590 research outputs found

    Hepatitis C and G in south east Scotland: studies in epidemiology, progression of disease and quality of life

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    Hepatitis C is now a global health problem with an estimated 170 million people infected worldwide. It is known to be the cause of the majority of cases of non-A, non-B hepatitis. It is known to be progressive with at least 20% of patients developing cirrhosis over 20 years. What is less clear is whether all infected people with eventually develop complications and whether certain factors are important in progression of this disease. There are other similar viruses that have been characterised including HGV and their importance is not yet entirely clear.The aims ofthis thesis were to: Study the epidemiology and natural history of HCV infection in our population of HCV infected patients in South East Scotland. Investigate the factors important in progression of chronic HCV infection and also the effects of chronic HCV infection on quality of life Examine another novel flavivirus, HGV, in Scottish blood donors.A database of all patients with chronic HCV referred to our hospital was set up. Data was gathered prospectively and analysed with regards to demographic variables and factors related to progression of disease. The importance of HLA status in development and severity of disease was also examined. Finally the impact of chronic HCV infection on QOL was assessed in a subgroup of this population.In a separate population the prevalence, natural history, clinical significance and risk factors for transmission of HGV were assessed.262 patients were initially included in the database. 214 patients were HCV-RNA positive and were investigated further. Various demographic variables were recorded. Nearly 20% had cirrhosis on biopsy. Factors important in progression were age at infection, male sex and alcohol consumption.When HLA status and progression were examined certain antigens were found to protect against development of chronic disease and cirrhosis. Quality of life was found to be significantly impaired across all domains of life in patients with chronic HCV infection.HGV is common amongst Scottish blood donors but is not associated with significant symptoms or liver disease. A risk factor for infection was not identified in the majority of infected donors

    Responding to unexpected infant deaths : experience in one English region

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    New national procedures for responding to the unexpected death of a child in England require a joint agency approach to investigate each death and support the bereaved family. As part of a wider population-based study of sudden unexpected deaths in infancy (SUDI) we evaluated the implementation of this approach. Methods: A process evaluation using a population-based study of all unexpected deaths from birth to 2 years in the South West of England between January 2003 and December 2006. Local police and health professionals followed a standardised approach to the investigation of each death, supported by the research team set up to facilitate this joint approach as well as collect data for a wider research project. Results: We were notified of 155/157 SUDI, with a median time to notification of 2 hours. Initial multi-agency discussions took place in 93.5% of cases. A joint home visit by police officers with health professionals was carried out in 117 cases, 75% within 24 hours of the death. Time to notification and interview reduced during the 4 years of the study. Autopsies were conducted on all cases, the median time to autopsy being 3 days. At the conclusion of the investigation, a local multi-agency case discussion was held in 88% of cases. The median time for the whole process (including family support) was 5 months. Conclusions: This study has demonstrated that with appropriate protocols and support, the joint agency approach to the investigation of unexpected infant deaths can be successfully implemented

    Hazardous cosleeping environments and risk factors amenable to change: case-control study of SIDS in south west England

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    Objectives: To investigate the factors associated with sudden infant death syndrome (SIDS) from birth to age 2 years, whether recent advice has been followed, whether any new risk factors have emerged, and the specific circumstances in which SIDS occurs while cosleeping (infant sharing the same bed or sofa with an adult or child). Design: Four year population based case-control study. Parents were interviewed shortly after the death or after the reference sleep (within 24 hours) of the two control groups. Setting: South west region of England (population 4.9 million, 184 800 births). Participants: 80 SIDS infants and two control groups weighted for age and time of reference sleep: 87 randomly selected controls and 82 controls at high risk of SIDS (young, socially deprived, multiparous mothers who smoked). Results: The median age at death (66 days) was more than three weeks less than in a study in the same region a decade earlier. Of the SIDS infants, 54% died while cosleeping compared with 20% among both control groups. Much of this excess may be explained by a significant multivariable interaction between cosleeping and recent parental use of alcohol or drugs (31% v 3% random controls) and the increased proportion of SIDS infants who had coslept on a sofa (17% v 1%). One fifth of SIDS infants used a pillow for the last sleep (21% v 3%) and one quarter were swaddled (24% v 6%). More mothers of SIDS infants than random control infants smoked during pregnancy (60% v 14%), whereas one quarter of the SIDS infants were preterm (26% v 5%) or were in fair or poor health for the last sleep (28% v 6%). All of these differences were significant in the multivariable analysis regardless of which control group was used for comparison. The significance of covering the infant’s head, postnatal exposure to tobacco smoke, dummy use, and sleeping in the side position has diminished although a significant proportion of SIDS infants were still found prone (29% v 10%). Conclusions: Many of the SIDS infants had coslept in a hazardous environment. The major influences on risk, regardless of markers for socioeconomic deprivation, are amenable to change and specific advice needs to be given, particularly on use of alcohol or drugs before cosleeping and cosleeping on a sofa

    Gender and Political Leadership in a Time of COVID

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    The COVID-19 pandemic has undermined the division between the private sphere of the home and the public sphere of politics that has traditionally disadvantaged women political leaders. Whereas male political leaders historically drew on their traditional role as the male head of household to display forms of masculine protectionism toward citizens, women leaders are now able to draw on their traditional motherly role—for example, as the member of the household who traditionally cares for the sick—to display forms of feminine protectionism. As a result, international women leaders have managed to leverage women's role in the home to their advantage in the political sphere. Significantly, an appreciation of traditionally feminine attributes in women political leaders has been displayed in much media coverage, providing more favorable coverage of female political leaders than was previously the case

    Transmission dynamics of an insect-specific flavivirus in a naturally infected Culex pipiens laboratory colony and effects of co-infection on vector competence for West Nile virus

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    AbstractWe established a laboratory colony of Culex pipiens mosquitoes from eggs collected in Colorado and discovered that mosquitoes in the colony are naturally infected with Culex flavivirus (CxFV), an insect-specific flavivirus. In this study we examined transmission dynamics of CxFV and effects of persistent CxFV infection on vector competence for West Nile virus (WNV). We found that vertical transmission is the primary mechanism for persistence of CxFV in Cx. pipiens, with venereal transmission potentially playing a minor role. Vector competence experiments indicated possible early suppression of WNV replication by persistent CxFV infection in Cx. pipiens. This is the first description of insect-specific flavivirus transmission dynamics in a naturally infected mosquito colony and the observation of delayed dissemination of superinfecting WNV suggests that the presence of CxFV may impact the intensity of enzootic transmission of WNV and the risk of human exposure to this important pathogen

    Human monoclonal antibodies to West Nile virus identify epitopes on the prM protein

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    AbstractHybridoma cell lines (2E8, 8G8 and 5G12) producing fully human monoclonal antibodies (hMAbs) specific for the pre-membrane (prM) protein of West Nile virus (WNV) were prepared using a human fusion partner cell line, MFP-2, and human peripheral blood lymphocytes from a blood donor diagnosed with WNV fever in 2004. Using site-directed mutagenesis of a WNV-like particle (VLP) we identified 4 amino acid residues in the prM protein unique to WNV and important in the binding of these hMAbs to the VLP. Residues V19 and L33 are important epitopes for the binding of all three hMAbs. Mutations at residue, T20 and T24 affected the binding of hMAbs, 8G8 and 5G12 only. These hMAbs did not significantly protect AG129 interferon-deficient mice or Swiss Webster outbred mice from WNV infection

    Aedes aegypti uses RNA interference in defense against Sindbis virus infection

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    <p>Abstract</p> <p>Background</p> <p>RNA interference (RNAi) is an important anti-viral defense mechanism. The <it>Aedes aegypti </it>genome encodes RNAi component orthologs, however, most populations of this mosquito are readily infected by, and subsequently transmit flaviviruses and alphaviruses. The goal of this study was to use <it>Ae. aegypti </it>as a model system to determine how the mosquito's anti-viral RNAi pathway interacts with recombinant Sindbis virus (SINV; family <it>Togaviridae</it>, genus <it>Alphavirus</it>).</p> <p>Results</p> <p>SINV (TR339-eGFP) (+) strand RNA, infectious virus titers and infection rates transiently increased in mosquitoes following dsRNA injection to cognate <it>Ago2</it>, <it>Dcr2</it>, or <it>TSN </it>mRNAs. Detection of SINV RNA-derived small RNAs at 2 and 7 days post-infection in non-silenced mosquitoes provided important confirmation of RNAi pathway activity. Two different recombinant SINV viruses (MRE16-eGFP and TR339-eGFP) with significant differences in infection kinetics were used to delineate vector/virus interactions in the midgut. We show virus-dependent effects on RNAi component transcript and protein levels during infection. Monitoring midgut <it>Ago2</it>, <it>Dcr2</it>, and <it>TSN </it>transcript levels during infection revealed that only <it>TSN </it>transcripts were significantly increased in midguts over blood-fed controls. Ago2 protein levels were depleted immediately following a non-infectious bloodmeal and varied during SINV infection in a virus-dependent manner.</p> <p>Conclusion</p> <p>We show that silencing RNAi components in <it>Ae. aegypti </it>results in transient increases in SINV replication. Furthermore, <it>Ae. aegypti </it>RNAi is active during SINV infection as indicated by production of virus-specific siRNAs. Lastly, the RNAi response varies in a virus-dependent manner. These data define important features of RNAi anti-viral defense in <it>Ae. aegypti</it>.</p
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