Correction: Decentralization and Integration of Advanced Cardiac Care for the World's Poorest Billion Through the PEN-Plus Strategy for Severe Chronic Non-Communicable Disease.

[This corrects the article DOI: 10.5334/gh.1313.].

Decentralization and Integration of Advanced Cardiac Care for the World's Poorest Billion Through the PEN-Plus Strategy for Severe Chronic Non-Communicable Disease.

Rheumatic and congenital heart disease, cardiomyopathies, and hypertensive heart disease are major causes of suffering and death in low- and lower middle-income countries (LLMICs), where the world's poorest billion people reside. Advanced cardiac care in these counties is still predominantly provided by specialists at urban tertiary centers, and is largely inaccessible to the rural poor. This situation is due to critical shortages in diagnostics, medications, and trained healthcare workers. The Package of Essential NCD Interventions - Plus (PEN-Plus) is an integrated care model for severe chronic noncommunicable diseases (NCDs) that aims to decentralize services and increase access. PEN-Plus strategies are being initiated by a growing number of LLMICs. We describe how PEN-Plus addresses the need for advanced cardiac care and discuss how a global group of cardiac organizations are working through the PEN-Plus Cardiac expert group to promote a shared operational strategy for management of severe cardiac disease in high-poverty settings.

Cost-effectiveness of severe acute malnutrition treatment delivered by community health workers in the district of Mayahi, Niger.

BACKGROUND: A non-randomized controlled trial, conducted from June 2018 to March 2019 in two rural communes in the health district of Mayahi in Niger, showed that including community health workers (CHWs) in the treatment of severe acute malnutrition (SAM) resulted in a better recovery rate (77.2% vs. 72.1%) compared with the standard treatment provided solely at the health centers. The present study aims to assess the cost and cost-effectiveness of the CHWs led treatment of uncomplicated SAM in children 6-59 months compared to the standard national protocol. METHODS: To account for all relevant costs, the cost analysis included activity-based costing and bottom-up approaches from a societal perspective and on a within-trial time horizon. The cost-effectiveness analysis was conducted through a decision analysis network built with OpenMarkov and evaluated under two approaches: (1) with recovery rate and cost per child admitted for treatment as measures of effectiveness and cost, respectively; and (2) assessing the total number of children recovered and the total cost incurred. In addition, a multivariate probabilistic sensitivity analysis was carried out to evaluate the effect of uncertainty around the base case input data. RESULTS: For the base case data, the average cost per child recovered was 116.52 USD in the standard treatment and 107.22 USD in the CHWs-led treatment. Based on the first approach, the CHWs-led treatment was more cost-effective than the standard treatment with an average cost per child admitted for treatment of 82.81 USD vs. 84.01 USD. Based on the second approach, the incremental cost-effectiveness ratio of the transition from the standard to the CHWs-led treatment amounted to 98.01 USD per additional SAM case recovered. CONCLUSIONS: In the district of Mayahi in Niger, the CHWs-led SAM treatment was found to be cost-effective when compared to the standard protocol and provided additional advantages such as the reduction of costs for households. TRIAL REGISTRATION: ISRCTN with ID 31143316. https://doi.org/10.1186/ISRCTN31143316.

Attributable mortality of infections caused by carbapenem-resistant Enterobacterales: results from a prospective, multinational case-control-control matched cohorts study (EURECA).

OBJECTIVES: To assess the mortality attributable to infections caused by carbapenem-resistant Enterobacterales (CRE) and to investigate the effect of clinical management on differences in observed outcomes in a multinational matched cohort study. METHODS: A prospective matched-cohorts study (NCT02709408) was performed in 50 European hospitals from March 2016 to November 2018. The main outcome was 30-day mortality with an active post-discharge follow-up when applied. The CRE cohort included patients with complicated urinary tract infections, complicated intra-abdominal infections, pneumonia, or bacteraemia from other sources because of CRE. Two control cohorts were selected: patients with infection caused by carbapenem-susceptible Enterobacterales (CSE) and patients without infection. Matching criteria included type of infection for the CSE group, hospital ward of CRE detection, and duration of hospital admission up to CRE detection. Multivariable and stratified Cox regression was applied. RESULTS: The cohorts included 235 patients with CRE infection, 235 patients with CSE infection, and 705 non-infected patients. The 30-day mortality (95% CI) was 23.8% (18.8-29.6), 10.6% (7.2-15.2), and 8.4% (6.5-10.6), respectively. The difference in 30-day mortality rates between patients with CRE infection when compared with patients with CSE infection was 13.2% (95% CI, 6.3-20.0), (HR, 2.57; 95% CI, 1.55-4.26; p < 0.001), and 15.4% (95% CI, 10.5-20.2) when compared with non-infected patients (HR, 3.85; 95% CI, 2.57-5.77; p < 0.001). The population attributable fraction for 30-day mortality for CRE vs. CSE was 19.28%, and for CRE vs. non-infected patients was 9.61%. After adjustment for baseline variables, the HRs for mortality were 1.87 (95% CI, 0.99-3.50; p 0.06) and 3.65 (95% CI, 2.29-5.82; p < 0.001), respectively. However, when treatment-related time-dependent variables were added, the HR of CRE vs. CSE reduced to 1.44 (95% CI, 0.78-2.67; p 0.24). DISCUSSION: CRE infections are associated with significant attributable mortality and increased adjusted hazard of mortality when compared with CSE infections or patients without infection. Underlying patient characteristics and a delay in appropriate treatment play an important role in the CRE mortality.

Effectiveness of gamification and game-based learning in Spanish adolescents with dyslexia: A longitudinal quasi-experimental research.

BACKGROUND: Gamification and game-based learning can provide motivating learning opportunities. The scientific literature suggests that these play strategies could be supportive tools for the learning of students with diagnosed dyslexia. AIMS: This study compares the effectiveness of an educational gamification and game-based learning (GBL) methodology versus a transmissive methodology for the improvement of reading processes and academic performance in the subject of Spanish Language and Literature in Spanish high school students with dyslexia. METHODS AND PROCEDURES: Longitudinal quasi-experimental research was conducted with control and experimental groups. Ninety students with a mean age of 14.22 years (SD = 0.95) participated in the study. The assessment instruments used were the PROLEC-SE reading process assessment battery and academic performance through subject grades. The intervention with the experimental group consisted of gamification and GBL of 15 one-hour sessions in which students' oral and written skills were worked with playful learning strategies. OUTCOMES AND RESULTS: The results indicate that the experimental group had statistically significant improvement in their reading skills (η2g = 0.616) and academic performance, albeit less in pseudoword speed, compared to the control group (η2g = 0.197). CONCLUSION AND IMPLICATIONS: The study highlights the usefulness of gamification and GBL as practical tools for meaningful learning in students with dyslexia.

Patient-derived tumor models in cancer research: Evaluation of the oncostatic effects of melatonin.

The development of new anticancer therapies tends to be very slow. Although their impact on potential candidates is confirmed in preclinical studies, ∼95 % of these new therapies are not approved when tested in clinical trials. One of the main reasons for this is the lack of accurate preclinical models. In this context, there are different patient-derived models, which have emerged as a powerful oncological tool: patient-derived xenografts (PDXs), patient-derived organoids (PDOs), and patient-derived cells (PDCs). Although all these models are widely applied, PDXs, which are created by engraftment of patient tumor tissues into mice, is considered more reliable. In fundamental research, the PDX model is used to evaluate drug-sensitive markers and, in clinical practice, to select a personalized therapeutic strategy. Melatonin is of particular importance in the development of innovative cancer treatments due to its oncostatic impact and lack of adverse effects. However, the literature regarding the oncostatic effect of melatonin in patient-derived tumor models is scant. This review aims to describe the important role of patient-derived models in the development of anticancer treatments, focusing, in particular, on PDX models, as well as their use in cancer research. This review also summarizes the existing literature on the anti-tumoral effect of melatonin in patient-derived models in order to propose future anti-neoplastic clinical applications.

Shall we play together? Game-based learning for engagement and classroom climate in Spanish socially deprived communities.

Purpose: The purpose of this study is to analyze the effects of a game-based learning (GBL) program on the classroom climate and engagement of high schools in socially deprived communities in Spain. Methods: The study included 277 students from two secondary schools located in Southern Spain, situated in Zones in Need of Social Transformation. Sampling was non-probabilistic and accidental, based on the accessibility of the school and the willingness of the management and teaching staff to participate in the GBL program. The study employed a control group and two experimental groups (cooperative games group only and cooperative and competitive games group) to compare pre-test and post-test data in both groups. The Brief Class Climate Scale and Engagement Inventory, validated in academic literature, were used as assessment instruments. Results: The study used a series of ANOVA tests to compare the experimental groups with the control group. The results indicated statistically significant changes in all study variables. In all cases, the experimental groups demonstrated greater benefits than the control group. Discussion and conclusion: The study findings reveal that games can provide significant benefits to students, regardless of whether they are cooperative or competitive. The study provides evidence of the benefits of GBL in high schools located in socially deprived communities in Spain.

Population health impact and economic evaluation of the CARDIO4Cities approach to improve urban hypertension management.

Cardiovascular disease (CVD) is the leading cause of mortality worldwide, with 80% of that mortality occurring in low- and middle-income countries. Hypertension, its primary risk factor, can be effectively addressed through multisectoral, multi-intervention initiatives. However, evidence for the population-level impact on cardiovascular (CV) event rates and mortality, and the cost-effectiveness of such initiatives is scarce as long-term longitudinal data is often lacking. Here, we model the long-term population health impact and cost-effectiveness of a multisectoral urban population health initiative designed to reduce hypertension, conducted in Ulaanbaatar (Mongolia), Dakar (Senegal), and in the district of Itaquera in São Paulo (Brazil) in collaboration with the local governments. We based our analysis on cohort-level data among hypertensive patients on treatment and control rates from a real-world effectiveness study of the CARDIO4Cities approach (built on quality of care, early access, policy reform, data and digital, Intersectoral collaboration, and local ownership). We built a decision tree model to estimate the CV event rates during implementation (1-2 years) and a Markov model to project health outcomes over 10 years. We estimated the number of CV events averted and quality-adjusted life-years gained (QALYs through the initiative and assessed its cost-effectiveness based on the costs reported by the funder using the incremental cost effectiveness ratio (ICER) and published thresholds. A one-way sensitivity analysis was performed to assess the robustness of the results. The modelled patient cohorts included 10,075 patients treated for hypertension in Ulaanbaatar, 5,236 in Dakar, and 5,844 in São Paulo. We estimated that 3.3-12.8% of strokes and 3.0-12.0% of coronary heart disease (CHD) events were averted during 1-2 years of implementation in the three cities. We estimated that over the subsequent 10 years, 3.6-9.9% of strokes, 2.8-7.8% of CHD events, and 2.7-7.9% of premature deaths would be averted. The estimated ICER was USD 748 QALY gained in Ulaanbaatar, USD 3091 in Dakar, and USD 784 in São Paulo. With that, the intervention was estimated to be cost-effective in Ulaanbaatar and São Paulo. For Dakar, cost-effectiveness was met under WHO-CHOICE standards, but not under more conservative standards adjusted for purchasing power parity (PPP) and opportunity costs. The findings were robust to the sensitivity analysis. Our results provide evidence that the favorable impact of multisector systemic interventions designed to reduce the hypertension burden extend to long-term population-level CV health outcomes and are likely cost-effective. The CARDIO4Cities approach is predicted to be a cost-effective solution to alleviate the growing CVD burden in cities across the world.

Risk factors for infections caused by carbapenem-resistant Enterobacterales: an international matched case-control-control study (EURECA).

Background: Data on risk factors for carbapenem-resistant Enterobacterales (CRE) with wider applicability are needed to inform preventive measures and efficient design of randomised trials. Methods: An international matched case-control-control study was performed in 50 hospitals with high CRE incidence from March 2016 to November 2018 to investigate different aspects of infections caused by CRE (NCT02709408). Cases were patients with complicated urinary tract infection (cUTI), complicated intraabdominal (cIAI), pneumonia or bacteraemia from other sources (BSI-OS) due to CRE; control groups were patients with infection caused by carbapenem-susceptible Enterobacterales (CSE), and by non-infected patients, respectively. Matching criteria included type of infection for CSE group, ward and duration of hospital admission. Conditional logistic regression was used to identify risk factors. Findings: Overall, 235 CRE case patients, 235 CSE controls and 705 non-infected controls were included. The CRE infections were cUTI (133, 56.7%), pneumonia (44, 18.7%), cIAI and BSI-OS (29, 12.3% each). Carbapenemase genes were found in 228 isolates: OXA-48/like, 112 (47.6%), KPC, 84 (35.7%), and metallo-ß-lactamases, 44 (18.7%); 13 produced two. The risk factors for CRE infection in both type of controls were (adjusted OR for CSE controls; 95% CI; p value) previous colonisation/infection by CRE (6.94; 2.74-15.53; <0.001), urinary catheter (1.78; 1.03-3.07; 0.038) and exposure to broad spectrum antibiotics, as categorical (2.20; 1.25-3.88; 0.006) and time-dependent (1.04 per day; 1.00-1.07; 0.014); chronic renal failure (2.81; 1.40-5.64; 0.004) and admission from home (0.44; 0.23-0.85; 0.014) were significant only for CSE controls. Subgroup analyses provided similar results. Interpretation: The main risk factors for CRE infections in hospitals with high incidence included previous colonization, urinary catheter and exposure to broad spectrum antibiotics. Funding: The study was funded by the Innovative Medicines Initiative Joint Undertaking (https://www.imi.europa.eu/) under Grant Agreement No. 115620 (COMBACTE-CARE).

Game-Based Learning and Service-Learning to Teach Inclusive Education in Higher Education.

This study evaluates the impact of game-based learning (GBL) and Service-Learning on the flow and engagement of teacher education students. A quasi-experimental between-group comparison design with pre-test and post-test measures was conducted with a sample of 113 students majoring in childhood education. The results indicate that the experimental group statistically significantly improved their flow and engagement scores compared to the control group. It is concluded that the GBL and SL methodology in initial teacher training allows students to learn about inclusive education in a motivating way and to design different strategies and resources that they will be able to use in their professional future.

Implementing a multisector public-private partnership to improve urban hypertension management in low-and middle- income countries.

BACKGROUND: Cardiovascular disease presents an increasing health burden to low- and middle-income countries. Although ample therapeutic options and care improvement frameworks exist to address its prime risk factor, hypertension, blood pressure control rates remain poor. We describe the results of an effectiveness study of a multisector urban population health initiative that targets hypertension in a real-world implementation setting in cities across three continents. The initiative followed the "CARDIO4Cities" approach (quality of Care, early Access, policy Reform, Data and digital technology, Intersectoral collaboration, and local Ownership). METHOD: The approach was applied in Ulaanbaatar in Mongolia, Dakar in Senegal, and São Paulo in Brazil. In each city, a portfolio of evidence-based practices was implemented, tailored to local priorities and available data. Outcomes were measured by extracting hypertension diagnosis, treatment and control rates from primary health records. Data from 18,997 patients with hypertension in primary health facilities were analyzed. RESULTS: Over one to two years of implementation, blood pressure control rates among enrolled patients receiving medication tripled in São Paulo (from 12·3% to 31·2%) and Dakar (from 6·7% to 19·4%) and increased six-fold in Ulaanbaatar (from 3·1% to 19·7%). CONCLUSIONS: This study provides first evidence that a multisectoral population health approach to implement known best-practices, supported by data and digital technologies, and relying on local buy-in and ownership, can improve hypertension control in high-burden urban primary care settings in low-and middle-income countries.

A Web-Based Escape Room to Raise Awareness About Severe Mental Illness Among University Students: Randomized Controlled Trial.

BACKGROUND: People with severe mental illness (SMI) face discriminatory situations because of prejudice toward them, even among health care personnel. Escape rooms can be a novel educational strategy for learning about and empathizing with SMI, thus reducing stigma among health care students. OBJECTIVE: This study aimed to examine the effect of the Without Memories escape room on nursing students' stigma against SMI. METHODS: A pre- and postintervention study was conducted with a control group and an experimental group. A total of 306 students from 2 Andalusian universities participated in the study. Data were collected through a pre-post study questionnaire, consisting of an adapted version of the Attributional Style Questionnaire and a questionnaire on motivation for cooperative playful learning strategies. The control group carried out an escape room scenario without sensitizing content, whereas the experimental group carried out an escape room scenario on SMI, with both escape rooms being carried out in a 1-hour session of subjects related to mental health. To answer the research questions, a 2-way analysis of variance with repeated measures, a linear regression, and a 2-way analysis of variance were performed. RESULTS: After the intervention, a significant reduction (P<.001) was observed in the experimental group in stigmatizing attitudes compared with the control group, in which no statistically significant changes (P>.05) were observed. In contrast, the linear regression (t195=-22.15; P<.001) showed that there was an inverse relationship between flow and the level of reduced stigma. When controlling for having or not having a close relative, the intervention was also shown to be effective (P<.001) in reducing the stigma displayed, both for people with affected and unaffected relatives. CONCLUSIONS: Our findings suggest that the Without Memories escape room can be used as an effective tool to educate and raise awareness about stigmatizing attitudes toward SMI in university students studying health care. Future testing of the effectiveness of educational escape rooms should be designed with new programs through playful strategies of longer duration to evaluate whether they can achieve a greater impact on motivation, acquisition of knowledge, and awareness. In addition, the feasibility of implementing the Without Memories escape room in other careers related to health and community should be investigated.

The CHIVA strategy applied to large-diameter saphenous veins.

BACKGROUND: CHIVA (Cure Conservatrice et Hemodynamique de l'Insufficience Veineuse en Ambulatoire) is a conservative outpatient treatment strategy for chronic venous disease (CVD) that preserves the superficial venous system. A modified two-stage strategy is used in patients with a great saphenous vein (GSV) diameter ≥9 mm with the goal to decrease the risk of symptomatic superficial vein thrombosis (SVT), as the risk of complications is higher when first and second stage is performed simultaneously. METHODS: We conducted a retrospective observational study of 111 patients with CVD and a GVS diameter ≥9 mm treated with two possible stages of the CHIVA strategy, between January 2010 and December 2019. The goal of the first stage was to interrupt the main reflux escape point (incompetent saphenofemoral junction), thereby lowering the venous pressure and achieving a sufficient reduction in GSV diameter to enable, if necessary, a second stage that consists of disconnection of secondary reflux exit point (incompetent saphenous tributaries), with a lower risk of symptomatic SVT when patients do not show significant clinical improvement. Reductions in GSV diameter, postoperative complications and clinical improvement were analyzed. RESULTS: There were 60 men (54.1%) and 51 women (45.9%) with a mean age of 57±11.9 years. All patients undergone first surgical stage, and this interruption of the saphenofemoral junction was the single procedure in 77.5% of cases (86 patients). Mean follow-up time was 19.8 months. The second stage was performed in 25 patients (22.5%). Mean preoperative GSV diameter was 10.2±1.1 mm and this decreased to 7.1±1.5 mm after the first surgery (mean reduction, 3±1.5 mm, P<0.001). Six patients (5.4%) experienced recurrence due to recanalization of the reflux point and 16 patients (14.4%) developed SVT, which was symptomatic in 12 cases (10.8%). CONCLUSIONS: Interruption of the main reflux escape point as a single procedure in patients with a GSV diameter ≥9 mm led to a significant reduction in diameter and sufficient clinical improvement in almost 80% of cases.

Acquisition of Learning and Empathy Towards Patients in Nursing Students Through Online Escape Room: An Exploratory Qualitative Study.

BACKGROUND: Currently, there are still prejudices and negative beliefs towards people with severe mental disorder. The stigma of healthcare professionals can affect both recovery time and patients' own self-stigma. In universities, it is necessary to reduce these prejudices through training on mental health. PURPOSE: The purpose of this research has been to assess the use of educational escape rooms as a learning and awareness strategy on stigmatizing attitudes towards people with serious mental disorders in university students. METHODS: An online escape room has been designed whose narrative shows the daily life of a person with a serious mental illness. An exploratory qualitative study has been carried out to explore the perception of 44 university students from two Andalusian universities about this escape room. RESULTS: The results of the study show that most of the interviewed students consider that the educational escape room has been a fun and motivating learning strategy, which has allowed them to learn cooperatively and empathize with the protagonist with a mental disorder. CONCLUSION: Online escape rooms can be a useful strategy for teaching health sciences students. Considering it a fun activity, students are more participatory and engaged to the curricular content, in our case, stigmatizing attitudes towards people with serious mental disorders.

Testing the Factorial Validity of the Classroom Engagement Inventory with Spanish Students.

INTRODUCTION: The purpose of the study was to test the factorial validity of Classroom Engagement Inventory of Wang, Bergin and Bergin with Spanish high school students. METHODS: In this study, 546 students participated (mean = 13.27, standard deviation = 0.629), from several high schools in Andalusia. To analyze the psychometric properties of the scale, several analyses were carried out. RESULTS: The results offered support for the five-factor structure. The analysis of invariance with respect to gender showed that the factor structure of the questionnaire was invariant. The Cronbach alpha values were higher than 0.70 in the subscales. DISCUSSION: The results of this study demonstrated the reliability and validity of the Spanish version of the Classroom Engagement Inventory with high school students.

Escape Rooms as a Learning Strategy for Special Education Master's Degree Students.

Escape rooms and breakout are learning strategies that can facilitate motivation of learning through challenges. In these strategies, students must work as a team and use their reasoning, knowledge, and skills to solve puzzles and challenges related to the content of the curriculum, allowing them to solve the game in a limited time. The aim of this study was to determine the effects of the implementation of an escape room on classroom flow, academic performance, school motivation, and prosocial and antisocial behaviours with higher students in a Special Education master's degree course. The quantitative results show a significant improvement in classroom flow, academic performance, and classroom climate, and a better score in prosocial and antisocial behaviours. The qualitative findings provide a better understanding of these results, and support the conclusion that the use of escape rooms is fun and motivating for students, and facilitates their learning achievement.

Fostering cardiovascular health at work - case study from Senegal.

BACKGROUND: Of the 15 million annual premature deaths from non-communicable diseases (NCDs), 85% occur in low- and middle-income countries (LMICs). Affecting individuals in the prime of their lives, NCDs impose severe economic damage to economies and businesses, owing to the high mortality and morbidity within the workforce. The Novartis Foundation urban health initiative, Better Hearts Better Cities, was designed to improve cardiovascular health in Dakar, Senegal through a combination of interventions including a workplace health program. In this study, we describe the labor policy environment in Senegal and the outcomes of a Novartis Foundation-supported multisector workplace health coalition bringing together volunteering private companies. METHODS: A mixed method design was applied between April 2018 and February 2020 to evaluate the workplace health program as a case study. Qualitative methods included a desk review of documents relevant to the Senegalese employment context and work environment and in-depth interviews with eight key informants including human resource representatives and physicians working in the participating companies. Quantitative methods involved an analysis of workplace health program indicators, including data on diagnosis, treatment and control of hypertension in employees, provided by the coalition companies, and a cost estimate of NCD-related ill-health as compared to the investment needed for hypertension screening and awareness raising events. RESULTS: Senegal has a legal and regulatory system that ensures employee protection, supports social security benefits, and promotes health and hygiene in companies. The Dakar Workplace Health Coalition comprised 18 companies, with a range of staff between 300 and 4'220, covering 36'268 employees in total. Interviews suggested that the main enablers for workplace program success were strong leadership support within the company and a central coordination mechanism for the program. The main barrier to monitor progress and outcomes was the reluctance of companies to share data. Four companies provided aggregated anonymized cohort data, documenting a total of 21'392 hypertension screenings and an increasing trend in blood pressure control (from 34% in Q4 2018 to 39% in Q2 2019) in employees who received antihypertensive treatment. CONCLUSION: Evidence on workplace health and wellness programs in Africa is scarce. This study highlights how private sector companies can play a significant role in improving cardiovascular population health in LMICs.

Social Acceptance of Aquaculture in Spain: An Instrument to Achieve Sustainability for Society.

Aquaculture is a technique to produce food that is under debate, due to its possible consequences for altering the economy, traditional fishing included, or the environment, even with doubts about the health of consumers. This document studies its social acceptance from the point of view of carrying capacity. This term is defined as the level at which this activity begins to be disproportionate and poses important disadvantages for society. In this context, we conducted 803 surveys in six coastal provinces in Spain. The results show that the acceptance of these products is good, implying that aquaculture is far from reaching its saturation point in society. Additionally, the respondents gave a higher priority to socio-economic objectives than to environmental ones. We can conclude that the further development of this sector is advisable in these provinces. The general perception of aquaculture is better among men, and also among higher-income consumers. Informative activities should be organized to target these more hesitant groups. Production structures should be revised to overcome biases in the population about the idea that the food obtained from aquaculture harms the environment or is less natural or healthy. The possible abuse of feed and chemicals spreads this idea, and this could affect the taste and quality adversely.

Social Acceptance of Aquaculture in Andalusian Atlantic Coast (Spain): An Emerging Economy Sector.

Aquaculture is an important source of food. This document analyses its acceptance by consumers from the perspective of social carrying capacity. This concept determines the point at which its development begins to be excessive, and poses difficulties to its geographical area. In this context, our work is innovative, since, although Spain is the leading aquaculture producer in the European Union, not much research on this aspect has been developed. With this objective, we carried out 579 personal interviews with consumers from the Andalusian Atlantic coast (Spain), to determine an index of acceptance for this food and its industry. After applying a principal component analysis, we stratified the samples following Dalenius-Hodges method. According to our surveys, there is a high level of acceptance, which would place aquaculture far from its saturation point, the level at which this sector generates relevant problems for society in terms of economy or environment. Respondents also recommended its further development. Women and low-income consumers were the groups with the greatest reticence about this sector. We consider that general acceptance would be improved by implementing informative campaigns, especially for these groups, that would extend consumers' knowledge and improve their perception of this kind of food.

Melatonin Enhances Cisplatin and Radiation Cytotoxicity in Head and Neck Squamous Cell Carcinoma by Stimulating Mitochondrial ROS Generation, Apoptosis, and Autophagy.

Head and neck cancer is the sixth leading cancer by incidence worldwide. Unfortunately, drug resistance and relapse are the principal limitations of clinical oncology for many patients, and the failure of conventional treatments is an extremely demoralizing experience. It is therefore crucial to find new therapeutic targets and drugs to enhance the cytotoxic effects of conventional treatments without potentiating or offsetting the adverse effects. Melatonin has oncostatic effects, although the mechanisms involved and doses required remain unclear. The purpose of this study is to determine the precise underlying mitochondrial mechanisms of melatonin, which increase the cytotoxicity of oncological treatments, and also to propose new melatonin treatments in order to alleviate and reverse radio- and chemoresistant processes. We analyzed the effects of melatonin on head and neck squamous cell carcinoma (HNSCC) cell lines (Cal-27 and SCC-9), which were treated with 0.1, 0.5, 1, and 1.5 mM melatonin combined with 8 Gy irradiation or 10 µM cisplatin. Clonogenic and MTT assays, as well as autophagy and apoptosis, involving flow cytometry and western blot, were performed in order to determine the cytotoxic effects of the treatments. Mitochondrial function was evaluated by measuring mitochondrial respiration, mtDNA content (RT-PCR), and mitochondrial mass (NAO). ROS production, antioxidant enzyme activity, and GSH/GSSG levels were analyzed using a fluorometric method. We show that high concentrations of melatonin potentiate the cytotoxic effects of radiotherapy and CDDP in HNSCC, which are associated with increased mitochondrial function in these cells. In HNSCC, melatonin induces intracellular ROS, whose accumulation plays an upstream role in mitochondria-mediated apoptosis and autophagy. Our findings indicate that melatonin, at high concentrations, combined with cisplatin and radiotherapy to improve its effectiveness, is a potential adjuvant agent.