Ears of the Armadillo: Global Health Research and Neglected Diseases in Texas

Neglected tropical diseases (NTDs) have\ud been recently identified as significant public\ud health problems in Texas and elsewhere in\ud the American South. A one-day forum on the\ud landscape of research and development and\ud the hidden burden of NTDs in Texas\ud explored the next steps to coordinate advocacy,\ud public health, and research into a\ud cogent health policy framework for the\ud American NTDs. It also highlighted how\ud U.S.-funded global health research can serve\ud to combat these health disparities in the\ud United States, in addition to benefiting\ud communities abroad

Synchronization in complex networks

Synchronization processes in populations of locally interacting elements are in the focus of intense research in physical, biological, chemical, technological and social systems. The many efforts devoted to understand synchronization phenomena in natural systems take now advantage of the recent theory of complex networks. In this review, we report the advances in the comprehension of synchronization phenomena when oscillating elements are constrained to interact in a complex network topology. We also overview the new emergent features coming out from the interplay between the structure and the function of the underlying pattern of connections. Extensive numerical work as well as analytical approaches to the problem are presented. Finally, we review several applications of synchronization in complex networks to different disciplines: biological systems and neuroscience, engineering and computer science, and economy and social sciences.Comment: Final version published in Physics Reports. More information available at http://synchronets.googlepages.com

Addressing the double-burden of diabetes and tuberculosis : Lessons from Kyrgyzstan

Background: The incidence of diabetes and tuberculosis co-morbidity is rising, yet little work has been done to understand potential implications for health systems, healthcare providers and individuals. Kyrgyzstan is a priority country for tuberculosis control and has a 5% prevalence of diabetes in adults, with many health system challenges for both conditions. Methods: Patient exit interviews collected data on demographic and socio-economic characteristics, health spending and care seeking for people with diabetes, tuberculosis and both diabetes and tuberculosis. Qualitative data were collected through semi-structured interviews with healthcare workers involved in diabetes and tuberculosis care, to understand delivery of care and how providers view effectiveness of care. Results: The experience of co-affected individuals within the health system is different than those just with tuberculosis or diabetes. Co-affected patients do not receive more care and also have different care for their tuberculosis than people with only tuberculosis. Very high levels of catastrophic spending are found among all groups despite these two conditions being included in the Kyrgyz state benefit package especially for medicines. Conclusions: This study highlights that different patterns of service provision by disease group are found. Although Kyrgyzstan has often been cited as an example in terms of health reforms and developing Primary Health Care, this study highlights the challenge of managing conditions that are viewed as "too complicated" for non-specialists and the impact this has on costs and management of individuals

Risk of tuberculosis in patients with diabetes: population based cohort study using the UK Clinical Practice Research Datalink.

BACKGROUND: Previous cohort studies demonstrate diabetes as a risk factor for tuberculosis (TB) disease. Public Health England has identified improved TB control as a priority area and has proposed a primary care-based screening program for latent TB. We investigated the association between diabetes and risk of tuberculosis in a UK General Practice cohort in order to identify potential high-risk groups appropriate for latent TB screening. METHODS: Using data from the UK Clinical Practice Research Datalink we constructed a cohort of patients with incident diabetes. We included 222,731 patients with diabetes diagnosed from 1990-2013 and 1,218,616 controls without diabetes at index date who were matched for age, sex and general practice. The effect of diabetes was explored using a Poisson analysis adjusted for age, ethnicity, body mass index, socioeconomic status, alcohol intake and smoking. We explored the effects of age, diabetes duration and severity. The effects of diabetes on risk of incident TB were explored across strata of chronic disease care defined by cholesterol and blood pressure measurement and influenza vaccination rates. RESULTS: During just under 7 million person-years of follow-up, 969 cases of TB were identified. The incidence of TB was higher amongst patients with diabetes compared with the unexposed group: 16.2 and 13.5 cases per 100,000 person-years, respectively. After adjustment for potential confounders the association between diabetes and TB remained (adjusted RR 1.30, 95 % CI 1.01 to 1.67, P = 0.04). There was no evidence that age, time since diagnosis and severity of diabetes affected the association between diabetes and TB. Diabetes patients with the lowest and highest rates of chronic disease management had a higher risk of TB (P <0.001 for all comparisons). CONCLUSIONS: Diabetes as an independent risk factor is associated with only a modest overall increased risk of TB in our UK General Practice cohort and is unlikely to be sufficient cause to screen for latent TB. Across different consulting patterns, diabetes patients accessing the least amount of chronic disease care are at highest risk for TB.This article presents independent research supported by a National Institute for Health Research (NIHR) In Practice Fellowship to LP (grant number NIHR/IPF/11/05). DAJM received Wellcome Trust funding (grant number 092691/Z/10/Z). LS is supported by a Wellcome Trust Senior Research Fellowship in Clinical Science

The Kuramoto model in complex networks

181 pages, 48 figures. In Press, Accepted Manuscript, Physics Reports 2015 Acknowledgments We are indebted with B. Sonnenschein, E. R. dos Santos, P. Schultz, C. Grabow, M. Ha and C. Choi for insightful and helpful discussions. T.P. acknowledges FAPESP (No. 2012/22160-7 and No. 2015/02486-3) and IRTG 1740. P.J. thanks founding from the China Scholarship Council (CSC). F.A.R. acknowledges CNPq (Grant No. 305940/2010-4) and FAPESP (Grants No. 2011/50761-2 and No. 2013/26416-9) for financial support. J.K. would like to acknowledge IRTG 1740 (DFG and FAPESP).Peer reviewedPreprin

Differential Release and Phagocytosis of Tegument Glycoconjugates in Neurocysticercosis: Implications for Immune Evasion Strategies

Neurocysticercosis (NCC) is an infection of the central nervous system (CNS) by the metacestode of the helminth Taenia solium. The severity of the symptoms is associated with the intensity of the immune response. First, there is a long asymptomatic period where host immunity seems incapable of resolving the infection, followed by a chronic hypersensitivity reaction. Since little is known about the initial response to this infection, a murine model using the cestode Mesocestoides corti (syn. Mesocestoides vogae) was employed to analyze morphological changes in the parasite early in the infection. It was found that M. corti material is released from the tegument making close contact with the nervous tissue. These results were confirmed by infecting murine CNS with ex vivo–labeled parasites. Because more than 95% of NCC patients exhibit humoral responses against carbohydrate-based antigens, and the tegument is known to be rich in glycoconjugates (GCs), the expression of these types of molecules was analyzed in human, porcine, and murine NCC specimens. To determine the GCs present in the tegument, fluorochrome-labeled hydrazides as well as fluorochrome-labeled lectins with specificity to different carbohydrates were used. All the lectins utilized labeled the tegument. GCs bound by isolectinB4 were shed in the first days of infection and not resynthesized by the parasite, whereas GCs bound by wheat germ agglutinin and concavalinA were continuously released throughout the infectious process. GCs bound by these three lectins were taken up by host cells. Peanut lectin-binding GCs, in contrast, remained on the parasite and were not detected in host cells. The parasitic origin of the lectin-binding GCs found in host cells was confirmed using antibodies against T. solium and M. corti. We propose that both the rapid and persistent release of tegumental GCs plays a key role in the well-known immunomodulatory effects of helminths, including immune evasion and life-long inflammatory sequelae seen in many NCC patients

Evaluation of Lionex TB kits and mycobacterial antigens for IgG and IgA detection in cerebrospinal fluid from tuberculosis meningitis patients

To evaluate commercial Lionex TB together with four antigens of Mycobacterium tuberculosis (MPT-64, MT10.3, 16 kDa and 38 kDa) for IgG and IgA cerebrospinal fluid (CSF) detection in the diagnosis of tuberculosis meningitis (TBM) with CSF negative acid-fast bacilli staining, 19 cases of TBM, 64 cases of other infectious meningoencephalitis and 73 cases of other neurological disorders were tested by enzyme linked immunosorbent assay. IgA-MPT-64 and IgG Lionex showed the highest sensitivities, specificities, positive predictive value and negative predictive value (63.2%, 47.4%; 95%, 93.7%; 40%, 98% and 28.4%, 97.1%, respectively). However, while grey zone was 12.7% and 6%, respectively, lowering sensitivity but maintains high specificity (> 95%). High protein concentration in CSF was associated with antibody positivity CSF/HIV+ which did not influence the sensitivity of both tests. To our knowledge, this is the first description of IgA-MPT-64 and IgG Lionex antibodies in CSF-TBM and, although there is good specificity, adjustments are needed based on antigen composition to enhance sensitivity

Characterisation of silent and active genes for a variable large protein of Borrelia recurrentis

BACKGROUND: We report the characterisation of the variable large protein (vlp) gene expressed by clinical isolate A1 of Borrelia recurrentis; the agent of the life-threatening disease louse-borne relapsing fever. METHODS: The major vlp protein of this isolate was characterised and a DNA probe created. Use of this together with standard molecular methods was used to determine the location of the vlp1(B. recurrentis A1) gene in both this and other isolates. RESULTS: This isolate was found to carry silent and expressed copies of the vlp1(B. recurrentis A1) gene on plasmids of 54 kbp and 24 kbp respectively, whereas a different isolate, A17, had only the silent vlp1(B. recurrentis A17) on a 54 kbp plasmid. Silent and expressed vlp1 have identical mature protein coding regions but have different 5' regions, both containing different potential lipoprotein leader sequences. Only one form of vlp1 is transcribed in the A1 isolate of B. recurrentis, yet both 5' upstream sequences of this vlp1 gene possess features of bacterial promoters. CONCLUSION: Taken together these results suggest that antigenic variation in B. recurrentis may result from recombination of variable large and small protein genes at the junction between lipoprotein leader sequence and mature protein coding region. However, this hypothetical model needs to be validated by further identification of expressed and silent variant protein genes in other B. recurrentis isolates

Monounsaturated fatty acid, carbohydrate intake, and diabetes status are associated with arterial pulse pressure

<p>Abstract</p> <p>Background</p> <p>Diabetes is a global epidemic. Cardiovascular disease (CVD) is one of the most prevalent consequences of diabetes. Nutrition is considered a modifiable risk factor for CVD, particularly for individuals with diabetes; albeit, there is little consensus on the role of carbohydrates, proteins and fats for arterial health for persons with or without diabetes. In this study, we examined the association of macronutrients with arterial pulse pressure (APP), a surrogate measure of arterial health by diabetes status and race.</p> <p>Methods</p> <p>Participants were 892 Mexican Americans (MA), 1059 Black, non-Hispanics (BNH) and 2473 White, non-Hispanics (WNH) with and without diabetes of a weighted sample from the National Nutrition and Health Examination Survey (NHANES) 2007-2008. The cross-sectional analysis was performed with IBM-SPSS version 18 with the complex sample analysis module. The two-year sample weight for the sub-sample with laboratory values was applied to reduce bias and approximate a nationally, representative sample. Arterial stiffness was assessed by arterial pulse pressure (APP).</p> <p>Results</p> <p>APP was higher for MA [B = 0.063 (95% CI 0.015 to 0.111), p = 0.013] and BNH [B = 0.044 (95% CI 0.006 to 0.082), p = 0.018] than WNH, controlling for diabetes, age, gender, body mass index (BMI), fiber intake, energy intake (Kcal) and smoking. A two-way interaction of diabetes by carbohydrate intake (grams) was inversely associated with APP [B = -1.18 (95% CI -0.178 to -0.058), p = 0.001], controlling for race, age, gender, BMI, Kcal and smoking. BNH with diabetes who consumed more mono-unsaturated fatty acids (MUFA) than WNH with diabetes had lower APP [B = -0.112 (95%CI-0.179 to -0.045), p = 0.003] adjusting for saturated fatty acids, Kcal, age, gender, BMI and smoking.</p> <p>Conclusion</p> <p>Higher MUFA and carbohydrate intake for persons with diabetes reflecting lower APP may be due to replacement of saturated fats with CHO and MUFA. The associations of APP with diabetes, race and dietary intake need to be confirmed with intervention and prospective studies. Confirmation of these results would suggest that dietary interventions for minorities with diabetes may improve arterial health.</p