<i>Trypanosoma brucei rhodesiense</i> transmitted by a single tsetse fly bite in vervet monkeys as a model of human African trypanosomiasis

Sleeping sickness is caused by a species of trypanosome blood parasite that is transmitted by tsetse flies. To understand better how infection with this parasite leads to disease, we provide here the most detailed description yet of the course of infection and disease onset in vervet monkeys. One infected tsetse fly was allowed to feed on each host individual, and in all cases infections were successful. The characteristics of infection and disease were similar in all hosts, but the rate of progression varied considerably. Parasites were first detected in the blood 4-10 days after infection, showing that migration of parasites from the site of fly bite was very rapid. Anaemia was a key feature of disease, with a reduction in the numbers and average size of red blood cells and associated decline in numbers of platelets and white blood cells. One to six weeks after infection, parasites were observed in the cerebrospinal fluid (CSF), indicating that they had moved from the blood into the brain; this was associated with a white cell infiltration. This study shows that fly-transmitted infection in vervets accurately mimics human disease and provides a robust model to understand better how sleeping sickness develops

Development of a validation algorithm for 'present on admission' flagging

Background. The use of routine hospital data for understanding patterns of adverse outcomes has been limited in the past by the fact that pre-existing and post-admission conditions have been indistinguishable. The use of a 'Present on Admission' (or POA) indicator to distinguish pre-existing or co-morbid conditions from those arising during the episode of care has been advocated in the US for many years as a tool to support quality assurance activities and improve the accuracy of risk adjustment methodologies. The USA, Australia and Canada now all assign a flag to indicate the timing of onset of diagnoses. For quality improvement purposes, it is the 'not-POA' diagnoses (that is, those acquired in hospital) that are of interest. Methods. Our objective was to develop an algorithm for assessing the validity of assignment of 'not-POA' flags. We undertook expert review of the International Classification of Diseases, 10th Revision, Australian Modification (ICD-10-AM) to identify conditions that could not be plausibly hospital-acquired. The resulting computer algorithm was tested against all diagnoses flagged as complications in the Victorian (Australia) Admitted Episodes Dataset, 2005/06. Measures reported include rates of appropriate assignment of the new Australian 'Condition Onset' flag by ICD chapter, and patterns of invalid flagging. Results. Of 18,418 diagnosis codes reviewed, 93.4% (n = 17,195) reflected agreement on status for flagging by at least 2 of 3 reviewers (including 64.4% unanimous agreement; Fleiss' Kappa: 0.61). In tests of the new algorithm, 96.14% of all hospital-acquired diagnosis codes flagged were found to be valid in the Victorian records analysed. A lower proportion of individual codes was judged to be acceptably flagged (76.2%), but this reflected a high proportion of codes use

Avaliação da intensidade do treinamento técnico-tático e da fadiga causada em jogadores de futebol da categoria sub-20

Resumo Visto que o calendário atual do futebol não disponibiliza um tempo hábil para a devida recuperação dos atletas, fadiga e recuperação têm sido amplamente estudadas por pesquisadores. O que levou ao surgimento de alguns instrumentos com o propósito de fornecer informações e dar suporte aos profissionais visando a alta performance. O objetivo deste estudo foi analisar a intensidade do Treinamento Técnico-tático e a fadiga causada em jogadores de futebol da categoria sub-20, através do desempenho em testes de salto vertical e horizontal e da percepção subjetiva de esforço da sessão (PSE da sessão). Os jogadores (n = 25) realizaram o salto vertical contra movimento (SCM) e horizontal (SH), antes e após a uma sessão de Treinamento Técnico-tático (TTT), sendo a intensidade avaliada pela Escala de Borg (CR 10). O SCM não apresentou diferença significativa (p > 0,05), enquanto que o SH foi maior no Pós-TTT em relação ao Pré-TTT (p = 0,02). Quanto a PSE da sessão, 92% dos jogadores classificaram a intensidade do TTT como sendo de fácil à moderada. Os resultados deste estudo indicam que o TTT de baixa intensidade não compromete a potência nos testes de salto vertical e horizontal. Sugere-se que além de proporcionar a operacionalização dos padrões de comportamento táticos coletivos, o TTT de baixa intensidade possa ser utilizado em treinamentos de caráter regenerativo ou em momentos que o calendário esportivo não possibilite a recuperação completa dos jogadores

Claudin 13, a Member of the Claudin Family Regulated in Mouse Stress Induced Erythropoiesis

Mammals are able to rapidly produce red blood cells in response to stress. The molecular pathways used in this process are important in understanding responses to anaemia in multiple biological settings. Here we characterise the novel gene Claudin 13 (Cldn13), a member of the Claudin family of tight junction proteins using RNA expression, microarray and phylogenetic analysis. We present evidence that Cldn13 appears to be co-ordinately regulated as part of a stress induced erythropoiesis pathway and is a mouse-specific gene mainly expressed in tissues associated with haematopoietic function. CLDN13 phylogenetically groups with its genomic neighbour CLDN4, a conserved tight junction protein with a putative role in epithelial to mesenchymal transition, suggesting a recent duplication event. Mechanisms of mammalian stress erythropoiesis are of importance in anaemic responses and expression microarray analyses demonstrate that Cldn13 is the most abundant Claudin in spleen from mice infected with Trypanosoma congolense. In mice prone to anaemia (C57BL/6), its expression is reduced compared to strains which display a less severe anaemic response (A/J and BALB/c) and is differentially regulated in spleen during disease progression. Genes clustering with Cldn13 on microarrays are key regulators of erythropoiesis (Tal1, Trim10, E2f2), erythrocyte membrane proteins (Rhd and Gypa), associated with red cell volume (Tmcc2) and indirectly associated with erythropoietic pathways (Cdca8, Cdkn2d, Cenpk). Relationships between genes appearing co-ordinately regulated with Cldn13 post-infection suggest new insights into the molecular regulation and pathways involved in stress induced erythropoiesis and suggest a novel, previously unreported role for claudins in correct cell polarisation and protein partitioning prior to erythroblast enucleation

Surveillance biopsies in children post-kidney transplant

Surveillance biopsies are increasingly used in the post-transplant monitoring of pediatric renal allograft recipients. The main justification for this procedure is to diagnose early and presumably modifiable acute and chronic renal allograft injury. Pediatric recipients are theoretically at increased risk for subclinical renal allograft injury due to their relatively large adult-sized kidneys and their higher degree of immunological responsiveness. The safety profile of this procedure has been well investigated. Patient morbidity is low, with macroscopic hematuria being the most common adverse event. No patient deaths have been attributed to this procedure. Longitudinal surveillance biopsy studies have revealed a substantial burden of subclinical immunological and non-immunological injury, including acute cellular rejection, interstitial fibrosis and tubular atrophy, microvascular lesions and transplant glomerulopathy. The main impediment to the implementation of surveillance biopsies as the standard of care is the lack of demonstrable benefit of early histological detection on long-term outcome. The considerable debate surrounding this issue highlights the need for multicenter, prospective, and randomized studies

Trypanosoma vivax Infections: Pushing Ahead with Mouse Models for the Study of Nagana. II. Immunobiological Dysfunctions

Trypanosoma vivax is the main species involved in trypanosomosis, but very little is known about the immunobiology of the infective process caused by this parasite. Recently we undertook to further characterize the main parasitological, haematological and pathological characteristics of mouse models of T. vivax infection and noted severe anemia and thrombocytopenia coincident with rising parasitemia. To gain more insight into the organism's immunobiology, we studied lymphocyte populations in central (bone marrow) and peripherical (spleen and blood) tissues following mouse infection with T. vivax and showed that the immune system apparatus is affected both quantitatively and qualitatively. More precisely, after an initial increase that primarily involves CD4+ T cells and macrophages, the number of splenic B cells decreases in a step-wise manner. Our results show that while infection triggers the activation and proliferation of Hematopoietic Stem Cells, Granulocyte-Monocyte, Common Myeloid and Megacaryocyte Erythrocyte progenitors decrease in number in the course of the infection. An in-depth analysis of B-cell progenitors also indicated that maturation of pro-B into pre-B precursors seems to be compromised. This interferes with the mature B cell dynamics and renewal in the periphery. Altogether, our results show that T. vivax induces profound immunological alterations in myeloid and lymphoid progenitors which may prevent adequate control of T. vivax trypanosomosis

A Systematic Review of Cost-of-Illness Studies of Multimorbidity

Objectives: The economic burden of multimorbidity is considerable. This review analyzed the methods of cost-of-illness (COI) studies and summarized the economic outcomes of multimorbidity. Methods: A systematic review (2000–2016) was performed, which was registered with Prospero, reported according to PRISMA, and used a quality checklist adapted for COI studies. The inclusion criteria were peer-reviewed COI studies on multimorbidity, whereas the exclusion criterion was studies focusing on an index disease. Extracted data included the definition, measure, and prevalence of multimorbidity; the number of included health conditions; the age of study population; the variables used in the COI methodology; the percentage of multimorbidity vs. total costs; and the average costs per capita. Results: Among the 26 included articles, 14 defined multimorbidity as a simple count of 2 or more conditions. Methodologies used to derive the costs were markedly different. Given different healthcare systems, OOP payments of multimorbidity varied across countries. In the 17 and 12 studies with cut-offs of ≥2 and ≥3 conditions, respectively, the ratios of multimorbidity to non-multimorbidity costs ranged from 2–16 to 2–10. Among the ten studies that provided cost breakdowns, studies with and without a societal perspective attributed the largest percentage of multimorbidity costs to social care and inpatient care/medicine, respectively. Conclusion: Multimorbidity was associated with considerable economic burden. Synthesising the cost of multimorbidity was challenging due to multiple definitions of multimorbidity and heterogeneity in COI methods. Count method was most popular to define multimorbidity. There is consistent evidence that multimorbidity was associated with higher costs

The genome landscape of indigenous African cattle

Background: The history of African indigenous cattle and their adaptation to environmental and human selection pressure is at the root of their remarkable diversity. Characterization of this diversity is an essential step towards understanding the genomic basis of productivity and adaptation to survival under African farming systems. Results: We analyze patterns of African cattle genetic variation by sequencing 48 genomes from five indigenous populations and comparing them to the genomes of 53 commercial taurine breeds. We find the highest genetic diversity among African zebu and sanga cattle. Our search for genomic regions under selection reveals signatures of selection for environmental adaptive traits. In particular, we identify signatures of selection including genes and/ or pathways controlling anemia and feeding behavior in the trypanotolerant N’Dama, coat color and horn development in Ankole, and heat tolerance and tick resistance across African cattle especially in zebu breeds. Conclusions: Our findings unravel at the genome-wide level, the unique adaptive diversity of African cattle while emphasizing the opportunities for sustainable improvement of livestock productivity on the continent