Effects of sequential exposure to physical exercise and cognitive training on hippocampal neurogenesis in mice

AIMS: Physical exercise and cognitive training hippocampal dependent tasks are known to enhance adult hippocampal neurogenesis (AHN). Here we aimed to evaluate the effect of either a moderate-intensity exercise protocol, a working memory task and the combination of both treatments on mice AHN. METHODS: Adult male C57BL6/J mice (N=34) were submitted to a scheduled treadmill exercise protocol for 12 days (EX-groups) or remained at home cage (SED-groups). 24 hours later, animals either were perfused or trained in a spatial learning task in the Water Maze (WM groups) for 8 days while control groups remained at home cage (CAGE groups). Bromodeoxyuridine (BrdU) was injected at the beginning of every experimental procedure to label hippocampal cells that proliferated during the initial exercise sessions. RESULTS: Mice submitted to scheduled exercise showed an increased number of BrdU+ and PCNA+ dentate granule cells (DGCs) in the short but not in the long-term when compared to sedentary groups. Conversely, training in the WM solely reduced the amount of BrdU+ and PCNA+ DGCs compared to CAGE group. However, animals submitted to scheduled exercise and WM training showed increased proliferation/survival of DGCs in the long-term compared to all other groups. CONCLUSIONS: Our data suggests that the combination of moderate-intensity exercise with spatial training has a powerful neurogenic effect in the DG, being a valuable non-pharmacological strategy for the treatment of neurodegenerative diseases associated with impaired AHN. Funding: PSI2017-82604; PRE2018-085673; FPU20/00908; 08-2021-AREA3; B1-2020_06; Posdoc_21_00222; Posdoctoral_a32. I Plan Propio de Investigación, Transferencia y Divulgación Científica de la Universidad de Málaga.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Sequential treadmill exercise and cognitive training synergistically increase adult hippocampal neurogenesis in mice

Combining physical and cognitive training has been suggested to promote further benefits on brain and cognition, which could include synergistic improvement of hippocampal neuroplasticity. In this paper, we investigated whether treadmill exercise followed by a working memory training in the water maze increase adult hippocampal neurogenesis to a greater extent than either treatment alone. Our results revealed that ten days of scheduled running enhance cell proliferation/survival in the short-term as well as performance in the water maze. Moreover, exercised mice that received working memory training displayed more surviving dentate granule cells compared to those untreated or subjected to only one of the treatments. According to these findings, we suggest that combining physical and cognitive stimulation yield synergic effects on adult hippocampal neurogenesis by extending the pool of newly-born cells and subsequently favouring their survival. Future research could take advantage from this non-invasive, multimodal approach to achieve substantial and longer-lasting enhancement in adult hippocampal neurogenesis, which might be relevant for improving cognition in healthy or neurologically impaired conditions.This study received financial support from the Spanish Ministry of Economy and Competitiveness (Agencia Estatal de Investigación, AEI), which was cofounded by the European Regional Development Fund (AEI/FEDER, UE; PSI2017-82604R to L.J.S.); by the Spanish Ministry of Science and Innovation (PID2020-113806RB-I00 to L.J.S); by the Biomedical Research Institute of Málaga (IBIMA; 08-2021-AREA3 to D.L.G.M) and by the University of Málaga (B1-2020_06 to D.L.G-M). Funding for Open Access charge: Universidad de Málaga/CBU

Combinatorial wound dressings loaded with synergistic antibiotics in the treatment of chronic infected wounds

Advanced medicated wound dressings fabricated by electrospinning and electrospraying were prepared for the eradication of topical bacterial infections potentially applied in the management of infected acute and chronic non-healing wounds. Two different antibiotics (ciprofloxacin and rifampicin), with different aqueous solubilities and different mechanisms of antimicrobial action, were loaded within electrosprayed polymer microparticles and within electrospun nanofibers, respectively, to provide the resulting wound dressing with dually controlled antibiotic release kinetics. Due to the large surface area per volume ratio of the electrosprayed microparticles containing ciprofloxacin, an initial burst release was obtained. Simultaneously, the reduced surface area per volume ratio for the electrospun nanofibers together with the reduced aqueous solubility of rifampicin produced an extended rifampicin release over time. More importantly, a synergistic antimicrobial effect against Gram-positive and Gram-negative bacteria was observed when both antibiotics were combined. Biofilm formation prevention and the elimination of already formed mature bacterial biofilms were also successfully achieved using our advanced dressings. The lack of cytotoxicity of the advanced wound dressings here reported against eukaryotic cells at antimicrobial doses was also demonstrated using three different mammalian cell lines. Moreover, the advanced wound dressings successfully eliminated a Staphylococcus aureus mediated experimental infection in a chronic wound murine model showing their efficacy for the treatment of these complicated non-healing wounds. The strategy of advanced medicated wound dressings developed here may be used as a potential methodology for the fabrication of functional combinatorial materials that offer the ability to eradicate bacterial infections

Functional Recovery and Serum Angiogenin Changes According to Intensity of Rehabilitation Therapy After Stroke

Angiogenina; Terapia intensiva; RehabilitaciónAngiogenin; Intensive therapy; RehabilitationAngiogenina; Teràpia intensiva; RehabilitacióBackground: Rehabilitation is still the only treatment available to improve functional status after the acute phase of stroke. Most clinical guidelines highlight the need to design rehabilitation treatments considering starting time, intensity, and frequency, according to the tolerance of the patient. However, there are no homogeneous protocols and the biological effects are under investigation. Objective: To investigate the impact of rehabilitation intensity (hours) after stroke on functional improvement and serum angiogenin (ANG) in a 6-month follow-up study. Methods: A prospective, observational, longitudinal, and multicenter study with three cohorts: strokes in intensive rehabilitation therapy (IRT, minimum 15 h/week) vs. conventional therapy (NO-IRT, <15 h/week), and controls subjects (without known neurological, malignant, or inflammatory diseases). A total of seven centers participated, with functional evaluations and blood sampling during follow-up. The final cohort includes 62 strokes and 43 controls with demographic, clinical, blood samples, and exhaustive functional monitoring. Results: The median (IQR) number of weekly hours of therapy was different: IRT 15 (15–16) vs. NO-IRT 7.5 (5–9), p < 0.01, with progressive and significant improvements in both groups. However, IRT patients showed earlier improvements (within 1 month) on several scales (CAHAI, FMA, and FAC; p < 0.001) and the earliest community ambulation achievements (0.89 m/s at 3 months). There was a significant difference in ANG temporal profile between the IRT and NO-IRT groups (p < 0.01). Additionally, ANG was elevated at 1 month only in the IRT group (p < 0.05) whereas it decreased in the NO-IRT group (p < 0.05). Conclusions: Our results suggest an association of rehabilitation intensity with early functional improvements, and connect the rehabilitation process with blood biomarkers.NG-R holds a VHIR fellowship and MO-G a Joan Margarit VHIR fellowship. Research grants: from the Instituto de Salud Carlos III and European Regional Development Funds (PI16/00981, PI19/00186, RD16/0019/0021, and RD16/0019/0008), 2017-SGR-1427 program from the Generalitat de Catalunya-AGAUR, and Clinical Translational Program for Regenerative Medicine in Catalonia (P-CMR [C])

Potencial de integração de energia solar térmica de concentração em processos de secagem de resíduos

CIES2020 - XVII Congresso Ibérico e XIII Congresso Ibero-americano de Energia SolarRESUMO: A consciencialização dos problemas resultantes das atividades económicas relacionadas com a gestão de resíduos nas regiões transfronteiriças da Andaluzia-Algarve-Alentejo (AAA), conduziu ao desenvolvimento do projeto SECASOL. Este projeto de cooperação visa a integração de energia solar térmica de concentração (ESTC) nos processos de secagem de lamas de depuração de águas residuais (ETAR) e de resíduos sólidos urbanos (RSU). Foi avaliada a integração da energia solar de concentração em processos de secagem, através da identificação das principais soluções técnicas e tipologias de secagem de resíduos e caracterização dos processos tecnológicos com influência nos requisitos de valorização do produto final. Através da estimativa dos valores anuais para GHI e DNI nas principais instalações de tratamento de RSU e águas residuais do Algarve e Andaluzia, utilizou-se um modelo simplificado para estimativa do potencial de utilização da energia solar em dois processos de secagem de interesse – materiais CDR de RSU e lamas de depuração de ETAR- em termos de quantidade de matéria processada por unidade de área de captação de energia solar.ABSTRACT: Awareness of the problems resulting from economic activities related to waste management in the cross-border regions of Andalusia-Algarve-Alentejo (AAA) led to the development of the SECASOL project. This AAA cooperation project pointing to the integration of concentration solar thermal (CST) in the sludge drying processes for wastewater treatment (WWT) and RDF of solid urban waste (MSW). CST integration in the drying processes was evaluated through the identification of the main technical solutions and types of waste drying and related technological processes on the requirements for by-product valorization. Acknowledgment of the annual values for GHI and DNI at the main MSW and WWT facilities in the Algarve and Andalusia region´s had led to a simplified model used to estimate the potential use of solar energy in two drying processes of interest – RDF materials from MSW and sewage sludge from WWT - in terms of the amount of processed product per unit of solar energy capture area.info:eu-repo/semantics/publishedVersio

Multicenter study of plastic vs. self-expanding metal stents in endoscopic ultrasound-guided drainage of walled-off pancreatic necrosis - PROMETHEUS: a randomized controlled trial protocol.

Background: It seems that lumen-apposing metal stents (LAMS) are displacing plastic stents in the therapy of pancreatic-fluid collection in walled-off necrosis (WON). To date, there is no quality of evidence to recommend LAMS as the standard treatment in the management of WON. The theoretical benefit of LAMS over plastic stents needs to be proven. Methods/design: This is a randomized controlled, multicenter, prospective clinical trial with two parallel groups, without masking. One-hundred and fourteen patients with WON will undergo endoscopic ultrasound (EUS)-guided transmural draining in nine tertiary hospitals in Spain and will be randomized to the LAMS or plastic-stent group. The primary endpoint is the short-term (4 weeks) clinical success determined by the reduction of the collection (to < 50% or < 5 cm in size), along with clinical improvement. Secondary endpoints: long-term (4 months) clinical success (total resolution or 5 cm), procedure duration, level of difficulty, safety, and recurrences. Discussion: The PROMETHEUS trial has been designed to determine whether LAMS are superior to plastic stents in EUS-guided transmural drainage of WON

Interplay between gonadal hormones and postnatal overfeeding in defining sex-dependent differences in gut microbiota architecture

Aging is associated with a decline in sex hormones, variable between sexes, that has an impact on many different body systems and might contribute to age-related disease progression. We aimed to characterize the sex differences in gut microbiota; and. to explore the impact of depletion of gonacial hormones, alone or combined with postnatal overfeeding, in rats. Many of the differences in the gut microbiota between sexes persisted after gonadectomy, but removal of gonadal hormones shaped several gut microbiota features towards a more deleterious profile, the effect being greater in females than in males, mainly when animals were concurrently overfed. Moreover, we identified several intestinal miRNAs as potential mediators of the impact of changes in gut microbiota on host organism physiology. Our study points out that gonadal hormones contribute to defining sex-dependent differences of gut microbiota, and discloses a potential role of gonadal hormones in shaping gut microbidta, OS consequence of the interaction between sex and nutrition. Our data suggest that the changes in gut microbion, observed in conditions of sex hormone decline, as those caused by ageing in men and menopause in women, might exert different effects on the host organism, which are putatively mediated by gut microbiota-intestinal miRNA cross-talk

Surgical treatment for colorectal cancer: Analysis of the influence of an enhanced recovery programme on long-term oncological outcomes-a study protocol for a prospective, multicentre, observational cohort study

Introduction The evidence currently available from enhanced recovery after surgery (ERAS) programmes concerns their benefits in the immediate postoperative period, but there is still very little evidence as to whether their correct implementation benefits patients in the long term. The working hypothesis here is that, due to the lower response to surgical aggression and lower rates of postoperative complications, ERAS protocols can reduce colorectal cancer-related mortality. The main objective of this study is to analyse the impact of an ERAS programme for colorectal cancer on 5-year survival. As secondary objectives, we propose to analyse the weight of each of the predefined items in the oncological results as well as the quality of life. Methods and analysis A multicentre prospective cohort study was conducted in patients older than 18 years of age who are scheduled to undergo surgery for colorectal cancer. The study involved 12 hospitals with an implemented enhanced recovery protocol according to the guidelines published by the Spanish National Health Service. The intervention group includes patients with a minimum implementation level of 70%, and the control group includes those who fail to reach this level. Compliance will be studied using 18 key performance indicators, and the results will be analysed using cancer survival indicators, including overall survival, cancer-specific survival and relapse-free survival. The time to recurrence, perioperative morbidity and mortality, hospital stay and quality of life will also be studied, the latter using the validated EuroQol Five questionnaire. The propensity index method will be used to create comparable treatment and control groups, and a multivariate regression will be used to study each variable. The Kaplan-Meier estimator will be used to estimate survival and the log-rank test to make comparisons. A p value of less than 0.05 (two-tailed) will be considered to be significant. Ethics and dissemination Ethical approval for this study was obtained from the Aragon Ethical Committee (C.P.-C.I. PI20/086) on 4 March 2020. The findings of this study will be submitted to peer-reviewed journals (BMJ Open, JAMA Surgery, Annals of Surgery, British Journal of Surgery). Abstracts will be submitted to relevant national and international meetings. Trial registration number NCT04305314

Multicenter study of lumen-apposing metal stents with or without pigtail in endoscopic ultrasound-guided biliary drainage for malignant obstruction - BAMPI TRIAL: an open-label, randomized controlled trial protocol

Background It is unclear whether the insertion of an axis-orienting double-pigtail plastic stent (DPS) through biliary lumen-apposing meal stent (LAMS) in EUS-guided choledochoduodenostomy (CDS) improves the stent patency. The aim of this study is to determine whether this technical variant offers a clinical benefit in EUS-guided biliary drainage (BD) for the management of distal malignant biliary obstruction. Methods/design This is a multicenter open-label, randomized controlled trial with two parallel groups. Eighty-four patients with malignant biliary obstruction will undergo EUS-BD (CDS type) using LAMS in 7 tertiary hospitals in Spain and will be randomized to the LAMS and LAMS plus DPS groups. The primary endpoint is the rate of recurrent biliary obstruction, as a stent dysfunction parameter, detected during follow-up. Secondary endpoints: technical and clinical success (reduction in bilirubin > 50% within 14 days of stent placement), safety, and others (number of reinterventions, time to biliary obstruction, prognostic factors, survival rate). Discussion The BAMPI trial has been designed to determine whether the addition of a coaxial axis-orienting DPS through LAMS is superior to LAMS alone to prevent stent dysfunction

A genome-wide association study suggests the HLA Class II region as the major susceptibility locus for IgA vasculitis.

The genetic component of Immunoglobulin-A (IgA) vasculitis is still far to be elucidated. To increase the current knowledge on the genetic component of this vasculitis we performed the first genome-wide association study (GWAS) on this condition. 308 IgA vasculitis patients and 1,018 healthy controls from Spain were genotyped by Illumina HumanCore BeadChips. Imputation of GWAS data was performed using the 1000 Genomes Project Phase III dataset as reference panel. After quality control filters and GWAS imputation, 285 patients and 1,006 controls remained in the datasets and were included in further analysis. Additionally, the human leukocyte antigen (HLA) region was comprehensively studied by imputing classical alleles and polymorphic amino acid positions. A linkage disequilibrium block of polymorphisms located in the HLA class II region surpassed the genome-wide level of significance (OR = 0.56, 95% CI = 0.46-0.68). Although no polymorphic amino acid positions were associated at the genome-wide level of significance, P-values of potential relevance were observed for the positions 13 and 11 of HLA-DRB1 (P = 6.67E-05, P = 1.88E-05, respectively). Outside the HLA, potential associations were detected, but none of them were close to the statistical significance. In conclusion, our study suggests that IgA vasculitis is an archetypal HLA class II disease