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BACKGROUND: Digital self-management platforms have been proposed as a solution to better support people manage their musculoskeletal (MSK) condition. However, research studies often explicitly exclude people who can't access internet connected devices. An important consideration is that digital exclusion (for people without access to an internet connected device) from these new digital options will worsen already existing inequality and inequity in healthcare. AIM: To evaluate the acceptability and potential causes of digital exclusion of the South West London (SWL) MSK self-management app. OBJECTIVES: (1) Explore why some patients are not using the app and any barriers they have. Explore why some clinicians are not prescribing the app. (2) Make recommendations, based on these findings, to improve digital inclusion. METHODS/DESIGN: An explanatory sequential mixed method service evaluation that consisted of initial questionnaires to identify suitable collaborators, followed by structured interviews of patients and clinicians. RESULTS: Following a comprehensive data analysis, 10 sub-themes were grouped into four main themes: (1) Beliefs: Importance of understanding the role of digital; face to face consultation is still valued and needed. (2) Barriers: Lack of digital literacy; lack of physical examination/contact with a clinician. (3) Enablers: Immediate access to advice and information; perceived better control over health; ease of use; no appointment needed. (4) Solutions: Support and training; greater awareness. CONCLUSIONS: As digital health technology develops, strategies must change, requiring deliberate work and investments to improve inclusion. Our findings highlight how digital technology design and delivery can be adapted to address the causes of digital exclusion.
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Enfermedades Musculoesqueléticas , Automanejo , Humanos , Enfermedades Musculoesqueléticas/terapia , Femenino , Aplicaciones Móviles , Masculino , Adulto , Encuestas y Cuestionarios , Persona de Mediana Edad , Tecnología Digital , Londres , Salud DigitalRESUMEN
OBJECTIVES: Community pharmacies and their personnel present an opportunity to implement new services for bladder and bowel continence care. Underpinned by the COM-B model of capability (C), opportunity (O), motivation (M), Behaviour (B)), this study explored the opinions of healthcare staff and users of community pharmacy services, to inform the development of a new pharmacy bladder and bowel service (PBBS). METHODS: A qualitative design was adopted by conducting in-depth semi-structured interviews with pharmacy staff, users of community pharmacy services, bladder and bowel service staff, and professionals involved with commissioning services. A thematic analysis was used, and resulting themes were mapped onto the components of the COM-B model. RESULTS: A total of 27 participants were interviewed that represented the four groups of participants. A pro-active, protocolised PBBS was envisaged, involving targeted advice and provision of self-help materials, medication support, and referral/follow-up assessment as appropriate. Training programs for pharmacy staff, adequate funding/remuneration and information technology, awareness campaigns, policy support and guidance were identified as key behavioural targets for the success of a potential PBBS. Workforce time and capacity, service user embarrassment and stigma were potential barriers. CONCLUSIONS: The study identified a range of elements to be considered in the design and implementation of a successful PBBS. Informed by the evidence presented by this study, a multi-faceted approach to co-design the service will be required to ensure it is fit for purpose for all healthcare public and policy stakeholders.
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Servicios Comunitarios de Farmacia , Humanos , Servicios Comunitarios de Farmacia/organización & administración , Incontinencia Urinaria/tratamiento farmacológico , Incontinencia Fecal , Farmacéuticos/organización & administración , Actitud del Personal de Salud , Femenino , MasculinoRESUMEN
BACKGROUND: Musculoskeletal disorders (MSKDs) are a significant reason for general practice consultations in the United Kingdom. Current models of care include consultation with a General Practitioner (GP) or a First Contact Physiotherapy Practitioner (FCPP). Evidence suggests that FCPP led care is safe, yet it is unknown whether patients share this belief. PURPOSE: To explore patients' perspectives of general practice consultation for MSKDs, including views on safety, satisfaction and recommendations for future practice. METHODS: A secondary data analysis utilising qualitative data from the Patient Reported Experiences and Outcomes of Safety in Primary Care (PREOS-PC) questionnaire completed by 426 general practice patients who consulted with a MSKD between December 2019 and October 2022. Responses to the question 'What changes, if any, would you suggest to your GP surgery to make sure that health care is provided safely?' were analysed using content analysis. RESULTS: 606 responses across three timepoints were analysed. Two themes and six subthemes were identified; views on safety and satisfaction (inherent trust in the system, provision of face-to-face appointments, prompt access to care, person-centred care) and recommendations for future practice (appointment system: prompt access to face-to-face appointments, delivery of care: co-ordinated and collaborative person-centred care). CONCLUSIONS: Patients commented that FCPP consultations provided quick and accurate diagnoses and targeted advice. Recommendations for future practice included prompt access to face-to-face appointments, phone calls to be answered more quickly, improved communication for test results and follow ups, patients to feel listened to with a more individualised approach, and better continuity of care.
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Medicina General , Enfermedades Musculoesqueléticas , Satisfacción del Paciente , Investigación Cualitativa , Derivación y Consulta , Humanos , Enfermedades Musculoesqueléticas/terapia , Femenino , Masculino , Persona de Mediana Edad , Adulto , Anciano , Encuestas y Cuestionarios , Reino UnidoRESUMEN
BACKGROUND: First contact physiotherapy practitioners (FCPPs) are embedded within general practice, providing expert assessment, diagnosis, and management plans for patients with musculoskeletal disorders (MSKDs), without the prior need for GP consultation. AIM: To determine the clinical effectiveness and costs of FCPP models compared with GP-led models of care. DESIGN AND SETTING: Multiple site case-study design of general practices in the UK. METHOD: General practice sites were recruited representing the following three models: 1) GP-led care; 2) FCPPs who could not prescribe or inject (FCPPs-standard [St]); and 3) FCPPs who could prescribe and/or inject (FCPPs-additional qualifications [AQ]). Patient participants from each site completed outcome data at baseline, 3 months, and 6 months. The primary outcome was the SF-36 Physical Component Summary (PCS) score. Healthcare usage was collected for 6 months. RESULTS: In total, 426 adults were recruited from 46 practices across the UK. Non-inferiority analysis showed no significant difference in physical function (SF-36 PCS) across all three arms at 6 months (P = 0.667). At 3 months, a significant difference in numbers improving was seen between arms: 54.7% (n = 47) GP consultees, 72.4% (n = 71) FCPP-St, and 66.4% (n = 101) FCPP-AQ (P = 0.037). No safety issues were identified. Following initial consultation, a greater proportion of patients received medication (including opioids) in the GP-led arm (44.7%, n = 42), compared with FCPP-St (18.4%, n = 21) and FCPP-AQ (24.7%, n = 40) (P<0.001). NHS costs (initial consultation and over 6-month follow-up) were significantly higher in the GP-led model (median £105.5 per patient) versus FCPP-St (£41.0 per patient) and FCPP-AQ (£44.0 per patient) (P<0.001). CONCLUSION: FCPP-led models of care provide safe, clinically effective patient management, with cost-benefits and reduced opioid use in this cohort.
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Objective: Osteoarthritis (OA) affects 8.75 million people in the UK. Physical activity (PA) is recommended as a core treatment, yet nearly half of people with OA are inactive. Accessible and user-friendly interventions are needed to motivate people with OA to be active. Digital behaviour change interventions (DBCIs) might help to support people with OA to self-manage their own levels of PA. The aim of this project was to co-develop and test a DBCI to motivate people with OA to be active. Methods: A mixed methods design was adopted to build the theoretical foundations, develop, and test a complex DBCI. Two patient research partners with lived experience of OA were recruited onto the project team to assist with intervention development, which was guided by the intervention mapping (IM) approach. Interviews and think-aloud sessions were then used to explore attitudes, values, and perceived effectiveness of the website. Results: The IM approach enabled the development of a prototype website to be illustrated in a clear and transparent way, showing a link between the practical materials adopted within the website and the theoretical constructs they were attempting to change. Potential users highlighted the importance of clear, easy-to-understand information, focusing on enjoyment and social connectedness. Conclusions: DBCI development should be based on theory, adequately described, and thoroughly tested with potential users to understand how they might choose to integrate digital interventions into everyday life.
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INTRODUCTION: Managing symptoms, resisting functional decline and maintaining health and independence are key motivators for people with Rheumatoid Arthritis (RA) who successfully engage with physical activity (PA). To inform PA support for people with RA the aim was to determine whether the broader RA population share similar beliefs and strategies regarding PA to those who report successful engagement. METHODS: A modified two-stage Delphi approach. 200 patients from four National Health Service rheumatology departments received a postal questionnaire containing statements relating to engagement with PA derived from prior interview data from physically active individuals with RA. Statements rated as agree or strongly agree by >50% of respondents were retained and the same respondents asked to rate and prioritize potential PA intervention components. Ethical approval: Oxford C Research Ethics Committee (ref 13/SC/0418). RESULTS: Questionnaire one received 49 responses (11 males, 37 females, 1 unknown), mean age 65 years (range 29-82). Low levels of PA were reported by 60% of respondents. Questionnaire two responses (n = 36) indicated that a PA intervention should include information about prevention of RA symptoms worsening and benefits of PA for joints; help participants to achieve improved pain management and a feeling of being in control of their RA. For PA maintenance it was important that medication controlled symptoms, and PA instructors understood RA to ensure safety. CONCLUSIONS: A key factor to consider when designing a PA intervention for people with RA is that education from a knowledgeable instructor should underpin programme delivery alongside effective medication. Programmes may need tailoring based on demographics; this should be explored in future studies.
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Artritis Reumatoide , Medicina Estatal , Masculino , Femenino , Humanos , Adulto , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Ejercicio Físico , Encuestas y CuestionariosRESUMEN
BACKGROUND: First Contact Physiotherapists (FCPs) were introduced to reduce demands on GPs by providing improving access to expert musculoskeletal care. FCPs experience similar workplace stressors to GPs and there is an emerging concern that remote consultations are causing further impacts to their wellbeing. AIM: To explore the impact of remote consultations on FCPs. METHODS: A mixed methods sequential explanatory study with FCPs was conducted. An online survey measured the usage and impact of remote consultations. Semi-structured interviews explored the lived experiences of using remote consultations. RESULTS: The online survey was completed by 109 FCPs. A key benefit of remote consultations was patient convenience; perceived challenges included IT issues, poor efficacy, FCP anxiety, isolation, and increased workload. FCPs viewed remote consultations as a 'challenge' rather than a 'threat'. Nearly two thirds of the FCPs had not received relevant training, yet over half were interested. Follow-up interviews with 16 FCPs revealed 4 themes: (1) Remote consultations provide logistical benefits to the patient; (2) Compromised efficacy is the key challenge of remote consultations; (3) Challenges for FCPs working in areas of high deprivation; and (4) Remote consultations impact the health, wellbeing and work satisfaction of FCPs. CONCLUSIONS: Remote consultations offer a convenient alternative for patients, but may add to FCP stress particularly in areas of high socioeconomic deprivation. Further research is required to understand how remote consultations can be enhanced when communication barriers and lower levels of digital literacy exist. Continued monitoring of job satisfaction and resilience levels is important to ensure FCPs remain in their role.
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Fisioterapeutas , Consulta Remota , Humanos , Consulta Remota/métodos , Atención Primaria de Salud , Investigación Cualitativa , Satisfacción del PacienteRESUMEN
Objectives: We developed a brief cognitive behavioural, one-to-one intervention to reduce fatigue impact for patients with inflammatory arthritis. This qualitative process evaluation explored intervention acceptability and potential refinements from the perspective of patients who attended sessions and rheumatology health professionals (RHPs) who delivered the intervention. Methods: Interviews were conducted with patients and RHPs from five National Health Service (NHS) sites. Data were analysed using inductive thematic analysis. Results: Twenty-two patients and 11 RHPs participated. Patient themes: Collaborative, non-judgemental consultations: patients valued having space to reflect, where their fatigue was validated. Relevant content, but not ground-breaking: patients appreciated the opportunity to tailor content to individual priorities. Daily diaries were useful to visualize fatigue. Self-awareness: patients reported increased acceptance, sense of control, and confidence to manage fatigue. Degrees of openness to change: sessions prompted patients to engage in behaviour change. For some, complicated lives made it difficult to plan for change. RHP themes: Engagement with intervention: RHPs liked training face to face, and sessions were more enjoyable with experience of delivery. Research vs clinical practice: RHPs expressed concern about fitting sessions into NHS clinic appointments. It was difficult to offer follow-up sessions within 2 weeks. Collaborating with patients: RHPs reported that patients engaged with the tools and strategies. Some RHPs followed the manual in a linear way, whereas others used it flexibly. Conclusion: There is potential for this brief fatigue intervention to benefit patients. Future research will focus on flexibility to fit with local services and creating educational resources to use in a range of contexts.
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OBJECTIVES: Patients with inflammatory arthritis report that fatigue is challenging to manage. We developed a manualised, one-to-one, cognitive-behavioural intervention, delivered by rheumatology health professionals (RHPs). The Fatigue - Reducing its Effects through individualised support Episodes in Inflammatory Arthritis (FREE-IA) study tested the feasibility of RHP training, intervention delivery and outcome collection ahead of a potential trial of clinical and cost-effectiveness. METHODS: In this single-arm feasibility study, eligible patients were ≥18 years, had a clinician-confirmed diagnosis of an inflammatory arthritis and scored ≥6/10 on the Bristol Rheumatoid Arthritis Fatigue (BRAF) Numerical Rating Scale (NRS) Fatigue Effect. Following training, RHPs delivered two to four sessions to participants. Baseline data were collected before the first session (T0) and outcomes at 6 weeks (T1) and 6 months (T2). The proposed primary outcome was fatigue impact (BRAF NRS Fatigue Effect). Secondary outcomes included fatigue severity and coping, disease impact and disability, and measures of therapeutic mechanism (self-efficacy and confidence to manage health). RESULTS: Eight RHPs at five hospitals delivered 113 sessions to 46 participants. Of a potential 138 primary and secondary outcome responses at T0, T1 and T2, there were 13 (9.4%) and 27 (19.6%) missing primary and secondary outcome responses, respectively. Results indicated improvements in all measures except disability, at either T1 or T2, or both. CONCLUSIONS: This study showed it was feasible to deliver the intervention, including training RHPs, and recruit and follow-up participants with high retention. While there was no control group, observed within-group improvements suggest potential promise of the intervention and support for a definitive trial to test effectiveness.
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Artritis Reumatoide , Fatiga , Adolescente , Adulto , Artritis Reumatoide/complicaciones , Artritis Reumatoide/terapia , Fatiga/etiología , Fatiga/prevención & control , Estudios de Factibilidad , Humanos , Proyectos de Investigación , Resultado del TratamientoRESUMEN
BACKGROUND: Musculoskeletal conditions such as joint pain are a growing problem, affecting 18.8 million people in the United Kingdom. Digital health interventions (DHIs) are a potentially effective way of delivering information and supporting self-management. It is vital that the development of such interventions is transparent and can illustrate how individual components work, how they link back to the theoretical constructs they are attempting to change, and how this might influence outcomes. getUBetter is a DHI developed to address the lack of personalized, supported self-management tools available to patients with musculoskeletal conditions by providing knowledge, skills, and confidence to navigate through a self-management journey. OBJECTIVE: The aim of this study was to map a logic model of behavior change for getUBetter to illustrate how the content and functionality of the DHI are aligned with recognized behavioral theory, effective behavior change techniques, and clinical guidelines. METHODS: A range of behavior change models and frameworks were used, including the behavior change wheel and persuasive systems design framework, to map the logic model of behavior change underpinning getUBetter. The three main stages included understanding the behavior the intervention is attempting to change, identifying which elements of the intervention might bring about the desired change in behavior, and describing intervention content and how this can be optimally implemented. RESULTS: The content was mapped to 25 behavior change techniques, including information about health consequences, instruction on how to perform a behavior, reducing negative emotions, and verbal persuasion about capability. Mapping to the persuasive system design framework illustrated the use of a number of persuasive design principles, including tailoring, personalization, simulation, and reminders. CONCLUSIONS: This process enabled the proposed mechanisms of action and theoretical foundations of getUBetter to be comprehensively described, highlighting the key techniques used to support patients to self-manage their condition. These findings provide guidance for the ongoing evaluation of the effectiveness (including quality of engagement) of the intervention and highlight areas that might be strengthened in future iterations.
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INTRODUCTION: Musculoskeletal (MSK) conditions are the leading cause of disability in the United Kingdom, leading to ever-growing waiting lists. Clinical guidelines highlight that most musculoskeletal conditions resolve in time and with little clinical input, and so supporting people to self-manage is recommended to optimise healthcare resources. Despite this, the term self-management remains ambiguous and to date no systematic review has evaluated if self-management is a suitable, acceptable, and effective intervention/strategy for managing all MSK conditions. METHODS AND ANALYSIS: This protocol is informed and reported in line with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA). An advanced convergent qualitative meta-integration mixed-studies design will be used. Using a comprehensive predetermined search strategy, databases, key journals and grey literature will be searched independently by two reviewers. The reviewers will independently assess eligibility, complete data extraction, and evaluate for risk of bias using the Mixed Methods Appraisal Tool (MMAT). The overall quality of included studies will be evaluated using Grading of Recommendations, Assessment, Development and Evaluation (GRADE) guidelines. Data from mixed-methods studies will be transformed using a process of fractionation and analysed alongside the data extracted from the quantitative and qualitative studies, using descriptive analysis and thematic analysis, respectively. ETHICS AND DISSEMINATION: No research ethics are required for this systematic review since patient data will not be collected. The review will help to inform healthcare professionals and researchers on the most suitable, acceptable, and effective intervention/strategy for self-managing MSK conditions. Results of this review will be submitted for publication in a peer-reviewed journal and conference presentations.
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Enfermedades Musculoesqueléticas , Sistema Musculoesquelético , Automanejo , Humanos , Enfermedades Musculoesqueléticas/terapia , Investigación Cualitativa , Proyectos de Investigación , Revisiones Sistemáticas como AsuntoRESUMEN
ExlA is a highly virulent pore-forming toxin that has been recently discovered in outlier strains from Pseudomonas aeruginosa. ExlA is part of a two-partner secretion system, in which ExlA is the secreted passenger protein and ExlB the transporter embedded in the bacterial outer membrane. In previous work, we observed that ExlA toxicity in a host cell was contact-dependent. Here, we show that ExlA accumulates at specific points of the outer membrane, is likely entrapped within ExlB pore, and is pointing outside. We further demonstrate that ExlA is maintained at the membrane in conditions where the intracellular content of second messenger cyclic-di-GMP is high; lowering c-di-GMP levels enhances ExlB-dependent ExlA secretion. In addition, we set up an ELISA to detect ExlA, and we show that ExlA is poorly secreted in liquid culture, while it is highly detectable in broncho-alveolar lavage fluids of mice infected with an exlA+ strain. We conclude that ExlA translocation is halted at mid-length in the outer membrane and its secretion is regulated by c-di-GMP. In addition, we developed an immunological test able to quantify ExlA in biological samples.
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Proteínas Bacterianas/genética , Toxinas Bacterianas/metabolismo , Membrana Celular/química , GMP Cíclico/análogos & derivados , Pseudomonas aeruginosa/fisiología , Animales , Proteínas Bacterianas/metabolismo , Toxinas Bacterianas/genética , GMP Cíclico/metabolismo , Ensayo de Inmunoadsorción Enzimática , Ratones , Infecciones por Pseudomonas , Pseudomonas aeruginosa/genética , Pseudomonas aeruginosa/aislamiento & purificaciónRESUMEN
INTRODUCTION: Management of rheumatoid arthritis has changed dramatically over the last decade and is characterised by early start of intensive treatment and tight monitoring of disease activity until remission. The role of nurse-led care at early stage of disease is not well understood. AIMS: To develop an understanding of rheumatology nurse-led care from the perspective of patients with early rheumatoid arthritis. METHODS: A systematic review of qualitative studies, reported in line with PRISMA checklist. In March 2019, the following databases were searched: MEDLINE, EMBASE, CINAHL, PsycINFO and OpenGrey. Studies were included if they: included adults with rheumatoid arthritis; were qualitative studies with data on patients' perspectives of nurse-led care; and published in peer-reviewed journals, in English, between 2010-2019. Due to few studies in early rheumatoid arthritis, inclusion was extended to adults with established rheumatoid arthritis. Two reviewers screened abstracts and full texts. Joanna Briggs Institute Critical Appraisal Tool was used for quality assessment. Thematic synthesis was conducted according to the framework of Thomas and Harden (2008). RESULTS: The search identified 1034 records. After screening and assessing for eligibility, eight qualitative studies were included in the review (133 patients). Three themes were identified from the synthesis. Nurse-led care was seen to provide professional expertise in planning and delivery of care. A person-centred approach was used combined with good communication skills, thus creating a positive therapeutic environment. Nurse-led care was described as providing a sense of empowerment and psychological support. CONCLUSION: Patients with rheumatoid arthritis are supportive of nurse-led care. They value its professionalism and person-centred approach which provide a sense of security and confidence. RELEVANCE TO CLINICAL PRACTICE: The findings outline ingredients of nurse-led care that are important to patients. These can inform nurses' professional development plans, service improvement and the competence framework for rheumatology nursing.
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Artritis Reumatoide/enfermería , Enfermeras y Enfermeros , Adulto , Consejo , Atención a la Salud , Humanos , Investigación CualitativaRESUMEN
OBJECTIVES: Osteoarthritis (OA) affects approximately 8.75 million people in the United Kingdom. Physical activity is recommended as a core treatment, yet 44% of people with OA are inactive. Motivation and self-efficacy for exercise are considered to be key factors contributing to sustained engagement with physical activity. The aim of this study was to explore the beliefs, motives (what an individual aims to attain through participating in physical activity) and gains (what people feel they might get from participation) associated with physical activity engagement in a group of people with OA. DESIGN AND METHOD: This study adopted a cross-sectional survey research design, using two validated questionnaires: the Exercise Motives and Gains Inventory and the Exercise Self-Efficacy Scale. RESULTS: Data were gathered from 262 people with OA between August 2015 and January 2016. Those who were most active reported higher levels of both motivation and self-efficacy and were active for enjoyment, to avoid negative health, and for health and fitness reasons. A comparison of motives and gains revealed higher gain scores for social engagement and enjoyment, compared with associated motive scores. CONCLUSION: This study provides evidence of the central role that motives, gains and self-efficacy play in facilitating engagement with physical activity in this population. Future interventions should aim to foster increased self-efficacy for physical activity and promote autonomous forms of motivation by emphasising the importance of choosing activities which are enjoyable, as well as highlighting the value of social engagement.
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Motivación , Osteoartritis , Estudios Transversales , Ejercicio Físico , Humanos , Encuestas y CuestionariosRESUMEN
Pseudomonas aeruginosa is a highly adaptive opportunistic pathogen that can have serious health consequences in patients with lung disorders. Taxonomic outliers of P. aeruginosa of environmental origin have recently emerged as infectious for humans. Here, we present the first genome-wide analysis of an isolate that caused fatal haemorrhagic pneumonia. In two clones, CLJ1 and CLJ3, sequentially recovered from a patient with chronic pulmonary disease, insertion of a mobile genetic element into the P. aeruginosa chromosome affected major virulence-associated phenotypes and led to increased resistance to the antibiotics used to combat the infection. Comparative genome, proteome and transcriptome analyses revealed that this ISL3-family insertion sequence disrupted the genes for flagellar components, type IV pili, O-specific antigens, translesion polymerase and enzymes producing hydrogen cyanide. Seven-fold more insertions were detected in the later isolate, CLJ3, than in CLJ1, some of which modified strain susceptibility to antibiotics by disrupting the genes for the outer-membrane porin OprD and the regulator of ß-lactamase expression AmpD. In the Galleria mellonella larvae model, the two strains displayed different levels of virulence, with CLJ1 being highly pathogenic. This study revealed insertion sequences to be major players in enhancing the pathogenic potential of a P. aeruginosa taxonomic outlier by modulating both its virulence and its resistance to antimicrobials, and explains how this bacterium adapts from the environment to a human host.
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Elementos Transponibles de ADN , Hemorragia/etiología , Neumonía/microbiología , Pseudomonas aeruginosa/clasificación , Secuenciación Completa del Genoma/métodos , Animales , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Modelos Animales de Enfermedad , Perfilación de la Expresión Génica , Regulación Bacteriana de la Expresión Génica , Genoma Bacteriano , Genómica , Hemorragia/microbiología , Hemorragia/mortalidad , Humanos , Mariposas Nocturnas , Filogenia , Neumonía/complicaciones , Neumonía/mortalidad , Proteómica , Infecciones por Pseudomonas/microbiología , Infecciones por Pseudomonas/mortalidad , Pseudomonas aeruginosa/aislamiento & purificación , Pseudomonas aeruginosa/patogenicidad , Factores de Virulencia/genética , Factores de Virulencia/metabolismoRESUMEN
The formation of chromophore arrays using a DNA templating approach leads to the creation of supramolecular assemblies, where the optical properties of the overall system can be fine-tuned to a large extent. In particular, porphyrin derivatives have been shown to be versatile building blocks; mostly covalent chemistry was used for embedding the units into DNA strands. Self-assembly of porphyrin modified nucleosides, on the other hand, has not been investigated as a simplified approach. We report on the synthesis of a magnesium(II) tetraaza porphine (MgTAP) coupled to deoxyuridine, and array formation on DNA templates which contain well-defined oligo(dA) segments showing strong fluorescence enhancement which is significantly larger than that with a Zn-porphyrin. The use of the deep-eutectic solvent glycholine is essential for successful assembly formation. The system allows for sizing of short tandem repeat markers with multiple adenosines, thus the concept could be adaptable to in vitro forensic DNA profiling with a suitable set of different chromophores on all nucleosides.
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OBJECTIVE: Osteoporotic vertebral fractures (OVFs) are common and present a significant burden to patients and healthcare services. Poor posture can increase vertebral pressure, pain and the risk of further fractures. The aim of the present study was to investigate the effects of postural taping on pain, function and quality of life when used in addition to usual care. METHODS: A feasibility randomized, controlled trial was carried out in men and women with at least one clinically diagnosed painful OVF. Participants were randomly allocated to use an adhesive postural taping device at home for 4 weeks or to continue with usual care. Outcomes assessed at baseline and 4 weeks included pain at rest and on movement (visual analogue scales [VASs]), and function and quality of life (Quality of Life Questionnaire of the European Foundation for Osteoporosis [QUALEFFO]). Health resource use and acceptability were explored using a specifically designed questionnaire. RESULTS: Twenty-four participants completed the trial (taping, n = 13; control, n = 11). Groups were comparable in age, although the control group contained more men (n = 3 versus n = 0) and scored slightly lower on most outcome measures at baseline. Descriptive analysis favoured the taping group for most outcome measures. Effect sizes were small to medium (0.37, 0.45 and 0.66 for VAS rest, VAS movement and QUALEFFO, respectively). CONCLUSIONS: The taping device demonstrated potential to improve pain and function. However, the findings need to be replicated in an appropriately powered study. The study procedures were largely acceptable. A more extensive pilot trial is recommended prior to a definitive trial.
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Dolor Musculoesquelético/terapia , Fracturas Osteoporóticas/diagnóstico por imagen , Fracturas Osteoporóticas/terapia , Fracturas de la Columna Vertebral/diagnóstico por imagen , Fracturas de la Columna Vertebral/terapia , Anciano , Anciano de 80 o más Años , Estudios de Factibilidad , Femenino , Estudios de Seguimiento , Humanos , Masculino , Dolor Musculoesquelético/diagnóstico , Fracturas Osteoporóticas/fisiopatología , Dimensión del Dolor , Medición de Resultados Informados por el Paciente , Valores de Referencia , Medición de Riesgo , Índice de Severidad de la Enfermedad , Método Simple Ciego , Fracturas de la Columna Vertebral/fisiopatología , Cinta Quirúrgica , Resultado del TratamientoRESUMEN
The two-partner secretion system ExlBA, expressed by strains of Pseudomonas aeruginosa belonging to the PA7 group, induces hemorrhage in lungs due to disruption of host cellular membranes. Here we demonstrate that the exlBA genes are controlled by a pathway consisting of cAMP and the virulence factor regulator (Vfr). Upon interaction with cAMP, Vfr binds directly to the exlBA promoter with high affinity (equilibrium binding constant [Keq] of ≈2.5 nM). The exlB and exlA expression was diminished in the Vfr-negative mutant and upregulated with increased intracellular cAMP levels. The Vfr binding sequence in the exlBA promoter was mutated in situ, resulting in reduced cytotoxicity of the mutant, showing that Vfr is required for the exlBA expression during intoxication of epithelial cells. Vfr also regulates function of type 4 pili previously shown to facilitate ExlA activity on epithelial cells, which indicates that the cAMP/Vfr pathway coordinates these two factors needed for full cytotoxicity. As in most P. aeruginosa strains, the adenylate cyclase CyaB is the main provider of cAMP for Vfr regulation during both in vitro growth and eukaryotic cell infection. We discovered that the absence of functional Vfr in the reference strain PA7 is caused by a frameshift in the gene and accounts for its reduced cytotoxicity, revealing the conservation of ExlBA control by the CyaB-cAMP/Vfr pathway in P. aeruginosa taxonomic outliers.IMPORTANCE The human opportunistic pathogen Pseudomonas aeruginosa provokes severe acute and chronic human infections associated with defined sets of virulence factors. The main virulence determinant of P. aeruginosa taxonomic outliers is exolysin, a membrane-disrupting pore-forming toxin belonging to the two-partner secretion system ExlBA. In this work, we demonstrate that the conserved CyaB-cAMP/Vfr pathway controls cytotoxicity of outlier clinical strains through direct transcriptional activation of the exlBA operon. Therefore, despite the fact that the type III secretion system and exolysin are mutually exclusive in classical and outlier strains, respectively, these two major virulence determinants share similarities in their mechanisms of regulation.
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Proteínas Bacterianas/metabolismo , Toxinas Bacterianas/genética , Proteína Receptora de AMP Cíclico/metabolismo , AMP Cíclico/metabolismo , Pseudomonas aeruginosa/metabolismo , Pseudomonas aeruginosa/patogenicidad , Adenilil Ciclasas/genética , Adenilil Ciclasas/metabolismo , Proteínas Bacterianas/genética , Toxinas Bacterianas/metabolismo , Toxinas Bacterianas/toxicidad , Secuencia de Bases , Línea Celular , Proteína Receptora de AMP Cíclico/genética , Mutación del Sistema de Lectura , Regulación Bacteriana de la Expresión Génica , Humanos , Regiones Promotoras Genéticas , Infecciones por Pseudomonas/microbiología , Pseudomonas aeruginosa/clasificación , Pseudomonas aeruginosa/genética , VirulenciaRESUMEN
PURPOSE: The aim of this review was to summarize and evaluate studies on training direct-care staff to provide communication intervention to adults with intellectual disability. METHOD: Systematic searches identified 22 studies. These were summarized and evaluated in terms of (a) participants; (b) settings; (c) training aims and procedures; (d) research designs; (e) reliability, integrity, and social validity; (f) outcomes; (g) generalization and follow-up; and (h) certainty of evidence. RESULTS: A total of 437 staff and 254+ adults with intellectual disability participated. Staff training most frequently involved combinations of verbal instruction, role play, modeling, practice, and feedback. Reliability was assessed in 18 studies with acceptable standards for most of these studies. Treatment integrity and social validity were assessed in 1 and 3 studies, respectively, with positive outcomes. Generalization and maintenance were assessed in 5 and 8 studies, respectively, with predominantly positive outcomes. Most studies reported positive outcomes for staff and positive or mixed outcomes for the adults with intellectual disability. Certainty of evidence was rated as conclusive in 1 study, suggestive in 14 studies, and inconclusive in 7 studies. CONCLUSIONS: There is sufficient evidence to conclude that direct-care staff can be taught to provide effective communication intervention to adults with intellectual disability. Professionals involved in providing training and support to direct-care staff could expect positive outcomes from multicomponent training programs that include opportunities for practice and feedback.
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Comunicación , Personal de Salud/educación , Capacitación en Servicio/métodos , Discapacidad Intelectual/rehabilitación , Personas con Discapacidades Mentales/rehabilitación , Adulto , Actitud del Personal de Salud , Conocimientos, Actitudes y Práctica en Salud , Humanos , Discapacidad Intelectual/diagnóstico , Discapacidad Intelectual/psicología , Personas con Discapacidades Mentales/psicología , Relaciones Profesional-Paciente , Resultado del TratamientoRESUMEN
The export of bacterial toxins across the bacterial envelope requires the assembly of complex, membrane-embedded protein architectures. Pseudomonas aeruginosa employs type III secretion (T3S) injectisome to translocate exotoxins directly into the cytoplasm of a target eukaryotic cell. This multi-protein channel crosses two bacterial membranes and extends further as a needle through which the proteins travel. We show in this work that PscI, proposed to form the T3S system (T3SS) inner rod, possesses intrinsic properties to polymerize into flexible and regularly twisted fibrils and activates IL-1ß production in mouse bone marrow macrophages in vitro. We also found that point mutations within C-terminal amphipathic helix of PscI alter needle assembly in vitro and T3SS function in cell infection assays, suggesting that this region is essential for an efficient needle assembly. The overexpression of PscF partially compensates for the absence of the inner rod in PscI-deficient mutant by forming a secretion-proficient injectisome. All together, we propose that the polymerized PscI in P. aeruginosa optimizes the injectisome function by anchoring the needle within the envelope-embedded complex of the T3S secretome and - contrary to its counterpart in Salmonella - is not involved in substrate switching.