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In silico drug repurposing for the identification of potential candidate molecules against arboviruses infection
Arboviral diseases caused by dengue (DENV), Zika (ZIKV) and chikungunya (CHIKV) viruses represent a major public health problem worldwide, especially in tropical areas where millions of infections occur every year. The aim of this research was to identify candidate molecules for the treatment of these diseases among the drugs currently available in the market, through in silico screening and subsequent in vitro evaluation with cell culture models of DENV and ZIKV infections. Numerous pharmaceutical compounds from antibiotics to chemotherapeutic agents presented high in silico binding affinity for the viral proteins, including ergotamine, antrafenine, natamycin, pranlukast, nilotinib, itraconazole, conivaptan and novobiocin. These five last compounds were tested in vitro, being pranlukast the one that exhibited the best antiviral activity. Further in vitro assays for this compound showed a significant inhibitory effect on DENV and ZIKV infection of human monocytic cells and human hepatocytes (Huh-7 cells) with potential abrogation of virus entry. Finally, intrinsic fluorescence analyses suggest that pranlukast may have some level of interaction with three viral proteins of DENV: envelope, capsid, and NS1. Due to its promising results, suitable accessibility in the market and reduced restrictions compared to other pharmaceuticals; the anti-asthmatic pranlukast is proposed as a drug candidate against DENV, ZIKV, and CHIKV, supporting further in vitro and in vivo assessment of the potential of this and other lead compounds that exhibited good affinity scores in silico as therapeutic agents or scaffolds for the development of new drugs against arboviral diseases. © 2019 Elsevier B.V. ; Universidad Tecnológica de Pereira, UTP: TRFCI-1P2016 National Institutes of Health, NIH National Institutes of Health, NIH: R01 AI24493 Department of Science, Information Technology and Innovation, Queensland Government, DSITI: 811-2018 Universidad Autónoma de Bucaramanga, UNAB ; The authors wish to thank the Administrative Department of Science, Technology and Innovation of Colombia [Grant: Colciencias No. 811-2018 ], Universidad Nacional Autónoma de México [Grant: Programa de Becas Posdoctorales en la UNAM 2016 ], Universidad Tecnológica de Bolívar [Grant: TRFCI-1P2016 ] and the National Institutes of Health [NIH grant R01 AI24493 ] for their financial support. Appendix A ; A continuación se relacionan los compuestos químicos y su número de registro CAS (Chemical Abstracts Service) antrafenine, 55300-29-3; conivaptan, 168626-94-6, 210101-16-9; ergotamine, 113-15-5, 52949-35-6; itraconazole, 84625-61-6; natamycin, 52882-37-8, 7681-93-8; nilotinib, 641571-10-0; novobiocin, 1476-53-5, 303-81-1, 39301-00-3, 4309-70-0; pranlukast, 103177-37-3
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Books in review
In: African studies, Band 6, Heft 3, S. 151-156
ISSN: 1469-2872
Assessing the health impact of transnational corporations: A case study on McDonald's Australia
© 2017 The Author(s). Background: The practices of transnational corporations affect population health through production methods, shaping social determinants of health, or influencing the regulatory structures governing their activities. There has been limited research on community exposures to TNC policies and practices. Our pilot research used McDonald's Australia to test methods for assessing the health impacts of one TNC within Australia. Methods: We adapted existing Health Impact Assessment methods to assess McDonald's activities. Data identifying potential impacts were sourced through document analysis, including McDonald's corporate literature; media analysis and semi-structured interviews. We commissioned a spatial and socioeconomic analysis of McDonald's restaurants in Australia through Geographic Information System technology. The data was mapped against a corporate health impact assessment framework which included McDonald's Australia's political and business practices; products and marketing; workforce, social, environmental and economic conditions; and consumers' health related behaviours. Results: We identified both positive and detrimental aspects of McDonald's Australian operations across the scope of the CHIA framework. We found that McDonald's outlets were slightly more likely to be located in areas of lower socioeconomic status. McDonald's workplace conditions were found to be more favourable than those in many other countries which reflects compliance with Australian employment regulations. The breadth of findings revealed the need for governments to strengthen regulatory mechanisms that are conducive to health; the opportunity for McDonald's to augment their corporate social responsibility initiatives and bolster reputational endorsement; and civil society actors to inform their advocacy towards health and equity outcomes from TNC operations. Conclusion: Our study indicates that undertaking a corporate health impact assessment is possible, with the different methods revealing sufficient information to realise that strong regulatory frameworks are need to help to avoid or to mediate negative health impacts.
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Recovering convict lives: a historical archaeology of the Port Arthur Penitentiary
In: Studies in Australasian historical archaeology
The World Heritage-listed Port Arthur penitentiary is one of Australia's most visited historical sites, attracting over 400,000 visitors each year. Designed to incarcerate 480 men, between 1856 and 1877 thousands of convicts passed through it. In 2016, archaeologists began one of the largest ever excavations of an Australian convict site. Recovering Convict Lives: Historical Archaeology of the Port Arthur Penitentiary makes their findings available to general readers for the first time. Extensively illustrated, it is a fascinating journey into the inner workings of the penal system and the day-to-day lives of Port Arthur convicts. Through the things they left behind - the sandstone base of a prison wall, a clay pipe discarded in a washroom, gambling tokens dropped between floorboards - this book tells their stories
Risk of revision arthroplasty surgery after exposure to physically demanding occupational or leisure activities: a systematic review
Introduction: lower limb arthroplasty is successful at relieving symptoms associated with joint failure. However, physically-demanding activities can cause primary osteoarthritis and accordingly such exposure post-operatively might increase the risk of prosthetic failure. Therefore, we systematically reviewed the literature to investigate whether there was any evidence of increased risk of revision arthroplasty after exposure to intensive, physically-demanding activities at work or during leisure-time. Methods: we searched Medline, Embase and Scopus databases (1985—July 2021) for original studies including primary lower limb arthroplasty recipients that gathered information on physically-demanding occupational and/or leisure activities and rates of revision arthroplasty. Methodological assessment was performed independently by two assessors using SIGN, AQUILA and STROBE. The protocol was registered in PROSPERO [CRD42017067728]. Results: thirteen eligible studies were identified: 9 (4,432 participants) after hip arthroplasty and 4 (7,137participants) after knee arthroplasty. Narrative synthesis was performed due to considerable heterogeneity in quantifying exposures. We found limited evidence that post-operative activities (work or leisure) did not increase the risk of knee revision and could even be protective. We found insufficient high-quality evidence to indicate that exposure to physically-demanding occupations increased the risk of hip revision although "heavy work", agricultural work and, in women, health services work, may be implicated. We found conflicting evidence about risk of revision hip arthroplasty associated with either leisure-time or total physical activities (occupational or leisure-time). Conclusion: there is currently a limited evidence base to address this important question. There is weak evidence that the risk of revision hip arthroplasty may be increased by exposure to physically-demanding occupational activities but insufficient evidence about the impact on knee revision and about exposure to leisure-time activities after both procedures. More evidence is urgently needed to advise lower limb arthroplasty recipients, particularly people expecting to return to jobs in some sectors (e.g., construction, agriculture, military).
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Health in all policies in south Australia—did it promote and enact an equity perspective?
© 2017 by the authors. Licensee MDPI, Basel, Switzerland. Mobilising cross-sectoral action is helpful in addressing the range of social determinants that contribute to health inequities. The South Australian Health in All Policies (SA HiAP) approach was implemented from 2007 to stimulate cross-sector policy activity to address the social determinants of health to improve population wellbeing and reduce health inequities. This paper presents selected findings from a five year multi-methods research study of the SA HiAP approach and draws on data collected during interviews, observation, case studies, and document analysis. The analysis shows that SA HiAP had dual goals of facilitating joined-up government for co-benefits (process focus); and addressing social determinants of health and inequities through cross-sectoral policy activity (outcomes focus). Government agencies readily understood HiAP as providing tools for improving the process of intersectoral policy development, while the more distal outcome-focused intent of improving equity was not well understood and gained less traction. While some early rhetorical support existed for progressing an equity agenda through SA HiAP, subsequent economic pressures resulted in the government narrowing its priorities to economic goals. The paper concludes that SA HiAP's initial intentions to address equity were only partially enacted and little was done to reduce inequities. Emerging opportunities in SA, and internationally, including the UN Sustainable Development Goals, may revive interest in addressing equity.
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Regional trends in awards of incapacity benefit by cause
In: Cattrell , A , Harris , E C , Palmer , K T , Kim , M , Aylward , M & Coggon , D 2011 , ' Regional trends in awards of incapacity benefit by cause ' , Occupational Medicine , vol. 61 , no. 3 , pp. 148 - 151 . https://doi.org/10.1093/occmed/kqr008
Background Since the early 1990s, rates of incapacity benefit ( IB) in Britain for musculoskeletal complaints have declined, and they have been overtaken by mental and behavioural disorders as the main reason for award of IB. Aims To explore reasons for this change. Methods Using data supplied by the Department for Work and Pensions, we analysed trends in the ratio of new IB awards for mental and behavioural disorders to those for musculoskeletal disorders during 1997-2007 by Government region. Results In Great Britain overall, the above ratio more than doubled over the study period, as a consequence of falling numbers of new awards for musculoskeletal disorders. The extent to which the ratio increased was smallest in London (50%) and South-East England (56%), and was progressively larger in more northerly regions (> 150% in North-East England and Scotland). Conclusions The differences in trends between regions seem too large to be explained by differential changes in working conditions, patterns of employment or the rigour with which claims were assessed. An alternative explanation could be that the main driver for the trends has been culturally determined changes in health beliefs and expectations, and that these cultural changes began in London and the South-East, only later spreading to other parts of Britain.
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Relationships between informal caregiving, health and work in the Health and Employment After Fifty study, England
Background: to investigate the prevalence of caregiving, and its relationship with work, health, and socio-economic circumstances in the Health and Employment After Fifty (HEAF) study. Methods: the HEAF study comprises 8,134 men and women aged 50-64 years recruited from 24 general practices. Socio-demographic, lifestyle, and health characteristics, and hours/week giving personal care were elicited by postal questionnaire. Objective clinical information about diagnoses/medications was retrieved from health records. Work-related and health risk factors for intense caring responsibilities (≥20 hours/week vs no hours) were explored using logistic regression with adjustment for age and social class. Results: 644(17%) men and 1153(26%) women reported caring responsibilities, of whom 93 and 199 were intense caregivers, who were: more likely to be socio-economically disadvantaged; less likely to be working; and, if combining caring with working (41 men, 90 women), more likely to be part-time/working shifts, than non-carers. Men caring ≥20 hours/week were more likely to have COPD and to report musculoskeletal pain, poor/fair self-rated health, depression and sleep problems. Among working women, caring ≥20 hours/week was associated with these same health outcomes and also with a doctor-diagnosed mental health problem or musculoskeletal pain in the previous year. Conclusions: caregiving is common and unequal in the HEAF cohort, with more high-intensity informal care provided by those with greater levels of socio-economic deprivation, which could affect their employment and health. Caregivers need support to lead long, healthy lives, rather than becoming care needers themselves. Employers and governments need to take caregiving into account and support it actively.
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Recent UK retirees' views about the work-related factors which influenced their decision to retire: a qualitative study within the Health and Employment After Fifty (HEAF) cohort
Background Lower birth rates and increasing longevity have resulted in ageing populations in European countries. These demographic changes place challenges on pension provision as numbers of those who are economically inactive and retired increase relative to those in paid work. Therefore, governments need workers to postpone retirement and work to older ages. Whilst health and wealth are important in retirement decision-making, considerably less is known about the effects of workplace factors. The aim of this study was to explore the views of recent UK retirees about the role that work-related factors played in their decision to retire. Methods This qualitative study was nested within the Health and Employment After Fifty (HEAF) cohort. People who had retired 3-6 years previously (not for health reasons) were purposively sampled to obtain the views of men and women from a range of socio-economic backgrounds and jobs. Semi-structured interviews were carried out by telephone using a pre-defined topic guide. Interviews were audio-recorded, transcribed and analysed thematically. Results Seventeen interviews were conducted. Thematic analysis showed that retirement decisions were complex and multi-factorial but that work-related factors contributed to decision-making in two main ways. First, some work factors pushed participants towards retirement. These were perceptions that: workplace change had affected the way they were valued or increased pressure on them; work demands, including commuting, had intruded excessively on personal time, effects that were exacerbated by modern technology; work was draining, isolating or under-appreciated; and /or that work was causing physical strain or discomfort relative to their perception of their capacity. In contrast, work factors could also cause participants to pull back towards work, particularly: autonomy; supportive work colleagues; a sense of being appreciated; and perceived job flexibility. Conclusions Recent retirees explained that their decision to retire was multi-factorial but work-related factors contributed importantly. Potentially, employers could: review workers' perceptions about their work; their capacity in relation to job demands; increase flexibility; and facilitate a supportive work community to encourage longer working lives.
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Recent UK retirees' views about the work-related factors which influenced their decision to retire: a qualitative study within the Health and Employment After Fifty (HEAF) cohort
BACKGROUND: Lower birth rates and increasing longevity have resulted in ageing populations in European countries. These demographic changes place challenges on pension provision as numbers of those who are economically inactive and retired increase relative to those in paid work. Therefore, governments need workers to postpone retirement and work to older ages. Whilst health and wealth are important in retirement decision-making, considerably less is known about the effects of workplace factors. The aim of this study was to explore the views of recent UK retirees about the role that work-related factors played in their decision to retire. METHODS: This qualitative study was nested within the Health and Employment After Fifty (HEAF) cohort. People who had retired 3-6 years previously (not for health reasons) were purposively sampled to obtain the views of men and women from a range of socio-economic backgrounds and jobs. Semi-structured interviews were carried out by telephone using a pre-defined topic guide. Interviews were audio-recorded, transcribed and analysed thematically. RESULTS: Seventeen interviews were conducted. Thematic analysis showed that retirement decisions were complex and multi-factorial but that work-related factors contributed to decision-making in two main ways. First, some work factors pushed participants towards retirement. These were perceptions that: workplace change had affected the way they were valued or increased pressure on them; work demands, including commuting, had intruded excessively on personal time, effects that were exacerbated by modern technology; work was draining, isolating or under-appreciated; and /or that work was causing physical strain or discomfort relative to their perception of their capacity. In contrast, work factors could also cause participants to pull back towards work, particularly: autonomy; supportive work colleagues; a sense of being appreciated; and perceived job flexibility. CONCLUSIONS: Recent retirees explained that their decision to retire was ...
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Scope, quality, and inclusivity of clinical guidelines produced early in the covid-19 pandemic: rapid review
OBJECTIVE: To appraise the availability, quality, and inclusivity of clinical guidelines produced in the early stage of the coronavirus disease 2019 (covid-19) pandemic. DESIGN: Rapid review. DATA SOURCES: Ovid Medline, Ovid Embase, Ovid Global Health, Scopus, Web of Science Core Collection, and WHO Global Index Medicus, searched from inception to 14 Mar 2020. Search strategies applied the CADTH database guidelines search filter, with no limits applied to search results. Further studies were identified through searches of grey literature using the ISARIC network. INCLUSION CRITERIA: Clinical guidelines for the management of covid-19, Middle East respiratory syndrome (MERS), and severe acute respiratory syndrome (SARS) produced by international and national scientific organisations and government and non-governmental organisations relating to global health were included, with no exclusions for language. Regional/hospital guidelines were excluded. Only the earliest version of any guideline was included. QUALITY ASSESSMENT: Quality was assessed using the Appraisal of Guidelines for Research and Evaluation (AGREE) II tool. The quality and contents of early covid-19 guidelines were also compared with recent clinical guidelines for MERS and SARS. RESULTS: 2836 studies were identified, of which 2794 were excluded after screening. Forty two guidelines were considered eligible for inclusion, with 18 being specific to covid-19. Overall, the clinical guidelines lacked detail and covered a narrow range of topics. Recommendations varied in relation to, for example, the use of antiviral drugs. The overall quality was poor, particularly in the domains of stakeholder involvement, applicability, and editorial independence. Links between evidence and recommendations were limited. Minimal provision was made for vulnerable groups such as pregnant women, children, and older people. CONCLUSIONS: Guidelines available early in the covid-19 pandemic had methodological weaknesses and neglected vulnerable groups such as older people. A ...
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Contemporary challenges for specialist nursing in interstitial lung disease
The role of clinical nurse specialists (CNSs) in interstitial lung disease (ILD) is evolving in response to clinical guidelines and the growth of clinical research. The role is well established in the UK, although more ILD posts are needed to ensure supply meets clinical demand. This phenomenon is also happening across Europe. An appreciation of the similarities and differences between CNS and advanced nurse practitioners is important given the challenges in defining, developing and supporting this nursing specialisation. Globally, different models exist. In some countries charitable organisations take a leading role in supporting patients. Many European centres look to the National Institute for Health and Care Excellence guidelines and quality standards as a template to develop and evaluate the role of the ILD CNS. We present a UK perspective in the context of a government subsidised healthcare system to promote professional discussion and debate regarding the future of nursing practice in the ILD specialty.
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Social determinants of prostate cancer in the Caribbean: a systematic review and meta-analysis
BACKGROUND: Prostate cancer remains the leading cause of cancer deaths among Caribbean men. However, little data exists on the influence of social factors on prostate cancer in the Caribbean setting. This article supports the 2011 Rio Political Declaration on addressing health inequalities by presenting a systematic review of evidence on the role of social determinants on prostate cancer in Caribbean men. It aims to determine the distribution, by known social determinants of health, of the frequency and adverse outcomes of prostate cancer among Caribbean populations. METHODS: Observational studies reporting an association between a social determinant and prostate cancer frequency and outcomes were sought in MEDLINE, EMBASE, SciELO, CINAHL, CUMED, LILACS, and IBECS databases. Fourteen social determinants and 7 prostate cancer endpoints were chosen, providing 98 possible relationship groups exploring the role of social determinants on prostate cancer. Observational studies with > 50 participants conducted in Caribbean territories between 2004 and 2016 were eligible. The review was conducted according to STROBE and PRISMA guidelines. Random-effects meta-analyses were performed. RESULTS: From 843 potentially relevant citations, 13 articles from 9 studies were included. From these included studies, 24 relationships were reported looking at 11 distinct relationship groups, leaving 90 relationship groups (92% of all relationship groups) unexplored. Study heterogeneity and risk of bias restricted results to a narrative synthesis in most instances. Meta-analyses showed more diagnosed prostate cancer among men with less formal education (n = 2 studies, OR 1.60, 95%CI 1.18-2.19) and among men who were married (n = 3 studies, OR 1.54, 95%CI 1.22-1.95). CONCLUSIONS: This review highlights limited evidence for a higher occurrence of diagnosed prostate cancer among Caribbean men with lower levels of education and among men who are married. The role of social determinants on prostate cancer among Caribbean men remains poorly understood. Improvements in study quantity and quality, and reduced variability in outcomes and reporting are needed. This report represents the current evidence, and provides a roadmap to future research priorities for a better understanding of Caribbean prostate cancer inequalities. ; This study was fully supported by grant number U24MD006959 from the National Institute on Minority Health and Health Disparities.
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