Differential sensitivity of brainstem vs cortical astrocytes to changes in pH reveals functional regional specialization of astroglia

Astrocytes might function as brain interoceptors capable of detecting different (chemo)sensory modalities and transmitting sensory information to the relevant neural networks controlling vital functions. For example, astrocytes which reside near the ventral surface of the brainstem (central respiratory chemosensitive area) respond to physiological decreases in pH with vigorous elevations in intracellular Ca(2+) and release of ATP. ATP transmits astroglial excitation to the brainstem respiratory network and contributes to adaptive changes in lung ventilation. Here we show that in terms of pH-sensitivity ventral brainstem astrocytes are clearly distinct from astrocytes residing in the cerebral cortex. We monitored vesicular fusion in cultured rat brainstem astrocytes using total internal reflection fluorescence microscopy and found that approximately 35% of them respond to acidification with an increased rate of exocytosis of ATP-containing vesicular compartments. These fusion events require intracellular Ca(2+) signaling and are independent of autocrine ATP actions. In contrast, the rate of vesicular fusion in cultured cortical astrocytes is not affected by changes in pH. Compared to cortical astrocytes, ventral brainstem astrocytes display higher levels of expression of genes encoding proteins associated with ATP vesicular transport and fusion, including vesicle-associated membrane protein-3 and vesicular nucleotide transporter. These results suggest that astrocytes residing in different parts of the rat brain are functionally specialized. In contrast to cortical astrocytes, astrocytes of the brainstem chemosensitive area(s) possess signaling properties which are functionally relevant – they are able to sense changes in pH and respond to acidification with enhanced vesicular release of ATP

On the Effects of Core Microstructure on Energy Absorbing Capabilities of Sandwich Panels Intended for Additive Manufacturing

Increasing transportation safety can be observed as one of the biggest engineering chal-lenges. This challenge often needs to be combined with the need to deliver engineering solutions that are able to lower the environmental impact of transportation, by reducing fuel consumption. Consequentially, these topics have attracted considerable research efforts. The present work aims to address the previously cited challenges by maximizing the energy absorption capabilities of hybrid aluminum/composite shock absorbers with minimal thickness and mass. This engineering solution makes it possible to lighten vehicles and reduce fuel consumption, without compromising safety, in terms of crashworthiness capabilities. A numerical sensitivity study is presented, where the absorbed energy/mass (AE/m) and the absorbed energy/total panel thickness (AE/Htot) ratios, as a consequence of low-velocity impact simulations performed on six different shock absorbers, are compared. These hybrid shock absorbers have been numerically designed by modifying the core thickness of two basic absorbers’ configurations, characterized, respectively, by a metallic lattice core, intended to be produced through additive manufacturing, and a standard metallic honeycomb core. This work provides interesting information for the development of shock absorbers, which should be further developed with an experimental approach. Indeed, it demonstrates that, by inte-grating composite skins with a very light core producible, by means of additive manufacturing ca-pabilities, it is possible to design shock absorbers with excellent performance, even for very thin configurations with 6 mm thickness, and to provide a significant increase in AE/m ratios when compared to the respective equal volume standard honeycomb core configurations. This difference between the AE/m ratios of configurations with different core designs increases with the growth in volume. In detail, for configurations with a total thickness of 6 mm, the AE/m increases in additive manufacturing configurations by approximately 93%; for those with a total thickness of 10 mm, the increase is 175%, and, finally, for those with a total thickness of 14 mm, the increase is 220%

Salivary cytokines and airways disease severity in patients with cystic fibrosis

About 50% of patients with cystic fibrosis (CF) have sinonasal complications, which include inferior turbinate hypertrophy (NTH) and/or nasal polyposis (NP), and different degrees of lung disease, which represents the main cause of mortality. Monitoring of sinonasal disease requires complex instrumental procedures, while monitoring of lung inflammation requires invasive collection of bronchoalveolar lavage fluid. The aim of this study was to investigate the associations between salivary cytokines levels and CF-related airway diseases. Salivary biochemical parameters and cytokines, i.e., interleukin-6 (IL-6), IL-8, and tumor necrosis factor alpha (TNF-α), were analyzed in resting saliva from healthy subjects and patients with CF. Patients with CF showed significantly higher levels of salivary chloride, IL-6, IL-8, and TNF-α and lower calcium levels than healthy subjects. Among patients with CF, IL-6 and IL-8 were significantly higher in patients with NTH, while TNF-α was significantly lower in patients with NP. A decreasing trend of TNF-α in patients with severe lung disease was also observed. On the other hand, we did not find significant correlation between cytokine levels and Pseudomonas aeruginosa or Stenotrophomonas maltophilia colonization. These preliminary results suggest that salivary IL-6 and IL-8 levels increase during the acute phase of sinonasal disease (i.e., NTH), while the end stages of pulmonary disease and sinonasal disease (i.e., NP) show decreased TNF-α level

TAS2R38 is a novel modifer gene in patients with cystic fbrosis

The clinical manifestation of cystic fbrosis (CF) is heterogeneous also in patients with the same cystic fbrosis transmembrane regulator (CFTR) genotype and in afected sibling pairs. Other genes, inherited independently of CFTR, may modulate the clinical manifestation and complications of patients with CF, including the severity of chronic sinonasal disease and the occurrence of chronic Pseudomonas aeruginosa colonization. The T2R38 gene encodes a taste receptor and recently its functionality was related to the occurrence of sinonasal diseases and upper respiratory infections. We assessed the T2R38 genotype in 210 patients with CF and in 95 controls, relating the genotype to the severity of sinonasal disease and to the occurrence of P. aeruginosa pulmonary colonization. The frequency of the PAV allele i.e., the allele associated with the high functionality of the T2R38 protein, was signifcantly lower in i) CF patients with nasal polyposis requiring surgery, especially in patients who developed the complication before 14 years of age; and ii) in CF patients with chronic pulmonary colonization by P. aeruginosa, especially in patients who were colonized before 14 years of age, than in control subjects. These data suggest a role for T2R38 as a novel modifer gene of sinonasal disease severity and of pulmonary P. aeruginosa colonization in patients with CF

Determinants of health sector efficiency: evidence from a two-step analysis on 30 OECD countries

This study aims to assess the efficiency of expenditure on health in 30 OECD countries over the period 2005-2015 by regressing Data Envelopment Analysis (DEA) output efficiency scores on discretionary and non-discretionary variables, with a two-stage DEA/Tobit and bootstrap procedure. We show that health inefficiency in OECD countries is related to per capita GDP, vaccine coverage and tobacco consumption, also controlling for geographical and institutional variables (i.e., bureaucratic red tape and weather temperature)

Do Patients with Bronchiectasis Have an Increased Risk of Developing Lung Cancer? A Systematic Review

Background: Initial evidence supports the hypothesis that patients with non-cystic fibrosis bronchiectasis (NCFB) have a higher risk of lung cancer. We systematically reviewed the available literature to define the characteristics of lung malignancies in patients with bronchiectasis and the characteristics of patients who develop bronchiectasis-associated lung cancer. Method: This study was performed based on the PRISMA guidelines. The review protocol was registered in PROSPERO. Results: The frequency rates of lung cancer in patients with NCFB ranged from 0.93% to 8.0%. The incidence rate was 3.96. Cancer more frequently occurred in the elderly and males. Three studies found an overall higher risk of developing lung cancer in the NCFB population compared to the non-bronchiectasis one, and adenocarcinoma was the most frequently reported histological type. The effect of the co-existence of NCFB and COPD was unclear. Conclusions: NCFB is associated with a higher risk of developing lung cancer than individuals without NCFB. This risk is higher for males, the elderly, and smokers, whereas concomitant COPD’s effect is unclear

Endoscopic Technologies for Peripheral Pulmonary Lesions: From Diagnosis to Therapy

Peripheral pulmonary lesions (PPLs) are frequent incidental findings in subjects when performing chest radiographs or chest computed tomography (CT) scans. When a PPL is identified, it is necessary to proceed with a risk stratification based on the patient profile and the characteristics found on chest CT. In order to proceed with a diagnostic procedure, the first-line examination is often a bronchoscopy with tissue sampling. Many guidance technologies have recently been developed to facilitate PPLs sampling. Through bronchoscopy, it is currently possible to ascertain the PPL’s benign or malignant nature, delaying the therapy’s second phase with radical, supportive, or palliative intent. In this review, we describe all the new tools available: from the innovation of bronchoscopic instrumentation (e.g., ultrathin bronchoscopy and robotic bronchoscopy) to the advances in navigation technology (e.g., radial-probe endobronchial ultrasound, virtual navigation, electromagnetic navigation, shape-sensing navigation, cone-beam computed tomography). In addition, we summarize all the PPLs ablation techniques currently under experimentation. Interventional pulmonology may be a discipline aiming at adopting increasingly innovative and disruptive technologies

Ex vivo model predicted in vivo efficacy of CFTR modulator therapy in a child with rare genotype

Background: New drugs that target the basic defect in cystic fibrosis (CF) patients may now be used in a large number of patients carrying responsive mutations. Nevertheless, further research is needed to extend the benefit of these treatments to patients with rare mutations that are still uncharacterized in vitro and that are not included in clinical trials. For this purpose, ex vivo models are necessary to preliminary assessing the effect of CFTR modulators in these cases. Method: We report the clinical effectiveness of lumacaftor/ivacaftor therapy prescribed to a CF child with a rare genetic profile (p.Phe508del/p.Gly970Asp) after testing the drug on nasal epithelial cells. We observed a significant drop of the sweat chloride value, as of the lung clearance index. A longer follow-up period is needed to define the effects of therapy on pancreatic status, although an increase of the fecal elastase values was found. Conclusion: Drug response obtained on nasal epithelial cells correlates with changes in vivo therapeutic endpoints and can be a predictor of clinical efficacy of novel drugs especially in pediatric patients

The impact of crustal rheology on natural seismicity: Campi Flegrei caldera case study

We analyze the crustal rheology beneath the active resurgent Campi Flegrei caldera (CFc) in Southern Italy by modelling the 3D brittle-ductile (B/D) transition, based on available thermal, geological and geophysical data. Firstly, the thermal field in the conductive physical regime is modeled using a finite element method; based on an optimization tool, this method is applied to evaluate the location and dimensions of the deep thermal source beneath the caldera. A horizontally-extended thermal anomaly located at about 5000 m depth below sea level is identified beneath Pozzuoli Bay, a part of the CFc. The same isotherm is located at a depth of 20,000 m beyond the caldera. This indicates a higher horizontal temperature gradient in the caldera with respect to the surrounding area. Next, we utilize this thermal model to image the 3D rheological stratification of the shallow crust below the caldera with two different values of strain rates. Within the caldera, the B/D transitions with 3equal to 1012 s 1 and 108 s 1 are located at 3000 m and 5000 m depths, respectively. Outside the caldera, the transition is very deep (15,000e20,000 m), seemingly uninfluenced by the thermal state of the CFc volcanism. Finally, we compare these results with the spatial distribution of earthquake hypocenters, Benioff strain release and b-value distribution to investigate the relationship between crustal rheology and seismicity characteristics. Our analysis reveals that the image of the B/D transition is in agreement with the distribution of earthquake hypocenters, constraining the potential seismogenic volume of the region. Our study demonstrates that knowledge of the rheological state of a volcanic system is an important element to interpret its dynamic, forecast future activity and improve evaluation of the associated seismic hazard. 2018, China University of Geosciences (Beijing) and Peking University. Production and hosting by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/ licenses/by-nc-nd/4.0/)