106 research outputs found

    The Immune Response to Herpes Simplex Virus Type 1 Infection in Susceptible Mice is a Major Cause of CNS Pathology Resulting in Fatal Encephalitis

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    This study was undertaken to investigate possible immune mechanisms in fatal HSV-1 encephalitis (HSE) after HSV-1 corneal inoculation. Susceptible 129S6 (129) but not resistant C57BL/6 (B6) mice developed intense focal inflammatory brainstem lesions of primarily F4/80+ macrophages and Gr-1+ neutrophils detectable by MRI as early as day 6 post infection (PI). Depletion of macrophages and neutrophils significantly enhanced survival of infected 129 mice. Immunodeficient B6 (IL-7R-/-Kitw41/w41) mice lacking adaptive cells (B6-E mice) transplanted with 129 bone marrow showed significantly accelerated fatal HSE compared to B6-E mice transplanted with B6 marrow or control non-transplanted B6-E mice. In contrast, there was no difference in ocular viral shedding in B6-E mice transplanted with 129 bone marrow or B6 bone marrow. Acyclovir treatment of 129 mice beginning day 4 PI (24 h after HSV-1 first reaches the brain stem) reduced nervous system viral titers to undetectable levels but did not alter brainstem inflammation or mortality. We conclude that fatal HSE in 129 mice results from widespread damage in the brainstem caused by destructive inflammatory responses initiated early in infection by massive infiltration of innate cells

    Effect of evacuation and displacement on the association between flooding and mental health outcomes: a cross-sectional analysis of UK survey data.

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    BACKGROUND: Extensive flooding occurred during the winter of 2013-14 in England. Previous studies have shown that flooding affects mental health. Using data from the 2013-14 Public Health England National Study of Flooding and Health, we compared the prevalence of symptoms of depression, anxiety, and post-traumatic stress disorder between participants displaced by flooding and those flooded, but not displaced, 1 year after flooding. METHODS: In this multivariable ordinal regression analysis, we collected data from a cross-sectional survey collected 1 year after the flooding event from flood-affected postcodes in five counties in England. The analysis was restricted to individuals whose homes were flooded (n=622) to analyse displacement due to flooding. The primary outcome measures were depression (measured by the PHQ-2 depression scale) and anxiety (measured by the two-item Generalised Anxiety Disorder [GAD]-2 anxiety scale), and post-traumatic stress disorder (measured by the Post-Traumatic Stress Disorder Checklist [PCL]-6 scale). We adjusted analyses for recorded potential confounders. We also analysed duration of displacement and amount of warning received. FINDINGS: People who were displaced from their homes were significantly more likely to have higher scores on each scale; odds ratio (OR) for depression 1·95 (95% CI 1·30-2·93), for anxiety 1·66 (1·12-2·46), and for post-traumatic stress disorder 1·70 (1·17-2·48) than people who were not displaced. The increased risk of depression was significant even after adjustment for severity of flooding. Scores for depression and post-traumatic stress disorder were higher in people who were displaced and reported receiving no warning than those who had received a warning more than 12 h in advance of flooding (p=0·04 for depression, p=0·01 for post-traumatic stress disorder), although the difference in anxiety scores was not significant. INTERPRETATION: Displacement after flooding was associated with higher reported symptoms of depression, anxiety, and post-traumatic stress disorder 1 year after flooding. The amount of warning received showed evidence of being protective against symptoms of the three mental illnesses studied, and the severity of flooding might be the reason for some, but not all, of the differences between the groups. FUNDING: National Institute for Health Research Health Protection Research Units (HPRU) in Emergency Preparedness and Response at King's College London, Environmental Change and Health at the London School of Hygiene and Tropical Medicine, and Evaluation of Interventions at the University of Bristol, Public Health England

    Impacts of Climate Change on indirect human exposure to pathogens and chemicals from agriculture

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    Objective: Climate change is likely to affect the nature of pathogens and chemicals in the environment and their fate and transport. Future risks of pathogens and chemicals could therefore be very different from those of today. In this review, we assess the implications of climate change for changes in human exposures to pathogens and chemicals in agricultural systems in the United Kingdom and discuss the subsequent effects on health impacts. Data sources: In this review, we used expert input and considered literature on climate change ; health effects resulting from exposure to pathogens and chemicals arising from agriculture ; inputs of chemicals and pathogens to agricultural systems ; and human exposure pathways for pathogens and chemicals in agricultural systems. Data synthesis: We established the current evidence base for health effects of chemicals and pathogens in the agricultural environment ; determined the potential implications of climate change on chemical and pathogen inputs in agricultural systems ; and explored the effects of climate change on environmental transport and fate of different contaminant types. We combined these data to assess the implications of climate change in terms of indirect human exposure to pathogens and chemicals in agricultural systems. We then developed recommendations on future research and policy changes to manage any adverse increases in risks. Conclusions: Overall, climate change is likely to increase human exposures to agricultural contaminants. The magnitude of the increases will be highly dependent on the contaminant type. Risks from many pathogens and particulate and particle-associated contaminants could increase significantly. These increases in exposure can, however, be managed for the most part through targeted research and policy changes

    The English National Cohort Study of Flooding and Health: the change in the prevalence of psychological morbidity at year two.

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    BACKGROUND: The longer term impact of flooding on health is poorly understood. In 2015, following widespread flooding in the UK during winter 2013/14, Public Health England launched the English National Study of Flooding and Health. The study identified a higher prevalence of probable psychological morbidity one year after exposure to flooding. We now report findings after two years. METHODS: In year two (2016), a self-assessment questionnaire including flooding-related exposures and validated instruments to screen for probable anxiety, depression and post-traumatic stress disorder (PTSD) was sent to all participants who consented to further follow-up. Participants exposure status was categorised according to responses in year one; we assessed for exposure to new episodes of flooding and continuing flood-related problems in respondents homes. We calculated the prevalence and odds ratio for each outcome by exposure group relative to unaffected participants, adjusting for confounders. We used the McNemar test to assess change in outcomes between year one and year two. RESULTS: In year two, 1064 (70%) people responded. The prevalence of probable psychological morbidity remained elevated amongst flooded participants [n = 339] (depression 10.6%, anxiety 13.6%, PTSD 24.5%) and disrupted participants [n = 512] (depression 4.1%, anxiety 6.4%, PTSD 8.9%), although these rates were reduced compared to year one. A greater reduction in anxiety 7.6% (95% confidence interval [CI] 4.6-9.9) was seen than depression 3.8% (95% CI 1.5-6.1) and PTSD: 6.6% (95% CI 3.9-9.2). Exposure to flooding was associated with a higher odds of anxiety (adjusted odds ratio [aOR] 5.2 95%, 95% CI 1.7-16.3) and depression (aOR 8.7, 95% CI 1.9-39.8) but not PTSD. Exposure to disruption caused by flooding was not significantly associated with probable psychological morbidity. Persistent damage in the home as a consequence of the original flooding event was reported by 119 participants (14%). The odds of probable psychological morbidity amongst flooded participants who reported persistent damage, compared with those who were unaffected, were significantly higher than the same comparison amongst flooded participants who did not report persistent damage. CONCLUSIONS: This study shows a continuance of probable psychological morbidity at least two years following exposure to flooding. Commissioners and providers of health and social care services should be aware that the increased need in populations may be prolonged. Efforts to resolve persistent damage to homes may reduce the risk of probable psychological morbidity

    La “ideología de género” frente a los derechos sexuales y reproductivos. El escenario español

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    Se analiza el caso español como laboratorio europeo en el que se han ensayado las estrategias de movilización basadas en el discurso de la “ideología de género” contra los derechos sexuales y de las mujeres por parte de actores ultraconservadores, con especial atención a los actores católicos. Se presentan cuatro momentos: el discurso de la Iglesia Católica, como fuente originaria del lenguaje de este nuevo pánico moral; las reformas legales progresistas que detonan el ciclo de protesta; la contestación social de los grupos conservadores y la posterior reacción conservadora moderada desde la acción de gobierno

    Emergency department visits, ambulance calls, and mortality associated with an exceptional heat wave in Sydney, Australia, 2011: a time-series analysis

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    <p>Abstract</p> <p>Background</p> <p>From January 30-February 6, 2011, New South Wales was affected by an exceptional heat wave, which broke numerous records. Near real-time Emergency Department (ED) and ambulance surveillance allowed rapid detection of an increase in the number of heat-related ED visits and ambulance calls during this period. The purpose of this study was to quantify the excess heat-related and all-cause ED visits and ambulance calls, and excess all-cause mortality, associated with the heat wave.</p> <p>Methods</p> <p>ED and ambulance data were obtained from surveillance and administrative databases, while mortality data were obtained from the state death registry. The observed counts were compared with the average counts from the same period from 2006/07 through 2009/10, and a Poisson regression model was constructed to calculate the number of excess ED visits, ambulance and deaths after adjusting for calendar and lag effects.</p> <p>Results</p> <p>During the heat wave there were 104 and 236 ED visits for heat effects and dehydration respectively, and 116 ambulance calls for heat exposure. From the regression model, all-cause ED visits increased by 2% (95% CI 1.01-1.03), all-cause ambulance calls increased by 14% (95% CI 1.11-1.16), and all-cause mortality increased by 13% (95% CI 1.06-1.22). Those aged 75 years and older had the highest excess rates of all outcomes.</p> <p>Conclusions</p> <p>The 2011 heat wave resulted in an increase in the number of ED visits and ambulance calls, especially in older persons, as well as an increase in all-cause mortality. Rapid surveillance systems provide markers of heat wave impacts that have fatal outcomes.</p

    Host dispersal shapes the population structure of a tick-borne bacterial pathogen

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    Birds are hosts for several zoonotic pathogens. Because of their high mobility, especially of longdistance migrants, birds can disperse these pathogens, affecting their distribution and phylogeography. We focused on Borrelia burgdorferi sensu lato, which includes the causative agents of Lyme borreliosis, as an example for tick-borne pathogens, to address the role of birds as propagation hosts of zoonotic agents at a large geographical scale. We collected ticks from passerine birds in 11 European countries. B. burgdorferi s.l. prevalence in Ixodes spp. was 37% and increased with latitude. The fieldfare Turdus pilaris and the blackbird T. merula carried ticks with the highest Borrelia prevalence (92 and 58%, respectively), whereas robin Erithacus rubecula ticks were the least infected (3.8%). Borrelia garinii was the most prevalent genospecies (61%), followed by B. valaisiana (24%), B. afzelii (9%), B. turdi (5%) and B. lusitaniae (0.5%). A novel Borrelia genospecies "Candidatus Borrelia aligera" was also detected. Multilocus sequence typing (MLST) analysis of B. garinii isolates together with the global collection of B. garinii genotypes obtained from the Borrelia MLST public database revealed that: (a) there was little overlap among genotypes from different continents, (b) there was no geographical structuring within Europe, and (c) there was no evident association pattern detectable among B. garinii genotypes from ticks feeding on birds, questing ticks or human isolates. These findings strengthen the hypothesis that the population structure and evolutionary biology of tick-borne pathogens are shaped by their host associations and the movement patterns of these hosts.Peer reviewe

    A Major Histocompatibility Class I Locus Contributes to Multiple Sclerosis Susceptibility Independently from HLA-DRB1*15:01

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    Background: In Northern European descended populations, genetic susceptibility for multiple sclerosis (MS) is associated with alleles of the human leukocyte antigen (HLA) Class II gene DRB1. Whether other major histocompatibility complex (MHC) genes contribute to MS susceptibility is controversial. Methodology/Principal Findings: A case control analysis was performed using 958 single nucleotide polymorphisms (SNPs) spanning the MHC assayed in two independent datasets. The discovery dataset consisted of 1,018 cases and 1,795 controls and the replication dataset was composed of 1,343 cases and 1,379 controls. The most significantly MS-associated SNP in the discovery dataset was rs3135391, a Class II SNP known to tag the HLA-DRB1*15:01 allele, the primary MS susceptibility allele in the MHC (O.R. = 3.04, p&lt;1×10−78). To control for the effects of the HLA-DRB1*15:01 haplotype, case control analysis was performed adjusting for this HLA-DRB1*15:01 tagging SNP. After correction for multiple comparisons (false discovery rate = .05) 52 SNPs in the Class I, II and III regions were significantly associated with MS susceptibility in both datasets using the Cochran Armitage trend test. The discovery and replication datasets were merged and subjects carrying the HLA-DRB1*15:01 tagging SNP were excluded. Association tests showed that 48 of the 52 replicated SNPs retained significant associations with MS susceptibility independently of the HLA-DRB1*15:01 as defined by the tagging SNP. 20 Class I SNPs were associated with MS susceptibility with p-values ≤1×10−8. The most significantly associated SNP was rs4959039, a SNP in the downstream un-translated region of the non-classical HLA-G gene (Odds ratio 1.59, 95% CI 1.40, 1.81, p = 8.45×10−13) and is in linkage disequilibrium with several nearby SNPs. Logistic regression modeling showed that this SNP's contribution to MS susceptibility was independent of the Class II and Class III SNPs identified in this screen. Conclusions: A MHC Class I locus contributes to MS susceptibility independently of the HLA-DRB1*15:01 haplotype
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