How do Zimbabweans value health states?

Background Quality of life weights based on valuations of health states are often used in cost utility analysis and population health measures. This paper reports on an attempt to develop quality of life weights within the Zimbabwe context. Methods 2,384 residents in randomly selected small residential plots of land in a high-density suburb of Harare valued descriptors of 38 health states based on different combinations of the five domains of the EQ-5D (mobility, self-care, usual activities, pain or discomfort and anxiety or depression). The English version of the EQ-5D was used. The time trade-off method was used to determine the values, and 19,020 individual preferences for health states were analysed. A residual maximum likelihood linear mixed model was used to estimate a function for predicting the values of all possible combinations of levels on the five domains. The model was fit to a random subset of two-thirds of the observations, with the remaining observations reserved for analysis of predictive validity. The results were compared to a similar study undertaken in the United Kingdom. Results A credible model was developed to predict the values of states that were not valued directly. In the subset of observations reserved for validation, the mean absolute difference between predicted and observed values was 0.045. All domains of the EQ-5D were found to contribute significantly to the model, both at the moderate and severe levels. Severe pain was found to have the largest negative coefficient, followed by the inability to wash and dress oneself. Conclusion Despite a generally lower education level than their European counterparts, urban Zimbabweans appear to value health states in a consistent manner, and the determination of a global method of establishing quality of life weights may be feasible and valid. However, as the relative weightings of the different domains, although correlated, differed from the standard set of weights recommended by the EuroQol Group, the locally determined coefficients should be used within the Zimbabwean context

Probing host pathogen cross-talk by transcriptional profiling of both Mycobacterium tuberculosis and infected human dendritic cells and macrophages

This study provides the proof of principle that probing the host and the microbe transcriptomes simultaneously is a valuable means to accessing unique information on host pathogen interactions. Our results also underline the extraordinary plasticity of host cell and pathogen responses to infection, and provide a solid framework to further understand the complex mechanisms involved in immunity to M. tuberculosis and in mycobacterial adaptation to different intracellular environments

Cortical and Striatal Reward Processing in Parkinson's Disease Psychosis

Psychotic symptoms frequently occur in Parkinson's disease (PD), but their pathophysiology is poorly understood. According to the National Institute of Health RDoc programme, the pathophysiological basis of neuropsychiatric symptoms may be better understood in terms of dysfunction of underlying domains of neurocognition in a trans-diagnostic fashion. Abnormal cortico-striatal reward processing has been proposed as a key domain contributing to the pathogenesis of psychotic symptoms in schizophrenia. This theory has received empirical support in the study of schizophrenia spectrum disorders and preclinical models of psychosis, but has not been tested in the psychosis associated with PD. We, therefore, investigated brain responses associated with reward expectation and prediction error signaling during reinforcement learning in PD-associated psychosis. An instrumental learning task with monetary gains and losses was conducted during an fMRI study in PD patients with (n = 12), or without (n = 17), a history of psychotic symptoms, along with a sample of healthy controls (n = 24). We conducted region of interest analyses in the ventral striatum (VS), ventromedial prefrontal and posterior cingulate cortices, and whole-brain analyses. There was reduced activation in PD patients with a history of psychosis, compared to those without, in the posterior cingulate cortex and the VS during reward anticipation (p < 0.05 small volume corrected). The results suggest that cortical and striatal abnormalities in reward processing, a putative pathophysiological mechanism of psychosis in schizophrenia, may also contribute to the pathogenesis of psychotic symptoms in PD. The finding of posterior cingulate dysfunction is in keeping with prior results highlighting cortical dysfunction in the pathogenesis of PD psychosis.This study was supported by a Medical Research Council Clinician Scientist award (G0701911), and an Isaac Newton Trust award to Dr. Murray; by support to Dr. Fletcher from the Wellcome Trust and Bernard Wolfe Health Neuroscience Fund; by a Wellcome Trust strategic award to University of Cambridge (097814/Z/11), by the NIHR Cambridge Biomedical Research Centre and University of Cambridge Behavioural and Clinical Neuroscience Institute, supported by a joint award from the Medical Research Council (G1000183) and Wellcome Trust (093875/Z/10/Z)

Transition of plasmodium sporozoites into liver stage-like forms is regulated by the RNA binding protein pumilio

Many eukaryotic developmental and cell fate decisions that are effected post-transcriptionally involve RNA binding proteins as regulators of translation of key mRNAs. In malaria parasites (Plasmodium spp.), the development of round, non-motile and replicating exo-erythrocytic liver stage forms from slender, motile and cell-cycle arrested sporozoites is believed to depend on environmental changes experienced during the transmission of the parasite from the mosquito vector to the vertebrate host. Here we identify a Plasmodium member of the RNA binding protein family PUF as a key regulator of this transformation. In the absence of Pumilio-2 (Puf2) sporozoites initiate EEF development inside mosquito salivary glands independently of the normal transmission-associated environmental cues. Puf2- sporozoites exhibit genome-wide transcriptional changes that result in loss of gliding motility, cell traversal ability and reduction in infectivity, and, moreover, trigger metamorphosis typical of early Plasmodium intra-hepatic development. These data demonstrate that Puf2 is a key player in regulating sporozoite developmental control, and imply that transformation of salivary gland-resident sporozoites into liver stage-like parasites is regulated by a post-transcriptional mechanism

Transcriptome analyses of mouse and human mammary cell subpopulations reveal multiple conserved genes and pathways

INTRODUCTION: Molecular characterization of the normal epithelial cell types that reside in the mammary gland is an important step toward understanding pathways that regulate self-renewal, lineage commitment, and differentiation along the hierarchy. Here we determined the gene expression signatures of four distinct subpopulations isolated from the mouse mammary gland. The epithelial cell signatures were used to interrogate mouse models of mammary tumorigenesis and to compare with their normal human counterpart subsets to identify conserved genes and networks. METHODS: RNA was prepared from freshly sorted mouse mammary cell subpopulations (mammary stem cell (MaSC)-enriched, committed luminal progenitor, mature luminal and stromal cell) and used for gene expression profiling analysis on the Illumina platform. Gene signatures were derived and compared with those previously reported for the analogous normal human mammary cell subpopulations. The mouse and human epithelial subset signatures were then subjected to Ingenuity Pathway Analysis (IPA) to identify conserved pathways. RESULTS: The four mouse mammary cell subpopulations exhibited distinct gene signatures. Comparison of these signatures with the molecular profiles of different mouse models of mammary tumorigenesis revealed that tumors arising in MMTV-Wnt-1 and p53-/- mice were enriched for MaSC-subset genes, whereas the gene profiles of MMTV-Neu and MMTV-PyMT tumors were most concordant with the luminal progenitor cell signature. Comparison of the mouse mammary epithelial cell signatures with their human counterparts revealed substantial conservation of genes, whereas IPA highlighted a number of conserved pathways in the three epithelial subsets. CONCLUSIONS: The conservation of genes and pathways across species further validates the use of the mouse as a model to study mammary gland development and highlights pathways that are likely to govern cell-fate decisions and differentiation. It is noteworthy that many of the conserved genes in the MaSC population have been considered as epithelial-mesenchymal transition (EMT) signature genes. Therefore, the expression of these genes in tumor cells may reflect basal epithelial cell characteristics and not necessarily cells that have undergone an EMT. Comparative analyses of normal mouse epithelial subsets with murine tumor models have implicated distinct cell types in contributing to tumorigenesis in the different models

Risk Factors for Buruli Ulcer: A Case Control Study in Cameroon

Buruli ulcer (BU) is a neglected tropical infectious disease caused by Mycobacterium ulcerans. While BU is associated with areas where the water is slow-flowing or stagnant, the exact mechanism of transmission of the bacillus is unknown, impairing efficient control programs. Two hypotheses are proposed in the literature: previous trauma at the lesion site, and transmission through aquatic insect bites. Using results from a face-to-face questionnaire, our study compared characteristics from Cameroonian patients with Buruli ulcer to people without Buruli ulcer. This latter group of people was chosen within the community or within the family of case patients. The statistical analysis confirmed some well-known factors associated with the presence of BU, such as wearing short lower-body clothing while farming, but it showed that the use of bed nets and the treatment of wounds with leaves is less frequent in case patients. These newly identified factors may provide new insight into the mode of transmission of M. ulcerans. The implication of domestic or peridomestic insects, suggested by the influence of the use of bed nets, should be confirmed in specific studies

Socio-Demographic Determinants of Condom Use Among Sexually Active Young Adults in Rural KwaZulu-Natal, South Africa

AIM: To investigate patterns, levels and socio-demographic determinants of condom use and consistency of use among young adults aged 15-24 years.BACKGROUND: Condoms are known to prevent HIV infection. However, HIV prevalence and incidence remain high.METHODS: This study was conducted in the Africa Centre Demographic Surveillance Area (ACDSA) in rural KwaZulu-Natal. Analysis focused on resident young adults aged 15-24 years in 2005. In univariable and multivariable analyses, determinants of condom use and consistency of use among 15-24 year olds were estimated using data collected in 2005. 'Ever' condom use was defined as the proportion who reported having used a condom; consistent use among those ever using as "always" using condoms with most recent partner in the last year.RESULTS: 3,914 participants aged 15-24 years reported ever having sex, of whom 52% reported condom use. Adjusting for age, sex, number of partners, residence of partner, partner age difference, type of partner and socio-economic status (SES), having an older partner decreased likelihood (aOR=0.69, p&lt;0.01), while belonging to a household in a higher SES increased likelihood of ever using condoms (aOR=1.82, p&lt;0.01). Being female (aOR=0.61 p&lt;0.01) and having a regular partner (aOR=0.65 p&lt;0.01) were independently associated with low consistent condom use.CONCLUSIONS: In this rural South African setting, condom use remains low, especially among females and with an older partner, situations commonly associated with increased HIV acquisition. Targeted supportive interventions to increase condom use need to be developed if HIV prevention programmes are to be successful

Acquiring a pet dog significantly reduces stress of primary carers for children with autism spectrum disorder: a prospective case control study

This study describes the impact of pet dogs on stress of primary carers of children with Autism Spectrum Disorder (ASD). Stress levels of 38 primary carers acquiring a dog and 24 controls not acquiring a dog were sampled at: Pre-intervention (17 weeks before acquiring a dog), post-intervention (3–10 weeks after acquisition) and follow-up (25–40 weeks after acquisition), using the Parenting Stress Index. Analysis revealed significant improvements in the intervention compared to the control group for Total Stress, Parental Distress and Difficult Child. A significant number of parents in the intervention group moved from clinically high to normal levels of Parental Distress. The results highlight the potential of pet dogs to reduce stress in primary carers of children with an ASD