279 research outputs found

    Health related quality of life trajectories and predictors following coronary artery bypass surgery

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    BACKGROUND: Many studies have demonstrated that health related quality of life (HRQoL) improves, on average, after coronary artery bypass graft surgery (CABGS). However, this average improvement may not be realized for all patients, and it is possible that there are two or more distinctive groups with different, possibly non-linear, trajectories of change over time. Furthermore, little is known about the predictors that are associated with these possible HRQoL trajectories after CABGS. METHODS: 182 patients listed for elective CABGS at The Royal Melbourne Hospital completed a postal battery of questionnaires which included the Short-Form-36 (SF-36), Profile of Mood States (POMS) and the Everyday Functioning Questionnaire (EFQ). These data were collected on average a month before surgery, and at two months and six months after surgery. Socio-demographic and medical characteristics prior to surgery, as well as surgical and post-surgical complications and symptoms were also assessed. Growth curve and growth mixture modelling were used to identify trajectories of HRQoL. RESULTS: For both the physical component summary scale (PCS) and the mental component summary scale (MCS) of the SF-36, two groups of patients with distinct trajectories of HRQoL following surgery could be identified (improvers and non-improvers). A series of logistic regression analyses identified different predictors of group membership for PCS and MCS trajectories. For the PCS the most significant predictors of non-improver membership were lower scores on POMS vigor-activity and higher New York Heart Association dyspnoea class; for the MCS the most significant predictors of non-improver membership were higher scores on POMS depression-dejection and manual occupation. CONCLUSION: It is incorrect to assume that HRQoL will improve in a linear fashion for all patients following CABGS. Nor was there support for a single response trajectory. It is important to identify characteristics of each patient, and those post-operative symptoms that could be possible targets for intervention to improve HRQoL outcomes

    Exploring local knowledge and perceptions on zoonoses among pastoralists in northern and eastern Tanzania

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    Background: Zoonoses account for the most commonly reported emerging and re-emerging infectious diseases in Sub-Saharan Africa. However, there is limited knowledge on how pastoral communities perceive zoonoses in relation to their livelihoods, culture and their wider ecology. This study was carried out to explore local knowledge and perceptions on zoonoses among pastoralists in Tanzania. Methodology and principal findings: This study involved pastoralists in Ngorongoro district in northern Tanzania and Kibaha and Bagamoyo districts in eastern Tanzania. Qualitative methods of focus group discussions, participatory epidemiology and interviews were used. A total of 223 people were involved in the study. Among the pastoralists, there was no specific term in their local language that describes zoonosis. Pastoralists from northern Tanzania possessed a higher understanding on the existence of a number of zoonoses than their eastern districts' counterparts. Understanding of zoonoses could be categorized into two broad groups: a local syndromic framework, whereby specific symptoms of a particular illness in humans concurred with symptoms in animals, and the biomedical framework, where a case definition is supported by diagnostic tests. Some pastoralists understand the possibility of some infections that could cross over to humans from animals but harm from these are generally tolerated and are not considered as threats. A number of social and cultural practices aimed at maintaining specific cultural functions including social cohesion and rites of passage involve animal products, which present zoonotic risk. Conclusions: These findings show how zoonoses are locally understood, and how epidemiology and biomedicine are shaping pastoralists perceptions to zoonoses. Evidence is needed to understand better the true burden and impact of zoonoses in these communities. More studies are needed that seek to clarify the common understanding of zoonoses that could be used to guide effective and locally relevant interventions. Such studies should consider in their approaches the pastoralists' wider social, cultural and economic set up

    Antioxidant activity and antimicrobial properties of <i>Entada leptostachya</i> and <i>Prosopis juliflora</i> extracts

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    Background: Natural phytoconstituents produced by plants for their sustenance have been reported to reduce disease. Objectives: This study determined the phytoconstituents, antioxidant and antimicrobial activity of crude methanolic extracts of Entada leptostachya and Prosopis juliflora extracts. Methodology: Antioxidant activity was determined using 2,2-diphenyl-1-picrylhydrazyl and β-carotene assays; the total phenolic and flavonoid were estimated using Folin–Ciocalteau and aluminium chloride, whereas antimicrobial activity was determined using the zone of inhibition method. Results: Screening of the extracts revealed the presence of terpenoids, flavonoids, saponins and phenols. Fourier transform infrared spectra of the extracts revealed presence of hydrogen bonded –OH functional group. E. leptostachya barks had the highest antioxidant activity followed by P. juliflora roots, E. leptostachya roots and P. juliflora leaves [μg/mL]. Prosopis juliflora (roots) had the highest bleaching effect, whereas E. leptostachya (barks) had the lowest bleaching effect. The total flavonoids were determined to be 0.15 ± 0.02 mg/g, 1.18 ± 0.18 mg/g, 0.39 ± 0.05 mg/g and 0.64 ± 0.03 mg/g for E. leptostachya roots, E. leptostachya barks, P. juliflora leaves and P. juliflora roots extracts, respectively. The total phenols were determined to be 0.93 ± 0.18 mg/g, 2.69 ± 0.41 mg/g, 0.62 ± 0.08 mg/g and 0.62 ± 0.08 mg/g for E. leptostachya roots, E. leptostachya barks, P. juliflora roots and P. juliflora leaves extracts. All plant extracts exhibited moderate activity against the growth of selected microorganisms. Conclusion: Antimicrobial and antioxidant activity of the two plants was as a result of secondary metabolites found in the crude extracts

    SEMA4D compromises blood–brain barrier, activates microglia, and inhibits remyelination in neurodegenerative disease

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    AbstractMultiple sclerosis (MS) is a chronic neuroinflammatory disease characterized by immune cell infiltration of CNS, blood–brain barrier (BBB) breakdown, localized myelin destruction, and progressive neuronal degeneration. There exists a significant need to identify novel therapeutic targets and strategies that effectively and safely disrupt and even reverse disease pathophysiology. Signaling cascades initiated by semaphorin 4D (SEMA4D) induce glial activation, neuronal process collapse, inhibit migration and differentiation of oligodendrocyte precursor cells (OPCs), and disrupt endothelial tight junctions forming the BBB. To target SEMA4D, we generated a monoclonal antibody that recognizes mouse, rat, monkey and human SEMA4D with high affinity and blocks interaction between SEMA4D and its cognate receptors. In vitro, anti-SEMA4D reverses the inhibitory effects of recombinant SEMA4D on OPC survival and differentiation. In vivo, anti-SEMA4D significantly attenuates experimental autoimmune encephalomyelitis in multiple rodent models by preserving BBB integrity and axonal myelination and can be shown to promote migration of OPC to the site of lesions and improve myelin status following chemically-induced demyelination. Our study underscores SEMA4D as a key factor in CNS disease and supports the further development of antibody-based inhibition of SEMA4D as a novel therapeutic strategy for MS and other neurologic diseases with evidence of demyelination and/or compromise to the neurovascular unit

    Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis.

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    Multiple sclerosis is a common disease of the central nervous system in which the interplay between inflammatory and neurodegenerative processes typically results in intermittent neurological disturbance followed by progressive accumulation of disability. Epidemiological studies have shown that genetic factors are primarily responsible for the substantially increased frequency of the disease seen in the relatives of affected individuals, and systematic attempts to identify linkage in multiplex families have confirmed that variation within the major histocompatibility complex (MHC) exerts the greatest individual effect on risk. Modestly powered genome-wide association studies (GWAS) have enabled more than 20 additional risk loci to be identified and have shown that multiple variants exerting modest individual effects have a key role in disease susceptibility. Most of the genetic architecture underlying susceptibility to the disease remains to be defined and is anticipated to require the analysis of sample sizes that are beyond the numbers currently available to individual research groups. In a collaborative GWAS involving 9,772 cases of European descent collected by 23 research groups working in 15 different countries, we have replicated almost all of the previously suggested associations and identified at least a further 29 novel susceptibility loci. Within the MHC we have refined the identity of the HLA-DRB1 risk alleles and confirmed that variation in the HLA-A gene underlies the independent protective effect attributable to the class I region. Immunologically relevant genes are significantly overrepresented among those mapping close to the identified loci and particularly implicate T-helper-cell differentiation in the pathogenesis of multiple sclerosis

    Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

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    BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London
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