The Roles Of MicroRNAs On Tuberculosis Infection: Meaning Or Myth?

The central proteins for protection against tuberculosis are attributed to interferon-γ, tumor necrosis factor-α, interleukin (IL)-6 and IL-1β, while IL-10 primarily suppresses anti-mycobacterial responses. Several studies found alteration of expression profile of genes involved in anti-mycobacterial responses in macrophages and natural killer (NK) cells from active and latent tuberculosis and from tuberculosis and healthy controls. This alteration of cellular composition might be regulated by microRNAs (miRNAs). Albeit only 1% of the genomic transcripts in mammalian cells encode miRNA, they are predicted to control the activity of more than 60% of all protein-coding genes and they have a huge influence in pathogenesis theory, diagnosis and treatment approach to some diseases. Several miRNAs have been found to regulate T cell differentiation and function and have critical role in regulating the innate function of macrophages, dendritic cells and NK cells. Here, we have reviewed the role of miRNAs implicated in tuberculosis infection, especially related to their new roles in the molecular pathology of tuberculosis immunology and as new targets for future tuberculosis diagnostics

Collective behavior and self-organization in neural rosette morphogenesis

Neural rosettes develop from the self-organization of differentiating human pluripotent stem cells. This process mimics the emergence of the embryonic central nervous system primordium, i.e., the neural tube, whose formation is under close investigation as errors during such process result in severe diseases like spina bifida and anencephaly. While neural tube formation is recognized as an example of self-organization, we still do not understand the fundamental mechanisms guiding the process. Here, we discuss the different theoretical frameworks that have been proposed to explain self-organization in morphogenesis. We show that an explanation based exclusively on stem cell differentiation cannot describe the emergence of spatial organization, and an explanation based on patterning models cannot explain how different groups of cells can collectively migrate and produce the mechanical transformations required to generate the neural tube. We conclude that neural rosette development is a relevant experimental 2D in-vitro model of morphogenesis because it is a multi-scale self-organization process that involves both cell differentiation and tissue development. Ultimately, to understand rosette formation, we first need to fully understand the complex interplay between growth, migration, cytoarchitecture organization, and cell type evolution

ALTERNATIVE DESIGN AND ECONOMIC FEASIBILITY OF AN EXPERIMENTAL WHR FOR INTAKE AIR CONDITIONING OF A LARGE INTERNAL COMBUSTION ENGINE

This work presents an alternative design for an experimental waste heat recovery thermal system to be coupled to a large turbocharged internal combustion engine for combustion air conditioning. The goal is to carry out a design of a new thermal system under restricted economic requirements for one of the generators set of Luiz Oscar Rodrigues de Melo Thermoelectric Power Plant. Thereby, a comparison with the original proposal from previous works is also developed in order to demonstrate the differences in terms of thermo-economic design parameters. The waste recovery thermal system produces sufficient chilled water through a single-effect absorption chiller, powered by hot water which is produced by recovering the exhaust gases residual heat to supply cooling applications on the combustion air. The results showed a significant reduction for the chiller capacity demand, from 550 to 185 RT, that would be enough to provide chilled water for 98.72% of the analyzed operation historical period. The economic feasibility indicators reveal the proposal for the alternative waste heat recovery system as the best financial option, presenting a lower investment cost (US$316,793.27 of savings) and a time for capital recovery of 2.14 years, 1.61 years shorter when compared with the initial WHR system

Relationship between gastric pouch and GERD after laparoscopic sleeve gastrectomy

open9noAims and objectives Laparoscopic Sleeve Gastrectomy (LSG) is considered safe and effective even as conversion procedure after primary bariatric operations. The correlation between gastric pouch volumes and gastro-esophageal reflux disease's (GERD) symptoms (heartburn, reflux, regurgitation) remains unclear (1, 2). With this study we want to assess a correlation between the gastric remnant size and GERD.openPomerri, F.; Romanucci, G.; Barbiero, G.; Zuliani, M.; Ortu, V.; Miotto, D.; Albanese, A.; Prevedello, L.; Foletto, M.Pomerri, Fabio; Romanucci, G.; Barbiero, G.; Zuliani, M.; Ortu, V.; Miotto, Diego; Albanese, A.; Prevedello, L.; Foletto, M

Preserving Differential Privacy in Convolutional Deep Belief Networks

The remarkable development of deep learning in medicine and healthcare domain presents obvious privacy issues, when deep neural networks are built on users' personal and highly sensitive data, e.g., clinical records, user profiles, biomedical images, etc. However, only a few scientific studies on preserving privacy in deep learning have been conducted. In this paper, we focus on developing a private convolutional deep belief network (pCDBN), which essentially is a convolutional deep belief network (CDBN) under differential privacy. Our main idea of enforcing epsilon-differential privacy is to leverage the functional mechanism to perturb the energy-based objective functions of traditional CDBNs, rather than their results. One key contribution of this work is that we propose the use of Chebyshev expansion to derive the approximate polynomial representation of objective functions. Our theoretical analysis shows that we can further derive the sensitivity and error bounds of the approximate polynomial representation. As a result, preserving differential privacy in CDBNs is feasible. We applied our model in a health social network, i.e., YesiWell data, and in a handwriting digit dataset, i.e., MNIST data, for human behavior prediction, human behavior classification, and handwriting digit recognition tasks. Theoretical analysis and rigorous experimental evaluations show that the pCDBN is highly effective. It significantly outperforms existing solutions

In vitro efficacy of alphacypermethrin on the buffalo louse Haematopinus tuberculatus (Burmeister, 1839).

In Italy buffalo farms adopted intensive breeding techniques, however the high density of animals in intensive breeding favours the diffusion of ectoparasites, such as louse. The aim of this study was to determine the in vitro efficacy of the insecticide alphacypermethrin (ACYP) against the buffalo louse, Haematopinus tuberculatus. The study was performed by using louse collected from animals in a commercial buffalo farm located in the Campania region of Southern Italy. Lice (adults and nymphs) were collected from highly infested buffaloes. The ACYP was diluted with physiological solution to different concentrations: 1.5%, 0.75%, 0.37%. A volume of 600 μl of the diluted sample was spread evenly over a filter paper held in the lower half of Petri dish. Ten adult lice and ten nymphs were placed on the top of each filter paper disc. The control groups were treated with physiological solution. Seven replicates were used for each concentration. The louse vitality was assessed at different time intervals: 1, 2, 4, 8, 10, 15, 20, 30, 40, 50, 60 minutes, after every 10 min until 240 min or at the louse death. After 240 min the louse vitality was examined each 60 min until 540 min. In vitro bioassays revealed that the lousicidal efficacy of ACYP improved as the concentration and the exposure time increased. The results of this in vitro study confirm that ACYP at 1.5% concentration can also be used in buffalo for the control of lice, as already in use in cattle. Further field trials will need to be conducted to confirm the safety, the dosage and the in vivo parasitological efficacy of this drug on buffaloes

Predictors Of Early Treatment Discontinuation And Severe Anemia In A Brazilian Cohort Of Hepatitis C Patients Treated With First-generation Protease Inhibitors

The aim of this study was to determine risk factors for adverse events (AE)-related treatment discontinuation and severe anemia among patients with chronic hepatitis C virus (HCV) genotype 1 infection, treated with first-generation protease inhibitor (PI)-based therapy. We included all patients who initiated treatment with PI-based therapy at a Brazilian university hospital between November 2013 and December 2014. We prospectively collected data from medical records using standardized questionnaires and used Epi Info 6.0 for analysis. Severe anemia was defined as hemoglobin <= 8.5 mg/dL. We included 203 patients: 132 treated with telaprevir (TVR) and 71 treated with boceprevir (BOC). AE-related treatment discontinuation rate was 19.2% and anemia was the main reason (38.5%). Risk factors for treatment discontinuation were higher comorbidity index (OR=1.85, CI=1.05-3.25) for BOC, and higher bilirubin count (OR=1.02, CI=1.01-1.04) and lower BMI (OR=0.98, CI=0.96-0.99) for TVR. Severe anemia occurred in 35 (17.2%) patients. Risk factors for this outcome were lower estimated glomerular filtration rate (eGFR; OR=0.95, CI=0.91-0.98) for patients treated with TVR, and higher comorbidity index (OR=2.21, CI=1.04-4.67) and ribavirin dosage (OR=0.84, CI=0.72-0.99) for those treated with BOC. Fifty-five (57.3%) patients treated with TVR and 15 (27.3%) patients treated with BOC achieved sustained virological response (SVR). Among patients who received TVR and interrupted treatment due to AE (n=19), only 26.3% (n=5) achieved SVR (P=0.003). Higher number of comorbidities, lower eGFR and advanced liver disease are associated with severe anemia and early treatment cessation, which may compromise SVR achievement.49

PERFORMANCE ASSESSMENT OF A LARGE INTERNAL COMBUSTION ENGINE DUE TO INLET AIR COOLING AND DEHUMIDIFICATION: GT-POWER SOFTWARE SIMULATION

Large internal combustion engines (ICEs) performance is limited by knocking phenomenon due to harsh ambient conditions such as hot temperature and excessive humidity. The performance of these engines can be enhanced by cooling and dehumidifying the inlet air on turbocharger upstream under safe operation conditions through a cooling coil heat exchanger, hence, increasing the power output as well as reducing the brake specific fuel consumption and pollutant specific emissions. Analysis have been performed in the GT-POWER software through a 1-D thermodynamic modelling of the Wärtsilä W20V34SG engine, making it possible to verify the influence of cooled and dehumidified ambient air, considering a temperature range from 9.5°C (282.7 K) to 15.5°C (288.7 K), while keeping 1 bar for pressure and relative humidity of 100%. Furthermore, the brake mean effective pressure (BMEP) has been set from 20 to 23.45 bar with a step of 1.15 bar. Such simulations are aimed to find the maximum air temperature at the cooling coil outlet in which the average of maximum cylinder pressures does not exceed the safety limit pressure of 186 bar while maintaining control on the wastegate valve. As a result, it was possible to evaluate that the maximum temperature to be chosen, under the conditions already mentioned, should be lower than 13.8°C (287 K)

Increased mitophagy in the skeletal muscle of spinal and bulbar muscular atrophy patients

Spinal and bulbar muscular atrophy (SBMA) is a neuromuscular disorder caused by polyglutamine expansion in the androgen receptor (AR) and characterized by the loss of lower motor neurons. Here we investigated pathological processes occurring in muscle biopsy specimens derived from SBMA patients and, as controls, age-matched healthy subjects and patients suffering from amyotrophic lateral sclerosis (ALS) and neurogenic atrophy. We detected atrophic fibers in the muscle of SBMA, ALS and neurogenic atrophy patients. In addition, SBMA muscle was characterized by the presence of a large number of hypertrophic fibers, with oxidative fibers having a larger size compared with glycolytic fibers. Polyglutamine-expanded AR expression was decreased in whole muscle, yet enriched in the nucleus, and localized to mitochondria. Ultrastructural analysis revealed myofibrillar disorganization and streaming in zones lacking mitochondria and degenerating mitochondria. Using molecular (mtDNA copy number), biochemical (citrate synthase and respiratory chain enzymes) and morphological (dark blue area in nicotinamide adenine dinucleotide-stained muscle cross-sections) analyses, we found a depletion of the mitochondria associated with enhanced mitophagy. Mass spectrometry analysis revealed an increase of phosphatidylethanolamines and phosphatidylserines in mitochondria isolated from SBMA muscles, as well as a 50% depletion of cardiolipin associated with decreased expression of the cardiolipin synthase gene. These observations suggest a causative link between nuclear polyglutamine-expanded AR accumulation, depletion of mitochondrial mass, increased mitophagy and altered mitochondrial membrane composition in SBMA muscle patients. Given the central role of mitochondria in cell bioenergetics, therapeutic approaches toward improving the mitochondrial network are worth considering to support SBMA patients

Transient elastography and APRI score: looking at false positives and false negatives. Diagnostic performance and association to fibrosis staging in chronic hepatitis C

Although long regarded as the gold standard for liver fibrosis staging in chronic hepatitis C (CHC), liver biopsy (LB) implies both the risk of an invasive procedure and significant variability. The aim of this study was to evaluate the diagnostic performance for transient elastography (TE) and aspartate aminotransferase to platelet index (APRI) used alone and in combination compared to liver biopsy and to analyze false positive/negative results. Patients with CHC, and no previous clinical diagnosis of cirrhosis were enrolled to undergo liver biopsy, TE and APRI. A total of 182 adult patients with a median age of 55 years and median body mass index of 26.71 kg/m2 were analyzed. On LB, 56% of patients had significant levels of fibrosis (METAVIR F≥2) and 28% had advanced fibrosis (F3/F4). The strongest performance for both tests was observed for exclusion of advanced fibrosis with good negative predictive values (89 and 86%, respectively). Low necroinflammatory activity on LB was associated with false negative TE. False positives were associated with NASH and smaller LB fragments. Correlation between APRI and Fibroscan for F≥2 was 100% and 84% for F≥3 and remained high in both false negative and false positive instances, correctly identifying F<2 in 71% of cases and F<3 in 78% (and potentially foregoing up to 84% of LB). We concluded that low individual performance indicators could be attributable to limitations of LB. Poorer differentiation of lower levels of fibrosis is a known issue for LB and remains so for noninvasive tests. Good predictability is possible, however, for advanced fibrosis4991