RESUMEN
OBJECTIVE: Identify barriers and enablers for remote Tasmanians participating in bowel cancer screening through the National Bowel Cancer Screening Program. SETTING: A small remote Tasmanian community. PARTICIPANTS: Tasmanian remote community members aged 50 years and over. DESIGN: A qualitative study conducted 16 semi-structured interviews. Two researchers conducted in-person and telephone interviews. Questions were directed by an interview guide developed using the Theoretical Domains Framework for behaviour change and Behaviour Change Wheel. Two researchers analysed data using directed content analysis with a flexible inductive approach. RESULTS: Four themes related to barriers and enablers to completing the National Bowel Cancer Screening Program screening kit in remote Tasmania. Themes included the subject of screening, physical screening kit, the process and outcome of the kit. Several barrier and enabler sub-themes overlapped or were linked, as many enablers mitigated barriers. For example, social influences, awareness level, steps in completing screening, and planning and timing to screen. Social support and discussing screening with others were key enablers, whereas lack of these were barriers. For remote communities, taking the kit to the post office was a barrier from often knowing the post officer. A bowel bus providing screening and information support services may reduce the travel burden of follow-up diagnostic tests and support low-literacy individuals to screen. CONCLUSION: Barriers and enablers exist within each stage of the screening process, from what influences an individual decision to screen, through to the outcome. To improve screening rates in rural/remote Tasmania, barriers and enablers to screening must be considered.
Asunto(s)
Detección Precoz del Cáncer , Investigación Cualitativa , Humanos , Tasmania , Persona de Mediana Edad , Femenino , Masculino , Anciano , Detección Precoz del Cáncer/psicología , Población Rural/estadística & datos numéricos , Neoplasias Colorrectales/diagnóstico , Entrevistas como Asunto , Accesibilidad a los Servicios de Salud , Tamizaje MasivoRESUMEN
Increasingly, evidence is accumulating pointing at a protective role of a healthy diet at decreasing the risk of Alzheimer's disease. To test the effectiveness of nutritional components, the following food-derived compounds: curcumin alone (curcumin), curcumin combined with (-)epigallocatechin-3-gallate (EGCG), docosahexaenoic acid (DHA) and α-lipoic acid (ALA) (curcuminâ¯+â¯EDA), or a combination of EGCG, DHA and ALA (EDA) were assessed in male Tg2576 transgenic mice on amyloid plaque load, amyloid levels (Aß40/Aß42, but not oligomers due to tissue limitations), microglial activation and memory using the contextual and cued fear conditioning test. The combination diet EDA, resulted in the strongest reduction of amyloid plaque load in both the cortical (pâ¯<â¯.0001) and hippocampal (pâ¯<â¯.0001) areas of the Tg2576 mouse brain, along with lower Aß40/Aß42 levels in the frontal cortex (pâ¯=â¯.000129 and pâ¯=â¯.000039, respectively) and Aß42 levels in the temporal lobe (pâ¯=â¯.000082). A curcumin only diet was shown to lower amyloid plaque load (pâ¯=â¯.028), but when combined with EGCG, DHA and ALA did not result in further decreases in amyloid plaque load. The EDA combination group showed the most prominent decrease in microglial activation (number of microglia around plaques: pâ¯<â¯.05 and pâ¯<â¯.0001, respectively, for the cortex and hippocampus). Analysing the hippocampal associated contextual fear conditioning revealed that both the curcumin+EDA (pâ¯<â¯.0001) and EDA groups (pâ¯=â¯.001) spent increased time on freezing compared to the control group. In addition, the curcumin+EDA group showed a significant increase in time spent freezing compared with the curcumin only group. In the amygdala associated cued test, all mice demonstrated the ability to associate the conditioned stimulus with the unconditioned stimulus as evidenced by a significant increase in freezing behaviour in response to the presentation of the cue (pâ¯<â¯.0001). Post-hoc analysis showed that only curcumin+EDA (pâ¯<â¯.0001) and EDA groups (pâ¯<â¯.0001) developed a significant increase in freezing during the cue presentation. The results from this study show that the combination of EGCG, DHA and ALA (EDA) appeared to have the most potent anti-inflammatory and neuroprotective effect. Our results also demonstrate that interactions between nutraceutical products might result in counterproductive outcomes, highlighting the fact that manufacturers of nutraceuticals containing multiple compounds should be careful not to claim additive or synergistic effects of their combination products in vivo without having tested it in animal models and/or human clinical trials.
Asunto(s)
Enfermedad de Alzheimer , Dieta Saludable , Suplementos Dietéticos , Inflamación , Enfermedad de Alzheimer/metabolismo , Enfermedad de Alzheimer/patología , Péptidos beta-Amiloides/metabolismo , Animales , Antioxidantes/administración & dosificación , Curcumina/administración & dosificación , Modelos Animales de Enfermedad , Ácidos Docosahexaenoicos/administración & dosificación , Masculino , Ratones , Ratones Transgénicos , Fármacos Neuroprotectores/administración & dosificación , Placa Amiloide/patología , Ácido Tióctico/administración & dosificaciónRESUMEN
BACKGROUND: To evaluate a new semi-automated segmentation method for calculating hippocampal volumes and to compare results with standard software tools in a cohort of people with subjective memory complaints (SMC) and mild cognitive impairment (MCI). METHODS: Data from 58 participants, 39 with SMC (17 male, 22 female, mean age 72.6) and 19 with MCI (6 male, 13 female, mean age 74.3), were analyzed. For each participant, T1-weighted images were acquired using an MPRAGE sequence on a 3 Tesla MRI system. Hippocampal volumes (left, right, and total) were calculated with a new, age appropriate registration template, based on older people and using the advanced software tool ANTs (Advanced Normalization Tools). The results were compared with manual tracing (seen as the reference standard) and two widely accepted automated software tools (FSL, FreeSurfer). RESULTS: The hippocampal volumes, calculated by using the age appropriate registration template were significantly (P < 0.05) more accurate (mean volume accuracy more than 90%) than those obtained with FreeSurfer and FSL (both less than 70%). Dice coefficients for the hippocampal segmentations with the new template method (75.3%) were slightly, but significantly (P < 0.05) higher than those from FreeSurfer (72.4%). CONCLUSION: These results suggest that an age appropriate registration template might be a more accurate alternative to calculate hippocampal volumes when manual segmentation is not feasible.
Asunto(s)
Envejecimiento/patología , Disfunción Cognitiva/patología , Hipocampo/patología , Interpretación de Imagen Asistida por Computador/métodos , Trastornos de la Memoria/patología , Técnica de Sustracción , Anciano , Disfunción Cognitiva/complicaciones , Femenino , Humanos , Aumento de la Imagen/métodos , Masculino , Trastornos de la Memoria/complicaciones , Reconocimiento de Normas Patrones Automatizadas/métodos , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Programas InformáticosRESUMEN
Objectives: Summarise theory informed educational interventions for improving bowel cancer awareness and screening. Methods: A search was conducted in PubMed, EMBASE, Web of Science and CINAHL. English studies from 2016 to 2022 which implemented community-based bowel cancer awareness and/or screening education interventions for adults in Organisation for Economic Co-operation and Development countries were included. Results: Sixty-two studies were included, 32 measured both screening and awareness (24 measured screening only, 6 measured awareness only). Education interventions were grouped and summarised in five education types: lay community health education/counselling (n = 28), education material (n = 5), health professional education/counselling (n = 10), mass media (n = 5) and other (n = 19). Other included education interventions which did not fit into the four types previously mentioned. Six studies tested more than one education type. Each type within these studies were reported/summarised separately within the appropriate education type. Lay educators resulted in improved awareness and screening. Brochures were effective education materials for screening and combined with lay educators resulted in increased awareness. State-wide mass media campaigns significantly improved screening uptake for up to 2-months post-campaign. Fear and loss-framed messaging improved screening intentions compared to humour or gain-based messaging. Decision aids had limited improvements in awareness. Facebook campaign and telephone counselling had limited improvements in screening. Conclusions: Lay community health educators, brochures, and mass media campaigns occurring multiple times a year may be effective interventions in improving screening and/or awareness. Such approaches should be considered when developing community education. Education interventions should include multiple components suggested above to maximise improvements of awareness and screening.
RESUMEN
In this paper, we report the inter-laboratory validation (ILV) of a recently developed indirect competitive multiplex dipstick (Bee4sensor®) which is capable of the simultaneous detection of residues of some of the most frequently detected antibiotic residues in honey: sulfonamides, tylosin, fluoroquinolones and chloramphenicol. The multi-sensor dipstick can be interpreted via visual observation or by an instrumental measurement of four test lines. Statistical analysis of the ILV data demonstrated that the multi-sensor can reliably detect the presence of sulfathiazole at 25 µg kg(-1) and tylosin at 10 µg kg(-1), which fully meet the 'recommended concentrations' of the EU. Ciprofloxacin and chloramphenicol can be detected at 25 and 5 µg kg(-1) in honey, respectively. Whilst the concentration for chloramphenicol is above the EU minimum required performance limit of 0.3 µg kg(-1), this part of the multiplex test may still be of use to both the industry and enforcement authorities, to provide an early warning of contaminated honey. The estimated false-negative and false-positive rates for this easy-to-use and robust assay were less than 5%.
Asunto(s)
Antibacterianos/análisis , Bioensayo/normas , Residuos de Medicamentos/análisis , Miel/análisis , Animales , Abejas , Variaciones Dependientes del ObservadorRESUMEN
We have used systematic evolution of ligands by exponential enrichment (SELEX) to isolate RNA aptamers against aminoglycoside antibiotics. The SELEX rounds were toggled against four pairs of aminoglycosides with the goal of isolating reagents that recognize conserved structural features. The resulting aptamers bind both of their selection targets with nanomolar affinities. They also bind the less structurally related targets, although they show clear specificity for this class of antibiotics. We show that this lack of aminoglycoside specificity is a common property of aptamers previously selected against single compounds and described as "specific". Broad target specificity aptamers would be ideal for sensors detecting the entire class of aminoglycosides. We have used ligand-induced aggregation of gold-nanoparticles coated with our aptamers as a rapid and sensitive assay for these compounds. In contrast to DNA aptamers, unmodified RNA aptamers cannot be used as the recognition ligand in this assay, whereas 2'-fluoro-pyrimidine derivatives work reliably. We discuss the possible application of these reagents as sensors for drug residues and the challenges for understanding the structural basis of aminoglycoside-aptamer recognition highlighted by the SELEX results.
Asunto(s)
Antibacterianos/análisis , Aptámeros de Nucleótidos/química , Oro/química , Nanopartículas del Metal/química , Resonancia por Plasmón de Superficie , Aminoglicósidos/análisis , Biotinilación , Cinética , Técnica SELEX de Producción de AptámerosRESUMEN
BACKGROUND: Older adults free of dementia but with subjective memory complaints (SMC) or mild cognitive impairment (MCI) are considered at increased risk of cognitive decline. Vascular risk factors (VRF), including hypertension, heart disease, smoking, hypercholesterolemia and lack of physical activity (PA) have been identified as modifiable risk factors contributing to cognitive decline, and white matter hyperintensities (WMH) are associated with VRF, SMC and cognitive impairment. Findings from a growing number of clinical trials with older adults are providing strong evidence for the benefits of physical activity for maintaining cognitive function, but few studies are investigating these benefits in high-risk populations. The aim of AIBL Active is to determine whether a 24-month physical activity program can delay the progression of white matter changes on magnetic resonance imaging (MRI). METHODS/DESIGN: This single-blind randomized controlled trial (RCT) is offered to 156 participants, aged 60 and older, in the Melbourne arm of the Australian Imaging Biomarkers and Lifestyle Flagship Study of Aging (AIBL). Participants must have SMC with or without MCI and at least one VRF. The PA intervention is a modification of the intervention previously trialed in older adults with SMC and MCI (Fitness for the Ageing Brain Study). It comprises 24 months of moderate, home-based PA (150 minutes per week) and a behavioral intervention package. The primary outcome measure will be change in WMH after 24 months on MRI. Cognition, quality of life, functional fitness, level of physical activity, plasma biomarkers for cerebrovascular disease and amyloid positron emission tomography (PET) imaging comprise secondary measures. DISCUSSION: Currently, there is no effective pharmacological treatment available to delay cognitive decline and dementia in older adults at risk. Should our findings show that physical activity can slow down the progression of WMH, this RCT would provide an important proof of concept. Since imbedded in AIBL this RCT will also be able to investigate the interaction between vascular and Alzheimer's disease pathologies. TRIAL REGISTRATION: Australia New Zealand Clinical Trials Registry ACTRN12611000612910.
Asunto(s)
Encéfalo/patología , Disfunción Cognitiva , Progresión de la Enfermedad , Terapia por Ejercicio/métodos , Imagen por Resonancia Magnética/métodos , Trastornos de la Memoria , Adulto , Anciano , Encéfalo/fisiopatología , Terapia Cognitivo-Conductual/métodos , Disfunción Cognitiva/fisiopatología , Disfunción Cognitiva/prevención & control , Disfunción Cognitiva/terapia , Terapia por Ejercicio/normas , Femenino , Evaluación Geriátrica , Humanos , Imagen por Resonancia Magnética/instrumentación , Masculino , Trastornos de la Memoria/patología , Trastornos de la Memoria/fisiopatología , Trastornos de la Memoria/terapia , Persona de Mediana Edad , Método Simple Ciego , Resultado del TratamientoRESUMEN
AIM: The purpose of this research was to use metabolomics to investigate the cystic phenotype in the Lewis polycystic kidney rat. METHODS: Spot urine samples were collected from four male Lewis control and five male Lewis polycystic kidney rats aged 5 weeks, before kidney function was significantly impaired. Metabolites were extracted from urine and analysed using gas chromatography-mass spectrometry. Principal component analysis was used to determine key metabolites contributing to the variance observed between sample groups. RESULTS: With the development of a metabolomics method to analyse Lewis and Lewis polycystic kidney rat urine, 2-ketoglutaric acid, allantoin, uric acid and hippuric acid were identified as potential biomarkers of cystic disease in the rat model. CONCLUSION: The findings of this study demonstrate the potential of metabolomics to further investigate kidney disease.
Asunto(s)
Metabolómica , Enfermedades Renales Poliquísticas/orina , Alantoína/orina , Animales , Biomarcadores/orina , Modelos Animales de Enfermedad , Cromatografía de Gases y Espectrometría de Masas , Hipuratos/orina , Ácidos Cetoglutáricos/orina , Masculino , Metabolómica/métodos , Fenotipo , Análisis de Componente Principal , Ratas , Ratas Endogámicas Lew , Ácido Úrico/orina , UrinálisisRESUMEN
The diet quality of rural Australians is under researched. Characterising disparities in diet quality between rural and urban populations may inform targeted interventions in at- risk groups. A cross-sectional study aimed to determine the relationship between diet quality, rurality and sociodemographic characteristics in a sample of Australian adults. Participants were recruited at rural and regional events between 2017 and 2020, in New South Wales, Australia. Diet quality was measured using the Healthy Eating Quiz or Australian Eating Survey to generate an Australian Recommended Food Score (ARFS). ARFS was compared by rurality and sociodemographic characteristics using multivariate regression. Participants (n = 247; 53% female) had a mean ± SD ARFS of 34.5 ± 9.0. There was no significant effect of rurality on ARFS (ß-coefficient = -0.4; 95%CI -3.0, 2.3). Compared to participants aged 18-30 years, higher ARFS was evident for those aged 31-50 (ß = 5.4; 95%CI 0.3, 10.4), 51-70 (ß = 4.4; 95%CI 0.3, 8.5) and >71 years (ß = 6.5; 95% CI 1.6-11.4). Compared to those living alone, participants living with a partner (ß = 5.2; 95%CI 2.0, 8.4) and families with children (ß = 5.6; 95%CI 1.4, 9.8) had significantly higher ARFS. ARFS was significantly lower with each additional self-reported chronic health condition (ß = -1.4; 95%CI -2.3, -0.4). Our results indicate that diet quality as defined by the ARFS was classified as 'getting there' and that age, living arrangements and chronic health conditions, but not rurality, influenced diet quality in a sample of Australian adults.
Asunto(s)
Dieta Saludable/estadística & datos numéricos , Población Rural/estadística & datos numéricos , Población Urbana/estadística & datos numéricos , Adolescente , Adulto , Factores de Edad , Anciano , Enfermedad Crónica , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Nueva Gales del Sur , Análisis de Regresión , Características de la Residencia/estadística & datos numéricos , Adulto JovenRESUMEN
Lack of physical activity is a risk factor for dementia, however, the utility of interventional physical activity programs as a protective measure against brain atrophy and cognitive decline is uncertain. Here we present the effect of a randomized controlled trial of a 24-month physical activity intervention on global and regional brain atrophy as characterized by longitudinal voxel-based morphometry with T1-weighted MRI images. The study sample consisted of 98 participants at risk of dementia, with mild cognitive impairment or subjective memory complaints, and having at least one vascular risk factor for dementia, randomized into an exercise group and a control group. Between 0 and 24 months, there was no significant difference detected between groups in the rate of change in global, or regional brain volumes.
Asunto(s)
Disfunción Cognitiva , Demencia , Anciano , Atrofia/patología , Encéfalo/diagnóstico por imagen , Encéfalo/patología , Cognición , Disfunción Cognitiva/diagnóstico por imagen , Disfunción Cognitiva/patología , Demencia/diagnóstico por imagen , Demencia/patología , Ejercicio Físico , Humanos , Imagen por Resonancia MagnéticaRESUMEN
A robust screening assay employing solid phase extraction (SPE) followed by a novel aptamer-based procedure is presented for the rapid detection and semiquantitation of the triphenylmethane dye, Malachite Green (MG) and its primary metabolite Leucomalachite Green (LMG) in fish tissue. To the authors' knowledge, this is the first reported use of an RNA aptamer for the development of a diagnostic assay for the detection of chemical residues in food. The aptamer based screening assay is found to be highly specific for MG; but has negligible affinity for the LMG metabolite. However, because the LMG metabolite is lipophilic and known to be highly persistent in tissues, an oxidation step has been incorporated within the sample cleanup procedure to ensure that all LMG residues are converted to MG prior to measurement. This article provides evidence that an oligonucleotide aptamer can be used as an alternative recognition element to conventional antibodies with application to the detection of residues in food. Furthermore, this finding has the future potential to reduce the number of animals currently being used in the production of antibodies for immunodiagnostic kits.
Asunto(s)
Aptámeros de Nucleótidos/química , Electroforesis en Gel de Poliacrilamida/métodos , ARN/química , Colorantes de Rosanilina/análisis , Animales , Peces/metabolismo , Contaminación de Alimentos/análisis , Colorantes de Rosanilina/aislamiento & purificación , Extracción en Fase SólidaRESUMEN
BACKGROUND: There is a paucity of information on the role of microvascular and inflammatory biomarkers in cognitive dysfunction. OBJECTIVE: This study sought to evaluate the relationships between established and a number of peripheral biomarkers on cognitive patterns in 108 older adults with memory complaints. METHODS: Participants in the AIBL Active study aged 60 years and older with at least one vascular risk factor and memory complaints completed a neuropsychological test battery and provided cross-sectional health data. Linear regression models adjusted for covariates examined associations between cognitive performance and a panel of vascular risk factors (Framingham cardiovascular scores, hs-CRP, homocysteine, fasting glucose, LDL-cholesterol) and peripheral biomarkers (TNF-α, BDNF, VCAM-1, ICAM-1, PAI-1, CD40L). RESULTS: Higher fasting glucose and homocysteine levels were independent factors associated with poorer performance in Trail Making Test (TMT) B (adjusted ß=â0.40±0.10 and 0.43±0.09, respectively). Increasing homocysteine levels were weakly associated with poorer global cognition and delayed recall (adjusted ß=â0.23±0.10 and -0.20±0.10 respectively). Increasing Framingham cardiovascular scores were related to poorer performance in TMT B (ß â=â0.42±0.19). There was early evidence of associations between increasing plasma TNF-α and poorer TMT B (adjusted ß â=â0.21±0.10) and between increasing BDNF and better global cognition (ß=â-0.20±0.09). CONCLUSION: This study provides evidence to support the associations between vascular risk factors (Framingham scores, fasting glucose, and homocysteine) and poorer cognitive functions. Additionally, we measured several peripheral biomarkers to further investigate their associations with cognition. The relationship between TNF-α, BDNF, and cognitive performance in various domains may offer new insights into potential mechanisms in vascular cognitive impairment.
Asunto(s)
Cognición , Disfunción Cognitiva/epidemiología , Factores de Riesgo de Enfermedad Cardiaca , Anciano , Anciano de 80 o más Años , Australia/epidemiología , Biomarcadores , Disfunción Cognitiva/diagnóstico , Estudios Transversales , Función Ejecutiva , Femenino , Humanos , Inflamación/patología , Mediadores de Inflamación/análisis , Masculino , Memoria , Pruebas de Estado Mental y Demencia , Microcirculación , Persona de Mediana Edad , Desempeño Psicomotor , Factores de Riesgo , Prueba de Secuencia AlfanuméricaRESUMEN
White matter hyperintensities (WMHs) are a risk factor for cognitive decline. Physical activity (PA) is associated with lower WMH. Whether long-term exposure to PA programs has beneficial effects on WMH progression in older adults with memory complaints and comorbid conditions has had limited exploration. This study explored whether a 24-month moderate-intensity PA intervention can delay the progression of WMH and hippocampus loss in older adults at risk for cognitive decline. Data acquired on magnetic resonance imaging were used to measure the progression of WMH and hippocampus loss. The results of this study showed no effect of intervention on either the primary outcome measure "WMH" or the secondary outcome measure "hippocampal volume." In addition, neither beta amyloid status nor the adherence to the intervention had any effect on the outcome. In this cohort of subjective memory complaints and mild cognitive impairment participants with vascular risk factors, there was no effect of long-term moderate-intensity PA on WMH or hippocampal loss.
Asunto(s)
Encéfalo/diagnóstico por imagen , Encéfalo/patología , Ejercicio Físico/fisiología , Resultados Negativos , Servicios Preventivos de Salud/métodos , Evaluación de Programas y Proyectos de Salud , Anciano , Anciano de 80 o más Años , Enfermedad de Alzheimer/prevención & control , Disfunción Cognitiva/prevención & control , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Tomografía de Emisión de Positrones , Riesgo , Factores de TiempoRESUMEN
White matter (WM) microstructure is a sensitive marker to distinguish individuals at risk of Alzheimer's disease. The association of objective physical fitness (PF) measures and WM microstructure has not been explored and mixed results reported with physical activity (PA). Longitudinal studies of WM with PA and PF measures have had limited investigation. This study explored the relationship between objective PF measures over 24-months with "normal-appearing" WM microstructure. Data acquired on magnetic resonance imaging was used to measure "normal-appearing" WM microstructure at baseline and 24-months. Clinical variables such as cognitive and blood-based measures were collected longitudinally. Also, as part of the randomized controlled trial of a PA, extensive measures of PA and fitness were obtained over the 24 months. Bilateral corticospinal tracts (CST) and the corpus callosum showed a significant association between PF performance over 24-months and baseline WM microstructural measures. There was no significant longitudinal effect of the intervention or PF performance over 24-months. Baseline WM microstructural measures were significantly associated with PF performance over 24-months in this cohort of participants with vascular risk factors and at risk of Alzheimer's disease with distinctive patterns for each PF test.
RESUMEN
Alzheimer's disease (AD) is the most common neurodegenerative disorder, affecting millions of people worldwide. Apart from age, the major risk factor identified so far for the sporadic form of AD is possession of the epsilon4 allele of apolipoprotein E (APOE), which is also a risk factor for coronary artery disease (CAD). Other apolipoproteins known to play an important role in CAD such as apolipoprotein B are now gaining attention for their role in AD as well. AD and CAD share other risk factors, such as altered cholesterol levels, particularly high levels of low density lipoproteins together with low levels of high density lipoproteins. Statins--drugs that have been used to lower cholesterol levels in CAD, have been shown to protect against AD, although the protective mechanism(s) involved are still under debate. Enzymatic production of the beta amyloid peptide, the peptide thought to play a major role in AD pathogenesis, is affected by membrane cholesterol levels. In addition, polymorphisms in several proteins and enzymes involved in cholesterol and lipoprotein transport and metabolism have been linked to risk of AD. Taken together, these findings provide strong evidence that changes in cholesterol metabolism are intimately involved in AD pathogenic processes. This paper reviews cholesterol metabolism and transport, as well as those aspects of cholesterol metabolism that have been linked with AD.
Asunto(s)
Enfermedad de Alzheimer/etiología , Enfermedad de Alzheimer/metabolismo , Transporte Biológico/fisiología , Colesterol/metabolismo , Enfermedad de Alzheimer/tratamiento farmacológico , Enfermedad de Alzheimer/genética , Péptidos beta-Amiloides/metabolismo , Precursor de Proteína beta-Amiloide/metabolismo , Animales , Apolipoproteínas/metabolismo , Transporte Biológico/efectos de los fármacos , Encéfalo/metabolismo , Encéfalo/patología , Humanos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/farmacología , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Modelos Biológicos , Receptores de LDL/fisiologíaRESUMEN
Studies of the brains of Alzheimer's disease (AD) patients have revealed key neuropathological features, such as the deposition of aggregates of insoluble amyloid-ß (Aß) peptides and neurofibrillary tangles (NFTs). These pathological protein deposits, including Aß peptides (which form senile plaques) and hyperphosphorylated tau (which aggregates into NFTs), have been assumed to be 'the cause of AD'. Aß has been extensively targeted to develop an effective disease-modifying therapy, but with limited clinical success. Emerging therapies are also now targeting further pathological processes in AD, including neuroinflammation. This review focuses on the inflammatory and oxidative stress-related changes that occur in AD, and discusses some emerging anti-inflammatory natural products and phytomedicines. Many of the promising compounds are cytokine-suppressive anti-inflammatory drugs (CSAIDs), which target the proinflammatory AP1 and nuclear factor-κB signalling pathways and inhibit the expression of many proinflammatory cytokines, such as interleukin (IL)-1, IL-6, tumour necrosis factor-α, or nitric oxide produced by inducible nitric oxide synthase. However, many of these phytomedicines have not been tested in rigorous clinical trials in AD patients. It is not yet clear if the active compounds reach an effective concentration in the brain (due to limited bioavailability) or if they can slow down AD progression in long-term trials. The authors suggest that it is crucial for both the pharmacological and complementary medicine industries to conduct and fund those studies to significantly advance the field.
Asunto(s)
Enfermedad de Alzheimer/tratamiento farmacológico , Antiinflamatorios/uso terapéutico , Productos Biológicos/uso terapéutico , Estrés Oxidativo/efectos de los fármacos , Enfermedad de Alzheimer/inmunología , Enfermedad de Alzheimer/metabolismo , Ensayos Clínicos como Asunto , Citocinas/metabolismo , Productos Finales de Glicación Avanzada/metabolismo , Humanos , Inflamación , FN-kappa B/metabolismo , Estrés Oxidativo/inmunologíaRESUMEN
BACKGROUND: Previous studies have demonstrated that physical activity (PA) interventions can improve physical and cognitive outcomes in older adults, but most have been relatively short in duration (<1 year) with a few having specifically targeting individuals at risk of developing Alzheimer's disease. OBJECTIVE: To examine adherence and physical health outcomes in a 24-month home-based PA intervention in older adults at risk of Alzheimer's disease. METHODS: Participants 60 years and older with mild cognitive impairment (MCI) or subjective memory complaints (SMC) with at least 1 cerebrovascular risk factor recruited from The Australian Imaging Biomarkers and Lifestyle Flagship Study of Aging (AIBL) were randomized to a PA or control group (nâ=â106). The control group continued with their usual lifestyle. The PA group received a 24-month home-based program with a target of 150 minutes/week of moderate PA and a behavioral intervention. Retention (participants remaining) and PA adherence (PA group only, percent PA completed to the PA prescribed) were determined at 6, 12, 18, and 24 months. Assessments at baseline, 6, 12, and 24 months included, PA; fitness; body composition and fat distribution. Key outcome measures were PA adherence and PA. RESULTS: The 24-month retention rate (97.2%) and the median PA adherence 91.67% (Q1-Q3, 81.96, 100.00) were excellent. In the long-term the intervention group achieved significantly better improvements in PA levels, leg strength, fat mass and fat distribution compared to the control. CONCLUSION: This study demonstrates that in this target group, long-term PA adherence is achievable and has physical health benefits.
Asunto(s)
Envejecimiento/psicología , Enfermedad de Alzheimer/prevención & control , Disfunción Cognitiva/prevención & control , Ejercicio Físico/psicología , Estilo de Vida , Cooperación del Paciente , Anciano , Enfermedad de Alzheimer/psicología , Disfunción Cognitiva/psicología , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
Ambient mass spectrometry has been used for the analysis of strobilurin residues in wheat. The use of this novel, challenging technique, employing a direct analysis in a real time (DART) ion-source coupled with a time-of-flight mass spectrometer (TOF MS) and a desorption electrospray ionization (DESI) source coupled with a linear ion trap tandem MS (LIT MS(n)), permitted a direct screen of the occurrence of target fungicides in treated grains in less than 1 min. For quantification purpose by DART-TOF MS, an ethyl acetate extract had to be prepared. With the use of a prochloraz as an internal standard, the performance characteristics obtained by repeated analyses of extract, spiked at 50 microg kg(-1) with six strobilurins (azoxystrobin, picoxystrobin, dimoxystrobin, kresoxim-methyl, pyraclostrobin, and trifloxystrobin), were in the following range: recoveries 78-92%, repeatability (RSD) 8-15%, linearity (R(2)) 0.9900-0.9978. The analysis of wheat with incurred strobilurin residues demonstrated good trueness of data generated by the DART-TOF MS method; the results were in a good agreement with those obtained by the conventional approach, i.e., by the QuEChERS sample handling procedure followed by identification/quantification employing high-performance liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). Tandem mass spectrometry using DESI-LIT MS(n) provided a sufficient number of product ions for confirmation of the identity of azoxystrobin and pyraclostrobin in incurred wheat samples.
RESUMEN
Carbohydrate-restricted diets (CRDs) promote weight loss, reductions in plasma triacylglycerol (TAG) levels, and increases in high-density lipoprotein cholesterol (HDL-C) levels but may cause undesirable low-density lipoprotein cholesterol (LDL-C) responses in some people. The objective of the present study was to determine the effect of adding soluble fiber to a CRD on plasma LDL-C and other traditionally measured markers of cardiovascular disease. Using a parallel-arm, double-blind, placebo-controlled design, 30 overweight and obese men (body mass index, 25-35 kg/m(2)) were randomly assigned to supplement a CRD with soluble fiber (Konjac-mannan, 3g/d) (n = 15) or placebo (n = 15). Plasma lipids, anthropometrics, body composition, blood pressure, and nutrient intake were evaluated at baseline and at 6 and 12 weeks. Compliance was excellent as assessed by 7-day weighed dietary records and ketonuria. Both groups experienced decreases in (P < .01) body weight, percent body fat, systolic blood pressure, waist circumference, and plasma glucose levels. After 12 weeks, HDL-C and TAG improved significantly in the fiber (10% and -34%) and placebo (14%, -43%) groups. LDL-C decreased by 17.6% (P < .01) at week 6 and 14.1% (P < .01) at week 12 in the fiber group. Conversely, LDL-C reductions were significant in the placebo group only after 12 weeks (-6.0%, P < .05). We conclude that although clearly effective at lowering LDL-C, adding soluble fiber to a CRD during active and significant weight loss provides no additional benefits to the diet alone. Furthermore, a CRD led to clinically important positive alterations in cardiovascular disease risk factors.
Asunto(s)
Enfermedades Cardiovasculares/prevención & control , LDL-Colesterol/sangre , Dieta Baja en Carbohidratos/métodos , Mananos/farmacología , Adulto , Anciano , Glucemia/metabolismo , Presión Sanguínea , Composición Corporal/fisiología , Peso Corporal/fisiología , Enfermedades Cardiovasculares/sangre , HDL-Colesterol/sangre , Fibras de la Dieta/administración & dosificación , Método Doble Ciego , Humanos , Insulina/sangre , Masculino , Persona de Mediana Edad , Triglicéridos/sangreRESUMEN
Although the use of chloramphenicol (CAP) as a veterinary drug is banned in the European Union and many other countries, monitoring for CAP residues in food is routine. Positive detections are few, but taken extremely seriously. European Union laboratories analysing for CAP should validate methods according to European Commission Decision 2002/657/EC, must be accredited to ISO 17025, and will generally participate in proficiency testing (PT) schemes, such as those offered by the Food Analysis Performance Assessment Scheme (FAPAS®). The FAPAS PTs aim to cover a wide range of relevant matrices including honey, prawns, fish, milk and kidney. Test materials are prepared either by animal dosing studies or by spiking raw matrix. The most common method reported by FAPAS participants used to screen for CAP residues is LC-MS/MS, but ELISA kits are increasingly being used. A recent PT round highlighted that the result obtained might be correlated with the type of analytical method being employed. Follow-up investigations have demonstrated that some of these variations in data are a function of the different stereoisomeric forms of CAP. This paper discusses the implication of this research on method validation requirements and European Union legislation.