Multiple pathways of programmed cell death are important in liver homeostasis. Hepatocyte death is associated with progression of nonalcoholic fatty liver disease, and inhibition of apoptosis ...partially protects against liver injury in response to a high‐fat diet (HFD). However, the contribution of necroptosis, a caspase‐independent pathway of cell death, to HFD‐induced liver injury is not known. Wild‐type C57BL/6 and receptor interacting protein (RIP) 3−/− mice were randomized to chow or HFD. HFD‐fed C57BL/6 mice increased expression of RIP3, the master regulator of necroptosis, as well as phosphorylated mixed lineage kinase domain‐like, an effector of necroptotic cell death, in liver. HFD did not increase phosphorylated mixed lineage kinase domain‐like in RIP3−/− mice. HFD increased fasting insulin and glucose, as well as glucose intolerance, in C57BL/6 mice. RIP3−/− mice were glucose‐intolerant even on the chow diet; HFD further increased fasting glucose and insulin but not glucose intolerance. HFD also increased hepatic steatosis, plasma alanine aminotransferase activity, inflammation, oxidative stress, and hepatocellular apoptosis in wild‐type mice; these responses were exacerbated in RIP3−/− mice. Importantly, increased inflammation and injury were associated with early indicators of fibrosis in RIP3−/− compared to C57BL/6 mice. Culture of AML12 hepatocytes with palmitic acid increased cytotoxicity through apoptosis and necrosis. Inhibition of RIP1 with necrostatin‐1 or small interfering RNA knockdown of RIP3 reduced palmitic acid‐induced cytotoxicity. Conclusion: Absence of RIP3, a key mediator of necroptosis, exacerbated HFD‐induced liver injury, associated with increased inflammation and hepatocyte apoptosis, as well as early fibrotic responses; these findings indicate that shifts in the mode of hepatocellular death can influence disease progression and have therapeutic implications because manipulation of hepatocyte cell death pathways is being considered as a target for treatment of nonalcoholic fatty liver disease. (Hepatology 2016;64:1518‐1533)
Decision support systems are appropriate tools for guiding policymaking processes, especially in mental health (MH), where care provision should be delivered in a balanced and integrated way. This ...study aims to develop an analytical process for (i) assessing the performance of an MH ecosystem and (ii) identifying benchmark and target-for-improvement catchment areas. MH provision (inpatient, day and outpatient types of care) was analysed in the Mental Health Network of Gipuzkoa (Osakidetza, Basque Country, Spain) using a decision support system that integrated data envelopment analysis, Monte Carlo simulation and artificial intelligence. The unit of analysis was the 13 catchment areas defined by a reference MH centre. MH ecosystem performance was assessed by the following indicators: relative technical efficiency, stability and entropy to guide organizational interventions. Globally, the MH system of Gipuzkoa showed high efficiency scores in each main type of care (inpatient, day and outpatient), but it can be considered unstable (small changes can have relevant impacts on MH provision and performance). Both benchmark and target-for-improvement areas were identified and described. This article provides a guide for evidence-informed decision-making and policy design to improve the continuity of MH care after inpatient discharges. The findings show that it is crucial to design interventions and strategies (i) considering the characteristics of the area to be improved and (ii) assessing the potential impact on the performance of the global MH care ecosystem. For performance improvement, it is recommended to reduce admissions and readmissions for inpatient care, increase workforce capacity and utilization of day care services and increase the availability of outpatient care services.
Major efforts worldwide have been made to provide balanced Mental Health (MH) care. Any integrated MH ecosystem includes hospital and community-based care, highlighting the role of outpatient care in ...reducing relapses and readmissions. This study aimed (i) to identify potential expert-based causal relationships between inpatient and outpatient care variables, (ii) to assess them by using statistical procedures, and finally (iii) to assess the potential impact of a specific policy enhancing the MH care balance on real ecosystem performance. Causal relationships (Bayesian network) between inpatient and outpatient care variables were defined by expert knowledge and confirmed by using multivariate linear regression (generalized least squares). Based on the Bayesian network and regression results, a decision support system that combines data envelopment analysis, Monte Carlo simulation and fuzzy inference was used to assess the potential impact of the designed policy. As expected, there were strong statistical relationships between outpatient and inpatient care variables, which preliminarily confirmed their potential and a priori causal nature. The global impact of the proposed policy on the ecosystem was positive in terms of efficiency assessment, stability and entropy. To the best of our knowledge, this is the first study that formalized expert-based causal relationships between inpatient and outpatient care variables. These relationships, structured by a Bayesian network, can be used for designing evidence-informed policies trying to balance MH care provision. By integrating causal models and statistical analysis, decision support systems are useful tools to support evidence-informed planning and decision making, as they allow us to predict the potential impact of specific policies on the ecosystem prior to its real application, reducing the risk and considering the population's needs and scientific findings.
In Europe, sports food supplements (SSFs) are subject to specific laws and regulations. Up to 70% of athletes are highly influenced by the information on the label or the advertisement of the SSF, ...which often does not correspond to the scientific evidence, such as health claims. The aim is to analyze such claims relating to sports drinks (SDs) in commercial messages. To this end, an observational and cross-sectional study was conducted based on the analysis of the content and degree of adequacy of the health claims indicated on the labelling or technical data sheet of the SDs with those established by the European legislation in force according to the European Food Safety Authority (EFSA). The SSFs were searched for via Amazon and Google Shopping. A total of 114 health claims were evaluated. No claim fully conformed with the recommendations. A total of 14 claims (n = 13 products) almost conformed to the recommendations; they were “Maintain endurance level in exercises requiring prolonged endurance”, “Improve water absorption during physical exercise”, and “Improved physical performance during high intensity, high duration physical exercise in trained adults”, representing 12.3% of the total (n = 114). The vast majority of the claims identified indicated an unproven cause–effect and should be modified or eliminated, which amounts to food fraud towards the consumer.
The cytoplasmic protein tumor progression locus 2 (TPL2), also known as cancer Osaka thyroid (Cot), or MAP3K8, is thought to have a significant role in a variety of cancers and illnesses and it is a ...key component in the activation pathway for the expression of inflammatory mediators. Despite the tight connection between inflammation and TPL2, its function has not been extensively studied in chronic liver disease (CLD), a major cause of morbidity and mortality worldwide. Here, we analyze more in detail the significance of TPL2 in CLD to shed light on the pathological and molecular transduction pattern of TPL2 during the progression of CLD. This might result in important advancements and enable progress in the diagnosis and treatment of CLD.
Display omitted
•Chronic Liver Disease affects thousands of people worldwide without a treatment.•MAPKs are related with inflammation and their regulation can mitigate CLD advance.•TPL2 plays an important role in the expression of inflammatory mediators in immunity.•TPL2 could allow innovative strategies in the diagnosis and therapy of CLD.
A new underwater robot arm was developed through intensive cooperation between different academic institutions and an industrial company. The manipulator, which was initially designed to be ...teleoperated, was adapted for our autonomy needs. Its dimensions and weight were reduced, and its kinematic model was developed so that autonomous control can be performed with it. We compare several commercially available underwater manipulators and describe the development of the new one, from its initial configuration to its mechanical adaptation, modeling, control, and final assembly on an autonomous underwater vehicle (AUV). The feasibility and reliability of this arm is demonstrated in water tank conditions, where various innovative autonomous object-recovery operations are successfully performed, both in stand-alone operation and integrated in an AUV prototype.
The monoclonal antibody nirsevimab was at least 70% effective in preventing hospitalisations in infants with lower respiratory tract infections (LRTI) positive for respiratory syncytial virus (RSV) ...in Spain (Oct 2023-Jan 2024), where a universal immunisation programme began late September (coverage range: 79-99%). High protection was confirmed by two methodological designs (screening and test-negative) in a multicentre active surveillance in nine hospitals in three regions. No protection against RSV-negative LRTI-hospitalisations was shown. These interim results could guide public-health decision-making.
Decision-making in mental health systems should be supported by the evidence-informed knowledge transfer of data. Since mental health systems are inherently complex, involving interactions between ...its structures, processes and outcomes, decision support systems (DSS) need to be developed using advanced computational methods and visual tools to allow full system analysis, whilst incorporating domain experts in the analysis process. In this study, we use a DSS model developed for interactive data mining and domain expert collaboration in the analysis of complex mental health systems to improve system knowledge and evidence-informed policy planning.
We combine an interactive visual data mining approach, the self-organising map network (SOMNet), with an operational expert knowledge approach, expert-based collaborative analysis (EbCA), to develop a DSS model. The SOMNet was applied to the analysis of healthcare patterns and indicators of three different regional mental health systems in Spain, comprising 106 small catchment areas and providing healthcare for over 9 million inhabitants. Based on the EbCA, the domain experts in the development team guided and evaluated the analytical processes and results. Another group of 13 domain experts in mental health systems planning and research evaluated the model based on the analytical information of the SOMNet approach for processing information and discovering knowledge in a real-world context. Through the evaluation, the domain experts assessed the feasibility and technology readiness level (TRL) of the DSS model.
The SOMNet, combined with the EbCA, effectively processed evidence-based information when analysing system outliers, explaining global and local patterns, and refining key performance indicators with their analytical interpretations. The evaluation results showed that the DSS model was feasible by the domain experts and reached level 7 of the TRL (system prototype demonstration in operational environment).
This study supports the benefits of combining health systems engineering (SOMNet) and expert knowledge (EbCA) to analyse the complexity of health systems research. The use of the SOMNet approach contributes to the demonstration of DSS for mental health planning in practice.
Suicide is the second leading cause of death in adolescents and young adults aged 15 to 29 years. Specifically, the presence of internalizing and externalizing symptomatology is related to increased ...risk for suicide at these ages. Few studies have analyzed the relations between these symptoms and their role as mediators in predicting suicide behavior. This study aimed to examine the relation between internalizing and externalizing symptomatology and suicide behaviors through a longitudinal study. The sample consisted of 238 adolescents aged 12 to 18 years. The data were analyzed via the PROCESS Statistical Package. The main results showed that previous depression symptoms had a significant indirect effect, through previous suicide behaviors and current depression symptoms, on current suicide behaviors, accounting for 61% of the total variance explained. Additionally, being a girl increased this risk. Therefore, the implementation of early identification and intervention programs to address youth symptoms of depression and suicidal behaviors could significantly reduce the risk for future suicidal behaviors in adolescence.
PDF
