Nutritional Quality of Available Forages for Small Stock during a Drought in an Arid Pastoral Landscape in South Africa

This study aimed to assess the nutritional quality of the available forage species during a drought in an arid pastoral system in South Africa. Forage biomass was collected during the wet and dry seasons whilst following livestock herds consisting of boer goats, swakara sheep and mixed breed sheep, in both the summer and winter rainfall regions of the pastoral system. Mineral nutrient content in the plant species revealed that the forages utilized by the livestock generally contained adequate concentrations of Mg, Ca, Na, and K to meet the dietary requirements of the small stock in both the winter and summer rainfall areas. Zinc concentrations in more than half of the forages sampled in the summer rainfall area, during both wet and dry seasons, however, were below the required concentrations for small stock. When considering all plant species utilised, the diets were generally adequate in all mineral nutrients. However, none of the forage species contained sufficiently high concentrations of protein to meet the minimum requirements for small stock. These findings therefore show that pastoralists have to deal with chronic low levels of protein during droughts, and their inability to purchase supplementary feed, or to cultivate fodder crops, or temporary emigrate out of the system puts their livelihoods at high risk to climate change

Non-communicable diseases in the Western Area District, Sierra Leone, before and during the Ebola outbreak.

Setting: Twenty-seven peripheral health units, five secondary hospitals and one tertiary hospital, Western Area District, Sierra Leone. Objectives: To describe reporting systems, monthly attendances and facility-based patterns of six non-communicable diseases (NCDs) in the pre-Ebola and Ebola virus disease outbreak periods. Design: A cross-sectional study using programme data. Results: Reporting was 89% complete on the six selected NCDs pre-Ebola and 86% during the Ebola outbreak (P < 0.01). Overall, marked declining trends in NCDs were reported during the Ebola period, with a monthly mean of 342 cases pre-Ebola and 164 during the Ebola outbreak. The monthly mean number of cases per disease in the pre-Ebola and Ebola outbreak periods was respectively 228 vs. 85 for hypertension, 43 vs. 27 for cardiovascular diseases, 36 vs. 18 for diabetes and 25 vs. 29 for peptic ulcer disease; this last condition increased during the outbreak. There were higher proportions of NCDs among females during the Ebola outbreak compared with the pre-Ebola period. Except for peptic ulcer disease, the number of patients with NCDs declined by 25% in peripheral health units, 91% in the secondary hospitals and 70% in the tertiary hospital between the pre-Ebola and the Ebola outbreak periods. Conclusion: Comprehensive reporting of NCDs was suboptimal, and declined during the Ebola epidemic. There were decreases in reported attendances for NCDs between the pre-Ebola and the Ebola outbreak periods, which were even more marked in the hospitals. This study has important policy implications

Lumped Parameter Models of the Central Nervous System for VIIP Research

INTRODUCTION: Current long-duration missions to the International Space Station and future exploration-class missions beyond low-Earth orbit, such as to Mars and asteroids, expose astronauts to increased risk of Visual Impairment and Intracranial Pressure (VIIP) syndrome [1]. It has been hypothesized that the headward shift of cerebral spinal fluid (CSF) and blood in microgravity may cause significant elevation of intracranial pressure (ICP), which in turn induces VIIP syndrome through biomechanical pathways [1, 2]. However, there is insufficient evidence to confirm this hypothesis. In this light, we are developing lumped-parameter models of fluid transport in the central nervous system (CNS) as a means to simulate the influence of microgravity on ICP. The CNS models will also be used in concert with the lumped parameter and finite element models of the eye described in the realted IWS abstracts submitted by Nelson et al., Feola et al. and Ethier et al. METHODS: We have developed a nine compartment CNS model (Figure 1) capable of both time-dependent and steady state fluid transport simulations, based on the works of Stevens et al. [3]. The breakdown of compartments within the model includes: vascular (3), CSF (2), brain (1) and extracranial (3). The boundary pressure in the Central Arteries [A] node is prescribed using an oscillating pressure function PA(t) simulating the carotid pulsatile pressure wave as developed by Linninger et al. [4]. For each time step, pressures are integrated through time using an adaptive-timestep 4th and 5th order Runga-Kutta solver. Once pressures are found, constitutive equations are used to solve for flowrates (Q) between each compartment. In addition to fluid flow between the different compartments, compliance (C) interactions between neighboring compartments are represented. We are also developing a second CNS model based on the works of Linninger et al. [4] which takes a more granular approach to represent the interactions of the intracranial and spinal compartments with the inclusion of arteries, arterioles, capillaries, venules, veins, venous sinus, and ventricles. The flow through the arteries, veins and CSF compartments are governed by continuity, momentum and distensibility balance equations. Furthermore, unlike the Stevens et al. approach, the Monro-Kellie doctrine of constant cranial volume and the bi-phasic nature of the brain parenchyma are implemented. These features appear to be more consistent with the physiologic and anatomical behavior of the CNS, and follow a modeling philosophy similar to the lumped parameter eye model that is intended to be integrated with the CNS model. However, Linningers approach has never been implemented to include hydrostatic gradient and microgravity simulation capabilities. Therefore, we aim at implement this modeling approach for spaceflight simulations and assess its overall applicability to VIIP research. OBJECTIVES: We will present verification and validation test results for both models, as well as head-to-head comparison to explore their strengths and limitations with respect to mathematical implementation and physiological significance for VIIP research. In doing so, we hope to provide some guidance to the HRP research community on how to appropriately leverage lumped parameter models for space biomedical research

Human Galectin-9 Is a Potent Mediator of HIV Transcription and Reactivation.

Identifying host immune determinants governing HIV transcription, latency and infectivity in vivo is critical to developing an HIV cure. Based on our recent finding that the host factor p21 regulates HIV transcription during antiretroviral therapy (ART), and published data demonstrating that the human carbohydrate-binding immunomodulatory protein galectin-9 regulates p21, we hypothesized that galectin-9 modulates HIV transcription. We report that the administration of a recombinant, stable form of galectin-9 (rGal-9) potently reverses HIV latency in vitro in the J-Lat HIV latency model. Furthermore, rGal-9 reverses HIV latency ex vivo in primary CD4+ T cells from HIV-infected, ART-suppressed individuals (p = 0.002), more potently than vorinostat (p = 0.02). rGal-9 co-administration with the latency reversal agent "JQ1", a bromodomain inhibitor, exhibits synergistic activity (p&lt;0.05). rGal-9 signals through N-linked oligosaccharides and O-linked hexasaccharides on the T cell surface, modulating the gene expression levels of key transcription initiation, promoter proximal-pausing, and chromatin remodeling factors that regulate HIV latency. Beyond latent viral reactivation, rGal-9 induces robust expression of the host antiviral deaminase APOBEC3G in vitro and ex vivo (FDR&lt;0.006) and significantly reduces infectivity of progeny virus, decreasing the probability that the HIV reservoir will be replenished when latency is reversed therapeutically. Lastly, endogenous levels of soluble galectin-9 in the plasma of 72 HIV-infected ART-suppressed individuals were associated with levels of HIV RNA in CD4+ T cells (p&lt;0.02) and with the quantity and binding avidity of circulating anti-HIV antibodies (p&lt;0.009), suggesting a role of galectin-9 in regulating HIV transcription and viral production in vivo during therapy. Our data suggest that galectin-9 and the host glycosylation machinery should be explored as foundations for novel HIV cure strategies

Association of blood pressure variability and neurocognition in children with chronic kidney disease

Children with chronic kidney disease (CKD) and hypertension have increased blood pressure variability (BPV). Increased BPV has been associated with lower neurocognitive test scores in adults. Children with CKD are at risk for decreased neurocognitive function. Our objective was to determine if children with CKD and increased BPV had worse performance on neurocognitive testing compared with children with CKD and lower BPV

Numerical Modeling of Ophthalmic Response to Space

To investigate ophthalmic changes in spaceflight, we would like to predict the impact of blood dysregulation and elevated intracranial pressure (ICP) on Intraocular Pressure (IOP). Unlike other physiological systems, there are very few lumped parameter models of the eye. The eye model described here is novel in its inclusion of the human choroid and retrobulbar subarachnoid space (rSAS), which are key elements in investigating the impact of increased ICP and ocular blood volume. Some ingenuity was required in modeling the blood and rSAS compartments due to the lack of quantitative data on essential hydrodynamic quantities, such as net choroidal volume and blood flowrate, inlet and exit pressures, and material properties, such as compliances between compartments

Validation of a mouse xenograft model system for gene expression analysis of human acute lymphoblastic leukaemia

<p>Abstract</p> <p>Background</p> <p>Pre-clinical models that effectively recapitulate human disease are critical for expanding our knowledge of cancer biology and drug resistance mechanisms. For haematological malignancies, the non-obese diabetic/severe combined immunodeficient (NOD/SCID) mouse is one of the most successful models to study paediatric acute lymphoblastic leukaemia (ALL). However, for this model to be effective for studying engraftment and therapy responses at the whole genome level, careful molecular characterisation is essential.</p> <p>Results</p> <p>Here, we sought to validate species-specific gene expression profiling in the high engraftment continuous ALL NOD/SCID xenograft. Using the human Affymetrix whole transcript platform we analysed transcriptional profiles from engrafted tissues without prior cell separation of mouse cells and found it to return highly reproducible profiles in xenografts from individual mice. The model was further tested with experimental mixtures of human and mouse cells, demonstrating that the presence of mouse cells does not significantly skew expression profiles when xenografts contain 90% or more human cells. In addition, we present a novel <it>in silico </it>and experimental masking approach to identify probes and transcript clusters susceptible to cross-species hybridisation.</p> <p>Conclusions</p> <p>We demonstrate species-specific transcriptional profiles can be obtained from xenografts when high levels of engraftment are achieved or with the application of transcript cluster masks. Importantly, this masking approach can be applied and adapted to other xenograft models where human tissue infiltration is lower. This model provides a powerful platform for identifying genes and pathways associated with ALL disease progression and response to therapy <it>in vivo</it>.</p