via NFκB and Stat3 activation.


Assuntos
NADPH Oxidases , Xantina Oxidase , Animais , Poeira , Mediadores da Inflamação/metabolismo , Pulmão/metabolismo , Camundongos , NADP , NADPH Oxidase 4 , NADPH Oxidases/metabolismo , Extratos Vegetais/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Xantinas/farmacologia
7.
Microb Ecol ; 85(1): 330-334, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34997310

RESUMO

Along with bacteria, fungi can represent a significant component of animal- and plant-associated microbial communities. However, we have only begun to describe these fungi, much less examine their effects on most animals and plants. Bacteria associated with the honey bee, Apis mellifera, have been well characterized across different regions of the gut. The mid- and hindgut of foraging bees house a deterministic set of core species that affect host health, whereas the crop, or the honey stomach, harbors a more diverse set of bacteria that is highly variable in composition among individual bees. Whether this contrast between the two regions of the gut also applies to fungi remains unclear despite their potential influence on host health. In honey bees caught foraging at four sites across the San Francisco Peninsula of California, we found that fungi were less distinct in species composition between the crop and the mid- and hindgut than bacteria. Unlike bacteria, fungi varied substantially in species composition throughout the honey bee gut, and much of this variation could be predicted by the location where we collected the bees. These observations suggest that fungi may be transient passengers and unimportant as gut symbionts. However, our findings also indicate that honey bees could be vectors of infectious plant diseases as many of the fungi we found in the honey bee gut are recognized as plant pathogens.


Assuntos
Trato Gastrointestinal , Microbiota , Abelhas , Animais , Trato Gastrointestinal/microbiologia , Bactérias , Estômago , Fungos
8.
BMC Health Serv Res ; 23(1): 87, 2023 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-36703146

RESUMO

INTRODUCTION: Opioid-related hospitalizations have risen dramatically, placing hospitals at the frontlines of the opioid epidemic. Medicaid expansion and 1115 waivers for substance use disorders (SUDs) are two key policies aimed at expanding access to care, including opioid use disorder (OUD) services. Yet, little is known about the relationship between these policies and the availability of hospital based OUD programs. The aim of this study is to determine whether state Medicaid expansion and adoption of 1115 waivers for SUDs are associated with hospital provision of OUD programs. METHODS: We conducted a cross-sectional study of a random sample of hospitals (n = 457) from the American Hospital Association's 2015 American Hospital Directory, compiled with the most recent publicly available community health needs assessment (2015-2018). RESULTS: Controlling for hospital characteristics, overdose burden, and socio-demographic characteristics, both Medicaid policies were associated with hospital adoption of several OUD programs. Hospitals in Medicaid expansion states had significantly higher odds of implementing any program related to SUDs (OR: 1.740; 95% CI: 1.032-2.934) as well as some specific activities such as programs for OUD treatment (OR: 1.955; 95% CI: 1.245-3.070) and efforts to address social determinants of health (OR: 6.787; 95% CI: 1.308-35.20). State 1115 waivers for SUDs were not significantly associated with any hospital-based SUD activities. CONCLUSIONS: Medicaid expansion was associated with several hospital programs for addressing OUD. The differential availability of hospital-based OUD programs may indicate an added layer of disadvantage for low-income patients with SUD living in non-expansion states.


Assuntos
Medicaid , Transtornos Relacionados ao Uso de Opioides , Humanos , Estados Unidos/epidemiologia , Estudos Transversais , Transtornos Relacionados ao Uso de Opioides/terapia , Analgésicos Opioides/uso terapêutico , Hospitais
9.
J Healthc Manag ; 68(1): 25-37, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36602453

RESUMO

GOALS: Throughout the COVID-19 pandemic, hospitals and their staffs have been pushed to their limits. Hospitals have had to rethink how they support community health while also providing critical acute care services to combat the morbidity and mortality associated with COVID-19. As anchor institutions, hospitals have a significant effect on not only community health and well-being but also on local economies as primary employers and contractors. This study aimed to understand how the pandemic reshaped interactions with community members, staff, and other community organizations and changed the nature of hospital-community engagement among for-profit hospitals. METHODS: We recruited leaders of for-profit hospitals, systems, and a business association that represents for-profit hospitals. We interviewed 28 participants in various leadership roles via telephone or videoconferencing and then thematically coded interview transcriptions. The themes identified in early interviews guided the structure of forthcoming interviews. PRINCIPAL FINDINGS: For-profit hospitals appear motivated to address community health needs as anchor institutions in their communities, and these efforts have strengthened and changed in important ways as a result of the COVID-19 pandemic. In this study, three themes emerged regarding the influence of COVID-19 on hospital-community relationships: Hospitals refocused outreach and engagement efforts to support employees, found essential new ways to safely engage with the community through partnerships and collaborations, and were reminded of the critical roles of social and cultural factors in the health and well-being of individuals and communities. PRACTICAL APPLICATIONS: Hospitals may be able to use lessons learned during the pandemic to support the growing need for community engagement and attention to social determinants of health. The themes that emerged from this study present valuable opportunities for hospitals to carry forward the lessons learned over the course of the pandemic, as they have the potential to improve the delivery of healthcare and community engagement in day-to-day operations as well as in crises.


Assuntos
COVID-19 , Pandemias , Humanos , Atenção à Saúde , Hospitais Comunitários
10.
J Public Health Manag Pract ; 29(6): E231-E236, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37499100

RESUMO

OBJECTIVE: This study examined approaches that nonprofit hospitals use to evaluate community benefit activities in the Community Health Needs Assessment/Implementation Plan (CHNA/IP) process. DESIGN: Content analysis of CHNAs/IPs completed between 2018 and 2021 from a 20% stratified random sample (n = 503) of US nonprofit hospitals. MAIN OUTCOME MEASURES: A coding sheet was used to record details about the evaluation content reported by hospitals in their CHNAs/IPs. Evaluation was coded into 4 categories: (1) no mention of evaluation; (2) description of evaluation without reporting any measures; (3) reporting reach (number of people served) only; and (4) reporting social/health outcomes. For logistic regression analyses, categories 1 and 2 were grouped together into "no evaluation measures" and categories 3 and 4 were grouped into "evaluation measures" for binary comparison. Multinomial logistic regression was also used to individually examine categories 3 and 4 compared with no evaluation measures. RESULTS: While a majority of nonprofit hospitals (71.4%, n = 359) mentioned evaluation in their CHNAs, almost half (49.7%, n = 250) did not report any evaluation measures. Among the 50.3% (n = 253) of hospitals that reported evaluation measures, 67.2% (n = 170) only reported reach. Fewer than 1 in 5 hospitals (16.5%, n = 83) reported social/health outcomes. Hospitals that hired a consultant (adjusted odds ratio [AOR] = 1.61; 95% confidence interval [CI], 1.08-2.43) and system members (AOR = 1.76; 95% CI, 1.12-2.75) had higher odds of reporting evaluation measures. Using hospitals that reported no measures as the base category, system members (AOR = 7.71; 95% CI, 2.97-20.00) also had significantly higher odds of reporting social/health outcomes, while rural locations had lower odds (AOR = 0.43; 95% CI, 0.20-0.94). CONCLUSIONS: Although hospitals are required to evaluate the impact of actions taken to address the health needs identified in their CHNAs, few hospitals are reporting social/health outcomes of such activities. This represents a missed opportunity, as health/social outcomes could be used to inform the allocation of resources to maximize community benefits and the expansion of successful community initiatives.


Assuntos
Participação da Comunidade , Hospitais , Humanos , Planejamento em Saúde Comunitária , Organizações sem Fins Lucrativos , Avaliação das Necessidades , Hospitais Comunitários
11.
J Public Health Manag Pract ; 29(2): E50-E57, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36332229

RESUMO

CONTEXT: Nonprofit hospitals are required to provide community benefits in exchange for their tax-exempt status. This includes a community health needs assessment (CHNA) to identify community needs and an implementation plan (IP) with strategies to address top needs every 3 years. In addition, hospitals are required to engage community members in these assessments. OBJECTIVE: The objective of this study was to explore community engagement and representation in CHNAs and IPs. DESIGN: The researchers conducted a content analysis of CHNAs and IPs from a nationally representative sample of 503 nonprofit hospitals between 2018 and 2021. MAIN OUTCOME MEASURES: For CHNAs, a coding sheet was used to record the types of community members engaged by hospitals. For IPs, the team coded whether community engagement was reported at all and then performed an in-depth analysis to identify categories of community members, engagement methods used, and roles of community input. Finally, frequencies of categories across IPs were quantified. RESULTS: Eighty-nine percent of hospitals (n = 449) engaged community members in their CHNA, but only 14% (n = 71) engaged community members in their IP. An in-depth look at these IPs found that hospitals engaged underserved/minority populations, low-income populations, high school students, public health experts, and stakeholder organizations. Community members were involved in multiple steps, including brainstorming ideas, narrowing down needs, developing strategies, and reacting to proposed strategies. CONCLUSIONS: Although IPs are intended to benefit the community, there is a lack of community involvement reported in IPs. Hospitals may need incentives, resources, and personnel support to ensure representation of community members throughout the entire CHNA and IP process.


Assuntos
Hospitais Comunitários , Saúde Pública , Humanos , Avaliação das Necessidades , Saúde Pública/métodos , Participação da Comunidade/métodos , Organizações sem Fins Lucrativos
12.
J Public Health Manag Pract ; 29(6): E237-E244, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37350619

RESUMO

OBJECTIVE: To identify the prevalence of group reporting of hospital community benefit efforts to the Internal Revenue Service (IRS) and understand hospital and community characteristics associated with this practice. DESIGN: The study was based on data collected from publicly available community benefit reports from 2010 to 2019, as well as secondary data from the 2020 American Hospital Association (AHA) Annual Survey. The sample was drawn from the entire nonprofit US hospital population reporting community benefit activities. The analytic plan employed descriptive statistics and bivariate analysis. SETTING: The United States. PARTICIPANTS: All data are self-reported by US hospitals, either through the publication of community benefit reports (IRS Form 990 Schedule H) or a response to the AHA Annual Survey. MAIN OUTCOME MEASURES: Analyzed variables include whether a hospital reported its community benefit expenditures individually or as a group member; community benefit spending as a percentage of hospital operating expenses; and whether the hospital was part of a multihospital system, with consideration of hospital and community characteristics. RESULTS: Between 2010 and 2019, more than 40% of hospitals participated in group reporting, with most doing so consistently. System membership and hospital size were significantly and positively tied to group reporting, with state community benefit policy tied to the lower prevalence of group reporting. CONCLUSIONS: The high prevalence of group reporting limits accountability to communities and restricts an accurate assessment of community benefit expenditures, counter to policy intentions. Stakeholders should consider what modifications to reporting rules could be made to promote transparency and to ensure that the effects of community benefit policies align with intentions.


Assuntos
Hospitais Comunitários , Isenção Fiscal , Humanos , Estados Unidos , Inquéritos e Questionários , Gastos em Saúde , Responsabilidade Social
13.
J Public Health Manag Pract ; 29(2): E44-E49, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36240509

RESUMO

CONTEXT: As substance use continues to be a public health crisis nationally, it disproportionately affects the Appalachian region. OBJECTIVES: Our research seeks to explore whether there is a greater substance use burden in Appalachia and whether that burden is being prioritized in local hospital systems' community health needs assessments (CHNAs) and implementation strategies (ISs). SETTING: The setting for this study is the 13 states that are represented within the Appalachian region. PARTICIPANTS: This study examines CHNAs and ISs of a stratified random sample (n = 140) representing 20% of the hospital population within the identified states (those with counties within the Appalachian region). Each sampled hospital is labeled as Appalachian or non-Appalachian based on its county designation. MAIN OUTCOME MEASURES: Our main outcome measures were the percentage of hospitals listing substance abuse in their CHNAs, with comparisons between Appalachian and non-Appalachian subgroups, and percent addressing substance use in their ISs in Appalachia and non-Appalachia. DESIGN: Community health needs assessments and ISs produced between the years 2018 and 2021 were gathered for each hospital within the sample; each document was then coded for the inclusion of substance use. Chi-square tests and logistic regression were employed to conduct the analysis and draw conclusions. RESULTS: Although all non-Appalachian Counties that had substance use listed as a need within a CHNA correspondingly addressed that need in their ISs, only 75% of Appalachian counties that listed substance use a need went on to prioritize substance use in an IS. In addition, logistic regression indicated no significant link between overdose rates and addressing substance use. CONCLUSIONS: These findings further support other literature that suggests that lack of resources is limiting Appalachian health care organizations' ability to address substance use issues.


Assuntos
Transtornos Relacionados ao Uso de Substâncias , Humanos , Região dos Apalaches/epidemiologia , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Hospitais Comunitários , Organizações sem Fins Lucrativos , População Rural
14.
Mol Plant Microbe Interact ; 35(2): 157-169, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34732057

RESUMO

Increasingly, new evidence has demonstrated variability in the epitope regions of bacterial flagellin, including in regions harboring the microbe-associated molecular patterns flg22 and flgII-28 that are recognized by the pattern recognition receptors FLS2 and FLS3, respectively. Additionally, because bacterial motility is known to contribute to pathogen virulence and chemotaxis, reductions in or loss of motility can significantly reduce bacterial fitness. In this study, we determined that variations in flg22 and flgII-28 epitopes allow some but not all Xanthomonas spp. to evade both FLS2- and FLS3-mediated oxidative burst responses. We observed variation in the motility for many isolates, regardless of their flagellin sequence. Instead, we determined that past growth conditions may have a significant impact on the motility status of isolates, because we could minimize this variability by inducing motility using chemoattractant assays. Additionally, motility could be significantly suppressed under nutrient-limited conditions, and bacteria could "remember" its prior motility status after storage at ultracold temperatures. Finally, we observed larger bacterial populations of strains with flagellin variants predicted not to be recognized by either FLS2 or FLS3, suggesting that these bacteria can evade flagellin recognition in tomato plants. Although some flagellin variants may impart altered motility and differential recognition by the host immune system, external growth parameters and gene expression regulation appear to have more significant impacts on the motility phenotypes for these Xanthomonas spp.[Formula: see text] Copyright © 2022 The Author(s). This is an open access article distributed under the CC BY 4.0 International license.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Xanthomonas , Arabidopsis/microbiologia , Proteínas de Arabidopsis/metabolismo , Flagelina , Regulação da Expressão Gênica , Polimorfismo Genético , Proteínas Quinases/metabolismo , Xanthomonas/genética , Xanthomonas/metabolismo
15.
J Am Chem Soc ; 144(18): 8296-8305, 2022 05 11.
Artigo em Inglês | MEDLINE | ID: mdl-35486956

RESUMO

Aryl halides are a fundamental motif in synthetic chemistry, playing a critical role in metal-mediated cross-coupling reactions and serving as important scaffolds in drug discovery. Although thermal decarboxylative functionalization of aryl carboxylic acids has been extensively explored, the scope of existing halodecarboxylation methods remains limited, and there currently exists no unified strategy that provides access to any type of aryl halide from an aryl carboxylic acid precursor. Herein, we report a general catalytic method for direct decarboxylative halogenation of (hetero)aryl carboxylic acids via ligand-to-metal charge transfer. This strategy accommodates an exceptionally broad scope of substrates. We leverage an aryl radical intermediate toward divergent functionalization pathways: (1) atom transfer to access bromo- or iodo(hetero)arenes or (2) radical capture by copper and subsequent reductive elimination to generate chloro- or fluoro(hetero)arenes. The proposed ligand-to-metal charge transfer mechanism is supported through an array of spectroscopic studies.


Assuntos
Ácidos Carboxílicos , Halogenação , Ácidos Carboxílicos/química , Catálise , Cobre/química , Ligantes
16.
J Trauma Stress ; 35(2): 461-472, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-34811818

RESUMO

Many returning military service members and veterans who were deployed following the September 11, 2001, terrorist attacks (9/11) suffer from posttraumatic stress disorder (PTSD) and insomnia. Although intensive treatment programs for PTSD have shown promise in the treatment of PTSD symptoms, recent research has demonstrated that sleep disturbance shows little improvement following intensive trauma-focused treatment. The aim of the present study was to evaluate changes in self-reported insomnia symptoms among veterans and service members following participation in a 2-week intensive program for PTSD. We further aimed to investigate if residual PTSD symptoms, specifically hyperarousal, were associated with residual insomnia symptoms. Participants (N = 326) completed self-report assessments of insomnia, PTSD symptoms, and depressive symptoms at pre- and posttreatment. At pretreatment, 73.9% of participants (n = 241) met the criteria for moderate or severe insomnia, whereas at posttreatment 67.7% of participants (n = 203) met the criteria. Results of paired t tests demonstrated statistically significant differences between pre- and posttreatment Insomnia Severity Index scores; however, the effect size was small, d = 0.34. Analyses revealed that posttreatment hyperarousal symptoms were associated with posttreatment insomnia. These findings suggest that although an intensive program for service members and veterans with PTSD may significantly reduce insomnia symptoms, clinically meaningful residual insomnia symptoms remain. Further research is warranted to elucidate the association between residual hyperarousal and insomnia symptoms following intensive trauma-focused treatment.


Assuntos
Distúrbios do Início e da Manutenção do Sono , Transtornos de Estresse Pós-Traumáticos , Veteranos , Nível de Alerta , Progressão da Doença , Humanos , Pacientes Ambulatoriais , Distúrbios do Início e da Manutenção do Sono/complicações , Distúrbios do Início e da Manutenção do Sono/terapia , Transtornos de Estresse Pós-Traumáticos/complicações , Transtornos de Estresse Pós-Traumáticos/diagnóstico , Transtornos de Estresse Pós-Traumáticos/terapia
17.
Health Care Manage Rev ; 47(1): E11-E20, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-33507040

RESUMO

BACKGROUND: In 2014, Maryland established a global budget policy for all hospitals in the state. Under this policy, hospitals are incentivized to not only provide clinical care services to individual patients but also address the health needs of their broader patient population through prevention efforts and investment in the upstream social and economic factors that determine health. PURPOSE: To better understand the incentives created for hospitals under this policy, our study assessed whether the implementation of global budgets changed the levels and patterns of Maryland hospitals' investments in community benefits. APPROACH: Data on hospital community benefit spending from the Internal Revenue Service Form 990 Schedule H for the years 2010-2016 were utilized for this study. RESULTS: We found that Maryland hospitals' total spending on community benefits decreased under the global budget policy. Unlike hospitals in similar states without a global budget policy, Maryland hospitals did not experience any increases in Medicaid shortfalls between 2014 and 2016. Although Maryland hospitals provided more subsidized health services, their investment in broader community health improvement activities remained unchanged. CONCLUSION: Our analysis suggests that Maryland hospitals have shifted strategies because of the implementation of the global budget policy. The ability to report community benefit in a way that accurately considers the context and constraints of a state's policies would provide hospitals better means of communicating these efforts to stakeholders. PRACTICE IMPLICATIONS: Our results suggest that global budgets impact the levels and patterns of hospitals' community benefit investments.


Assuntos
Orçamentos , Hospitais Comunitários , Humanos , Maryland , Medicaid , Estados Unidos
18.
J Public Health Manag Pract ; 28(1): E146-E154, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-32810071

RESUMO

CONTEXT: There is growing evidence that social factors contribute disproportionately to health outcomes in the United States as compared with health care services. As a result, nonprofit hospitals are incorporating strategies to address social needs into their Internal Revenue Service (IRS)-mandated community benefit work. Much of the research base on this subject, however, has focused on the efforts of adult-serving hospitals. OBJECTIVE: The aim of this study was to determine whether communities surrounding children's hospitals are unique with regard to social needs and categorize how children's hospitals are addressing social needs in their IRS-mandated community benefit work. METHODS: Using county-level health and economic data, we compared community characteristics of children's hospital counties with the national average. We then coded and analyzed the community benefit reports of all nonprofit children's hospitals in the United States to categorize the different strategies that hospitals adopt to address social needs. RESULTS: Children's hospitals (N = 168) serve communities with greater social needs than the national average. In terms of community benefit investments, children's hospitals were more likely to identify social needs in their community health needs assessment than adult-serving hospitals, but still less than half identified or addressed 1 or more social needs. Children's hospitals were more likely to adopt interventions that address broader population health rather than strategies that focus on clinical services or children and adolescents in particular. CONCLUSIONS: Pediatric health care institutions have a profound opportunity to reduce health disparities by altering the social environments in which children develop. Policy makers and scholars should provide support and resources to increase community benefit investments in this area.


Assuntos
Determinantes Sociais da Saúde , Fatores Sociais , Adolescente , Adulto , Criança , Cidades , Hospitais , Humanos , Avaliação das Necessidades , Estados Unidos
19.
J Public Health Manag Pract ; 28(5): E764-E767, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35867515

RESUMO

Nonprofit hospitals frequently partner with their local health department on developing community health needs assessments (CHNAs); yet, little is known about the role that such partnerships play in strengthening the alignment between needs identified in hospitals' assessments and the strategies adopted by hospitals to address identified needs. Using data for 486 hospitals from the third round of CHNAs (spanning the years 2018-2021), this study showed strong alignment between the health needs identified in the CHNAs and those addressed in hospitals' implementation strategies, independent of collaboration with the local health department. One noteworthy exception to this finding was that hospital-public health collaboration remained important for improved alignment of needs related to substance use. Involvement of the local health department may strengthen hospitals' capacity to address needs outside their traditional areas of expertise, such as substance use.


Assuntos
Organizações sem Fins Lucrativos , Saúde Pública , Hospitais , Hospitais Comunitários , Humanos , Avaliação das Necessidades
20.
Inorg Chem ; 60(12): 8394-8403, 2021 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-34097407

RESUMO

A new long-lived, visible-light-absorbing homoleptic Cu(I) metal-to-ligand charge transfer (MLCT) photosensitizer, [Cu(dchtmp)2]PF6 (dchtmp = 2,9-dicyclohexyl-3,4,7,8-tetramethyl-1,10-phenanthroline), has been synthesized, structurally characterized, and evaluated in terms of its molecular photophysics, electrochemistry, and electronic structure. Static and time-resolved transient absorption (TA) and photoluminescence (PL) spectroscopy measured on the title compound in CH2Cl2 (τ = 2.6 µs, ΦPL = 5.5%), CH3CN (τ = 1.5 µs, ΦPL = 2.6%), and THF (τ = 2.0 µs, ΦPL = 3.7%) yielded impressive photophysical metrics even when dissolved in Lewis basic solvents. The combined static spectroscopic data along with ultrafast TA experiments revealed that the pseudo-Jahn-Teller distortion and intersystem crossing dynamics in the MLCT excited state displayed characteristics of being sterically arrested throughout its evolution. Electrochemical and static PL data illustrate that [Cu(dchtmp)2]PF6 is a potent photoreductant (-1.77 V vs Fc+/0 in CH3CN) equal to or greater than all previously investigated homoleptic Cu(I) diimine complexes. Although we successfully prepared the cyclopentyl analog dcptmp (2,9-dicyclopentyl-3,4,7,8-tetramethyl-1,10-phenanthroline) using the same C-C radical coupling photochemistry as dchtmp, the corresponding Cu(I) complex could not be isolated due to the steric hindrance presented at the metal center. Ultimately, the successful preparation of [Cu(dchtmp)2]+ represents a major step forward for the design and discovery of novel earth-abundant photosensitizers made possible through a newly conceived ligand synthetic strategy.

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