Three-dimensional modeling of a primary health care clinic in Ho, Ghana: its contribution to student engagement, fundraising, and program planning

Improvements in computer-based technologies can be leveraged to enhance engagement of remote stakeholders with the health needs of a geographically distant community. Three-dimensional (3D) modeling offers a platform to create detailed spatial representations through which stakeholders can experience improvements in shared understanding as well as increased involvement in community health projects occurring anywhere in the world. This case study describes the development of a 3D model of a community health clinic in rural Ghana used to encourage fundraising and sustain global engagement among students at Northwestern University. The resulting ‘virtual clinic’ was achieved quickly and at little cost, suggesting a broader utility of 3D modeling for global health practitioners for increasing donor engagement and resource mapping

Locomotor adaptability in persons with unilateral transtibial amputation

Background Locomotor adaptation enables walkers to modify strategies when faced with challenging walking conditions. While a variety of neurological injuries can impair locomotor adaptability, the effect of a lower extremity amputation on adaptability is poorly understood. Objective Determine if locomotor adaptability is impaired in persons with unilateral transtibial amputation (TTA). Methods The locomotor adaptability of 10 persons with a TTA and 8 persons without an amputation was tested while walking on a split-belt treadmill with the parallel belts running at the same (tied) or different (split) speeds. In the split condition, participants walked for 15 minutes with the respective belts moving at 0.5 m/s and 1.5 m/s. Temporal spatial symmetry measures were used to evaluate reactive accommodations to the perturbation, and the adaptive/de-adaptive response. Results Persons with TTA and the reference group of persons without amputation both demonstrated highly symmetric walking at baseline. During the split adaptation and tied post-adaptation walking both groups responded with the expected reactive accommodations. Likewise, adaptive and de-adaptive responses were observed. The magnitude and rate of change in the adaptive and de-adaptive responses were similar for persons with TTA and those without an amputation. Furthermore, adaptability was no different based on belt assignment for the prosthetic limb during split adaptation walking. Conclusions Reactive changes and locomotor adaptation in response to a challenging and novel walking condition were similar in persons with TTA to those without an amputation. Results suggest persons with TTA have the capacity to modify locomotor strategies to meet the demands of most walking conditions despite challenges imposed by an amputation and use of a prosthetic limb

Metabolic correlates of prevalent mild cognitive impairment and Alzheimer's disease in adults with Down syndrome.

IntroductionDisruption of metabolic function is a recognized feature of late onset Alzheimer's disease (LOAD). We sought to determine whether similar metabolic pathways are implicated in adults with Down syndrome (DS) who have increased risk for Alzheimer's disease (AD).MethodsWe examined peripheral blood from 292 participants with DS who completed baseline assessments in the Alzheimer's Biomarkers Consortium-Down Syndrome (ABC-DS) using untargeted mass spectrometry (MS). Our sample included 38 individuals who met consensus criteria for AD (DS-AD), 43 who met criteria for mild cognitive impairment (DS-MCI), and 211 who were cognitively unaffected and stable (CS).ResultsWe measured relative abundance of 8,805 features using MS and 180 putative metabolites were differentially expressed (DE) among the groups at false discovery rate-corrected q< 0.05. From the DE features, a nine-feature classifier model classified the CS and DS-AD groups with receiver operating characteristic area under the curve (ROC AUC) of 0.86 and a two-feature model classified the DS-MCI and DS-AD groups with ROC AUC of 0.88. Metabolite set enrichment analysis across the three groups suggested alterations in fatty acid and carbohydrate metabolism.DiscussionOur results reveal metabolic alterations in DS-AD that are similar to those seen in LOAD. The pattern of results in this cross-sectional DS cohort suggests a dynamic time course of metabolic dysregulation which evolves with clinical progression from non-demented, to MCI, to AD. Metabolomic markers may be useful for staging progression of DS-AD

An improved method for isolation of RNA from bone

<p>Abstract</p> <p>Background</p> <p>Bone physiology is increasingly appreciated as an important contributor to metabolic disorders such as type 2 diabetes. However, progress in understanding the role of bone in determining metabolic health is hampered by the well-described difficulty of obtaining high quality RNA from bone for gene expression analysis using the currently available approaches.</p> <p>Results</p> <p>We developed a simple approach to isolate bone RNA that combines pulverizing the bone and the phenol-guanidinium based RNA extraction in a single step while maintaining near-freezing temperatures. This single step method increases the yield of high quality RNA by eight-fold, with RNA integrity numbers ranging from 6.7 to 9.2.</p> <p>Conclusions</p> <p>Our streamlined approach substantially increases the yield of high-quality RNA from bone tissue while facilitating safe and efficient processing of multiple samples using readily available platforms. The RNA obtained from this method is suitable for use in gene expression analysis in real-time quantitative PCR, microarray, and next generation sequencing applications.</p

Development and formative evaluation of the e-Health implementation toolkit

&lt;b&gt;Background&lt;/b&gt; The use of Information and Communication Technology (ICT) or e-Health is seen as essential for a modern, cost-effective health service. However, there are well documented problems with implementation of e-Health initiatives, despite the existence of a great deal of research into how best to implement e-Health (an example of the gap between research and practice). This paper reports on the development and formative evaluation of an e-Health Implementation Toolkit (e-HIT) which aims to summarise and synthesise new and existing research on implementation of e-Health initiatives, and present it to senior managers in a user-friendly format.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Results&lt;/b&gt; The content of the e-HIT was derived by combining data from a systematic review of reviews of barriers and facilitators to implementation of e-Health initiatives with qualitative data derived from interviews of "implementers", that is people who had been charged with implementing an e-Health initiative. These data were summarised, synthesised and combined with the constructs from the Normalisation Process Model. The software for the toolkit was developed by a commercial company (RocketScience). Formative evaluation was undertaken by obtaining user feedback. There are three components to the toolkit - a section on background and instructions for use aimed at novice users; the toolkit itself; and the report generated by completing the toolkit. It is available to download from http://www.ucl.ac.uk/pcph/research/ehealth/documents/e-HIT.xls&lt;p&gt;&lt;/p&gt; &lt;b&gt;Conclusions&lt;/b&gt; The e-HIT shows potential as a tool for enhancing future e-Health implementations. Further work is needed to make it fully web-enabled, and to determine its predictive potential for future implementations

An Efficient Method of Modeling Material Properties Using a Thermal Diffusion Analogy: An Example Based on Craniofacial Bone

The ability to incorporate detailed geometry into finite element models has allowed researchers to investigate the influence of morphology on performance aspects of skeletal components. This advance has also allowed researchers to explore the effect of different material models, ranging from simple (e.g., isotropic) to complex (e.g., orthotropic), on the response of bone. However, bone's complicated geometry makes it difficult to incorporate complex material models into finite element models of bone. This difficulty is due to variation in the spatial orientation of material properties throughout bone. Our analysis addresses this problem by taking full advantage of a finite element program's ability to solve thermal-structural problems. Using a linear relationship between temperature and modulus, we seeded specific nodes of the finite element model with temperatures. We then used thermal diffusion to propagate the modulus throughout the finite element model. Finally, we solved for the mechanical response of the finite element model to the applied loads and constraints. We found that using the thermal diffusion analogy to control the modulus of bone throughout its structure provides a simple and effective method of spatially varying modulus. Results compare favorably against both experimental data and results from an FE model that incorporated a complex (orthotropic) material model. This method presented will allow researchers the ability to easily incorporate more material property data into their finite element models in an effort to improve the model's accuracy

The Rewiring of Ubiquitination Targets in a Pathogenic Yeast Promotes Metabolic Flexibility, Host Colonization and Virulence

Funding: This work was funded by the European Research Council [http://erc.europa.eu/], AJPB (STRIFE Advanced Grant; C-2009-AdG-249793). The work was also supported by: the Wellcome Trust [www.wellcome.ac.uk], AJPB (080088, 097377); the UK Biotechnology and Biological Research Council [www.bbsrc.ac.uk], AJPB (BB/F00513X/1, BB/K017365/1); the CNPq-Brazil [http://cnpq.br], GMA (Science without Borders fellowship 202976/2014-9); and the National Centre for the Replacement, Refinement and Reduction of Animals in Research [www.nc3rs.org.uk], DMM (NC/K000306/1). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Acknowledgments We thank Dr. Elizabeth Johnson (Mycology Reference Laboratory, Bristol) for providing strains, and the Aberdeen Proteomics facility for the biotyping of S. cerevisiae clinical isolates, and to Euroscarf for providing S. cerevisiae strains and plasmids. We are grateful to our Microscopy Facility in the Institute of Medical Sciences for their expert help with the electron microscopy, and to our friends in the Aberdeen Fungal Group for insightful discussions.Peer reviewedPublisher PD

Ovine pedomics : the first study of the ovine foot 16S rRNA-based microbiome

We report the first study of the bacterial microbiome of ovine interdigital skin based on 16S rRNA by pyrosequencing and conventional cloning with Sanger-sequencing. Three flocks were selected, one a flock with no signs of footrot or interdigital dermatitis, a second flock with interdigital dermatitis alone and a third flock with both interdigital dermatitis and footrot. The sheep were classified as having either healthy interdigital skin (H), interdigital dermatitis (ID) or virulent footrot (VFR). The ovine interdigital skin bacterial community varied significantly by flock and clinical condition. The diversity and richness of operational taxonomic units was greater in tissue from sheep with ID than H or VFR affected sheep. Actinobacteria, Bacteriodetes, Firmicutes and Proteobacteria were the most abundant phyla comprising 25 genera. Peptostreptococcus, Corynebacterium and Staphylococcus were associated with H, ID and VFR respectively. Sequences of Dichelobacter nodosus, the causal agent of ovine footrot, were not amplified due to mismatches in the 16S rRNA universal forward primer (27F). A specific real time PCR assay was used to demonstrate the presence of D. nodosus which was detected in all samples including the flock with no signs of ID or VFR. Sheep with ID had significantly higher numbers of D. nodosus (104-109 cells/g tissue) than those with H or VFR feet

Atomic structures of TDP-43 LCD segments and insights into reversible or pathogenic aggregation.

The normally soluble TAR DNA-binding protein 43 (TDP-43) is found aggregated both in reversible stress granules and in irreversible pathogenic amyloid. In TDP-43, the low-complexity domain (LCD) is believed to be involved in both types of aggregation. To uncover the structural origins of these two modes of β-sheet-rich aggregation, we have determined ten structures of segments of the LCD of human TDP-43. Six of these segments form steric zippers characteristic of the spines of pathogenic amyloid fibrils; four others form LARKS, the labile amyloid-like interactions characteristic of protein hydrogels and proteins found in membraneless organelles, including stress granules. Supporting a hypothetical pathway from reversible to irreversible amyloid aggregation, we found that familial ALS variants of TDP-43 convert LARKS to irreversible aggregates. Our structures suggest how TDP-43 adopts both reversible and irreversible β-sheet aggregates and the role of mutation in the possible transition of reversible to irreversible pathogenic aggregation

Associations between insulin and glucose concentrations and anthropometric measures of fat mass in Australian adolescents

<p>Abstract</p> <p>Background</p> <p>One of the most serious, yet common co-morbidities of obesity is insulin resistance, which if untreated may progress to type 2 diabetes. This paper describes the insulin and glucose concentration distributions, the prevalence of elevated insulin, the associations between insulin and body mass index (BMI), waist circumference, waist-to-height ratio (WHtR) and fat mass index in a representative sample of Australian adolescents.</p> <p>Methods</p> <p>Cross-sectional population-based study of adolescent boys and girls (N = 496, mean age 15.3 years) attending schools in metropolitan Sydney, Australia. Fasting venous blood collected and analysed for insulin and glucose concentrations. Height, weight, waist circumference measured, BMI and waist-to-height ratio calculated. Pubertal status self-reported.</p> <p>Results</p> <p>Glucose concentrations were normally distributed and were not associated with adiposity. Insulin concentrations were distributed logarithmically, were higher among girls than boys overall and within the same ranges of BMI and waist circumference, but were lower among girls than boys within the same ranges of fat mass adjusted for height. The prevalence of elevated insulin concentration (defined as > 100 pmol/L) was 15.9% and 17.1% among boys and girls, respectively. Correlations between insulin concentration and BMI, waist circumference, WHtR and fat mass adjusted for height were 0.53, 0.49, 0.51 and 0.55, among boys, respectively, and 0.35, 0.40, 0.42 and 0.34, among girls, respectively.</p> <p>Conclusions</p> <p>Elevated insulin is highly correlated with adiposity in adolescents. BMI and WHtR are simple measures that can be used to identify young people who should be screened for insulin resistance and other co-morbidities.</p