373 research outputs found

    Impact of inactivated poliovirus vaccine on mucosal immunity: implications for the polio eradication endgame.

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    The polio eradication endgame aims to bring transmission of all polioviruses to a halt. To achieve this aim, it is essential to block viral replication in individuals via induction of a robust mucosal immune response. Although it has long been recognized that inactivated poliovirus vaccine (IPV) is incapable of inducing a strong mucosal response on its own, it has recently become clear that IPV may boost immunity in the intestinal mucosa among individuals previously immunized with oral poliovirus vaccine. Indeed, mucosal protection appears to be stronger following a booster dose of IPV than oral poliovirus vaccine, especially in older children. Here, we review the available evidence regarding the impact of IPV on mucosal immunity, and consider the implications of this evidence for the polio eradication endgame. We conclude that the implementation of IPV in both routine and supplementary immunization activities has the potential to play a key role in halting poliovirus transmission, and thereby hasten the eradication of polio

    The Crabtree effect shapes the Saccharomyces cerevisiae lag phase during the switch between different carbon sources

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    When faced with environmental changes, microbes often enter a temporary growth arrest during which they reprogram the expression of specific genes to adapt to the new conditions. A prime example of such a lag phase occurs when microbes need to switch from glucose to other, less-preferred carbon sources. Despite its industrial relevance, the genetic network that determines the duration of the lag phase has not been studied in much detail. Here, we performed a genome-wide Bar-Seq screen to identify genetic determinants of the Saccharomyces cerevisiae glucose-to-galactose lag phase. The results show that genes involved in respiration, and specifically those encoding complexes III and IV of the electron transport chain, are needed for efficient growth resumption after the lag phase. Anaerobic growth experiments confirmed the importance of respiratory energy conversion in determining the lag phase duration. Moreover, overexpression of the central regulator of respiration, HAP4, leads to significantly shorter lag phases. Together, these results suggest that the glucose-induced repression of respiration, known as the Crabtree effect, is a major determinant of microbial fitness in fluctuating carbon environments. IMPORTANCE: The lag phase is arguably one of the prime characteristics of microbial growth. Longer lag phases result in lower competitive fitness in variable environments, and the duration of the lag phase is also important in many industrial processes where long lag phases lead to sluggish, less efficient fermentations. Despite the immense importance of the lag phase, surprisingly little is known about the exact molecular processes that determine its duration. Our study uses the molecular toolbox of S. cerevisiae combined with detailed growth experiments to reveal how the transition from fermentative to respirative metabolism is a key bottleneck for cells to overcome the lag phase. Together, our findings not only yield insight into the key molecular processes and genes that influence lag duration but also open routes to increase the efficiency of industrial fermentations and offer an experimental framework to study other types of lag behavior

    Aortic dissection at the University hospital of the West Indies: A 20-year clinicopathological study of autopsy cases

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    <p>Abstract</p> <p>Background</p> <p>An autopsy study of aortic dissection (AD) at our institution was previously reported. In the approximately 20 years since then, however, many aspects of diagnosis and treatment of this disease have changed, with a fall in mortality reported in many centers around the world. An impression amongst our pathologists that, there might be an increase in the prevalence of AD in the autopsy service at our hospital, since that earlier report, led to this repeated study, in an attempt to validate that notion. We also sought to identify any changes in clinicopathological features between the two series or any occurring during this study period itself.</p> <p>Findings</p> <p>All cases of AD identified at autopsy, during the 20-year period since the conclusion of the last study, were collected and pertinent clinical and pathological data were analyzed and compared, both within the two decades of this study period and against the results of the last study.</p> <p>Fifty-six cases comprised this study group including 36 males and 20 females, with a mean age of 63.9 years. There were, more patients in the second decade (n = 33; 59%) compared with the first decade (n = 23; 41%). Hypertension as a risk factor was identified in 52 (93%) cases and rupture occurred in 49 (88%) cases. A clinical diagnosis of AD was considered prior to surgery or autopsy in 25 (45%) cases overall, more during the second decade. Surgery was attempted in 25% of all cases with an increase in the second decade compared with the first.</p> <p>Conclusions</p> <p>Compared with the earlier review, a variety of changes in the profile of patients with AD in the autopsy service has been noted, including a reversal in the female predominance seen previously. Other observations include an increase in cases where the correct clinical diagnosis was considered and in which surgical treatment was attempted, changes also evident when the second decade of the present study was compared with the earlier decade. Overall, there were many positive trends. However, areas that could still be improved include an increased index of suspicion for the diagnosis of AD and perhaps in the initiation of treatment, earlier, in those cases where the correct diagnosis was considered.</p

    Neurobehavioral consequences of chronic intrauterine opioid exposure in infants and preschool children: a systematic review and meta-analysis

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    &lt;b&gt;Background&lt;/b&gt;&lt;p&gt;&lt;/p&gt; It is assumed within the accumulated literature that children born of pregnant opioid dependent mothers have impaired neurobehavioral function as a consequence of chronic intrauterine opioid use.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Methods&lt;/b&gt;&lt;p&gt;&lt;/p&gt; Quantitative and systematic review of the literature on the consequences of chronic maternal opioid use during pregnancy on neurobehavioral function of children was conducted using the Meta-analysis of Observational Studies in Epidemiology (MOOSE) and the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. We searched Cinahl, EMBASE, PsychINFO and MEDLINE between the periods of January 1995 to January 2012.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Results&lt;/b&gt;&lt;p&gt;&lt;/p&gt; There were only 5 studies out of the 200 identified that quantitatively reported on neurobehavioral function of children after maternal opioid use during pregnancy. All 5 were case control studies with the number of exposed subjects within the studies ranging from 33–143 and 45–85 for the controls. This meta-analysis showed no significant impairments, at a non-conservative significance level of p &#60; 0.05, for cognitive, psychomotor or observed behavioural outcomes for chronic intra-uterine exposed infants and pre-school children compared to non-exposed infants and children. However, all domains suggested a trend to poor outcomes in infants/children of opioid using mothers. The magnitude of all possible effects was small according to Cohen’s benchmark criteria.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Conclusions&lt;/b&gt;&lt;p&gt;&lt;/p&gt; Chronic intra-uterine opioid exposed infants and pre-school children experienced no significant impairment in neurobehavioral outcomes when compared to non-exposed peers, although in all domains there was a trend to poorer outcomes. The findings of this review are limited by the small number of studies analysed, the heterogenous populations and small numbers within the individual studies. Longitudinal studies are needed to determine if any neuropsychological impairments appear after the age of 5 years and to help investigate further the role of environmental risk factors on the effect of ‘core’ phenotypes

    Acute kidney disease and renal recovery : consensus report of the Acute Disease Quality Initiative (ADQI) 16 Workgroup

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    Consensus definitions have been reached for both acute kidney injury (AKI) and chronic kidney disease (CKD) and these definitions are now routinely used in research and clinical practice. The KDIGO guideline defines AKI as an abrupt decrease in kidney function occurring over 7 days or less, whereas CKD is defined by the persistence of kidney disease for a period of > 90 days. AKI and CKD are increasingly recognized as related entities and in some instances probably represent a continuum of the disease process. For patients in whom pathophysiologic processes are ongoing, the term acute kidney disease (AKD) has been proposed to define the course of disease after AKI; however, definitions of AKD and strategies for the management of patients with AKD are not currently available. In this consensus statement, the Acute Disease Quality Initiative (ADQI) proposes definitions, staging criteria for AKD, and strategies for the management of affected patients. We also make recommendations for areas of future research, which aim to improve understanding of the underlying processes and improve outcomes for patients with AKD

    Community Health Environment Scan Survey (CHESS): a novel tool that captures the impact of the built environment on lifestyle factors

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    Background: Novel1 1This study was performed on behalf of the Community Interventions for Health (CIH) collaboration. efforts and accompanying tools are needed to tackle the global burden of chronic disease. This paper presents an approach to describe the environments in which people live, work, and play. Community Health Environment Scan Survey (CHESS) is an empirical assessment tool that measures the availability and accessibility, of healthy lifestyle options lifestyle options. CHESS reveals existing community assets as well as opportunities for change, shaping community intervention planning efforts by focusing on community-relevant opportunities to address the three key risk factors for chronic disease (i.e. unhealthy diet, physical inactivity, and tobacco use). Methods: The CHESS tool was developed following a review of existing auditing tools and in consultation with experts. It is based on the social-ecological model and is adaptable to diverse settings in developed and developing countries throughout the world. Results: For illustrative purposes, baseline results from the Community Interventions for Health (CIH) Mexico site are used, where the CHESS tool assessed 583 food stores and 168 restaurants. Comparisons between individual-level survey data from schools and community-level CHESS data are made to demonstrate the utility of the tool in strategically guiding intervention activities. Conclusion: The environments where people live, work, and play are key factors in determining their diet, levels of physical activity, and tobacco use. CHESS is the first tool of its kind that systematically and simultaneously examines how built environments encourage/discourage healthy eating, physical activity, and tobacco use. CHESS can help to design community interventions to prevent chronic disease and guide healthy urban planning

    Backbone and side chain NMR assignments for the intrinsically disordered cytoplasmic domain of human neuroligin-3

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    Neuroligins act as heterophilic adhesion molecules at neuronal synapses. Their cytoplasmic domains interact with synaptic scaffolding proteins, and have been shown to be intrinsically disordered. Here we report the backbone and side chain 1H, 13C and 15N resonance assignments for the cytoplasmic domain of human neuroligin 3

    Mental health literacy as a function of remoteness of residence: an Australian national study

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    <p>Abstract</p> <p>Background</p> <p>Although there have been many population studies of mental health literacy, little is known about the mental health literacy of people who reside in rural areas. This study sought to determine the impact of remoteness on public knowledge of depression and schizophrenia.</p> <p>Methods</p> <p>The mental health literacy of residents of major cities, inner regional, and outer-remote (including outer regional, remote, and very remote) regions were compared using data from a 2003–04 Australian national survey of the mental health literacy of 3998 adults. Measures included the perceived helpfulness of a range of professionals, non-professionals and interventions, and the causes, prognosis, and outcomes after treatment for four case vignettes describing depression, depression with suicidal ideation, early schizophrenia and chronic schizophrenia. Participant awareness of Australia's national depression initiative and depression in the media, their symptoms of depression and exposure to the conditions depicted in the vignettes were also compared.</p> <p>Results</p> <p>Mental health literacy was similar across remoteness categories. However, inner regional residents showed superior identification of the disorders depicted in the suicidal ideation and chronic schizophrenia vignettes. They were also more likely to report having heard of Australia's national depression health promotion campaign. Conversely, they were less likely than major city residents to rate the evidence-based treatment of psychotherapy helpful for depression. Both inner regional and outer-remote residents were less likely to rate psychologists as helpful for depression alone. The rural groups were more likely to rate the non-evidence based interventions of drinking and painkillers as helpful for a depression vignette. In addition, outer-remote residents were more likely to identify the evidence based treatment of antipsychotics as harmful for early schizophrenia and less likely to endorse psychiatrists, psychologists, social workers and general practitioners as helpful for the condition.</p> <p>Conclusion</p> <p>Mental health awareness campaigns in rural and remote regions may be most appropriately focused on communicating which interventions are effective for depression and schizophrenia and which mental health and other professionals are trained in the best-practice delivery and management of these. There is also a need to communicate to rural residents that alcohol and pain relievers are not an effective solution for depression.</p
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