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INTRODUCTION: The CGG repeats in the 5' untranslated region of the fragile X mental retardation 1 gene (FMR1) gene shows increased instability upon maternal transmission. Maternal FMR1 intermediate (45-54 repeats) and premutation (PM: 55-<200 repeats) alleles usually expand to full mutation (>200 repeats) alleles in offspring and consequently, cause fragile X syndrome (FXS) in them. METHODS: In a prospective cohort study, Pakistani pregnant women in prenatal care were first screened for FMR1 expanded alleles. In the follow-up, pregnancy outcomes in women carrying FMR1 expanded alleles were recorded and their newborn offspring were also screened for FXS. RESULTS: In a total of 1950 pregnant women, 89 (4.6%) were detected carriers for FMR1 expanded alleles; however, rates of detection of expanded alleles were found significantly high in women with a history of FXS. In addition, miscarriages and birth of affected newborns with FXS were significantly more common in women carrying large size PM alleles and had a history of FXS (P = 0.0494 and P = 0.0494, respectively). CONCLUSIONS: The current study provides the first evidence of screening Pakistani pregnant women for FMR1 expanded alleles in prenatal care. Moreover, the miscarriage was also detected as a clinical predictor for FXS. IMPACT: Offspring would have a higher risk of developing FXS due to maternal FMR1 alleles expansions during transmission. This is the first prospective cohort study in Pakistan for finding FMR1 allelic status of pregnant women and their newborn offspring in follow-up. The robust offspring risk for FXS estimated in this study may be valuable information for genetic counseling of women carriers for FMR1 expanded alleles. The family history and miscarriage were detected as effective indicators for FXS carrier screening in Pakistani women.
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Aborto Espontáneo , Síndrome del Cromosoma X Frágil , Humanos , Femenino , Recién Nacido , Embarazo , Alelos , Estudios Prospectivos , Aborto Espontáneo/genética , Síndrome del Cromosoma X Frágil/diagnóstico , Síndrome del Cromosoma X Frágil/genética , Mutación , Proteína de la Discapacidad Intelectual del Síndrome del Cromosoma X Frágil/genéticaRESUMEN
OBJECTIVE: To provide an overview of systems available for peripheral arterial disease (PAD) screening, together with respective accuracies and a clinical evaluation to identify a system suitable for use in a community screening programme. METHODS: A systematic review of the diagnostic accuracy of six ankle brachial pressure index (ABPI) and toe brachial pressure index (TBPI) devices deemed to be portable, which were Conformité Européenne (CE) marked, and were automated or semi-automated was carried out compared with gold standard handheld Doppler and duplex ultrasound. The devices were MESI-ABPI-MD, Huntleigh Dopplex Ability, Huntleigh ABPI and TBPI systems, Systoe TBPI system, and BlueDop. Seven databases (MEDLINE, EMBASE, Scopus, Web of Science, Cochrane Database of Systematic Reviews, Cochrane Register of Controlled Trials (CENTRAL), and Cumulative Index to Nursing and Allied Health Literature (CINAHL)) were searched, and 11 studies were identified as eligible for review. This was followed by hands on clinical evaluation by abdominal aortic aneurysm (AAA) screening staff (n = 39). During this, devices were demonstrated to staff which they then tested on volunteers and gave feedback using pre-designed questionnaires on their suitability for use in a screening programme. Finally, accuracy data and staff preferences were combined during a consensus conference that was held between study and screening staff to determine the most appropriate device to use in a community screening programme. RESULTS: Generally, the evaluated systems have a moderate level of sensitivity and a high level of specificity: Dopplex ability sensitivity 20% - 70%, specificity 86% - 96%; MESI sensitivity 57% - 74%, specificity 85% - 99%; BlueDop sensitivity 95%, specificity 89%; and Systoe sensitivity 71%, specificity 77%. Clinical evaluation by screening staff identified a preference for the MESI system. The consensus conference concluded that the MESI device was a good candidate for use in a community PAD screening programme. CONCLUSION: The MESI system is a good candidate to consider for community PAD screening.
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Tobillo , Enfermedad Arterial Periférica , Humanos , Índice Tobillo Braquial , Enfermedad Arterial Periférica/diagnóstico , Dedos del PieRESUMEN
In this paper, we have developed a 'phosphine-free' method for synthesising copper telluride nanocrystals using diphenyl ditelluride as an air-stable tellurium source. The diphenyl ditelluride is shown to have optimal reactivity for the colloidal synthesis of Cu2Te, allowing optimal control over the phase and morphology. Using this unexplored Te precursor for copper telluride synthesis, 1D nanorods of hexagonal phase (Cu2Te) were synthesised at a moderate temperature of 180 °C. The precise control over key parameters for this system results in Cu2-xTe nanocrystals forming with varied shapes (1D nanorods and 2D nanoplates), sizes, and crystal phases (hexagonal Cu2Te and orthorhombic Cu1.43Te).
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PURPOSE: Women of reproductive age who carry fragile X premutation (PM) alleles have 56 to 200 CGG repeats in the 5'-untranslated region of FMR1 gene are at increased risk for producing children with intellectual disabilities (ID) or autism spectrum disorders (ASD) due to expansion of PM alleles to full mutation alleles (> 200 repeats) during maternal transmission. METHODS: In present study fragile X PM carrier screening was performed in total 808 women who were consulting primary health care centers for preconception care in Khyber Pakhtunkhwa region of Pakistan between April, 2018 and December, 2020. Polymerase chain reaction (PCR) was performed for detection of PM carrier women and the CGG repeats number was confirmed by Southern blotting and capillary electrophoresis. RESULTS: The prevalence rate for PM carriers among preconception women was found to be 0.7% that was contributed by 0.5% women in risk group (RG1) with family history of ID and 0.2% in risk group 2 (RG2) with family history of ASD. PM carrier women had at least one affected child or sibling. In addition, the preconception women with FMR1 PM alleles were found to be at increased risk for primary ovary insufficiency (RG1: P = 0.0265, RG2: P = 0.0389), postpartum depression (RG1: P = 0.0240, RG2: P = 0.0501) and neuropsychiatric disorders (RG1: P = 0.0389, RG2: P = 0.0432). CONCLUSIONS: Current study provides first evidence of fragile X PM carrier screening in Pakistani preconception women in primary care consultation. Findings of current study may help to improve preconception care and to reduce burden of fragile X associated disorders in our population.
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Proteína de la Discapacidad Intelectual del Síndrome del Cromosoma X Frágil , Síndrome del Cromosoma X Frágil , Niño , Femenino , Proteína de la Discapacidad Intelectual del Síndrome del Cromosoma X Frágil/genética , Síndrome del Cromosoma X Frágil/diagnóstico , Síndrome del Cromosoma X Frágil/epidemiología , Síndrome del Cromosoma X Frágil/genética , Humanos , Masculino , Mutación , Pakistán , Atención Primaria de Salud , Derivación y ConsultaRESUMEN
BACKGROUND: Cardiovascular disease is a major contributor to poor health in the UK and the leading cause of death in England. Peripheral arterial disease and high blood pressure are conditions that identify individuals at high cardiovascular disease risk, likely to benefit from cardiovascular risk management. Both conditions remain considerably underdiagnosed and untreated. The National Health Service abdominal aortic aneurysm (AAA) screening programmes represent an opportunity to screen for these conditions with potentially minimal additional effort or cost. We explored AAA screening programme staff views on the proposed introduction of such additional screening within AAA screening. METHODS: Nine focus groups and seven follow-on interviews were undertaken with 38 AAA screening staff. Our study methods were oriented broadly towards a grounded theory methodology, and data were analysed using thematic analysis. RESULTS: Three themes were identified: (i) 'Perceptions of patient experience and health-related outcomes', (ii) 'Opportunities and challenges for programme staff', and (iii) 'Maintaining and improving programme standards'. Staff talked about the high uptake of AAA screening, staff experience and skills in their role, and the programme's high quality standards as both opportunities and potential challenges linked to the proposed additions to AAA screening. While positive about the potential to improve patients' health outcomes, participants had questions about the practicalities of incorporating additional procedures within their time- and resource-constrained context, and how this may reconfigure work processes, roles and relationships. CONCLUSIONS: The proposed additions to the programme require taking staff's views into account. Key areas that need to be addressed relate to ensuring follow-up support for patients, clarity around staff responsibilities, and availability of sufficient resources for the programme.
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Aneurisma de la Aorta Abdominal , Enfermedades Cardiovasculares , Aneurisma de la Aorta Abdominal/diagnóstico , Aneurisma de la Aorta Abdominal/prevención & control , Humanos , Investigación Cualitativa , Medicina Estatal , Reino UnidoRESUMEN
Humans are variously and continuously exposed to a wide range of different DNA-damaging agents, some of which are classed as carcinogens. DNA damage can arise from exposure to exogenous agents, but damage from endogenous processes is probably far more prevalent. That said, epidemiological studies of migrant populations from regions of low cancer risk to high cancer risk countries point to a role for environmental and/or lifestyle factors playing a pivotal part in cancer aetiology. One might reasonably surmise from this that carcinogens found in our environment or diet are culpable. Exposure to carcinogens is associated with various forms of DNA damage such as single-stand breaks, double-strand breaks, covalently bound chemical DNA adducts, oxidative-induced lesions and DNA-DNA or DNA-protein cross-links. This review predominantly concentrates on DNA damage induced by the following carcinogens: polycyclic aromatic hydrocarbons, heterocyclic aromatic amines, mycotoxins, ultraviolet light, ionising radiation, aristolochic acid, nitrosamines and particulate matter. Additionally, we allude to some of the cancer types where there is molecular epidemiological evidence that these agents are aetiological risk factors. The complex role that carcinogens play in the pathophysiology of cancer development remains obscure, but DNA damage remains pivotal to this process.
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Carcinógenos/química , Daño del ADN , Hidrocarburos Policíclicos Aromáticos/efectos adversos , Aminas/efectos adversos , Animales , Ácidos Aristolóquicos/efectos adversos , Benzo(a)pireno/efectos adversos , Reactivos de Enlaces Cruzados/química , ADN , Reparación del ADN , Dieta , Femenino , Humanos , Inflamación , Neoplasias Pulmonares/inducido químicamente , Neoplasias Pulmonares/genética , Masculino , Neoplasias/inducido químicamente , Neoplasias/genética , Estrés Oxidativo , Neoplasias de la Próstata/inducido químicamente , Neoplasias de la Próstata/genética , Fumar/efectos adversos , Rayos Ultravioleta/efectos adversos , Neoplasias de la Vejiga Urinaria/inducido químicamente , Neoplasias de la Vejiga Urinaria/genéticaRESUMEN
INTRODUCTION: care home residents have high healthcare needs not fully met by prevailing healthcare models. This study explored how healthcare configuration influences resource use. METHODS: a realist evaluation using qualitative and quantitative data from case studies of three UK health and social care economies selected for differing patterns of healthcare delivery to care homes. Four homes per area (12 in total) were recruited. A total of 239 residents were followed for 12 months to record resource-use. Overall, 181 participants completed 116 interviews and 13 focus groups including residents, relatives, care home staff, community nurses, allied health professionals and General Practitioners. RESULTS: context-mechanism-outcome configurations were identified explaining what supported effective working between healthcare services and care home staff: (i) investment in care home-specific work that legitimises and values work with care homes; (ii) relational working which over time builds trust between practitioners; (iii) care which 'wraps around' care homes; and (iv) access to specialist care for older people with dementia. Resource use was similar between sites despite differing approaches to healthcare. There was greater utilisation of GP resource where this was specifically commissioned but no difference in costs between sites. CONCLUSION: activities generating opportunities and an interest in healthcare and care home staff working together are integral to optimal healthcare provision in care homes. Outcomes are likely to be better where: focus and activities legitimise ongoing contact between healthcare staff and care homes at an institutional level; link with a wider system of healthcare; and provide access to dementia-specific expertise.
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Actitud del Personal de Salud , Prestación Integrada de Atención de Salud/normas , Conocimientos, Actitudes y Práctica en Salud , Personal de Salud/normas , Servicios de Salud para Ancianos/normas , Hogares para Ancianos/normas , Casas de Salud/normas , Mejoramiento de la Calidad/normas , Indicadores de Calidad de la Atención de Salud/normas , Personal de Salud/psicología , Humanos , Grupo de Atención al Paciente/normas , Investigación Cualitativa , Medicina Estatal/normas , Reino UnidoRESUMEN
BACKGROUND: Care home residents in England have variable access to health care services. There is currently no coherent policy or consensus about the best arrangements to meet these needs. The purpose of this review was to explore the evidence for how different service delivery models for care home residents support and/or improve wellbeing and health-related outcomes in older people living and dying in care homes. METHODS: We conceptualised models of health care provision to care homes as complex interventions. We used a realist review approach to develop a preliminary understanding of what supported good health care provision to care homes. We completed a scoping of the literature and interviewed National Health Service and Local Authority commissioners, providers of services to care homes, representatives from the Regulator, care home managers, residents and their families. We used these data to develop theoretical propositions to be tested in the literature to explain why an intervention may be effective in some situations and not others. We searched electronic databases and related grey literature. Finally the findings were reviewed with an external advisory group. RESULTS: Strategies that support and sustain relational working between care home staff and visiting health care professionals explained the observed differences in how health care interventions were accepted and embedded into care home practice. Actions that encouraged visiting health care professionals and care home staff jointly to identify, plan and implement care home appropriate protocols for care, when supported by ongoing facilitation from visiting clinicians, were important. Contextual factors such as financial incentives or sanctions, agreed protocols, clinical expertise and structured approaches to assessment and care planning could support relational working to occur, but of themselves appeared insufficient to achieve change. CONCLUSION: How relational working is structured between health and care home staff is key to whether health service interventions achieve health related outcomes for residents and their respective organisations. The belief that either paying clinicians to do more in care homes and/or investing in training of care home staff is sufficient for better outcomes was not supported.
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Hogares para Ancianos , Calidad de la Atención de Salud , Cuidado Terminal , Anciano , Inglaterra , Enfermería Geriátrica , Accesibilidad a los Servicios de Salud , Humanos , Programas Nacionales de Salud , Planificación de Atención al PacienteRESUMEN
OBJECTIVE: Studies indicate a limited understanding of dementia and its associated symptoms, causes and consequences among South Asian older adults. As a consequence, fewer people from this ethnic group receive a diagnosis of dementia. The aim of this study was to adapt the previously designed Barts Explanatory Model Inventory Checklist (BEMI-C), a tool designed to elicit perceptions of mental illness from people with different cultural backgrounds, for use with people with dementia in the South Asian population. METHOD: Both a literature review and 25 qualitative interviews were conducted to find themes and perceptions that are relevant to the South Asian culture in recognising and dealing with symptoms of dementia. The emergent themes and perceptions were then added to the BEMI-C through synthesis of findings. RESULTS: The initial four checklists of symptoms, causes, consequences and treatments from the BEMI-C were retained in the new BEMI-Dementia (BEMI-D) and expanded with six additional themes, including 123 new perceptions relevant to the understanding of dementia. All new themes emerged from the qualitative interviews, some of which were also found in the literature. CONCLUSION: Given the national priority of improving dementia awareness and timely diagnosis, the BEMI-D can serve as a useful tool, in research and perhaps practice, to assess the barriers to dementia service uptake in this population and their understandings of dementia. Based on the detailed methodological description of the adaptation of the BEMI-C, this paper further suggests how this tool can be adapted to suit other ethnic minority groups.
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Demencia/etnología , Conocimientos, Actitudes y Práctica en Salud/etnología , Grupos Minoritarios , Psicometría/instrumentación , Encuestas y Cuestionarios/normas , Adulto , Lista de Verificación/normas , Femenino , Humanos , India/etnología , Masculino , Pakistán/etnología , Reino Unido/etnologíaRESUMEN
OBJECTIVE: With increasing international migration, mental health care of migrants and ethnic minorities is a public health priority. South Asian older adults experience difficulties in accessing services for memory impairment, dementia and mental illness. This review examines barriers and facilitators in the pathway to culturally appropriate mental health care. METHODS: Web of Knowledge, Pubmed and Ovid databases were searched for literature on South Asian older adults or their family carers, their understandings of mental illness and dementia and their pattern of service use. Dates were from 1984 to 2012. Abstracts were assessed for relevance, followed by detailed reading of salient papers. Three researchers rated the quality of each included study. A narrative synthesis was undertaken of extracted and charted data. RESULTS: Eighteen studies met the eligibility criteria for the review. South Asians and health professionals highlighted several difficulties which deterred help seeking and access to care: a lack of knowledge of dementia and mental illness, and of local services; stigma; culturally preferred coping strategies; and linguistic and cultural barriers in communication and decision making. CONCLUSIONS: To improve access for these groups, service users and providers need to be better informed; services need to be more culturally tailored, sometimes employing staff with similar cultural backgrounds; and health professionals can benefit from dementia education and knowledge of local services. These factors are key to the delivery of the National Dementia Strategy in England.
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Asistencia Sanitaria Culturalmente Competente , Demencia/terapia , Accesibilidad a los Servicios de Salud , Anciano , Asia Occidental/etnología , Inglaterra , Conocimientos, Actitudes y Práctica en Salud , Humanos , Servicios de Salud Mental/estadística & datos numéricos , Grupos Minoritarios , Aceptación de la Atención de Salud , GalesRESUMEN
Antimony has a high theoretical capacity and suitable alloying/dealloying potentials to make it a future anode for potassium-ion batteries (PIBs); however, substantial volumetric changes, severe pulverization, and active mass delamination from the Cu foil during potassiation/depotassiation need to be overcome. Herein, we present the use of electrophoretic deposition (EPD) to fabricate binder-free electrodes consisting of Sb nanoparticles (NPs) embedded in interconnected multiwalled carbon nanotubes (MWCNTs). The anode architecture allows volume changes to be accommodated and prevents Sb delamination within the binder-free electrodes. The Sb mass ratio of the Sb/CNT nanocomposites was varied, with the optimized Sb/CNT nanocomposite delivering a high reversible capacity of 341.30 mA h g-1 (â¼90% of the initial charge capacity) after 300 cycles at C/5 and 185.69 mA h g-1 after 300 cycles at 1C. Postcycling investigations reveal that the stable performance is due to the unique Sb/CNT nanocomposite structure, which can be retained over extended cycling, protecting Sb NPs from volume changes and retaining the integrity of the electrode. Our findings not only suggest a facile fabrication method for high-performance alloy-based anodes in PIBs but also encourage the development of alloying-based anodes for next-generation PIBs.
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Solution-based synthesis of mixed ionic and electronic conductors (MIECs) has enabled the development of novel inorganic materials with implications for a wide range of energy storage applications. However, many technologically relevant MIECs contain toxic elements (Pb) or are prepared by using traditional high-temperature solid-state synthesis. Here, we provide a simple, low-temperature and size-tunable (50-90 nm) colloidal hot injection approach for the synthesis of NaSbS2 based MIECs using widely available and non-toxic precursors. Key synthetic parameters (cationic precursor, reaction temperature, and ligand) are examined to regulate the shape and size of the NaSbS2 nanocrystals (NCs). FTIR studies revealed that ligands with carboxylate functionality are coordinated to the surface of the synthesized NaSbS2 NCs. The synthesized NaSbS2 nanocrystals have electronic and ionic conductivities of 3.31 × 10-10 (e-) and 1.9 × 10-5 (Na+) S cm-1 respectively, which are competitive with the ionic and electrical conductivities of perovskite materials generated by solid-state reactions. This research gives a mechanistic understanding and post-synthetic evaluation of parameters influencing the formation of sodium antimony chalcogenides materials.
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Chronic, non-healing wounds constitute a major health problem, and the current therapeutic options are limited. Therefore, pharmaceuticals that can be locally applied to complicated wounds are urgently needed. Such treatments should directly target the underlying causes, which include diabetes mellitus, chronic local pressure and/or vascular insufficiency. A common consequence of these disorders is impaired wound angiogenesis. Here, we investigated the effect of topical application of a nitric oxide-releasing phosphodiesterase 5 inhibitor (TOP-N53)-containing liquid hydrogel on wound repair in mice. The drug-loaded hydrogel promoted re-epithelialization and angiogenesis in wounds of healthy and healing-impaired diabetic mice. Using a non-invasive label-free optoacoustic microscopy approach combined with automated vessel analysis, we show that the topical application of TOP-N53 formulation increases the microvascular network density and promotes the functionality of the newly formed blood vessels, resulting in enhanced blood perfusion of the wounds. These results demonstrate a remarkable healing-stimulating activity of topically applied TOP-N53 formulation, supporting its further development as a wound therapeutic.
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The solution-based colloidal synthesis of multinary semiconductor compositions has allowed the design of new inorganic materials impacting a large variety of applications. Yet there are certain compositions that have remained elusive-particularly quaternary structures of transition metal-based (e.g., Co, Zn, Ni, Fe, Mn, and Cr) copper antimony chalcogenides. These are widely sought for tuning the electrical and thermal conductivity as a function of the size, composition, and crystal phase. In this work, a facile hot injection approach for the synthesis of three different tetrahedrite-substituted nanocrystals (NCs) (Cu10Zn2Sb4S13, Cu10Co2Sb4S13, and Cu10Ni1.5Sb4S13) and their growth mechanisms are investigated. We reveal that the interplay between the Zn, Ni, and Co precursors on the basis of thiophilicity is key to obtaining pure phase NCs with controlled size and shape. While all of the synthesized crystal phases display outstanding low thermal conductivity, the Cu10.5Sb4Ni1.5S13 system shows the most enhanced electrical conductivity compared to Cu10Zn2Sb4S13 and Cu10Co2Sb4S13. This study highlights an effective synthesis strategy for the growth of complex quaternary nanocrystals and their high potential for application in thermoelectrics.
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Cancer-associated fibroblasts (CAF) are key regulators of tumorigenesis. Further insights into the tumor-promoting mechanisms of action of CAFs could help improve cancer diagnosis and treatment. Here we show that the formin mDia2 regulates the positioning and function of mitochondria in dermal fibroblasts, thereby promoting a protumorigenic CAF phenotype. Mechanistically, mDia2 stabilized the mitochondrial trafficking protein MIRO1. Loss of mDia2 or MIRO1 in fibroblasts or CAFs reduced the presence of mitochondria and ATP levels near the plasma membrane and at CAF-tumor cell contact sites, caused metabolic alterations characteristic of mitochondrial dysfunction, and suppressed the secretion of protumorigenic proteins. In mouse models of squamous carcinogenesis, genetic or pharmacologic inhibition of mDia2, MIRO1, or their common upstream regulator activin A inhibited tumor formation. Consistently, co-upregulation of mDia2 and MIRO1 in the stroma of various human cancers negatively correlated with survival. This work unveils a key role of mitochondria in the protumorigenic CAF phenotype and identifies an activin A-mDia2-MIRO1 signaling axis in CAFs with diagnostic and therapeutic potential. SIGNIFICANCE: Inhibition of mDia2/MIRO1-mediated mitochondrial positioning in CAFs induces mitochondrial dysfunction and suppresses tumor growth, revealing a promising therapeutic strategy to target tumor-stroma cross-talk.
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Fibroblastos Asociados al Cáncer , Animales , Humanos , Ratones , Adenosina Trifosfato/metabolismo , Fibroblastos Asociados al Cáncer/metabolismo , Carcinogénesis/patología , Fibroblastos/metabolismo , Forminas , Mitocondrias/fisiología , Membranas MitocondrialesRESUMEN
BACKGROUND AND OBJECTIVES: Understanding the influences of marginalized cultural and social identities as experienced by the African Caribbean diaspora within the context of dementia care is essential to minimize the gaps in current practice and policy in the health care setting. This study explores the impact of marginalized identities upon the meaning-making process, access to services and experience of care provisions through a scoping review and consultancy exercises with key stakeholders. RESEARCH DESIGN: Fourteen databases were searched using key terms. Primary studies in English, any year, study design, and country of origin were eligible. Titles, abstracts, and full texts were screened for inclusion and data were extracted in stages. Thematic analysis was performed and the findings were discussed in a series of consultation meetings with people with dementia, carers, and health care professionals in Manchester (United Kingdom) and Jamaica. RESULTS: The scoping review retrieved n = 1,989 research articles. Nineteen were included, most were qualitative (n = 14), 3 quantitative, and 2 mixed-method. The findings revealed limited insight into cultural and multiple individual identities in explaining conceptualization and service access. Consultation meetings confirmed these findings and highlighted differences in health care services and systems in the United Kingdom and Jamaica. DISCUSSION AND IMPLICATIONS: This study suggests there is a complex interaction of sociocultural processes that marginalize African Caribbean persons in and across various national settings within the context of dementia care. The study highlights the importance of acknowledging and addressing how prevalent racialized- and class-based divides and related marginalized social locations are reflected in inequities in access to and use of dementia services.
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Demencia , Derivación y Consulta , Región del Caribe , Demencia/terapia , Migración Humana , Humanos , Reino UnidoRESUMEN
In this study, the binding tendency of bisnitrophenoxy compounds (BN) having different methylene (-CH2-)n spacer groups (n = 8-11) with fish sperm double stranded deoxyribonucleic acid (dsDNA) was explored. Cyclic voltammetry (CV) was used to evaluate various kinetic and binding parameters (Ks,h, Do, K b and binding site sizes). Performed electrochemical studies designated strong contact of these symmetric molecules with dsDNA in threading intercalation mode of binding. The number (n) of methylene spacer group in the molecular structure of bisnitrophenoxy compounds, e.g., BN-8 (1-nitro-4-(8-(4-nitrophenoxy)octyloxy)benzene, was observed to have a strong influence on their binding affinity. Decreased peak current values and positively shifted peak potentials recorded via cyclic voltammetry clearly depicted that bisnitrophenoxy compounds can intercalate with dsDNA. Results demonstrated the following order of binding constants; K b (M-1): BN-8 (2.32 × 104) < BN-9 (5.73 × 104) < BN-10 (8.97 × 104) < BN-11 (17.34 × 104). The order of increasing binding sites from BN-8 (0.13) to BN-11 (1.38), revealed the maximum threading intercalation strength by bisnitrophenoxy compound having the longest methylene spacer (n = 11). Thermodynamic studies augmented the strong binding of BN-11 with dsDNA as compared to BN-8 because of the long-chain, -CH2- spacer in its structure. The spontaneity of dsDNA-binding was revealed by the negative ΔG values for interaction of all the compounds. Moreover, binding parameters from thermodynamic and kinetic studies also corresponded to the threading intercalation mode of interaction, which itself points to the potency of the envisioned drug-like molecules.
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OBJECTIVES: Comprehensive geriatric assessment (CGA) may be a way to deliver optimal care for care home residents. We used realist review to develop a theory-driven account of how CGA works in care homes. DESIGN: Realist review. SETTING: Care homes. METHODS: The review had three stages: first, interviews with expert stakeholders and scoping of the literature to develop programme theories for CGA; second, iterative searches with structured retrieval and extraction of the literature; third, synthesis to refine the programme theory of how CGA works in care homes.We used the following databases: Medline, CINAHL, Scopus, PsychInfo, PubMed, Google Scholar, Greylit, Cochrane Library and Joanna Briggs Institute. RESULTS: 130 articles informed a programme theory which suggested CGA had three main components: structured comprehensive assessment, developing a care plan and working towards patient-centred goals. Each of these required engagement of a multidisciplinary team (MDT). Most evidence was available around assessment, with tension between structured assessment led by a single professional and less structured assessment involving multiple members of an MDT. Care planning needed to accommodate visiting clinicians and there was evidence that a core MDT often used care planning as a mechanism to seek external specialist support. Goal-setting processes were not always sufficiently patient-centred and did not always accommodate the views of care home staff. Studies reported improved outcomes from CGA affecting resident satisfaction, prescribing, healthcare resource use and objective measures of quality of care. CONCLUSION: The programme theory described here provides a framework for understanding how CGA could be effective in care homes. It will be of use to teams developing, implementing or auditing CGA in care homes. All three components are required to make CGA work-this may explain why attempts to implement CGA by interventions focused solely on assessment or care planning have failed in some long-term care settings. TRIAL REGISTRATION NUMBER: CRD42017062601.
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Evaluación Geriátrica/métodos , Hogares para Ancianos/organización & administración , Casas de Salud/organización & administración , Anciano , Humanos , Atención Dirigida al Paciente/métodos , Reino UnidoRESUMEN
INTRODUCTION: Care home residents are relatively high users of healthcare resources and may have complex needs. Comprehensive geriatric assessment (CGA) may benefit care home residents and improve efficiency of care delivery. This is an approach to care in which there is a thorough multidisciplinary assessment (physical and mental health, functioning and physical and social environments) and a care plan based on this assessment, usually delivered by a multidisciplinary team. The CGA process is known to improve outcomes for community-dwelling older people and those in receipt of hospital care, but less is known about its efficacy in care home residents. METHODS AND ANALYSIS: Realist review was selected as the most appropriate method to explore the complex nature of the care home setting and multidisciplinary delivery of care. The aim of the realist review is to identify and characterise a programme theory that underpins the CGA intervention. The realist review will extract data from research articles which describe the causal mechanisms through which the practice of CGA generates outcomes. The focus of the intervention is care homes, and the outcomes of interest are health-related quality of life and satisfaction with services; for both residents and staff. Further outcomes may include appropriate use of National Health Service services and resources of older care home residents. The review will proceed through three stages: (1) identifying the candidate programme theories that underpin CGA through interviews with key stakeholders, systematic search of the peer-reviewed and non-peer-reviewed evidence, (2) identifying the evidence relevant to CGA in UK care homes and refining the programme theories through refining and iterating the systematic search, lateral searches and seeking further information from study authors and (3) analysis and synthesis of evidence, involving the testing of the programme theories. ETHICS AND DISSEMINATION: The PEACH project was identified as service development following submission to the UK Health Research Authority and subsequent review by the University of Nottingham Research Ethics Committee. The study protocols have been reviewed as part of good governance by the Nottinghamshire Healthcare Foundation Trust. We aim to publish this realist review in a peer-reviewed journal with international readership. We will disseminate findings to public and stakeholders using knowledge mobilisation techniques. Stakeholders will include the Quality Improvement Collaboratives within PEACH study. National networks, such as British Society of Gerontology and National Care Association will be approached for wider dissemination. TRIAL REGISTRATION NUMBER: The realist review has been registered on International Prospective Register of Systematic Reviews (PROSPERO 2017: CRD42017062601).