68 research outputs found
Morphological and Functional Changes in the Retina after Chronic Oxygen-Induced Retinopathy
The mouse model of oxygen-induced retinopathy (OIR) has been widely used for studies of retinopathy of prematurity (ROP). This disorder, characterized by abnormal vascularization of the retina, tends to occur in low birth weight neonates after exposure to high supplemental oxygen. Currently, the incidence of ROP is increasing because of increased survival of these infants due to medical progress. However, little is known about changes in the chronic phase after ROP. Therefore, in this study, we examined morphological and functional changes in the retina using a chronic OIR model. Both the a- and b-waves in the OIR model recovered in a time-dependent manner at 4 weeks (w), 6 w, and 8 w, but the oscillatory potential (OP) amplitudes remained depressed following a return to normoxic conditions. Furthermore, decrease in the thicknesses of the inner plexiform layer (IPL) and inner nuclear layer (INL) at postnatal day (P) 17, 4 w, and 8 w and hyperpermeability of blood vessels were observed in conjunction with the decrease in the expression of claudin-5 and occludin at 8 w. The chronic OIR model revealed the following: (1) a decrease in OP amplitudes, (2) morphological abnormalities in the retinal cells (limited to the IPL and INL) and blood vessels, and (3) an increase in retinal vascular permeability via the impairment of the tight junction proteins. These findings suggest that the experimental animal model used in this study is suitable for elucidating the pathogenesis of ROP and may lead to the development of potential therapeutic agents for ROP treatment
Expected Performance of the ATLAS Experiment - Detector, Trigger and Physics
A detailed study is presented of the expected performance of the ATLAS
detector. The reconstruction of tracks, leptons, photons, missing energy and
jets is investigated, together with the performance of b-tagging and the
trigger. The physics potential for a variety of interesting physics processes,
within the Standard Model and beyond, is examined. The study comprises a series
of notes based on simulations of the detector and physics processes, with
particular emphasis given to the data expected from the first years of
operation of the LHC at CERN
Frequent HPV-independent p16/INK4A overexpression in head and neck cancer
Objectives
p16INK4A (p16) is the most widely used clinical biomarker for Human Papillomavirus (HPV) in head and neck squamous cell cancer (HNSCC). HPV is a favourable prognostic marker in HNSCC and is used for patient stratification. While p16 is a relatively accurate marker for HPV within the oropharynx, recent reports suggest it may be unsuitable for use in other HNSCC subsites, where a smaller proportion of tumors are HPV-driven.
Materials and methods
We integrated reverse phase protein array (RPPA) data for p16 with HPV status based on detection of viral transcripts by RNA-seq in a set of 210 HNSCCs profiled by The Cancer Genome Atlas project. Samples were queried for alterations in CDKN2A, and other pathway genes to investigate possible drivers of p16 expression.
Results
While p16 levels as measured by RPPA were significantly different by HPV status, there were multiple HPV (?) samples with similar expression levels of p16 to HPV (+) samples, particularly at non-oropharyngeal subsites. In many cases, p16 overexpression in HPV (?) tumors could not be explained by mutation or amplification of CDKN2A or by RB1 mutation. Instead, we observed enrichment for inactivating mutations in the histone H3 lysine 36 methyltransferase, NSD1 in HPV (?)/p16-high tumors.
Conclusions
RPPA data suggest high p16 protein expression in many HPV (?) non-oropharyngeal HNSCCs, limiting its potential utility as an HPV biomarker outside of the oropharynx. HPV-independent overexpression of wild-type p16 in non-oropharyngeal HNSCC may be linked to global deregulation of chromatin state by inactivating mutations in NSD1
Omecamtiv mecarbil in chronic heart failure with reduced ejection fraction, GALACTICâHF: baseline characteristics and comparison with contemporary clinical trials
Aims:
The safety and efficacy of the novel selective cardiac myosin activator, omecamtiv mecarbil, in patients with heart failure with reduced ejection fraction (HFrEF) is tested in the Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure (GALACTICâHF) trial. Here we describe the baseline characteristics of participants in GALACTICâHF and how these compare with other contemporary trials.
Methods and Results:
Adults with established HFrEF, New York Heart Association functional class (NYHA)ââ„âII, EF â€35%, elevated natriuretic peptides and either current hospitalization for HF or history of hospitalization/ emergency department visit for HF within a year were randomized to either placebo or omecamtiv mecarbil (pharmacokineticâguided dosing: 25, 37.5 or 50âmg bid). 8256 patients [male (79%), nonâwhite (22%), mean age 65âyears] were enrolled with a mean EF 27%, ischemic etiology in 54%, NYHA II 53% and III/IV 47%, and median NTâproBNP 1971âpg/mL. HF therapies at baseline were among the most effectively employed in contemporary HF trials. GALACTICâHF randomized patients representative of recent HF registries and trials with substantial numbers of patients also having characteristics understudied in previous trials including more from North America (n = 1386), enrolled as inpatients (n = 2084), systolic blood pressureâ<â100âmmHg (n = 1127), estimated glomerular filtration rate <â30âmL/min/1.73 m2 (n = 528), and treated with sacubitrilâvalsartan at baseline (n = 1594).
Conclusions:
GALACTICâHF enrolled a wellâtreated, highârisk population from both inpatient and outpatient settings, which will provide a definitive evaluation of the efficacy and safety of this novel therapy, as well as informing its potential future implementation
Avaliação da genotoxicidade e mutagenicidade das ĂĄguas dos rios Jaguari, Atibaia e Piracicaba, na regiĂŁo de influĂȘncia da refinaria de PaulĂnia - SP
Os avanços tecnolĂłgicos trazem muitos benefĂcios, no entanto vĂȘm acompanhados de um aumento dos efluentes provenientes de diferentes tipos de indĂșstrias, os quais geram subprodutos indesejĂĄveis que carregam consigo muitos contaminantes quĂmicos que sĂŁo lançados todo ano no solo, ar e ĂĄgua. Em especial, as indĂșstrias de refino de petrĂłleo produzem efluentes ricos em metais pesados, quĂmicos inorgĂąnicos e orgĂąnicos. Dentre os contaminantes orgĂąnicos mais importantes do petrĂłleo, encontram-se os Hidrocarbonetos, em especial os Hidrocarbonetos PolicĂclicos AromĂĄticos (HPA). De maneira geral, tanto os HPA quanto seus derivados estĂŁo associados ao aumento da incidĂȘncia de diversos tipos de cĂąnceres no homem. Neste contexto, faz-se necessĂĄrio o desenvolvimento e aplicação de ferramentas para avaliação de amostras ambientais possivelmente impactadas por dejetos quĂmicos. Sendo assim, o presente trabalho tem por objetivo avaliar a genotoxicidade e a mutagenicidade das ĂĄguas dos rios Jaquari-SP, Atibaia-SP e Piracicaba-SP, numa regiĂŁo influenciada pelos efluentes gerados pela refinaria de petrĂłleo da cidade de PaulĂnia â SP. As avaliaçÔes foram feitas por meio de dois organismos-testes distintos: raĂzes de Allium cepa e cultura de CĂ©lulas de OvĂĄrio de Hamster ChinĂȘs (CHO-K1). Para os ensaios com A. cepa, foram aplicados os testes de aberraçÔes cromossĂŽmicas (AC) e micronĂșcleos (MN) em cĂ©lulas de meristemas de raĂzes e micronĂșcleos em cĂ©lulas F1 deste mesmo ĂłrgĂŁo. Para os ensaios com cĂ©lulas CHO-K1, foram a plicadas as tĂ©cnicas do ensaio do cometa e do teste do MicronĂșcleo. Os resultados obtidos nessa pesquisa mostraram que as substĂąncias quĂmicas geradas pelo processo de refino do petrĂłleo apresentam caracterĂsticas genotĂłxicas e/ou mutagĂȘnicas. Os resultados tambĂ©m permitiram o esclarecimento...Technological advances bring many advances; however they are accompanied by an increase in the effluents derived from different types of industries, which generate undesirable by-products that carry several chemical contaminants that are discharged every year in the soil, air and water. Industries of petroleum refinery, in particular, produce effluents rich in heavy metals, inorganic and organic chemicals. Among the most important organic contaminants of the petroleum, we can highlight the Hydrocarbons, in special the Polycyclic Aromatic Hydrocarbons (PAHs). In general, both PAHs and their derivatives are associated with the increase in the incidence of several types of cancer in humans. In this context, it is necessary to develop and apply tools to assess environmental samples possibly impacted by chemical waste. Thus, this study aims to evaluate the genotoxicity and mutagenicity of waters of the Jaquari-SP, Atibaia-SP and Piracicaba-SP rivers, in a region influenced by effluents generated by a petroleum refinery of the city of PaulĂnia â SP. The evaluations were carried out with two distinct test organisms: roots of Allium cepa and culture of cells of Chinese Hamster Ovary (CHO-K1). For the assays with A. cepa, the tests of chromosome aberrations (CA) and micronuclei (MN) in meristematic cells of roots and micronuclei in F1 cells of the same organ were applied. For the assays with CHO-K1 cells, the techniques of comet assay and the micronucleus test were used. The results obtained in this study showed that the chemical substances generated by the petroleum refining process present genotoxic and/or mutagenic characteristics. The results also allowed the elucidation of the modes of action of these compounds on the genetic material of the organisms exposed. Particularly, it was observed, by the tests performed... (Complete abstract click electronic access below)Fundação de Amparo Ă Pesquisa do Estado de SĂŁo Paulo (FAPESP
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