Fast spin echo sequences for BOLD functional MRI

At higher field strengths, spin echo (SE) functional MRI (fMRI) is an attractive alternative to gradient echo (GE) as the increased weighting towards the microvasculature results in intrinsically better localization of the BOLD signal. Images are free of signal voids but the commonly used echo planar imaging (EPI) sampling scheme causes geometric distortions, and T2* effects often contribute considerably to the signal changes measured upon brain activation. Multiply refocused SE sequences such as fast spin echo (FSE) are essentially artifact free but their application to fast fMRI is usually hindered due to high energy deposition, and long sampling times. In the work presented here, a combination of parallel imaging and partial Fourier acquisition is used to shorten FSE acquisition times to near those of conventional SE-EPI, permitting sampling of eight slices (matrix 64  ×  64) per second. Signal acquisition is preceded by a preparation experiment that aims at increasing the relative contribution of extravascular dynamic averaging to the BOLD signal. Comparisons are made with conventional SE-EPI using a visual stimulation paradigm. While the observed signal changes are approximately 30% lower, most likely due to the absence of T2* contamination, activation size and t-scores are comparable for both methods, suggesting that HASTE fMRI is a viable alternative, particularly if distortion free images are required. Our data also indicate that the BOLD post-stimulus undershoot is most probably attributable to persistent elevated oxygen metabolism rather than to delayed vascular compliance

Spatial Guilds in the Serengeti Food Web Revealed by a Bayesian Group Model

Food webs, networks of feeding relationships among organisms, provide fundamental insights into mechanisms that determine ecosystem stability and persistence. Despite long-standing interest in the compartmental structure of food webs, past network analyses of food webs have been constrained by a standard definition of compartments, or modules, that requires many links within compartments and few links between them. Empirical analyses have been further limited by low-resolution data for primary producers. In this paper, we present a Bayesian computational method for identifying group structure in food webs using a flexible definition of a group that can describe both functional roles and standard compartments. The Serengeti ecosystem provides an opportunity to examine structure in a newly compiled food web that includes species-level resolution among plants, allowing us to address whether groups in the food web correspond to tightly-connected compartments or functional groups, and whether network structure reflects spatial or trophic organization, or a combination of the two. We have compiled the major mammalian and plant components of the Serengeti food web from published literature, and we infer its group structure using our method. We find that network structure corresponds to spatially distinct plant groups coupled at higher trophic levels by groups of herbivores, which are in turn coupled by carnivore groups. Thus the group structure of the Serengeti web represents a mixture of trophic guild structure and spatial patterns, in contrast to the standard compartments typically identified in ecological networks. From data consisting only of nodes and links, the group structure that emerges supports recent ideas on spatial coupling and energy channels in ecosystems that have been proposed as important for persistence.Comment: 28 pages, 6 figures (+ 3 supporting), 2 tables (+ 4 supporting

Breast-Milk Substitutes: A New Old-Threat for Breastfeeding Policy in Developing Countries. A Case Study in a Traditionally High Breastfeeding Country

Background: Developing countries with traditionally breastfeeding are now experiencing the increasing pressure of formula milk marketing. This may endanger lives and undermine the efforts of national policies in achieving the objectives of the Millennium Development Goals. We examined the use of, and factors for use, of all available breast-milk substitutes (BMS) in a country with a traditionally high rate of breastfeeding. Methods: Randomised multi-stage sampling surveys in 90 villages in 12/17 provinces in Laos. Participants: 1057 mothers with infants under 24 months of age. Tools: 50-query questionnaire and a poster of 22 BMS (8 canned or powdered milk; 6 non-dairy; 6 formulas; 2 non-formulas). Outcome measures included: prevalence of use and age of starting BMS in relation to socio-demographic characteristics and information sources, by univariate and multivariate analyses

The context of HIV risk behaviours among HIV-positive injection drug users in Viet Nam: Moving toward effective harm reduction

<p>Abstract</p> <p>Background</p> <p>Injection drug users represent the largest proportion of all HIV reported cases in Viet Nam. This study aimed to explore the perceptions of risk and risk behaviours among HIV-positive injection drug users, and their experiences related to safe injection and safe sex practices.</p> <p>Methods</p> <p>This study used multiple qualitative methods in data collection including in-depth interviews, focus group discussions and participant observation with HIV-positive injection drug users.</p> <p>Results</p> <p>The informants described a change in the sharing practices among injection drug users towards more precautions and what was considered 'low risk sharing', like sharing among seroconcordant partners and borrowing rather than lending. However risky practices like re-use of injection equipment and 'syringe pulling' i.e. the use of left-over drugs in particular, were frequently described and observed. Needle and syringe distribution programmes were in place but carrying needles and syringes and particularly drugs could result in being arrested and fined. Fear of rejection and of loss of intimacy made disclosure difficult and was perceived as a major obstacle for condom use among recently diagnosed HIV infected individuals.</p> <p>Conclusion</p> <p>HIV-positive injection drug users continue to practice HIV risk behaviours. The anti-drug law and the police crack-down policy appeared as critical factors hampering ongoing prevention efforts with needle and syringe distribution programmes in Viet Nam. Drastic policy measures are needed to reduce the very high HIV prevalence among injection drug users.</p

Realist evaluation to improve health systems responsiveness to neglected health needs of vulnerable groups in Ghana and Vietnam: Study protocol

Background Socio-economic growth in many low and middle-income countries has resulted in more available, though not equitably accessible, healthcare. Such growth has also increased demands from citizens for their health systems to be more responsive to their needs. This paper shares a protocol for the RESPONSE study which aims to understand, co-produce, implement and evaluate context-sensitive interventions to improve health systems responsiveness to health needs of vulnerable groups in Ghana and Vietnam. Methods We will use a realist mixed-methods theory-driven case study design, combining quantitative (household survey, secondary analysis of facility data) and qualitative (in-depth interviews, focus groups, observations and document and literature review) methods. Data will be analysed retroductively. The study will comprise three Phases. In Phase 1, we will understand actors’ expectations of responsive health systems, identify key priorities for interventions, and using evidence from a realist synthesis we will develop an initial theory and generate a baseline data. In Phase 2, we will co-produce jointly with key actors, the context-sensitive interventions to improve health systems responsiveness. The interventions will seek to improve internal (i.e. intra-system) and external (i.e. people-systems) interactions through participatory workshops. In Phase 3, we will implement and evaluate the interventions by testing and refining our initial theory through comparing the intended design to the interventions’ actual performance. Discussion The study’s key outcomes will be: (1) improved health systems responsiveness, contributing to improved health services and ultimately health outcomes in Ghana and Vietnam and (2) an empirically-grounded and theoretically-informed model of complex contexts-mechanisms-outcomes relations, together with transferable best practices for scalability and generalisability. Decision-makers across different levels will be engaged throughout. Capacity strengthening will be underpinned by in-depth understanding of capacity needs and assets of each partner team, and will aim to strengthen individual, organisational and system level capacities

Non-Overlapping Functions for Pyk2 and FAK in Osteoblasts during Fluid Shear Stress-Induced Mechanotransduction

Mechanotransduction, the process by which cells convert external mechanical stimuli such as fluid shear stress (FSS) into biochemical changes, plays a critical role in maintenance of the skeleton. We have proposed that mechanical stimulation by FSS across the surfaces of bone cells results in formation of unique signaling complexes called mechanosomes that are launched from sites of adhesion with the extracellular matrix and with other bone cells [1]. Deformation of adhesion complexes at the cell membrane ultimately results in alteration of target gene expression. Recently, we reported that focal adhesion kinase (FAK) functions as a part of a mechanosome complex that is required for FSS-induced mechanotransduction in bone cells. This study extends this work to examine the role of a second member of the FAK family of non-receptor protein tyrosine kinases, proline-rich tyrosine kinase 2 (Pyk2), and determine its role during osteoblast mechanotransduction. We use osteoblasts harvested from mice as our model system in this study and compared the contributions of Pyk2 and FAK during FSS induced mechanotransduction in osteoblasts. We exposed Pyk2+/+ and Pyk2−/− primary calvarial osteoblasts to short period of oscillatory fluid flow and analyzed downstream activation of ERK1/2, and expression of c-fos, cyclooxygenase-2 and osteopontin. Unlike FAK, Pyk2 was not required for fluid flow-induced mechanotransduction as there was no significant difference in the response of Pyk2+/+ and Pyk2−/− osteoblasts to short periods of fluid flow (FF). In contrast, and as predicted, FAK−/− osteoblasts were unable to respond to FF. These data indicate that FAK and Pyk2 have distinct, non-redundant functions in launching mechanical signals during osteoblast mechanotransduction. Additionally, we compared two methods of generating FF in both cell types, oscillatory pump method and another orbital platform method. We determined that both methods of generating FF induced similar responses in both primary calvarial osteoblasts and immortalized calvarial osteoblasts

The insecticide resistance status of malaria vectors in the Mekong region

<p>Abstract</p> <p>Background</p> <p>Knowledge on insecticide resistance in target species is a basic requirement to guide insecticide use in malaria control programmes. Malaria transmission in the Mekong region is mainly concentrated in forested areas along the country borders, so that decisions on insecticide use should ideally be made at regional level. Consequently, cross-country monitoring of insecticide resistance is indispensable to acquire comparable baseline data on insecticide resistance.</p> <p>Methods</p> <p>A network for the monitoring of insecticide resistance, MALVECASIA, was set up in the Mekong region in order to assess the insecticide resistance status of the major malaria vectors in Cambodia, Laos, Thailand, and Vietnam. From 2003 till 2005, bioassays were performed on adult mosquitoes using the standard WHO susceptibility test with diagnostic concentrations of permethrin 0.75% and DDT 4%. Additional tests were done with pyrethroid insecticides applied by the different national malaria control programmes.</p> <p>Results</p> <p><it>Anopheles dirus s.s</it>., the main vector in forested malaria foci, was susceptible to permethrin. However, in central Vietnam, it showed possible resistance to type II pyrethroids. In the Mekong delta, <it>Anopheles epiroticus </it>was highly resistant to all pyrethroid insecticides tested. It was susceptible to DDT, except near Ho Chi Minh City where it showed possible DDT resistance. In Vietnam, pyrethroid susceptible and tolerant <it>Anopheles minimus s.l</it>. populations were found, whereas <it>An. minimus s.l</it>. from Cambodia, Laos and Thailand were susceptible. Only two <it>An. minimus s.l</it>. populations showed DDT tolerance. <it>Anopheles vagus </it>was found resistant to DDT and to several pyrethroids in Vietnam and Cambodia.</p> <p>Conclusion</p> <p>This is the first large scale, cross-country survey of insecticide resistance in <it>Anopheles </it>species in the Mekong Region. A unique baseline data on insecticide resistance for the Mekong region is now available, which enables the follow-up of trends in susceptibility status in the region and which will serve as the basis for further resistance management. Large differences in insecticide resistance status were observed among species and countries. In Vietnam, insecticide resistance was mainly observed in low or transmission-free areas, hence an immediate change of malaria vector control strategy is not required. Though, resistance management is important because the risk of migration of mosquitoes carrying resistance genes from non-endemic to endemic areas. Moreover, trends in resistance status should be carefully monitored and the impact of existing vector control tools on resistant populations should be assessed.</p

Comparative Analysis of Dengue and Zika Outbreaks Reveals Differences by Setting and Virus.

The pacific islands of Micronesia have experienced several outbreaks of mosquito-borne diseases over the past decade. In outbreaks on small islands, the susceptible population is usually well defined, and there is no co-circulation of pathogens. Because of this, analysing such outbreaks can be useful for understanding the transmission dynamics of the pathogens involved, and particularly so for yet understudied pathogens such as Zika virus. Here, we compared three outbreaks of dengue and Zika virus in two different island settings in Micronesia, the Yap Main Islands and Fais, using a mathematical model of transmission dynamics and making full use of commonalities in disease and setting between the outbreaks. We found that the estimated reproduction numbers for Zika and dengue were similar when considered in the same setting, but that, conversely, reproduction number for the same disease can vary considerably by setting. On the Yap Main Islands, we estimated a reproduction number of 8.0-16 (95% Credible Interval (CI)) for the dengue outbreak and 4.8-14 (95% CI) for the Zika outbreak, whereas for the dengue outbreak on Fais our estimate was 28-102 (95% CI). We further found that the proportion of cases of Zika reported was smaller (95% CI 1.4%-1.9%) than that of dengue (95% CI: 47%-61%). We confirmed these results in extensive sensitivity analysis. They suggest that models for dengue transmission can be useful for estimating the predicted dynamics of Zika transmission, but care must be taken when extrapolating findings from one setting to another

VLDL Hydrolysis by Hepatic Lipase Regulates PPARδ Transcriptional Responses

PPARs (α,γ,δ) are a family of ligand-activated transcription factors that regulate energy balance, including lipid metabolism. Despite these critical functions, the integration between specific pathways of lipid metabolism and distinct PPAR responses remains obscure. Previous work has revealed that lipolytic pathways can activate PPARs. Whether hepatic lipase (HL), an enzyme that regulates VLDL and HDL catabolism, participates in PPAR responses is unknown.Using PPAR ligand binding domain transactivation assays, we found that HL interacted with triglyceride-rich VLDL (>HDL≫LDL, IDL) to activate PPARδ preferentially over PPARα or PPARγ, an effect dependent on HL catalytic activity. In cell free ligand displacement assays, VLDL hydrolysis by HL activated PPARδ in a VLDL-concentration dependent manner. Extended further, VLDL stimulation of HL-expressing HUVECs and FAO hepatoma cells increased mRNA expression of canonical PPARδ target genes, including adipocyte differentiation related protein (ADRP), angiopoietin like protein 4 and pyruvate dehydrogenase kinase-4. HL/VLDL regulated ADRP through a PPRE in the promoter region of this gene. In vivo, adenoviral-mediated hepatic HL expression in C57BL/6 mice increased hepatic ADRP mRNA levels by 30%. In ob/ob mice, a model with higher triglycerides than C57BL/6 mice, HL overexpression increased ADRP expression by 70%, demonstrating the importance of triglyceride substrate for HL-mediated PPARδ activation. Global metabolite profiling identified HL/VLDL released fatty acids including oleic acid and palmitoleic acid that were capable of recapitulating PPARδ activation and ADRP gene regulation in vitro.These data define a novel pathway involving HL hydrolysis of VLDL that activates PPARδ through generation of specific monounsaturated fatty acids. These data also demonstrate how integrating cell biology with metabolomic approaches provides insight into specific lipid mediators and pathways of lipid metabolism that regulate transcription

Diagnosis of chronic conditions with modifiable lifestyle risk factors in selected urban and rural areas of Bangladesh and sociodemographic variability therein

<p>Abstract</p> <p>Background</p> <p>Bangladesh suffers from a lack of healthcare providers. The growing chronic disease epidemic's demand for healthcare resources will further strain Bangladesh's limited healthcare workforce. Little is known about how Bangladeshis with chronic disease seek care. This study describes chronic disease patients' care seeking behavior by analyzing which providers diagnose these diseases.</p> <p>Methods</p> <p>During 2 month periods in 2009, a cross-sectional survey collected descriptive data on chronic disease diagnoses among 3 surveillance populations within the International Center for Diarrheal Disease Research, Bangladesh (ICDDR, B) network. The maximum number of respondents (over age 25) who reported having ever been diagnosed with a chronic disease determined the sample size. Using SAS software (version 8.0) multivariate regression analyses were preformed on related sociodemographic factors.</p> <p>Results</p> <p>Of the 32,665 survey respondents, 8,591 self reported having a chronic disease. Chronically ill respondents were 63.4% rural residents. Hypertension was the most prevalent disease in rural (12.4%) and urban (16.1%) areas. In rural areas chronic disease diagnoses were made by MBBS doctors (59.7%) and Informal Allopathic Providers (IAPs) (34.9%). In urban areas chronic disease diagnoses were made by MBBS doctors (88.0%) and IAP (7.9%). Our analysis identified several groups that depended heavily on IAP for coverage, particularly rural, poor and women.</p> <p>Conclusion</p> <p>IAPs play important roles in chronic disease care, particularly in rural areas. Input and cooperation from IAPs are needed to minimize rural health disparities. More research on IAP knowledge and practices regarding chronic disease is needed to properly utilize this potential healthcare resource.</p