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At early stages, the corrosion behavior of Mg alloys used as implant materials plays a key role to ensure a safe implantation process. Therefore, the early electrochemical corrosion behavior of Mg–2Zn-0.6Zr-xNd alloys in a simulating orthopedic environment is investigated. Results show that the T2 and T3 phases have lower electronic work function (2.93–3.48 eV) compared to α-Mg, therefore they are more prone to lose electrons and act as anodes during micro-galvanic corrosion. The priority dissolution of secondary phases is conducive to the uniform degradation, and the corrosion activity is reduced under the synergy of protective corrosion product film. However, the film cannot provide a stable protection in the initial stage: its destruction and reconstruction are monitored at around 12 and 20 h, while corrosion current densities are gradually reduced and eventually fluctuate at about 5 μA cm−2. The microstructure, corrosion products, and corrosion activity evolution are interrelated and jointly affect the early electrochemical corrosion behavior of Mg–2Zn-0.6Zr-xNd alloy in a simulated orthopedic environment, among which the Mg–2Zn-0.6Zr-1.0Nd alloy exhibit better performance for the proposed application.

Abstract Multiple stressor research in aquaria is a useful approach to better understand the ecophysiology of marine species under different environmental conditions, including global change scenarios. Long‐term experiments are helpful to detect the response of sustained exposure to selected environmental conditions. Here, we present an experimental set‐up suitable to run long‐term experiments, composed of a life support system, a cost‐effective aquaria set‐up and an open‐source controller based on the use of a Raspberry Pi. In this set‐up, temperature, pH and dissolved oxygen (DO) are individually manipulated and simultaneously controlled in eight different treatments. To prove the efficacy of the set‐up, we provide an assessment over a nine‐month experiment on a deep‐sea coral species, combining values from current in situ and IPCC AR5 RCP 8.5 scenarios for the aforementioned parameters. Recorded data from the controllers and independent measurements (e.g. cross‐checking with portable multiparameter devices and laboratory analyses) throughout the experimental time have been analysed and results have been discussed. Overall, the experimental set‐up performed well, proving the stability of the parameters over time, both individually and in combination. On average, low and high‐temperature treatments varied ~0.4 and 0.3°C, respectively. Low pH treatments were maintained within 0.05 pH units, whereas ambient pH treatments varied ~0.04 pH units. Low DO treatments had a variation of ~0.3 mg L−1, and ambient DO treatments varied ~0.2 mg L−1. No significant differences between scenarios for any parameter were detected (p

Trypanosoma vivax displays distinct mitochondrial genomes: intact in Africa and degraded in South America. This finding, formerly reported from four isolates, suggested an association between mitochondrial mutations and adaptation to exclusive mechanical transmission outside Africa, circumventing mitochondrial activity essential for cyclical transmission by tsetse flies. Here, we characterized the mitochondrial ND7 and COIII genes in 25 South American isolates of T. vivax from livestock from Argentina, Brazil, Colombia, Ecuador, and Venezuela, as well as in 11 African isolates from Mozambique, Ethiopia, Uganda, Nigeria, and Burkina Faso from tsetse flies, antelopes, and cattle. Phylogenetic inference supported the lineages TVV (Trypanosoma vivax vivax) and TVL (Trypanosoma vivax-like), predominant in South America/West Africa and East Africa, respectively. Both ND7 and COIII genes were intact in all African TVV and TVL isolates and, for the first time, in 10 South American isolates from Brazil. Remaining South American isolates exhibited some degree of gene erosion, including ~142 bp deletion at the 3′ end of ND7 disclosed in Venezuela and Colombia, ~163 bp deletion at the 3′ end of ND7 in Brazil and Argentina, and ~750 bp deletion from the 5′ end of ND7 to the 3′ end of COIII in Venezuela. Comprehensive analyses of whole mitochondrial genomes from additional South American and African isolates are crucial for formulating reliable hypotheses regarding the origin, absence, and rapid mitochondrial degradation observed in South American T. vivax.

Reading official letters and being able to react to them appropriately is part of the daily life of every adult in many countries. Although the history of the plain language movement dates to the past century, it is only now that efforts are being made in Poland to adapt official documents to their audience. In this paper, we describe the results of a study (N = 685) in which we examined how particular linguistic forms and text structure affect the reception of an official-looking text – comprehension as well as emotions experienced, trust in the office, feelings of helplessness in the situation of reading the writing, and many other variables. Based on Imbir’s (2016, New Ideas in Psychology, 43, 39–49), two-system theory of emotions, we aim to examine how emotions – triggered by these complex stimuli – affect their processing. We hope that the results of our interdisciplinary research will answer the questions and hypotheses posed by researchers and find application in the reforms currently underway. We believe that by linking findings from cognitive psychology, the psychology of emotions and linguistics, we will also expand knowledge in the broad discussion on overcoming barriers between administrative offices and target audiences.

Abstract The CARLO (cold ablation robot-guided laser osteotome) is a compact device with integrated multiple sensory, steering and safety checking elements. A multi-center study was performed to evaluate the CARLO device for the linear part of midface osteotomy in 28 patients. Feasibility, success rate, safety, performance and experience of the surgeons were assessed and evaluated. All 28 procedures were completed with CARLO without falling back to the conventional methods, giving a technical success rate of 100%. For 27 (96%) cases, procedural success was achieved with cutting lines deviation less than 2 mm. For 25 procedures, the CARLO-cutting was conducted smoothly. In the other 3 cases, some minor difficulties related to the reference markers were reported. For 18 procedures, no change for the cutting path was necessary. For the other 10 cases, cut path was adapted. Intraoperative re-planning was possible, easy and quick without significant delay of the procedures. No CARLO-related adverse events were recorded. Especially, there was no unexpected and unusual bleeding during the CARLO-conducted osteotomy. The time needed for the registration ranged from 1 to 12 min (median = 4). The CARLO-cutting lasted for 5 to 21 min (median = 7). The present study demonstrated feasibility, simplicity, safety, reliability and accuracy of CARLO for the linear part of midface osteotomy.

Abstract Heart failure is a highly prevalent disease, which courses with frequent readmissions, mainly by Acute Heart Failure (AHF). Reduced renal function is associated with increased mortality in patients with HF. Therefore, an accurate and precise evaluation of renal function in patients with HF is crucial. The error of estimated GFR (eGFR) is wide and common, showing a ± 30% variability compared to measured GFR (mGFR). However, there is no evidence on the error of formulas in reflecting real renal function and particularly the consequences of this error in patients with AHF. This is a prospective study comparing the impact of mGFR versus eGFR in the onset of cardiovascular (CV) outcomes in patients with AHF. This was tested with cox survival analysis. Measured GFR was determined by the plasma clearance of iohexol-dbs and eGFR by Cockroft-Gould, MDRD, CKD-EPI creatinine, CKD-EPI cystatin-C and CKD-EPI creatinine + cystatin-C equations formulas. Also the agreement between mGFR and eGFR was analyzed. A total of 90 patients were included. Average age was 66 (± 12 years) and 52 (58%) were male. Of them 53 patients (59%) had a cardiovascular event during follow-up, 22 fatal (41%). The agreement between mGFR and eGFR indicated moderate precision and accuracy (concordance correlation coefficient of 0.77; CI = 0.73–0.82). In multiple cox survival analysis, mGFR was significantly associated with cardiovascular events together with NTproBNP, BMI, LVEF and previous coronary artery disease (p = 0.037; HR = 0.98, 95% CI = 0.95–0.99). Estimated GFR by formulas was not significant. In patients with AHF the error of formulas is large, frequent and random, also, mGFR and not eGFR predicted future CV events. The error of eGFR may have clinical consequences in specific subpopulations.

There has been a rapid expansion in the quantity and complexity of data, information and knowledge created in the behavioural and social sciences, yet the field is not advancing understanding, practice or policy to the extent that the insights warrant. One challenge is that research often progresses in disciplinary silos and is reported using inconsistent and ambiguous terminology. This makes it difficult to integrate and aggregate findings to produce cumulative bodies of knowledge that can be translated to applied settings. Ontologies can address these challenges; their development and use have the potential to accelerate the behavioural and social sciences. Ontologies can facilitate communication through precise specification and dissemination of terms, and enable efficient data integration, sharing, comparison and analysis. The widespread use of ontologies in the biomedical and biological sciences has led to multiple successes. It is time now for the behavioural and social sciences to follow that lead. In recent years, a number of ontologies have been developed within the behavioural and social sciences; however, efforts have tended to be isolated, with limited resources to support developers and those who work (or would like to work) with and use ontologies. There is a need for coordination and exchange to reduce duplication of work and leverage the value of a community to support the interoperability of these ontologies (linking of entities across domains and datasets). We have therefore initiated the Behavioural and Social Sciences Ontology (BSSO) Foundry, a community of practice and online repository for the development, adoption and use of ontologies in the behavioural and social sciences. The BSSO Foundry aligns with and builds upon the model provided by the Open Biological and Biomedical Ontology Foundry. We describe this new initiative and how to join and contribute to the community of interoperable ontologies for the behavioural and social sciences.

Background and ObjectiveIn recent years, the consumption of fish products has led to a worrying trend where approximately two-thirds of the total amount of fish is discarded as waste. At the same time, scientific interest in exploring natural collagen sources for cosmetics and dietary supplements has increased. This study explores the potential of valorizing sardine scales (Sardina pilchardus), a by-product of the canning industry, through the extraction of collagen for potential use in dermocosmetic formulations and food supplements.MethodsCollagen from sardine scales was obtained though acid and enzymatic extraction. The collagen extracts were characterized by UV-Vis, FTIR spectroscopy, SDS-PAGE, powder X-ray diffraction (PXRD) and scanning electron microscopy (SEM). The collagen was hydrolysed with papain to small peptides. Subsequently, the biological activities of acid-soluble collagen as well as the collagen peptides in terms of antioxidant and antimicrobial activity were evaluated. Furthermore, the capacity of collagen peptides to permeate the intestinal barrier, simulated with caco-2 cells, was evaluated.ResultsPurified collagen extracts were obtained from sardine scales, with enzymatic extraction method having a yield three times higher than the acid method. The SDS-PAGE analysis confirmed the extraction of type I collagen as well as its hydrolysis into small fragments (25–12 kDa). In terms of biological activities, collagen and collagen peptides have not demonstrated antimicrobial activity. However, regarding antioxidant activity, collagen peptides showed three times more capacity compared to non-hydrolyzed collagen. Meanwhile, in 6 h, about 6.37% of collagen peptides could permeate the intestinal barrier.ConclusionThis work represents a continuous effort to advance our understanding and utilization of Portuguese marine waste resources, with focus on the valorization of sardine co-products for the development of food supplement or cosmetic formulations, contributing to the sustainable evolution of the circular blue economy.

Background and Purpose: Radiotherapy for paediatric posterior fossa tumours may cause complications in the brainstem and upper spinal cord due to high doses. With proton therapy (PT) this risk may increase due to higher relative biological effectiveness (RBE) from elevated linear energy transfer (LET). This study assesses variations in LET in the brainstem and spinal cord in proton treatment plans from European centres. Materials and Methods: Ten European PT centres using spot-scanning PT planned two paediatric posterior fossa cases: One overlapping partly with the brainstem and upper spinal cord, prescribed 54 Gy(RBE), and the second wrapping around these organs, prescribed 59.4 Gy(RBE). Dose-averaged LET distributions were assessed in volumes of the brainstem and spinal cord irradiated to over 50 Gy(RBE = 1.1). The maximum hinge angle effect on near-maximum RBE-weighted doses using the Unkelbach RBE model was also investigated. Results: In the first case, the mean LET in brainstem volumes receiving more than 50 Gy(RBE = 1.1) ranged from 2.8 keV/µm to 3.6 keV/µm across centres (median: 3.3 keV/µm). In the second case, treatment plans showed a narrower range of mean LET in the brainstem, from 2.5 keV/µm to 2.8 keV/µm (median: 2.7 keV/µm). There was no statistically significant impact of the maximum hinge angle. Conclusions: LET distributions vary across centres due to different techniques but are also influenced significantly by factors like shape and position of the target volume.

Background: Some cancer survivors experience difficulties with concentration, attention, and memory; however, there are no studies on neurodevelopment in patients under 5 years of age who are undergoing cancer treatment. Our aim was to evaluate neurodevelopment in cancer patients under 5 years of age using the Early Development Instrument (EDI) test, considering factors such as nutritional status, type of cancer, and treatment effect. Methods: A cross-sectional study was conducted from February 2018 to March 2019. Patients with cancer diagnoses outside the central nervous system in any phase of cancer treatment were included. Results: A total of 45 patients were included. Regarding fine motor skills, 28% of patients with retinoblastoma and 23% of patients with leukemia or lymphoma had a risk of developmental delay compared to 0% of patients with solid tumors (p = 0.025). The final results showed that 19 (42.2%) patients had normal neurodevelopment (gray), 7 (15.5%) had a delay in neurodevelopment (light gray), and 19 (42.2%) had a risk of developmental delay (black). Regarding developmental delay, 52% of patients in the leukemia and lymphoma group, 71% in the retinoblastoma group, and 23% in the solid tumor group presented developmental delay (p = 0.06). Conclusions: The risk of delay and lag in neurodevelopment is common in cancer patients under 5 years of age undergoing treatment. However, more studies are required to evaluate the effect of treatment on this group of patients as it may be affected by various factors.

Oncolytic viruses (OVs) are biological therapeutic agents that selectively destroy cancer cells while sparing normal healthy cells. Besides direct oncolysis, OV infection induces a proinflammatory shift in the tumor microenvironment and the release of tumor‐associated antigens (TAAs) that might induce an anti‐tumor immunity. Due to their immunostimulatory effect, OVs have been explored for cancer vaccination against specific TAAs. However, this approach usually requires genetic modification of the virus and the production of a new viral vector for each target, which is difficult to implement for low prevalent antigens. In a recent study, Chiaro et al. presented an elegant proof of concept on how to implement the PeptiCRAd vaccination platform to overcome this limitation for the treatment of mesothelioma. Authors showed the feasibility of identifying immunogenic TAAs in human mesothelioma and using them to coat oncolytic adenovirus particles. The result was a customized virus‐based cancer vaccine that circumvents time and resource‐consuming steps incurred from genetically engineering viruses. Although some questions remain to be addressed, this interesting approach suggests novel strategies for personalized cancer medicine using oncolytic virotherapy.

Abstract Background Recurrences of low back pain (LBP) are frequent and associated with high levels of disability and medical costs. Regular exercise practice may be an effective strategy to prevent recurrences of LBP, however, the promotion of this behaviour by physiotherapists seems to be challenging. This study aims to explore physiotherapists’ perceived barriers and facilitators to the implementation of a behaviour change-informed exercise intervention to promote the adoption of regular exercise practice by patients at risk of recurrence of low back pain. Methods Two focus groups with primary healthcare physiotherapists were conducted, based on a semi-structured interview schedule informed by the Behaviour Change Wheel, including the Capability, Opportunity, Motivation–Behaviour (COM-B) model and the Theoretical Domains Framework (TDF). All focus groups were held through videoconference, audio and video recorded and transcribed verbatim. A deductive content analysis, using a coding matrix based on the COM-B and TDF, was performed by two independent researchers. A third researcher was approached to settle disagreements. Results In total, 14 physiotherapists participated in the focus groups. The analysis revealed a total of 13 barriers (4 COM-B components and 7 TDF domains) and 23 facilitators (5 COM-B and 13 TDF) to physiotherapists’ implementation of a behaviour change-informed exercise intervention. The most common barriers were the lack of skills and confidence to implement the proposed intervention. These were explained by the fact that it differs from the usual practice of most participants and requires the learning of new skills applied to their contexts. However, for those who had already implemented other similar interventions or whose rationale is aligned with the new intervention, there seemed to exist more positive determinants, such as potential benefits for physiotherapists and the profession, improvement of quality of care and willingness to change clinical practice. For others who did not previously succeed in implementing these types of interventions, more context-related barriers were mentioned, such as lack of time to implement the intervention, schedule incompatibilities and lack of material and human resources. Conclusions This study identified modifiable barriers and facilitators to physiotherapists’ implementation of a behaviour change-informed exercise intervention for patients at risk of recurrence of LBP in primary healthcare. The findings of this study will allow the systematic and theory-based development of a behaviour change-informed training programme, aimed at physiotherapists and supporting the successful implementation of the exercise intervention.

Aim: The aim of this study was to evaluate the relationship between oral hygiene (OH) efficiency and manual dexterity skills in Spanish five-year-old children using two fine motor tests. Methods: A cross-sectional study with a pre–post evaluation was designed. The children’s OH was measured according to the Silness and Löe plaque index (PI) before toothbrushing upon arrival at school (pre) and after supervised toothbrushing (post). Motor skills (children’s dexterity) were determined with the Visual Motor Skills and Resistance to Fatigue test (VMSRF test) and the scale for the Behavioural Assessment of Preschool Skills (BAPS scale). Data were analysed with the SPSS® statistics software with a 95% confidence interval and bilateral significance. Results: One hundred and twenty-nine children were evaluated. The mean PI was 2.5, indicating generally poor OH in the sample. No difference in OH was observed between genders or in the brushing frequency categories. No significant differences in OH or the PI were found between right- and left-handed children either (p > 0.05). Significant differences were found between the OH category pre and post toothbrushing in the total sample, as well as in the various sextants and surfaces evaluated. The results of the VMSRF and BAPS tests indicate moderate visuomotor skills and fatigue resistance and a poor average skill level. A statistically significant improvement in the PI was found in children with higher scores in the VMSRF and BAPS tests. Conclusions: A significantly higher OH efficacy was found in children with better motor skills, although five-year-old children showed moderate visuomotor skills and fatigue resistance and a poor average preschool skill level.

Peroxisomes are organelles involved in many cellular metabolic functions, including the degradation of very-long-chain fatty acids (VLCFAs; C ≥ 22), the initiation of ether-phospholipid synthesis, and the metabolism of reactive oxygen species. All of these processes are essential for the maintenance of cellular lipid and redox homeostasis, and their perturbation can trigger inflammatory response in immune cells, including in the central nervous system (CNS) resident microglia and astrocytes. Consistently, peroxisomal disorders, a group of congenital diseases caused by a block in peroxisomal biogenesis or the impairment of one of the peroxisomal enzymes, are associated with neuroinflammation. Peroxisomal function is also dysregulated in many neurodegenerative diseases and during brain aging, both of which are associated with neuroinflammation. This suggests that deciphering the role of peroxisomes in neuroinflammation may be important for understanding both congenital and age-related brain dysfunction. In this review, we discuss the current advances in understanding the role and function of peroxisomes in neuroinflammation.

Abstract Purpose Preventing weight regain can only be achieved by sustained changes in energy balance-related behaviors that are associated with weight, such as diet and physical activity. Changes in motivation and self-regulatory skills can support long-term behavioral changes in the context of weight loss maintenance. We propose that experiencing a supportive climate care is associated with enhanced satisfaction of basic psychological needs, intrinsic goals, and autonomous motivation. These factors are expected to be associate with the utilization of self-regulation skills, leading to more sustained behavior changes and ultimately preventing weight regain. This hypothesis was tested in this ancillary analysis of the NoHoW trial, where the study arms were pooled and followed for 12 months. Methods The NoHoW was a three-center, large-scale weight regain prevention full factorial trial. In this longitudinal study, data were collected in adults who lost > 5% weight in the past year (N = 870, complete data only, 68.7% female, 44.10 ± 11.86 years, 84.47 ± 17.03 kg) during their participation in a 12-month digital behavior change intervention. Weight and validated measures of motivational- and self-regulatory skills-related variables were collected at baseline, six- and 12 months. Change variables were used in Mplus’ path analytical models informed by NoHoW’s logic model. Results The bivariate correlations confirmed key mediators’ potential effect on weight outcomes in the expected causal direction. The primary analysis showed that a quarter of the variance (r2 = 23.5%) of weight regain prevention was achieved via the mechanisms of action predicted in the logic model. Specifically, our results show that supportive climate care is associated with needs satisfaction and intrinsic goal content leading to better weight regain prevention via improvements in self-regulatory skills and exercise-controlled motivation. The secondary analysis showed that more mechanisms of action are significant in participants who regained or maintained their weight. Conclusions These results contribute to a better understanding of the mechanisms of action leading to behavior change in weight regain prevention. The most successful participants used only a few intrinsic motivation-related mechanisms of action, suggesting that habits may have been learned. While developing a digital behavior change intervention, researchers and practitioners should consider creating supportive climate care to improve needs satisfaction and intrinsic goal contents. Trial registration ISRCTN, ISRCTN88405328 , registered 12/22/2016.

Despite decades of research, the prognosis of high-grade pediatric brain tumors (PBTs) remains dismal; however, recent cases of favorable clinical responses were documented in clinical trials using oncolytic viruses (OVs). In the current study, we employed four different species of OVs: adenovirus Delta24-RGD, herpes simplex virus rQNestin34.5v1, reovirus R124, and the non-virulent Newcastle disease virus rNDV-F0-GFP against three entities of PBTs (high-grade gliomas, atypical teratoid/rhabdoid tumors, and ependymomas) to determine their in vitro efficacy. These four OVs were screened on 14 patient-derived PBT cell cultures and the degree of oncolysis was assessed using an ATP-based assay. Subsequently, the observed viral efficacies were correlated to whole transcriptome data and Gene Ontology analysis was performed. Although no significant tumor type-specific OV efficacy was observed, the analysis revealed the intrinsic biological processes that associated with OV efficacy. The predictive power of the identified expression profiles was further validated in vitro by screening additional PBTs. In summary, our results demonstrate OV susceptibility of multiple patient-derived PBT entities and the ability to predict in vitro responses to OVs using unique expression profiles. Such profiles may hold promise for future OV preselection with effective oncolytic potency in a specific tumor, therewith potentially improving OV responses.

Background The Behaviour Change Technique Taxonomy v1 (BCTTv1) specifies the potentially active content of behaviour change interventions. Evaluation of BCTTv1 showed the need to extend it into a formal ontology, improve its labels and definitions, add BCTs and subdivide existing BCTs. We aimed to develop a Behaviour Change Technique Ontology (BCTO) that would meet these needs. Methods The BCTO was developed by: (1) collating and synthesising feedback from multiple sources; (2) extracting information from published studies and classification systems; (3) multiple iterations of reviewing and refining entities, and their labels, definitions and relationships; (4) refining the ontology via expert stakeholder review of its comprehensiveness and clarity; (5) testing whether researchers could reliably apply the ontology to identify BCTs in intervention reports; and (6) making it available online and creating a computer-readable version. Results Initially there were 282 proposed changes to BCTTv1. Following first-round review, 19 BCTs were split into two or more BCTs, 27 new BCTs were added and 26 BCTs were moved into a different group, giving 161 BCTs hierarchically organised into 12 logically defined higher-level groups in up to five hierarchical levels. Following expert stakeholder review, the refined ontology had 247 BCTs hierarchically organised into 20 higher-level groups. Independent annotations of intervention evaluation reports by researchers familiar and unfamiliar with the ontology resulted in good levels of inter-rater reliability (0.82 and 0.79, respectively). Following revision informed by this exercise, 34 BCTs were added, resulting in the first published version of the BCTO containing 281 BCTs organised into 20 higher-level groups over five hierarchical levels. Discussion The BCTO provides a standard terminology and comprehensive classification system for the content of behaviour change interventions that can be reliably used to describe interventions. The development and maintenance of an ontology is an iterative and ongoing process; no ontology is ever ‘finished’. The BCTO will continue to evolve and grow (e.g. new BCTs or improved definitions) as a result of user feedback and new available evidence.

INTRODUCTION: Carotid revascularization is a well-established technique for preventing stroke in patients with significant symptomatic or asymptomatic carotid artery stenosis. Carotid artery stenting (CAS) has become an alternative to carotid endarterectomy (CEA), especially in high-risk surgical patients. However, restenosis after CAS is a potentially severe complication that can impact the medium and long-term success of the procedure and increase the risk of cerebrovascular events. METHODS: Relevant articles on restenosis after carotid stenting were searched in the PubMed database. The selected studies were evaluated for quality and relevance, and the information was summarized to provide an overview of the causes, risk factors, diagnosis, and treatment options for restenosis after CAS due to atherosclerotic carotid artery disease. RESULTS: Restenosis after CAS can occur due to various factors, including thrombosis, intimal hyperplasia, and stent migration. Several risk factors have been identified, such as age, diabetes, hypertension, dyslipidemia, and smoking. Restenosis can be diagnosed with carotid Doppler ultrasound, contrast-enhanced computed tomography, or arteriography. Treatment options include angioplasty with or without rescue stent placement, CEA associated with stent explantation, or medical treatment. CONCLUSION: Restenosis after carotid stenting is a potentially serious complication. It is especially important to identify the risk factors for restenosis and maintain close follow-up with patients after the procedure. The treatment of restenosis should be individualized. Further studies are needed to define the best strategies for preventing and treating restenosis after carotid stenting.

Hydroxyapatite (HAp) is a widely used biocompatible material in orthopedic composite preparations. However, HAp composites that exhibit both anticancer and antibacterial activities through bioactive coordination complexes are relatively rare. To explore orthopedic applications, we blended several silver camphorimine compounds with HAp to create [Ag(I)] composites. All compounds [Ag(NO3)(L)n] (n = 1,2) based on camphorimine (LA), camphor sulfonimine (LB) or imine bi-camphor (LC) ligands demonstrated significant cytotoxic activity (IC50 = 0.30–2.6 μgAg/mL) against osteosarcoma cancer cells (HOS). Based on their structural and electronic characteristics, four complexes (1–4) were selected for antibacterial evaluation against Escherichia coli, Burkholderia contaminans, Pseudomonas aeruginosa, and Staphylococcus aureus. All complexes (1–4) revealed combined anticancer and antibacterial activities; therefore, they were used to prepare [Ag(I)]:HAp composites of 50:50% and 20:80% weight compositions and the activities of the composites were assessed. Results showed that they retain the dual anticancer and antibacterial characteristics of their precursor complexes. To replicate the clinical context of bone-filling applications, hand-pressed surfaces (pellets) were prepared. It is worth highlighting that no agglutination agent was necessary for the pellet’s consistency. The biological properties of the so-prepared pellets were assessed, and the HOS cells and bacteria spreading on the pellet’s surface were analyzed by SEM. Notably, composite 4B, derived from the bicamphor (LC) complex [Ag(NO3)(OC10H14N(C6H4)2NC10H14O)], exhibited significant anticancer activity against HOS cells and antibacterial activity against P. aeruginosa, fostering potential clinical applications on post-surgical OS treatment.

Summary: The immune response is a fundamental process in the treatment of solid tumors. Here, we present a protocol for implanting diffuse midline glioma cells in the brain of immune-competent mice and characterizing the different immune populations in the tumor microenvironment in a flow cytometry panel. We describe steps for processing of brain tumors, isolating the immune cells, and subsequent staining with antibodies for flow cytometry. We then detail procedures for implementing the gating strategy.For complete details on the use and execution of this protocol, please refer to Ausejo-Mauleon et al.1 : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

Background The Behaviour Change Techniques Taxonomy v1 (BCTTv1) is the most widely used classification of behaviour change techniques (BCTs), contributing to the accurate report and evaluation of behaviour change interventions and accumulation of evidence. This study reports a structured approach to adapt the BCTTv1 into European Portuguese (BCTTv1-PT). Methods A collaborative and iterative approach was used. The translation process encompassed four phases: (1) independent forward translation by two native Portuguese speakers proficient in English, (2) forward translation reconciliation, (3) expert consultation by involving seven experts in behaviour change to collect feedback on the draft version of the taxonomy through a structured online form; and (4) feedback analysis and improvement of the BCTTv1-PT. Results Independent forward translations and a reconciled version of the BCTTv1-PT were produced. All experts agreed with the groupings designation (100%). Recommendations were made to improve BCTs labels, definitions and/or examples in all groupings, except for Feedback and monitoring. Experts disagreed with the translated definitions in 40.9% of the BCTs (38/93), with examples in 21.5% (20/93) and with labels in 11.8% (11/93). Recommendations were made for all instances where there was disagreement (n = 69) and were enacted entirety, yielding the final version (BCTTv1-PT). Conclusions Researchers, educators, students and health and other professionals will be able to standardise terminology and have a common language, contributing to the impact of the BCTTv1-PT. This study presents a systematic and rigorous approach for the adaptation of the BCTTv1 and similar taxonomies, which may guide others.

Background: Langerhans cell histiocytosis (LCH) is a rare neoplastic disease characterized by clonal proliferation of dendritic cells. It is Mexico’s ninth most frequent malignancy in patients under 18 years of age. The aim of the study was to determine the clinical characteristics, treatment, and survival of Mexican pediatric patients diagnosed with LCH treated from January 2010 to December 2018. Methods: We conducted a retrospective study of LCH using data from 19 accredited hospitals throughout the Mexican Republic. Patients < 18 years who were diagnosed with LCH between January 2010 and December 2018 were included (253 patients) in the study. Results: All patients had a histopathological diagnosis, and extension studies were performed at their treatment centers. The median age at diagnosis was 19 months. The most frequently affected sites included the bone (178 cases; 70%) and the skin (131 cases; 51.7%). Of the patients in Group 1, 48 (42%) had bone marrow involvement, 62 (53%) had splenomegaly, and 39 (34.8%) had liver involvement. Of the patients who underwent chemotherapy treatment, 61.2% exhibited a complete response, and 36 patients (14.2%) relapsed after complete remission. The most frequent sites of relapse were the skin, bone, lymph nodes, and liver. The overall survival rate was 91.3% and was lower for patients in Group 1 (77%) compared with those in Groups 2 (97%) and 3 (100%), p = 0.001. Conclusion: The current report aims to demonstrate the findings of a multicenter study conducted on Mexican children with LCH; consequently, these treatment results for a relatively infrequent disease merit further research.

The use of lactic acid bacteria as a low-cost sustainable management tool to prevent further build-up of Fusarium mycotoxins during grain storage is increasingly propagated. It has been reported that even deoxynivalenol contamination already formed in the field can be reduced by such treatment in unknown ways. An enigmatic deoxynivalenol derivative, 3-lactyl-deoxynivalenol, has been reported already in 1982 as the toxic principle of Fusarium-infected barley from China, but very little is known about this metabolite. Here, we show that the enzymatic machinery of Fusarium graminearum is sufficient for its biosynthesis. Similarly, when challenged with propionic acid, F. graminearum can form a novel modified mycotoxin, 3-propionyl-deoxynivalenol. Lactic acid and propionic acid are first converted into lactyl-CoA and propionyl-CoA, respectively. These acyl-CoA derivatives can subsequently be used by the 3-O-acyltransferase encoded by TRI101. We expressed the respective genes in E. coli and utilized the affinity-purified proteins for enzymatic synthesis of the reference substances 3-lactyl- and 3-propionyl-deoxynivalenol. The structures of the purified compounds were confirmed by nuclear magnetic resonance spectroscopy. Preliminary toxicological assessment using in vitro translation assays indicated residual toxicity, most likely due to reactivation of deoxynivalenol by de-acylation. In conclusion, this study reports a method to synthesize 3-lactyl- and 3-propionyl-deoxynivalenol reference substances, which will be highly useful to determine occurrences of these acylated deoxynivalenol-derivatives in cereal samples and to perform more detailed studies to evaluate their toxicological relevance.

Abstract Advancements in artificial intelligence (AI) are enabling the development of clinical support tools (CSTs) in psychiatry to facilitate the review of patient data and inform clinical care. To promote their successful integration and prevent over-reliance, it is important to understand how psychiatrists will respond to information provided by AI-based CSTs, particularly if it is incorrect. We conducted an experiment to examine psychiatrists’ perceptions of AI-based CSTs for treating major depressive disorder (MDD) and to determine whether perceptions interacted with the quality of CST information. Eighty-three psychiatrists read clinical notes about a hypothetical patient with MDD and reviewed two CSTs embedded within a single dashboard: the note’s summary and a treatment recommendation. Psychiatrists were randomised to believe the source of CSTs was either AI or another psychiatrist, and across four notes, CSTs provided either correct or incorrect information. Psychiatrists rated the CSTs on various attributes. Ratings for note summaries were less favourable when psychiatrists believed the notes were generated with AI as compared to another psychiatrist, regardless of whether the notes provided correct or incorrect information. A smaller preference for psychiatrist-generated information emerged in ratings of attributes that reflected the summary’s accuracy or its inclusion of important information from the full clinical note. Ratings for treatment recommendations were also less favourable when their perceived source was AI, but only when recommendations were correct. There was little evidence that clinical expertise or familiarity with AI impacted results. These findings suggest that psychiatrists prefer human-derived CSTs. This preference was less pronounced for ratings that may have prompted a deeper review of CST information (i.e. a comparison with the full clinical note to evaluate the summary’s accuracy or completeness, assessing an incorrect treatment recommendation), suggesting a role of heuristics. Future work should explore other contributing factors and downstream implications for integrating AI into psychiatric care.

Abstract Background Despite an existing body of literature on anxiety reduction using multi-component methods, little is known about the effect of active student participation in research and communication of scientific information on anxiety and fear reduction. The aim of this study is to evaluate the impact of quality scientific information research and the production of informative videos on the preventive aspects of COVID-19 on fear and anxiety reduction. Methods A randomised controlled trial was conducted with 220 undergraduate nursing students in the first year of the nursing degree. The participating students were randomised into two groups. The experimental group carried out an intervention based on a database search for information on preventing COVID-19 and production of a video giving scientific reasons why prevention measures should be followed. In the control group, students created posters and videos about theoretical aspects of one module of the nursing degree. Both groups were surveyed before and after the intervention, measuring their state of resilience, preventive behaviours, level of anxiety, and fear of COVID-19. Results The intervention group showed a greater decrease in fear levels after the intervention than those in the control group. There were no differences between the groups in terms of resilience, preventive behaviours, or anxiety. In the experimental group, there was a significant decrease in anxiety levels and fear levels after the intervention compared to the baseline levels. Conclusions An intervention based on active participation in searches for high-quality scientific information and production of information videos on COVID-19 prevention reduced fear and anxiety caused by COVID-19 among nursing students. Trial registration We have retrospectively registered the trial in Open Science Framework and the identification number is https://doi.org/10.17605/OSF.IO/6QU5S .

Abstract The ability to synchronise with other people is a core socio-motor competence acquired during human development. In this study we aimed to understand the impact of individual emotional arousal on joint action performance. We asked 15 mixed-gender groups (of 4 individuals each) to participate in a digital, four-way movement synchronisation task. Participants shared the same physical space, but could not see each other during the task. In each trial run, every participant was induced with an emotion-laden acoustic stimulus (pre-selected from the second version of International Affective Digitized Sounds). Our data demonstrated that the human ability to synchronise is overall robust to fluctuations in individual emotional arousal, but performance varies in quality and movement speed as a result of valence of emotional induction (both on the individual and group level). We found that three negative inductions per group per trial led to a drop in overall group synchronisation performance (measured as the median and standard deviation of Kuramoto’s order parameter—an index measuring the strength of synchrony between oscillators, in this study, players) in the 15 sec post-induction. We report that negatively-valenced inductions led to slower oscillations, whilst positive induction afforded faster oscillations. On the individual level of synchronisation performance we found an effect of empathetic disposition (higher competence linked to better performance during the negative induction condition) and of participant’s sex (males displayed better synchronisation performance with others). We believe this work is a blueprint for exploring the frontiers of inextricably bound worlds of emotion and joint action, be it physical or digital.

Curcumin, a phytochemical, exhibits several biological properties and has been studied for the treatment of psoriasis. To facilitate its transdermal permeation, permeation enhancers such as choline and geranic acid ionic liquid (CAGE-IL) have been studied. From this perspective, the research effort entertained herein aimed at developing and evaluating the stability of an emulsion prepared with curcumin (phytochemical from Curcuma longa L.) and locust bean gum (extracted from the seeds of the carob tree, Ceratonia siliqua), with CAGE-IL as a facilitator of transdermal permeation. Stability studies were carried out for six months, with analyses being performed at time intervals of 0 (24 h), 30, 60, 90, and 180 days. The samples were kept at 40 ± 2 °C, with 75 ± 5% relative humidity (RH). The parameters analyzed were morphological characteristics, pH (5.8-6.0), and spreadability. The samples were shown to be stable during the timeframe studied, maintaining adequate physicochemical characteristics and meeting quality specifications for cutaneous applications. CAGE-IL, in addition to facilitating permeation of the active substance, also favored the formation of a stable emulsion encompassing nanosized particles (134.3 ± 2.6 nm) in a simple fashion and with only a few components.

Abstract Introduction Ontologies are a formal way to represent knowledge in a particular field and have the potential to transform the field of health promotion and digital interventions. However, few researchers in physical activity (PA) are familiar with ontologies, and the field can be difficult to navigate. This systematic review aims to (1) identify ontologies in the field of PA, (2) assess their content and (3) assess their quality. Methods Databases were searched for ontologies on PA. Ontologies were included if they described PA or sedentary behavior, and were available in English language. We coded whether ontologies covered the user profile, activity, or context domain. For the assessment of quality, we used 12 criteria informed by the Open Biological and Biomedical Ontology (OBO) Foundry principles of good ontology practice. Results Twenty-eight ontologies met the inclusion criteria. All ontologies covered PA, and 19 included information on the user profile. Context was covered by 17 ontologies (physical context, n = 12; temporal context, n = 14; social context: n = 5). Ontologies met an average of 4.3 out of 12 quality criteria. No ontology met all quality criteria. Discussion This review did not identify a single comprehensive ontology of PA that allowed reuse. Nonetheless, several ontologies may serve as a good starting point for the promotion of PA. We provide several recommendations about the identification, evaluation, and adaptation of ontologies for their further development and use.

Abstract Background Spain as multiple other countries has been experiencing an increasing and sustained trend in the use of psychotropic medications since the mid 90s. Recent studies show public health measures implemented to control SARS-Cov2, such as mobility restrictions and the shutdown of nonessential activities increased mental suffering, even contributing to a higher number of anxiety, depression and insomnia disorders that could lead to an increase in the consumption of psychotropics. The aims were: 1) Evaluate the temporal trend in psychotropic consumption by pharmacological subgroup, sex, and age group 2) Estimate the effect of the COVID-19 pandemic in the use of psychotropic drugs. Methods We conducted a retrospective observational study, retrieving all prescriptions of anxiolytics, hypnotics and sedatives, and antidepressants dispensed in pharmacies of Asturias (Northern Spain) for Primary Care patients for the period 2018–2021. We presented the data expressed in Daily Defined Doses (DDDs) for 1000 persons/day (DHD). To estimate changes in DHDs by year and age group we conducted two multiple linear regressions (one for males and one for females) for every pharmacological subgroup studied. Changes were considered statistically significant when the regression coefficient was p

Incorporating switched-capacitor structures into isolated dc-dc converters is a promising approach to alleviate the limitations of topologies fully based on the use of high step-down transformers. In this paper, the combination of a forward converter with a series-capacitor structure is proposed for applications that require a very high step-down conversion ratio, low output voltage ripple, high output current and isolation. The result of the combination only adds one series-capacitor, one inductor, one switch and one diode (or synchronous rectifier switch) to the component count of a conventional forward converter, thus avoiding the use of a complete second phase. The topology provides high step-down conversion ratio and low output voltage ripple, a characteristic that can be used to decrease the total energy stored by inductors (i.e., higher power density) and/or to reduce the switching frequency (i.e., higher efficiency). Moreover, the converter provides inherent current sharing between the two inductors, natural balance of the voltage across the series-capacitor and lower conduction losses. The converter operation is validated with a 100W and 48V-to-5/3.3/2.5/1.8V prototype that achieves a peak efficiency of 95.8% and a full load efficiency of 91.1%.

Artificial lighting is complementary and single-source lighting for controlled Environment Agriculture (CEA) to increase crop productivity. Installations to control CO2 levels and luminaires with variable spectrum and intensity are becoming increasingly common. In order to see the net assimilation of CO2 based on the relationship between the three factors: intensity, spectrum and CO2 concentration, tests are proposed on tomatoes seedling with combinations of ten spectra (100B, 80B20G, 20B80G, 100G, 80G20R, 20G80R, 100R, 80R20B, 20R80B, 37R36G27B) seven light intensities (30, 90, 200, 350, 500, 700 and 1000 μmol·m-2 s-1) and nine CO2 concentrations (200, 300, 400, 500, 600, 700, 800 and 900 ppm). These tomato seedlings grew under uniform conditions with no treatments applied up to the moment of measurement by a differential gas analyzer. We have developed a model to evaluate and determine under what spectrum and intensity of light photosynthesis the Net assimilation of CO2 (An) is more significant in the leaves of tomato plants, considering the CO2 concentration as an independent variable in the model. The evaluation of the model parameters for each spectrum and intensity shows that the intensity has a more decisive influence on the maximum An rate than the spectra. For intensities lower than 350 μmol·m-2 s-1, it is observed that the spectrum has a greater influence on the variable An. The spectra with the best behaviour were 80R20B and 80B20R, which maintained An values between 2 and 4 (μmol CO2·m-2·s-1) above the spectra with the worst behaviour (100G, 80G20R, 20G80R and 37B36G27R) in practically all situations. Photosynthetic Light-Use Efficiency (PLUE) was also higher for the 80B20R and 20R80B spectra with values of 36,07 and 33,84 mmol CO2·mol photon-1, respectively, for light intensities of 200 μmol·m-2 s-1 and 400 ppm of CO2that increased to values of 49,65 and 48,38 mmol CO2·mol photon-1 for the same light intensity and concentrations of 850 ppm. The choice of spectrum is essential, as indicated by the data from this study, to optimize the photosynthesis of the plant species grown in the plant factory where light intensities are adjusted for greater profitability.

Small-scale fisheries (SSF, boats

Mycotoxins are toxic secondary metabolites produced by various fungi that can contaminate food crops, which, in turn, may lead to human exposure. Chronic exposure to mycotoxins can cause adverse health effects including reproductive and developmental toxicity. Pregnant women and their foetuses present a vulnerable group for exposure to mycotoxins that can cross the placenta. Human biomonitoring of mycotoxins provides a real-life approach to estimate internal exposure. In this pilot study, 24-h urine samples from 36 pregnant Dutch women were analysed for aflatoxin M1 (AFM1), total deoxynivalenol (DON), de-epoxy-deoxynivalenol (DOM-1), total zearalenone (ZEN), total α-zearalenol (α-ZEL), total β-zearalenol (β-ZEL) and total zearalanone (ZAN), where ‘total’ refers to mycotoxins and their conjugated forms. Serum samples from these women were analysed for fumonisin B1 (FB1) and ochratoxin A (OTA). All samples were measured using liquid chromatography–tandem mass spectrometry (LC-MS/MS). The most prevalent mycotoxins were total DON, total ZEN and OTA, with a detection frequency of 100%. DOM-1, total α-ZEL and total β-ZEL were detected but to a lesser extent, while AFM1, total ZAN and FB1 were undetected. Median concentrations were 4.75 μg total DON/L, 0.0350 μg DOM-1/L, 0.0413 μg total ZEN/L, 0.0379 μg total α-ZEL/L, 0.0189 μg total β-ZEL/L, and 0.121 μg OTA/L. The calculated median concentration for total ZEN and its metabolites was 0.105 μg/L. Based on two separate risk assessment approaches, total DON exposure in this group was considered to be of low concern. Similarly, exposure to total ZEN and its metabolites in this group was of low concern. For OTA, the risk of non-neoplastic effects was of low concern based on exposure in this group, and the risk of neoplastic effects was of low concern in the majority of participants in this group. The findings of this pilot study confirm the presence of mycotoxins in the urine and serum of pregnant Dutch women, with total DON, total ZEN, and OTA most frequently detected. Exposure to all measured mycotoxins was considered to be of low concern in this group, except for exposure to OTA, which was of low concern for the majority of participants. The study’s findings offer valuable insights but should be confirmed using a larger and more diverse sample of the Dutch general population.

A 77-year-old male presented to the emergency department with dyspnea. A third-degree atrioventricular block was present in the electrocardiogram and an echocardiography showed a moderate mitral regurgitation with a diastolic functional insufficiency. Hemodynamic variations were assessed in the context of heart rhythm disturbances. (Level of Difficulty: Intermediate.)

While immunotherapy for pediatric cancer has made great strides in recent decades, including the FDA approval of agents such as dinutuximab and tisgenlecleucel, these successes have rarely impacted children with pediatric central nervous system (CNS) tumors. As our understanding of the biological underpinnings of these tumors evolves, new immunotherapeutics are undergoing rapid clinical translation specifically designed for children with CNS tumors. Most recently, there have been notable clinical successes with oncolytic viruses, vaccines, adoptive cellular therapy, and immune checkpoint inhibition. In this article, the immunotherapy working group of the Pacific Pediatric Neuro-Oncology Consortium (PNOC) reviews the current and future state of immunotherapeutic CNS clinical trials with a focus on clinical trial development. Based on recent therapeutic trials, we discuss unique immunotherapy clinical trial challenges, including toxicity considerations, disease assessment, and correlative studies. Combinatorial strategies and future directions will be addressed. Through internationally collaborative efforts and consortia, we aim to direct this promising field of immuno-oncology to the next frontier of successful application against pediatric CNS tumors.

IntroductionChronic non-communicable diseases (NCDs) are predominantly related to modifiable health behaviors and account for 74% of global deaths at present. Behavior modification through self-management is a strategy to prevent NCDs. Chronic Disease Self-Management Programs (CDSMPs) have demonstrated improvements in health behaviors, health status, and use of healthcare.ObjectiveWe evaluated the effects of a 6-week CDSMP on self-efficacy, health behaviors, mental health, health-related quality of life (HR-QoL), and health responsibilities among vulnerable populations with chronic disease in Europe.MethodsA prospective cohort study with a 6-month pre-post single-group design was conducted in five European countries. The intervention targeted adults with chronic conditions and low socioeconomic status, as well as their caregivers. The intervention was a 6-week community-based CDSMP in a group setting. Outcomes were measured per self-report questionnaire at baseline and 6-month follow-up: self-efficacy, health behaviors, mental health, HR-QoL, and health responsibilities.ResultsOf 1,844 participants, 1,248 (67.7%) completed follow-up and attended ≥4 sessions. For the chronic condition group, the following outcome measures at follow-up significantly improved compared with baseline (all P < 0.002): self-efficacy (SEMCD-6 6.7 vs. 6.4), mental health (PHQ-8 6.3 vs. 7.0), HR-QoL (SF-12 PCS 42.3 vs. 40.2, SF-12 MCS 42.8 vs. 41.4), health utility (EQ-5D-5L 0.88 vs. 0.86), self-rated health (EQ-5D-5L 67.2 vs. 63.9), communication with healthcare providers (2.28 vs. 2.11), understanding information (3.10 vs. 3.02), number of doctor visits (3.61 vs. 4.97), accident and emergency department visits (0.25 vs. 0.48), total nights in a hospital (0.65 vs. 1.13), and perceived medical errors (19.6 vs. 28.7%). No significant changes were detected in dietary habits, physical activity, substance use, and sleep and fatigue. For caregivers without a chronic condition, only doctor visits significantly decreased (1.54 vs. 2.25, P < 0.001).DiscussionThis CDSMP was associated with improvement in self-efficacy, depression, HR-QoL, and health responsibilities over 6 months in a diverse European population with a chronic condition. However, additional interventions targeting lifestyle risk factors are needed to improve health outcomes.

Background: The Behaviour Change Technique Taxonomy v1 (BCTTv1) specifies the potentially active content of behaviour change interventions. Evaluation of BCTTv1 showed the need to extend it into a formal ontology, improve its labels and definitions, add BCTs and subdivide existing BCTs. We aimed to develop a Behaviour Change Technique Ontology (BCTO) that would meet these needs. Methods: The BCTO was developed by: (1) collating and synthesising feedback from multiple sources; (2) extracting information from published studies and classification systems; (3) multiple iterations of reviewing and refining entities, and their labels, definitions and relationships; (4) refining the ontology via expert stakeholder review of its comprehensiveness and clarity; (5) testing whether researchers could reliably apply the ontology to identify BCTs in intervention reports; and (6) making it available online and creating a machine-readable version. Results: Initially there were 282 proposed changes to BCTTv1. Following first-round review, 19 BCTs were split into two or more BCTs, 27 new BCTs were added and 26 BCTs were moved into a different group, giving 161 BCTs hierarchically organised into 12 logically defined higher-level groups in up to five hierarchical levels. Following expert stakeholder review, the refined ontology had 247 BCTs hierarchically organised into 20 higher-level groups. Independent annotations of intervention evaluation reports by researchers familiar and unfamiliar with the ontology resulted in good levels of inter-rater reliability (0.82 and 0.79, respectively). Following revision informed by this exercise, 34 BCTs were added, resulting in a final version of the BCTO containing 281 BCTs organised into 20 higher-level groups over five hierarchical levels. Discussion: The BCT Ontology provides a standard terminology and comprehensive classification system for the content of behaviour change interventions that can be reliably used to describe interventions.

La inmunoterapia con el bacilo Calmette-Guérin (BCG) es el agente intravesical más efectivo para el tratamiento de carcinoma vesical in situ tras la resección transuretral del tumor. Pese a ser un agente seguro y las complicaciones sistémicas son infrecuentes, las complicaciones locales leves son frecuentes. La afectación pulmonar es inusual (< 1%) suele ser grave, en forma de patrón micronodulillar y su mecanismo etiopatológico es controvertido. Se presenta el caso clínico de un varón con afectación pulmonar micronodulillar secundaria a instilaciones de BCG intravesical.

The outcomes of metastatic and nonresponder pediatric osteosarcoma patients are very poor and have not improved in the last 30 years. These tumors harbor a highly immunosuppressive environment, making existing immunotherapies ineffective. Here, we evaluated the use of Semliki Forest virus (SFV) vectors expressing galectin-3 (Gal3) inhibitors as therapeutic tools, since both the inhibition of Gal3, which is involved in immunosuppression and metastasis, and virotherapy based on SFV have been demonstrated to reduce tumor progression in different tumor models. In vitro, inhibitors based on the Gal3 amino-terminal domain alone (Gal3-N) or fused to a Gal3 peptide inhibitor (Gal3-N-C12) were able to block the binding of Gal3 to the surface of activated T cells. In vivo, SFV expressing Gal3-N-C12 induced strong antitumor responses in orthotopic K7M2 and MOS-J osteosarcoma tumors, leading to complete regressions in 47% and 30% of mice, respectively. Pulmonary metastases were also reduced in K7M2 tumor-bearing mice after treatment with SFV-Gal3-N-C12. Both the antitumor and antimetastatic responses were dependent on modulation of the immune system, primarily including an increase in tumor-infiltrating lymphocytes and a reduction in the immunosuppressive environment inside tumors. Our results demonstrated that SFV-Gal3-N-C12 could constitute a potential therapeutic agent for osteosarcoma patients expressing Gal3.

Abstract Background Hip-worn accelerometer cut-points have poor validity for assessing children’s sedentary time, which may partly explain the equivocal health associations shown in prior research. Improved processing/classification methods for these monitors would enrich the evidence base and inform the development of more effective public health guidelines. The present study aimed to develop and evaluate a novel computational method (CHAP-child) for classifying sedentary time from hip-worn accelerometer data. Methods Participants were 278, 8–11-year-olds recruited from nine primary schools in Melbourne, Australia with differing socioeconomic status. Participants concurrently wore a thigh-worn activPAL (ground truth) and hip-worn ActiGraph (test measure) during up to 4 seasonal assessment periods, each lasting up to 8 days. activPAL data were used to train and evaluate the CHAP-child deep learning model to classify each 10-s epoch of raw ActiGraph acceleration data as sitting or non-sitting, creating comparable information from the two monitors. CHAP-child was evaluated alongside the current practice 100 counts per minute (cpm) method for hip-worn ActiGraph monitors. Performance was tested for each 10-s epoch and for participant-season level sedentary time and bout variables (e.g., mean bout duration). Results Across participant-seasons, CHAP-child correctly classified each epoch as sitting or non-sitting relative to activPAL, with mean balanced accuracy of 87.6% (SD = 5.3%). Sit-to-stand transitions were correctly classified with mean sensitivity of 76.3% (SD = 8.3). For most participant-season level variables, CHAP-child estimates were within ± 11% (mean absolute percent error [MAPE]) of activPAL, and correlations between CHAP-child and activPAL were generally very large (> 0.80). For the current practice 100 cpm method, most MAPEs were greater than ± 30% and most correlations were small or moderate (≤ 0.60) relative to activPAL. Conclusions There was strong support for the concurrent validity of the CHAP-child classification method, which allows researchers to derive activPAL-equivalent measures of sedentary time, sit-to-stand transitions, and sedentary bout patterns from hip-worn triaxial ActiGraph data. Applying CHAP-child to existing datasets may provide greater insights into the potential impacts and influences of sedentary time in children.

This review aims at presenting the main strategies that are currently available for the delivery of bacteriophages to combat bacterial infections in humans, animals, and plants. It can be seen that the main routes for phage delivery are topical, oral, systemic, and airways for humans. In animals, the topical and oral routes are the most used. To combat infections in plant species, spraying the plant’s phyllosphere or drenching the soil are the most commonly used methods. In both phage therapy and biocontrol using phages, very promising results have been obtained so far. However, more experiments are needed to establish forms of treatment and phage doses, among other parameters. Furthermore, in general, there is a lack of specific standards for the use of phages to combat bacterial infections.

Abstract Introduction The Chronic Disease Self‐Management Programme (CDSMP) has resulted in improved health outcomes for patients. However, research has focused mainly on those with chronic conditions and has not extensively explored prevention programmes targeting individuals with specific vulnerability profiles. Aim This study aimed to understand the effects of the CDSMP on the lived experience of vulnerable patients included in the EFFICHRONIC project in France, based on their needs and expectations before and after participation. Methods We conducted a qualitative phenomenological semio‐pragmatic study based on 37 in‐depth interviews with 20 patients (20 before/17 after CDSMP). Results By transforming existential dimensions (identity, relationship with others and bodily experience), chronic illness generates new needs in the vulnerable person. By resonating with the expectations and needs of participants, the CDSMP induces motivation and a sense of belonging to a community of peers. It has enabled the participants to become actors of their own health until empowerment. Although some limitations are reported, the programme has awakened a desire in the participants to take better care of their health and to develop personal skills with, for some, a desire to become involved in health education. Conclusion Our phenomenological approach highlighted the resonance between the programme (its design and implementation) and the lived experience of patients, as an effective element of empowerment. This necessitates training the facilitators to elicit the lived experience of patients. Furthermore, as a patient‐centred approach is required, the facilitators need to learn how to adapt the design of the programme to the singularity of the patient. Patient or Public Contribution Patients provided the data that were collected through in‐depth interviews, and their experiences before and after the programme were analysed.

Mutations in the GBA1 gene are the single most frequent genetic risk factor for Parkinson’s disease (PD). Neurodegenerative changes in GBA1-associated PD have been linked to the defective lysosomal clearance of autophagic substrates and aggregate-prone proteins. To elucidate novel mechanisms contributing to proteinopathy in PD, we investigated the effect of GBA1 mutations on the transcription factor EB (TFEB), the master regulator of the autophagy-lysosomal pathway (ALP). Using PD patients’ induced-pluripotent stem cells (iPSCs), we examined TFEB activity and regulation of the ALP in dopaminergic neuronal cultures generated from iPSC lines harboring heterozygous GBA1 mutations and the CRISPR/Cas9-corrected isogenic controls. Our data showed a significant decrease in TFEB transcriptional activity and attenuated expression of many genes in the CLEAR network in GBA1 mutant neurons, but not in the isogenic gene-corrected cells. In PD neurons, we also detected increased activity of the mammalian target of rapamycin complex1 (mTORC1), the main upstream negative regulator of TFEB. Increased mTORC1 activity resulted in excess TFEB phosphorylation and decreased nuclear translocation. Pharmacological mTOR inhibition restored TFEB activity, decreased ER stress and reduced α-synuclein accumulation, indicating improvement of neuronal protiostasis. Moreover, treatment with the lipid substrate reducing compound Genz-123346, decreased mTORC1 activity and increased TFEB expression in the mutant neurons, suggesting that mTORC1-TFEB alterations are linked to the lipid substrate accumulation. Our study unveils a new mechanism contributing to PD susceptibility by GBA1 mutations in which deregulation of the mTORC1-TFEB axis mediates ALP dysfunction and subsequent proteinopathy. It also indicates that pharmacological restoration of TFEB activity could be a promising therapeutic approach in GBA1-associated neurodegeneration.

PurposeThe aim of this systematic review is to evaluate the perception of the patient, the chairside time, and the reliability and/or reproducibility of intraoral scanners for full arch in pediatric patients.MethodsA data search was performed in four databases (Medline-Pubmed, Scopus, ProQuest and Web of Science) in accordance with the PRISMA 2020 statements. Studies were classified in three categories (patient perception, scanning or impression time and reliability and/or reproducibility). The resources, the data extraction and the quality assessment were carried out independently by two operators. The variables recorded were population characteristics, material and methods aspects and included country, study design and main conclusion. A quality assessment of the selected studies was performed with QUADAS-2 tool, and Kappa-Cohen Index was calculated to analyze examiner agreement.ResultsThe initial search obtained 681 publications, and finally four studies matching inclusion criteria were selected. The distribution of the studies in the categories was three for the analysis of the patient's perception and scanning or impression time; and two items to assess the reliability and/or reproducibility of intraoral scans. All included studies have a repeated measures–transversal design. The sample size ranged between 26 and 59 children with a mean age. The intraoral scanners evaluated were Lava C.O.S, Cerec Omnicam, TRIOS Classic, TRIOS 3-Cart and TRIOS Ortho. The quality assessment of the studies using QUADAS-2 tool revealed a low risk of bias while evaluating patient perception, but an unclear risk of bias in the analysis of accuracy or chairside time. In relation to the applicability concerns, the patient selection was of high risk of bias. All studies agreed that the patient perception and comfort is better with intraoral scanners in comparison with the conventional method. The accuracy or reliability of the digital procedure is not clear, being clinically acceptable. In relation with the chairside time, it depends on the intraoral scanner, with contradictory data in the different analyzed studies.ConclusionThe use of intraoral scanners in children is a favorable option, finding a significantly higher patient perception and comfort with intraoral scanners compared to the conventional impression method. The evidence for reliability or reproducibility is not strong to date, however, the differences between the intraoral measurements and the digital models would be clinically acceptable.

In this paper we address a new hierarchical multicriteria routing model associated with a two-path traffic splitting routing method in MPLS networks whereby the bandwidth required by a given node-to-node traffic flow is divided by two disjoint paths. The model has two levels of objective functions and several constraints. An algorithmic approach is presented for calculating non-dominated solutions and selecting good compromise solutions to this problem. Also a number of computational experiments are presented.

Resumen La sintomatología de Covid persistente aparece en 1-2 de cada 10 personas infectadas por el virus SARS-CoV-2 y pueden presentar severas dificultades de adaptación a su nueva condición de salud. Por un lado, este artículo presenta nuestra propuesta de tratamiento psicológico grupal basada en la ya conocida terapia de aceptación y compromiso. Se ha descrito brevemente el contenido de la psicoterapia sesión a sesión y se han detallado los aspectos formales para su correcta implementación y posibilidad de replicación. Por otro lado, se describen las particularidades metodológicas de un ensayo controlado aleatorizado: diseño experimental pre-post con asignación aleatoria a dos modalidades de tratamiento; criterios de inclusión y exclusión de la muestra; proceso de reclutamiento y aleatorización, procedimiento, variables e instrumentos de evaluación y análisis y contraste estadístico de los resultados. El protocolo que hemos elaborado pretende evaluar, de forma metodológicamente rigurosa, la efectividad de un tratamiento específicamente dirigido a mejorar la calidad de vida y el funcionamiento psicosocial de las personas que sufren síntomas persistentes de Covid-19. Los resultados permitirán saber si dicho tratamiento es realmente eficaz.

Abstract Rapid developments in educational technology in higher education are intended to make learning more engaging and effective. At the same time, cognitive load theory stresses limitations of human cognitive architecture and urges educational developers to design learning tools that optimise learners’ mental capacities. In a 2-month study we investigated university students’ learning with an AI-enriched digital biology textbook that integrates a 5000-concept knowledge base and algorithms offering the possibility to ask questions and receive answers. The study aimed to shed more light on differences between three sub-types (intrinsic, germane and extraneous) of cognitive load and their relationship with learning gain, self-regulated learning and usability perception while students interacted with the AI-enriched book during an introductory biology course. We found that students displayed a beneficial learning pattern with germane cognitive load significantly higher than both intrinsic and extraneous loads showing that they were engaged in meaningful learning throughout the study. A significant correlation between germane load and accessing linked suggested questions available in the AI-book indicates that the book may support deep learning. Additionally, results showed that perceived non-optimal design, which deflects cognitive resources away from meaningful processing accompanied lower learning gains. Nevertheless, students reported substantially more favourable than unfavourable opinions of the AI-book. The findings provide new approaches for investigating cognitive load types in relation to learning with emerging digital tools in higher education. The findings also highlight the importance of optimally aligning educational technologies and human cognitive architecture.