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1.
N Z Med J ; 136(1586): 73-83, 2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-38033242

RESUMO

AIM: Mate wareware (dementia) presents a significant social and economic burden for Maori in Aotearoa New Zealand. Previous literature has highlighted the need to improve health literacy for Maori regarding the causes and management of mate wareware, yet there is a lack of Maori-centred educational resources. It was determined that a mobile phone application (app) could meet this need and that early consultation with Maori was required to ensure the digital solution would be culturally safe and relevant. METHOD: This study explored the perspectives of kaumatua (Maori elders) regarding how to cater the mate wareware mobile app to Maori. Through a qualitative approach based on Kaupapa Maori principles, two focus groups were held with 15 kaumatua. Focus group data were thematically analysed. RESULTS: The analysis identified four themes related to the content of the proposed app and its design features. "Information about mate wareware" and "Caregiver support" were prominent themes that kaumatua prioritised for inclusion in the proposed app. To ensure uptake, kaumatua emphasised that the "Access" and "Appeal" of the proposed app should be considered. CONCLUSION: The findings have informed the design of the Mate Wareware app and should be considered when developing other digital health interventions for Maori.


Assuntos
Demência , Aplicativos Móveis , Humanos , Povo Maori , Havaiano Nativo ou Outro Ilhéu do Pacífico , Nova Zelândia
2.
N Z Med J ; 136(1582): 64-86, 2023 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-37708487

RESUMO

AIMS: Routinely collected health data can provide rich information for research and epidemiological monitoring of different diseases, but using the data presents many challenges. This study aims to explore the attitudes and preferences of people aged 55 and over regarding the use of their de-identified health data, and their concerns and comfort in different scenarios. METHODS: An anonymous online survey was conducted with people aged 55 and over currently engaged with health services in a New Zealand health district during June-October 2022. The survey could be completed online or by telephone and was available in eight languages. RESULTS: Seventy-nine percent of respondents knew that their health information was currently being used in the ways described in the scenarios, and between 80-87% felt comfortable or very comfortable with their data being used as described in the scenarios. In contrast, 4% (n=9) felt "uncomfortable" or "very uncomfortable" across all of the scenarios. Participants expressed concerns about data accuracy, privacy and confidentiality, security, transparency of use, consent, feedback and the risk of data being sold to commercial companies. Some participants identified situations where permission should be required to link data, including being used by people other than health professionals, containing sensitive health issues, or being used for commercial purposes. CONCLUSION: This study finds general support from patients for the use of their routinely collected data for secondary purposes as long as its use will benefit the population from which the data are taken. It also highlights the necessity of including the perspectives of different cultures in the collection, storage, use and analysis of health information, particularly concerning Maori cultural considerations.


Assuntos
Conhecimentos, Atitudes e Prática em Saúde , Povo Maori , Preferência do Paciente , Humanos , Atitude , Atenção à Saúde , Nova Zelândia
3.
N Z Med J ; 136(1580): 48-61, 2023 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-37536311

RESUMO

AIMS: Diabetes-related dementia (DRD) is a new dementia subtype associated with type 2 diabetes mellitus, first described in 2013. This study investigated data from a local New Zealand memory service to identify patients that met the criteria for DRD. METHODS: Using routinely collected data from 2013-2021, we selected a sample of people with dementia, diabetes, and no CT evidence of Alzheimer's disease (AD), vascular dementia, or frontotemporal dementia. We compared their socio-demographic, clinical, and cognitive characteristics with a sample of patients with diabetes and Alzheimer's disease. RESULTS: Forty (16%) of 249 patients with diabetes and dementia had "normal" CT scans (DRD subgroup), and 38 (15%) had AD (AD subgroup). Compared to NZ Europeans, disproportionally more Maori and Pacific Islanders (70.2%) were in the DRD subgroup. In the Pacific subgroup (n=31), the DRD subgroup had higher memory subscores than the AD subgroup (p=0.047), and the Kaplan-Meier plot suggested poorer survival (p=0.13). Maori patients with diabetes and dementia were more likely to meet all four criteria for DRD. CONCLUSION: We have replicated the findings of the 2013 DRD research and have demonstrated a higher risk for the DRD subtype of dementia among the Maori and Pacific Islander patients in our sample.


Assuntos
Demência , Diabetes Mellitus Tipo 2 , Humanos , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/epidemiologia , Povo Maori , Nova Zelândia/epidemiologia , Dados de Saúde Coletados Rotineiramente , Demência/epidemiologia , Demência/etiologia
4.
Dementia (London) ; : 14713012231173012, 2023 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-37137731

RESUMO

INTRODUCTION: Recent estimations have projected a threefold increase in dementia prevalence in Aotearoa New Zealand (NZ) by 2050, particularly in Maori and Pacific peoples. However, to date, there are no national data on dementia prevalence, and overseas data are used to estimate the NZ dementia statistics. The aim of this feasibility study was to prepare the groundwork for the first full-scale NZ dementia prevalence study that is representative of Maori, European, Pacific and Asian peoples living in NZ. METHODS: The main feasibility issues were: (i) Sampling to ensure adequate community representation from the included ethnic groups, (ii) Preparing a workforce to conduct the fieldwork and developing quality control, (iii) Raising awareness of the study in the communities (iv) Maximizing recruitment by door-knocking, (v) Retaining those we have recruited to the study and (vi) Acceptability of study recruitment and assessment using adapted versions of the 10/66 dementia protocol in different ethnic groups living in South Auckland. RESULTS: We found that a probability sampling strategy using NZ Census data was reasonably accurate and all ethnic groups were sampled effectively. We demonstrated that we were able to train up a multi-ethnic workforce consisting of lay interviewers who were able to administer the 10/66 dementia protocol in community settings. The response rate (224/297, 75.5%) at the door-knocking stage was good but attrition at subsequent stages was high and only 75/297 (25.2%) received the full interview. CONCLUSIONS: Our study showed that it would be feasible to conduct a population-based dementia prevalence study using the 10/66 dementia protocol in Maori, European and Asian communities living in NZ, utilizing a qualified, skilled research team representative of the families participating in the study. The study has demonstrated that for recruitment and interviewing in Pacific communities a different but culturally appropriate approach is required.

5.
N Z Med J ; 135(1548): 42-53, 2022 01 21.
Artigo em Inglês | MEDLINE | ID: mdl-35728129

RESUMO

AIMS: Dementia is an important health concern for Maori and therefore it is essential to explore the extent and impact of dementia in this community. The 10/66 dementia protocol, a widely used research tool for measuring the prevalence of dementia, was developed to minimise cultural and educational bias in comparisons of dementia prevalence across different countries and/or cultures. The aims of this study are to (i) adapt the 10/66 dementia protocol for use in research within the Maori community and (ii) test the diagnostic accuracy of the adapted (ie, Maori-friendly) 10/66 dementia protocol against the reference standard of a clinical diagnosis of dementia (or no dementia). METHOD: The sample included Maori aged 65 and over who had been assessed at a local memory service. Ten dementia cases and 10 controls were included. The sample was further enriched by the inclusion of 6 controls from a concurrent dementia-prevalence feasibility study in the local community. The Maori-friendly 10/66 dementia protocol was measured against the reference standard. Sensitivity, specificity, positive and negative predictive values and Youden's Index were calculated. RESULTS: The Maori-friendly 10/66 dementia protocol had a sensitivity of 90.0% (95% CI 62.8-99.4), specificity of 93.8% (95% CI 75.3-99.6), positive predictive value of 90.0% (95% CI 62.8-99.4), negative predictive value of 93.8% (95% CI 75.3-99.6) and Youden's Index of 0.83. CONCLUSIONS: Our study results provide preliminary evidence that the Maori-friendly 10/66 dementia protocol has adequate discriminatory abilities for the diagnosis of dementia. Our study also demonstrates that the Maori-friendly 10/66 dementia protocol has the potential to be used in a dementia-population-based study for Maori in Aotearoa New Zealand.


Assuntos
Demência , Havaiano Nativo ou Outro Ilhéu do Pacífico , Idoso , Estudos de Coortes , Demência/diagnóstico , Demência/epidemiologia , Humanos , Nova Zelândia/epidemiologia
6.
Artigo em Inglês | MEDLINE | ID: mdl-35162453

RESUMO

Currently, there are estimated to be 70,000 people living with dementia in Aotearoa, New Zealand (NZ). This figure is projected to more than double by 2040, but due to the more rapid growth of older age groups in non-European populations, prevalence will at least triple amongst the NZ Indian population. The impact of dementia in the NZ Indian community is currently unknown. The aim of this study was to explore the lived experiences of NZ Indians living with dementia and their caregivers. Ten caregivers (age range: 41-81) and five people living with mild dementia (age range: 65-77) were recruited from a hospital memory service and two not-for-profit community organisations in Auckland, Aotearoa, NZ. Semi-structured interviews were conducted by bilingual/bicultural researchers and transcribed for thematic analysis in the original languages. Dementia was predominantly thought of as being part of normal ageing. Getting a timely diagnosis was reported as difficult, with long waiting times. Cultural practices and religion played a large part in how both the diagnosis and ongoing care were managed. Caregivers expressed concerns about societal stigma and about managing their own health issues, but the majority also expressed a sense of duty in caring for their loved ones. Services were generally well-received, but gaps were identified in the provision of culturally appropriate services. Future health services should prioritise a timely diagnosis, and dementia care services should consider specific cultural needs to maximise uptake and benefit for Indian families living with dementia.


Assuntos
Cuidadores , Demência , Adulto , Idoso , Idoso de 80 Anos ou mais , Demência/diagnóstico , Serviços de Saúde , Humanos , Pessoa de Meia-Idade , Nova Zelândia/epidemiologia , Pesquisa Qualitativa
7.
Artigo em Inglês | MEDLINE | ID: mdl-35162305

RESUMO

Little is known about the lived experience of dementia in the New Zealand Chinese community. This study aims to explore the understanding and experiences of living with dementia in Chinese New Zealanders. Participants were recruited from a memory service and a community dementia day programme. In-depth interviews were conducted by bilingual and bicultural researchers. The recorded interviews were transcribed and thematically analysed. Sixteen people living with dementia and family carers participated in this study. The first theme revealed the lack of understanding of dementia prior to diagnosis, the commonly used term of "brain shrinkage" and that dementia is associated with getting older. The second theme covered the symptoms experienced by people with dementia and how family carers found anhedonia and apathy particularly concerning. The third theme highlighted the tension between cultural obligation and carer stress. The fourth theme is about the stigma attached to dementia. Our results provide some insight into ways to improve dementia care for Chinese New Zealanders, including targeted psychoeducation in the Chinese community to improve awareness and to reduce stigma, access to person-centred interventions, and learning about strategies for healthy ageing to live well with dementia, and emotional support and psychoeducation for family carers to reduce carer stress.


Assuntos
Demência , Cuidadores , China/epidemiologia , Demência/diagnóstico , Humanos , Nova Zelândia/epidemiologia , Grupos Raciais
8.
Artigo em Inglês | MEDLINE | ID: mdl-34063626

RESUMO

The 10/66 dementia protocol was developed as a language and culture-fair instrument to estimate the prevalence of dementia in non-English speaking communities. The aim of this study was to validate the 10/66 dementia protocol in elders of Indian ethnicity born in the Fiji Islands (Fijian-Indian) living in New Zealand. To our knowledge, this is the first time a dementia diagnostic tool has been evaluated in the Fijian-Indian population in New Zealand. We translated and adapted the 10/66 dementia protocol for use in in Fijian-Indian people. Individuals (age ≥ 65) who self-identified as Fijian-Indian and had either been assessed for dementia at a local memory service (13 cases, eight controls) or had participated in a concurrent dementia prevalence feasibility study (eight controls) participated. The sensitivity, specificity, positive predictive value, and Youden's index were obtained by comparing the 10/66 diagnosis and its sub-components against the clinical diagnosis (reference standard). The 10/66 diagnosis had a sensitivity of 92.3% (95% CI 70.3-99.5), specificity of 93.8% (95% CI 75.3-99.6), positive predictive value of 92.3% (95% CI 70.3-99.5), and negative predictive value of 93.8% (95% CI 75.3-99.6). The study results show that the Fijian-Indian 10/66 dementia protocol has adequate discriminatory abilities to diagnose dementia in our sample. This instrument would be suitable for future dementia population-based studies in the Fijian-Indian population living in Aotearoa/New Zealand or the Fiji-Islands.


Assuntos
Demência , Idioma , Idoso , Demência/diagnóstico , Demência/epidemiologia , Etnicidade , Fiji/epidemiologia , Humanos , Nova Zelândia/epidemiologia
9.
BMJ Open ; 11(5): e046143, 2021 05 03.
Artigo em Inglês | MEDLINE | ID: mdl-33941631

RESUMO

INTRODUCTION: Aotearoa/New Zealand (NZ) is officially recognised as a bicultural country composed of Maori and non-Maori. Recent estimations have projected a threefold increase in dementia prevalence in NZ by 2050, with the greatest increase in non-NZ-Europeans. The NZ government will need to develop policies and plan services to meet the demands of the rapid rise in dementia cases. However, to date, there are no national data on dementia prevalence and overseas data are used to estimate the NZ dementia statistics. The overall aim of the Living with Dementia in Aotearoa study was to prepare the groundwork for a large full-scale NZ dementia prevalence study. METHODS AND ANALYSIS: The study has two phases. In phase I, we will adapt and translate the 10/66 dementia assessment protocol to be administered in Maori, Samoan, Tongan and Fijian-Indian elders. The diagnostic accuracy of the adapted 10/66 protocol will be tested in older people from these ethnic backgrounds who were assessed for dementia at a local memory service. In phase II, we will address the feasibility issues of conducting a population-based prevalence study by applying the adapted 10/66 protocol in South Auckland and will include NZ-European, Maori, Samoan, Tongan, Chinese and Fijian-Indian participants. The feasibility issues to be explored are as follows: (1) how do we sample to ensure we get accurate community representation? (2) how do we prepare a workforce to conduct the fieldwork and develop quality control? (3) how do we raise awareness of the study in the community to maximise recruitment? (4) how do we conduct door knocking to maximise recruitment? (5) how do we retain those we have recruited to remain in the study? (6) what is the acceptability of study recruitment and the 10/66 assessment process in different ethnic groups? ETHICS AND DISSEMINATION: The validity and feasibility studies were approved by the New Zealand Northern A Health and Disability Ethics Committee (numbers 17NTA234 and 18NTA176, respectively). The findings will be disseminated through peer-reviewed academic journals, national and international conferences, and public events. Data will be available on reasonable request from the corresponding author.


Assuntos
Demência , Havaiano Nativo ou Outro Ilhéu do Pacífico , Idoso , Estudos Transversais , Demência/epidemiologia , Estudos de Viabilidade , Humanos , Nova Zelândia/epidemiologia
10.
Int J Geriatr Psychiatry ; 35(5): 516-524, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-31957058

RESUMO

BACKGROUND: As the economic impact of dementia on health and social care increases, governments require disease-specific epidemiological data that will help inform spending and policy decisions. The aim of this study is to examine predictors of mortality in dementia in consecutive referrals to a New Zealand (NZ) memory service that includes Maori, Pacific Islander, and NZ European patients. METHODS: Date of birth, sex, ethnicity, living situation, cognitive function, dementia subtype, dementia severity, physical comorbidity, and medication data were collected from electronic health records. The resulting data set was linked to administrative data on mortality and last hospital contact dates to allow time-dependent survival analyses. RESULTS: The risk of death in people with dementia was increased by age (adjusted HR per year 1.08, 95%CI:1.05-1.12) and lower cognitive score at baseline (adjusted HR for severe impairment:2.54, 95% CI:1.25-5.16), and was reduced by cholinesterase inhibitors (adjusted HR:0.54, 95% CI:0.34-0.88). Compared to NZ Europeans (HR:1.19, 95% CI:0.63-2.25), antipsychotics increased the risk of death three-fold in Maori (adjusted HR:3.62, 95% CI:0.79-16.7) and Pacific Islanders (adjusted HR:2.54, 95%CI:1.10-5.85). CONCLUSIONS: Further research is required to elucidate the mechanisms underlying the survival rates in Maori and Pacific Islanders living with dementia in NZ,and their increased risk of death if antipsychotics are used.


Assuntos
Demência/mortalidade , Mortalidade/etnologia , Havaiano Nativo ou Outro Ilhéu do Pacífico/estatística & dados numéricos , População Branca/estatística & dados numéricos , Antipsicóticos/uso terapêutico , Inibidores da Colinesterase/uso terapêutico , Comorbidade , Demência/diagnóstico , Demência/tratamento farmacológico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mortalidade/tendências , Nova Zelândia/epidemiologia , Ilhas do Pacífico/etnologia
11.
Int J Geriatr Psychiatry ; 33(8): 1098-1104, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29766582

RESUMO

OBJECTIVE: Ethnicity may affect presentation to clinical services in people with dementia; however, no studies have examined this in Maori or Pacific peoples in New Zealand (NZ). Our objective was to examine the routinely collected clinical data from a memory assessment service in South Auckland to examine the presentation of dementia in the major NZ ethnic groups. METHODS: A total of 360 patients presenting to a memory service with a new diagnosis of dementia were included in this study. Demographic data (age, sex, and ethnicity) and dementia sub-type and severity were analyzed. RESULTS: There were 142 NZ European (mean age: 79.2, SD 7.4), 43 Maori (mean age: 70.2, SD 7.6), 126 Pacific (mean age: 74.3, SD 7.6), and 49 other ethnicities (mean age: 78.0, SD 8.5) presenting with a new diagnosis of dementia. After adjustment for gender and dementia subtype, Maori and Pacific patients were 8.5 and 5.3 years younger than NZ European patients (P < 0.0001). Pacific peoples tended to present with more advanced dementia (OR = 1.63, 95% CI: 0.98-2.70, P = 0.06) after adjustment for age and gender. There was little difference in the subtypes of dementia between ethnic groups. CONCLUSIONS: Maori and Pacific peoples with dementia presented to an NZ memory service at a younger age than NZ Europeans, and Pacific peoples presented with more advanced dementia. A population-based epidemiological study is critical to determine whether Maori and Pacific peoples have indeed a higher risk of developing dementia at a younger age.


Assuntos
Demência/epidemiologia , Havaiano Nativo ou Outro Ilhéu do Pacífico/estatística & dados numéricos , População Branca/estatística & dados numéricos , Idade de Início , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Vida Independente , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Nova Zelândia/epidemiologia , Prevalência , Fatores de Risco
12.
N Z Med J ; 131(1474): 20-26, 2018 05 04.
Artigo em Inglês | MEDLINE | ID: mdl-29723175

RESUMO

AIM: To describe the biopsychosocial characteristics of a series of Pacific men living in South Auckland with a history of boxing presenting with early onset dementia. We discuss the history of boxing in Pacific people and the possibility of increased risk of early onset dementia in New Zealand Pacific men compared to their European counterparts. METHOD: We reviewed the files of Pacific men with a history of amateur or professional boxing who presented to our memory and older adult mental health services with early onset dementia over a 45-month period. We gathered relevant information to construct a biopsychosocial paradigm as possible explanation of this phenomenon. RESULTS: We identified a series of eight New Zealand Pacific men with early onset dementia and with a history of boxing. Alcohol was a contributing factor in seven of the eight cases, and vascular risk factors in five. CONCLUSION: Historical, cultural and socio-economic factors underpin the attraction of some Pacific men to boxing as a sport. Given that New Zealand Pacific peoples may have an earlier onset of dementia than their European counterparts, further research is required to establish whether boxing is a contributory factor. Sports physicians should advise young New Zealand Pacific boxers about the long-term risks associated with their sport.


Assuntos
Consumo de Bebidas Alcoólicas/fisiopatologia , Consumo de Bebidas Alcoólicas/psicologia , Boxe/psicologia , Demência/fisiopatologia , Demência/psicologia , Estudos de Coortes , Demência/terapia , Humanos , Masculino , Testes de Estado Mental e Demência , Nova Zelândia , Fatores de Risco
13.
Thorax ; 73(6): 557-564, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29378859

RESUMO

INTRODUCTION: Urban homeless populations in the UK have been shown to have high rates of active tuberculosis, but less is known about the prevalence of latent tuberculosis infection (LTBI). This study aimed to estimate the prevalence of LTBI among individuals using homeless hostels in London. METHODS: We performed a cross-sectional survey with outcome follow-up in homeless hostels in London. Our primary outcome was prevalence of LTBI. Recruitment for the study took place between May 2011 and June 2013. To estimate an LTBI prevalence of 10% with 95% CIs between 8% and 13%, we required 500 participants. RESULTS: 491/804 (61.1%) individuals agreed to be screened. The prevalence of LTBI was 16.5% (81/491; 95% CI 13.2 to 19.8). In UK-born individuals, a history of incarceration was associated with increased risk of LTBI (OR 3.49; 95% CI 1.10 to 11.04; P=0.018) after adjusting for age, length of time spent homeless and illicit drug use. Of the three subjects who met English treatment guidelines for LTBI at the time of the study, none engaged with services after referral for treatment. Prevalence of past hepatitis B infection was 10.4% (51/489; 95% CI 7.7 to 13.1), and 59.5% (291/489; 95% CI 55.1 to 63.9) of individuals were non-immune. Prevalence of current hepatitis C infection was 10.4% (51/489; 95% CI 7.8 to 13.1). CONCLUSIONS: This study demonstrates the high prevalence of LTBI in homeless people in London and the associated poor engagement with care. There is a large unmet need for LTBI and hepatitis C infection treatment, and hepatitis B vaccination, in this group.


Assuntos
Infecções por HIV/epidemiologia , Hepatite B/epidemiologia , Hepatite C/epidemiologia , Pessoas Mal Alojadas , Tuberculose Latente/epidemiologia , Adulto , Estudos Transversais , Feminino , Infecções por HIV/sangue , Hepatite B/sangue , Hepatite C/sangue , Humanos , Londres/epidemiologia , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores de Risco
14.
Philos Trans R Soc Lond B Biol Sci ; 367(1602): 2656-68, 2012 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-22889914

RESUMO

The switch between the Krebs cycle and the glyoxylate bypass is controlled by isocitrate dehydrogenase kinase/phosphatase (AceK). AceK, a bifunctional enzyme, phosphorylates and dephosphorylates isocitrate dehydrogenase (IDH) with its unique active site that harbours both the kinase and ATP/ADP-dependent phosphatase activities. AceK was the first example of prokaryotic phosphorylation identified, and the recent characterization of the structures of AceK and its complex with its protein substrate, IDH, now offers a new understanding of both previous and future endeavours. AceK is structurally similar to the eukaryotic protein kinase superfamily, sharing many of the familiar catalytic and regulatory motifs, demonstrating a close evolutionary relationship. Although the active site is shared by both the kinase and phosphatase functions, the catalytic residues needed for phosphatase function are readily seen when compared with the DXDX(T/V) family of phosphatases, despite the fact that the phosphatase function of AceK is strictly ATP/ADP-dependent. Structural analysis has also allowed a detailed look at regulation and its stringent requirements for interacting with IDH.


Assuntos
Domínio Catalítico , Fosfoproteínas Fosfatases/química , Fosforilação , Proteínas Serina-Treonina Quinases/química , Monofosfato de Adenosina/química , Sequência de Aminoácidos , Ativação Enzimática , Escherichia coli/enzimologia , Escherichia coli/genética , Proteínas de Escherichia coli/química , Proteínas de Escherichia coli/genética , Regulação Enzimológica da Expressão Gênica , Interações Hidrofóbicas e Hidrofílicas , Isocitrato Desidrogenase , Dados de Sequência Molecular , Complexos Multienzimáticos/química , Complexos Multienzimáticos/genética , Fosfoproteínas Fosfatases/genética , Processamento de Proteína Pós-Traducional , Proteínas Serina-Treonina Quinases/genética , Estrutura Terciária de Proteína , Relação Estrutura-Atividade
15.
Biochemistry ; 50(38): 8103-6, 2011 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-21870819

RESUMO

Isocitrate dehydrogenase kinase/phosphatase (AceK) regulates entry into the glyoxylate bypass by reversibly phosphorylating isocitrate dehydrogenase (ICDH). On the basis of the recently determined structure of the AceK-ICDH complex from Escherichia coli, we have classified the structures of homodimeric NADP(+)-ICDHs to rationalize and predict which organisms likely contain substrates for AceK. One example is Burkholderia pseudomallei (Bp). Here we report a crystal structure of Bp-ICDH that exhibits the necessary structural elements required for AceK recognition. Kinetic analyses provided further confirmation that Bp-ICDH is a substrate for AceK. We conclude that the highly stringent AceK binding sites on ICDH are maintained only in Gram-negative bacteria.


Assuntos
Proteínas de Escherichia coli/química , Proteínas de Escherichia coli/metabolismo , Complexos Multienzimáticos/química , Complexos Multienzimáticos/metabolismo , Burkholderia pseudomallei/enzimologia , Domínio Catalítico , Dimerização , Escherichia coli/enzimologia , Bactérias Gram-Negativas/enzimologia , Isocitrato Desidrogenase/química , Isocitrato Desidrogenase/classificação , Isocitrato Desidrogenase/metabolismo , Cinética , Modelos Moleculares , Conformação Proteica , Domínios e Motivos de Interação entre Proteínas , Estrutura Quaternária de Proteína , Especificidade por Substrato
16.
Biochem Cell Biol ; 87(6): 853-65, 2009 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-19935871

RESUMO

Previous work has shown that purified double mutant A204C/C374A yeast actin is polymerization-deficient in vitro under physiological concentrations. To understand the importance of the 204 residue in subdomain 4, a series of actin proteins with a single mutation at this position were created with Cys-374 retained. Only yeast expressing A204G-, A204S-, or A204C-actin were viable. The A204G and A204S strains were sensitive to cold temperature and hyperosmolarity, whereas the A204C strain showed more profound effects on growth under these conditions. Cells expressing A204C-actin exhibited anomalies previously observed for A204C/C374A actin, including abnormal actin structures. A204G- and A204S-actin proteins had 12- and 13-fold increased critical concentrations, respectively, relative to wild-type. Only at very high concentrations could A204C actin polymerize when ATP was bound; when hydrolyzed, the ADP-containing A204C filaments depolymerized, demonstrating a profound difference in critical concentration between ATP and ADP states with A204C actin. A correlation between size of the residue substituted at position 204 and energy minimization of actin filament models was observed. We propose that the region surrounding residue 204 is involved in interactions that change depending on the phosphorylation state of the bound nucleotide that might reflect different conformations of F-actin subunits.


Assuntos
Actinas , Estrutura Quaternária de Proteína , Proteínas de Saccharomyces cerevisiae , Citoesqueleto de Actina/metabolismo , Citoesqueleto de Actina/ultraestrutura , Actinas/química , Actinas/genética , Actinas/metabolismo , Adenosina Trifosfatases/metabolismo , Trifosfato de Adenosina/metabolismo , Modelos Moleculares , Mutagênese Sítio-Dirigida , Polímeros/química , Polímeros/metabolismo , Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/química , Proteínas de Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/metabolismo
17.
Eur J Public Health ; 18(6): 600-3, 2008 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-18948366

RESUMO

BACKGROUND: The National Knowledge Service (NKS) is a National Health Service initiative to make patient and public information available to patients and healthcare professionals. The current study was carried out with a view to determine whether the resources developed by the NKS Tuberculosis Pilot have improved knowledge about tuberculosis among the target group in the short term. METHODS: Information resources specifically targeted and developed for homeless sector staff, managers and prison officials were used for this study. Questionnaires were designed to assess a change in the level of knowledge by completing a 'before' and 'after 'questionnaire. A total of 51 participants took part in the evaluation. McNemar's test for matched pairs was used to determine observed change in knowledge. RESULTS: Staff knowledge on symptoms of tuberculosis (TB) increased significantly after reading the targeted information resources. Knowledge gain for symptoms ranged from 17% (P = 0.007) for weight loss to 45% (P = 0.00001) for persistent fever. Knowledge about general guidelines that are available to this target group also improved, as did knowledge about the potential role of staff in supporting directly observed treatment (by 68% P = 0.00001) and the usual length of TB treatment (by 32% P = 0.0001). Pre-existing knowledge about the infectiousness of TB, risks for transmission and the likely period of hospitalization of patients with TB was high. CONCLUSIONS: This study demonstrates that purposefully designed and targeted information leaflets can be used successfully to translate complex information into a simple understandable format and impart knowledge of TB.


Assuntos
Educação em Saúde/métodos , Pessoas Mal Alojadas , Prisões/organização & administração , Medicina Estatal/organização & administração , Tuberculose Pulmonar , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Prática de Saúde Pública , Reino Unido
18.
Biomed Instrum Technol ; Suppl: 19-20, 22-31, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-17929650

RESUMO

This paper reports the results of a survey to investigate nurses' comfort with, and concerns regarding, the electromedical and computer equipment they use in their daily practice. Hospitals were surveyed in Australia, Canada, Great Britain, Singapore, and South Africa. Fourteen hospitals participated and a total of 933 responses were received. The analysis of the responses revealed that nurses are concerned about the training they are receiving on both technologies, the impact that computer time has on their workload, and the reliability and accessibility of these systems and devices.


Assuntos
Sistemas Computacionais , Educação em Enfermagem , Ciência de Laboratório Médico/educação , Saúde Ocupacional , Adulto , Coleta de Dados , Tomada de Decisões , Humanos , Internacionalidade , Projetos Piloto
19.
Arch Biochem Biophys ; 466(1): 58-65, 2007 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-17765196

RESUMO

The influence of the promoter and an N-terminal hexahistidine tag on human cardiac actin (ACTC) expression and function was investigated using four baculovirus constructs. It was found that both non-tagged ACTC and hisACTC expression from the p10 promoter was higher than from the polh promoter. Characterization showed that an N-terminal hexahistidine tag has a negative effect on ACTC. Recombinant ACTC inhibits DNase-I and binds myosin S1, indicative of proper folding. Our data support the hypothesis that the actin protein down-regulates the polh promoter.


Assuntos
Actinas/genética , Baculoviridae/genética , Vetores Genéticos/genética , Miocárdio/metabolismo , Regiões Promotoras Genéticas/genética , Engenharia de Proteínas/métodos , Proteínas Recombinantes/metabolismo , Spodoptera/genética , Spodoptera/metabolismo , Transfecção/métodos , Animais , Linhagem Celular , Spodoptera/virologia
20.
Trends Biochem Sci ; 31(2): 123-33, 2006 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-16406634

RESUMO

Diphtheria toxin and exotoxin A are well-characterized members of the ADP-ribosyltransferase toxin family that function as virulence factors in the pathogenic bacteria Corynebacterium diphtheriae and Pseudomonas aeruginosa. Recent high-resolution structural data of the Michaelis (enzyme-substrate) complex of the P. aeruginosa toxin with an NAD(+) analog and eukaryotic elongation factor 2 (eEF2) have provided insights into the mechanism of inactivation of protein synthesis caused by these protein factors. In addition, rigorous steady-state and stopped-flow kinetic analyses of the toxin-catalyzed reaction, in combination with inhibitor studies, have resulted in a quantum leap in our understanding of the mechanistic details of this deadly enzyme mechanism. It is now apparent that these toxins use stealth and molecular mimicry in unleashing their toxic strategy in the infected host eukaryotic cell.


Assuntos
ADP Ribose Transferases/farmacologia , Toxinas Bacterianas/farmacologia , Toxina Diftérica/farmacologia , Exotoxinas/farmacologia , Mimetismo Molecular , Fatores de Virulência/farmacologia , ADP Ribose Transferases/química , ADP Ribose Transferases/metabolismo , Sequência de Aminoácidos , Toxinas Bacterianas/química , Toxinas Bacterianas/metabolismo , Sítios de Ligação , Sequência Consenso , Toxina Diftérica/química , Toxina Diftérica/metabolismo , Exotoxinas/química , Exotoxinas/metabolismo , Histidina/análogos & derivados , Histidina/química , Modelos Moleculares , Dados de Sequência Molecular , Alinhamento de Sequência , Fatores de Virulência/química , Fatores de Virulência/metabolismo , Exotoxina A de Pseudomonas aeruginosa
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