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1.
Ann Behav Med ; 56(2): 176-192, 2022 02 11.
Artigo em Inglês | MEDLINE | ID: mdl-34114597

RESUMO

BACKGROUND: To help implement behavior change interventions (BCIs) it is important to be able to characterize their key components and determine their effectiveness. PURPOSE: This study assessed and compared the components of BCIs in terms of intervention functions identified using the Behaviour Change Wheel Framework (BCW) and in terms of their specific behavior change techniques (BCTs) identified using the BCT TaxonomyV1, across six behavioral domains and the association of these with cost-effectiveness. METHODS: BCIs in 251 studies targeting smoking, diet, exercise, sexual health, alcohol and multiple health behaviors, were specified in terms of their intervention functions and their BCTs, grouped into 16 categories. Associations with cost-effectiveness measured in terms of incremental cost-effectiveness ratio (ICER) upper and lower estimates were determined using regression analysis. RESULTS: The most prevalent functions were increasing knowledge through education (72.1%) and imparting skills through training (74.9%). The most prevalent BCT groupings were shaping knowledge (86.5%), changing behavioral antecedents (53.0%), supporting self-regulation (47.7%), and providing social support (44.6%). Intervention functions associated with better cost-effectiveness were those based on training (ßlow = -15044.3; p = .002), persuasion (ßlow = -19384.9; p = .001; ßupp = -25947.6; p < .001) and restriction (ßupp = -32286.1; p = .019), and with lower cost-effectiveness were those based on environmental restructuring (ß = 15023.9low; p = .033). BCT groupings associated with better cost-effectiveness were goals and planning (ßlow = -8537.3; p = .019 and ßupp = -12416.9; p = .037) and comparison of behavior (ßlow = -13561.9, p = .047 and ßupp = -30650.2; p = .006). Those associated with lower cost-effectiveness were natural consequences (ßlow = 7729.4; p = .033) and reward and threat (ßlow = 20106.7; p = .004). CONCLUSIONS: BCIs that focused on training, persuasion and restriction may be more cost-effective, as may those that encourage goal setting and comparison of behaviors with others.


Assuntos
Terapia Comportamental , Comportamentos Relacionados com a Saúde , Exercício Físico , Humanos , Fumar
2.
AIDS Behav ; 26(11): 3620-3629, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35536520

RESUMO

Poor engagement in HIV care is associated with poorer health outcomes and increased mortality. Our survey examined experiential and circumstantial factors associated with clinic attendance among women (n = 250) and men (n = 106) in London with heterosexually-acquired HIV. While no associations were found for women, among men, sub-optimal attendance was associated with insecure immigration status (25.6% vs. 1.8%), unstable housing (32.6% vs. 10.2%) and reported effect of HIV on daily activities (58.7% vs. 40.0%). Among women and men on ART, it was associated with missing doses of ART (OR = 2.96, 95% CI:1.74-5.02), less belief in the necessity of ART (OR = 0.56, 95% CI:0.35-0.90) and more concern about ART (OR = 3.63, 95% CI:1.45-9.09). Not wanting to think about being HIV positive was the top reason for ever missing clinic appointments. It is important to tackle stigma and the underlying social determinants of health to improve HIV prevention, and the health and well-being of people living with HIV.


Assuntos
Infecções por HIV , Heterossexualidade , Instituições de Assistência Ambulatorial , Feminino , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Infecções por HIV/prevenção & controle , Humanos , Londres/epidemiologia , Masculino , Estigma Social
3.
Public Health ; 204: 33-39, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35144152

RESUMO

OBJECTIVES: To test whether public knowledge and confidence in one's understanding of the local restrictions, motivation to adhere to local restrictions, and self-reported behaviour (going out for exercise, to work, socially) differed according to tier level. STUDY DESIGN: Cross-sectional, nationally representative, online survey of 1728 participants living in England (data collection: 26 to 28 October 2020). METHODS: We conducted logistic regression analyses to investigate whether knowledge of restrictions, confidence in knowledge of restrictions, motivation to adhere to restrictions, and self-reported behaviour were associated with personal characteristics and tier. RESULTS: Between 81% (tier 2) and 89% (tier 3) of participants correctly identified which tier they lived in. Knowledge of specific restrictions was variable. 73% were confident that they understood which tier was in place in their local area, whereas 71% were confident they understood the guidance in their local area. Confidence was associated with being older and living in a less deprived area. 73% were motivated to adhere to restrictions in their local area. Motivation was associated with being female and older. People living in tiers with greater restrictions were less likely to report going out to meet people from another household socially; reported rates of going out for exercise and for work did not differ. CONCLUSIONS: Although recognition of local tier level was high, knowledge of specific guidance for tiers was variable. There was some indication that nuanced guidance (e.g. behaviour allowed in some settings but not others) was more poorly understood than guidance which was absolute (i.e. behaviour is either allowed or not allowed).


Assuntos
COVID-19 , Motivação , Estudos Transversais , Exercício Físico , Feminino , Humanos , Autorrelato
4.
HIV Med ; 22(8): 641-649, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-33949070

RESUMO

OBJECTIVES: To investigate the association between chemsex drug use and HIV clinic attendance among gay and bisexual men in London. METHODS: A cross-sectional survey of adults (> 18 years) diagnosed with HIV for > 4 months, attending seven London HIV clinics (May 2014 to August 2015). Participants self-completed an anonymous questionnaire linked to clinical data. Sub-optimal clinic attenders had missed one or more HIV clinic appointments in the past year, or had a history of non-attendance for > 1 year. RESULTS: Over half (56%) of the 570 men who identified as gay or bisexual reported taking recreational drugs in the past 5 years and 71.5% of these men had used chemsex drugs in the past year. Among men reporting chemsex drug use (past year), 32.1% had injected any drugs in the past year. Sub-optimal clinic attenders were more likely than regular attenders to report chemsex drug use (past year; 46.9% vs. 33.2%, P = 0.001), injecting any drugs (past year; 17.1% vs. 8.9%, P = 0.011) and recreational drug use (past 5 years; 65.5% vs. 48.8%, P < 0.001). One in five sub-optimal attenders had missed an HIV clinic appointment because of taking recreational drugs (17.4% vs. 1.8%, P < 0.001). In multivariable logistic regression, chemsex drug use was significantly associated with sub-optimal clinic attendance (adjusted odds ratio = 1.71, 95% confidence interval: 1.10-2.65, P = 0.02). CONCLUSIONS: Our findings highlight the importance of systematic assessment of drug use and development of tools to aid routine assessment. We suggest that chemsex drug use should be addressed when developing interventions to improve engagement in HIV care among gay and bisexual men.


Assuntos
Infecções por HIV , Minorias Sexuais e de Gênero , Transtornos Relacionados ao Uso de Substâncias , Adulto , Estudos Transversais , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Homossexualidade Masculina , Humanos , Londres/epidemiologia , Masculino , Assunção de Riscos , Comportamento Sexual , Transtornos Relacionados ao Uso de Substâncias/epidemiologia
5.
Diabet Med ; 38(5): e14430, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33073393

RESUMO

AIMS: Sustained engagement in type 1 diabetes self-management behaviours is a critical element in achieving improvements in glycated haemoglobin (HbA1c) and minimising risk of complications. Evaluations of self-management programmes, such as Dose Adjustment for Normal Eating (DAFNE), typically find that initial improvements are rarely sustained beyond 12 months. This study identified behaviours involved in sustained type 1 diabetes self-management, their influences and relationships to each other. METHODS: A mixed-methods study was conducted following the first two steps of the Behaviour Change Wheel framework. First, an expert stakeholder consultation identified behaviours involved in self-management of type 1 diabetes. Second, three evidence sources (systematic review, healthcare provider-generated 'red flags' and participant-generated 'frequently asked questions') were analysed to identify and synthesise modifiable barriers and enablers to sustained self-management. These were characterised according to the Capability-Opportunity-Motivation-Behaviour (COM-B) model. RESULTS: 150 distinct behaviours were identified and organised into three self-regulatory behavioural cycles, reflecting different temporal and situational aspects of diabetes self-management: Routine (e.g. checking blood glucose), Reactive (e.g. treating hypoglycaemia) and Reflective (e.g. reviewing blood glucose data to identify patterns). Thirty-four barriers and five enablers were identified: 10 relating to Capability, 20 to Opportunity and nine to Motivation. CONCLUSIONS: Multiple behaviours within three self-management cycles are involved in sustained type 1 diabetes self-management. There are a wide range of barriers and enablers that should be addressed to support self-management behaviours and improve clinical outcomes. The present study provides an evidence base for refining and developing type 1 diabetes self-management programmes.


Assuntos
Diabetes Mellitus Tipo 1/terapia , Motivação/fisiologia , Autogestão , Diabetes Mellitus Tipo 1/epidemiologia , Diabetes Mellitus Tipo 1/psicologia , Prova Pericial/estatística & dados numéricos , Comportamentos Relacionados com a Saúde/fisiologia , Humanos , Defesa do Paciente/estatística & dados numéricos , Sistemas de Apoio Psicossocial , Autogestão/métodos , Autogestão/psicologia , Autogestão/estatística & dados numéricos , Comportamento Social , Revisões Sistemáticas como Assunto , Reino Unido/epidemiologia
6.
Public Health ; 198: 106-113, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34411993

RESUMO

OBJECTIVES: Working from home where possible is important in reducing the spread of COVID-19. In early 2021, a quarter of people in England who believed they could work entirely from home reported attending their workplace. To inform interventions to reduce this, this study examined associated factors. STUDY DESIGN: Data from the ongoing COVID-19 Rapid Survey of Adherence to Interventions and Responses survey series of nationally representative samples of people in the UK aged 16+ years in January-February 2021 were used. METHODS: The study sample was 1422 respondents who reported that they could work completely from home. The outcome measure was self-reported workplace attendance at least once during the preceding week. Factors of interest were analysed in three blocks: 1) sociodemographic variables, 2) variables relating to respondents' circumstances and 3) psychological variables. RESULTS: 26.8% (95% confidence interval [CI] = 24.5%-29.1%) of respondents reported having attended their workplace at least once in the preceding week. Sociodemographic variables and living circumstances significantly independently predicted non-essential workplace attendance: male gender (odds ratio [OR] = 1.85, 95% CI = 1.33-2.58); dependent children in the household (OR = 1.65, 95% CI = 1.17-2.32); financial hardship (OR = 1.14, 95% CI = 1.08-1.21); lower socio-economic grade (C2DE; OR = 1.65, 95% CI = 1.19-2.53); working in sectors such as health or social care (OR = 4.18, 95% CI = 2.56-6.81), education and childcare (OR = 2.45, 95% CI = 1.45-4.14) and key public service (OR = 3.78, 95% CI = 1.83-7.81) and having been vaccinated (OR = 2.08, 95% CI = 1.33-3.24). CONCLUSIONS: Non-essential workplace attendance in the UK in early 2021 during the COVID-19 pandemic was significantly independently associated with a range of sociodemographic variables and personal circumstances. Having been vaccinated, financial hardship, socio-economic grade C2DE, having a dependent child at home and working in certain key sectors were associated with higher likelihood of workplace attendance.


Assuntos
COVID-19 , Pandemias , Criança , Estudos Transversais , Humanos , Masculino , SARS-CoV-2 , Inquéritos e Questionários , Reino Unido/epidemiologia , Local de Trabalho
7.
Public Health ; 198: 260-262, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34487869

RESUMO

OBJECTIVES: This study aimed to investigate public use of lateral flow tests (LFT) and polymerase chain reaction (PCR) tests when experiencing key COVID-19 symptoms. STUDY DESIGN: In this study, data from two waves of a cross-sectional nationally representative online survey (data collected 1 and 2 June, and 14 and 15 June 2021; n = 3665 adults aged ≥18 years living in England or Scotland) were used. METHODS: We report data investigating which type of test, if any, the public think Government guidance asks people to use if they have COVID-19 symptoms. In people with key COVID-19 symptoms (high temperature / fever; new, continuous cough; loss of sense of smell; loss of taste), we also describe the uptake of testing, if any. RESULTS: Ten percent of respondents thought Government guidance stated that they should take an LFT if symptomatic, whereas 18% of people thought that they should take a PCR test; 60% of people thought they should take both types of test (12% did not select either option). In people who were symptomatic, 32% reported taking a test to confirm whether they had COVID-19. Of these, 53% reported taking a PCR test and 44% reported taking an LFT. CONCLUSIONS: Despite Government guidance stating that anyone with key COVID-19 symptoms should complete a PCR test, a significant percentage of the population use LFT tests when symptomatic. Communications should emphasise the superiority of, and need for, PCR tests in people with symptoms.


Assuntos
COVID-19 , Adolescente , Adulto , Estudos Transversais , Humanos , Reação em Cadeia da Polimerase , SARS-CoV-2 , Inquéritos e Questionários
8.
BMC Public Health ; 19(1): 905, 2019 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-31286908

RESUMO

BACKGROUND: Delay to start antiretroviral therapy (ART) and nonadherence compromise the health and wellbeing of people living with HIV (PLWH), raise the cost of care and increase risk of transmission to sexual partners. To date, interventions to improve adherence to ART have had limited success, perhaps because they have failed to systematically elicit and address both perceptual and practical barriers to adherence. The primary aim of this study is to determine the efficacy of the Supporting UPtake and Adherence (SUPA) intervention. METHODS: This study comprises 2 phases. Phase 1 is an observational cohort study, in which PLWH who are ART naïve and recommended to take ART by their clinician complete a questionnaire assessing their beliefs about ART over 12 months. Phase 2 is a randomised controlled trial (RCT) nested within the observational cohort study to investigate the effectiveness of the SUPA intervention on adherence to ART. PLWH at risk of nonadherence (based on their beliefs about ART) will be recruited and randomised 1:1 to the intervention (SUPA intervention + usual care) and control (usual care) arms. The SUPA intervention involves 4 tailored treatment support sessions delivered by a Research Nurse utilising a collaborative Cognitive Behavioural Therapy (CBT) and Motivational Interviewing (MI) approach. Sessions are tailored to individual needs and preferences based on the individual patient's perceptions and practical barriers to ART. An animation series and intervention manual have been developed to communicate a rationale for the personal necessity for ART and illustrate concerns and potential solutions. The primary outcome is adherence to ART measured using Medication Event Monitoring System (MEMS). Three hundred seventy-two patients will be sufficient to detect a 15% difference in adherence with 80% power and an alpha of 0.05. Costs will be compared between intervention and control groups. Costs will be combined with the primary outcome in cost-effectiveness analyses. Quality adjusted life-years (QALYs) will also be estimated over the follow-up period and used in the analyses. DISCUSSION: The findings will enable patients, healthcare providers and policy makers to make informed decisions about the value of the SUPA intervention. TRIAL REGISTRATION: The trial was retrospectively registered 21/02/2014, ISRCTN35514212 .


Assuntos
Antirretrovirais/uso terapêutico , Terapia Cognitivo-Comportamental/métodos , Infecções por HIV/psicologia , Entrevista Motivacional/métodos , Cooperação do Paciente/psicologia , Adulto , Terapia Cognitivo-Comportamental/economia , Estudos de Coortes , Análise Custo-Benefício , HIV , Infecções por HIV/tratamento farmacológico , Infecções por HIV/economia , Humanos , Masculino , Entrevista Motivacional/economia , Estudos Observacionais como Assunto , Anos de Vida Ajustados por Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto
9.
Public Health ; 174: 11-17, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31265975

RESUMO

OBJECTIVES: In England, in 2013, responsibility for some public health (PH) functions transferred from the National Health Service (NHS) to local government. This moved PH from a health-focussed into a broader and more politically oriented context. This article reports on the perceptions of those involved in this transition about how the PH function was changing as it transited to local government. STUDY DESIGN: This is a cross-sectional interview study. METHODS: The study included semi-structured interviews with 31 local government councillors, directors and deputy directors of PH, PH team members and members of clinical commissioning groups. Interviews and data analysis were informed by a theoretical framework, COM-B and an inductive and deductive approach was taken to identify relevant themes. RESULTS: There was a mixed picture of perceived gains and losses for PH. The transition from NHS to local government was seen by some as a 'homecoming', providing the opportunity for PH to have further reach through influence and collaboration with departments like housing, transport and planning. The opportunity to promote evidence-based practice across local government was also seen as a positive aspect of the transition. However, professional roles of PH and individual PH practitioners were perceived to have less influence and autonomy than in the NHS, with some uncertainty about roles within local government. PH practitioners perceived the need to develop other skills to fulfil their roles in local government. Shorter timescales for action and pressure for faster responses were reported to be the reason for less emphasis on using PH evidence to inform policy and decision-making than hitherto in the NHS. CONCLUSION: This study illustrates a variety of consequences of transitioning from NHS to local government. There were perceived benefits afforded by proximity to related local government departments but at the costs of reduction in status for PH practitioners and working to a timescale which in some cases reduced drawing on scientific evidence.


Assuntos
Governo Local , Administração em Saúde Pública , Medicina Estatal/organização & administração , Estudos Transversais , Inglaterra , Humanos , Pesquisa Qualitativa
10.
HIV Med ; 18(4): 267-274, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-27535219

RESUMO

OBJECTIVES: Commonly used measures of engagement in HIV care do not take into account that the frequency of attendance is related to changes in treatment and health status. This study developed a new measure of engagement in care (EIC) incorporating clinical factors. METHODS: We conducted semi-structured interviews with eight HIV physicians to identify factors associated with the timing of patients' next scheduled appointments. These factors informed the development of an algorithm to classify each month of follow-up as "in care" (on or before the time of the next expected attendance) or "out of care" (after the time of the next expected attendance). The EIC algorithm was applied to data from the UK Collaborative HIV Cohort (UK CHIC) study, a large clinical cohort study. RESULTS: The interviews indicated that time to next appointment varied depending on psychosocial and physical comorbidities, and clinical factors (time since diagnosis, AIDS diagnosis, treatment status, CD4 count and viral load). The resulting EIC algorithm was applied to 44 432 patients; 83.9% of the 3 021 224 person-months were "in care". Greater EIC was independently associated with older age, white ethnicity, HIV acquisition through sex between men, current use of antiretroviral therapy (ART), a higher nadir CD4 count, later calendar year and being seen at the clinic for the first time within the last year. CONCLUSIONS: This algorithm describing engagement in HIV care incorporates a time-updated measure of patients' treatment and health status. It adds to the options available for measuring this key performance indicator.


Assuntos
Assistência Ambulatorial/estatística & dados numéricos , Infecções por HIV/diagnóstico , Infecções por HIV/tratamento farmacológico , Aceitação pelo Paciente de Cuidados de Saúde , Adolescente , Adulto , Idoso , Estudos de Coortes , Feminino , Humanos , Entrevistas como Assunto , Masculino , Pessoa de Meia-Idade , Reino Unido , Adulto Jovem
11.
J Public Health (Oxf) ; 39(4): 678-684, 2017 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-28184452

RESUMO

Background: In 2013, many public health functions transferred from the National Health Service to local government in England. From 2006 NICE had produced public health guidelines based on the principles of evidence-based medicine. This study explores how the guidelines were received in the new environment in local government and related issues raised relating to the use of evidence in local authoritites. Methods: In depth, interviews with 31 elected members and officers, including Directors of Public Health, from four very different local government organizations ('local authorities'). Results: Participants reported that (i) there were tensions between evidence-based, and political decision-making; (ii) there were differences in views about what constituted 'good' evidence and (iii) that organizational life is an important mediator in the way evidence is used. Conclusions: Democratic political decision-making does not necessarily naturally align with decision-making based on evidence from the international scientific literature, and local knowledge and local evidence are very important in the ways that public health decisions are made.


Assuntos
Tomada de Decisões , Medicina Baseada em Evidências , Relações Interprofissionais , Governo Local , Política , Administração em Saúde Pública , Democracia , Inglaterra , Guias como Assunto , Humanos , Entrevistas como Assunto , Saúde Pública , Medicina Estatal
13.
Gesundheitswesen ; 78(3): 175-88, 2016 03.
Artigo em Alemão | MEDLINE | ID: mdl-26824401

RESUMO

Without a complete published description of interventions, clinicians and patients cannot reliably implement interventions that are shown to be useful, and other researchers cannot replicate or build on research findings. The quality of description of interventions in publications, however, is remarkably poor. To improve the completeness of reporting, and ultimately the replicability, of interventions, an international group of experts and stakeholders developed the Template for Intervention Description and Replication (TIDieR) checklist and guide. The process involved a literature review for relevant checklists and research, a Delphi survey of an international panel of experts to guide item selection, and a face-to-face panel meeting. The resultant 12-item TIDieR checklist (brief name, why, what (materials), what (procedure), who intervened, how, where, when and how much, tailoring, modifications, how well (planned), how well (actually carried out)) is an extension of the CONSORT 2010 statement (item 5) and the SPIRIT 2013 statement (item 11). While the emphasis of the checklist is on trials, the guidance is intended to apply across all evaluative study designs. This paper presents the TIDieR checklist and guide, with a detailed explanation of each item, and examples of good reporting. The TIDieR checklist and guide should improve the reporting of interventions and make it easier for authors to structure the accounts of their interventions, reviewers and editors to assess the descriptions, and readers to use the information.


Assuntos
Lista de Checagem/normas , Gerenciamento Clínico , Documentação/normas , Fidelidade a Diretrizes/normas , Avaliação de Resultados em Cuidados de Saúde/normas , Registros/normas , Algoritmos , Medicina Baseada em Evidências , Controle de Formulários e Registros/normas , Alemanha , Guias de Prática Clínica como Assunto
14.
Public Health ; 129(12): 1553-62, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26603602

RESUMO

OBJECTIVES: Members of the public are often sceptical about warnings of an impending public health crisis. Breaking through this scepticism is important if we are to convince people to take urgent protective action. In this paper we explored correlates of perceiving that 'too much fuss' was being made about the 2009/10 influenza A H1N1v ('swine flu') pandemic. STUDY DESIGN: A secondary analysis of data from 39 nationally representative telephone surveys conducted in the UK during the pandemic. METHODS: Each cross-sectional survey (combined n = 42,420) collected data over a three day period and asked participants to state whether they agreed or disagreed that 'too much fuss is being made about the risk of swine flu.' RESULTS: Overall, 55.1% of people agreed or strongly agreed with this sentiment. Perceiving that too much fuss was being made was associated with: being male, being white, being generally healthy, trusting most in a primary care physician to provide advice, not knowing someone who had contracted the illness, believing you know a lot about the outbreak, not wishing to receive additional information about the outbreak and possessing worse factual knowledge about the outbreak than other people. CONCLUSIONS: In future disease outbreaks merely providing factual information is unlikely to engage people who are sceptical about the need to take action. Instead, messages which challenge their perceived knowledge and which present case studies of people who have been affected may prove more effective, especially when delivered through trusted channels.


Assuntos
Atitude Frente a Saúde , Vírus da Influenza A Subtipo H1N1 , Influenza Humana/psicologia , Pandemias , Adolescente , Adulto , Idoso , Estudos Transversais , Feminino , Humanos , Influenza Humana/epidemiologia , Masculino , Pessoa de Meia-Idade , Medição de Risco , Inquéritos e Questionários , Reino Unido/epidemiologia , Adulto Jovem
16.
J Exp Med ; 168(5): 1929-34, 1988 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-2903215

RESUMO

The traffic of T cells between the thymus and peripheral lymphoid organs is generally thought to be unidirectional. Using a technique of lymphocyte transfer between Thy-1 congenic mice, we demonstrate here the entry of rare peripheral lymph node T cells into the normal mouse thymus. At time points from 3 h to 24 wk after transfer, donor peripheral T cells were present in the host thymus, mainly as scattered single cells confined to the medulla. At 2 wk after transfer, donor T cells constituted 0.2% of the medullary thymocytes (compared with 11% of the peripheral lymph node T cells). As a population, these cells exhibited a stable mature immunophenotype (Ly-1hi, PNAlo, and mixed L3T4- and Lyt-2+). A minority of the donor T cells expressed high levels of the MEL-14 "homing receptor". The thymic medulla thus exhibits features of a peripheral lymphoid organ but differs in its low rate of turnover of recirculating T cells.


Assuntos
Linfócitos T/fisiologia , Timo/citologia , Timo/fisiologia , Antígenos de Diferenciação de Linfócitos T/análise , Antígenos Ly/análise , Antígenos de Superfície/análise , Movimento Celular , Linfócitos T/classificação , Linfócitos T/transplante , Antígenos Thy-1
17.
J Cell Biol ; 131(5): 1303-14, 1995 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-8522591

RESUMO

The two major intermediate filament proteins in glandular epithelia are keratin polypeptides 8 and 18 (K8/18). To evaluate the function and potential disease association of K18, we examined the effects of mutating a highly conserved arginine (arg89) of K18. Expression of K18 arg89-->his/cys and its normal K8 partner in cultured cells resulted in punctate staining as compared with the typical filaments obtained after expression of wild-type K8/18. Generation of transgenic mice expressing human K18 arg89-->cys resulted in marked disruption of liver and pancreas keratin filament networks. The most prominent histologic abnormalities were liver inflammation and necrosis that appeared at a young age in association with hepatocyte fragility and serum transaminase elevation. These effects were caused by the mutation since transgenic mice expressing wild-type human K18 showed a normal phenotype. A relative increase in the phosphorylation and glycosylation of detergent solubilized K8/18 was also noted in vitro and in transgenic animals that express mutant K18. Our results indicate that the highly conserved arg plays an important role in glandular keratin organization and tissue fragility as already described for epidermal keratins. Phosphorylation and glycosylation alterations in the arg mutant keratins may account for some of the potential changes in the cellular function of these proteins. Mice expressing mutant K18 provide a novel animal model for human chronic hepatitis, and for studying the tissue specific function(s) of K8/18.


Assuntos
Hepatite Animal/genética , Proteínas de Filamentos Intermediários/fisiologia , Queratinas/fisiologia , Células 3T3 , Animais , Arginina/fisiologia , Linhagem Celular , Doença Crônica , Cisteína/fisiologia , Citoesqueleto/metabolismo , Modelos Animais de Doenças , Glicoproteínas/metabolismo , Glicosilação , Células HT29 , Histidina/fisiologia , Humanos , Proteínas de Filamentos Intermediários/genética , Queratinas/genética , Camundongos , Camundongos Transgênicos , Mutagênese Sítio-Dirigida , Fosforilação , Solubilidade , Spodoptera
18.
J Cell Biol ; 143(7): 2023-32, 1998 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-9864372

RESUMO

Simple epithelia express keratins 8 (K8) and 18 (K18) as their major intermediate filament (IF) proteins. One important physiologic function of K8/18 is to protect hepatocytes from drug-induced liver injury. Although the mechanism of this protection is unknown, marked K8/18 hyperphosphorylation occurs in association with a variety of cell stresses and during mitosis. This increase in keratin phosphorylation involves multiple sites including human K18 serine-(ser)52, which is a major K18 phosphorylation site. We studied the significance of keratin hyperphosphorylation and focused on K18 ser52 by generating transgenic mice that overexpress a human genomic K18 ser52--> ala mutant (S52A) and compared them with mice that overexpress, at similar levels, wild-type (WT) human K18. Abrogation of K18 ser52 phosphorylation did not affect filament organization after partial hepatectomy nor the ability of mouse livers to regenerate. However, exposure of S52A-expressing mice to the hepatotoxins, griseofulvin or microcystin, which are associated with K18 ser52 and other keratin phosphorylation changes, resulted in more dramatic hepatotoxicity as compared with WT K18-expressing mice. Our results demonstrate that K18 ser52 phosphorylation plays a physiologic role in protecting hepatocytes from stress-induced liver injury. Since hepatotoxins are associated with increased keratin phosphorylation at multiple sites, it is likely that unique sites aside from K18 ser52, and phosphorylation sites on other IF proteins, also participate in protection from cell stress.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas/genética , Filamentos Intermediários/fisiologia , Queratinas/química , Células 3T3 , Citoesqueleto de Actina/ultraestrutura , Substituição de Aminoácidos , Animais , Predisposição Genética para Doença , Griseofulvina/toxicidade , Hepatectomia , Humanos , Filamentos Intermediários/ultraestrutura , Queratinas/genética , Queratinas/metabolismo , Regeneração Hepática , Camundongos , Camundongos Transgênicos , Microcistinas , Ácido Okadáico/farmacologia , Peptídeos Cíclicos/toxicidade , Fosforilação , Mutação Puntual , Processamento de Proteína Pós-Traducional
19.
J Mol Histol ; 39(6): 585-93, 2008 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-18979174

RESUMO

The histologic hallmark of the development of type 1 diabetes (T1D) is insulitis, characterized by leukocytic infiltration of the pancreatic islets. The molecules controlling the early influx of leukocytes into the islets are poorly understood. Tumor necrosis factor alpha (TNFalpha)-stimulated gene 6 (TSG-6) is involved in inflammation, extracellular matrix formation, cell migration, and development. In the present study, we examined the expression and cellular localization of TSG-6 protein in islets of female non-obese diabetic (NOD) mice using frozen section immunofluorescence staining. Pancreata from nondiabetic (8 and 25 weeks old), prediabetic (230-280 mg/dl blood glucose) and diabetic (>300 mg/dl blood glucose) NOD mice were stained for TSG-6, insulin, CD3, CD11c, Mac3 and CD31. TSG-6 protein was detected in 67% of islets of prediabetic mice, 27% of islets of 25-week old nondiabetic mice, and less than 7% of islets of diabetic mice and 8-week old nondiabetic mice. Lastly, islet-derived TSG-6 protein was localized to the infiltrating CD3 and CD11c positive leukocytes.


Assuntos
Moléculas de Adesão Celular/metabolismo , Ilhotas Pancreáticas/metabolismo , Animais , Antígeno CD11c/metabolismo , Complexo CD3/metabolismo , Moléculas de Adesão Celular/genética , Diabetes Mellitus Tipo 1/metabolismo , Feminino , Células HeLa , Humanos , Ilhotas Pancreáticas/citologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos NOD
20.
J Hosp Infect ; 68(3): 222-9, 2008 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-18478625

RESUMO

Previous observational measures of healthcare worker (HCW) hand-hygiene behaviour (HHB) fail to provide adequate standard operating procedures (SOPs), accounts of inter-rater agreement testing or evidence of sensitivity to change. This study reports the development of an observational tool in a way that addresses these deficiencies. Observational categories were developed systematically, guided by a clinical guideline, previous measures and pilot hand-hygiene behaviour observations (HHOs). The measure, a simpler version of the Geneva tool, consists of HHOs (before and after low-risk, high-risk or unobserved contact), HHBs (soap, alcohol hand rub, no action, unknown), and type of HCW. Inter-observer agreement for each category was assessed by observation of 298 HHOs and HHBs by two independent observers on acute elderly and intensive care units. Raw agreement (%) and Kappa were 77% and 0.68 for HHB; 83% and 0.77 for HHO; and 90% and 0.77 for HCW. Inter-observer agreement for overall compliance of a group of HCWs was assessed by observation of 1191 HHOs and HHBs by two pairs of independent observers. Overall agreement was good (intraclass correlation coefficient = 0.79). Sensitivity to change was examined by autoregressive time-series modelling of longitudinal observations for 8 months on the intensive therapy unit during an Acinetobacter baumannii outbreak and subsequent strengthening of infection control measures. Sensitivity to change was demonstrated by a rise in compliance from 80 to 98% with an odds ratio of increased compliance of 7.00 (95% confidence interval: 4.02-12.2) P < 0.001.


Assuntos
Infecção Hospitalar/prevenção & controle , Fidelidade a Diretrizes , Desinfecção das Mãos/normas , Humanos , Transmissão de Doença Infecciosa do Profissional para o Paciente , Observação , Variações Dependentes do Observador , Competência Profissional , Sensibilidade e Especificidade
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