The Multifarious Role of Microglia in Brain Metastasis

The immune landscape in brain metastasis is a very heterogeneous framework. Amongst a broad plethora of cells within the tumor microenvironment, the presence of activated microglia has been perfectly described. The innate role of microglial cells is to detect and eliminate any insults that may disturb the regular behavior of the brain. As part of its defensive role, it releases pro- and anti-inflammatory cytokines that aim to modulate the inflammatory scenario at the metastatic foci. However, the long term effects that these cells may exert on the metastatic progression is not clear. One of the biggest challenges in the field is to distinguish between brain resident microglial cells and infiltrated bone-marrow derived macrophages. Part of this issue is the fact that both cell types share similar phenotypes. Current studies are based on the modulation of the immune response against cancer cells (immunotherapy). However, most of current clinical trials and newly developed drugs focus on the adaptive immune response (e.g., immune blockade check-points). Additionally, the unique structure of the central nervous system with the presence of the blood-brain barrier have hindered a significant advance in novel therapies against brain metastasis. In this manuscript, we describe current advances in characterization of tumor-associated microglia and macrophages, the importance of microglia during the anti-cancerous response, and the future direction for the development of new strategies against this complex disease

PPAR gamma pro12Ala polymorphism and type 2 diabetes: a study in a spanish cohort

Type 2 diabetes (T2D) is a disease whose occurrence is increasing prevalent in westernized civilizations and is responsible for the proliferation in the morbidity and total mortality of patients with cardiovascular diseases, worldwide. However, the complexity in the treatment and prevention of T2D arises from the intricacy of the many physical and biological factors involved in its etiology. Impaired pathways for insulin signaling have been implicated as one the many factors in the development of T2D Individual peroxisome proliferator-activated receptors (PPARs) have previously exhibited associations with alterations of lipid profiles, fat tissue and T2D and displayed complications derived from high levels of glucose. However, PPARgamma has not yet been associated with the development or developmental pathways of T2D. We performed an observational study a Spanish cohort in order to better understand the association between the SNP PPARgamma polymorphism Pro12Ala in our patients and the incidence of T2D and other cardiovascular complications. We study did not find a statistically significant relationship between the Pro12Ala and T2D development in our cohort, future observations will help us to know the association with vascular disease in patients with T2D

Cognitive outcome and gamma noise power unrelated to neuregulin 1 and 3 variation in schizophrenia

Background Neuregulins are a family of signalling proteins that orchestrate a broad range of cellular responses. Four genes encoding Neuregulins 1–4 have been identified so far in vertebrates. Among them, Neuregulin 1 and Neuregulin 3 have been reported to contribute to an increased risk for developing schizophrenia. We hypothesized that three specific variants of these genes (rs6994992 and rs3924999 for Neuregulin 1 and rs10748842 for Neuregulin 3) that have been related to this illness may modify information processing capacity in the cortex, which would be reflected in electrophysiological parameters (P3b amplitude or gamma noise power) and/or cognitive performance. Methods We obtained DNA from 31 patients with schizophrenia and 23 healthy controls and analyzed NRG1 rs6994992, NRG1 rs3924999 and NRG3 rs10748842 promoter polymorphisms by allelic discrimination with real-time polymerase chain reaction (PCR). We compared cognitive outcome, P300 amplitude parameters and an electroencephalographic measure of noise power in the gamma band between the groups dichotomized according to genotype. Results Contrary to our hypothesis, we could not detect any significant influence of variation in Neuregulin 1/Neuregulin 3 polymorphisms on cognitive performance or electrophysiological parameters of patients with schizophrenia. Conclusions Despite our findings, we cannot discard that other genetic variants and, more likely, interactions between those variants and with genetic variation related to different pathways may still influence cerebral processing in schizophrenia

Genetic study in patients operated dentally and anesthetized with articaine-epinephrine

Aims: In this study we wanted to figure out if there was a correlation between OPRM1 N40D, TRPV1 I316M, TRPV1 I585V, NOS3 −786T>C and IL6 −174C>G polymorphisms and the response to locally applied articaine-epinephrine anesthetic. Methods: In this observational study, 114 oral cell samples of patients anesthetized with articaine-epinephrine (54 from men 60 from women), were collected from dental centers in Madrid (Spain). High molecular weight DNA was obtained from oral mucosa cells. The analysis of OPRM1 N40D (rs1799971), TRPV1 I316M (rs222747), TRPV1 I585V (rs8065080) and IL6 −174C>G polymorphism was performed through real-time PCR allelic discrimination using TaqMan probes. Polymorphism NOS3 −786T> C (rs2070744) was analyzed using RFLP-PCR. Results: The studied polymorphisms are involved neither in the response to the anesthetic, nor in the intensity of perceived dental pain. However, in a subset of female patients we found that TRPV1 I316M was associated with a delayed onset of anesthesia. Conclusions: There is no association among these polymorphisms and the time elapsed between the application of the anesthetic and the onset of its effect

The contribution of targeted therapy to the neoadjuvant chemoradiation of rectal cancer.

Neoadjuvant chemoradiation therapy is a commonly used option aimed to make less aggressive surgery approaches and to improve quality of life allowing a high proportion of patients operated with sphincter-sparing surgical techniques in locally advanced rectal cancer (LARC). During the last 5 years a number of studies have tested the efficacy of more intensive chemotherapeutic approaches by combining irinotecan or oxaliplatin with fluoropyrimidines and standard radiation treatments as well as testing combined treatments with targeted agents directed against epidermal growth factor receptor (EGFR) or angiogenesis. Herein, we review the results and critiques of the published studies based on the introduction of novel targeted agents in neoadjuvant therapy of LARC

High-cadence spectroscopy of M-dwarfs – II. Searching for stellar pulsations with HARPS

Stellar oscillations appear all across the Hertzsprung–Russell diagram. Recent theoretical studies support their existence also in the atmosphere of M dwarfs. These studies predict for them short periodicities ranging from 20 min to 3 h. Our Cool Tiny Beats (CTB) programme aims at finding these oscillations for the very first time. With this goal, CTB explores the short time domain of M dwarfs using radial velocity data from the High Accuracy Radial velocity Planet Searcher (HARPS)-European Southern Observatory and HARPS-N high-precision spectrographs. Here we present the results for the two most long-term stable targets observed to date with CTB, GJ 588 and GJ 699 (i.e. Barnard's star). In the first part of this work we detail the correction of several instrumental effects. These corrections are especially relevant when searching for subnight signals. Results show no significant signals in the range where M dwarfs pulsations were predicted. However, we estimate that stellar pulsations with amplitudes larger than ∼0.5 m s−1 can be detected with a 90 per cent completeness with our observations. This result, along with the excess of power regions detected in the periodograms, opens the possibility of non-resolved very low amplitude pulsation signals. Next generation more precise instrumentation would be required to detect such oscillations. However, the possibility of detecting pulsating M-dwarf stars with larger amplitudes is feasible due to the short size of the analysed sample. This motivates the need for completeness of the CTB survey

From Object Detection to Room Categorization in Robotics

This article deals with the problem of room categorization, i.e. the classification of a room as being a bathroom, kitchen, living-room, bedroom, etc., by an autonomous robot operating in home environments. For that, we propose a room categorization system based on a Bayesian probabilistic framework that combines object detections and its semantics. For detecting objects we resort to a state-of-the-art CNN, Mask R-CNN, while the meaning or semantics of those detections is provided by an ontology. Such an ontology encodes the relations between object and room categories, that is, in which room types the different object categories are typically found (toilets in bathrooms, microwaves in kitchens, etc.). The Bayesian framework is in charge of fusing both sources of information and providing a probability distribution over the set of categories the room can belong to. The proposed system has been evaluated in houses from the Robot@Home dataset, validating its effectiveness under real-world conditions.</p