Classical BSE dismissed as the cause of CWD in Norwegian red deer despite strain similarities between both prion agents.

The first case of CWD in a Norwegian red deer was detected by a routine ELISA test and confirmed by western blotting and immunohistochemistry in the brain stem of the animal. Two different western blotting tests were conducted independently in two different laboratories, showing that the red deer glycoprofile was different from the Norwegian CWD reindeer and CWD moose and from North American CWD. The isolate showed nevertheless features similar to the classical BSE (BSE-C) strain. Furthermore, BSE-C could not be excluded based on the PrPSc immunohistochemistry staining in the brainstem and the absence of detectable PrPSc in the lymphoid tissues. Because of the known ability of BSE-C to cross species barriers as well as its zoonotic potential, the CWD red deer isolate was submitted to the EURL Strain Typing Expert Group (STEG) as a BSE-C suspect for further investigation. In addition, different strain typing in vivo and in vitro strategies aiming at identifying the BSE-C strain in the red deer isolate were performed independently in three research groups and BSE-C was not found in it. These results suggest that the Norwegian CWD red deer case was infected with a previously unknown CWD type and further investigation is needed to determine the characteristics of this potential new CWD strain.

The genotype of barley cultivars influences multiple aspects of their associated microbiota via differential root exudate secretion.

Plant-associated microbes play vital roles in promoting plant growth and health, with plants secreting root exudates into the rhizosphere to attract beneficial microbes. Exudate composition defines the nature of microbial recruitment, with different plant species attracting distinct microbiota to enable optimal adaptation to the soil environment. To more closely examine the relationship between plant genotype and microbial recruitment, we analysed the rhizosphere microbiomes of landrace (Chevallier) and modern (NFC Tipple) barley (Hordeum vulgare) cultivars. Distinct differences were observed between the plant-associated microbiomes of the 2 cultivars, with the plant-growth promoting rhizobacterial genus Pseudomonas substantially more abundant in the Tipple rhizosphere. Striking differences were also observed between the phenotypes of recruited Pseudomonas populations, alongside distinct genotypic clustering by cultivar. Cultivar-driven Pseudomonas selection was driven by root exudate composition, with the greater abundance of hexose sugars secreted from Tipple roots attracting microbes better adapted to growth on these metabolites and vice versa. Cultivar-driven selection also operates at the molecular level, with both gene expression and the abundance of ecologically relevant loci differing between Tipple and Chevallier Pseudomonas isolates. Finally, cultivar-driven selection is important for plant health, with both cultivars showing a distinct preference for microbes selected by their genetic siblings in rhizosphere transplantation assays.

Early hospital discharge through prediction of post-thyroidectomy hypoparathyroidism.

INTRODUCTION: Hypoparathyroidism is the most common postsurgical complication of total thyroidectomy. Furthermore, it is the main cause of prolonged hospitalisation after this procedure. OBJECTIVE: To predict the probability of post-thyroidectomy hypocalcaemia according to the levels of intact parathyroid hormone (iPTH), as well as to determine the needs for treatment with exogenous calcium according to the levels of serum calcium (Ca). MATERIALS AND METHODS: Retrospective study was carried out on patients who underwent total thyroidectomy between January 2017 and January 2020 at Los Arcos del Mar Menor University Hospital (HULAMM). iPTH and Ca levels ​​were measured at 4, 24 and 48 h after the surgery. Follow-up was 6 months. RESULTS: Ninety-four patients were operated on. Temporary and permanent postoperative hypoparathyroidism percentages were, respectively, 51.06% and 6.38%. iPTH level 24 h after the procedure was the most reliable predictor of post-thyroidectomy temporary hypoparathyroidism (Area Under the ROC Curve (AUC) = 0.933, p < .001). iPTH levels ​​≥29 pg/mL predicted normal parathyroid metabolism. CONCLUSIONS: The combined values of iPTH and Ca levels 24 h after thyroidectomy seems to be a reliable, safe and efficient method to control the post-thyroidectomy hypoparathyroidism. Our protocol could reduce the hospital stay of patients at low risk of hypocalcaemia, allowing them to be discharged from the hospital on the first postoperative morning and identifying patients at high risk of hypocalcaemia early.

Integrative single-cell expression and functional studies unravels a sensitization to cytarabine-based chemotherapy through HIF pathway inhibition in AML leukemia stem cells.

Relapse remains a major challenge in the clinical management of acute myeloid leukemia (AML) and is driven by rare therapy-resistant leukemia stem cells (LSCs) that reside in specific bone marrow niches. Hypoxia signaling maintains cells in a quiescent and metabolically relaxed state, desensitizing them to chemotherapy. This suggests the hypothesis that hypoxia contributes to the chemoresistance of AML-LSCs and may represent a therapeutic target to sensitize AML-LSCs to chemotherapy. Here, we identify HIFhigh and HIFlow specific AML subgroups (inv(16)/t(8;21) and MLLr, respectively) and provide a comprehensive single-cell expression atlas of 119,000 AML cells and AML-LSCs in paired diagnostic-relapse samples from these molecular subgroups. The HIF/hypoxia pathway signature is attenuated in AML-LSCs compared with more differentiated AML cells but is more expressed than in healthy hematopoietic cells. Importantly, chemical inhibition of HIF cooperates with standard-of-care chemotherapy to impair AML growth and to substantially eliminate AML-LSCs in vitro and in vivo. These findings support the HIF pathway in the stem cell-driven drug resistance of AML and unravel avenues for combinatorial targeted and chemotherapy-based approaches to specifically eliminate AML-LSCs.

Assessment of the zoonotic potential of atypical scrapie prions in humanized mice reveals rare phenotypic convergence but not identity with sporadic CJD prions.

BACKGROUND: Atypical/Nor98 scrapie (AS) is an idiopathic infectious prion disease affecting sheep and goats. Recent findings suggest that zoonotic prions from bovine spongiform encephalopathy (C-BSE) may co-propagate with atypical/Nor98 prions in AS sheep brains. Investigating the risk AS poses to humans is crucial. METHODS: To assess the risk of sheep/goat-to-human transmission of AS, we serially inoculated brain tissue from field and laboratory isolates into transgenic mice overexpressing human prion protein (Met129 allele). We studied clinical outcomes as well as presence of prions in brains and spleens. RESULTS: No transmission occurred on the primary passage, with no clinical disease or pathological prion protein in brains and spleens. On subsequent passages, one isolate gradually adapted, manifesting as prions with a phenotype resembling those causing MM1-type sporadic Creutzfeldt-Jakob disease in humans. However, further characterization using in vivo and in vitro techniques confirmed both prion agents as different strains, revealing a case of phenotypic convergence. Importantly, no C-BSE prions emerged in these mice, especially in the spleen, which is more permissive than the brain for C-BSE cross-species transmission. CONCLUSIONS: The results obtained suggest a low the zoonotic for AS. Rare adaptation may allow the emergence of prions phenotypically resembling those spontaneously forming in humans.

Prosocial behaviours and emotional intelligence as factors associated with healthy lifestyles and violence in adolescents.

Adolescence is a stage of life characterised by vulnerability, which shapes young people's trajectories and potentially influences their behaviour. In this crucial period, the promotion of prosocial behaviours and the development of emotional intelligence are understood as key factors influencing adolescents' psychological and personal well-being. The general objective of this study was to find out the relationship between these two variables - prosocial behaviours and emotional intelligence - and their correlation with the maintenance of a healthy lifestyle and another fundamental aspect such as violence among young people in the academic context. A total of 743 secondary school students participated in this research with a descriptive-cross-sectional design. This study used several instruments, including an ad hoc questionnaire to assess socio-demographic aspects and school violence, the Prosocial Behaviour Questionnaire (PBQ), the TMMS-24 for the assessment of Emotional Intelligence, the Healthy Lifestyles Questionnaire (HLQ-II) and the Satisfaction with Life Scale (SLS). The results highlighted a convincing link between the display of prosocial behaviours and emotional intelligence with various dimensions of healthy living such as healthy diet or respect for mealtimes. In particular, the research revealed a pronounced correlation between adolescents who showed greater emotional repair and respect and their lower involvement in school violence and substance use. In addition, the likelihood of having a healthy life was found to be linked to variables such as being male, respect, social relationships and emotional repair. In contrast, the likelihood of having an excessive consumption of certain harmful substances such as alcohol or tobacco was found to be linked to age, empathy and emotional clarity. These results highlight the crucial role that prosocial behaviours and emotional intelligence play in shaping adolescents' lives. In conclusion, the need to promote such variables as prosocial behaviours and emotional intelligence in adolescent students in order to promote healthy lifestyles and reduce school violence and substance use in this age group is discussed.

Use of botulinum toxin type A in the prehabilitation of abdominal wall musculature for hernia repair: a consensus proposal.

The prehabilitation of the abdominal wall through the infiltration of botulinum toxin type A, which induces temporary chemical denervation ("chemical component separation") in the lateral abdominal musculature, is a common practice in units specialized in abdominal wall surgery. However, its use for this indication is currently off-label. The main objective of this article is to describe a consensus proposal regarding indications, contraindications, dosages employed, potential side effects, administration method, and measurement of possible outcomes. Additionally, a proposal for an informed consent document endorsed by the Abdominal Wall Section of the Spanish Association of Surgeons is attached.

Chromosomal instability in aneuploid acute lymphoblastic leukemia associates with disease progression.

Chromosomal instability (CIN) lies at the core of cancer development leading to aneuploidy, chromosomal copy-number heterogeneity (chr-CNH) and ultimately, unfavorable clinical outcomes. Despite its ubiquity in cancer, the presence of CIN in childhood B-cell acute lymphoblastic leukemia (cB-ALL), the most frequent pediatric cancer showing high frequencies of aneuploidy, remains unknown. Here, we elucidate the presence of CIN in aneuploid cB-ALL subtypes using single-cell whole-genome sequencing of primary cB-ALL samples and by generating and functionally characterizing patient-derived xenograft models (cB-ALL-PDX). We report higher rates of CIN across aneuploid than in euploid cB-ALL that strongly correlate with intraclonal chr-CNH and overall survival in mice. This association was further supported by in silico mathematical modeling. Moreover, mass-spectrometry analyses of cB-ALL-PDX revealed a "CIN signature" enriched in mitotic-spindle regulatory pathways, which was confirmed by RNA-sequencing of a large cohort of cB-ALL samples. The link between the presence of CIN in aneuploid cB-ALL and disease progression opens new possibilities for patient stratification and offers a promising new avenue as a therapeutic target in cB-ALL treatment.

Prosocial Behaviours and Resilience in School Coexistence: Implications of Creative Self-Efficacy and Stress in Adolescents.

Adolescence brings with it a number of problems such as school violence. To reduce stress and increase the well-being of students, it is necessary to enhance certain skills such as prosocial behaviours, resilience, and creative self-efficacy. This cross-sectional study investigated the impact of prosocial behaviours and creative self-efficacy on school violence, stress, and resilience in adolescent students. A total of 743 students aged 14-19 years participated. The results revealed positive correlations between the dimensions of prosocial behaviours, creative self-efficacy, and resilience, and negative correlations with perceived stress. Differences were also observed in the relationship between prosocial behaviours, school violence, and stress. Mediation models indicated that creative self-efficacy acted as a mediator between prosocial behaviours and resilience. In addition, stress was found to moderate the relationship between prosocial behaviours and resilience. This study provides evidence on how prosocial behaviours, resilience, and creative self-efficacy act as a positive element in adolescence.

Creativity as a Positive Factor in the Adolescence Stage: Relations with Academic Performance, Stress and Self-Esteem.

Creativity is a construct that aids in conflict resolution. Through the development of creative skills in adolescence, young people can carry out a series of strategies to make decisions or respond to a problem. The possession of creative skills helps students' personal wellbeing. The aim of this research is to analyze the relationships established between creativity and other individual variables such as academic performance, self-esteem and stress in adolescent students. The following descriptive cross-sectional study was carried out with a total sample of 743 adolescent students, between 14 and 19 years of age, from different educational centers in the province of Almería (Spain). The results obtained indicate a positive correlation between creativity and self-esteem and significant differences in the level of creativity among students who have repeated an academic year. Regression analyses indicate that both stress and creativity are two predictor variables of self-esteem. On the other hand, another of the findings obtained is that creativity acts as a mediating variable between self-esteem and repeating an academic year. It is discussed how creativity is a beneficial element in adolescence and, therefore, how its promotion can help the optimal development of adolescent students.

Experimental transmission of ovine atypical scrapie to cattle.

Classical bovine spongiform encephalopathy (BSE) in cattle was caused by the recycling and feeding of meat and bone meal contaminated with a transmissible spongiform encephalopathy (TSE) agent but its origin remains unknown. This study aimed to determine whether atypical scrapie could cause disease in cattle and to compare it with other known TSEs in cattle. Two groups of calves (five and two) were intracerebrally inoculated with atypical scrapie brain homogenate from two sheep with atypical scrapie. Controls were five calves intracerebrally inoculated with saline solution and one non-inoculated animal. Cattle were clinically monitored until clinical end-stage or at least 96 months post-inoculation (mpi). After euthanasia, tissues were collected for TSE diagnosis and potential transgenic mouse bioassay. One animal was culled with BSE-like clinical signs at 48 mpi. The other cattle either developed intercurrent diseases leading to cull or remained clinical unremarkable at study endpoint, including control cattle. None of the animals tested positive for TSEs by Western immunoblot and immunohistochemistry. Bioassay of brain samples from the clinical suspect in Ov-Tg338 and Bov-Tg110 mice was also negative. By contrast, protein misfolding cyclic amplification detected prions in the examined brains from atypical scrapie-challenged cattle, which had a classical BSE-like phenotype. This study demonstrates for the first time that a TSE agent with BSE-like properties can be amplified in cattle inoculated with atypical scrapie brain homogenate.

Clinical findings, treatment and outcome in cats diagnosed with precursor-targeted immune-mediated anaemia in a referral hospital in the UK: 30 cases (2010-2021).

Aims: This retrospective study aimed to report clinical findings, treatment response and survival in cats diagnosed with precursor-targeted immune-mediated anaemia (PIMA) in a referral hospital in the UK. Methods: Feline cases diagnosed with presumed PIMA between January 2010 and February 2021 were retrospectively recruited. Signalment, clinical signs, diagnostic tests, treatment and outcome were recorded. Descriptive analytics were performed. Outcomes were documented according to survival to discharge, 30-day survival, total survival time, response to immunosuppressive treatment and frequency of relapses. Results: Thirty cats met the inclusion criteria. A higher prevalence of females (19/30) was identified (p = 0.001). Most cats (25/30) presented with haematocrit below 0.15 L/L. Concurrent cytopenias occurred in 18 of 30 cats. Bone marrow diagnosis was erythroid hyperplasia in 24 of 30 cases. Survival to discharge was documented in 26 of 30 cats, of which 23 survived more than 30 days since diagnosis. Initial treatment included blood products (26/30) and prednisolone (26/30) or prednisolone with ciclosporin (3/30); 18 of 30 cats responded to treatment, with a normal haematocrit at a mean of 28 days. The initial haematocrit and the presence of concurrent cytopenia were not statistically different between responders and non-responders. The median survival time was 140 days (range 1-3930 days). Conclusions and relevance: The treatment response rate of feline PIMA was high (60%), with a mortality rate of 23% over the 30 days following diagnosis. Relapses occur frequently (77%) but the response rate after treatment modification was high (76%) and therefore ongoing treatment may be justified at that point. Long survival times (up to 3930 days) can be achieved.

Genome analysis for the identification of genes involved in phenanthrene biodegradation pathway in Stenotrophomonas indicatrix CPHE1. Phenanthrene mineralization in soils assisted by integrated approaches.

Phenanthrene (PHE) is a highly toxic compound, widely present in soils. For this reason, it is essential to remove PHE from the environment. Stenotrophomonas indicatrix CPHE1 was isolated from an industrial soil contaminated by polycyclic aromatic hydrocarbons (PAHs) and was sequenced to identify the PHE degrading genes. Dioxygenase, monooxygenase, and dehydrogenase gene products annotated in S. indicatrix CPHE1 genome were clustered into different trees with reference proteins. Moreover, S. indicatrix CPHE1 whole-genome sequences were compared to genes of PAHs-degrading bacteria retrieved from databases and literature. On these basis, reverse transcriptase-polymerase chain reaction (RT-PCR) analysis pointed out that cysteine dioxygenase (cysDO), biphenyl-2,3-diol 1,2-dioxygenase (bphC), and aldolase hydratase (phdG) were expressed only in the presence of PHE. Therefore, different techniques have been designed to improve the PHE mineralization process in five PHE artificially contaminated soils (50 mg kg-1), including biostimulation, adding a nutrient solution (NS), bioaugmentation, inoculating S. indicatrix CPHE1 which was selected for its PHE-degrading genes, and the use of 2-hydroxypropyl-ß-cyclodextrin (HPBCD) as a bioavailability enhancer. High percentages of PHE mineralization were achieved for the studied soils. Depending on the soil, different treatments resulted to be successful; in the case of a clay loam soil, the best strategy was the inoculation of S. indicatrix CPHE1 and NS (59.9% mineralized after 120 days). In sandy soils (CR and R soils) the highest percentage of mineralization was achieved in presence of HPBCD and NS (87.3% and 61.3%, respectively). However, the combination of CPHE1 strain, HPBCD, and NS showed to be the most efficient strategy for sandy and sandy loam soils (LL and ALC soils showed 35% and 74.6%, respectively). The results indicated a high degree of correlation between gene expression and the rates of mineralization.

Relación existente entre creatividad y rendimiento académico en la adolescencia: Una revisión sistemática / The relationship between creativity and academic achievement in adolescence: A systematic review

La creatividad es una capacidad propia del ser humano que sirve para dar respuestas originales y novedosas a problemas que surgen en la vida cotidiana, por lo que potencia el desarrollo de los estudiantes. Por otro lado, el logro académico es uno de los principales elementos que se utilizan para identificar si los sujetos han adquirido ciertos conocimientos. El objetivo de este trabajo de revisión sistemática es analizar la relación existente entre la creatividad y rendimiento académico en los estudiantes adolescentes, así como, examinar cualitativamente las diferencias entre las distintas dimensiones que evalúan la creatividad en el rendimiento académico. Atendiendo a la metodología se ha consultado en las bases de datos Web of Science, Scopus, PsycINFO y ERIC a partir de unas fórmulas de búsqueda elaboradas mediante los descriptores creatividad y rendimiento que, a partir de la utilización de unos criterios de elegibilidad, han dado lugar a un total de 15 estudios. La mayoría de las investigaciones señalan que existe una relación bidireccional entre creatividad y rendimiento académico, siendo las dimensiones de fluidez, originalidad y flexibilidad las más examinadas. Además, se ha obtenido que ciertos elementos de la creatividad como la expresividad creativa actúan como un factor moderador en el rendimiento de los estudiantes; aunque también existen estudios indican que no existe ningún tipo de relación significativa entre ambas variables. Se debe llevar a cabo una serie de estrategias o recursos educativos que potencien la formación del alumnado. (AU)

Creativity is a human capacity that servesto provide original and novel answers to problems that arise in everyday life, and therefore enhances students’ development. On the other hand, academic achievement is one of the main elements used to identify whether subjects have acquired certain knowledge. The aim of this systematic review is to analyse the relationship between creativity and academic achievement in adolescent students, as well as to examine qualitatively the differences between the different dimensions that assess creativity in academic achievement. In terms of methodology, the databases Web of Science, Scopus, PsycINFO and ERIC have been consulted based on search formulas elaborated using the descriptors creativity and performance which, based on the use of eligibility criteria, have given rise to a total of 15 studies. Most of the studies indicate that there is a two-way relationship between creativity and academic performance, with the dimensions of fluency, originality and flexibility being the most examined. In addition, it has been found that certain elements of creativity such as creative expressiveness act as a moderating factor in students’ performance; although there are also studies indicating that there is no significant relationship between the two variables. A series of educational strategies or resources should be implemented to enhance student learning. (AU)

Bienestar personal durante la adolescencia según el modelo Perma: una revisión sistemática

(analítico) El bienestar es uno de los constructos más estudiados dentro de la psicología positiva en la actualidad. El objetivo de este trabajo de revisión sistemática es analizar la evidencia existente en los últimos cinco años acerca del bienestar en relación a cada uno de los elementos que constituyen el modelo Perma. La metodología ha consistido en consultar las bases de datos Web of Science y Scopus mediante la elaboración de unas fórmulas de búsqueda. Se han seleccionado un total de 42 artículos entre los distintos estudios pertenecientes a las cinco dimensiones del modelo Perma. Los resultados confirman que el bienestar promueve las conductas positivas y favorece a otras variables como la autoestima y el rendimiento académico. Se debate cómo el bienestar potencia el desarrollo personal en los adolescentes.

(analytical) Well-being is currently one of the most studied areas within Positive Psychology. The objective of this systematic review was to analyze existing evidence in the area of well-being in relation to each of the elements that make up the PERMA model during the last five years The methodology consisted of consulting the Web of Science and Scopus databases through the design of search formulas. A total of 42 articles were selected from different studies that covered the five dimensions of the PERMA model. The results confirm that well-being promotes positive behaviors and favors other variables such as self-esteem and academic performance. The authors also identify that well-being enhances personal development in adolescents from the articles.

(analítico) O bem-estar é um dos construtos mais estudados dentro da Psicologia Positiva atualmente. O objetivo deste trabalho de revisão sistemática é analisar as evidências existentes nos últimos cinco anos sobre o bem-estar em relação a cada um dos elementos que compõem o modelo Perma. A metodologia consistiu em consultar as bases de dados Web of Science e Scopus desenvolvendo fórmulas de busca. Um total de 42 artigos foram selecionados entre os diferentes estudos pertencentes às cinco dimensões do modelo Perma. Os resultados confirmam como o bem-estar promove comportamentos positivos e favorece outras variáveis como autoestima e desempenho acadêmico. Debate-se como o bem-estar potencializa o desenvolvimento pessoal em adolescentes.

Analysis of the different subpeptidomes presented by the HLA class I molecules of the B7 supertype.

MHC-I molecules of the HLA-B7 supertype preferentially bind peptides with proline at position 2. HLA-B*51:01 and B*51:08 present two predominant subpeptidomes, one with Pro2 and hydrophobic residues at P1, and another with Ala2 and Asp enriched at position 1. Here, we present a meta-analysis of the peptidomes presented by molecules of the B7 supertype to investigate the presence of subpeptidomes across different allotypes. Several allotypes presented subpeptidomes differing in the presence of Pro or another residue at P2. The Ala2 subpeptidomes preferred Asp1 except in HLA-B*54:01, where ligands with Ala2 contained Glu1. Sequence alignment and the analysis of crystal structures allowed us to propose positions 45 and 67 of the MHC heavy chain as relevant for the presence of subpeptidomes. Deciphering the principles behind the presence of subpeptidomes could improve our understanding of antigen presentation in other MHC-I molecules. Running title: HLA-B7 supertype subpeptidomes.

Transgenic Mouse Models for the Study of Neurodegenerative Diseases.

Neurodegenerative diseases (NDs) are some of the most important health challenges modern medicine and advanced societies face. Indeed, the number of patients affected by one of these illnesses will increase in the following years at the same rate that human life expectancy allows us to live longer. Despite many years of research, NDs remain invariably fatal. A complete understanding of the exact mechanisms leading to neuronal death, which will ideally allow preclinical detection and the development of effective treatments, has not yet been achieved. However, a great deal of information about ND pathology and the search for possible therapies has been acquired using animal models and more precisely transgenic mouse models. In this review, the main contributions of these powerful research tools in NDs as well as their advantages and caveats are discussed.

Genome sequence of Stenotrophomonas indicatrix CPHE1, a powerful phenanthrene-degrading bacterium.

Environmental pollution caused by polycyclic aromatic hydrocarbons (PAHs) involves a high-risk and have received considerable attention due to their carcinogenic, teratogenic, and mutagenic properties. Phenanthrene (PHE) is a low molecular weight PAH, which has three benzene rings. It is one of the most common PAH found in contaminated environments mainly due to its low volatilization ability and hydrophobic character. A PHE degrading bacterium was isolated from an industrial contaminated soil using enrichment culture techniques. Based on macroscopic, microscopic examination and phylogenetic analysis, this bacterium was classified as Stenotrophomonas indicatrix and named strain CPHE1. Several authors have reported about bacteria stains, which can degrade PHE, but this is the first time where the ability of S. indicatrix to biodegrade and mineralize PHE has been demonstrated.

Healthy Lifestyle in Adolescence: Associations with Stress, Self-Esteem and the Roles of School Violence.

A healthy lifestyle is considered by young people as the adoption of positive behaviors, such as a balanced diet, regular exercise, or the decreased consumption of harmful substances. Living a healthy lifestyle during adolescence promotes a better quality of life and psychological well-being in adulthood. The objective of this research is to identify how a healthy lifestyle is related to stress, self-esteem, and school violence roles. The sample is composed of a total of 743 adolescents aged between 14 and 19 years. The instruments used were the Healthy Lifestyles Questionnaire (CEVS-II), the Student Stress Inventory (SSI-SM), the Rosenberg Self-Esteem Scale (RSES), and an ad hoc questionnaire to evaluate school violence roles. The results obtained indicate that there are negative correlations between healthy lifestyle and stress, but positive correlations between healthy lifestyle and self-esteem. Adolescents who participate in situations of school violence have a higher mean of substance use and stress. However, those who do not experience such situations have higher mean self-esteem and lead a healthy lifestyle. In addition, the fact of suffering stress increases the probability of being a victim or an aggressor. Living a healthy lifestyle can have significant implications for health promotion and positive adolescent development.

Efficient preclinical treatment of cortical T cell acute lymphoblastic leukemia with T lymphocytes secreting anti-CD1a T cell engagers.

BACKGROUND: The dismal clinical outcome of relapsed/refractory (R/R) T cell acute lymphoblastic leukemia (T-ALL) highlights the need for innovative targeted therapies. Although chimeric antigen receptor (CAR)-engineered T cells have revolutionized the treatment of B cell malignancies, their clinical implementation in T-ALL is in its infancy. CD1a represents a safe target for cortical T-ALL (coT-ALL) patients, and fratricide-resistant CD1a-directed CAR T cells have been preclinically validated as an immunotherapeutic strategy for R/R coT-ALL. Nonetheless, T-ALL relapses are commonly very aggressive and hyperleukocytic, posing a challenge to recover sufficient non-leukemic effector T cells from leukapheresis in R/R T-ALL patients. METHODS: We carried out a comprehensive study using robust in vitro and in vivo assays comparing the efficacy of engineered T cells either expressing a second-generation CD1a-CAR or secreting CD1a x CD3 T cell-engaging Antibodies (CD1a-STAb). RESULTS: We show that CD1a-T cell engagers bind to cell surface expressed CD1a and CD3 and induce specific T cell activation. Recruitment of bystander T cells endows CD1a-STAbs with an enhanced in vitro cytotoxicity than CD1a-CAR T cells at lower effector:target ratios. CD1a-STAb T cells are as effective as CD1a-CAR T cells in cutting-edge in vivo T-ALL patient-derived xenograft models. CONCLUSIONS: Our data suggest that CD1a-STAb T cells could be an alternative to CD1a-CAR T cells in coT-ALL patients with aggressive and hyperleukocytic relapses with limited numbers of non-leukemic effector T cells.