Macrophages direct cancer cells through a LOXL2-mediated metastatic cascade in pancreatic ductal adenocarcinoma

The lysyl oxidase-like protein 2 (LOXL2) contributes to tumour progression and metastasis in different tumour entities, but its role in pancreatic ductal adenocarcinoma (PDAC) has not been evaluated in immunocompetent in vivo PDAC models.Towards this end, we used PDAC patient data sets, patient-derived xenograft in vivo and in vitro models, and four conditional genetically-engineered mouse models (GEMMS) to dissect the role of LOXL2 in PDAC. For GEMM-based studies, K-Ras +/LSL-G12D;Trp53 LSL-R172H;Pdx1-Cre mice (KPC) and the K-Ras +/LSL-G12D;Pdx1-Cre mice (KC) were crossed with Loxl2 allele floxed mice (Loxl2 Exon2 fl/fl) or conditional Loxl2 overexpressing mice (R26Loxl2 KI/KI) to generate KPCL2 KO or KCL2 KO and KPCL2 KI or KCL2 KI mice, which were used to study overall survival; tumour incidence, burden and differentiation; metastases; epithelial to mesenchymal transition (EMT); stemness and extracellular collagen matrix (ECM) organisation. Using these PDAC mouse models, we show that while Loxl2 ablation had little effect on primary tumour development and growth, its loss significantly decreased metastasis and increased overall survival. We attribute this effect to non-cell autonomous factors, primarily ECM remodelling. Loxl2 overexpression, on the other hand, promoted primary and metastatic tumour growth and decreased overall survival, which could be linked to increased EMT and stemness. We also identified tumour-associated macrophage-secreted oncostatin M (OSM) as an inducer of LOXL2 expression, and show that targeting macrophages in vivo affects Osm and Loxl2 expression and collagen fibre alignment.Taken together, our findings establish novel pathophysiological roles and functions for LOXL2 in PDAC, which could be potentially exploited to treat metastatic diseaseg JCL-G received support from a ’la Caixa’ Foundation (ID 100010434) fellowship (LCF/BQ/DR21/11880011). This study was supported by ISCIII FIS grants PI18/00757 and PI21/01110 (BSJ) and PI18/00267 (LG-B), and grants from the Spanish Ministry of Economy and Innovation SAF2016-76504-R (ACan and FP), PID2019-111052RB-I00 (FP), PID2019-104644RB-I00 (GM-B), a Ramón y Cajal Merit Award RYC-2012–12104 (BSJ) and ISCIII, CIBERONC, CB16/12/00446 (ACar) and CB16/12/00295 (ACan and GM-B), all of them co-financed through Fondo Europeo de Desarrollo Regional (FEDER) ’Una manera de hacer Europa’; a Fero Foundation Grant (BSJ); a Coordinated grant (GC16173694BARB) from the Fundación Científica Asociación Española Contra el Cáncer (FC-AECC) (BSJ); a Miguel Servet award (CP16/00121) (PS); a DFG, German Research Foundation Grant—Project no: 492 436 553 (KG); and a Max Eder Fellowship of the German Cancer Aid (111746) (PCH

Effect of Myofascial Therapy on Pain and Functionality of the Upper Extremities in Breast Cancer Survivors: A Systematic Review and Meta-Analysis

(1) Objective: The purpose was to analyze the effectiveness of myofascial therapy on musculoskeletal pain and functionality of the upper extremities in female breast cancer survivors, and to evaluate the changes in range of motion, quality of life, and mood state of these patients. (2) Methods: Systematic searches were performed on the MEDLINE/PubMed, Web of Science, Scopus, and Physiotherapy Evidence Databases for articles published until October 2020, in order to identify randomized controlled trials which analyzed the effectiveness of myofascial therapy as compared to a control group, passive treatment, placebo, or another intervention, and allowed co-interventions on female breast cancer survivors. Two reviewers examined the sources individually, calculated the risk of bias and extracted the data (PROSPERO number CRD42020215823). (3) Results: A total of eight RCTs were included. The results suggested that myofascial therapy does not have a greater statistically significant immediate effect on pain intensity (SMD: -0.15; 95% CI -0.48, 0.19), functionality (SMD: -0.17; 95% CI -0.43, 0.09) and range of motion in flexion (SMD: 0.30; 95% CI -0.13, 0.74) than an inactive, passive treatment or another intervention. However, a statistically significant result was observed for the abduction shoulder in favor of the experimental group (SMD: 0.46; 95% CI 0.05, 0.87; p = 0.03). (4) Conclusion: In general, although we found greater overall effects in support of the intervention with myofascial therapy than other control groups/types of interventions, the subgroup analysis revealed inconsistent results supporting myofascial therapy applied to breast cancer survivors

Visual system and motor development in children: a systematic review

Purpose The aim of this study was to review the available scientific literature on the possible relationship between the visual system and motor development in children.MethodsThis study was performed according to the Preferred Reporting Items for Systematic Reviews (PRISMA) statement recommendations. The review protocol is available in PROSPERO (CRD42021245341). Four different databases, namely Scopus, PubMed, CINAHL and Web of Science, were assessed from April 2005 to February 2021. To determine the quality of the articles, we used the Critical Appraisal Skills Programme (CASP) Quality Appraisal Scale, and a protocol was followed to define the levels of evidence on the basis of the Centre for Evidence-Based Medicine Levels of Evidence. The search strategy included terms describing motor development in children and adolescents with visual disorders.Results Among the identified studies, 23 were included in the study. All selected articles examined the relationship between the visual system and development in children. The quality of most of the studies was moderate–high, and they were between evidence levels 2 and 4.ConclusionsOur systematic review revealed that all included studies established a relationship between the visual system and development in children. However, the methods for measuring the visual system and motor skills lacked uniformity

Hydrotherapy for the Treatment of Pain in People with Multiple Sclerosis: A Randomized Controlled Trial

Background. Multiple sclerosis (MS) is a chronic demyelinating neurological disease. Several studies have reported that complementary and alternative therapies can have positive effects against pain in these patients. Objective. The objective was to investigate the effectiveness of an Ai-Chi aquatic exercise program against pain and other symptoms in MS patients. Methods. In this randomized controlled trial, 73 MS patients were randomly assigned to an experimental or control group for a 20-week treatment program. The experimental group underwent 40 sessions of Ai-Chi exercise in swimming pool and the control group 40 sessions of abdominal breathing and contraction-relaxation exercises in therapy room. Outcome variables were pain, disability, spasm, depression, fatigue, and autonomy, which were assessed before the intervention and immediately and at 4 and 10 weeks after the last treatment session. Results. The experimental group showed a significant (P < 0.028) and clinically relevant decrease in pain intensity versus baseline, with an immediate posttreatment reduction in median visual analogue scale scores of 50% that was maintained for up to 10 weeks. Significant improvements were also observed in spasm, fatigue, disability, and autonomy. Conclusion. According to these findings, an Ai-Chi aquatic exercise program improves pain, spasms, disability, fatigue, depression, and autonomy in MS patients

Fresnel solar cooling plant for buildings: Optimal operation of an absorption chiller through inverse modelling

Increasing comfort conditions in buildings imply higher energy demands. However, these needs can be mitigated by solar cooling solutions. These systems, such as absorption chillers, are complex and require stable operation, with strict control to maximise the solar fraction and minimise gas consumption. This is incompatible with the variability of renewable resources, so they are often coupled with auxiliary gas systems. Although gas-free operation is possible if these systems are optimally controlled, they would require special supervision. This paper aims to develop an experimental validation of an inverse model to manage an absorption chiller coupled with a solar cooling plant. To know its real behaviour, long-term experiments have been performed using this plant, which consists of a linear Fresnel solar collector and an auxiliary natural gas boiler. The inverse model is used as a predictive control tool to decide the auxiliary boiler commands of the absorption chiller to optimise its operation: maximum cooling production by minimising gas consumption and maximising solar contribution. It has been identified with data from two weeks and validated with data from one summer month. Results show that the model estimates, on a time base of fewer than 30 min, are acceptable with errors of less than 5%. In addition, the maximum error of the estimated seasonal COP and the renewable fraction are less than 6% per day. Therefore, the results prove the usefulness of the proposal as a predictive control for optimal operation. Furthermore, it could be used as a baseline for preventive maintenance. If the proposed model is used for optimal management of the absorption chiller, the thermal efficiency of the plant increases significantly, doubling the solar contribution. As a result, the gas consumption of the solar cooling plant is halved and the total cost of air conditioning the building decreases by 16%.Comisión Europea A_B.4.3_02

Small molecules targeting glycogen synthase kinase 3 as potential drug candidates for the treatment of retinitis pigmentosa

6 p.-5 fig.Retinitis pigmentosa (RP) is an inherited retinal dystrophy that courses with progressive degeneration of retinal tissue and loss of vision. Currently, RP is an unpreventable, incurable condition. We propose glycogen synthase kinase 3 (GSK-3) inhibitors as potential leads for retinal cell neuroprotection, since the retina is also a part of the central nervous system and GSK-3 inhibitors are potent neuroprotectant agents. Using a chemical genetic approach, diverse small molecules with different potency and binding mode to GSK-3 have been used to validate and confirm GSK-3 as a pharmacological target for RP. Moreover, this medicinal chemistry approach has provided new leads for the future disease-modifying treatment of RP.This work has been partially funded by the Spanish MINECO grants (SAF2012-37979-C03-01 to AM and SAF2013-41059-R to EJdlR).Peer reviewe

Adaptative Cover to Achieve Thermal Comfort in Open Spaces of Buildings: Experimental Assessment and Modelling

The global need for healthy and safe open spaces faces continuous temperature rise due to the heat island phenomenon and climate change. This problem requires new strategies for improving the habitability of open spaces (indoor and outdoor conditions in buildings). These techniques include reducing solar radiation, reducing the temperature of surrounding surfaces, and reducing the air temperature. The radiant solutions are essential for outdoor comfort, both in summer and in winter. They are easy to integrate into open spaces. This study explores a new concept of radiant solutions adapted for outdoor spaces. The solution was evaluated in a test cell to obtain its thermal behaviour in different operation conditions. Solutions were optimised for operating in a cooling regimen since it has been identified that the demands for comfort in open spaces in hot climates during the most severe summer months are more pronounced. Experimental results have allowed getting an inverse model to analyse the thermal behaviour of the solution. The inverse model achieved high precision in its estimations. Also, it facilitated knowing the radiant and convective effects. Only the radiant heat flux is relevant in open spaces with a low level of air confinement. Finally, the discussion describes the application of the proposed model. The model allows the replicability of the solution—creating new designs (integration) or evaluating into different operating conditions of the system. This discussion demonstrates the high level of knowledge acquired in the characterisation of the solution studied.e European Commission / European Regional Development Funds (ERDF) UIA03-301-CartujaQanat of Urban Innovative Action (UIA

The Efficacy of Strength Exercises for Reducing the Symptoms of Menopause: A Systematic Review

Background: The aim of this systematic review was to determine whether strength exercises improve the symptoms of menopause and to provide an update on the most recent scientific evidence on the type and regimen of exercise that help reduce the symptoms. Methods: An electronic search of scientific databases was performed from 2015 to 2022. Randomized clinical trials that analyzed the effects of strength exercises versus other types of interventions, considering all the outcome measures of interest, were included in this review. Results: We found 5964 potential articles. After applying the selection criteria, we selected 12 of the articles. The studies compared strength exercises versus other therapies or compared strength exercises versus no intervention in one of the groups. The results showed improvements in the strength of the legs and pelvic floor, physical activity, bone density, metabolic and hormonal changes, heart rate and blood pressure and a change in hot flashes. Conclusions: There is evidence that strength exercises can be beneficial for improving strength, physical activity, bone density and hormonal and metabolic levels. In terms of the appropriate type of strength training, the evidence is still unclear given that the same benefits are achieved by various types of exercises

Physical Therapists’ Opinion of E-Health Treatment of Chronic Low Back Pain

1) Background: Using new technologies to manage home exercise programmes is an approach that allows more patients to benefit from therapy. The objective of this study is to explore physical therapists’ opinions of the efficacy and disadvantages of implementing a web-based telerehabilitation programme for treating chronic low back pain (CLBP). (2) Methods: Nineteen physical therapists from academic and healthcare fields in both the public and private sector participated in the qualitative study. Texts extracted from a transcript of semi-structured, individual, in-depth interviews with each consenting participant were analysed to obtain the participants’ prevailing opinions. The interviews lasted approximately 40 min each. The participants’ responses were recorded. (3) Results: The results suggest that telerehabilitation can only be successful if patients become actively involved in their own treatment. However, exercise programmes for LBP are not always adapted to patient preferences. New technologies allow physical therapists to provide their patients with the follow-up and remote contact they demand, but long-term adherence to treatment stems from knowledge of the exercises and the correct techniques employed by the patients themselves. (4) Conclusions: Physical therapists treating patients with chronic non-specific low back pain believe that new technologies can provide highly effective means of reaching a greater number of patients and achieving significant savings in healthcare costs, despite the limitations of a telerehabilitation approach in developing an appropriate and effective patient-based physiotherapy programme