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1.
PLoS Pathog ; 18(2): e1009989, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-35143593

RESUMO

The enteric nervous system (ENS) controls many aspects of intestinal homeostasis, including parameters that shape the habitat of microbial residents. Previously we showed that zebrafish lacking an ENS, due to deficiency of the sox10 gene, develop intestinal inflammation and bacterial dysbiosis, with an expansion of proinflammatory Vibrio strains. To understand the primary defects resulting in dysbiosis in sox10 mutants, we investigated how the ENS shapes the intestinal environment in the absence of microbiota and associated inflammatory responses. We found that intestinal transit, intestinal permeability, and luminal pH regulation are all aberrant in sox10 mutants, independent of microbially induced inflammation. Treatment with the proton pump inhibitor, omeprazole, corrected the more acidic luminal pH of sox10 mutants to wild type levels. Omeprazole treatment also prevented overabundance of Vibrio and ameliorated inflammation in sox10 mutant intestines. Treatment with the carbonic anhydrase inhibitor, acetazolamide, caused wild type luminal pH to become more acidic, and increased both Vibrio abundance and intestinal inflammation. We conclude that a primary function of the ENS is to regulate luminal pH, which plays a critical role in shaping the resident microbial community and regulating intestinal inflammation.


Assuntos
Sistema Nervoso Entérico/fisiologia , Intestinos/microbiologia , Fenobarbital/metabolismo , Fatores de Transcrição SOXE/fisiologia , Proteínas de Peixe-Zebra/fisiologia , Peixe-Zebra/fisiologia , Animais , Disbiose/microbiologia , Microbioma Gastrointestinal , Homeostase , Concentração de Íons de Hidrogênio , Inflamação , Mutação
2.
Health Expect ; 26(5): 2064-2074, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37421272

RESUMO

INTRODUCTION: Carers of people with mental illness may face distinct challenges, including navigating fragmented health and social services during discharge from mental health hospitals. Currently, limited examples of interventions that support carers of people with mental illness in improving patient safety during transitions of care exist. We aimed to identify problems and solutions to inform future carer-led discharge interventions, which is imperative for ensuring patient safety and the well-being of carers. METHODS: The nominal group technique was used which combines both qualitative and quantitative data collection methods in four distinct phases: (1) problem identification, (2) solution generation, (3) decision making and (4) prioritisation. The aim was to combine expertise from different stakeholder groups (patients, carers and academics with expertise in primary/secondary care, social care or public health) to identify problems and generate solutions. RESULTS: Twenty-eight participants generated potential solutions that were grouped into four themes. The most acceptable solution for each was as follows: (1) 'Carer Involvement and Improving Carer Experience' a dedicated family liaison worker, (2) 'Patient Wellness and Education' adapting and implementing existing approaches to help implement the patient care plan, (3) 'Carer Wellness and Education' peer/social support interventions for carers and (4) 'Policy and System Improvements' understanding the co-ordination of care. CONCLUSION: The stakeholder group concurred that the transition from mental health hospitals to the community is a distressing period, where patients and carers are particularly vulnerable to safety and well-being risks. We identified numerous feasible/acceptable solutions to enable carers to improve patient safety and maintain their own mental wellbeing. PATIENT AND PUBLIC CONTRIBUTION: Patient and public contributors were represented in the workshop and the focus of the workshop was to identify the problems they faced and co-design potential solutions. Patient and public contributors were involved in the funding application and study design.


Assuntos
Cuidadores , Transtornos Mentais , Humanos , Cuidadores/psicologia , Hospitais Psiquiátricos , Segurança do Paciente , Saúde Mental , Transtornos Mentais/terapia
3.
Health Expect ; 26(3): 1236-1245, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36864604

RESUMO

INTRODUCTION: Clinical trials must include diverse participants to ensure the wide applicability of results. However, people from ethnic minorities are included in clinical trials at rates lower than expected given their share of the population. Working with South Riverside Community Development Centre (SRCDC), Talking Trials used public engagement to foster discussions around the underrepresentation of those from minority ethnic communities in clinical trials and to identify and address concerns surrounding trial participation. METHODS: We conducted three workshops with 13 co-researchers from minority ethnic backgrounds. We explored perceptions and understanding of clinical trials alongside participatory art activities to help move away from verbocentric methods of communication. These artworks formed an exhibition that was presented to the community, prompting further discussions and engagement. FINDINGS: Co-production workshops were an effective tool to introduce the public to trial research. With little knowledge of clinical trials at the beginning of the process, our co-researchers formed a cohesive group, sharing initial fears and mistrust towards trials. As conversations progressed these attitudes clearly shifted. Artwork produced during the workshops was incorporated into an exhibition. Quotes and creative pieces from the group were included to reflect the themes identified. Presenting the exhibition at Riverside Festival enabled further engagement with a wider diverse community. The focus on co-production helped build a network of individuals new to research and keen to become involved further. CONCLUSION: Inclusive and democratic co-production, enriched by participatory art practices, provided a powerful means of enabling our group to create new insights and foster new relationships. Projects like Talking Trials can diversify the research process itself-for example, four co-researchers have commenced lay research partner roles on trial management groups and a lay advisory group is in development. PATIENT OR PUBLIC CONTRIBUTION: Three members of staff at SRCDC were on the project delivery group and involved in the initial project design, subsequently helping to connect us with members of the Riverside community to work as co-researchers. Two of the SRCDC staff are co-authors of this manuscript. The project had 13 public co-researchers guiding the direction of this research and creating the artwork displayed in the art exhibition.


Assuntos
Etnicidade , Grupos Minoritários , Humanos , Atitude
4.
J Neurol Neurosurg Psychiatry ; 93(9): 1001-1009, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-34667103

RESUMO

BACKGROUND: Common memory aids for people with dementia at home are recommended. However, rigorous evaluation is lacking, particularly what guidance or support is valued. OBJECTIVE: To investigate effects of memory aids and guidance by dementia support practitioners (DSPs) for people in early-stage dementia through a pragmatic, randomised controlled trial. METHODS: Of 469 people with mild-to-moderate dementia and their informal carers, 468 were randomised to a DSP with memory aids or to usual care plus existing dementia guide. Allocation was stratified by Trust/Health Board; time since first attendance at memory service; gender; age; and living with primary carer or not. Primary outcome was Bristol Activities of Daily Living Scale (BADLS) Score at 3 and 6 months (primary end-point). Secondary outcomes for people with dementia: quality of life (CASP-19; DEMQOL); cognition and functioning (Clinical Dementia Rating Scale; S-MMSE); capability (ICECAP-O); social networks (LSNS-R); and instrumental daily living activities (R-IDDD). Secondary outcomes for carers: psychological health (GHQ-12); sense of competence (SSCQ). RESULTS: DSPs were successfully trained, compliance was good and welcomed by participants. Mean 6 months BADLS Score increased to 14.6 (SD: 10.4) in intervention and 12.6 (SD: 8.1) in comparator, indicative of greater dependence in the activities of daily living. Adjusted between-group difference was 0.38 (95% CI: -0.89 to 1.65, p=0.56). Though this suggests greater dependency in the intervention group the difference was not significant. No differences were found in secondary outcomes. CONCLUSIONS: This intervention did not maintain independence in the activities of daily living with no improvement in other outcomes for people with dementia or carers. TRIAL REGISTRATION NUMBER: Current Controlled Trials ISRCTN12591717.


Assuntos
Demência , Atividades Cotidianas/psicologia , Cuidadores/psicologia , Cognição , Demência/psicologia , Demência/terapia , Humanos , Qualidade de Vida
5.
Depress Anxiety ; 39(7): 564-572, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35536094

RESUMO

BACKGROUND: Prevalence estimates of COVID-19-related posttraumatic stress disorder (PTSD) have ranged from 1% to over 60% in the general population. Individuals with lived experience of a psychiatric disorder may be particularly vulnerable to COVID-19-related PTSD but this has received inadequate attention. METHODS: Participants were 1571 adults with lived experience of psychiatric disorder who took part in a longitudinal study of mental health during the COVID-19 pandemic. PTSD was assessed by the International Trauma Questionnaire (ITQ) anchored to the participant's most troubling COVID-19-related experiencevent. Factors hypothesised to be associated with traumatic stress symptoms were investigated by linear regression. RESULTS: 40.10% of participants perceived some aspect of the pandemic as traumatic. 5.28% reported an ICD-11 PTSD qualifying COVID-19 related traumatic exposure and 0.83% met criteria for probable ICD-11 COVID-19-related PTSD. Traumatic stress symptoms were associated with younger age, lower income, lower social support, and financial worries, and lived experience of PTSD/complex PTSD. Depression and anxiety measured in June 2020 predicted traumatic stress symptoms at follow-up approximately 20 weeks later in November 2020. CONCLUSIONS: We did not find evidence of widespread COVID-19-related PTSD among individuals with lived experience of a psychiatric disorder. There is a need for future research to derive valid prevalence estimates of COVID-19-related PTSD.


Assuntos
COVID-19 , Transtornos de Estresse Pós-Traumáticos , Adulto , Humanos , Classificação Internacional de Doenças , Estudos Longitudinais , Pandemias , Transtornos de Estresse Pós-Traumáticos/psicologia
6.
PLoS Biol ; 16(12): e2006893, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30532251

RESUMO

All animals live in intimate association with microorganisms that profoundly influence their health and development, yet the traits that allow microorganisms to establish and maintain host associations are not well understood. To date, most investigations aimed at identifying traits required for host association have focused on intrahost niches. Consequently, little is known about the relative contribution of extrahost factors such as environmental growth and survival and immigration into hosts from the external environment, as promoters of host association. To address this, we developed a tractable experimental evolution system that investigates both intra- and extrahost factors contributing to bacterial adaptation to the vertebrate gut. We passaged replicate lines of a zebrafish bacterial isolate, Aeromonas veronii, through populations of germ-free larval zebrafish (Danio rerio), each time using gut-associated Aeromonas populations to inoculate the aquatic environment of the next zebrafish population. We observed rapid increased adaptation to the host in all replicate lines. The initial adaptations present in early-evolved isolates did not increase intrahost fitness but rather enhanced both immigration from the environment and interhost transmission. Only in later-evolved isolates did we find evidence for intrahost-specific adaptations, as demonstrated by comparing their competitive fitness in the host genotype to which they evolved to that in a different genotype. Our results show how selection for bacterial transmission between hosts and their environment can shape bacterial-host association. This work illuminates the nature of selective forces present in host-microbe systems and reveals specific mechanisms of increased host association. Furthermore, our findings demonstrate that the entire host-microbe-environment system must be considered when identifying microbial traits that contribute to host adaptation.


Assuntos
Adaptação Biológica/fisiologia , Trato Gastrointestinal/microbiologia , Interações entre Hospedeiro e Microrganismos/fisiologia , Adaptação Biológica/genética , Aeromonas veronii/metabolismo , Aeromonas veronii/fisiologia , Animais , Bactérias , Evolução Biológica , Microbioma Gastrointestinal/fisiologia , Interações entre Hospedeiro e Microrganismos/imunologia , Larva/microbiologia , Filogenia , Seleção Genética/genética , Seleção Genética/fisiologia , Peixe-Zebra/microbiologia
7.
Conserv Biol ; 35(3): 1002-1008, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-32852067

RESUMO

Indigenous Peoples' lands cover over one-quarter of Earth's surface, a significant proportion of which is still free from industrial-level human impacts. As a result, Indigenous Peoples and their lands are crucial for the long-term persistence of Earth's biodiversity and ecosystem services. Yet, information on species composition on these lands globally remains largely unknown. We conducted the first comprehensive analysis of terrestrial mammal composition across mapped Indigenous lands based on data on area of habitat (AOH) for 4460 mammal species assessed by the International Union for Conservation of Nature. We overlaid each species' AOH on a current map of Indigenous lands and found that 2695 species (60% of assessed mammals) had ≥10% of their ranges on Indigenous Peoples' lands and 1009 species (23%) had >50% of their ranges on these lands. For threatened species, 473 (47%) occurred on Indigenous lands with 26% having >50% of their habitat on these lands. We also found that 935 mammal species (131 categorized as threatened) had ≥ 10% of their range on Indigenous Peoples' lands that had low human pressure. Our results show how important Indigenous Peoples' lands are to the successful implementation of conservation and sustainable development agendas worldwide.


La Importancia de las Tierras de los Pueblos Indígenas para la Conservación de los Mamíferos Terrestres Resumen Las tierras pertenecientes a pueblos indígenas cubren más de un cuarto de la superficie del planeta, una proporción importante que se encuentra aún libre de impactos humanos a nivel industrial. Como resultado, los pueblos indígenas y sus tierras son cruciales para la persistencia a largo plazo de la biodiversidad en la Tierra y de los servicios ecosistemicos. Sin embargo, la información sobre la composición de especies en estas tierras a nivel mundial todavía permanece desconocida en su mayoría. Realizamos el primer análisis integral de la composición de mamíferos terrestres a lo largo de las tierras indígenas mapeadas con base en los datos sobre el área del hábitat (ADH) de 4,460 especies de mamíferos valorados por la Unión Internacional para la Conservación de la Naturaleza. Sobrepusimos el ADH de cada especie en un mapa actual de tierras indígenas y encontramos que 2,695 especies (60% de los mamíferos valorados) tienen ≥10% de su distribución dentro de tierras de pueblos indígenas y que 1,009 especies (23%) tienen >50% de su distribución dentro de estas tierras. De las especies amenazadas, 473 (47%) ocurrieron en tierras indígenas.También descubrimos que 935 especies de mamíferos (131 categorizadas como amenazadas) tienen ≥ 10% de su distribución dentro de tierras de pueblos indígenas con baja presión humana. Nuestros resultados muestran cuán importantes son las tierras de los pueblos indígenas para la implementación exitosa de la conservación y las agendas globales de desarrollo sustentable.


Assuntos
Conservação dos Recursos Naturais , Ecossistema , Animais , Biodiversidade , Espécies em Perigo de Extinção , Humanos , Povos Indígenas , Mamíferos
8.
Crim Behav Ment Health ; 31(2): 131-142, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33306258

RESUMO

BACKGROUND: The widespread use of drugs in prisons leads to avoidable deaths, poorer health and a poor living environment. The contribution of psychoactive prescription drugs to this problem has received little attention in prison policy or at individual prescriber level. AIMS: To determine the extent of unsafe and inappropriate prescribing of psychoactive medications in one UK prison using a newly developed medicines optimisation framework. METHOD: A medicines optimisation framework was developed based on principles of good prescribing. It was initiated on the opening of a new prison-HMP Berwyn-in February 2017. During the study period, all prisoners at HMP Berwyn were transferred from other prisons. The safety and appropriateness of psychoactive medications were evaluated de novo on reception at HMP Berwyn and during follow up, using the medicines optimisation framework. RESULTS: About 1941 sentenced men arrived at HMP Berwyn between February 2017 and November 2018. Nearly one-third (634, 33%) were on a prescribed psychoactive medication. Seventy-five percent of these (474/634) required a prescription change due to appropriateness or safety concerns. Nearly half (295, 46.5%) received changes at reception despite having already undergone medicines reconciliation at their previous prison. Forty-three percent (275/634) received changes at follow up, most commonly those who had no prior risks identified at reception. CONCLUSIONS: Inappropriate and unsafe prescribing of psychoactive medications is occurring in prisons despite mandatory medication reviews. Ongoing monitoring is required to reduce the risk from these medications. A medicines optimisation framework such as this could be adopted across other prisons, worldwide, to help contribute to risk reduction from drug use in prisons. Appropriately modified, a similar framework might help reduce inappropriate and harmful prescribing in hospitals and in the community.


Assuntos
Prisioneiros , Transtornos Relacionados ao Uso de Substâncias , Humanos , Estudos Longitudinais , Masculino , Prisões , Reino Unido
9.
Int J Mol Sci ; 20(6)2019 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-30909440

RESUMO

To identify whether parent-of-origin effects (POE) of the 15q11.2 BP1-BP2 microdeletion are associated with differences in clinical features in individuals inheriting the deletion, we collected 71 individuals reported with phenotypic data and known inheritance from a clinical cohort, a research cohort, the DECIPHER database, and the primary literature. Chi-squared and Mann-Whitney U tests were used to test for differences in specific and grouped clinical symptoms based on parental inheritance and proband gender. Analyses controlled for sibling sets and individuals with additional variants of uncertain significance (VOUS). Among all probands, maternal deletions were associated with macrocephaly (p = 0.016) and autism spectrum disorder (ASD; p = 0.02), while paternal deletions were associated with congenital heart disease (CHD; p = 0.004). Excluding sibling sets, maternal deletions were associated with epilepsy as well as macrocephaly (p < 0.05), while paternal deletions were associated with CHD and abnormal muscular phenotypes (p < 0.05). Excluding sibling sets and probands with an additional VOUS, maternal deletions were associated with epilepsy (p = 0.019) and paternal deletions associated with muscular phenotypes (p = 0.008). Significant gender-based differences were also observed. Our results supported POEs of this deletion and included macrocephaly, epilepsy and ASD in maternal deletions with CHD and abnormal muscular phenotypes seen in paternal deletions.


Assuntos
Estudos de Associação Genética , Predisposição Genética para Doença , Deficiência Intelectual/diagnóstico , Deficiência Intelectual/genética , Criança , Pré-Escolar , Aberrações Cromossômicas , Cromossomos Humanos Par 15/genética , Estudos de Coortes , Feminino , Impressão Genômica , Humanos , Masculino , Fenótipo , Fatores Sexuais , Irmãos
11.
Med Educ ; 50(8): 866-79, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27402046

RESUMO

CONTEXT: Attitudinal objectives are difficult to formulate, teach and assess; yet good attitudes are fundamental to good practice. For instance, studies highlight negative attitudes to disability in the medical student community that contrast with the self-conceptions of disabled persons. This study was designed to better understand attitudinal learning, inadequately addressed by contemporary programmes, through the application of Mezirow's 'transformative learning theory' (TLT) to a novel educational intervention. METHODS: Participating students went to sea, for voyages of 5-7 days, in tall ships operated by the Jubilee Sailing Trust. Each student was buddied with another sailor living with disability. Disabilities included cerebral palsy, loss of sight, loss of limbs and paraplegia. Students recorded their experiences using audio diaries, written logs, formal voyage reports and art work and in post-voyage seminars. The data were analysed using interpretive phenomenological analysis, and the results are considered under five themes suggested by Mezirow. RESULTS: Sixteen students were recruited, with four students sailing on each of four separate voyages. Each student recorded audio-diary entries, which had a total duration of between 10 and 212 minutes. For seven of the 16 students, the five key elements of TLT were demonstrable, suggesting that transformative learning, as described by Mezirow, was occurring. Drawing on diverse qualitative data, insights into different aspects of this transformation are provided. CONCLUSIONS: TLT can be used to characterise, and thus design, educational interventions to meet attitudinal learning objectives. Students can be helped to discover their less helpful frames of reference. In safe environments these frames can be challenged and subjected to personal and communal reflection. Drawing on audio diaries and other evidence, and in answer to critiques of contemporary medical teaching on disability, we demonstrate such transformation in students 'at sea with disability', highlighting elements that could potentially be transferred to the mainstream curriculum.


Assuntos
Pessoas com Deficiência , Relações Interpessoais , Aprendizagem , Estereotipagem , Estudantes de Medicina/psicologia , Currículo , Pessoas com Deficiência/psicologia , Educação de Graduação em Medicina , Feminino , Humanos , Masculino , Modelos Educacionais , Pesquisa Qualitativa
12.
Soc Psychiatry Psychiatr Epidemiol ; 51(9): 1285-91, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27059660

RESUMO

BACKGROUND: Rehabilitation services have received little attention in the literature compared with other types of mental health service provision over the past 15 years. However, they are an important component of whole-system functioning in mental health services. Lack of provision has a particular impact on acute in-patient services. Poor pathway management can result in delayed discharges, placement of service users far from home, and resultant loss of resource for the local mental health economy. METHODS: A cross-sectional study gathered demographic, clinical, service utilisation, and financial data on 100 participants from out of area, rehabilitation and acute mental health units. Financial data was provided by the Health Board. Other data were gathered by two clinicians from case records and staff interviews. FINDINGS: 26.0 % of people were inappropriately placed, with frequent overprovision of support. It was calculated that within an annual budget of £12.7 M, £2.5 M (19.7 % of the total expenditure on this patient group) could be saved if all placements were appropriate. INTERPRETATION: There were differences between the three cohorts. Those placed out of area had the most complex needs, although those in rehabilitation placements were similar. Most participants had been in contact with services for more than 5 years. A system better matched to their needs would benefit these patients and would also generate financial savings for reinvestment in the mental health economy.


Assuntos
Pacientes Internados , Transtornos Mentais/reabilitação , Avaliação das Necessidades , Reabilitação Psiquiátrica/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Feminino , Gastos em Saúde , Humanos , Masculino , Serviços de Saúde Mental/economia , Pessoa de Meia-Idade , Reabilitação Psiquiátrica/economia , Medicina Estatal , País de Gales , Adulto Jovem
13.
Crim Behav Ment Health ; 30(1): 1-5, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31837040
14.
J Child Sex Abus ; 24(2): 135-51, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25747417

RESUMO

The impact of child sexual abuse on the adult self is not yet clearly understood. We explored adult perspectives through the use of narrative interviews (N = 30). Three key themes or views of self were identified in all narratives to varying degrees: the worthless self, the self as unknown, and the potential/developing self. Ambivalence and tension were present in all narratives. Individuals were challenged to integrate the sexual abuse experience in a constructive way and develop a more coherent perception of the self. The narrative method highlighted the dynamic nature of peoples' experiences at the same time recognizing that the narratives themselves are in progress. Reactions to disclosure, social support, and interpersonal connections are crucial at every turn.


Assuntos
Sobreviventes Adultos de Maus-Tratos Infantis/psicologia , Abuso Sexual na Infância/psicologia , Autoimagem , Adaptação Psicológica , Adulto , Transtornos de Ansiedade/diagnóstico , Transtornos de Ansiedade/psicologia , Criança , Transtorno Depressivo/diagnóstico , Transtorno Depressivo/psicologia , Feminino , Humanos , Incesto/psicologia , Relações Interpessoais , Entrevista Psicológica , Masculino , Narração , Desenvolvimento da Personalidade , Pesquisa Qualitativa , Autorrevelação , Apoio Social , Transtornos Relacionados ao Uso de Substâncias/diagnóstico , Transtornos Relacionados ao Uso de Substâncias/psicologia
15.
Infect Immun ; 82(7): 2815-25, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24733099

RESUMO

Clostridium difficile infection is the most common cause of severe cases of antibiotic-associated diarrhea (AAD) and is a significant health burden. Recent increases in the rate of C. difficile infection have paralleled the emergence of a specific phylogenetic clade of C. difficile strains (ribotype 027; North American pulsed-field electrophoresis 1 [NAP1]; restriction endonuclease analysis [REA] group BI). Initial reports indicated that ribotype 027 strains were associated with increased morbidity and mortality and might be hypervirulent. Although subsequent work has raised some doubt as to whether ribotype 027 strains are hypervirulent, the strains are considered epidemic isolates that have caused severe outbreaks across the globe. We hypothesized that one factor that could lead to the increased prevalence of ribotype 027 strains would be if these strains had increased competitive fitness compared to strains of other ribotypes. We developed a moderate-throughput in vitro model of C. difficile infection and used it to test competition between four ribotype 027 clinical isolates and clinical isolates of four other ribotypes (001, 002, 014, and 053). We found that ribotype 027 strains outcompeted the strains of other ribotypes. A similar competitive advantage was observed when two ribotype pairs were competed in a mouse model of C. difficile infection. Based upon these results, we conclude that one possible mechanism through which ribotype 027 strains have caused outbreaks worldwide is their increased ability to compete in the presence of a complex microbiota.


Assuntos
Clostridioides difficile/classificação , Clostridioides difficile/fisiologia , Animais , Epidemias , Fezes/microbiologia , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Proibitinas , RNA Ribossômico 16S , Ribotipagem
16.
Blood ; 119(19): 4441-50, 2012 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-22310911

RESUMO

Immune responses to foreign and self-Ags can be controlled by regulatory T cells (Tregs) expressing CD4 and IL-2Rα chain (CD25). Defects in Tregs lead to autoimmunity, whereas induction of Ag-specific CD4+CD25+ Tregs restores tolerance. Ag-specific CD4+CD25+ FOXP3+Tregs activated by the T helper type 2 (Th2) cytokine, IL-4, and specific alloantigen promote allograft tolerance. These Tregs expressed the specific IL-5Rα and in the presence of IL-5 proliferate to specific but not third-party Ag. These findings suggest that recombinant IL-5 (rIL-5) therapy may promote Ag-specific Tregs to mediate tolerance. This study showed normal CD4+CD25+ Tregs cultured with IL-4 and an autoantigen expressed Il-5rα. Treatment of experimental autoimmune neuritis with rIL-5 markedly reduced clinical paralysis, weight loss, demyelination, and infiltration of CD4+ (Th1 and Th17) CD8+ T cells and macrophages in nerves. Clinical improvement was associated with expansion of CD4+CD25+FOXP3+ Tregs that expressed Il-5rα and proliferated only to specific autoantigen that was enhanced by rIL-5. Depletion of CD25+ Tregs or blocking of IL-4 abolished the benefits of rIL-5. Thus, rIL-5 promoted Ag-specific Tregs, activated by autoantigen and IL-4, to control autoimmunity. These findings may explain how Th2 responses, especially to parasitic infestation, induce immune tolerance. rIL-5 therapy may be able to induce Ag-specific tolerance in autoimmunity.


Assuntos
Autoimunidade/efeitos dos fármacos , Antígenos CD4/metabolismo , Subunidade alfa de Receptor de Interleucina-2/metabolismo , Interleucina-5/farmacologia , Linfócitos T Reguladores/efeitos dos fármacos , Animais , Antígenos de Diferenciação de Linfócitos T/metabolismo , Autoimunidade/imunologia , Células CHO , Cricetinae , Cricetulus , Regulação para Baixo/efeitos dos fármacos , Regulação para Baixo/imunologia , Avaliação Pré-Clínica de Medicamentos , Feminino , Tolerância Imunológica/efeitos dos fármacos , Ratos , Ratos Endogâmicos Lew , Proteínas Recombinantes/farmacologia , Especificidade do Receptor de Antígeno de Linfócitos T/efeitos dos fármacos , Linfócitos T Reguladores/metabolismo , Linfócitos T Reguladores/fisiologia
17.
Aging Ment Health ; 18(2): 255-9, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23962313

RESUMO

OBJECTIVES: The sociocultural model of stress and coping, which despite receiving support from several studies conducted with diverse ethnic groups, has yet to be tested longitudinally or used within the context of positive caregiver outcomes. The aim of the current study was to test a specific component of the model, which posits that caregiver coping will be influenced by the cultural value of familism (feelings of solidarity and loyalty among family members), which will in turn affect caregiver outcomes. METHOD: A questionnaire was completed by 123 family caregivers in the UK assessing familism, use of coping strategies, caregiver gains, anxiety and depression at three time points over nine months. RESULTS: Mediation analysis followed guidelines proposed by Baron and Kenny. Religious coping and positive reframing at time 2 (T2) were found to significantly mediate between familism values at time 1 (T1) and caregiver gains at time 3 (T3). Behavioural disengagement at T2 was found to mediate between familism at T1 and caregiver depression at T3. Additionally familism was found to be positively associated with both negative and positive aspects of caregiving. CONCLUSION: Our longitudinal findings suggest that interventions and services acknowledging caregiver values and the associated coping responses may prove beneficial.


Assuntos
Adaptação Psicológica/fisiologia , Cuidadores/psicologia , Relações Familiares , Idoso , Cultura , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Modelos Psicológicos , Valores Sociais/etnologia , Reino Unido/etnologia
18.
Aging Ment Health ; 18(5): 600-9, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24304370

RESUMO

OBJECTIVES: The current research explores how family caregivers (1) make sense of caregiving and (2) cope with their circumstance. METHOD: We analysed semistructured interviews of 13 caregivers of people with either stroke (n = 5) or dementia (n = 8) and used photographs that caregivers took exemplifying their caregiving experiences to elicit their description of how they made sense of caregiving. This enabled greater insight into caregivers' perspective of caregiving complementing our use of Interpretative Phenomenological Analysis (IPA) to analyse verbatim transcripts. RESULTS: Emerging themes included (1) making sense of illness including the implications of receiving a diagnosis, caregiving motivations and receiving support, and (2) coping with caregiving, with variance in coping depending on, in part, individual differences in sense making. Caregivers adopted active and information seeking techniques to deal with current problems and to increase their sense of control, but avoidant techniques when considering future logistics of caregiving and when feeling helpless due to the burden they faced. At times caregivers looked on the bright side and made downward comparisons. CONCLUSION: The combination of elicitation techniques and analysis using IPA established patterns across caregivers and individual differences between caregivers in the meaning they assigned to their caregiving experience. Differences in sense making were based on the context of the caregiving stressor, which in turn influenced the variability in caregiver's coping techniques adopted. The analysis detailed within this article provides evidence that information and service provision must be tailored to individual caregiver experiences.


Assuntos
Adaptação Psicológica , Cuidadores/psicologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Demência/psicologia , Demência/terapia , Família/psicologia , Feminino , Humanos , Entrevistas como Assunto , Masculino , Pessoa de Meia-Idade , Acidente Vascular Cerebral/psicologia , Acidente Vascular Cerebral/terapia
19.
Burns ; 50(2): 302-314, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37985272

RESUMO

INTRODUCTION: A key component in the classification of all injury types is to differentiate whether the injury was deliberately inflicted and by whom, commonly known as "intent" in the surveillance literature. These data guide patient care and inform surveillance strategies. South Asia is believed to have the greatest number of intentional burn injuries, but national surveillance data is not disaggregated by injury intent. Scientific literature can be used for injury surveillance where national data collection does not exist. In order to synthesise research findings, it is essential to assess the potential impact of misclassification bias. We therefore conducted a systematic scoping review to understand terminology and methods used to differentiate injury intent of hospital burn patients in South Asia. METHODS: We followed the methods in our registered protocol (https://doi.org/10.17605/OSF.IO/DCYNQ). Studies met defined population, concept, context, and study design criteria. The databases Embase, MEDLINE, CINAHL, PsycInfo, and PakMediNet were searched. Two reviewers independently screened results. Data were extracted in a standardised manner and verified. The rigour of the method used to differentiate injury intent was appraised. RESULTS: 1435 articles were screened. Of these, 89 met our inclusion criteria. Most articles were from India and Pakistan, and used an observational study design. There were 14 stem terms used in the articles. The most common was "cause". There were 40 classifier terms. The most common were "accident", "suicide", and "homicide". Few articles defined these terms. The method used to differentiate injury intent was only described explicitly in 17% of articles and the rigour of the methods used were low. Where methods of differentiation were described, they appear to be based on patient or family report rather than multidisciplinary assessment. CONCLUSION: The heterogeneity in terms, lack of definitions, and limited investigation of injury intent means this variable is likely to be prone to misclassification bias. We strongly recommend that the global burn community unites to develop a common data element, including definitions and methods of assessment, for the concept of burn injury intent to enable more reliable data collection practices and interstudy comparisons.


Assuntos
Queimaduras , Suicídio , Humanos , Queimaduras/epidemiologia , Homicídio , Ásia Meridional , Hospitais , Estudos Observacionais como Assunto
20.
Burns ; 2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38862344

RESUMO

INTRODUCTION: Burn registers are an important source of surveillance data on injury intent. These data are considered essential to inform prevention activities. In South Asia, intentional burn injuries are thought to disproportionately affect women. Assessment of injury intent is difficult because it is influenced by personal, family, social, and legal sensitivities. This can introduce misclassification into data, and bias analyses. We conducted a descriptive, hypothesis generating study to explore misclassification of injury intent using data from a newly digitised single centre burn register in south India. METHODS: Data from 1st February 2016 to 28th February 2022 were analysed. All patients in the data set were included in the study (n = 1930). Demographic and clinical characteristics for patients are described for each classification of injury intent. All data cleaning and analyses were completed using RStudio. RESULTS: Injury intent data were missing for 12.6% of cases. It was the most commonly missing variable in the data set. "Accidental" injuries had a similar distribution over time, age, and total body surface area (TBSA) for males and females. "Homicidal" injuries were more common in females. Injuries reported as "Suicidal" affected men and women equally. A decrease in reporting of "Suicidal" injuries in females corresponded to an increase in high TBSA injuries classified as 'Other' or with missing data. Overwriting of injury intent was present in 1.5% of cases. The overwritten group had a greater proportion of females (62.1% vs. 48.5%) and higher median TBSA (77.5% vs. 27.5%) compared to the group where intent was not overwritten. CONCLUSION: Our findings indicate that some subgroups, such as females with high TBSA burns, appear to be more likely to be misclassified and should be the focus of future research. They also highlight that quality of surveillance data could be improved by recording of clinical impression, change in patient reported intent, and use of a common data element for intent to standardise data collection. We also recommend that injury intent is recorded as a unique variable and should not be mixed with other elements of injury causation (e.g. mechanism). Although this is a single centre study, the methods will be of interest to those who utilise routinely collected data and wish to reduce misclassification of this important variable.

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