Crashworthiness of a composite bladder fuel tank for a tilt rotor aircraft

The fulfilment of the crash is a demanding requirement for a Tiltrotor. Indeed, such a kind of aircraft, being a hybrid between an airplane and a helicopter, inherits the requirements mainly from helicopters (EASA CS 29) due to its hovering ability. In particular, the fuel storage system must be designed in such a manner that it is crash resistant, under prescribed airworthiness requirements, in order to avoid the fuel leakage during such an event, preventing fire and, thus, increasing the survival chances of the crew and the passengers. The present work deals with the evaluation of crashworthiness of the fuel storage system of a Tiltrotor (bladder tank), and, in particular, it aims at describing the adopted numerical approach and some specific results. Crash resistance requirements are considered from the earliest design stages, and for this reason they are mainly addressed from a numerical point of view and by simulations that treat both single components and small/medium size assemblies. The developed numerical models include all the main parts needed for simulating the structural behavior of the investigated wing section: the tank, the structural components of the wing, the fuel sub-systems (fuel lines, probes, etc.) and the fuel itself. During the crash event there are several parts inside the tanks that can come into contact with the tank structure; therefore, it is necessary to evaluate which of these parts can be a damage source for the tank itself and could generate fuel loss. The SPH approach has been adopted to discretise fuel and to estimate the interaction forces with respect to the tank structure. Experimental data were used to calibrate the fuel tank and foam material models and to define the acceleration time-history to be applied. Thanks to the optimized foam’s configuration, the amount of dissipated impact energy is remarkable, and the evaluation of tanks/fuel system stress distribution allows estimating any undesired failure due to a survivable crash event

Second-generation nitazoxanide derivatives: thiazolides are effective inhibitors of the influenza A virus

Aim: The only small molecule drugs currently available for treatment of influenza A virus (IAV) are M2 ion channel blockers and sialidase inhibitors. The prototype thiazolide, nitazoxanide, has successfully completed Phase III clinical trials against acute uncomplicated influenza. Results: We report the activity of seventeen thiazolide analogs against A/PuertoRico/8/1934(H1N1), a laboratory-adapted strain of the H1N1 subtype of IAV, in a cell culture-based assay. A total of eight analogs showed IC50s in the range of 0.14–5.0 μM. Additionally a quantitative structure–property relationship study showed high correlation between experimental and predicted activity based on a molecular descriptor set. Conclusion: A range of thiazolides show useful activity against an H1N1 strain of IAV. Further evaluation of these molecules as potential new small molecule therapies is justified

Vitamin d deficiency induces chronic pain and microglial phenotypic changes in mice

The bioactive form of vitamin .D, 1,25‐dihydroxyvitamin D (1,25D3), exerts immunomodulatory actions resulting in neuroprotective effects potentially useful against neurodegenerative and autoimmune diseases. In fact, vitamin D deficiency status has been correlated with painful manifestations associated with different pathological conditions. In this study, we have investigated the effects of vitamin D deficiency on microglia cells, as they represent the main immune cells responsible for early defense at central nervous system (CNS), including chronic pain states. For this purpose, we have employed a model of low vitamin D intake during gestation to evaluate possible changes in primary microglia cells obtained from postnatal day(P)2‐ 3 pups. Afterwards, pain measurement and microglia morphological analysis in the spinal cord level and in brain regions involved in the integration of pain perception were performed in the parents subjected to vitamin D restriction. In cultured microglia, we detected a reactive—activated and proliferative—phenotype associated with intracellular reactive oxygen species (ROS) generation. Oxidative stress was closely correlated with the extent of DNA damage and increased β‐galactosidase (B‐gal) activity. Interestingly, the incubation with 25D3 or 1,25D3 or palmitoylethanolamide, an endogenous ligand of peroxisome proliferator‐activated‐receptor‐alpha (PPAR‐α), reduced most of these effects. Morphological analysis of ex‐vivo microglia obtained from vitamin‐D‐deficient adult mice revealed an increased number of activated microglia in the spinal cord, while in the brain microglia appeared in a dystrophic phenotype. Remarkably, activated (spinal) or dystrophic (brain) microglia were detected in a prominent manner in females. Our data indicate that vitamin D deficiency produces profound modifications in microglia, suggesting a possible role of these cells in the sensorial dysfunctions associated with hypovitaminosis D

Visualization of renal rotenone accumulation after oral administration and in situ detection of kidney injury biomarkers via MALDI mass spectrometry imaging

The examination of drug accumulation within complex biological systems offers valuable insights into the molecular aspects of drug metabolism and toxicity. Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI MSI) is an innovative methodology that enables the spatial visualization and quantification of biomolecules as well as drug and its metabolites in complex biological system. Hence, this method provides valuable insights into the metabolic profile and any molecular changes that may occur as a result of drug treatment. The renal system is particularly vulnerable to adverse effects of drug-induced harm and toxicity. In this study, MALDI MSI was utilized to examine the spatial distribution of drug and renal metabolites within kidney tissues subsequent to a single oral dosage of the anticancer compound rotenone. The integration of ion mobility spectrometry with MALDI MSI enhanced the data acquisition and analysis, resulting to improved mass resolution. Subsequently, the MS/MS fragment ions of rotenone reference drug were detected and characterized using MALDI HDMS/MS imaging. Notably, drug accumulation was observed in the cortical region of the representative kidney tissue sections treated with rotenone. The histological examination of treated kidney tissues did not reveal any observable changes. Differential ion intensity of renal endogenous metabolites was observed between untreated and rotenone-treated tissues. In the context of treated kidney tissues, the ion intensity level of sphingomyelin (D18:1/16:0), a sphingolipid indicator of glomerular cell injury and renal damage, was found to be elevated significantly compared to untreated kidney tissues. Conversely, the ion intensities of choline, glycero-3-phosphocholine (GPC), inosine, and a lysophosphatidylcholine LysoPC(18:0) exhibited a significant decrease. The results of this study demonstrate the potential of MALDI MSI as a novel technique for investigating the in situ spatial distribution of drugs and renal endogenous molecules while preserving the anatomical integrity of the kidney tissue. This technique can be used to study drug-induced metabolism and toxicity in a dynamic manner

Pharmacotherapy of LAMA/LABA inhaled therapy combinations for chronic obstructive pulmonary disease: a clinical overview

Introduction Long-acting muscarinic receptor antagonist (LAMA)/beta(2)-agonist (LABA) combinations represent a significant improvement in the treatment of chronic obstructive pulmonary disease (COPD) due to their remarkable ability to improve lung function, dyspnea, quality of life, and exercise capacity compared to mono-components. Areas covered This article aims to report the latest information on the clinical impact of dual bronchodilation in COPD. Expert opinion The available data supports the use of inhaled LAMA/LABA FDCs in treating COPD patients, particularly those with severe or very severe disease. These combinations provide short - and long-term benefits to COPD patients without increasing the dose of the single components, which reduces the risk of adverse events while ensuring an improvement in clinical efficacy. Unfortunately, head-to-head studies comparing all exiting LABA/LAMA combinations are relatively few. Since each available LAMA/LABA combination has a unique efficacy/safety profile that must be considered for personalized COPD therapy, further randomized controlled trials and real-world studies lasting at least one year are needed to assess what differences, if any, there are in terms of clinical outcomes when dual LAMA/LABA inhalers are compared to LAMA or LABA single inhalers, and to compare different LAMA/LABA FDCs

Activation of I kappa B kinase by herpes simplex virus type 1 - A novel target for anti-herpetic therapy

Herpes simplex viruses (HSV) are ubiquitous pathogens causing a variety of diseases ranging from mild illness to severe life-threatening infections. HSV utilize cellular signaling pathways and transcription factors to promote their replication. Here we report that HSV type 1 (HSV-1) induces persistent activation of transcription factor NF-kappaB, a critical regulator of genes involved in inflammation, by activating the I kappaB kinase (IKK) in the early phase of infection. Activated NF-kappaB enhances HSV-1 gene expression. HSV-1-induced NF-kappaB activation is dependent on viral early protein synthesis and is not blocked by the anti-herpetic drug acyclovir. IKK inhibition by the anti-inflammatory cyclopentenone prostaglandin A(1) blocks HSV-1 gene expression and reduces virus yield by more than 3000-fold. The results identify IKK as a potential target for anti-herpetic drugs and suggest that cyclopentenone prostaglandins or their derivatives could be used in the treatment of HSV infection