A novel approach : the propensity to propagate (PTP) method for controlling for host factors in studying the transmission of Mycobacterium tuberculosis

RATIONALE: Understanding the genetic variations among Mycobacterium tuberculosis (MTB) strains with differential ability to transmit would be a major step forward in preventing transmission. OBJECTIVES: To describe a method to extend conventional proxy measures of transmissibility by adjusting for patient-related factors, thus strengthening the causal association found with bacterial factors. METHODS: Clinical, demographic and molecular fingerprinting data were obtained during routine surveillance of verified MTB cases reported in the Netherlands between 1993 and 2011, and the phylogenetic lineages of the isolates were inferred. Odds ratios for host risk factors for clustering were used to obtain a measure of each patient's and cluster's propensity to propagate (CPP). Mean and median cluster sizes across different categories of CPP were compared amongst four different phylogenetic lineages. RESULTS: Both mean and median cluster size grew with increasing CPP category. On average, CPP values from Euro-American lineage strains were higher than Beijing and EAI strains. There were no significant differences between the mean and median cluster sizes among the four phylogenetic lineages within each CPP category. CONCLUSIONS: Our finding that the distribution of CPP scores was unequal across four different phylogenetic lineages supports the notion that host-related factors should be controlled for to attain comparability in measuring the different phylogenetic lineages' ability to propagate. Although Euro-American strains were more likely to be in clusters in an unadjusted analysis, no significant differences among the four lineages persisted after we controlled for host factors.Portuguese Foundation for Science and Technology (FCT) (SFRH/BD/33902/2009 to HN-G). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Divergent Effects of Human Cytomegalovirus and Herpes Simplex Virus-1 on Cellular Metabolism

Viruses rely on the metabolic network of the host cell to provide energy and macromolecular precursors to fuel viral replication. Here we used mass spectrometry to examine the impact of two related herpesviruses, human cytomegalovirus (HCMV) and herpes simplex virus type-1 (HSV-1), on the metabolism of fibroblast and epithelial host cells. Each virus triggered strong metabolic changes that were conserved across different host cell types. The metabolic effects of the two viruses were, however, largely distinct. HCMV but not HSV-1 increased glycolytic flux. HCMV profoundly increased TCA compound levels and flow of two carbon units required for TCA cycle turning and fatty acid synthesis. HSV-1 increased anapleurotic influx to the TCA cycle through pyruvate carboxylase, feeding pyrimidine biosynthesis. Thus, these two related herpesviruses drive diverse host cells to execute distinct, virus-specific metabolic programs. Current drugs target nucleotide metabolism for treatment of both viruses. Although our results confirm that this is a robust target for HSV-1, therapeutic interventions at other points in metabolism might prove more effective for treatment of HCMV

Treatment of displaced intra-articular calcaneal fractures by ligamentotaxis: current concepts’ review

Introduction: A large variety of therapeutic modalities for calcaneal fractures have been described in the literature. No single treatment modality for displaced intra-articular calcaneal fractures has proven superior over the other. This review describes and compares the different percutaneous distractional approaches for intra-articular calcaneal fractures. The history, technique, anatomical and fracture considerations, limitations and the results of different distractional approaches reported in the literature are reviewed. Method: Literature review on different percutaneous distractional approaches for displaced intra-articular calcaneal fractures. Results: Eight studies in which application of a distraction technique was used for the treatment of calcaneal fractures were identified. Because of the use of different classification, techniques, and outcome scoring systems, a meta-analysis was not possible. A literature review reveals overall fair to poor result in 10-29% of patients. Ten up to 26% of patients are unable to return to work after percutaneous treatment of their fracture. A secondary arthrodesis has to be performed in 2-15% of the cases. Infectious complications occur in 2-15%. Some loss of reduction is reported in 4-67%. Conclusion: Percutaneous distractional reduction and fixation appears to be a safe technique with overall good results and an acceptable complication rate, compared with other treatment modalities for displaced intra-articular calcaneal fractures. A meta-analysis, based on Cochrane Library criteria is not possible, because of a lack of level 1 and 2 trials on this subject

Genome analysis and physiological comparison of Alicycliphilus denitrificans strains BC and K601T

The genomes of the Betaproteobacteria Alicycliphilus denitrificans strains BC and K601T have been sequenced to get insight into the physiology of the two strains. Strain BC degrades benzene with chlorate as electron acceptor. The cyclohexanol-degrading denitrifying strain K601T is not able to use chlorate as electron acceptor, while strain BC cannot degrade cyclohexanol. The 16S rRNA sequences of strains BC and K601T are identical and the fatty acid methyl ester patterns of the strains are similar. Basic Local Alignment Search Tool (BLAST) analysis of predicted open reading frames of both strains showed most hits with Acidovorax sp. JS42, a bacterium that degrades nitro-aromatics. The genomes include strain-specific plasmids (pAlide201 in strain K601T and pAlide01 and pAlide02 in strain BC). Key genes of chlorate reduction in strain BC were located on a 120 kb megaplasmid (pAlide01), which was absent in strain K601T. Genes involved in cyclohexanol degradation were only found in strain K601T. Benzene and toluene are degraded via oxygenase-mediated pathways in both strains. Genes involved in the meta-cleavage pathway of catechol are present in the genomes of both strains. Strain BC also contains all genes of the ortho-cleavage pathway. The large number of mono- and dioxygenase genes in the genomes suggests that the two strains have a broader substrate range than known thus far.This research was supported by the Technology Foundation, the Applied Science Division (STW) of the Netherlands Organization for Scientific Research (NWO), project number 08053, the graduate school WIMEK (Wageningen Institute for Environment and Climate Research, which is part of SENSE Research School for Socio-Economic and Natural Sciences of the Environment, www.wimek-new.wur.nl and www.sense.nl), SKB (Dutch Centre for Soil Quality Management and Knowledge Transfer, www.skbodem.nl) and the Consolider project CSD-2007-00055. The research was incorporated in the TRIAS (TRIpartite Approaches 469 toward Soil systems processes) program (http://www.nwo.nl/en/research-and-results/programmes/alw/trias-tripartite-approach-to-soil-system-processes/index. html). Flávia Talarico Saia was supported by a FAPESP (the State of São Paulo Research Foundation) scholarship (2006-01997/5). The work conducted by the DOE JGI is supported by the Office of Science of the United States Department of Energy under contract number DE-AC02-05CH11231. Alfons Stams acknowledges support by an ERC (European Research Counsil) advanced grant (project 323009). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Cash Distribution Model with Safety Constraints

This article studies the cash distribution problem for bank correspondents that are geographically dispersed, and the associated risk indicators, service times, and logistics costs. The proposed model is a variant of the Inventory Routing Problem (IRP) that considers risk-management strategies. The model considers a single cash center with unlimited capacity, from which cash deliveries are carried out by a single vehicle with limited capacity for cash distribution. The bank correspondents to which the cash deliveries are made handles a limited storage capacity. This paper considers the routing decisions of vehicles with hard time window, and risk constraints focused on inducing unpredictability of routes in a cash supply chain. The proposed model is denoted as a risk constrained inventory routing problem with time Windows (RcIRPTW). A mathematical formulation based on mixed-integer programming is proposed, studying the impact of incidents risks in the transport of cash, generating computational experiments on test instances where four types of variations of the IRP are evaluated with several random demand scenarios. The results show the importance of simultaneously optimizing inventory decisions considering routing and inventory costs along with the consideration of risk mitigation strategies. These risk constraints force changing the routes of the vehicle, reducing incidents rates, and reducing route predictability for secure transportation and logistics.Este artículo estudia el problema de la distribución de efectivo para los corresponsales bancarios geográficamente dispersos y los indicadores de riesgo, tiempos de servicio y costos logísticos asociados. El modelo propuesto es una variante del problema de enrutamiento de inventario (IRP) que considera estrategias de gestión de riesgos. El modelo considera un único centro de efectivo con capacidad ilimitada, desde el cual las entregas de efectivo se realizan en un único vehículo con capacidad limitada para la distribución de efectivo. Los corresponsales bancarios a los que se realizan las entregas de efectivo manejan una capacidad de almacenamiento limitada. Este documento considera las decisiones de ruta de los vehículos con una ventana de tiempo difícil y las restricciones de riesgo enfocadas en inducir la imprevisibilidad de las rutas en una cadena de suministro de efectivo. El modelo propuesto se denota como un problema de enrutamiento de inventario con restricciones de riesgo con ventanas de tiempo (RcIRPTW). Se propone una formulación matemática basada en programación de enteros mixtos, estudiando el impacto de los riesgos de incidentes en el transporte de efectivo, generando experimentos computacionales en instancias de prueba donde se evalúan cuatro tipos de variaciones del PIR con varios escenarios de demanda aleatorios. Los resultados muestran la importancia de optimizar simultáneamente las decisiones de inventario considerando los costos de enrutamiento e inventario junto con la consideración de estrategias de mitigación de riesgos. Estas limitaciones de riesgo obligan a cambiar las rutas del vehículo, reducir las tasas de incidentes y reducir la previsibilidad de la ruta para un transporte y una logística seguros.International Conference on Computational Logistics 28-30 September 2020 Enschede, The Netherland

Comparative analysis of Mycobacterium tuberculosis pe and ppe genes reveals high sequence variation and an apparent absence of selective constraints.

Contains fulltext : 110619.pdf (publisher's version ) (Open Access)Mycobacterium tuberculosis complex (MTBC) genomes contain 2 large gene families termed pe and ppe. The function of pe/ppe proteins remains enigmatic but studies suggest that they are secreted or cell surface associated and are involved in bacterial virulence. Previous studies have also shown that some pe/ppe genes are polymorphic, a finding that suggests involvement in antigenic variation. Using comparative sequence analysis of 18 publicly available MTBC whole genome sequences, we have performed alignments of 33 pe (excluding pe_pgrs) and 66 ppe genes in order to detect the frequency and nature of genetic variation. This work has been supplemented by whole gene sequencing of 14 pe/ppe (including 5 pe_pgrs) genes in a cohort of 40 diverse and well defined clinical isolates covering all the main lineages of the M. tuberculosis phylogenetic tree. We show that nsSNP's in pe (excluding pgrs) and ppe genes are 3.0 and 3.3 times higher than in non-pe/ppe genes respectively and that numerous other mutation types are also present at a high frequency. It has previously been shown that non-pe/ppe M. tuberculosis genes display a remarkably low level of purifying selection. Here, we also show that compared to these genes those of the pe/ppe families show a further reduction of selection pressure that suggests neutral evolution. This is inconsistent with the positive selection pressure of "classical" antigenic variation. Finally, by analyzing such a large number of genes we were able to detect large differences in mutation type and frequency between both individual genes and gene sub-families. The high variation rates and absence of selective constraints provides valuable insights into potential pe/ppe function. Since pe/ppe proteins are highly antigenic and have been studied as potential vaccine components these results should also prove informative for aspects of M. tuberculosis vaccine design

Distance between residence and the dialysis unit does not impact self-perceived outcomes in hemodialysis patients

<p>Abstract</p> <p>Background</p> <p>Patients have to travel long distances to undergo hemodialysis (HD) in some regions. We aimed to search for an association of the distance between patients’ residence and the dialysis unit with quality of life, depression and coping among end-stage renal disease (ESRD) patients undergoing maintenance HD.</p> <p>Methods</p> <p>We studied 161 ESRD patients undergoing HD during April 2009. Quality of life, depression and coping were assessed by the SF-36, the 10-item CES-D and the Jalowiec Coping Scale, respectively. The sample was stratified in three groups: I-patients residing in Sobral (where the dialysis unit is located); II-patients residing in towns up to 100 km from Sobral; and III-patients residing in towns distant greater than 100 km from Sobral. Analysis of variance was used to detect differences in quality of life and coping scores between the groups. Logistic regression was used to test distance as a predictor of depression.</p> <p>Results</p> <p>There were 47 (29.2%) patients residing in Sobral, 46 (28.6%) up to 100 km away and 68 (42.2%) greater than 100 km from Sobral. There were no differences related to quality of life and coping scores between the groups. Distance was not a predictor of depression.</p> <p>Conclusions</p> <p>Social and cultural factors may explain the lack of differences. Studies from other regions are needed to clarify the distance effects on self-perceived outcomes among HD patients.</p