Review: Gastric cancer: Basic aspects

Gastric cancer is still one of the most prevalent and deadliest cancers in the world. Although our knowledge about the disease has progressed extraordinarily, this has not been accompanied by our capacity to effectively treat the disease. In the last years, immunotherapy made its way into the cancer field and was responsible for major changes in the treatment success rates for several cancer types. Although gastric cancer was not among the first successful targets of this type of therapy, the relationship between this type of cancer, immunosurveillance and immunotherapy is now being actively researched. In this article, we review the literature of the past year regarding the relationship between gastric cancer, its immune microenvironment and response to immunotherapy. Published data indicate that the immune microenvironment influences the clinical behaviour of gastric cancer, and is correlated with its histologic and molecular subtypes with an emphasis on the microsatellite‐ and EBV‐positive tumour subgroups. Although the literature regarding response to immunotherapy is scarce, there is good evidence that patient stratification for immunotherapy is going to become a reality in gastric cancer.     

P2X3 receptors contribute to transition from acute to chronic muscle pain

This study aimed to evaluate whether the development and/or maintenance of chronic-latent muscle hyperalgesia is modulated by P2X3 receptors. We also evaluate the expression of P2X3 receptors and PKCε of dorsal root ganglions during these processes. A mouse model of chronic-latent muscle hyperalgesia, induced by carrageenan and evidenced by PGE₂, was used. Mechanical muscle hyperalgesia was measured by Randall-Selitto analgesimeter. The involvement of P2X3 receptors was analyzed by using the selective P2X3 receptors antagonist A-317491 by intramuscular or intrathecal injections. Expression of P2X3 and PKCε in dorsal root ganglion (L4-S1) were evaluated by Western blotting. Intrathecal blockade of P2X3 receptors previously to carrageenan prevented the development and maintenance of acute and chronic-latent muscle hyperalgesia, while intramuscular blockade of P2X3 receptors previously to carrageenan only reduced the acute muscle hyperalgesia and had no effect on chronic-latent muscle hyperalgesia. Intrathecal, but not intramuscular, blockade of P2X3 receptors immediately before PGE₂, in animals previously sensitized by carrageenan, reversed the chronic-latent muscle hyperalgesia. There was an increase in total and phosphorylated PKCε 48 h after the beginning of acute muscle hyperalgesia, and in P2X3 receptors at the period of chronic muscle hyperalgesia. P2X3 receptors expressed on spinal cord dorsal horn contribute to transition from acute to chronic muscle pain. We also suggest an interaction of PKCε and P2X3 receptors in this process. Therefore, we point out P2X3 receptors of the spinal cord dorsal horn as a pharmacological target to prevent the development or reverse the chronic muscle pain conditions.

     

Nbn and Atm Cooperate in a Tissue and Developmental Stage-Specific Manner to Prevent Double Strand Breaks and Apoptosis in Developing Brain and Eye

Nibrin (NBN or NBS1) and ATM are key factors for DNA Double Strand Break (DSB) signaling and repair. Mutations in NBN or ATM result in Nijmegen Breakage Syndrome and Ataxia telangiectasia. These syndromes share common features such as radiosensitivity, neurological developmental defects and cancer predisposition. However, the functional synergy of Nbn and Atm in different tissues and developmental stages is not yet understood. Here, we show in vivo consequences of conditional inactivation of both genes in neural stem/progenitor cells using Nestin-Cre mice. Genetic inactivation of Atm in the central nervous system of Nbn-deficient mice led to reduced life span and increased DSBs, resulting in increased apoptosis during neural development. Surprisingly, the increase of DSBs and apoptosis was found only in few tissues including cerebellum, ganglionic eminences and lens. In sharp contrast, we showed that apoptosis associated with Nbn deletion was prevented by simultaneous inactivation of Atm in developing retina. Therefore, we propose that Nbn and Atm collaborate to prevent DSB accumulation and apoptosis during development in a tissue- and developmental stage-specific manner.     

Understanding the Role of Growth Factors in Modulating Stem Cell Tenogenesis

Current treatments for tendon injuries often fail to fully restore joint biomechanics leading to the recurrence of symptoms, and thus resulting in a significant health problem with a relevant social impact worldwide. Cell-based approaches involving the use of stem cells might enable tailoring a successful tendon regeneration outcome. As growth factors (GFs) powerfully regulate the cell biological response, their exogenous addition can further stimulate stem cells into the tenogenic lineage, which might eventually depend on stem cells source. In the present study we investigate the tenogenic differentiation potential of human- amniotic fluid stem cells (hAFSCs) and adipose-derived stem cells (hASCs) with several GFs associated to tendon development and healing; namely, EGF, bFGF, PDGF-BB and TGF-β1. Stem cells response to biochemical stimuli was studied by screening of tendon-related genes (collagen type I, III, decorin, tenascin C and scleraxis) and proteins found in tendon extracellular matrix (ECM) (Collagen I, III, and Tenascin C). Despite the fact that GFs did not seem to influence the synthesis of tendon ECM proteins, EGF and bFGF influenced the expression of tendon-related genes in hAFSCs, while EGF and PDGF-BB stimulated the genetic expression in hASCs. Overall results on cellular alignment morphology, immunolocalization and PCR analysis indicated that both stem cell source can be biochemically induced towards tenogenic commitment, validating the potential of hASCs and hAFSCs for tendon regeneration strategies.     

Optimal design of fair layouts

A relevant logistic issue in the organization of a fair is to determine how stands have to be placed in the exhibition space so as to satisfy all constraints on security, ease of access, services, and so on, while maximizing the revenues coming from the exhibitors. We consider in particular the problem of allocating the maximum number of stands by satisfying all the constraints required by practical implementations. We examine a number of real-world cases, and show how basic mathematical programming models can be improved to handle specific requests from the organizers. We report the solutions obtained through an original decision support system, that embeds a number of algorithms to solve the various cases by reduction to one or more linear programs.     

Impact of an Educational Intervention Implanted in a Neurological Intensive Care Unit on Rates of Infection Related to External Ventricular Drains

Background

Studies on the implantation of care routines showed reduction on EVD catheter-related infections rates; however zero tolerance is difficult to be achieved. The objective of this study was to assess the impact of an educational intervention on the maximal reduction on rates of EVD-related infections.

Methodology/Principal Findings

The quasi-experimental (before-after intervention) study occurred in two phases: pre-intervention, from April 2007 to July 2008, and intervention, from August 2008 to July 2010. Patients were followed for 30 days after the removal of the EVD, and EVD-related infections were considered as only those with laboratorial confirmation in the CSF. Observations were made of the care of the EVD and compliance with Hygiene of the Hands (HH), a routine of care was drawn up, training was given, and intervention was made to reduce the time the EVD catheter remained in place.

Results

during the study, 178 patients were submitted to 194 procedures, corresponding to 1217 EVD catheters-day. Gram-negative agents were identified in 71.4% of the infections during the pre-intervention period and in 60% during the intervention period. During the study, EVD-related infection rates were reduced from 9.5% to 4.8% per patient, from 8.8% to 4.4% per procedure, and the incidence density dropped from 14.0 to 6.9 infections per 1000 catheters-day (p = 0.027). The mortality reduced 12% (from 42% to 30%).

Conclusions/Significance

During one year after the fourth intervention, no microbiologically identified infection was documented. In light of these results, educational intervention proved to be a useful tool in reducing these rates and showed also impact on mortality.     

Biogeography of the Lizard Genus Tropidurus Wied-Neuwied, 1825 (Squamata: Tropiduridae): Distribution,Endemism, and Area Relationships in South America

Based on comprehensive distributional records of the 23 species currently assigned to the lizard genus Tropidurus, we investigated patterns of endemism and area relationships in South America. Two biogeographic methods were applied, Parsimony Analysis of Endemicity (PAE) and Brooks Parsimony Analysis (BPA). Two areas of endemism were detected by PAE: the first within the domains of the semiarid Brazilian Caatinga, which includes seven endemic species, and the second in the region of the Serranía de Huanchaca, eastern Bolivia, in which three endemic species are present. The area cladograms recovered a close relationship between the Atlantic Forest and areas of the South American open corridor. The results revealed a close relationship among the provinces Caatinga (Cerrado, Parana Forest (Pantanal+Chaco)). The uplift of the Brazilian Central Plateau in the Late Pliocene-Early Pleistocene (4-2 Myr BP) has been interpreted as a major event responsible for isolation and differentiation of biotas along these areas. However, we emphasize that without the establishment of a temporal framework concerning the diversification history of Tropidurus it is premature to correlate cladogenetic events with specific time periods or putative vicariant scenarios. The limiting factors hampering the understanding of the biogeographic history of this genus include (1) the absence of temporal references in relation to the diversification of distinct clades within Tropidurus; (2) the lack of an appropriate taxonomic resolution of the species complexes currently represented by widely distributed forms; and (3) the need for a comprehensive phylogenetic hypothesis. We suggest that these three important aspects should be prioritized in future investigations.     

Effect of Landscape Structure on Species Diversity

The effects of habitat fragmentation and their implications for biodiversity is a central issue in conservation biology which still lacks an overall comprehension. There is not yet a clear consensus on how to quantify fragmentation even though it is quite common to couple the effects of habitat loss with habitat fragmentation on biodiversity. Here we address the spatial patterns of species distribution in fragmented landscapes, assuming a neutral community model. To build up the fragmented landscapes, we employ the fractional Brownian motion approach, which in turn permits us to tune the amount of habitat loss and degree of clumping of the landscape independently. The coupling between the neutral community model, here simulated by means of the coalescent method, and fractal neutral landscape models enables us to address how the species–area relationship changes as the spatial patterns of a landscape is varied. The species–area relationship is one of the most fundamental laws in ecology, considered as a central tool in conservation biology, and is used to predict species loss following habitat disturbances. Our simulation results indicate that the level of clumping has a major role in shaping the species–area relationship. For instance, more compact landscapes are more sensitive to the effects of habitat loss and speciation rate. Besides, the level of clumping determines the existence and extension of the power-law regime which is expected to hold at intermediate scales. The distributions of species abundance are strongly influenced by the degree of fragmentation. We also show that the first and second commonest species have approximately self-similar spatial distributions across scales, with the fractal dimensions of the support of the first and second commonest species being very robust to changes in the spatial patterns of the landscape.