Acute Bacterial Meningitis

Purpose of review Community-acquired bacterial meningitis is a continually changing disease. This review summarises both dynamic epidemiology and emerging data on pathogenesis. Updated clinical guidelines are discussed, new agents undergoing clinical trials intended to reduce secondary brain damage are presented. Recent findings Conjugate vaccines are effective against serotype/serogroup-specific meningitis but vaccine escape variants are rising in prevalence. Meningitis occurs when bacteria evade mucosal and circulating immune responses and invade the brain: directly, or across the blood–brain barrier. Tissue damage is caused when host genetic susceptibility is exploited by bacterial virulence. The classical clinical triad of fever, neck stiffness and headache has poor diagnostic sensitivity, all guidelines reflect the necessity for a low index of suspicion and early Lumbar puncture. Unnecessary cranial imaging causes diagnostic delays. cerebrospinal fluid (CSF) culture and PCR are diagnostic, direct next-generation sequencing of CSF may revolutionise diagnostics. Administration of early antibiotics is essential to improve survival. Dexamethasone partially mitigates central nervous system inflammation in high-income settings. New agents in clinical trials include C5 inhibitors and daptomycin, data are expected in 2025. Summary Clinicians must remain vigilant for bacterial meningitis. Constantly changing epidemiology and emerging pathogenesis data are increasing the understanding of meningitis. Prospects for better treatments are forthcoming

The development of a protocol for the analysis of genetic expression through «differential display», as a means to reducing the number of false positives

Entre los métodos empleados para los análisis de la expresión de genes, el método de "differentialdisplay" ha sido ampliamente utilizado y, a pesar del uso extendido de los "microarrays", es aún unmétodo válido para el análisis con muestras cuyo transcriptoma es desconocido. Con el objeto de reducirel elevado número de falsos positivos que genera esta técnica, hemos optimizado el protocolo parareducir la posibilidad de generar falsos positivos. En primer lugar, hemos marcado radiactivamente elcebador oligo-dT con lo que los fragmentos de DNA identificados son extremos 3'-UTR de RNAm. Pormuestra hemos realizado dos transcripciones inversas y dos reacciones de PCR en cada una de ellas. Paraseleccionar un fragmento de DNA, debía estar diferencialmente expresado en las 4 reacciones de PCR.Por último, todos los fragmentos fueron clonados y secuenciados por triplicado. Estas modificacionesal protocolo nos ha permitido identificar 5 genes expresados diferencialmente entre células epitelialesde intestino en estado proliferativo y diferenciado.The analysis of genetic expression, the differential display (DD) method has been widely used, but inspite of the extensive use of the «microarrays» method, it is still to be considered as a valid methodfor the analysis of samples whose transcriptone is not known. In this work, an attempt has been madeto reduce the high number of false positives generated by this technique by optimising method protocol.As a preliminary step, we radioactively marked the oligo dT primer with which the fragments ofidentified DNA were extreme 3'-UTR of mRNA. For each sample two inverse transcriptions and twoPCR reactions were performed. Only fragments of DNA that are expressed differentially in all 4 PCRreactions should be selected. Finally, all of the fragments were cloned and sequenced in triplicate. Theseprotocol modifications have allowed us to identify 5 differentially expressed genes, in intestinal epithelialcells in both proliferative and differentiated states

Research on nonlinear and quantum optics at the photonics and quantum information group of the University of Valladolid

We outline the main research lines in Nonlinear and Quantum Optics of the Group of Photonics and Quantum Information at the University of Valladolid. These works focus on Optical Solitons, Quantum Information using Photonic Technologies and the development of new materials for Nonlinar Optics. The investigations on optical solitons cover both temporal solitons in dispersion managed fiber links and nonparaxial spatial solitons as described by the Nonlinear Helmholtz Equation. Within the Quantum Information research lines of the group, the studies address new photonic schemes for quantum computation and the multiplexing of quantum data. The investigations of the group are, to a large extent, based on intensive and parallel computations. Some associated numerical techniques for the development of the activities described are briefly sketched

The Mammalian Cell Cycle Regulates Parvovirus Nuclear Capsid Assembly.

It is unknown whether the mammalian cell cycle could impact the assembly of viruses maturing in the nucleus. We addressed this question using MVM, a reference member of the icosahedral ssDNA nuclear parvoviruses, which requires cell proliferation to infect by mechanisms partly understood. Constitutively expressed MVM capsid subunits (VPs) accumulated in the cytoplasm of mouse and human fibroblasts synchronized at G0, G1, and G1/S transition. Upon arrest release, VPs translocated to the nucleus as cells entered S phase, at efficiencies relying on cell origin and arrest method, and immediately assembled into capsids. In synchronously infected cells, the consecutive virus life cycle steps (gene expression, proteins nuclear translocation, capsid assembly, genome replication and encapsidation) proceeded tightly coupled to cell cycle progression from G0/G1 through S into G2 phase. However, a DNA synthesis stress caused by thymidine irreversibly disrupted virus life cycle, as VPs became increasingly retained in the cytoplasm hours post-stress, forming empty capsids in mouse fibroblasts, thereby impairing encapsidation of the nuclear viral DNA replicative intermediates. Synchronously infected cells subjected to density-arrest signals while traversing early S phase also blocked VPs transport, resulting in a similar misplaced cytoplasmic capsid assembly in mouse fibroblasts. In contrast, thymidine and density arrest signals deregulating virus assembly neither perturbed nuclear translocation of the NS1 protein nor viral genome replication occurring under S/G2 cycle arrest. An underlying mechanism of cell cycle control was identified in the nuclear translocation of phosphorylated VPs trimeric assembly intermediates, which accessed a non-conserved route distinct from the importin α2/β1 and transportin pathways. The exquisite cell cycle-dependence of parvovirus nuclear capsid assembly conforms a novel paradigm of time and functional coupling between cellular and virus life cycles. This junction may determine the characteristic parvovirus tropism for proliferative and cancer cells, and its disturbance could critically contribute to persistence in host tissues

Induced and logarithmic distances with multi-region aggregation operators

Copyright © 2019 The Author(s). Published by VGTU Press. This paper introduces the induced ordered weighted logarithmic averaging IOWLAD and multiregion induced ordered weighted logarithmic averaging MR-IOWLAD operators. The distinctive characteristic of these operators lies in the notion of distance measures combined with the complex reordering mechanism of inducing variables and the properties of the logarithmic averaging operators. The main advantage of MR-IOWLAD operators is their design, which is specifically thought to aid in decision-making when a set of diverse regions with different properties must be considered. Moreover, the induced weighting vector and the distance measure mechanisms of the operator allow for the wider modeling of problems, including heterogeneous information and the complex attitudinal character of experts, when aiming for an ideal scenario. Along with analyzing the main properties of the IOWLAD operators, their families and specific cases, we also introduce some extensions, such as the induced generalized ordered weighted averaging IGOWLAD operator and Choquet integrals. We present the induced Choquet logarithmic distance averaging ICLD operator and the generalized induced Choquet logarithmic distance averaging IGCLD operator. Finally, an illustrative example is proposed, including real-world information retrieved from the United Nations World Statistics for global regions

SWI/SNF regulates a transcriptional programme that induces senescence to prevent liver cancer

Oncogene-induced senescence (OIS) is a potent tumour suppressor mechanism. To identify senescence regulators relevant to cancer, we screened an shRNA library targeting genes deleted in hepatocellular carcinoma (HCC). Here, we describe how knockdown of the SWI/SNF component ARID1B prevents OIS and cooperates with RAS to induce liver tumours. ARID1B controls p16INK4a and p21CIP1a transcription but also regulates DNA damage, oxidative stress and p53 induction, suggesting that SWI/SNF uses additional mechanisms to regulate senescence. To systematically identify SWI/SNF targets regulating senescence, we carried out a focused shRNA screen. We discovered several new senescence regulators including ENTPD7, an enzyme that hydrolyses nucleotides. ENTPD7 affects oxidative stress, DNA damage and senescence. Importantly, expression of ENTPD7 or inhibition of nucleotide synthesis in ARID1B-depleted cells results in re-establishment of senescence. Our results identify novel mechanisms by which epigenetic regulators can affect tumor progression and suggest that pro-senescence therapies could be employed against SWI/SNF-mutated cancers

Effect of price-discount distribution in multi-unit price promotions on consumers' willingness to pay, sales value, and retailers' revenue

Using multi-unit auctions, we examined the effect of different distributions of price discount across multiple units of a relatively new product on consumers' Willingness to Pay (WTP), sales value and retailers' revenue. We found that allowing the price discount to be increasing in the number of units increases willingness to pay, sales value and retailers' revenue and that a price discount that is uniformly distributed across units also has the potential to motivate consumers to buy more units of the product. However, multi-unit price promotions that concentrate all the amount of price discount on the last unit only generate a weak positive effect on sales value. [EconLit Citations: C910, D120, M310]. (C) 2014 Wiley Periodicals, Inc