Estudo comparativo da cicatrizacao de retalho cutaneo dorsal em ratos com e sem a aplicacao do laser de Erbium : YAG /

Orientador: Jurandir Marcondes Ribas FilhoDissertacao (mestrado) - Universidade Federal do Parana. Setor de Ciencias da Saude. Programa de Pos-Graduacao em Clinica Cirurgica

Comprehensive Cancer-Predisposition Gene Testing in an Adult Multiple Primary Tumor Series Shows a Broad Range of Deleterious Variants and Atypical Tumor Phenotypes.

Multiple primary tumors (MPTs) affect a substantial proportion of cancer survivors and can result from various causes, including inherited predisposition. Currently, germline genetic testing of MPT-affected individuals for variants in cancer-predisposition genes (CPGs) is mostly targeted by tumor type. We ascertained pre-assessed MPT individuals (with at least two primary tumors by age 60 years or at least three by 70 years) from genetics centers and performed whole-genome sequencing (WGS) on 460 individuals from 440 families. Despite previous negative genetic assessment and molecular investigations, pathogenic variants in moderate- and high-risk CPGs were detected in 67/440 (15.2%) probands. WGS detected variants that would not be (or were not) detected by targeted resequencing strategies, including low-frequency structural variants (6/440 [1.4%] probands). In most individuals with a germline variant assessed as pathogenic or likely pathogenic (P/LP), at least one of their tumor types was characteristic of variants in the relevant CPG. However, in 29 probands (42.2% of those with a P/LP variant), the tumor phenotype appeared discordant. The frequency of individuals with truncating or splice-site CPG variants and at least one discordant tumor type was significantly higher than in a control population (χ2 = 43.642; p ≤ 0.0001). 2/67 (3%) probands with P/LP variants had evidence of multiple inherited neoplasia allele syndrome (MINAS) with deleterious variants in two CPGs. Together with variant detection rates from a previous series of similarly ascertained MPT-affected individuals, the present results suggest that first-line comprehensive CPG analysis in an MPT cohort referred to clinical genetics services would detect a deleterious variant in about a third of individuals.JW is supported by a Cancer Research UK Cambridge Cancer Centre Clinical Research Training Fellowship. Funding for the NIHR BioResource – Rare diseases project was provided by the National Institute for Health Research (NIHR, grant number RG65966). ERM acknowledges support from the European Research Council (Advanced Researcher Award), NIHR (Senior Investigator Award and Cambridge NIHR Biomedical Research Centre), Cancer Research UK Cambridge Cancer Centre and Medical Research Council Infrastructure Award. The University of Cambridge has received salary support in respect of EM from the NHS in the East of England through the Clinical Academic Reserve. The views expressed are those of the authors and not necessarily those of the NHS or Department of Health. DGE is an NIHR Senior Investigator and is supported by the all Manchester NIHR Biomedical Research Centre

Brain multiplexes reveal morphological connectional biomarkers fingerprinting late brain dementia states

Accurate diagnosis of mild cognitive impairment (MCI) before conversion to Alzheimer’s disease (AD) is invaluable for patient treatment. Many works showed that MCI and AD affect functional and structural connections between brain regions as well as the shape of cortical regions. However, ‘shape connections’ between brain regions are rarely investigated -e.g., how morphological attributes such as cortical thickness and sulcal depth of a specific brain region change in relation to morphological attributes in other regions. To fill this gap, we unprecedentedly design morphological brain multiplexes for late MCI/AD classification. Specifically, we use structural T1-w MRI to define morphological brain networks, each quantifying similarity in morphology between different cortical regions for a specific cortical attribute. Then, we define a brain multiplex where each intra-layer represents the morphological connectivity network of a specific cortical attribute, and each inter-layer encodes the similarity between two consecutive intra-layers. A significant performance gain is achieved when using the multiplex architecture in comparison to other conventional network analysis architectures. We also leverage this architecture to discover morphological connectional biomarkers fingerprinting the difference between late MCI and AD stages, which included the right entorhinal cortex and right caudal middle frontal gyrus

Multimodal and Multiscale Deep Neural Networks for the Early Diagnosis of Alzheimer’s Disease using structural MR and FDG-PET images

Alzheimer’s Disease (AD) is a progressive neurodegenerative disease where biomarkers for disease based on pathophysiology may be able to provide objective measures for disease diagnosis and staging. Neuroimaging scans acquired from MRI and metabolism images obtained by FDG-PET provide in-vivo measurements of structure and function (glucose metabolism) in a living brain. It is hypothesized that combining multiple different image modalities providing complementary information could help improve early diagnosis of AD. In this paper, we propose a novel deep-learning-based framework to discriminate individuals with AD utilizing a multimodal and multiscale deep neural network. Our method delivers 82.4% accuracy in identifying the individuals with mild cognitive impairment (MCI) who will convert to AD at 3 years prior to conversion (86.4% combined accuracy for conversion within 1–3 years), a 94.23% sensitivity in classifying individuals with clinical diagnosis of probable AD, and a 86.3% specificity in classifying non-demented controls improving upon results in published literature

Publisher Correction: Telomerecat: A ploidy-agnostic method for estimating telomere length from whole genome sequencing data.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper

Effects of Anacetrapib in Patients with Atherosclerotic Vascular Disease

BACKGROUND: Patients with atherosclerotic vascular disease remain at high risk for cardiovascular events despite effective statin-based treatment of low-density lipoprotein (LDL) cholesterol levels. The inhibition of cholesteryl ester transfer protein (CETP) by anacetrapib reduces LDL cholesterol levels and increases high-density lipoprotein (HDL) cholesterol levels. However, trials of other CETP inhibitors have shown neutral or adverse effects on cardiovascular outcomes. METHODS: We conducted a randomized, double-blind, placebo-controlled trial involving 30,449 adults with atherosclerotic vascular disease who were receiving intensive atorvastatin therapy and who had a mean LDL cholesterol level of 61 mg per deciliter (1.58 mmol per liter), a mean non-HDL cholesterol level of 92 mg per deciliter (2.38 mmol per liter), and a mean HDL cholesterol level of 40 mg per deciliter (1.03 mmol per liter). The patients were assigned to receive either 100 mg of anacetrapib once daily (15,225 patients) or matching placebo (15,224 patients). The primary outcome was the first major coronary event, a composite of coronary death, myocardial infarction, or coronary revascularization. RESULTS: During the median follow-up period of 4.1 years, the primary outcome occurred in significantly fewer patients in the anacetrapib group than in the placebo group (1640 of 15,225 patients [10.8%] vs. 1803 of 15,224 patients [11.8%]; rate ratio, 0.91; 95% confidence interval, 0.85 to 0.97; P=0.004). The relative difference in risk was similar across multiple prespecified subgroups. At the trial midpoint, the mean level of HDL cholesterol was higher by 43 mg per deciliter (1.12 mmol per liter) in the anacetrapib group than in the placebo group (a relative difference of 104%), and the mean level of non-HDL cholesterol was lower by 17 mg per deciliter (0.44 mmol per liter), a relative difference of -18%. There were no significant between-group differences in the risk of death, cancer, or other serious adverse events. CONCLUSIONS: Among patients with atherosclerotic vascular disease who were receiving intensive statin therapy, the use of anacetrapib resulted in a lower incidence of major coronary events than the use of placebo. (Funded by Merck and others; Current Controlled Trials number, ISRCTN48678192 ; ClinicalTrials.gov number, NCT01252953 ; and EudraCT number, 2010-023467-18 .)

Neocolagenização induzida pelo resurfacing com laser erbium:YAG isolado e associado a lifting cutâneo: estudo morfométrico comparativo em ratos Comparison of single erbium:YAG laser resurfacing to a combination with cutaneous lifting: a morphometric study of neocollagenization in rats

INTRODUÇÃO: Diferente do lifting, cuja tração mecânica é a responsável pelo efeito clínico de rejuvenescimento sobre rugas profundas, a fibroplasia (ou neocolagenização) é a responsável direta pelo resultado final da ação do laser sobre a pele com rugas superficiais, conferindo-lhe aparência mais jovem. O uso combinado dessas duas técnicas pode ser vantajoso, pois permite um resultado estético melhor com um único procedimento anestésico e cirúrgico em um curto período de recuperação. OBJETIVOS: O presente estudo morfométrico se propõe a avaliar se ocorre alguma alteração na espessura da fibroplasia induzida pelo resurfacing a laser erbium:YAG quando este se associa ao lifting cutâneo. MÉTODO: Foram utilizados 50 ratos da linhagem Wistar, divididos em dois grupos de 25, sendo que o primeiro grupo foi submetido à aplicação exclusiva de laser erbium:YAG no dorso de cada animal e o outro sofreu a aplicação de laser Erbium: YAG combinada ao lifting, o qual foi representado, no animal de experimentação, por retalho cutâneo dorsal pediculado. A fibroplasia foi avaliada nos dois grupos com medidas morfométricas lineares realizadas após o sacrifício dos animais nos dias 14, 28, 56, 84 e 112 do pós-operatório. RESULTADO: Foi observado aumento da fibroplasia em ambos os grupos estudados, porém o crescimento do colágeno foi superior no grupo submetido à terapia isolada com laser Erbium: YAG. CONCLUSÃO: A espessura da fibroplasia induzida pelo resurfacing a laser Erbium: YAG foi influenciada pela associação de um segundo procedimento cirúrgico no mesmo tempo operatório, neste caso, o lifting cutâneo.<br>INTRODUCTION: The fibroplasia is the responsible for the final aesthetic results induced by laser resurfacing upon skin with superficial wrinkles. On the other hand, the lifting is responsible for the deeper wrinkles removal, produced by mechanic results. The use of the combination of these two rejuvenation simultaneous techniques can cause surgical advantages and interesting esthetical results. OBJECTIVES: This morphometric study proposed to evaluate if there are any alteration of fibroplasia thickness during the accomplishment of the laser and lifting techniques joined. METHOD: There were used 50 Wistar rats divided in two groups. One of the groups was submitted to the exclusive application of laser Erbium: YAG, and the other group were submitted to the application of the laser Erbium: YAG combined with the lifting. The fibroplasia thickness was evaluated by the digital morphometrics techniques, after the sacrifice of animals on days 14, 28, 56, 84 and 112 after the surgery. RESULT: An increase in the fibroplasia was observed in both groups studied, although the collagen growth was superior in the group that was submitted to laser resurfacing isolated. CONCLUSION: The thickness of fibroplasia was modified by the use of simultaneous techniques: laser resurfacing and lifting