Involvement of cannabinoid signaling in vincristine-induced gastrointestinal dysmotility in the rat

[Background]: In different models of paralytic ileus, cannabinoid receptors are overexpressed and endogenous cannabinoids are massively released, contributing to gastrointestinal dysmotility. The antitumoral drug vincristine depresses gastrointestinal motility and a similar mechanism could participate in this effect. Therefore, our aim was to determine, using CB and CB antagonists, whether an increased endocannabinoid tone is involved in vincristine-induced gastrointestinal ileus. [Methods]: First, we confirmed the effects of vincristine on the gut mucosa, by conventional histological techniques, and characterized its effects on motility, by radiographic means. Conscious male Wistar rats received an intraperitoneal injection of vincristine (0.1-0.5 mg/kg), and barium sulfate (2.5 ml; 2 g/ml) was intragastrically administered 0, 24, or 48 h later. Serial X-rays were obtained at different time-points (0-8 h) after contrast. X-rays were used to build motility curves for each gastrointestinal region and determine the size of stomach and caecum. Tissue samples were taken for histology 48 h after saline or vincristine (0.5 mg/kg). Second, AM251 (a CB receptor antagonist) and AM630 (a CB receptor antagonist) were used to determine if CB and/or CB receptors are involved in vincristine-induced gastrointestinal dysmotility. [Key results]: Vincristine induced damage to the mucosa of ileum and colon and reduced gastrointestinal motor function at 0.5 mg/kg. The effect on motor function was particularly evident when the study started 24 h after administration. AM251, but not AM630, significantly prevented vincristine effect, particularly in the small intestine, when administered thrice. AM251 alone did not significantly alter gastrointestinal motility. [Conclusions]: The fact that AM251, but not AM630, is capable of reducing the effect of vincristine suggests that, like in other experimental models of paralytic ileus, an increased cannabinoid tone develops and is at least partially responsible for the alterations induced by the antitumoral drug on gastrointestinal motor function. Thus, CB1 antagonists might be useful to prevent/treat ileus induced by vincristine.This work was supported by Ministerio de Ciencia e Innovación (SAF2009-12422-C02-01, SAF2012-40075-C02-01), Universidad Rey Juan Carlos—Comunidad de Madrid (URJC-CM-2006-BIO-0604) and Comunidad de Madrid (S-SAL/0261/2006; S2010/BMD-2308).Peer Reviewe

Evaluation of Glycerylphytate Crosslinked Semi- and Interpenetrated Polymer Membranes of Hyaluronic Acid and Chitosan for Tissue Engineering

In the present study, semi- and interpenetrated polymer network (IPN) systems based on hyaluronic acid (HA) and chitosan using ionic crosslinking of chitosan with a bioactive crosslinker, glycerylphytate (G1Phy), and UV irradiation of methacrylate were developed, characterized and evaluated as potential supports for tissue engineering. Semi- and IPN systems showed significant differences between them regarding composition, morphology, and mechanical properties after physicochemical characterization. Dual crosslinking process of IPN systems enhanced HA retention and mechanical properties, providing also flatter and denser surfaces in comparison to semi-IPN membranes. The biological performance was evaluated on primary human mesenchymal stem cells (hMSCs) and the systems revealed no cytotoxic effect. The excellent biocompatibility of the systems was demonstrated by large spreading areas of hMSCs on hydrogel membrane surfaces. Cell proliferation increased over time for all the systems, being significantly enhanced in the semi-IPN, which suggested that these polymeric membranes could be proposed as an effective promoter system of tissue repair. In this sense, the developed crosslinked biomimetic and biodegradable membranes can provide a stable and amenable environment for hMSCs support and growth with potential applications in the biomedical field.The authors thanks to “La Caixa” Foundation (ID 100010434), which supported Ana Mora-Boza (scholarship code LCF/BQ/ES16/11570018) and to the Spanish Ministry of Economy and Competitiveness for financial support (project RTC-2016-5451-1) and the Fundación Mutua Madrileña (project FMM-AP17196-2019). M. R. Aguilar and B. Vázquez-Lasa are members of the SusPlast platform (Interdisciplinary Platform for Sustainable Plastics towards a Circular Economy) from the Spanish National Research Council (CSIC)

Surface passivation and optical characterization of Al2O3/a-SiCx stacks on c-Si substrates

The aim of this work is to study the surface passivation of aluminum oxide/amorphous silicon carbide (Al2O3/a-SiCx) stacks on both p-type and n-type crystalline silicon (c-Si) substrates as well as the optical characterization of these stacks. Al2O3 films of different thicknesses were deposited by thermal atomic layer deposition (ALD) at 200 °C and were complemented with a layer of a-SiCx deposited by plasma-enhanced chemical vapor deposition (PECVD) to form anti-reflection coating (ARC) stacks with a total thickness of 75 nm. A comparative study has been carried out on polished and randomly textured wafers. We have experimentally determined the optimum thickness of the stack for photovoltaic applications by minimizing the reflection losses over a wide wavelength range (300–1200 nm) without compromising the outstanding passivation properties of the Al2O3 films. The upper limit of the surface recombination velocity (Seff,max) was evaluated at a carrier injection level corresponding to 1-sun illumination, which led to values below 10 cm/s. Reflectance values below 2% were measured on textured samples over the wavelength range of 450–1000 nm.Postprint (published version

Survival analysis of time to SARS-CoV-2 PCR negativisation to optimise PCR prescription in health workers: the Henares COVID-19 healthcare workers cohort study.

Objectives Reverse transcriptase PCR (RT-PCR) is considered the gold standard in diagnosing COVID-19. Infected healthcare workers do not go back to work until RT-PCR has demonstrated that the virus is no longer present in the upper respiratory tract. The aim of this study is to determine the most efficient time to perform RT-PCR prior to healthcare workers’ reincorporation. Materials and methods This is a cohort study of healthcare workers with RT-PCR-confirmed COVID-19. Data were collected using the medical charts of healthcare workers and completed with a telephone interview. Kaplan-Meier curves were used to determine the influence of several variables on the time to RT-PCR negativisation. The impact of the variables on survival was assessed using the Breslow test. A Cox regression model was developed including the associated variables. Results 159 subjects with a positive RT-PCR out of 374 workers with suspected COVID-19 were included. The median time to negativisation was 25 days from symptom onset (IQR 20–35 days). Presence of IgG, dyspnoea, cough and throat pain were associated with significant longer time to negativisation. Cox logistic regression was used to adjust for confounding variables. Only dyspnoea and cough remained in the model as significant determinants of prolonged negativisation time. Adjusted HRs were 0.68 (0.48–096) for dyspnoea and 0.61 (0.42–0.88) for dry cough. Conclusions RT-PCR during the first 3 weeks leads to a high percentage of positive results. In the presence of respiratory symptoms, negativisation took nearly 1 week more. Those who developed antibodies needed longer time to negativisate.pre-print396 K

Base contacts and selective emitters processed by laser doping technique for p-type IBC c-Si solar cells

Abstract In this work, we describe a novel fabrication process of p-type interdigitated back contact (IBC) silicon solar developed by means of laser doping and laser firing techniques. We use dielectric layers both as dopant sources to create highly-doped regions and as passivating layers. In particular, we use phosphorus-doped silicon carbide stacks (a-SiCx (n)) deposited by Plasma Enhanced Chemical Vapor Deposition (PECVD) and aluminum oxide (Al2O3) layer deposited by atomic layer deposition (ALD). Emitters were fabricated with a light thermal phosphorus diffusion in order to reduce bulk and surface emitter recombination losses. Highly doped regions n++ (emitter) and p++ (base) were simultaneously created in a point-like structure using a pulsed Nd-YAG 1064 nm laser in the nanosecond regime by laser processing the dielectric layers. The results obtained for a cell, 3x3 cm2, are presented. Efficiencies up to 18.1% (Jsc = 39 mA/cm2, Voc = 632 mV, FF = 73.4%) have been achieved in our fabricated IBC cells.Postprint (published version

Should inflammatory bowel disease clinicians provide their patients with e-Health resources?: patients' and professionals' perspectives

[Abstract] Introduction: The internet is emerging as a source of information for patients with inflammatory bowel disease (IBD). However, it is not always reliable and may cause anxiety. We aim to assess patients' information habits and patients' and professionals' perceptions of a national website integrated as an educational resource for the IBD unit. Methods: Patients aged 18-65 years, comfortable with the internet, and attending follow-ups at participating IBD units (March-June 2019) and their professionals were invited to evaluate a recommended website through an online survey. Results: Three hundred eighty-nine patients and 95 professionals completed the survey. The internet (n = 109; 27.4%) was the second preferred source of information after the health care team (n = 229; 57.5%). Eighty percent of patients searched the internet for information on their disease and 28.6% did so at least once a week (n = 114), especially newly diagnosed ones (<2 years). Patients valued a website recommended by their professional (n = 379; 95.2%) and endorsed by the National Working Group (n = 377; 94.7%). They would attend online educational initiatives on the website (n = 279; 70.1%) and complete periodical surveys to improve its usefulness (n = 338; 84.9%). According to IBD professionals, this type of website is the best patient source of supplementary information (n = 76; 80%) and they "prescribe" it to most patients (67.0 ± 25.2%), especially the newly diagnosed patients (52.7 ± 26.5%). It effectively integrates routine face-to-face education (n = 95; 100%). Conclusions: Patients of IBD units, especially newly diagnosed ones, appreciate a trusted e-Health resource to back up professional information. The favorable opinion of patients and professionals will allow its use in training interventions

Changes in plasma fatty acid composition are associated with improvements in obesity and related metabolic disorders: A therapeutic approach to overweight adolescents

“This is an original manuscript published by Churchill Livingstone in Clinical Nutrition on February 2018, available at: doi: 10.1016/j.clnu.2016.11.006.”Background & aims: In recent years, obesity has reached alarming levels among children and adolescents. The study of plasma fatty acid (FA) composition, as a reflection of diet, and its associations with other parameters, that are closely linked to obesity and the cardiometabolic profile, may be useful for setting nutritional goals for obesity treatment and prevention. This study explored the role of plasma FA levels as modulators of body fat and cardiometabolic risk markers, in overweight adolescents. Methods: A multidisciplinary weight loss program was followed by 127 overweight and obese adolescents aged 12-17 years old. Plasma FA composition, anthropometric indicators of adiposity and biochemical parameters were analyzed at baseline, two months (the end of the intensive intervention phase) and six months (the end of the extensive phase). Results: While saturated fatty acid (SFA) and n-6 polyunsaturated fatty acid (PUFA) levels decreased significantly during the intervention, monounsaturated fatty acid (MUFA) and n-3 PUFA showed the opposite trend. The decrease in SFA C14:0 was associated with a reduction in total and LDL cholesterol, apolipoprotein B and insulin. The increase in MUFAs, especially C18:1n-9, was related to a reduction in weight, fat mass, fat mass index and glucose. Regarding PUFAs, changes in the n-3 series were not associated with any of the parameters studied, whereas the reduction in n-6 PUFAs was directly related to weight, fat mass, total and HDL cholesterol, apolipoprotein A1, glucose and insulin, and inversely associated with diastolic blood pressure. The adolescents with greater weight loss presented significant changes in MUFAs, n-6 PUFAs and C14:0. Conclusions: Modifications in plasma FA composition could help modulate adiposity and the cardiometabolic profile in anti-obesity programs aimed at adolescents. The changes observed in FA composition were related to the success of the treatment, since the individuals most affected by these variations were those who presented the greatest weight loss.This work is part of the EVASYON study funded by the Spanish 326 Ministry of Health and Consumption (Carlos III Institute of Health. FIS. Grant PI 051579). The EVASYON study has received the award from AESAN (Spanish Agency for Food Security and Nutrition) from the Spanish Ministry of Health and Consumption to the best applied research project in 2009

Second-line treatment in advanced gastric cancer : Data from the Spanish AGAMENON registry

Second-line treatments boost overall survival in advanced gastric cancer (AGC). However, there is a paucity of information as to patterns of use and the results achieved in actual clinical practice. The study population comprised patients with AGC in the AGAMENON registry who had received second-line. The objective was to describe the pattern of second-line therapies administered, progression-free survival following second-line (PFS-2), and post-progression survival since first-line (PPS). 2311 cases with 2066 progression events since first-line (89.3%) were recorded; 245 (10.6%) patients died during first-line treatment and 1326/2066 (64.1%) received a second-line. Median PFS-2 and PPS were 3.1 (95% CI, 2.9-3.3) and 5.8 months (5.5-6.3), respectively. The most widely used strategies were monoCT (56.9%), polyCT (15.0%), ramucirumab+CT (12.6%), platinum-reintroduction (8.3%), trastuzumab+CT (6.1%), and ramucirumab (1.1%). PFS-2/PPS medians gradually increased in monoCT, 2.6/5.1 months; polyCT 3.4/6.3 months; ramucirumab+CT, 4.1/6.5 months; platinum-reintroduction, 4.2/6.7 months, and for the HER2+ subgroup in particular, trastuzumab+CT, 5.2/11.7 months. Correlation between PFS since first-line and OS was moderate in the series as a whole (Kendall's τ = 0.613), lower in those subjects who received second-line (Kendall's τ = 0.539), especially with ramucirumab+CT (Kendall's τ = 0.413). This analysis reveals the diversity in second-line treatment for AGC, highlighting the effectiveness of paclitaxel-ramucirumab and, for a selected subgroup of patients, platinum reintroduction; both strategies endorsed by recent clinical guidelines

External validity of clinical trials with diverse trastuzumab-based chemotherapy regimens in advanced gastroesophageal adenocarcinoma: data from the AGAMENON-SEOM registry

Background: Trastuzumab combined with cisplatin and fluoropyrimidines, either capecitabine or 5-fluorouracile (XP/FP), is the standard first-line treatment for advanced, HER2-positive, gastric cancer patients based on the ToGA trial. Despite the lack of phase III trials, many clinicians administer trastuzumab with alternative regimens. One meta-analysis suggests that substituting cisplatin for oxaliplatin might lead to greater efficacy and less toxicity. Methods: 594 patients with HER2-positive gastroesophageal adenocarcinoma were recruited from the AGAMENON-SEOM registry. The objective was to evaluate the external validity of clinical trials with chemotherapy and trastuzumab. Results: The regimens used in at least 5% of the patients were XP (27%), oxaliplatin and capecitabine (CAPOX) (26%), oxaliplatin and 5-fluorouracil (FOLFOX) (14%), FP (14%), triplet with anthracycline/docetaxel (7%), and carboplatin-FU (5%). Median exposure to trastuzumab was longer with FOLFOX (11.4 months, 95% CI, 9.1-21.0) versus ToGA regimens (7.5, 6.4-8.5), p < 0.001. Patients with HER2-IHC 3+ cancers had higher response rates than those with IHC 2+/FISH+, odds-ratio 1.97 (95% CI, 1.25-3.09). The results achieved with CAPOX-trastuzumab were comparable to those attained with ToGA regimens. FOLFOX-trastuzumab was superior to ToGA schemes in terms of overall survival (OS), with a greater magnitude of effect in IHC 2+/FISH+ tumors (HR 0.47, 0.24-0.92) compared with IHC 3+ (HR 0.69, 0.49-0.96), and in diffuse (HR 0.37, 0.20-0.69) versus intestinal-type tumors (HR 0.76, 0.54-1.06). Conclusion: We have updated the external validity of clinical trials with trastuzumab in first-line treatment of gastric cancer. Our data confirm the comparable outcomes of ToGA regimens and CAPOX-trastuzumab in clinical practice and point toward a possible benefit of FOLFOX-trastuzumab, contingent on the subtypes typically less sensitive to trastuzumab, to be confirmed in clinical trials

Evaluation of the potential association of SOHLH2 polymorphisms with non-obstructive azoospermia susceptibility in a large European population

Non-obstructive azoospermia (NOA) or spermatogenic failure is a complex disease with an important genetic component that causes infertility in men. Known genetic factors associated with NOA include AZF microdeletions of the Y chromosome or karyotype abnormalities; however, most causes of NOA are idiopathic. During the last decade, a large list of associations between single-nucleotide polymorphisms (SNP) and NOA have been reported. However, most of the genetic studies have been performed only in Asian populations. We aimed to evaluate whether the previously described association in Han Chinese between NOA and two SNPs of the SOHLH2 gene (involved in the spermatogenesis process) may also confer risk for NOA in a population of European ancestry. We genotyped a total of 551 NOA patients (218 from Portugal and 333 from Spain) and 1,050 fertile controls (226 from Portugal and 824 from Spain) for the genetic variants rs1328626 and rs6563386 using TaqMan assays. To test for association, we compared the allele and genotype frequencies between cases and controls using an additive model. A haplotype analysis and a meta-analysis using the inverse variance method with our data and those of the original Asian study were also performed. No statistically significant differences were observed in any of the analyses described above. Therefore, considering the high statistical power of our study, it is not likely that the two analysed SOHLH2 genetic variants are related with an increase susceptibility to NOA in the European population.info:eu-repo/semantics/publishedVersio