Erythropoiesis-stimulating Agent Use among Patients with Lupus Nephritis Approaching End-stage Renal Disease

Objectives: Little is known about erythropoiesis-stimulating agents (ESAs) utilization among lupus nephritis (LN) patients with incipient ESRD. We aimed to identify sociodemographic and clinical factors associated with ESA use among incident LN ESRD patients. Methods: Among all individuals age ≥18 with incident ESRD from 1995-2008 in the U.S. Renal Data System (USRDS), we identified those with systemic lupus erythematosus (ICD-9 code 710.0) as the cause of ESRD. ESA use at ESRD onset was ascertained from the Medical Evidence Report. Year of onset, age, sex, race/ethnicity, medical insurance, employment status, residential region, clinical factors and comorbidities were considered potentially associated with ESA use in multivariable-adjusted logistic regression analyses. Results: We identified 12,533 individuals with incident LN ESRD (1% of entire population). Of those, 4,288 (34%) received an ESA preceding ESRD. In multivariable-adjusted models, ESA users had higher serum albumin and hemoglobin concentrations, were more likely to be women, and to live in the Northeast. Conversely, Medicaid beneficiaries, the uninsured, unemployed, African Americans, Hispanics, and those with IV drug use, congestive heart failure and obesity had lower ESA use. Conclusion: Among all U.S. patients and those with LN who developed ESRD, approximately one third received ESAs. Patient sex, race, age, medical insurance, residential region and clinical factors were significantly associated with ESA therapy. While there are no guidelines for ESA use in LN patients approaching ESRD, there has been wide sociodemographic variation, raising questions about ESA prescription practices

In silico drug repurposing for the identification of potential candidate molecules against arboviruses infection

Arboviral diseases caused by dengue (DENV), Zika (ZIKV) and chikungunya (CHIKV) viruses represent a major public health problem worldwide, especially in tropical areas where millions of infections occur every year. The aim of this research was to identify candidate molecules for the treatment of these diseases among the drugs currently available in the market, through in silico screening and subsequent in vitro evaluation with cell culture models of DENV and ZIKV infections. Numerous pharmaceutical compounds from antibiotics to chemotherapeutic agents presented high in silico binding affinity for the viral proteins, including ergotamine, antrafenine, natamycin, pranlukast, nilotinib, itraconazole, conivaptan and novobiocin. These five last compounds were tested in vitro, being pranlukast the one that exhibited the best antiviral activity. Further in vitro assays for this compound showed a significant inhibitory effect on DENV and ZIKV infection of human monocytic cells and human hepatocytes (Huh-7 cells) with potential abrogation of virus entry. Finally, intrinsic fluorescence analyses suggest that pranlukast may have some level of interaction with three viral proteins of DENV: envelope, capsid, and NS1. Due to its promising results, suitable accessibility in the market and reduced restrictions compared to other pharmaceuticals; the anti-asthmatic pranlukast is proposed as a drug candidate against DENV, ZIKV, and CHIKV, supporting further in vitro and in vivo assessment of the potential of this and other lead compounds that exhibited good affinity scores in silico as therapeutic agents or scaffolds for the development of new drugs against arboviral diseases. © 2019 Elsevier B.V.Universidad Tecnológica de Pereira, UTP: TRFCI-1P2016 National Institutes of Health, NIH National Institutes of Health, NIH: R01 AI24493 Department of Science, Information Technology and Innovation, Queensland Government, DSITI: 811-2018 Universidad Autónoma de Bucaramanga, UNABThe authors wish to thank the Administrative Department of Science, Technology and Innovation of Colombia [Grant: Colciencias No. 811-2018 ], Universidad Nacional Autónoma de México [Grant: Programa de Becas Posdoctorales en la UNAM 2016 ], Universidad Tecnológica de Bolívar [Grant: TRFCI-1P2016 ] and the National Institutes of Health [NIH grant R01 AI24493 ] for their financial support. Appendix AA continuación se relacionan los compuestos químicos y su número de registro CAS (Chemical Abstracts Service) antrafenine, 55300-29-3; conivaptan, 168626-94-6, 210101-16-9; ergotamine, 113-15-5, 52949-35-6; itraconazole, 84625-61-6; natamycin, 52882-37-8, 7681-93-8; nilotinib, 641571-10-0; novobiocin, 1476-53-5, 303-81-1, 39301-00-3, 4309-70-0; pranlukast, 103177-37-

Emergence of a new race of leaf rust with combined virulence to Lr14a and Lr72 genes on durum wheat

Leaf rust is a foliar disease caused by the fungus Puccinia triticina that may severely reduce durum wheat yield. Resistance to this pathogen is common in modern durum germplasm but is frequently based on Lr72 and Lr14a. After accounts of races with virulence to Lr14a gene in France in 2000, the present study reports the detection in 2013 for the first time of a new race with virulence to Lr14a and Lr72. The aim of this work was to characterize the virulence pattern of four Spanish isolates with virulence to Lr14a, and to discuss the consequences of this presence. Rusted leaves from cultivars ‘Don Jaime’ (Lr14a) and ‘Gallareta’ (Lr72) were collected in 2013 in the field at two Spanish sites, one in the south (near Cadiz) and another in the north (near Girona). Spores from single pustule for each cultivar and site were multiplied on susceptible cultivar ‘Don Rafael’. Then, the four isolates were inoculated on a set of 19 isogenic lines Thatcher to characterize their virulence spectrum. All isolates presented the same virulence pattern. They were virulent on both Lr14a and Lr72 and the race was named DBB/BS. This race was very similar to those reported in 2009-11, but with added virulence to Lr14a. The resistance based on Lr14a has therefore been overcome in Spain, by a new race that has likely emerged via stepwise mutation from the local predominating races. This information is important to guide breeders in their breeding programmes and gene deployment strategies

Perspectives on public involvement in health research from Singapore: The potential of a supported group model of involvement.

BACKGROUND: Singapore is an international research hub, with an emphasis on translational clinical research. Despite growing evidence of the positive impact of public involvement (PPI) in research, it remains rare in Singapore. AIMS: To investigate Singaporean public perspectives around the rationale, role and scope for being involved in health research To identify the potential, challenges, facilitators and strategies for implementing PPI in Singapore. DESIGN: Semi-structured qualitative interviews with members of the public, analysed using thematic framework analysis. RESULTS: Twenty people participated. Four main themes emerged: potential benefits; challenges; facilitators; and strategies for implementation. Whilst initially unfamiliar with the concept, all interviewees recognized potential benefits for the research itself and those involved, including researchers. PPI was seen to offer opportunities for public empowerment and strengthening of relationships and understanding between the public, academics and health professionals, resulting in more impactful research. Challenges included a Singaporean culture of passive citizenship and an education system that inculcates deferential attitudes. Facilitators comprised demographic and cultural changes, including trends towards greater individual openness and community engagement. Implementation strategies included formal government policies promoting involvement and informal community-based collaborative approaches. CONCLUSION: Given the socio-political framework in Singapore, a community-based approach has potential to address challenges to PPI and maximize impact. Careful consideration needs to be given to issues of resource and support to enable members of the public to engage in culturally sensitive and meaningful ways that will deliver research best placed to effectively address patient needs

Performance of Glass Resistive Plate Chambers for a high granularity semi-digital calorimeter

A new design of highly granular hadronic calorimeter using Glass Resistive Plate Chambers (GRPCs) with embedded electronics has been proposed for the future International Linear Collider (ILC) experiments. It features a 2-bit threshold semi-digital read-out. Several GRPC prototypes with their electronics have been successfully built and tested in pion beams. The design of these detectors is presented along with the test results on efficiency, pad multiplicity, stability and reproducibility.Comment: 16 pages, 15 figure

Physiology

Contains reports on seven research projects.Bell Laboratories, Inc.Ortho InstrumentsNational Institutes of Health (Grant 5 TO1 EY00090

Construction and commissioning of a technological prototype of a high-granularity semi-digital hadronic calorimeter

A large prototype of 1.3m3 was designed and built as a demonstrator of the semi-digital hadronic calorimeter (SDHCAL) concept proposed for the future ILC experiments. The prototype is a sampling hadronic calorimeter of 48 units. Each unit is built of an active layer made of 1m2 Glass Resistive Plate Chamber(GRPC) detector placed inside a cassette whose walls are made of stainless steel. The cassette contains also the electronics used to read out the GRPC detector. The lateral granularity of the active layer is provided by the electronics pick-up pads of 1cm2 each. The cassettes are inserted into a self-supporting mechanical structure built also of stainless steel plates which, with the cassettes walls, play the role of the absorber. The prototype was designed to be very compact and important efforts were made to minimize the number of services cables to optimize the efficiency of the Particle Flow Algorithm techniques to be used in the future ILC experiments. The different components of the SDHCAL prototype were studied individually and strict criteria were applied for the final selection of these components. Basic calibration procedures were performed after the prototype assembling. The prototype is the first of a series of new-generation detectors equipped with a power-pulsing mode intended to reduce the power consumption of this highly granular detector. A dedicated acquisition system was developed to deal with the output of more than 440000 electronics channels in both trigger and triggerless modes. After its completion in 2011, the prototype was commissioned using cosmic rays and particles beams at CERN.Comment: 49 pages, 41 figure

The Mechanisms of Codon Reassignments in Mitochondrial Genetic Codes

Many cases of non-standard genetic codes are known in mitochondrial genomes. We carry out analysis of phylogeny and codon usage of organisms for which the complete mitochondrial genome is available, and we determine the most likely mechanism for codon reassignment in each case. Reassignment events can be classified according to the gain-loss framework. The gain represents the appearance of a new tRNA for the reassigned codon or the change of an existing tRNA such that it gains the ability to pair with the codon. The loss represents the deletion of a tRNA or the change in a tRNA so that it no longer translates the codon. One possible mechanism is Codon Disappearance, where the codon disappears from the genome prior to the gain and loss events. In the alternative mechanisms the codon does not disappear. In the Unassigned Codon mechanism, the loss occurs first, whereas in the Ambiguous Intermediate mechanism, the gain occurs first. Codon usage analysis gives clear evidence of cases where the codon disappeared at the point of the reassignment and also cases where it did not disappear. Codon disappearance is the probable explanation for stop to sense reassignments and a small number of reassignments of sense codons. However, the majority of sense to sense reassignments cannot be explained by codon disappearance. In the latter cases, by analysis of the presence or absence of tRNAs in the genome and of the changes in tRNA sequences, it is sometimes possible to distinguish between the Unassigned Codon and Ambiguous Intermediate mechanisms. We emphasize that not all reassignments follow the same scenario and that it is necessary to consider the details of each case carefully.Comment: 53 pages (45 pages, including 4 figures + 8 pages of supplementary information). To appear in J.Mol.Evo