Pathogenesis and Clinical Relevance of Candida Biofilms in Vulvovaginal Candidiasis

The ability of Candida spp. to form biofilms is crucial for its pathogenicity, and thus, it should be considered an important virulence factor in vulvovaginal candidiasis (VVC) and recurrent VVC (RVVC). Its ability to generate biofilms is multifactorial and is generally believed to depend on the site of infection, species and strain involved, and the microenvironment in which the infection develops. Therefore, both cell surface proteins, such as Hwp1, Als1, and Als2, and the cell wall-related protein, Sun41, play a critical role in the adhesion and virulence of the biofilm. Immunological and pharmacological approaches have identified the NLRP3 inflammasome as a crucial molecular factor contributing to host immunopathology. In this context, we have earlier shown that Candida albicans associated with hyphae-secreted aspartyl proteinases (specifically SAP4-6) contribute to the immunopathology of the disease. Transcriptome profiling has revealed that non-coding transcripts regulate protein synthesis post-transcriptionally, which is important for the growth of Candida spp. Other studies have employed RNA sequencing to identify differences in the 1,245 Candida genes involved in surface and invasive cellular metabolism regulation. In vitro systems allow the simultaneous processing of a large number of samples, making them an ideal screening technique for estimating various physicochemical parameters, testing the activity of antimicrobial agents, and analyzing genes involved in biofilm formation and regulation (in situ) in specific strains. Murine VVC models are used to study C. albicans infection, especially in trials of novel treatments and to understand the cause(s) for resistance to conventional therapeutics. This review on the clinical relevance of Candida biofilms in VVC focuses on important advances in its genomics, transcriptomics, and proteomics. Moreover, recent experiments on the influence of biofilm formation on VVC or RVVC pathogenesis in laboratory animals have been discussed. A clear elucidation of one of the pathogenesis mechanisms employed by Candida biofilms in vulvovaginal candidiasis and its applications in clinical practice represents the most significant contribution of this manuscript

Startup facilitador de procesos de atenci?n, pago de cuentas y marketing de fidelizaci?n para aumentar el tr?fico de consumidores a los disco bares

En la actualidad, los startups que pertenecen al modelo de negocio del tipo orquestadores de redes son utilizados en diferentes sectores de negocio, facilitando sus operaciones y mejorando el servicio al cliente a trav?s de la tecnolog?a. Es as? que, teniendo conocimiento de un sector desatendido, se opta por el desarrollo de una soluci?n orientada al segmento de bares, donde estos puedan utilizar el modelo de negocio mencionado en sus locales. La idea de negocio que se ha planteado en el siguiente trabajo es la de ser intermediadores entre los bares y los consumidores, en la cual los consumidores puedan seleccionar el bar, realizar reservas de mesas en cualquiera de los diferentes bares afiliados, elegir piqueos y tragos, pagar la cuenta de manera individual, en conjunto o dividirla de acuerdo a la conveniencia de los consumidores. Por parte del bar, podr?n tener mayor informaci?n de sus clientes, presentar la carta del local, enviar promociones al aplicativo y brindar una soluci?n de pago r?pida y eficaz para sus clientes. El objetivo del presente proyecto de negocio es evaluar la viabilidad operativa, econ?mica y comercial para que el aplicativo sea atractivo y utilizado en los bares del distrito de Miraflores y Barranco

Estudio de los determinantes del comportamiento de reciclaje en los ejecutivos de Lima Metropolitana

La presente investigaci?n tiene como objetivo general el desarrollar un modelo conceptual para determinar los principales factores que influyen en la intenci?n de reciclar en los ejecutivos de Lima Metropolitana, tomando como base la Teor?a del Comportamiento Planificado de Ajzen (1991) y la Teor?a de la Motivaci?n para la Protecci?n de Rogers (1983), con una muestra no probabil?stica de 231 ejecutivos en Lima Metropolitana mayores a veinticinco a?os y que laboran en diferentes sectores econ?micos. El modelo conceptual elaborado ha considerado como variables la actitud, normas subjetivas e intenci?n de la Teor?a del Comportamiento Planificado de Ajzen (1991) y las variables severidad percibida, vulnerabilidad percibida, autoeficacia percibida, costo de respuesta y eficacia de respuesta de la Teor?a de la Motivaci?n para la Protecci?n de Rogers (1983)

Geostatistical Models for the Prediction of Water Supply Network Failures in Bogotá, Integrating Machine Learning Algorithms

[EN] Currently new strategies of spatial referencing, data analysis, and machine learning methods are integrated with Geographical Information Systems (GISs) to understand specific characteristics and water supply dynamics. This work explores the variables that can cause spacial failures and potential risk areas with application to a zone in the Bogotá water supply network. Machine learning algorithms are proposed to generate prediction models and potential failure maps. A sensitivity analysis was held to identify the model with the best fit for the estimation. This study will allow water supply decisions makers to focalize their efforts in the field.[ES] Actualmente se buscan nuevas estrategias y/o metodologías basadas en la integración de los Sistemas de Información Geográfica (SIGs) como forma de georeferenciacion espacial y visualización de las variables analizadas, junto con métodos de aprendizaje automático (Machine Learning) que permitan entender características puntuales, variables influyentes y dinámicas de los sistemas de abastecimiento de agua potable.En este trabajo se hace la identificación espacial de los fallos y zonas potenciales de riesgo que se presentan en una zona de la red de abastecimiento de Bogotá, explorando las variables que puedan tener mayor incidencia en los mismos. Se propone el uso de algoritmos de aprendizaje automático para la generación de modelos de predicción y la elaboración de mapas de fallos potenciales, identificando, a través de un análisis de sensibilidad, cuál de estos modelos presenta un mejor ajuste en la estimación. Este estudio permite a los gestores del abastecimiento una localización precisa y eficiente de los fallos en la red, apoyando el proceso de toma de decisiones.Navarrete-López, CF.; Calderón-Rivera, D.; Díaz Arévalo, JL.; Herrera Fernández, AM.; Izquierdo Sebastián, J. (2018). Modelos geoestadísticos para la predicción de fallos de una zona de la red de abastecimiento de agua de Bogotá, integrando algoritmos de Machine Learning. Social Science Research Network. 1-8. https://doi.org/10.2139/ssrn.3113048S1

Elliptic flow of charged particles in Pb-Pb collisions at 2.76 TeV

We report the first measurement of charged particle elliptic flow in Pb-Pb collisions at 2.76 TeV with the ALICE detector at the CERN Large Hadron Collider. The measurement is performed in the central pseudorapidity region (|$\eta$|<0.8) and transverse momentum range 0.2< $p_{\rm T}$< 5.0 GeV/$c$. The elliptic flow signal v$_2$, measured using the 4-particle correlation method, averaged over transverse momentum and pseudorapidity is 0.087 $\pm$ 0.002 (stat) $\pm$ 0.004 (syst) in the 40-50% centrality class. The differential elliptic flow v$_2(p_{\rm T})$ reaches a maximum of 0.2 near $p_{\rm T}$ = 3 GeV/$c$. Compared to RHIC Au-Au collisions at 200 GeV, the elliptic flow increases by about 30%. Some hydrodynamic model predictions which include viscous corrections are in agreement with the observed increase.Comment: 10 pages, 4 captioned figures, published version, figures at http://aliceinfo.cern.ch/ArtSubmission/node/389

Anti-tumour necrosis factor discontinuation in inflammatory bowel disease patients in remission: study protocol of a prospective, multicentre, randomized clinical trial

Background: Patients with inflammatory bowel disease who achieve remission with anti-tumour necrosis factor (anti-TNF) drugs may have treatment withdrawn due to safety concerns and cost considerations, but there is a lack of prospective, controlled data investigating this strategy. The primary study aim is to compare the rates of clinical remission at 1?year in patients who discontinue anti-TNF treatment versus those who continue treatment. Methods: This is an ongoing, prospective, double-blind, multicentre, randomized, placebo-controlled study in patients with Crohn?s disease or ulcerative colitis who have achieved clinical remission for ?6?months with an anti-TNF treatment and an immunosuppressant. Patients are being randomized 1:1 to discontinue anti-TNF therapy or continue therapy. Randomization stratifies patients by the type of inflammatory bowel disease and drug (infliximab versus adalimumab) at study inclusion. The primary endpoint of the study is sustained clinical remission at 1?year. Other endpoints include endoscopic and radiological activity, patient-reported outcomes (quality of life, work productivity), safety and predictive factors for relapse. The required sample size is 194 patients. In addition to the main analysis (discontinuation versus continuation), subanalyses will include stratification by type of inflammatory bowel disease, phenotype and previous treatment. Biological samples will be obtained to identify factors predictive of relapse after treatment withdrawal. Results: Enrolment began in 2016, and the study is expected to end in 2020. Conclusions: This study will contribute prospective, controlled data on outcomes and predictors of relapse in patients with inflammatory bowel disease after withdrawal of anti-TNF agents following achievement of clinical remission. Clinical trial reference number: EudraCT 2015-001410-1

Parental diet, pregnancy outcomes and offspring health:metabolic determinants in developing oocytes and embryos

The periconceptional period, embracing the terminal stages of oocyte growth and post-fertilisation development up to implantation, is sensitive to parental nutrition. Deficiencies or excesses in a range of macro- and micronutrients during this period can lead to impairments in fertility, fetal development and long-term offspring health. Obesity and genotype-related differences in regional adiposity are associated with impaired liver function and insulin resistance, and contribute to fatty acid-mediated impairments in sperm viability and oocyte and embryo quality, all of which are associated with endoplasmic reticulum stress and compromised fertility. Disturbances to maternal protein metabolism can elevate ammonium concentrations in reproductive tissues and disturb embryo and fetal development. Associated with this are disturbances to one-carbon metabolism, which can lead to epigenetic modifications to DNA and associated proteins in offspring that are both insulin resistant and hypertensive. Many enzymes involved in epigenetic gene regulation use metabolic cosubstrates (e.g. acetyl CoA and S-adenosyl methionine) to modify DNA and associated proteins, and so act as 'metabolic sensors' providing a link between parental nutritional status and gene regulation. Separate to their genomic contribution, spermatozoa can also influence embryo development via direct interactions with the egg and by seminal plasma components that act on oviductal and uterine tissues

Characterization and outcomes of 414 patients with primary SS who developed haematological malignancies

Objective: To characterize 414 patients with primary SS who developed haematological malignancies and to analyse how the main SS- and lymphoma-related features can modify the presentation patterns and outcomes. Methods: By January 2021, the Big Data Sjögren Project Consortium database included 11 966 patients fulfilling the 2002/2016 classification criteria. Haematological malignancies diagnosed according to the World Health Organization (WHO) classification were retrospectively identified. Results: There were 414 patients (355 women, mean age 57 years) with haematological malignancies (in 43, malignancy preceded at least one year the SS diagnosis). A total of 376 (91%) patients had mature B-cell malignancy, nearly half had extranodal marginal zone lymphoma (MZL) of mucosa-associated lymphoid tissue (MALT lymphoma) (n = 197), followed by diffuse large B-cell lymphoma (DLBCL) (n = 67), nodal MZL lymphoma (n = 29), chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) (n = 19) and follicular lymphoma (FL) (n = 17). Rates of complete response, relapses and death were 80%, 34% and 13%, respectively, with a 5-year survival rate of 86.5% after a mean follow-up of 8 years. There were significant differences in age at diagnosis (younger in MALT, older in CLL/SLL), predominant clinical presentation (glandular enlargement in MALT lymphoma, peripheral lymphadenopathy in nodal MZL and FL, constitutional symptoms in DLBCL, incidental diagnosis in CLL/SLL), therapeutic response (higher in MALT lymphoma, lower in DLBCL) and survival (better in MALT, nodal MZL and FL, worse in DLBCL). Conclusion: In the largest reported study of haematological malignancies complicating primary SS, we confirm the overwhelming predominance of B-cell lymphomas, especially MALT, with the salivary glands being the primary site of involvement. This highly-specific histopathological scenario is linked with the overall good prognosis with a 5-year survival rate of nearly 90%