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1.
Emerg Infect Dis ; 28(11): 2155-2164, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36287030

RESUMO

A multispecies outbreak of Nocardia occurred among heart transplant recipients (HTR), but not lung transplant recipients (LTR), in Sydney, New South Wales, Australia, during 2018-2019. We performed a retrospective review of 23 HTR and LTR who had Nocardia spp. infections during June 2015-March 2021, compared risk factors for Nocardia infection, and evaluated climate conditions before, during, and after the period of the 2018-2019 outbreak. Compared with LTR, HTR had a shorter median time from transplant to Nocardia diagnosis, higher prevalence of diabetes, greater use of induction immunosuppression with basiliximab, and increased rates of cellular rejection before Nocardia diagnosis. During the outbreak, Sydney experienced the lowest monthly precipitation and driest surface levels compared with time periods directly before and after the outbreak. Increased immunosuppression of HTR compared with LTR, coupled with extreme weather conditions during 2018-2019, may explain this outbreak of Nocardia infections in HTR.


Assuntos
Transplante de Coração , Nocardiose , Nocardia , Humanos , Basiliximab , Combinação Trimetoprima e Sulfametoxazol , Nocardiose/epidemiologia , Nocardiose/diagnóstico , Transplantados , Surtos de Doenças , Transplante de Coração/efeitos adversos
2.
Transpl Int ; 35: 10752, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36451683

RESUMO

Vascularized Composite Allotransplantation (VCA) involves transplantation of multiple tissues from a donor to a recipient (e.g., skin, muscle, bone). Little is known about the US public's perceptions of and attitudes toward VCA organ donation. This multi-site, cross-sectional, mixed methods study involved focus groups and surveys to assess members of the general public's attitudes about VCA, and willingness and barriers to donate VCA organs. Qualitative data were analyzed by thematic analysis; quantitative data were analyzed by descriptive statistics. In focus groups (n = 6, 42 participants), most participants were female (57%) and Black (62%) with mean age of 42.6 years. Three main themes emerged: 1) awareness and perceptions of VCA, 2) purpose of VCA donation, 3) and barriers to VCA donation. Participants had heard little about VCA and sought information about VCA donation. Participants perceived VCA as challenging their concepts of "normality" and voiced concerns that VCA would create "Frankenstein[s]." Barriers to VCA donation included disruptions to end-of-life arrangements and information gaps regarding the donation process. Participants reported moderate to high willingness to donate their hands (69%) and face (50%) Public education efforts should address the specific needs and concerns of the public to facilitate VCA donation and family authorization.


Assuntos
Transplante de Órgãos , Alotransplante de Tecidos Compostos Vascularizados , Feminino , Humanos , Adulto , Masculino , Estudos Transversais , Opinião Pública , Doadores de Tecidos
3.
Am J Ind Med ; 65(3): 173-195, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34897753

RESUMO

BACKGROUND: Janitors are a low-wage, ethnically and linguistically diverse, hard-to-reach population of workers with a high burden of occupational injury and illness. METHODS: Data from an extensive multimodal (mail, phone, web) survey of janitors in Washington State were analyzed to characterize their working conditions and occupational health experiences. The survey included questions on demographics, work organization and tasks, health and safety topics, and discrimination and harassment. The survey was administered in eight languages. RESULTS: There were 620 complete interviews. The majority completed the survey by mail (62.6%), and in English (85.8%). More than half of responding janitors were female (56.9%), and the mean age was 45 years. Twenty percent reported having a (health-care-provider diagnosed) work-related injury or illness (WRII) in the past twelve months. Women and janitors who were Latino had significantly higher relative risk of WRII. Increased risk was also associated with several work organization factors that may indicate poor working conditions, insufficient sleep, and possible depression. Half of injured janitors did not file workers' compensation (WC) claims. CONCLUSIONS: Janitors reported a high percentage of WRII, which exceeded previously published estimates from Washington State. Women and Latino janitors had significantly increased risk of WRII, and janitors' working conditions may influence the unequal distribution of risk. WRII surveillance via WC or medical care usage in janitors and other low-wage occupations may reflect substantial underreporting. Characterizing the nature of janitors' work experience can help identify avenues for prevention, intervention, and policy changes to protect the health and safety of janitors.


Assuntos
Traumatismos Ocupacionais , Indenização aos Trabalhadores , Feminino , Arquivamento , Humanos , Masculino , Pessoa de Meia-Idade , Traumatismos Ocupacionais/epidemiologia , Ocupações , Inquéritos e Questionários , Washington/epidemiologia
4.
Clin Transplant ; 34(11): e14066, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32810365

RESUMO

As the field of Vascular Composite Allotransplantation (VCA) grows, demand for VCA donations will increase. The public should be made aware of this treatment option to support patients' informed decision-making and authorization for deceased donation. We assessed the availability and quality of existing VCA public education materials from organ procurement organizations (OPOs), transplant centers, the Organ Procurement and Transplant Network, Veterans Affairs, and the Department of Defense. A content analysis was performed to identify topics covered and important gaps. In total, 1314 public education materials were analyzed, including OPO Facebook posts (61.6%), OPO Twitter posts (29.9%), websites (6.4%), and written documents (eg, fact sheets, research reports) (2.1%). Upper extremity (34.7%) and face (34.5%) transplants were more commonly covered than reproductive (6.4%) or other VCA types (2.8%). Most materials (76.6%) referenced a specific VCA story. However, few materials described which patient population could benefit from VCA (eg, Veterans, amputees, burn victims, 16.4%), the authorization requirements for VCA donation (6.6%), or the appearance of transplanted VCA organs (1.2%). Current VCA public education materials do not adequately educate the public. More comprehensive education materials are needed to prepare the public to authorize VCA donation, become potential donors, or learn about transplant options.


Assuntos
Aloenxertos Compostos , Obtenção de Tecidos e Órgãos , Transplantes , Alotransplante de Tecidos Compostos Vascularizados , Humanos , Doadores de Tecidos , Estados Unidos
5.
Health Expect ; 23(6): 1450-1465, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33037746

RESUMO

BACKGROUND: Despite available evidence-based interventions that decrease health disparities, these interventions are often not implemented. Northwestern Medicine's® Hispanic Kidney Transplant Program (HKTP) is a culturally and linguistically competent intervention designed to reduce disparities in living donor kidney transplantation (LDKT) among Hispanics/Latinos. The HKTP was introduced in two transplant programs in 2016 to evaluate its effectiveness. OBJECTIVE: This study assessed barriers and facilitators to HKTP implementation preparation. METHODS: Interviews and group discussions were conducted with transplant stakeholders (ie administrators, nurses, physicians) during implementation preparation. The Consolidated Framework for Implementation Research (CFIR) guided interview design and qualitative analysis. RESULTS: Forty-four stakeholders participated in 24 interviews and/or 27 group discussions. New factors, not found in previous implementation preparation research in health-care settings, emerged as facilitators and barriers to the implementation of culturally competent care. Implementation facilitators included: stakeholders' focus on a moral imperative to implement the HKTP, personal motivations related to their Hispanic heritage, and perceptions of Hispanic patients' transplant education needs. Implementation barriers included: stakeholders' perceptions that Hispanics' health insurance payer mix would negatively impact revenue, a lack of knowledge about LDKT disparities and patient data disaggregated by ethnicity/race, and a perception that the family discussion component was immoral because of the possibility of coercion. DISCUSSION AND CONCLUSIONS: Our study identified novel barriers and facilitators to the implementation preparation of a culturally competent care intervention. Healthcare administrators can facilitate organizations' implementation of culturally competent care interventions by understanding factors challenging care delivery processes and raising clinical team awareness of disparities in LDKT.


Assuntos
Assistência à Saúde Culturalmente Competente , Saúde da População , Idoso , Competência Cultural , Feminino , Disparidades nos Níveis de Saúde , Disparidades em Assistência à Saúde , Humanos , Masculino , Medicare , Estudos Prospectivos , Estados Unidos
6.
J Biol Chem ; 293(23): 8912-8921, 2018 06 08.
Artigo em Inglês | MEDLINE | ID: mdl-29666184

RESUMO

ATP-sensitive potassium channels (KATP) contribute to membrane currents in many tissues, are responsive to intracellular metabolism, and open as ATP falls and ADP rises. KATP channels are widely distributed in tissues and are prominently expressed in the heart. They have generally been observed in ventricular tissue, but they are also expressed in the atria and conduction tissues. In this study, we focused on the contribution and role of the inwardly rectifying KATP channel subunit, Kir6.1, in the sinoatrial node (SAN). To develop a murine, conduction-specific Kir6.1 KO model, we selectively deleted Kir6.1 in the conduction system in adult mice (cKO). Electrophysiological data in single SAN cells indicated that Kir6.1 underlies a KATP current in a significant proportion of cells and influences early repolarization during pacemaking, resulting in prolonged cycle length. Implanted telemetry probes to measure heart rate and electrocardiographic characteristics revealed that the cKO mice have a slow heart rate, with episodes of sinus arrest in some mice. The PR interval (time between the onset of the P wave to the beginning of QRS complex) was increased, suggesting effects on the atrioventricular node. Ex vivo studies of whole heart or dissected heart regions disclosed impaired adaptive responses of the SAN to hypoxia, and this may have had long-term pathological consequences in the cKO mice. In conclusion, Kir6.1-containing KATP channels in the SAN have a role in excitability, heart rate control, and the electrophysiological adaptation of the SAN to hypoxia.


Assuntos
Frequência Cardíaca , Canais KATP/metabolismo , Potássio/metabolismo , Nó Sinoatrial/metabolismo , Aclimatação , Potenciais de Ação , Animais , Células Cultivadas , Deleção de Genes , Hipóxia/metabolismo , Canais KATP/genética , Camundongos , Camundongos Knockout
7.
J Biol Chem ; 292(43): 17587-17597, 2017 10 27.
Artigo em Inglês | MEDLINE | ID: mdl-28893911

RESUMO

ATP-sensitive potassium (KATP) channels are widely expressed in the cardiovascular system, where they regulate a range of biological activities by linking cellular metabolism with membrane excitability. KATP channels in vascular smooth muscle have a well-defined role in regulating vascular tone. KATP channels are also thought to be expressed in vascular endothelial cells, but their presence and function in this context are less clear. As a result, we aimed to investigate the molecular composition and physiological role of endothelial KATP channels. We first generated mice with an endothelial specific deletion of the channel subunit Kir6.1 (eKO) using cre-loxP technology. Data from qRT-PCR, patch clamp, ex vivo coronary perfusion Langendorff heart experiments, and endothelial cell Ca2+ imaging comparing eKO and wild-type mice show that Kir6.1-containing KATP channels are indeed present in vascular endothelium. An increase in intracellular [Ca2+], which is central to changes in endothelial function such as mediator release, at least partly contributes to the endothelium-dependent vasorelaxation induced by the KATP channel opener pinacidil. The absence of Kir6.1 did not elevate basal coronary perfusion pressure in eKO mice. However, vasorelaxation was impaired during hypoxia in the coronary circulation, and this resulted in greater cardiac injury during ischemia-reperfusion. The response to adenosine receptor stimulation was impaired in eKO mice in single cells in patch clamp recordings and in the intact coronary circulation. Our data support the existence of an endothelial KATP channel that contains Kir6.1, is involved in vascular reactivity in the coronary circulation, and has a protective role in ischemia reperfusion.


Assuntos
Sinalização do Cálcio , Cálcio/metabolismo , Circulação Coronária , Endotélio Vascular/metabolismo , Canais KATP/metabolismo , Traumatismo por Reperfusão Miocárdica/metabolismo , Vasodilatação , Animais , Endotélio Vascular/fisiopatologia , Canais KATP/genética , Camundongos , Camundongos Knockout , Traumatismo por Reperfusão Miocárdica/genética , Traumatismo por Reperfusão Miocárdica/fisiopatologia
8.
Environ Sci Technol ; 51(3): 1110-1119, 2017 02 07.
Artigo em Inglês | MEDLINE | ID: mdl-28002664

RESUMO

Aging water infrastructure and increased water scarcity have resulted in higher interest in water reuse and decentralization. Rating systems for high-performance buildings implicitly promote the use of building-scale, decentralized water supply and treatment technologies. It is important to recognize the potential benefits and trade-offs of decentralized and centralized water systems in the context of high-performance buildings. For this reason and to fill a gap in the current literature, we completed a life cycle assessment (LCA) of the decentralized water system of a high-performance, net-zero energy, net-zero water building (NZB) that received multiple green building certifications and compared the results with two modeled buildings (conventional and water efficient) using centralized water systems. We investigated the NZB's impacts over varying lifetimes, conducted a break-even analysis, and included Monte Carlo uncertainty analysis. The results show that, although the NZB performs better in most categories than the conventional building, the water efficient building generally outperforms the NZB. The lifetime of the NZB, septic tank aeration, and use of solar energy have been found to be important factors in the NZB's impacts. While these findings are specific to the case study building, location, and treatment technologies, the framework for comparison of water and wastewater impacts of various buildings can be applied during building design to aid decision making. As we design and operate high-performance buildings, the potential trade-offs of advanced decentralized water treatment systems should be considered.


Assuntos
Meio Ambiente , Água , Águas Residuárias , Purificação da Água , Abastecimento de Água
9.
Am J Ind Med ; 60(8): 711-723, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28594073

RESUMO

INTRODUCTION: The trucking industry has a high burden of work-related injuries. This study examined factors, such as safety climate perceptions, that may impact injury risk. METHOD: A random sample of 9800 commercial driver's license holders (CDL) were sent surveys, only 4360 were eligible truck drivers. Descriptive statistics and logistic regression models were developed to describe the population and identify variables associated with work-related injury. RESULTS: 2189 drivers completed the pertinent interview questions. Driving less-than-truckload, daytime sleepiness, pressure to work faster, and having a poor composite score for safety perceptions were all associated with increased likelihood of work-related injury. Positive safety perception score was protective for odds of work-related injury, and increased claim filing when injured. CONCLUSIONS: Positive psychological safety climate is associated with decreased likelihood of work-related injury and increased likelihood that a driver injured on the job files a workers' compensation claim.


Assuntos
Condução de Veículo/psicologia , Indústrias , Traumatismos Ocupacionais/psicologia , Cultura Organizacional , Gestão da Segurança , Adolescente , Adulto , Idoso , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Veículos Automotores , Percepção , Inquéritos e Questionários , Adulto Jovem
10.
J Biol Chem ; 290(31): 19233-44, 2015 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-26088132

RESUMO

The description of potential molecular substrates for predisposition to atrial fibrillation (AF) is incomplete, and it is unknown what role regulators of G-protein signaling might play. We address whether the attenuation of RGS4 function may promote AF and the mechanism through which this occurs. For this purpose, we studied a mouse with global genetic deletion of RGS4 (RGS4(-/-)) and the normal littermate controls (RGS4(+/+)). In vivo electrophysiology using atrial burst pacing revealed that mice with global RGS4 deletion developed AF more frequently than control littermates. Isolated atrial cells from RGS4(-/-) mice show an increase in Ca(2+) spark frequency under basal conditions and after the addition of endothelin-1 and abnormal spontaneous Ca(2+) release events after field stimulation. Isolated left atria studied on a multielectrode array revealed modest changes in path length for re-entry but abnormal electrical events after a pacing train in RGS4(-/-) mice. RGS4 deletion results in a predisposition to atrial fibrillation from enhanced activity in the Gαq/11-IP3 pathway, resulting in abnormal Ca(2+) release and corresponding electrical events.


Assuntos
Fibrilação Atrial/genética , Cálcio/metabolismo , Proteínas RGS/genética , Potenciais de Ação , Animais , Fibrilação Atrial/metabolismo , Sinalização do Cálcio , Estimulação Elétrica , Predisposição Genética para Doença , Átrios do Coração/metabolismo , Átrios do Coração/patologia , Camundongos Endogâmicos C57BL , Camundongos Knockout , Miócitos Cardíacos/fisiologia , Proteínas RGS/metabolismo
11.
MMWR Morb Mortal Wkly Rep ; 64(32): 874-7, 2015 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-26292206

RESUMO

Exposure to hydrofluoric acid (HF) causes corrosive chemical burns and potentially fatal systemic toxicity. Car and truck wash cleaning products, rust removers, and aluminum brighteners often contain HF because it is efficient in breaking down roadway matter. The death of a truck wash worker from ingestion of an HF-based wash product and 48 occupational HF burn cases associated with car and truck washing in Washington State during 2001-2013 are summarized in this report. Among seven hospitalized workers, two required surgery, and all but one worker returned to the job. Among 48 injured workers, job titles were primarily auto detailer, car wash worker, truck wash worker, and truck driver. Because HF exposure can result in potentially severe health outcomes, efforts to identify less hazardous alternatives to HF-based industrial wash products are warranted.


Assuntos
Acidentes de Trabalho/estatística & dados numéricos , Automóveis , Queimaduras Químicas/epidemiologia , Detergentes/toxicidade , Ácido Fluorídrico/toxicidade , Acidentes de Trabalho/mortalidade , Adolescente , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Washington/epidemiologia , Adulto Jovem
12.
J Asthma ; 51(10): 1035-42, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24995660

RESUMO

OBJECTIVE: To estimate the prevalence of asthma in workers by occupation in Washington State. METHODS: Data from the 2006-2009 Behavioral Risk Factor Surveillance System (BRFSS) and the BRFSS Asthma Call-Back Survey (ACBS) in Washington State (WA) were analyzed. Using state-added and coded Industry and Occupation questions, we calculated prevalence ratios (PRs) for 19 occupational groups. RESULTS: Of the 41,935 respondents who were currently employed during 2006-2009, the prevalence of current asthma was 8.1% [95% confidence interval (CI) 7.8-8.5%] When compared with the reference group of executive, administration and managerial occupations, three occupational groups had significantly (p < 0.05) higher PRs of current asthma: "Teachers, all levels, and Counselors' (PR 1.3, 95% CI 1.1-1. 6%); 'Administrative Support, including Clerical" (PR 1. 5, 95% CI 1.2-1.9%); and "Other Health Services" (PR 1.5, 95% CI 1.2-1.9). Half of the 2511 ACBS respondent workers (55.1%) indicated that they believed exposure at work had caused or worsened their asthma, but only 10.7% had ever spoken with a health care professional about their asthma being work related. CONCLUSIONS: Some occupations have a higher prevalence of current asthma than other occupations. The systematic collection of industry and occupation data can help identify worker populations with a high burden of asthma and can be used to target disease prevention efforts as well as to aid clinician recognition and treatment. Workers indicated that work-related asthma exposures are not discussed with their health care provider and this communication gap has implications for asthma management.


Assuntos
Asma/epidemiologia , Doenças Profissionais/epidemiologia , Ocupações/estatística & dados numéricos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Sistema de Vigilância de Fator de Risco Comportamental , Feminino , Humanos , Masculino , Prevalência , Análise de Regressão , Washington/epidemiologia , Adulto Jovem
13.
J Occup Environ Hyg ; 10(11): 597-608, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24116665

RESUMO

Data from Washington State's work-related asthma surveillance system were used to characterize isocyanate-induced asthma cases occurring from 1999 through 2010. Injured worker interviews and medical records were used to describe the industry, job title, work process, workers' compensation cost, and exposure trends associated with 27 cases of isocyanate-induced asthma. The majority (81%) of cases were classified within the surveillance system as new-onset asthma while 19% were classified as work-aggravated asthma. The workers' compensation cost for isocyanate-induced asthma cases was $1.7 million; this was 14% of the total claims cost for all claims in the asthma surveillance system. The majority of cases (48%) occurred from paint processes, followed by foam application or foam manufacturing (22%). Nine of the asthma cases associated with spray application occurred during application to large or awkward-shaped objects. Six workers who did not directly handle isocyanates (indirect exposure) developed new-onset asthma. Two cases suggest that skin contact and processes secondary to the isocyanate spray application, such as cleanup, contributed to immune sensitization. Surveillance data provide insight for the prevention of isocyanate-induced respiratory disease. Key observations are made regarding the development of work-related asthma in association with a) paint application on large objects difficult to ventilate, b) indirect exposure to isocyanates, c) exposure during secondary or cleanup processes, and d) reports of dermal exposure.


Assuntos
Asma Ocupacional/prevenção & controle , Isocianatos , Asma Ocupacional/induzido quimicamente , Feminino , Humanos , Masculino , Exposição Ocupacional , Dispositivos de Proteção Respiratória , Washington , Indenização aos Trabalhadores
14.
Artigo em Inglês | MEDLINE | ID: mdl-37998308

RESUMO

Firefighters face many hazards on the job and have a high rate of work-related injuries and illnesses (WRII). We analyzed Washington workers' compensation claims from 2006-2020 to characterize WRII in firefighters compared to law enforcement officers and "all other" workers. There were 9187 compensable claims for firefighters, 7801 for law enforcement officers, and 586,939 for "all other" workers. Nearly 40% of claims for firefighters were work-related musculoskeletal disorders (WMSDs). The claim rate per 10,000 full-time equivalent (FTE) firefighters was 716.4, which is significantly higher than that of law enforcement officers (510.0) and "all other" workers (163.2). The rate per 10,000 FTE of WMSD claims was also higher in firefighters (277.0) than in law enforcement officers (76.2) and "all other" workers (57.6). Additional WRII among firefighters commonly included being struck or caught in objects, slipping or tripping, and exposure to caustic or noxious substances; and amongst law enforcement, transportation accidents and violence. Medical costs and time-loss days per claim were lower for firefighters and law enforcement than for "all other" workers. Common tasks associated with WMSDs in firefighters included lifting and transporting patients, using specific tools and equipment, and physical training. WMSDs stand out as an area for prevention and intervention activities.


Assuntos
Bombeiros , Doenças Profissionais , Traumatismos Ocupacionais , Humanos , Traumatismos Ocupacionais/epidemiologia , Washington/epidemiologia , Indenização aos Trabalhadores , Polícia , Doenças Profissionais/epidemiologia
15.
Circ Arrhythm Electrophysiol ; 16(9): e011870, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37646176

RESUMO

BACKGROUND: Hypoxia-ischemia predisposes to atrial arrhythmia. Atrial ATP-sensitive potassium channel (KATP) modulation during hypoxia has not been explored. We investigated the effects of hypoxia on atrial electrophysiology in mice with global deletion of KATP pore-forming subunits. METHODS: Whole heart KATP RNA expression was probed. Whole-cell KATP current and action potentials were recorded in isolated wild-type (WT), Kir6.1 global knockout (6.1-gKO), and Kir6.2 global knockout (6.2-gKO) murine atrial myocytes. Langendorff-perfused hearts were assessed for atrial effective refractory period (ERP), conduction velocity, wavefront path length (WFPL), and arrhymogenicity under normoxia/hypoxia using a microelectrode array and programmed electrical stimulation. Heart histology was assessed. RESULTS: Expression patterns were essentially identical for all KATP subunit RNA across human heart, whereas in mouse, Kir6.1 and SUR2 (sulphonylurea receptor subunit) were higher in ventricle than atrium, and Kir6.2 and SUR1 were higher in atrium. Compared with WT, 6.2-gKO atrial myocytes had reduced tolbutamide-sensitive current and action potentials were more depolarized with slower upstroke and reduced peak amplitude. Action potential duration was prolonged in 6.1-gKO atrial myocytes, absent of changes in other ion channel gene expression or atrial myocyte hypertrophy. In Langendorff-perfused hearts, baseline atrial ERP was prolonged and conduction velocity reduced in both KATP knockout mice compared with WT, without histological fibrosis. Compared with baseline, hypoxia led to conduction velocity slowing, stable ERP, and WFPL shortening in WT and 6.1-gKO hearts, whereas WFPL was stable in 6.2-gKO hearts due to ERP prolongation with conduction velocity slowing. Tolbutamide reversed hypoxia-induced WFPL shortening in WT and 6.1-gKO hearts through ERP prolongation. Atrial tachyarrhythmias inducible with programmed electrical stimulation during hypoxia in WT and 6.1-gKO mice correlated with WFPL shortening. Spontaneous arrhythmia was not seen. CONCLUSIONS: KATP block/absence leads to cellular and tissue level atrial electrophysiological modification. Kir6.2 global knockout prevents hypoxia-induced atrial WFPL shortening and atrial arrhythmogenicity to programmed electrical stimulation. This mechanism could be explored translationally to treat ischemically driven atrial arrhythmia.


Assuntos
Fibrilação Atrial , Canais KATP , Humanos , Animais , Camundongos , Canais KATP/genética , Fibrilação Atrial/genética , Tolbutamida , Taquicardia , Átrios do Coração , Hipóxia/complicações , Hipóxia/genética , Trifosfato de Adenosina
16.
Clin Genitourin Cancer ; 21(4): e242-e251, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-36922286

RESUMO

INTRODUCTION: Clinical markers of response in metastatic renal cell carcinoma (mRCC) are lacking. Low hemoglobin (Hb) is associated with poor outcomes in the IMDC risk score. This study evaluates the role of Hb as a marker of treatment outcomes in mRCC. PATIENTS AND METHODS: This multicenter retrospective study evaluated 276 patients with mRCC treated with frontline immune checkpoint inhibitor (ICI) therapy, ICI and vascular endothelial growth factor (VEGF) inhibitor (VEGFI) combinations (ICI/VEGFI), or VEGFI monotherapy between 2014 and 2021. Hb levels at baseline, week 6 and 12 and at disease progression or death were recorded. Patients were categorized as responders (CR+PR) or nonresponders (SD+PD) using cross-sectional imaging at week 12. The association between baseline and dynamic changes in Hb and oncological outcomes was assessed. RESULTS: Thirty-seven percent, 40% and 22% of patients received ICIs, ICI/VEGFI and VEGFI respectively. In patients receiving ICIs, there was a significant increase in Hb amongst responders from baseline to week 12 (P= .02). Amongst patients receiving ICI/VEGFI, there was an increase in Hb from baseline to week 12 which was greater in responders (P< .001). In patients receiving VEGFI monotherapy, responders had a higher Hb at baseline (P= .01), week 6 (P= .04), and week 12 (P= .003). An increase in Hb was a significant independent predictor of progression-free survival amongst patients receiving ICIs (HR 0.40, 95%CI, 0.19-0.83, P= .009). CONCLUSION: Baseline and dynamic changes in Hb are associated with first-line treatment outcomes in patients with mRCC and represent a pragmatic early serological marker.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Humanos , Carcinoma de Células Renais/patologia , Neoplasias Renais/patologia , Estudos Retrospectivos , Fator A de Crescimento do Endotélio Vascular , Inibidores de Proteínas Quinases/uso terapêutico , Prognóstico , Inibidores da Angiogênese/uso terapêutico , Hemoglobinas
18.
Am J Ind Med ; 55(10): 893-903, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22821712

RESUMO

BACKGROUND: Workers with depression and frequent mental distress (FMD) have lost work productivity. Limited systematic comparisons exist for the prevalence of depression and FMD across occupational groups. METHODS: Using a state-added question for occupation coupled to measures of depression and FMD on the Washington State (WA) 2006 and 2008 Behavioral Risk Factor Surveillance System survey, we estimated the prevalence and odds ratios (ORs) among the 20,560 WA workers. RESULTS: The prevalences of current depression and FMD were 5.2% and 7.5%, respectively. The prevalence varied considerably across occupations. Compared with Management occupation, Truck drivers had significantly increased odds for both current depression [OR = 6.18, 95% confidence interval (CI): 2.52-15.16] and FMD (OR = 1.85, 95% CI: 1.01-3.41). Cleaning/Building services (OR = 1.95, 95% CI: 1.11-3.40) and Protective services (OR = 1.97, 95% CI: 1.19-3.27) were associated with increased FMD. CONCLUSIONS: These findings demonstrate the need for research on possible sources of the differences for current depression and FMD across occupations.


Assuntos
Depressão/epidemiologia , Doenças Profissionais/epidemiologia , Exposição Ocupacional/efeitos adversos , Saúde Ocupacional/estatística & dados numéricos , Estresse Psicológico/epidemiologia , Adolescente , Adulto , Intervalos de Confiança , Depressão/psicologia , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Doenças Profissionais/psicologia , Razão de Chances , Prevalência , Psicometria , Fatores de Risco , Inquéritos e Questionários , Washington/epidemiologia , Adulto Jovem
19.
Implement Sci Commun ; 3(1): 59, 2022 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-35659156

RESUMO

BACKGROUND: Modifications to interventions can jeopardize intervention outcomes. Pre-existing perceived barriers and facilitators to the intervention arising in the implementation preparation phase may help explain why modifications to the intervention may occur during the implementation phase. This two-site comparative case study describes modifications made to a complex organizational-level intervention and examines how known implementation science factors may have enabled such changes to occur. METHODS: Northwestern Medicine'sTM Hispanic Kidney Transplant Program (HKTP) is a culturally competent transplant center-based intervention designed to reduce disparities in living donor kidney transplantation among Hispanics. In-depth qualitative interviews and discussions were longitudinally conducted with transplant stakeholders (i.e., physicians, administrators, clinicians) at two kidney transplant programs with large Hispanic populations during implementation preparation and implementation phases. The Consolidated Framework for Implementation Research (CFIR) guided interview design and qualitative analysis, and Stirman's Framework for Reporting Adaptations and Modifications-Expanded (FRAME) guided modification classification. RESULTS: Across sites, 57 stakeholders participated in an interview, group discussion, and/or learning collaborative discussion. Site-B made more modifications than Site-A (n = 29 versus n = 18). Sites differed in the proportions of delaying/skipping (Site-A 50% versus Site-B 28%) and adding (Site-A 11% versus Site-B 28%) but had comparable substituting (Site-A 17% versus Site-B 17%) and tweaking (Site-A 17% versus Site-B 14%) modification types. Across sites, the transplant team consistently initiated the most modifications (Site-A 66%; Site-B 62%). While individuals initiated slightly more modifications at Site-B (21% versus Site-A 17%), institutions instigated proportionately slightly more modifications at Site-A (17% versus Site-B 10%). CFIR inner setting factors (i.e., structural characteristics, culture, available resources, implementation climate) that prominently emerged during the implementation preparation phase explained similarities and differences in sites' modification numbers, types, and agents in the implementation phase. CONCLUSION: Organizations implementing a culturally competent care intervention made modifications. CFIR inner setting factors emerging in the implementation preparation phase largely explained similarities and differences in study sites' modifications. Identifying factors contributing to modifications may help institutions become better prepared to implement an intervention by addressing known factors in advance, which may foster greater fidelity leading to desired outcomes. TRIAL REGISTRATION: ClinicalTrials.gov NCT03276390 . We registered the study retrospectively on 9-7-17.

20.
Appl Ergon ; 105: 103836, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35777183

RESUMO

Janitors' jobs require repetitive work with low control (skill discretion, decision authority) and social support. Previous studies have found this constellation of work conditions leads to high stress levels. This study investigated the relationships among job demand-control-support, burnout, and musculoskeletal symptoms for commercial janitors in Washington State. Structural equation modeling was performed using data from 208 participants with analyses comparing models of daytime and nighttime janitors. Burnout fully mediated the relationship between job demands and musculoskeletal complaints among daytime janitors. Among nighttime janitors, burnout mediated between job demands, job control, and social support, and musculoskeletal complaints. The nighttime janitors' model was more fully supported compared to the daytime model. This study is one of a small number that examine and bring attention to the importance of janitors' burnout. Recommendations to improve the psychosocial work environment toward mitigating burnout and reducing musculoskeletal complaints are provided.

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