GWAS in Breast Cancer

Breast cancer is the most diagnosed cancer in women, and the second cause of cancer-related deaths among women worldwide. It is expected that more than 240,000 new cases and 40,450 deaths related to the disease will occur in 2016. It is well known that inherited genetic variants are drivers for breast cancer development. There are many mechanisms through which germline genetic variation affects prognosis, such as BRCA1 and BRCA2 genes, which account for approximately 20% of the increased hereditary risks. Therefore, it is evident that the genetic pathways that underlie cancer development are complex in which networks of multiple alleles confer disease susceptibility and risks. Global analyses through genome-wide association studies (GWAS) have revealed several loci across the genome are associated with the breast cancer. This chapter compiles all breast GWAS released since 2007, year of the first article published in this area, and discuss the future directions of this field. Currently, hundreds of genetic markers are linked to breast cancer, and understanding the underlying mechanisms of these variants might lead to the discover of biomarkers and targets for therapy in patients

The complete genome sequence of Chromobacterium violaceum reveals remarkable and exploitable bacterial adaptability

Chromobacterium violaceum is one of millions of species of free-living microorganisms that populate the soil and water in the extant areas of tropical biodiversity around the world. Its complete genome sequence reveals (i) extensive alternative pathways for energy generation, (ii) ≈500 ORFs for transport-related proteins, (iii) complex and extensive systems for stress adaptation and motility, and (iv) wide-spread utilization of quorum sensing for control of inducible systems, all of which underpin the versatility and adaptability of the organism. The genome also contains extensive but incomplete arrays of ORFs coding for proteins associated with mammalian pathogenicity, possibly involved in the occasional but often fatal cases of human C. violaceum infection. There is, in addition, a series of previously unknown but important enzymes and secondary metabolites including paraquat-inducible proteins, drug and heavy-metal-resistance proteins, multiple chitinases, and proteins for the detoxification of xenobiotics that may have biotechnological applications

A Network Perspective of the Ecosystem’s Health Provision Spectrum in the Tourist Trails of UNESCO Global Geoparks: Santo Sepulcro and Riacho do Meio Trails, Araripe UGG (NE of Brazil)

In this investigation, we formulated the Ecosystem’s Health Provision Spectrum and its centrality indicators, based on the identification of the Ecosystem Health Potentials and Opportunities on the trails of Santo Sepulcro and Riacho do Meio in the Araripe UNESCO Global Geopark (UGG), establishing a baseline for the promotion of green exercise and geotourism in the territory. Based on the network methodology for complex systems, we analyzed the closeness and strength of biotic, abiotic variables, nature phenomena, infrastructure, and sensory experiences in order to determine the configuration of these associations. In the Santo Sepulcro, regarding the association, two negative relations and two positive relations among the variables were highlighted; as for closeness and strength, Aquatic Diversity with the Scientific Values of Geodiversity stood out. In Riacho do Meio, we highlight three positive associations among the variables; as for connectivity, Biodiversity and Meteorological and Climate Exposure presented the highest values and, as for strength, the variables Biodiversity, Route Classification, and Aquatic Diversity were the most prominent. We conclude, based on the presented configuration, that the variables with greater connectivity act as hubs; if these variables are optimized, the network will present an acceptable theoretical configuration. However, neglecting central strength variables can cause the network to collapse

STING regulates metabolic reprogramming in macrophages via HIF-1α during Brucella infection.

Macrophages metabolic reprogramming in response to microbial insults is a major determinant of pathogen growth or containment. Here, we reveal a distinct mechanism by which stimulator of interferon genes (STING), a cytosolic sensor that regulates innate immune responses, contributes to an inflammatory M1-like macrophage profile upon Brucella abortus infection. This metabolic reprogramming is induced by STING-dependent stabilization of hypoxia-inducible factor-1 alpha (HIF-1α), a global regulator of cellular metabolism and innate immune cell functions. HIF-1α stabilization reduces oxidative phosphorylation and increases glycolysis during infection with B. abortus and, likewise, enhances nitric oxide production, inflammasome activation and IL-1β release in infected macrophages. Furthermore, the induction of this inflammatory profile participates in the control of bacterial replication since absence of HIF-1α renders mice more susceptible to B. abortus infection. Mechanistically, activation of STING by B. abortus infection drives the production of mitochondrial reactive oxygen species (mROS) that ultimately influences HIF-1α stabilization. Moreover, STING increases the intracellular succinate concentration in infected macrophages, and succinate pretreatment induces HIF-1α stabilization and IL-1β release independently of its cognate receptor GPR91. Collectively, these data demonstrate a pivotal mechanism in the immunometabolic regulation of macrophages during B. abortus infection that is orchestrated by STING via HIF-1α pathway and highlight the metabolic reprogramming of macrophages as a potential treatment strategy for bacterial infections

Quality of life and epilepsy surgery in childhood and adolescence

Epilepsy can affect the quality of life (QOL) of patients. The temporal lobe epilepsy (TLE) is often refractory to medication, which has an adverse impact on QOL. The surgery can be a form to control the seizures and to improve the QOL of the patients. OBJECTIVE: The aim of this study was to verify the QOL of children and adolescents with TLE who underwent surgery for epilepsy, comparing QOL before and after surgery and investigating which parameters showed improvement. METHOD: We used semi-structured questionnaire in the pre-and post-surgery in 13 patients. The data were analyzed using the Wilcoxon test. RESULTS: The analysis showed that there was general improvement in the QOL postoperatively. There was improvement in general health issues, adverse effects of antiepileptic drugs and the relationship with parents. CONCLUSION: When properly indicated, epilepsy surgery improves quality of life of patients with TLE

MANEJO ODONTOPEDIÁTRICO EM PACIENTES COM TRANSTORNO DO ESPECTRO AUTISTA

<p>A Odontologia Moderna, sobretudo em pacientes portadores do Espectro Autista, enfrenta, cada vez mais, desafios em seu manejo. Isso ocorre, principalmente, porque o manejo odontopediátrico em pacientes com esse transtorno é minimizado na atualidade, embora essa seja uma narrativa errônea acerca dessas pessoas, que precisam de uma atenção redobrada em seu cuidado bucal. O medo se apresenta como um desses entraves, ainda mais quando uma criança entra nesse cenário, meios comunicativos e o manejo correto do odontopediatra se faz necessário. O objetivo principal foi analisar a importância das condições de saúde bucal do indivíduo com Transtorno do Espectro Autista (TEA). Para isso, foram realizadas diversas buscas bibliográficas em bases de dados, como o PUBMED, WEB OF SCIENCE e SCOPUS, dos anos de 2016 e 2022, reconhecidos nesse meio. Foi visto que os portadores de TEA apresentam algumas condições especiais, que favorecem o surgimento de cáries e problemas odontológicos, as quais, muitas vezes, estão associadas ao hábito de alimentação, cuidado com a via oral e até mesmo, o uso crônico de medicamentos. É inexorável, portanto, a necessidade de enfatizar ainda mais a importância do conhecimento paterno a respeito dos cuidados necessários com os portadores de TEA, bem como o correto manejamento odontopediátrico, as constantes consultas e os corretos deveres no cuidado oral.</p&gt