Gene-environment interactions in chronic obstructive pulmonary disease

Chronic obstructive pulmonary disease (COPD) is one of the leading causes of death throughout the world and is largely associated with cigarette smoking. Despite the appreciation of the central role of smoking in the development of COPD, only a relatively small number of smokers (15%–20%) develop COPD. Recent studies depicting familial aggregation suggest that some subjects may have a genetic predisposition to developing COPD. In this respect, a number of single nucleotide polymorphisms have been reported in association with different COPD features (subphenotypes), although much of this data remains controversial. Classical genetic studies (including twin and family studies) assume an “equal-environment” scenario, but as gene-environment interactions occur in COPD, this assumption needs revision. Thus, new integrated models are needed to examine the major environmental factors associated with COPD which include smoking as well as air pollution, and respiratory infections, and not only genetic predisposition. Revisiting this area, may help answer the question of what has more bearing in the pathogenesis of COPD—the environment or the genomic sequence of the affected subjects. It is anticipated that an improved understanding of this interaction will both enable improved identification of individuals susceptible to developing this disease, as well as improved future treatments for this disease

Smoking and Idiopathic Pulmonary Fibrosis

Idiopathic pulmonary fibrosis (IPF) is a disease of unknown etiology with considerable morbidity and mortality. Cigarette smoking is one of the most recognized risk factors for development of IPF. Furthermore, recent work suggests that smoking may have a detrimental effect on survival of patients with IPF. The mechanism by which smoking may contribute to the pathogenesis of IPF is largely unknown. However, accumulating evidence suggests that increased oxidative stress might promote disease progression in IPF patients who are current and former smokers. In this review, potential mechanisms by which cigarette smoking affects IPF, the effects of cigarette smoking on accelerated loss of lung function in patients with IPF, key genetic studies evaluating the potential candidate genes and gene-environment (smoking) interaction, diagnosis, and treatment with emphasis on recently closed and ongoing clinical trials are presented

Metabolic reprogramming promotes myogenesis during aging

Sarcopenia is the age-related progressive loss of skeletal muscle mass and strength finally leading to poor physical performance. Impaired myogenesis contributes to the pathogenesis of sarcopenia, while mitochondrial dysfunctions are thought to play a primary role in skeletal muscle loss during aging. Here we studied the link between myogenesis and metabolism. In particular, we analyzed the effect of the metabolic modulator trimetazidine (TMZ) on myogenesis in aging. We show that reprogramming the metabolism by TMZ treatment for 12 consecutive days stimulates myogenic gene expression in skeletal muscle of 22-month-old mice. Our data also reveal that TMZ increases the levels of mitochondrial proteins and stimulates the oxidative metabolism in aged muscles, this finding being in line with our previous observations in cachectic mice. Moreover, we show that, besides TMZ also other types of metabolic modulators (i.e., 5-Aminoimidazole-4-Carboxamide Ribofuranoside-AICAR) can stimulate differentiation of skeletal muscle progenitors in vitro. Overall, our results reveal that reprogramming the metabolism stimulates myogenesis while triggering mitochondrial proteins synthesis in vivo during aging. Together with the previously reported ability of TMZ to increase muscle strength in aged mice, these new data suggest an interesting non-invasive therapeutic strategy which could contribute to improving muscle quality and neuromuscular communication in the elderly, and counteracting sarcopenia

An Algorithm for the semi-analytical Computation of Fields emitted in layered Ground by HVDC Electrodes

For the design of HVDC ground electrodes it is of the utmost importance the availability of reliable and fast numerical tools, to evaluate both the fields and corrosion risk of nearby structures. Among the used algorithms, the Complex Images Method is well-known. However such method is often based on Prony\u2019s interpolator, which may show poor convergence properties, or even instability in particularly ill-conditioned cases. In this paper the use of a substitute interpolator, efficiently solving these drawbacks, named GPOF (Generalized Pencil Of Functions) is presented and results are discussed

Position and Stiffness Control of One DoF Revolute Joint Using a Biphasic Media Variable Stiffness Actuator

At this time, several industrial processes and service tasks need safe interactions between humans and robots. This safety can be achieved using compliance design and control of mechanisms. This paper presents a compliant revolute joint mechanism using a variable stiffness actuator. The method for adapting the stiffness in the actuator includes a member onfigured to transmit motion that is connected to a fluidic circuit, into which a biphasic control fluid circulates. Actuator's stiffness is controlled by changing pressure of control fluid into distribution lines. The used control fluid is biphasic, composed of separated gas and liquid fractions with predefined ratio. A mathematical model of the actuator is presented, a modelbased control method is implemented to track the desired position and stiffness, and equations relating to the dynamics of the mechanism are provided. Results from force loaded and unloaded simulations and experiments with a physical prototype are discussed

A phase 1 study evaluating the pharmacokinetics, safety and tolerability of repeat dosing with a human IL-13 antibody (CAT-354) in subjects with asthma

<p>Abstract</p> <p>Background</p> <p>IL-13 has been implicated in the development of airway inflammation and hyperresponsiveness. This study investigated the multiple-dose pharmacokinetics and safety profile of human anti-IL-13 antibody (CAT-354) in adults with asthma.</p> <p>Methods</p> <p>This was a multiple-dose, randomised, double-blind, placebo-controlled phase 1 study in asthmatics (forced expiratory volume in 1 second [FEV₁] ≥ 80% predicted). Subjects were randomised to receive three intravenous infusions of CAT-354 (1 mg/kg, 5 mg/kg or 10 mg/kg) or placebo at 28-day intervals. Blood samples were taken for pharmacokinetic measurements. Safety was assessed by adverse events, vital signs, ECGs, laboratory and pulmonary function parameters.</p> <p>Results</p> <p>Twenty-three subjects (aged 21-60 years, FEV₁88-95% predicted) received ≥ 1 dose of study medication. The half-life of CAT-354 was 12-17 days and was dose-independent. The maximum serum concentration and area under the curve were dose-dependent. Clearance (2.2-2.6 mL/day/kg) and volume of distribution (44-57 mL/kg) were both low and dose-independent. The observed maximum serum concentration after each dose increased slightly from dose 1 through dose 3 at all dose levels, consistent with an accumulation ratio of 1.4 to 1.7 for area under the curve. Most adverse events were deemed mild to moderate and unrelated to study medication. One SAE was reported and deemed unrelated to study drug. There were no effects of clinical concern for vital signs, ECG, laboratory or pulmonary parameters.</p> <p>Conclusions</p> <p>CAT-354 exhibited linear pharmacokinetics and an acceptable safety profile. These findings suggest that at the doses tested, CAT-354 can be safely administered in multiple doses to patients with asthma.</p> <p>Trial registration</p> <p>NCT00974675.</p

Bioprinting as a food production technique: Conceptual and ethical aspects, advantages and disadvantages, and applications

3D bioprinters present techniques that have various applications in the food industry. For this reason, this work aims to compile and review various research works focused on the utilities and advantages of this type of machinery. Where we first mention the basis of these bioprinting techniques and then proceed to highlight the bioethical issues that surround their application in the food industry, analyze the current advantages and disadvantages, the user that has been given in the production of food for astronauts, and also mention some of the research that has been taking place in Latin America and the world. The greatest advantage of 3D bioprinting of food is the speed of production compared to traditional manufacturing methods, allowing one to obtain food with various geometric shapes; it allows control of the nutritional value, and the texture of the product, reduces environmental pollution and has the advantage of being able to take advantage of the greater performance of the materials required for production. Additionally, this technology is considered an alternative production technique that will be used to solve the problem of feeding in places of scarce resources such as space and areas not suitable for animal husbandry