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1.
Mult Scler Relat Disord ; 79: 105043, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37839367

RESUMO

BACKGROUND: Receiving a multiple sclerosis (MS) diagnosis is a significant stressor. Therefore, highly individualised counselling is needed, especially in early MS. Modifiable risk factors (e.g. smoking and obesity) are gaining relevance in MS. Despite evidence for worse MS-related health outcomes, prevalence of adverse health behaviours, such as smoking and physical inactivity, is high across all MS stages. However, knowledge regarding health behaviours as well as their association with MS-related health outcomes among newly diagnosed PwMS in Germany is scarce. Currently, the efficacy of an interactive digital lifestyle management application intended to be used as an add-on to standard care among newly diagnosed PwMS in Germany is evaluated in an ongoing multicentre randomised controlled trial (RCT) ('POWER@MS1'). OBJECTIVES: To describe baseline disease characteristics and health behaviours of the POWER@MS1 cohort and investigate associations between MS characteristics, quality of life (QOL), health behaviours and intention to optimise health behaviour habits. METHODS: This study included 234 persons with early MS from 20 study centres located across Germany who participate in the POWER@MS1 RCT. Participants were recruited by treating neurologists from different regions and health-care settings in Germany. Baseline data was obtained using paper-based questionnaires and a web-based healthy diet screener between July 2019 and end of March 2022 and analysed descriptively. RESULTS: In this early MS cohort (mean disease duration 4 months), a screening tool showed severe symptoms of anxiety in 15 % of the participants. Better means for stress management appeared to be particularly relevant for the whole cohort. Moreover, 19 % were current smokers, 15 % were obese and 36 % were insufficiently physically active. On average, participants only moderately adhered to dietary guidelines for recommended intake of key food groups (e.g. vegetables, fruits and fatty marine fish). Higher EDSS scores were associated with approximately 20 % higher T2-lesion burden (rate ratio RR=1.2, p<0.001) and 13 % higher relapse rate (RR=1.13,p=0.02) per EDSS disability level. Moreover, a higher T2-lesion burden was associated with current smoking (RR=0.76, p=0.033), resulting in approximately 24 % less T2-lesions at disease onset among non-smokers. In addition, smoking was associated with unhealthier dietary habits according to lower diet scores (linear regression coefficient ß=-1.27, p<0.001). Higher EDSS scores (ß=0.19,p<0.001) and higher BMI (ß=0.013,p=0.03) were associated with higher HAQUAMS (lower QOL). Further, lower diet scores (ß=-0.044,p=0.039) were associated with lower QOL. Moreover, higher HAQUAMS (lower QOL) indicated a higher intention to optimise stress management (ß=0.98,p<0.001), physical activity (ß=0.74,p=0.046) and sleep behaviour (ß=1.82,p<0.001). Further, higher intention to optimise stress management was accounted for by higher EDSS scores (ß=0.39,p=0.004) and a higher number of T2-lesions (ß=0.029,p=0.015) in this newly diagnosed MS cohort. CONCLUSION: Results indicate a clear need for modifications of health behaviours among newly diagnosed PwMS participating in POWER@MS1. Individualised psychological and health behaviour counselling appears to be an important factor in treatment, also for similar early MS cohorts and particularly in those who demonstrate a more severe disease in clinical and MRI metrics.


Assuntos
Esclerose Múltipla , Animais , Humanos , Esclerose Múltipla/terapia , Esclerose Múltipla/tratamento farmacológico , Comportamentos Relacionados com a Saúde , Doença Crônica , Estilo de Vida , Exercício Físico , Obesidade
2.
Front Neurol ; 14: 1172419, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37780722

RESUMO

Background: Health behaviors in persons with multiple sclerosis (pwMS) have been associated with MS-related disease outcomes. Objective: The aim of the study was to gain knowledge about current patient health behaviors in a convenience sample representative for pwMS presenting to a large university-based outpatient clinic and to investigate associations between modifiable risk factors with physical impairment, quality of life (QoL) and cardiovascular comorbidities. Methods: A questionnaire was administered at the MS Outpatient Clinic of the University Medical Center Hamburg Eppendorf asking for health behaviors regarding dietary habits assessed with the German adaptation of the validated Spanish short Diet Quality Screener (sDQS), level of physical activity assessed with the Godin Leisure Time Questionnaire (GLTEQ) and tobacco smoking. Participants were asked to report cardiovascular comorbidities using items from the Self-Report Comorbidity Questionnaire for Multiple Sclerosis. Additionally, cardiovascular risk factors like blood pressure, height and weight (to calculate BMI) and waist circumference were measured. MS specific clinical data, e.g., disease course, duration, disability and MS-specific QoL were collected from the clinical database. Descriptive analyses were performed and multivariate regression analyses for complete cases were carried out for each of the three outcome variables including all mentioned modifiable risk factors (dietary behavior, smoking, physical activity and BMI) as independent variables. Results: In this sample of 399 pwMS the mean age was 42 years (SD 12.8) with a mean disease duration since diagnosis of 7.4 years (SD 8.4) and a mean EDSS of 2.8 (SD 1.9). 24% were current smokers, 44% were insufficiently physically active and 54% did not follow a healthy dietary pattern. 49% of this relatively young clinical population was overweight and 27% reported one or more cardiovascular comorbidities. Most modifiable risk factors showed no convincing associations with MS-related disease outcomes in the multiple regression analyses. Conclusion: This clinical cohort of pwMS shows a high prevalence of critical health behaviors and comorbidities and emphasizes the need for monitoring, education and assistance for behavior change in this population.

3.
BMC Neurol ; 23(1): 382, 2023 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-37872471

RESUMO

BACKGROUND: Many persons with multiple sclerosis (pwMS) desire to learn how health behaviour changes (e.g., dietary adjustments, physical activity, improvements in stress management) might help them manage their disease. Previous research has shown that certain health behaviour changes can improve quality of life (QoL), fatigue and other MS outcomes. Digital health applications may be well suited to deliver relevant health behavioural interventions because of their accessibility and flexibility. The digital health application "levidex" was designed to facilitate health behaviour change by offering evidence-based patient information and cognitive-behavioural therapy techniques to pwMS. By doing so, levidex aims to improve QoL and MS symptoms such as fatigue and mental health. OBJECTIVES: A previous study reported on the development of levidex; this non-randomised pilot study examined the feasibility (practicability and acceptability) of levidex in pwMS with moderate to severe disability. Furthermore, the intervention's impact on empowerment, stress management, and relevant health behaviours (e.g., dietary behaviour, physical activity) was explored. METHODS: levidex was originally developed for newly diagnosed pwMS in the first year after diagnosis and eventually modified to offer access to pwMS with moderate to severe disability. Participants (n = 43) with an Expanded Disability Status Scale between 3.5 and 7.5 and a disease duration of more than one year were eligible to participate. The intervention was used over a period of six months with measurement time points at baseline, month 3 and month 6. RESULTS: Out of 38 participants who completed the six-month intervention period, 18 (47.4%) completed all 16 modules and 9 (23.7%) reached modules 13-16, the long-term maintenance part of levidex. Participants rated levidex positively in terms of practicability and acceptability and had only few points of criticism such as to include more physical exercise routine suggestions suitable for participants with severe impairment. Data on secondary endpoints showed no significant changes. CONCLUSION: This pilot study provided evidence for the practicability and acceptability of levidex, a digital health application designed to facilitate health behaviour change in pwMS with moderate to severe disability. Adequately powered randomised controlled studies with longer follow-up periods are needed to clarify the benefit of levidex in pwMS with moderate to severe disability. TRIAL REGISTRATION: German Clinical Trials Register (DRKS) DRKS00032667 (14/09/2023); Retrospectively registered.


Assuntos
Esclerose Múltipla , Humanos , Esclerose Múltipla/complicações , Qualidade de Vida , Projetos Piloto , Estudos Prospectivos , Fadiga/etiologia
4.
Mult Scler ; 29(14): 1709-1720, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37897326

RESUMO

BACKGROUND: Persons with multiple sclerosis (pwMS) might be particularly well suited to benefit from digital health applications because they are, on average, younger and less severely disabled than patients with many other chronic diseases. Many digital health applications for pwMS have been developed. OBJECTIVES: Analysis of the evidence of digital health applications to improve health outcomes from a patient perspective. METHODS: A systematic review was performed on all randomized controlled trials (RCTs) that have studied mobile health interventions for pwMS, that is, which can be applied with a smartphone, tablet, or laptop to improve patient-reported outcomes. RESULTS: Of the 1127 articles identified in the literature search, 13 RCTs fit the inclusion criteria. Two trials studied messaging systems, two depression interventions, one addressed MS fatigue, five cognition, and three mobility issues, of which two focused on spasticity management. One trial aimed to enhance physical activity. Most were pilot studies that cannot yield definitive conclusions regarding efficacy. One depression intervention and one fatigue intervention showed significant results across several outcomes. CONCLUSION: Several mobile self-guided digital health applications for pwMS have been tested in RCTs, and two interventions targeting depression and fatigue have demonstrated significant effects. Challenges remain regarding implementation into routine care.


Assuntos
Esclerose Múltipla , Telemedicina , Humanos , Smartphone , Doença Crônica , Esclerose Múltipla/terapia , Fadiga/etiologia , Fadiga/terapia
5.
AMA J Ethics ; 25(3): E228-237, 2023 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-36867171

RESUMO

A growing chorus of academicians, public health officials, and other science communicators have warned of what they see as an ill-informed public making poor personal or electoral decisions. Misinformation is often seen as an urgent new problem, so some members of these communities have pushed for quick but untested solutions without carefully diagnosing ethical pitfalls of rushed interventions. This article argues that attempts to "cure" public opinion that are inconsistent with best available social science evidence not only leave the scientific community vulnerable to long-term reputational damage but also raise significant ethical questions. It also suggests strategies for communicating science and health information equitably, effectively, and ethically to audiences affected by it without undermining affected audiences' agency over what to do with it.


Assuntos
Saúde Pública , Opinião Pública , Humanos
6.
New Media Soc ; 25(1): 141-162, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36620434

RESUMO

The COVID-19 pandemic went hand in hand with what some have called a "(mis)infodemic" about the virus on social media. Drawing on partisan motivated reasoning and partisan selective sharing, this study examines the influence of political viewpoints, anxiety, and the interactions of the two on believing and willingness to share false, corrective, and accurate claims about COVID-19 on social media. A large-scale 2 (emotion: anxiety vs relaxation) × 2 (slant of news outlet: MSNBC vs Fox News) experimental design with 719 US participants shows that anxiety is a driving factor in belief in and willingness to share claims of any type. Especially for Republicans, a state of heightened anxiety leads them to believe and share more claims. Our findings expand research on partisan motivated reasoning and selective sharing in online settings, and enhance the understanding of how anxiety shapes individuals' processing of risk-related claims in issue contexts with high uncertainty.

7.
Public Underst Sci ; 32(5): 596-604, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-36648007

RESUMO

Long-standing discussions of the so-called urban-rural divide in the United States have uncovered meaningful differences between urbanites and rural residents, but much of this work has focused on political attitudes. However, there is reason to believe that geographic divides also influence Americans' science attitudes, including, for example, positive affect toward scientists and levels of trust in them. Unfortunately, existing work has not clearly ruled out confounding factors such as religiosity, political views, media habits, and conspiracism. This brief article addresses this problem by drawing on survey data from 2016 to test the hypothesis that rural residency will be associated with colder feelings toward the scientific community, even with controls in place. The results offer support for this expectation. These findings lend support to recent arguments that rural Americans' science attitudes are influenced by factors that go beyond demographics, conspiracism, political polarization, differences of religiosity, and (partisan) media consumption.


Assuntos
Atitude , Confiança , Humanos , Estados Unidos , Emoções , Dissidências e Disputas , Inquéritos e Questionários
8.
Vaccine ; 41(4): 922-929, 2023 01 23.
Artigo em Inglês | MEDLINE | ID: mdl-36682880

RESUMO

Amid the COVID-19 pandemic, the scientific community has been understandably eager to combat misinformation about issues such as vaccine safety. In highly polarized information environments, however, even well-intentioned messages have the potential to produce adverse effects. In this study, we connect different disciplinary strands of social science to derive and experimentally test the novel hypothesis that although particular efforts to debunk misinformation about mRNA vaccines will reduce relevant misperceptions about that technology, these correctives will harm attitudes toward other types of vaccines. We refer to this as the "collateral damage hypothesis." Our study specifically examines a corrective message stating that "mRNA vaccines do not contain live virus," and our results offer some support for our hypothesis, with the corrective triggering increased societal risk perceptions of live vaccines. We also find that the effect is, predictably, most evident among those whose vaccine acceptance is low. Building on the theoretical grounding we outline, we test a "damage control" adjustment to the corrective message and present evidence supporting that it mitigates the collateral damage.


Assuntos
COVID-19 , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Humanos , Pandemias/prevenção & controle , COVID-19/prevenção & controle , Ácido Dioctil Sulfossuccínico , Fenolftaleína , Vacinas de mRNA , Comunicação
9.
Ther Adv Neurol Disord ; 15: 17562864221118729, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36092248

RESUMO

Background: A multiple sclerosis (MS) diagnosis urges decision-making on immunotherapies, while persons with MS (PwMS) need to develop a coping concept in parallel. At this stage, PwMS ask how they themselves may contribute to controlling the disease. Evidence suggests that maintaining a healthy lifestyle (e.g. physical activity and stress management) is a key factor for healthy aging and preserving activity, while data on MS are complex. Objectives: Following the Medical Research Council framework, this study aimed to develop and investigate the feasibility of a new digital health application that conveys evidence-based patient information about lifestyle factors in MS and engages PwMS in relevant behaviour change techniques. Methods: Based on a digital health application promoting lifestyle management in breast cancer survivors, an MS-specific adaptation ('levidex') was developed. Feasibility was tested with 15 PwMS and eight MS experts. Subsequently, a six-week pilot study with eight PwMS was conducted. All participants provided feedback on practicability and acceptability via a questionnaire and took part in a semi-structured telephone interview. Levidex was revised after each test phase. Results: The final levidex tool includes 16 modules, 177 references and several other functions. Feasibility results showed that PwMS and MS experts perceived levidex as understandable (14 out of 15; 6 out of 8), trustworthy (15 out of 15; 8 out of 8), and relevant (10 out of 15; 8 out of 8). Interviews revealed potential for improvement regarding the length and complexity of some content. Piloting of the revised version confirmed good feasibility and high acceptance. Most participants felt inspired to initiate (7 out of 8) or had already implemented (5 out of 8) lifestyle changes after working with levidex. Conclusion: Results suggest that levidex is feasible and well-accepted by PwMS and MS experts. It might be a useful tool to support PwMS in adapting to their diagnosis and initiating health-promoting lifestyle changes.

10.
Nat Commun ; 13(1): 4853, 2022 08 22.
Artigo em Inglês | MEDLINE | ID: mdl-35995772

RESUMO

Rod-shaped bacteria typically elongate and divide by transverse fission. However, several bacterial species can form rod-shaped cells that divide longitudinally. Here, we study the evolution of cell shape and division mode within the family Neisseriaceae, which includes Gram-negative coccoid and rod-shaped species. In particular, bacteria of the genera Alysiella, Simonsiella and Conchiformibius, which can be found in the oral cavity of mammals, are multicellular and divide longitudinally. We use comparative genomics and ultrastructural microscopy to infer that longitudinal division within Neisseriaceae evolved from a rod-shaped ancestor. In multicellular longitudinally-dividing species, neighbouring cells within multicellular filaments are attached by their lateral peptidoglycan. In these bacteria, peptidoglycan insertion does not appear concentric, i.e. from the cell periphery to its centre, but as a medial sheet guillotining each cell. Finally, we identify genes and alleles associated with multicellularity and longitudinal division, including the acquisition of amidase-encoding gene amiC2, and amino acid changes in proteins including MreB and FtsA. Introduction of amiC2 and allelic substitution of mreB in a rod-shaped species that divides by transverse fission results in shorter cells with longer septa. Our work sheds light on the evolution of multicellularity and longitudinal division in bacteria, and suggests that members of the Neisseriaceae family may be good models to study these processes due to their morphological plasticity and genetic tractability.


Assuntos
Divisão Celular , Neisseriaceae , Animais , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Evolução Biológica , Parede Celular/metabolismo , Mamíferos/microbiologia , Neisseriaceae/citologia , Peptidoglicano/metabolismo
11.
Proc Natl Acad Sci U S A ; 118(22)2021 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-34050014

RESUMO

Advances in gene editing technologies for human, plant, and animal applications have led to calls from bench and social scientists, as well as a wide variety of societal stakeholders, for broad public engagement in the decision-making about these new technologies. Unfortunately, there is limited understanding among the groups calling for public engagement on CRISPR and other emerging technologies about 1) the goals of this engagement, 2) the modes of engagement and what we know from systematic social scientific evaluations about their effectiveness, and 3) how to connect the products of these engagement exercises to societal decision or policy making. Addressing all three areas, we systematize common goals, principles, and modalities of public engagement. We evaluate empirically the likely successes of various modalities. Finally, we outline three pathways forward that deserve close attention from the scientific community as we navigate the world of Life 2.0.


Assuntos
Pesquisa Biomédica , Repetições Palindrômicas Curtas Agrupadas e Regularmente Espaçadas , Edição de Genes , Formulação de Políticas , Edição de Genes/ética , Edição de Genes/legislação & jurisprudência , Humanos
12.
BMJ Open ; 11(2): e041720, 2021 02 16.
Artigo em Inglês | MEDLINE | ID: mdl-33593774

RESUMO

INTRODUCTION: Multiple sclerosis (MS) is an inflammatory and degenerative disease of the central nervous system that mainly affects young adults. Uncertainty is a major psychological burden of the disease from diagnosis to prognosis, enhanced by the pressure to make early decisions on a diverse set of immunotherapies. Watchful waiting for 1-2 years while adapting goals and lifestyle habits to life with a chronic disease represents another reasonable option for persons with MS (PwMS). A behaviour change programme based on evidence-based patient information (EBPI) is not available in standard care. This randomised controlled trial (RCT) with an embedded process evaluation investigates the efficacy and cost-effectiveness of a web-based behavioural lifestyle programme to change lifestyle behaviour and reduce inflammatory disease activity in PwMS. METHODS AND ANALYSIS: A web-based behavioural intervention will be evaluated in an RCT aiming to recruit 328 persons with clinically isolated syndrome, suspected MS or confirmed MS for less than 1 year, who have not yet started immunotherapy. Moreover, a mixed-methods process evaluation and a health economic evaluation will be carried out. Participants will be recruited in at least 16 MS centres across Germany and randomised to an intervention group with 12 months of access to EBPI about lifestyle factors in MS, combined with a complex behaviour change programme or to a control group (optimised standard care). The combined primary endpoint is the incidence of new T2 lesions on MRI or confirmed relapses. ETHICS AND DISSEMINATION: The study has been approved by the Ethics Committee of the Hamburg Chamber of Physicians (PV6015). Trial results will be communicated at scientific conferences and meetings and presented on relevant patient websites and in patient education seminars. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Registry (NCT03968172); Pre-results.


Assuntos
Estilo de Vida , Esclerose Múltipla , Análise Custo-Benefício , Alemanha , Humanos , Internet , Esclerose Múltipla/terapia , Ensaios Clínicos Controlados Aleatórios como Assunto , Adulto Jovem
13.
Acta Physiol (Oxf) ; 230(1): e13521, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32506676

RESUMO

AIMS: The aim of the study was to investigate the role of cytochrome P450 (CYP) epoxygenase-derived epoxyeicosatrienoic acids (EETs) in sustained hypoxic pulmonary vasoconstriction (HPV). METHODS: Vasomotor responses of isolated mouse intrapulmonary arteries (IPAs) were assessed using wire myography. Key findings were verified by haemodynamic measurements in isolated perfused and ventilated mouse lungs. RESULTS: Pharmacological inhibition of EET synthesis with MS-PPOH, application of the EET antagonist 14,15-EEZE or deficiency of CYP2J isoforms suppressed sustained HPV. In contrast, knockdown of EET-degrading soluble epoxide hydrolase or its inhibition with TPPU augmented sustained HPV almost twofold. All EET regioisomers elicited relaxation in IPAs pre-contracted with thromboxane mimetic U46619. However, in the presence of KCl-induced depolarization, 5,6-EET caused biphasic contraction in IPAs and elevation of pulmonary vascular tone in isolated lungs, whereas other regioisomers had no effect. In patch-clamp experiments, hypoxia elicited depolarization in pulmonary artery smooth muscle cells (PASMCs), and 5,6-EET evoked inward whole cell currents in PASMCs depolarized to the hypoxic level, but not at their resting membrane potential. CONCLUSIONS: The EET pathway substantially contributes to sustained HPV in mouse pulmonary arteries. 5,6-EET specifically appears to be involved in HPV, as it is the only EET regioisomer able to elicit not only relaxation, but also sustained contraction in these vessels. 5,6-EET-induced pulmonary vasoconstriction is enabled by PASMC depolarization, which occurs in hypoxia. The discovery of the dual role of 5,6-EET in the regulation of pulmonary vascular tone may provide a basis for the development of novel therapeutic strategies for treatment of HPV-related diseases.


Assuntos
Ácido 8,11,14-Eicosatrienoico/análogos & derivados , Sistema Enzimático do Citocromo P-450/metabolismo , Artéria Pulmonar , Vasoconstrição , Vasodilatação , Ácido 8,11,14-Eicosatrienoico/metabolismo , Animais , Hipóxia , Pulmão , Camundongos
14.
Proc Natl Acad Sci U S A ; 116(16): 7662-7669, 2019 04 16.
Artigo em Inglês | MEDLINE | ID: mdl-30642953

RESUMO

Concerns about public misinformation in the United States-ranging from politics to science-are growing. Here, we provide an overview of how and why citizens become (and sometimes remain) misinformed about science. Our discussion focuses specifically on misinformation among individual citizens. However, it is impossible to understand individual information processing and acceptance without taking into account social networks, information ecologies, and other macro-level variables that provide important social context. Specifically, we show how being misinformed is a function of a person's ability and motivation to spot falsehoods, but also of other group-level and societal factors that increase the chances of citizens to be exposed to correct(ive) information. We conclude by discussing a number of research areas-some of which echo themes of the 2017 National Academies of Sciences, Engineering, and Medicine's Communicating Science Effectively report-that will be particularly important for our future understanding of misinformation, specifically a systems approach to the problem of misinformation, the need for more systematic analyses of science communication in new media environments, and a (re)focusing on traditionally underserved audiences.


Assuntos
Comunicação , Competência em Informação , Ciência , Enganação , Humanos , Meios de Comunicação de Massa , Motivação , Política , Mídias Sociais , Estados Unidos
15.
Exp Physiol ; 103(9): 1185-1191, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29917290

RESUMO

NEW FINDINGS: What is the central question of this study? Hypoxic pulmonary vasoconstriction has never been characterized in isolated mouse pulmonary arteries of different generations in detail. What is the main finding and its importance? We found that only small intrapulmonary arteries (80-200 µm in diameter) exhibit hypoxic pulmonary vasoconstriction. The observed response was sustained, significantly potentiated by depolarization-induced preconstriction and not dependent on the endothelium or TRPC6 channels. ABSTRACT: Hypoxic pulmonary vasoconstriction (HPV) is a physiological response of pulmonary arteries, which adapts lung perfusion to regional ventilation. The properties of HPV vary significantly between animal species. Despite extensive use of mouse models in studies of HPV, this physiological response has never been characterized in isolated mouse pulmonary arteries in detail. Using wire myography, we investigated the effect of 80 min exposure to hypoxia on the tone in mouse pulmonary arteries of different generations in the presence and absence of preconstriction. Hypoxia induced a sustained relaxation in non-preconstricted extrapulmonary arteries (500-700 µm in diameter), but not in the presence of KCl-induced preconstriction. Large intrapulmonary arteries (450-650 µm in diameter) did not exhibit a significant response to the hypoxic challenge. In contrast, in small intrapulmonary arteries (80-200 µm in diameter), hypoxia elicited a slowly developing sustained constriction, which was independent of the endothelium. The response was significantly potentiated in arteries preconstricted with KCl, but not with U46619. Hypoxic pulmonary vasoconstriction was not altered in pulmonary arteries of TRPC6-deficient mice, which suggests that this response corresponds to the sustained phase of biphasic HPV observed earlier in isolated, buffer-perfused and ventilated mouse lungs. In conclusion, we have established a protocol that allows the study of sustained HPV in isolated mouse pulmonary arteries. The data obtained might be useful for future studies of the mechanisms of HPV in mice.


Assuntos
Hipóxia/fisiopatologia , Artéria Pulmonar/fisiopatologia , Circulação Pulmonar , Vasoconstrição , Ácido 15-Hidroxi-11 alfa,9 alfa-(epoximetano)prosta-5,13-dienoico/farmacologia , Animais , Endotélio Vascular/fisiopatologia , Feminino , Técnicas In Vitro , Masculino , Camundongos , Camundongos Knockout , Tono Muscular , Músculo Liso Vascular , Miografia , Cloreto de Potássio/farmacologia , Canais de Cátion TRPC/genética , Canal de Cátion TRPC6 , Vasoconstritores/farmacologia
16.
Am J Physiol Regul Integr Comp Physiol ; 311(3): R607-17, 2016 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-27440715

RESUMO

In lung epithelial cells, hypoxia decreases the expression and activity of sodium-transporting molecules, thereby reducing the rate of transepithelial sodium absorption. The mechanisms underlying the sensing of hypoxia and subsequent coupling to sodium-transporting molecules remain unclear. Hydrogen sulfide (H2S) has recently been recognized as a cellular signaling molecule whose intracellular concentrations critically depend on oxygen levels. Therefore, it was questioned whether endogenously produced H2S contributes to hypoxic inhibition of sodium transport. In electrophysiological Ussing chamber experiments, hypoxia was established by decreasing oxygen concentrations in the chambers. Hypoxia concentration dependently and reversibly decreased amiloride-sensitive sodium absorption by cultured H441 monolayers and freshly dissected porcine tracheal epithelia due to inhibition of basolateral Na(+)/K(+)-ATPase. Exogenous application of H2S by the sulfur salt Na2S mimicked the effect of hypoxia and inhibited amiloride-sensitive sodium absorption by both tissues in an oxygen-dependent manner. Hypoxia increased intracellular concentrations of H2S and decreased the concentration of polysulfides. Pretreatment with the cystathionine-γ-lyase inhibitor d/l-propargylglycine (PAG) decreased hypoxic inhibition of sodium transport by H441 monolayers, whereas inhibition of cystathionine-ß-synthase (with aminooxy-acetic acid; AOAA) or 3-mercaptopyruvate sulfurtransferase (with aspartate) had no effect. Inhibition of all of these H2S-generating enzymes with a combination of AOAA, PAG, and aspartate decreased the hypoxic inhibition of sodium transport by H441 cells and pig tracheae and decreased H2S production by tracheae. These data suggest that airway epithelial cells endogenously produce H2S during hypoxia, and this contributes to hypoxic inhibition of transepithelial sodium absorption.


Assuntos
Hipóxia Celular/fisiologia , Sulfeto de Hidrogênio/metabolismo , Oxigênio/metabolismo , Mucosa Respiratória/metabolismo , Absorção pelo Trato Respiratório/fisiologia , Sódio/metabolismo , Animais , Células Cultivadas , Células Epiteliais/metabolismo , Suínos
17.
Am J Clin Nutr ; 90(2): 304-13, 2009 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-19458018

RESUMO

BACKGROUND: Food reinforcement, ie, motivation to obtain food, is associated with energy intake and obesity. Finding ways to decrease the reinforcing value of unhealthy foods may help with adherence to diets and maintenance of weight loss. Our previous study in nonobese adults showed that daily consumption of the same snack food (food consumed apart from meals) for 14 d significantly decreased its reinforcing value. OBJECTIVES: The aims of this study were to replicate and extend these findings to obese individuals and to examine the effects of different portion sizes of snack foods on food reinforcement. DESIGN: Food reinforcement and liking were tested in 31 obese and 27 nonobese women at baseline and after 2 wk of daily consumption of 0, 100, or 300 kcal/d of the same snack food. RESULTS: We found a significant interaction of phase, portion size, and body mass index on the pattern of operant responding for food. Obese women had a significant increase in food reinforcement after consuming the 300-kcal portion of food for 2 wk, whereas nonobese women had the opposite response. No significant differences were found on the reinforcing value with the 0- and 100-kcal portion-size conditions. Women in the 300-kcal group (obese and nonobese) reported a significant decrease in snack food liking from baseline to after daily intake. CONCLUSIONS: These findings suggest that obese and nonobese women respond differently to the daily intake of a snack food and that this may not be a viable mechanism for reducing food reinforcement in obese women. This trial was registered at www.clinicaltrials.gov as NCT00837694.


Assuntos
Ingestão de Alimentos/psicologia , Ingestão de Energia/fisiologia , Preferências Alimentares/psicologia , Obesidade/psicologia , Reforço Psicológico , Magreza/psicologia , Adulto , Índice de Massa Corporal , Comportamento de Escolha , Estudos Cross-Over , Comportamento Alimentar , Feminino , Humanos , Motivação , Obesidade/epidemiologia , Obesidade/etiologia , Fatores de Tempo
18.
J Appl Psychol ; 93(4): 778-88, 2008 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-18642983

RESUMO

It is commonly believed that human resource investments can yield positive performance-related outcomes for organizations. Utilizing the theory of organizational equilibrium (H. A. Simon, D. W. Smithburg, & V. A. Thompson, 1950; J. G. March & H. A. Simon, 1958), the authors proposed that organizational inducements in the form of competitive pay will lead to 2 firm-level performance outcomes--labor productivity and customer satisfaction--and that financially successful organizations would be more likely to provide these inducements to their employees. To test their hypotheses, the authors gathered employee-survey and objective performance data from a sample of 126 large publicly traded U.S. organizations over a period of 3 years. Results indicated that (a) firm-level financial performance (net income) predicted employees' shared perceptions of competitive pay, (b) shared pay perceptions predicted future labor productivity, and (c) the relationship between shared pay perceptions and customer satisfaction was fully mediated by employee morale.


Assuntos
Eficiência Organizacional , Mão de Obra em Saúde , Teoria Psicológica , Idoso , Comportamento do Consumidor , Avaliação de Desempenho Profissional , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Moral , Fatores Socioeconômicos
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