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1.
Metallomics ; 14(4)2022 04 30.
Article in English | MEDLINE | ID: mdl-35254441

ABSTRACT

Hemorrhagic transformation of ischemic stroke has devastating consequences, with high mortality and poor functional outcomes. Animal models of ischemic stroke also demonstrate the potential for hemorrhagic transformation, which complicates biochemical characterization, treatment studies, and hinders poststroke functional outcomes in affected subjects. The incidence of hemorrhagic transformation of ischemic stroke in animal model research is not commonly reported. The postmortem brain of such cases presents a complex milieu of biomarkers due to the presence of healthy cells, regions of varying degrees of ischemia, dead and dying cells, dysregulated metabolites, and blood components (especially reactive Fe species released from lysed erythrocytes). To improve the characterization of hemorrhage biomarkers on an ischemic stroke background, we have employed a combination of histology, X-ray fluorescence imaging (XFI), and Fourier transform infrared (FTIR) spectroscopic imaging to assess 122 photothrombotic (ischemic) stroke brains. Rapid freezing preserves brain biomarkers in situ and minimizes metabolic artifacts due to postmortem ischemia. Analysis revealed that 25% of the photothrombotic models had clear signs of hemorrhagic transformation. The XFI and FTIR metabolites provided a quantitative method to differentiate key metabolic regions in these models. Across all hemorrhage cases, it was possible to consistently differentiate otherwise healthy tissue from other metabolically distinct regions, including the ischemic infarct, the ischemic penumbra, blood vessels, sites of hemorrhage, and a region surrounding the hemorrhage core that contained elevated lipid oxidation. Chemical speciation of deposited Fe demonstrates the presence of heme-Fe and accumulation of ferritin.


Subject(s)
Brain Ischemia , Ischemic Stroke , Stroke , Animals , Biomarkers , Brain Ischemia/complications , Brain Ischemia/diagnostic imaging , Hemorrhage/complications , Humans , Ischemic Stroke/diagnostic imaging , Multimodal Imaging , Stroke/complications , Stroke/diagnostic imaging , Stroke/epidemiology
2.
Top Stroke Rehabil ; 29(4): 286-294, 2022 05.
Article in English | MEDLINE | ID: mdl-34018471

ABSTRACT

BACKGROUND & PURPOSE: Anxiety and depression are common among stroke survivors, and their effect on long-term outcome remains unknown in those under 65 years of age. We investigated the association between early anxiety/depression after stroke and 12-month disability, and whether this is modified by sex. METHODS: The Psychosocial Outcomes In StrokE (POISE) study was a prospective observational cohort study that recruited 441 younger (< 65 years) stroke survivors ≤28 days of acute stroke. Anxiety and depression were assessed using the Hospital Anxiety and Depression Scale, and disability using the World Health Organization Disability Assessment Scale version II (WHODAS-II). Associations between baseline anxiety/depression, and disability at 12-months was tested using analysis of covariance. Subgroup analysis was conducted using interaction term. RESULTS: 92 (25%) had anxiety and 53 (14%) depression at baseline. Multivariable models showed significant association between baseline anxiety and 12-month disability (WHODAS-II score 15.24 vs. 11.49, p < .05). Those with anxiety had more impairment in 'cognition' (WHODAS-II score 18.26 vs. 8.71, p < .001), 'getting along' (WHODAS-II score 11.87 vs. 7.42, p < .05) and 'participation' (WHODAS-II score 22.37 vs. 15.92, p < .005) WHODAS-II. No significant relationship was found between baseline depression and long-term disability. There was no differential effect of anxiety by sex found in this study. CONCLUSIONS: Post-stroke anxiety has an adverse effect on disability at one year among young stroke survivors.


Subject(s)
Anxiety , Stroke , Anxiety/epidemiology , Anxiety/etiology , Depression/epidemiology , Depression/etiology , Disability Evaluation , Humans , Prospective Studies , Stroke/complications , Stroke/epidemiology , Stroke/therapy , Survivors/psychology
3.
Environ Toxicol Chem ; 40(11): 2978-2989, 2021 11.
Article in English | MEDLINE | ID: mdl-34499761

ABSTRACT

Wild birds and mammals that feed in agricultural habitats are potentially exposed to pesticides through various routes. Until recently, it has been implicitly assumed that the existing European Union risk assessment scheme for birds and mammals also covered bats (Chiroptera). However, recent publications raised concerns and, in 2019, a scientific statement was published by the European Food Safety Authority (EFSA) that concluded that bats were not adequately covered by the current risk assessment scheme. We review the evidence presented and assumptions made in the EFSA bat statement relating to toxicity, bioaccumulation, and exposure pathways (oral, dermal, and inhalation), in terms of their relevance for bats potentially foraging in agricultural areas in the European Union; we highlight where uncertainties remain and how these could be addressed. Based on our review, it is clear that there is still much uncertainty with regard to the appropriateness of the assumptions made in the EFSA bat statement. Significantly more information needs to be gathered to answer fundamental questions regarding bat behavior in agricultural landscapes, together with the relative sensitivity of bats to pesticide exposure. Given the current critical information gaps, it is recommended that quantitative risk assessments for bats not be performed for pesticides until more robust, reliable, and relevant data are available. The risk to bats can then be compared with that for birds and ground-dwelling mammals, to determine the protectiveness of the existing scheme and thus whether a bat scenario is indeed required and under what circumstances. Environ Toxicol Chem 2021;40:2978-2989. © 2021 Cambridge Environmental Assessments, part of RSK ADAS Ltd. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.


Subject(s)
Chiroptera , Pesticides , Animals , Birds , Ecosystem , Food Safety , Mammals , Pesticides/toxicity , Risk Assessment
4.
Sci Rep ; 10(1): 17868, 2020 10 20.
Article in English | MEDLINE | ID: mdl-33082455

ABSTRACT

Stroke is a leading cause of long-term disability in adults and a leading cause of death in developed nations. The cascade of cellular events and signalling that occur after cerebral ischemia are complex, however, analyzing global element markers of metabolic state affords the means to monitor stroke severity, status of injury, and recovery. These markers provide a multi-parameter method for assessing changes through the post-stroke time course. We employ synchrotron-based elemental mapping to follow elemental changes in the brain at 1 h, 1-, 2-, and 3-days, and at 1-, 2-, 3-, and 4-weeks post-stroke in a photothrombotic stroke model in mice. Our analysis reveals a highly consistent metabolic penumbra that can be readily identified based on the level of dysregulated potassium and other key elements. Maps of elemental distributions are also useful to demarcate events in the cellular response to the inflammatory cascade, including ion dysregulation, recruitment of cells to the lesion, and glial scar formation.


Subject(s)
Ischemic Stroke/metabolism , Spectrometry, X-Ray Emission/methods , Trace Elements/metabolism , Animals , Disease Models, Animal , Ischemic Stroke/etiology , Mice , Reproducibility of Results , Thromboembolism/complications
5.
Int J Equity Health ; 19(1): 8, 2020 01 13.
Article in English | MEDLINE | ID: mdl-31931810

ABSTRACT

BACKGROUND: Aboriginal women are frequently called upon to support their families and other community members. At times, such supporting roles can be burdensome for these women. Many Aboriginal women live with chronic conditions. We explored the ways in which the women's caring roles impacted on how they maintained their own health. METHODS: The aim of this manuscript is to explore the psychosocial factors associated with the management of health and chronic disease in Aboriginal women. An interpretive phenomenological approach was used for the analysis of 72 in-depth semi-structured interviews. These interviews were conducted in four community controlled Aboriginal health services, in urban, rural and remote settings, across two states and a territory in Australia. RESULTS: Women living with chronic disease experience multiple challenges while caring for family, such as intergenerational trauma, mental health issues relating to addiction, domestic and family violence and incarceration. When these women become ill, they also have to take care of themselves. These women provided informal and unfunded care in response to a range of complex family and community problems. This continuous caring for family affected the women's ability to maintain their health and manage their own chronic conditions. CONCLUSION: The caring roles and responsibilities Aboriginal women have in their community impact on their health. Aboriginal women provide much needed refuge and support to family and the wider community. Underfunded and over-burdened formal support services are not meeting the needs of many Aboriginal women. Improved culturally secure resources and social services are required within communities to support Aboriginal women to successfully manage their own health.


Subject(s)
Chronic Disease/ethnology , Chronic Disease/therapy , Native Hawaiian or Other Pacific Islander/psychology , Self Care/psychology , Adult , Aged , Aged, 80 and over , Australia , Female , Health Services, Indigenous , Humans , Middle Aged , Native Hawaiian or Other Pacific Islander/statistics & numerical data , Qualitative Research
6.
J Anal At Spectrom ; 35(11): 2498-2508, 2020 Nov 01.
Article in English | MEDLINE | ID: mdl-33795908

ABSTRACT

Transition metal ions (Fe, Mn, Cu, Zn) are essential for healthy brain function, but altered concentration, distribution, or chemical form of the metal ions has been implicated in numerous brain pathologies. Currently, it is not possible to image the cellular or sub-cellular distribution of metal ions in vivo and therefore, studying brain-metal homeostasis largely relies on ex vivo in situ elemental mapping. Sample preparation methods that accurately preserve the in vivo elemental distribution are essential if one wishes to translate the knowledge of elemental distributions measured ex vivo toward increased understanding of chemical and physiological pathways of brain disease. The choice of sample preparation is particularly important for metal ions that exist in a labile or mobile form, for which the in vivo distribution could be easily distorted by inappropriate sample preparation. One of the most widely studied brain structures, the hippocampus, contains a large pool of labile and mobile Zn. Herein, we describe how sucrose cryoprotection, the gold standard method of preparing tissues for immuno-histochemistry or immuno-fluorescence, which is also often used as a sample preparation method for elemental mapping studies, drastically alters hippocampal Zn distribution. Based on the results of this study, in combination with a comparison against the strong body of published literature that has used either rapid plunge freezing of brain tissue, or sucrose cryo-protection, we strongly urge investigators in the future to cease using sucrose cryoprotection as a method of sample preparation for elemental mapping, especially if Zn is an analyte of interest.

7.
Metallomics ; 11(1): 151-165, 2019 01 23.
Article in English | MEDLINE | ID: mdl-30398510

ABSTRACT

A unique combination of sensitivity, resolution, and penetration make X-ray fluorescence imaging (XFI) ideally suited to investigate trace elemental distributions in the biological context. XFI has gained widespread use as an analytical technique in the biological sciences, and in particular enables exciting new avenues of research in the field of neuroscience. In this study, elemental mapping by XFI was applied to characterise the elemental content within neuronal cell layers of hippocampal sub-regions of mice and rats. Although classical histochemical methods for metal detection exist, such approaches are typically limited to qualitative analysis. Specifically, histochemical methods are not uniformly sensitive to all chemical forms of a metal, often displaying variable sensitivity to specific "pools" or chemical forms of a metal. In addition, histochemical methods require fixation and extensive chemical treatment of samples, creating the strong likelihood for metal redistribution, leaching, or contamination. Direct quantitative elemental mapping of total elemental pools, in situ within ex vivo tissue sections, without the need for chemical fixation or addition of staining reagents is not possible with traditional histochemical methods; however, such a capability, which is provided by XFI, can offer an enormous analytical advantage. The results we report herein demonstrate the analytical advantage of XFI elemental mapping for direct, label-free metal quantification, in situ within ex vivo brain tissue sections. Specifically, we definitively characterise for the first time, the abundance of Fe within the pyramidal cell layers of the hippocampus. Localisation of Fe to this cell layer is not reproducibly achieved with classical Perls histochemical Fe stains. The ability of XFI to directly quantify neuronal elemental (P, S, Cl, K, Ca, Fe, Cu, Zn) distributions, revealed unique profiles of Fe and Zn within anatomical sub-regions of the hippocampus i.e., cornu ammonis 1, 2 or 3 (CA1, CA2 or CA3) sub-regions. Interestingly, our study reveals a unique Fe gradient across neuron populations within the non-degenerating and pathology free rat hippocampus, which curiously mirrors the pattern of region-specific vulnerability of the hippocampus that has previously been established to occur in various neurodegenerative diseases.


Subject(s)
Hippocampus/cytology , Pyramidal Cells/chemistry , Animals , Elements , Hippocampus/chemistry , Iron/analysis , Male , Mice , Mice, Inbred C57BL , Potassium/analysis , Pyramidal Cells/cytology , Rats , Rats, Sprague-Dawley , Spectrometry, X-Ray Emission/methods , Zinc/analysis
8.
Analyst ; 143(16): 3761-3774, 2018 Aug 06.
Article in English | MEDLINE | ID: mdl-29961790

ABSTRACT

The incidence of brain disease and brain disorders is increasing on a global scale. Unfortunately, development of new therapeutic strategies has not increased at the same rate, and brain diseases and brain disorders now inflict substantial health and economic impacts. A greater understanding of the fundamental neurochemistry that underlies healthy brain function, and the chemical pathways that manifest in brain damage or malfunction, are required to enable and accelerate therapeutic development. A previous limitation to the study of brain function and malfunction has been the limited number of techniques that provide both a wealth of biochemical information, and spatially resolved information (i.e., there was a previous lack of techniques that provided direct biochemical or elemental imaging at the cellular level). In recent times, a suite of direct spectroscopic imaging techniques, such as Fourier transform infrared spectroscopy (FTIR), X-ray fluorescence microscopy (XFM), and X-ray absorption spectroscopy (XAS) have been adapted, optimized and integrated into the field of neuroscience, to fill the above mentioned capability-gap. Advancements at synchrotron light sources, such as improved light intensity/flux, increased detector sensitivities and new capabilities of imaging/optics, has pushed the above suite of techniques beyond "proof-of-concept" studies, to routine application to study complex research problems in the field of neuroscience (and other scientific disciplines). This review examines several of the major advancements that have occurred over the last several years, with respect to FTIR, XFM and XAS capabilities at synchrotron facilities, and how the increases in technical capabilities have being integrated and used in the field of neuroscience.


Subject(s)
Brain Diseases/diagnostic imaging , Brain/diagnostic imaging , Synchrotrons , Humans , Microscopy, Fluorescence , Spectroscopy, Fourier Transform Infrared , X-Ray Absorption Spectroscopy
9.
Metallomics ; 8(3): 305-12, 2016 Mar.
Article in English | MEDLINE | ID: mdl-26781816

ABSTRACT

Selenium is an essential micronutrient for many organisms, and in vertebrates has a variety of roles associated with protection from reactive oxygen species. Over the past two decades there have been conflicting reports upon human health benefits and detriments arising from consumption of selenium dietary supplements. Thus, early studies report a decrease in the incidence of certain types of cancer, whereas subsequent studies did not observe any anti-cancer effect, and adverse effects such as increased risks for type 2 diabetes have been reported. A possible contributing factor may be that different chemical forms of selenium were used in different studies. Using larval stage zebrafish (Danio rerio) as a model organism, we report a comparison of the toxicities and tissue selenium distributions of four different chemical forms of selenium. We find that the organic forms of selenium tested (Se-methyl-l-selenocysteine and l-selenomethionine) show considerably more toxicity than inorganic forms (selenite and selenate), and that this appears to be correlated with the level of bioaccumulation. Despite differences in concentrations, the tissue specific pattern of selenium accumulation was similar for the chemical forms tested; selenium was found to be highly concentrated in pigment (melanin) containing tissues especially for the organic selenium treatments, with lower concentrations in eye lens, yolk sac and heart. These results suggest that pigmented tissues might serve as a storage reservoir for selenium.


Subject(s)
Environmental Exposure , Inorganic Chemicals/toxicity , Organic Chemicals/toxicity , Selenium/metabolism , Zebrafish/metabolism , Animals , Larva/drug effects , Larva/metabolism , Organ Specificity/drug effects , Pigmentation/drug effects , Spectrometry, X-Ray Emission
10.
Mol Oral Microbiol ; 31(4): 354-64, 2016 Aug.
Article in English | MEDLINE | ID: mdl-26358096

ABSTRACT

Porphyromonas gingivalis is a Gram-negative anaerobe and keystone periodontal pathogen. A mariner transposon insertion mutant library has recently been used to define 463 genes as putatively essential for the in vitro growth of P. gingivalis ATCC 33277 in planktonic culture (Library 1). We have independently generated a transposon insertion mutant library (Library 2) for the same P. gingivalis strain and herein compare genes that are putatively essential for in vitro growth in complex media, as defined by both libraries. In all, 281 genes (61%) identified by Library 1 were common to Library 2. Many of these common genes are involved in fundamentally important metabolic pathways, notably pyrimidine cycling as well as lipopolysaccharide, peptidoglycan, pantothenate and coenzyme A biosynthesis, and nicotinate and nicotinamide metabolism. Also in common are genes encoding heat-shock protein homologues, sigma factors, enzymes with proteolytic activity, and the majority of sec-related protein export genes. In addition to facilitating a better understanding of critical physiological processes, transposon-sequencing technology has the potential to identify novel strategies for the control of P. gingivalis infections. Those genes defined as essential by two independently generated TnSeq mutant libraries are likely to represent particularly attractive therapeutic targets.


Subject(s)
Bacterial Proteins/genetics , DNA Transposable Elements , Gene Library , Genes, Bacterial , Heat-Shock Proteins/genetics , Porphyromonas gingivalis/genetics , Sigma Factor/genetics , Chromosome Mapping/methods , Genes, Essential , High-Throughput Nucleotide Sequencing/methods , Lipopolysaccharides/biosynthesis , Mutagenesis, Insertional , Mutation , Periodontal Diseases/microbiology , Porphyromonas gingivalis/growth & development , Pyrimidines/metabolism
11.
Eur J Prev Cardiol ; 21(4): 492-9, 2014 Apr.
Article in English | MEDLINE | ID: mdl-22605787

ABSTRACT

BACKGROUND: Supporting lifestyle change is an effective way of preventing recurrent events in people with cardiovascular disease (CVD). However, there is a need to develop innovative strategies that increase access to programmes for individuals at high risk of CVD. This study aimed to develop a bank of text messages designed to provide advice, motivation, and support for decreasing cardiovascular risk. DESIGN: Iterative development process with mixed methods METHODS: An initial bank of 120 text messages was drafted based on behaviour change techniques, guidelines, and input from clinicians and public health experts. A questionnaire was then administered to participants (n = 53) for evaluation of message content, usefulness, and language. To test the process of delivery, a pilot study was conducted using a specifically designed computer programme that delivered messages to multiple mobile phones according to a pre-specified schedule. Data were collected regarding message timing, delivery, and usefulness. RESULTS: In the qualitative questionnaire, 92% of participants found the messages easy to understand and 86% found the messages contained useful information. Positive feedback was also obtained from the pilot study. Based on these results, together with suggestions provided, several messages were reworded and an additional 44 were written. The need for semi-personalization was also identified and a random set of 103 individualized messages was created. CONCLUSIONS: A final bank of 137 mobile telephone text messages designed to support behaviour change and decrease cardiovascular risk have been developed through a multistep iterative process. This provides a scientific approach for future developers of health-related text messages.


Subject(s)
Cardiovascular Diseases/prevention & control , Cell Phone , Risk Reduction Behavior , Secondary Prevention/methods , Text Messaging , Cardiovascular Diseases/diagnosis , Cardiovascular Diseases/etiology , Health Knowledge, Attitudes, Practice , Humans , Motivation , Patient Acceptance of Health Care , Patient Satisfaction , Pilot Projects , Risk Factors , Time Factors , Treatment Outcome
12.
Mol Oral Microbiol ; 28(1): 70-81, 2013 Feb.
Article in English | MEDLINE | ID: mdl-23194602

ABSTRACT

The periodontal pathogen Porphyromonas gingivalis experiences a number of environmental conditions in the oral cavity, and must monitor and respond to a variety of environmental cues. However, the organism possesses only five full two-component systems, one of which is the hybrid system GppX. To investigate the regulon controlled by GppX we performed RNA-Seq on a ΔGppX mutant. Fifty-three genes were upregulated and 37 genes were downregulated in the ΔGppX mutant. Pathway analyses revealed no systemic function for GppX under nutrient-replete conditions; however, over 40% of the differentially abundant genes were annotated as encoding hypothetical proteins indicating a novel role for GppX. Abundance of small RNA was, in general, not affected by the absence of GppX. To further define the role of GppX with respect to regulation of a hypothetical protein observed with the greatest significant relative abundance change relative to a wild-type control, PGN_0151, we constructed a series of strains in which the ΔgppX mutation was complemented with a GppX protein containing specific domain and phosphotransfer mutations. The transmembrane domains, the DNA-binding domain and the phosphotransfer residues were all required for regulation of PGN_0151. In addition, binding of GppX to the PGN_0151 promoter regions was confirmed by an electrophoretic mobility shift assay. Both the ΔGppX mutant and a ΔPGN_0151 mutant were deficient in monospecies biofilm formation, suggesting a role for the GppX-PGN_0151 regulon in colonization and survival of the organism.


Subject(s)
Bacterial Proteins/genetics , Mutation/genetics , Porphyromonas gingivalis/genetics , Regulon/genetics , Alleles , AraC Transcription Factor/genetics , Aspartic Acid/genetics , Bacteriological Techniques , Biofilms/growth & development , Gene Expression Profiling , Gene Expression Regulation, Bacterial/genetics , Genes, Bacterial/genetics , Helix-Turn-Helix Motifs/genetics , Histidine Kinase , Humans , Membrane Proteins/genetics , Porphyromonas gingivalis/physiology , Promoter Regions, Genetic/genetics , Protein Kinases/genetics , Sequence Analysis, RNA , Signal Transduction/genetics
13.
Bone Marrow Transplant ; 47(12): 1520-5, 2012 Dec.
Article in English | MEDLINE | ID: mdl-22562079

ABSTRACT

Over the immediate past 4 years, our program has collected hematopoietic progenitor cells by apheresis from 48 individuals aged 61 and over (range 61-71 years of age). We have retrospectively analyzed the collection and transplant results associated with employing these donors, and have compared them with 175 donors aged 60 or less who were collected during the same time period. We have found no significant difference in venous access (P = 0.208), rate of post-transplant engraftment of neutrophils (P = 0.117) and platelets (P = 0.692), or in rate and grade of acute GVHD (P = 0.806). However, we have found that these older donors have a significantly lower mobilization of CD34 + cells as reflected in lower absolute counts of circulating CD34 + cells pre-apheresis (P = 0.016). This, in turn, results in lower CD34 + cell yields in apheresis products (P < 0.001), trending towards requiring more apheresis procedures (22.9 vs 13.7%, P = 0.095) to collect sufficient CD34 + cells for transplantation. We conclude that it is practical when necessary to employ donors aged 60 and above, as well as safe for both donor and intended recipient. However, concern over reduced CD34 + cell mobilization may be sufficient grounds to seek younger donors when possible.


Subject(s)
Blood Component Removal/methods , Hematopoietic Stem Cell Transplantation/methods , Age Factors , Aged , Female , Graft vs Host Disease/immunology , Hematopoietic Stem Cells/immunology , Humans , Male , Middle Aged , Retrospective Studies , Tissue Donors , Transplantation, Homologous
14.
BMJ Open ; 2(1): e000606, 2012.
Article in English | MEDLINE | ID: mdl-22267690

ABSTRACT

Background Although supporting lifestyle change is an effective way of preventing further events in people with cardiovascular disease, providing access to such interventions is a major challenge. This study aims to investigate whether simple reminders about behaviour change sent via mobile phone text message decrease cardiovascular risk. Methods and analysis Randomised controlled trial with 6 months of follow-up to evaluate the feasibility, acceptability and effect on cardiovascular risk of repeated lifestyle reminders sent via mobile phone text messages compared to usual care. A total of 720 patients with coronary artery disease will be randomised to either standard care or the TEXT ME intervention. The intervention group will receive multiple weekly text messages that provide information, motivation, support to quit smoking (if relevant) and recommendations for healthy diets and exercise. The primary end point is a change in plasma low-density lipoprotein cholesterol at 6 months. Secondary end points include a change in systolic blood pressure, smoking status, quality of life, medication adherence, waist circumference, physical activity levels, nutritional status and mood at 6 months. Process outcomes related to acceptability and feasibility of TEXT ME will also be collected. Ethics and dissemination Primary ethics approval was received from Western Sydney Local Health Network Human Research Ethics Committee-Westmead. Results will be disseminated via the usual scientific forums including peer-reviewed publications and presentations at international conferences. Clinical trials registration number ACTRN12611000161921.

15.
Int J Stroke ; 5(1): 52-6, 2010 Feb.
Article in English | MEDLINE | ID: mdl-20088995

ABSTRACT

RATIONALE: One in three patients experience depression after stroke and this risk is consistent over time. A strategy to prevent depression that could be economically delivered to most stroke patients and ideally which also has a low likelihood of adverse events needs to be developed and evaluated. Aims POST aims to determine whether a simple intervention (postcards) prevents depression (Hospital Anxiety and Depression rating Scale, HADS depression subscale score > or =8) in patients with a recent stroke. Secondary end-points include reduced anxiety (HADS anxiety subscale score > or =8) and improved health-related quality of life in patients with a recent stroke. DESIGN: A single-centre randomised, double-blind, pilot trial to prevent depression in patients with a recent (within 8 weeks) stroke presenting to hospital. Patients will be enrolled over 12 months and randomised to receive three trial-specific assessments (baseline, 3- and 6-month assessments of mood, HRQoL and social functioning), or three trial-specific assessments plus a postcard sent centrally in a sealed envelope at 1, 2, 3, 4 and 5 months after discharge from hospital. Blinded follow-up telephone assessments will be conducted for both groups. STUDY OUTCOMES AND SAMPLE SIZE: For the primary end-point the POST trial will have 80% power to detect a relative risk of 0.4 given an incidence of depression of 30%. For the secondary aims POST has 90% power to detect a difference of 3 points on the HADS depression subscale (assuming a standard deviation of 6 points) between randomised groups. This includes an inflation factor of 15% to account for patients lost to follow-up. DISCUSSION: Evidence of efficacy will determine whether a multi-centre, international trial is warranted.


Subject(s)
Depressive Disorder/psychology , Depressive Disorder/therapy , Stroke/psychology , Stroke/therapy , Activities of Daily Living , Anxiety/epidemiology , Anxiety/etiology , Anxiety/therapy , Clinical Protocols , Cost-Benefit Analysis , Depressive Disorder/etiology , Health Services Accessibility , Humans , Pilot Projects , Quality of Life , Research Design , Social Behavior , Social Environment , Stroke/complications , Suicide, Attempted/statistics & numerical data
16.
Diabetologia ; 52(11): 2328-2336, 2009 Nov.
Article in English | MEDLINE | ID: mdl-19688336

ABSTRACT

AIMS/HYPOTHESIS: The relationship between cognitive function, cardiovascular disease and premature death is not well established in patients with type 2 diabetes. We assessed the effects of cognitive function in 11,140 patients with type 2 diabetes who participated in the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) trial. Furthermore, we tested whether level of cognitive function altered the beneficial effects of the BP-lowering and glycaemic-control regimens in the trial. METHODS: Cognitive function was assessed using the Mini Mental State Examination at baseline, and defined by scores 28-30 ('normal', n = 8,689), 24-27 ('mild dysfunction', n = 2,231) and <24 ('severe dysfunction', n = 212). Risks of major cardiovascular events, death and hypoglycaemia and interactions with treatment were assessed using Cox proportional hazards analysis. RESULTS: Relative to normal function, both mild and severe cognitive dysfunction significantly increased the multiple-adjusted risks of major cardiovascular events (HR 1.27, 95% CI 1.11-1.46 and 1.42, 95% CI 1.01-1.99; both p < 0.05), cardiovascular death (1.41, 95% CI 1.16-1.71 and 1.56, 95% CI 0.99-2.46; both p

Subject(s)
Cognition , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/psychology , Diabetic Angiopathies/epidemiology , Diabetic Angiopathies/prevention & control , Gliclazide/therapeutic use , Hypoglycemia/epidemiology , Indapamide/therapeutic use , Perindopril/therapeutic use , Aged , Antihypertensive Agents/therapeutic use , Cognition/drug effects , Cognition Disorders/complications , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/mortality , Drug Combinations , Drug Therapy, Combination , Educational Status , Female , Humans , Hypoglycemic Agents/therapeutic use , Male , Mental Status Schedule , Myocardial Infarction/epidemiology , Risk Factors , Stroke/epidemiology
18.
J Dent Res ; 87(11): 1004-15, 2008 Nov.
Article in English | MEDLINE | ID: mdl-18946006

ABSTRACT

Quantitative proteomic analysis of microbial systems generates large datasets that can be difficult and time-consuming to interpret. Fortunately, many of the data display and gene-clustering tools developed to analyze large transcriptome microarray datasets are also applicable to proteomes. Plots of abundance ratio vs. total signal or spectral counts can highlight regions of random error and putative change. Displaying data in the physical order of the genes in the genome sequence can highlight potential operons. At a basic level of transcriptional organization, identifying operons can give insights into regulatory pathways as well as provide corroborating evidence for proteomic results. Classification and clustering algorithms can group proteins together by their abundance changes under different conditions, helping to identify interesting expression patterns, but often work poorly with noisy data such as typically generated in a large-scale proteomic analysis. Biological interpretation can be aided more directly by overlaying differential protein abundance data onto metabolic pathways, indicating pathways with altered activities. More broadly, ontology tools detect altered levels of protein abundance for different metabolic pathways, molecular functions, and cellular localizations. In practice, pathway analysis and ontology are limited by the level of database curation associated with the organism of interest.


Subject(s)
Bacterial Proteins/analysis , Gene Expression Profiling/methods , Protein Array Analysis/methods , Proteomics/methods , Classification , Cluster Analysis , Databases, Protein , Metabolic Networks and Pathways , Methanococcus/chemistry , Methanococcus/genetics , Porphyromonas gingivalis/chemistry , Porphyromonas gingivalis/genetics
19.
Arch. latinoam. nutr ; 57(1): 10-17, mar. 2007.
Article in English | LILACS | ID: lil-475643

ABSTRACT

The objective of this research is to assess the validity of a modified US Household Food Security Survey Module (HFSSM) through its correlation with food supply and demographic factors, and its fitness using Rasch model analysis in rural Ecuador. This study examines the relationship between household food insecurity and household food supplies in 52 Ecuadorian households. The sample was drawn from four rural communities participating in the project PLAN in Cantón Quijos. Questionnaires included a modified HFSSM, a household food shelf-inventory and demographic characteristics. Multiple ANOVA analysis resulted in statistically significant inverse relationships between household food insecurity and total food supply, as well as the supply of meat, vegetables, legumes, oils, and other food products (p=0.05). Rasch model measure values on the HFSSM illustrated food insecurity at different levels of severity. The majority of the items (>75%) presented adequate infit values. This study affirms that the proposed modified HFSSM may be useful to measure food insecurity and thus be used as a tool to monitor and evaluate programs aimed at improving quantity and variety of food items in rural Ecuador.


Inseguridad alimentaria y suministro de alimentos en hogares rurales de Ecuador. El objetivo de esta investigación es evaluar la validez de una escala doméstica de seguridad alimentaria modificada (HFSSM – en inglés: Household Food Security Survey Module) por medio de su correlación con el suministro de alimentos y características demográficas, así como su ajuste al modelo de Rasch en un área rural de Ecuador. En este estudio examinamos la relación entre la inseguridad alimentaria doméstica y el suministro de alimentos del hogar en 52 familias ecuatorianas. La muestra fue sacada de cuatro comunidades rurales participantes en el proyecto PLAN en el Cantón Quijos. Los cuestionarios aplicados incluyeron la HFSSM modificada, un inventario de despensa del hogar y características sociodemográficas. El análisis estadístico usando un modelo de ANOVA múltiple, mostró resultados inversamente significativos en la relación entre el nivel de seguridad alimentaria doméstica y el número total de alimentos disponibles, así como respecto a el suministro de carnes, verduras, legumbres, grasas y otros alimentos (p=0.05). Los valores de medida (measure values) de los insumos en la HFSSM usando el modelo Rasch muestran que la inseguridad alimentaria se presenta a diferentes niveles de severidad. La mayoría de las preguntas (>75%) presentaron valores de infit apropiados. Este estudio confirma que la HFSSM modificada puede ser útil para medir la inseguridad alimentaria y por eso puede ser usada como una herramienta para monitorear y evaluar programas enfocados en mejorar la cantidad y variedad de alimentos en el área rural de Ecuador.


Subject(s)
Humans , Food Supply/statistics & numerical data , Family Characteristics , Surveys and Questionnaires , Analysis of Variance , Ecuador , Reproducibility of Results , Rural Population , Socioeconomic Factors
20.
J Bacteriol ; 186(20): 6956-69, 2004 Oct.
Article in English | MEDLINE | ID: mdl-15466049

ABSTRACT

The genome sequence of the genetically tractable, mesophilic, hydrogenotrophic methanogen Methanococcus maripaludis contains 1,722 protein-coding genes in a single circular chromosome of 1,661,137 bp. Of the protein-coding genes (open reading frames [ORFs]), 44% were assigned a function, 48% were conserved but had unknown or uncertain functions, and 7.5% (129 ORFs) were unique to M. maripaludis. Of the unique ORFs, 27 were confirmed to encode proteins by the mass spectrometric identification of unique peptides. Genes for most known functions and pathways were identified. For example, a full complement of hydrogenases and methanogenesis enzymes was identified, including eight selenocysteine-containing proteins, with each being paralogous to a cysteine-containing counterpart. At least 59 proteins were predicted to contain iron-sulfur centers, including ferredoxins, polyferredoxins, and subunits of enzymes with various redox functions. Unusual features included the absence of a Cdc6 homolog, implying a variation in replication initiation, and the presence of a bacterial-like RNase HI as well as an RNase HII typical of the Archaea. The presence of alanine dehydrogenase and alanine racemase, which are uniquely present among the Archaea, explained the ability of the organism to use L- and D-alanine as nitrogen sources. Features that contrasted with the related organism Methanocaldococcus jannaschii included the absence of inteins, even though close homologs of most intein-containing proteins were encoded. Although two-thirds of the ORFs had their highest Blastp hits in Methanocaldococcus jannaschii, lateral gene transfer or gene loss has apparently resulted in genes, which are often clustered, with top Blastp hits in more distantly related groups.


Subject(s)
Archaeal Proteins/metabolism , Genome, Archaeal , Hydrogen/metabolism , Methane/metabolism , Methanococcus/genetics , Sequence Analysis, DNA , Archaeal Proteins/genetics , Methanococcus/metabolism , Molecular Sequence Data , Proteome
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