Exploring New Horizons in Microbiome Research

Leading scientists in microbiome research met at Lake Titisee, Germany, in April 2014 to discuss the current state of the field, the most urgent and unresolved questions, state-of-the-art technological advances, and new avenues of future research. We summarize some of the concepts and themes discussed at this meeting

Toward Novel Vaccines Against Tuberculosis: Current Hopes and Obstacles

Approximately 2 million people die of tuberculosis (TB) each year. The current vaccine, Bacille Calmette-Guérin (BCG), albeit widely employed, does not protect against adult pulmonary disease, and new vaccines are urgently needed to reduce the incidence of TB worldwide. New insights into the cellular and molecular mechanisms that underlie the interactions between Mycobacterium tuberculosis and its host have been exploited to develop novel vaccine candidates that recently have entered clinical trials. This review provides a brief overview of different approaches toward a new vaccination strategy and summarizes major challenges for the next decade

Obtención innovada de sidra de manzana caña (Malus doméstica. Granny Smith de color verde luminoso) por fermentación alcohólica (Saccharomyces Cerevisiae), en reactores Brewmart a nivel piloto para unidades familiares

Este documento tiene como objetivo principal, analizar la obtención innovada para la producción y elaboración de sidra de manzana caña Granny Smith de color verde luminoso (Malus pumila) Siendo posible establecer una relación entre el origen de las manzanas y la riqueza patrimonial de este fruto en nuestro país, lo que genera nuevas alternativas para el establecimiento de nuevos cultivos en las provincias de Huaral y Huacho, como las zonas de la Irrigación de Santa rosa, con ciertas variedades de manzanas caña (Malus pumila), delicia (red Delicious) interés. Al conocer la materia prima idónea, se establecieron los procesos y factores que garantizan obtener una sidra de calidad. El objetivo de esta tesis es describir la obtención innovada de sidra de manzana caña (Malus doméstica), por fermentación alcohólica (saccharomyces cerevisiae) en reactores Brewmart a nivel piloto, la creación de pequeñas y microempresas para unidades familiares. Hemos utilizando los mostos extraídos con un extractor Óster, de los cultivos de la irrigación Santa Rosa. Se han iniciado con la recepción de la materia prima manzana caña (Malus doméstica), se ha procedido con el control, elección y control de los parámetros características fisicoquímicos de calidad de la materia prima, que repercutirán en la calidad del producto, con énfasis en los aspectos prácticos de equipos, materiales y las buenas practicas alimentarias empleados. Estos fundamentos fueron complementados con actividades prácticas, cata de sidra, el resultado es consensuado por la participación de ocho personas para opinar sobre el aroma, sabor y gusto obteniendo como apreciación final hedónica de la calidad de la sidra elaborada en esta tesis en Huacho con la opinión de: “me gusta mucho

Inversión Pública y su incidencia en la pobreza en la región Lambayeque, periodo 2007-2020

En esta investigación al determinar la incidencia de la inversión pública en la pobreza de la región Lambayeque, periodo 2007-2020. Se plantea una metodología de tipo básica y correlacional ya que se busca analizar la influencia de la inversión pública en la pobreza de la región Lambayeque en el periodo 2007-2020. Siendo enfoque de la investigación es cuantitativo desde el abordaje del positivismo busca aborda con la data encontrada la relación entre las variables bajo análisis que permite identificar los objetos y patrones bajo estudio. Los resultados evidencian una relación negativa entre la inversión pública y la pobreza en la región Lambayeque, periodo 2007-2020. Mostrando que un incremento en 1% de la inversión pública se produce una reducción del 0.7% en la pobreza. Se concluyo que existe una relación negativa entre las variables bajo análisis. Evidenciando que conforme crece la inversión pública tiene un efecto negativo sobre la pobreza, demostrado estadística con el Rho de Pearson equivalente a -0.959 y significativo al 5%

Chemokines: A New Dendritic Cell Signal for T Cell Activation

Dendritic cells (DCs) are the main inducers and regulators of cytotoxic T lymphocyte (CTL) responses against viruses and tumors. One checkpoint to avoid misguided CTL activation, which might damage healthy cells of the body, is the necessity for multiple activation signals, involving both antigenic as well as additional signals that reflect the presence of pathogens. DCs provide both signals when activated by ligands of pattern recognition receptors and “licensed” by helper lymphocytes. Recently, it has been established that such T cell licensing can be facilitated by CD4+ T helper cells (“classical licensing”) or by natural killer T cells (“alternative licensing”). Licensing regulates the DC/CTL cross-talk at multiple layers. Direct recruitment of CTLs through chemokines released by licensed DCs has recently emerged as a common theme and has a crucial impact on the efficiency of CTL responses. Here, we discuss recent advances in our understanding of DC licensing for cross-priming and implications for the temporal and spatial regulation underlying this process. Future vaccination strategies will benefit from a deeper insight into the mechanisms that govern CTL activation

Immune-mediated mesangial cell injury—Biosynthesis and function of prostanoids

Immune-mediated mesangial cell injury—Biosynthesis and function of prostanoids. We studied the formation of cyclo-oxygenase products in a rat model of mesangial cell injury, in order to determine a possible role of prostaglandin E2 (PGE2), prostaglandin I2 (determined as 6-keto-PGF1α and thromboxane A2 (TxA2) in immune-mediated glomerular disease. Selective immune-mediated mesangial cell injury was induced by i.v. administration of a rabbit anti-rat thymocyte antiserum (ATS). Intravenous ATS leads to immune deposits in the mesangium followed by mesangiolysis and the infiltration of polymorphonuclear granulocytes and monocytes. Glomerular TxB2 formation two hours (292 ± 27 pg/mg/min) and 48 hours (396 ± 69 pg/mg/min) following antibody was significantly (P < 0.05) higher compared to animals receiving non-antibody rabbit IgG (TxB2: 2hr 143 ± 13; 48hr 171 ± 32 pg/mg/min). Treatment with cobra venom factor (CVF) and the reduction of glomerular monocyte infiltration inhibited the increase of glomerular TxB2 formation significantly. Depletion of granulocytes with a rabbit anti-rat granulocyte serum had no effect on glomerular prostanoid formation following ATS. Glomerular PGE2 and 6-keto PGF1α production was not altered following ATS. Inulin clearance in rats with immune-mediated mesangial cell injury was significantly (P < 0.001) lower at two hours (456 ± 24 µl/min/100g body wt) and 48 hours (433 ± 54 µl/min/lOO g body wt) compared to their corresponding control animals which were treated with non-antibody IgG (2 hr: 914 ± 51; 48 hr: 694 ± 79 µl/min/100g body wt). Pretreatment of rats with indomethacin (Indo) or with the thromboxane synthetase inhibitor UK 38485 prevented the decrease in inulin clearance following ATS at two hours (Indo: 800 ± 67; UK 38485: 923 ± 115) and at 48 hours (Indo: 697 ± 60; UK 38485: 654 ± 99). The data demonstrate that selective, immune-mediated mesangial cell injury in rats is associated with increased glomerular TxB2 formation. Complement and monocyte/macrophage depletion reduces TxB2 production. The fall in inulin clearance following ATS is ameliorated when the rats receive indomethacin or the Tx synthetase inhibitor UK 38485. Thus, elevated TxB2 formation might mediate the reduction in GFR in this model of glomerular immune injury

Mass Azithromycin Distribution and Community Microbiome: A Cluster-Randomized Trial.

BackgroundMass distributions of oral azithromycin have long been used to eliminate trachoma, and they are now being proposed to reduce childhood mortality. The observed benefit appears to be augmented with each additional treatment, suggesting a possible community-level effect. Here, we assess whether 2 biannual mass treatments of preschool children affect the community's gut microbiome at 6 months after the last distribution.MethodsIn this cluster-randomized controlled trial, children aged 1-60 months in the Dossa region of Niger were randomized at the village level to receive a single dose of azithromycin or placebo every 6 months. Fecal samples were collected 6 months after the second treatment for metagenomic deep sequencing. The prespecified primary outcome was the Euclidean PERMANOVA of the gut microbiome, or effectively the distance between the genus-level centroid at the community level, with the secondary outcome being the Simpson's α diversity.ResultsIn the azithromycin arm, the gut microbial structures were significantly different than in the placebo arm (Euclidean PERMANOVA, P &lt; .001). Further, the diversity of the gut microbiome in the azithromycin arm was significantly lower than in the placebo arm (inverse Simpson's index, P = .005).ConclusionsTwo mass azithromycin administrations, 6 months apart, in preschool children led to long-term alterations of the gut microbiome structure and community diversity. Here, long-term microbial alterations in the community did not imply disease but were associated with an improvement in childhood mortality.Clinical trials registrationNCT02048007

study protocol for a randomised controlled trial

Background Immunosuppression with calcineurin inhibitors remains the mainstay of treatment after kidney transplantation; however, long-term use of these drugs may be associated with nephrotoxicity. In this regard, the current approach is to optimise available immunosuppressive regimens to reduce the calcineurin inhibitor dose while protecting renal function without affecting the efficacy. The ATHENA study is designed to evaluate renal function in two regimens: an everolimus and reduced calcineurin inhibitor-based regimen versus a standard treatment protocol with mycophenolic acid and tacrolimus in de novo kidney transplant recipients. Method/Design ATHENA is a 12-month, multicentre, open-label, prospective, randomised, parallel-group study in de novo kidney transplant recipients (aged 18 years or older) receiving renal allografts from deceased or living donors. Eligible patients are randomised (1:1:1) prior to transplantation to one of the following three treatment arms: everolimus (starting dose 1.5 mg/day; C0 3–8 ng/mL) with cyclosporine or everolimus (starting dose 3 mg/day; C0 3–8 ng/mL) with tacrolimus or mycophenolic acid (enteric-coated mycophenolate sodium at 1.44 g/day or mycophenolate mofetil at 2 g/day) with tacrolimus; in combination with corticosteroids. All patients receive induction therapy with basiliximab. The primary objective is to demonstrate non-inferiority of renal function (eGFR by the Nankivell formula) in one of the everolimus arms compared with the standard group at month 12 post transplantation. The key secondary objective is to assess the incidence of treatment failure, defined as biopsy-proven acute rejection, graft loss, or death, among the treatment groups. Other objectives include assessment of the individual components of treatment failure, incidence and severity of viral infections, incidence and duration of delayed graft function, incidence of indication biopsies, slow graft function and wound healing complications, and overall safety and tolerability. Exploratory objectives include evaluation of left ventricular hypertrophy assessed by the left ventricular mass index, evolution of human leukocyte antigen and non-human leukocyte antigen antibodies, and a cytomegalovirus substudy. Discussion As one of the largest European multicentre kidney transplant studies, ATHENA will determine whether a de novo everolimus-based regimen can preserve renal function versus the standard of care. This study further assesses a number of clinical issues which impact long-term outcomes post transplantation; hence, its results will have a major clinical impact