The choice of appropriate biologic therapy for severe asthma remains challenging. The importance of finding biomarkers that can predict response continuous an open issue that needs to be further explored. This review describes the clinical effects of targeting the IL-5 pathway in severe asthma in adult and paediatric patients, focusing on predictors of response and non-response. The aim of this study is to identify the changes in patient age and stone sizes with technological advancement over time. This study was conducted retrospectively with 404 patients (504 renal units) who underwent percutaneous nephrolithotomy (PCNL) between January 1997 and June 2020. Patient characteristics and trends on instrument preferences were investigated. Median age was 7 (1-18) years. Male to female ratio was 1.481 (301/203). Median stone burden was 2 cm (0.20-25) and median operative time was 90minutes (20-240). The stone-free rate was 74.6%. Patients were divided into four groups according to the size of the instrument. It was found that the size of sheath used increased significantly with increasing age and stone burden. The micro-PCNL group had the shortest hospitalisation and lowest blood transfusion rate. Chronologically categorised four equal groups were compared to analyse changing patient profiles and trends. Median patient age, stone burden, operation time, sheath size, blood transfusion and complication rates decreased significantly with time. However, the use of tracts smaller than 20F and the number of patients with previous intervention increased significantly. Our study demonstrated that the patient's age and stone size at the time of initial diagnosis decrease over time while miniaturisation techniques increase in paediatric urology. Our study demonstrated that the patient's age and stone size at the time of initial diagnosis decrease over time while miniaturisation techniques increase in paediatric urology. Constipation and opioid-induced constipation (OIC) are common with limited treatment options. We investigated whether a noninvasive method of auricular vagal nerve stimulation (aVNS) could be used for treating OIC and explored its potential mechanisms and neural pathways in a rodent model of OIC. Sprague-Dawley were chronically implanted with one pair of auricular electrodes for aVNS. Sixteen rats were treated with loperamide for a week while another 16 rats received bilateral vagotomy, then randomly treated with aVNS or sham-aVNS for a week. In addition, eight normal rats were implanted with a polyethylene catheter in the proximal colon for assessing whole colon transit. 1) The number of fecal pellets and water content in feces increased after aVNS, compared with sham-aVNS. 2) aVNS accelerated colon transit and whole gut transit, compared with sham-aVNS. 3) In colon tissues, aVNS increased the protein expression of choline acetyltransferase, glial cell line-derived neurotrophic factor and the c-kit expression in myenteric interstitial cells of Cajal but decreased the protein expression of neural nitric oxide synthase (p < 0.05 for all, vs. sham-VNS). 4) The prokinetic effects of aVNS were abolished by both subdiaphragmatic vagotomy and atropine. 5) aVNS increased the c-fos expression in both nucleus tractus solitarius and dorsal motor nucleus of vagus, and increased vagal efferent activity (p < 0.05, vs. sham-VNS). aVNS improves OIC by enhancing colon motility and restoring enteric neural functions mediated via the central and vagal efferent pathway. aVNS improves OIC by enhancing colon motility and restoring enteric neural functions mediated via the central and vagal efferent pathway.A nickel-catalyzed intramolecular coupling of thioesters and olefins has been developed for the efficient synthesis of spirocycles, a privileged scaffold commonly found in natural products. This transformation is characterized by the simultaneous transfer of both acyl and thiol moieties to the alkene, with the suppression of decarbonylation and β-hydrogen elimination. Initial mechanistic investigations are consistent with an oxidative addition/olefin insertion/reductive elimination mechanism. The incorporated methylene sulfide substituent can undergo a variety of further reactions to increase molecular diversity and complexity. These results demonstrate that thioester derivatives can be used as powerful building blocks for the assembly of complex scaffolds.Free-living (FL) marine microbial communities differ from those attached to particles (PA). Likewise, biofilms (B) colonizing artificial surfaces, including plastics or ship hulls, hardly resemble their planktonic surroundings. However, few studies have examined the effect of the environment on these lifestyles and on the source of organisms colonizing marine surfaces. Using 16S rRNA gene metabarcoding, we identified specificities of marine prokaryotic community lifestyles (FL, PA or B) sampled in three coastal polluted locations with dissimilar environmental conditions the North-Western Mediterranean Sea and the Atlantic and Indian Oceans. Biofilms developed over polyvinyl chloride (PVC) were found to be significantly different from FL or PA collected during the immersions. Alpha-diversity increased from FL to PA and to B, illustrating the integrative aspect of the latter, with little proportion of operational taxonomic units shared with the first two. Beta-diversity clustered first the lifestyles and then the sites. FL and PA were more affected by water quality, especially by trace metal contamination, whereas B were as sensitive to trace metals as to nutrients. Although biofilms should be supplied by the planktonic (ultra) rare biosphere, source tracking could only detect small contributions of FL or PA taxa to B communities.The anabolic-androgenic steroids (AAS) are clinically used as an androgen replacement, in hypogonadism treatment, to induce puberty, and also in the treatment of chronic degenerative diseases. The AAS use out of clinical context is becoming massively, being used merely for aesthetic reasons. AAS abuse may cause severe disarrangement on the HPG axis and generate a significant decrease in testosterone synthesis and secretion by the testes. This review aims to evaluate whether the hypogonadism induced by AAS abuse is reversible and under what circumstances the reversibility is possible. For this, PRISMA guidelines and several databases are used between July and September 2020. Altogether, this systematic review identified and analysed 179 cases of AAS users. https://www.selleckchem.com/ALK.html Of these, 168 cases had the hypogonadism clearly diagnosed and proven to be linked exclusively to AAS abuse. However, between these 168 cases, only 38 cases presented fully known outcomes and among these, merely in 4, the hypogonadism was completely reversible (2 based on drug therapy) with HPG axis recovery.