Dependence on mitochondrial respiration of malignant T cells reveals a new therapeutic target for angioimmunoblastic T-cell lymphoma.

Cancer metabolic reprogramming has been recognized as one of the cancer hallmarks that promote cell proliferation, survival, as well as therapeutic resistance. Up-to-date regulation of metabolism in T-cell lymphoma is poorly understood. In particular, for human angioimmunoblastic T-cell lymphoma (AITL) the metabolic profile is not known. Metabolic intervention could help identify new treatment options for this cancer with very poor outcomes and no effective medication. Transcriptomic analysis of AITL tumor cells, identified that these cells use preferentially mitochondrial metabolism. By using our preclinical AITL mouse model, mimicking closely human AITL features, we confirmed that T follicular helper (Tfh) tumor cells exhibit a strong enrichment of mitochondrial metabolic signatures. Consistent with these results, disruption of mitochondrial metabolism using metformin or a mitochondrial complex I inhibitor such as IACS improved the survival of AITL lymphoma-bearing mice. Additionally, we confirmed a selective elimination of the malignant human AITL T cells in patient biopsies upon mitochondrial respiration inhibition. Moreover, we confirmed that diabetic patients suffering from T-cell lymphoma, treated with metformin survived longer as compared to patients receiving alternative treatments. Taking together, our findings suggest that targeting the mitochondrial metabolic pathway could be a clinically efficient approach to inhibit aggressive cancers such as peripheral T-cell lymphoma.

Interplay between the Glymphatic System and the Endocannabinoid System: Implications for Brain Health and Disease.

The intricate mechanisms governing brain health and function have long been subjects of extensive investigation. Recent research has shed light on two pivotal systems, the glymphatic system and the endocannabinoid system, and their profound role within the central nervous system. The glymphatic system is a recently discovered waste clearance system within the brain that facilitates the efficient removal of toxic waste products and metabolites from the central nervous system. It relies on the unique properties of the brain's extracellular space and is primarily driven by cerebrospinal fluid and glial cells. Conversely, the endocannabinoid system, a multifaceted signaling network, is intricately involved in diverse physiological processes and has been associated with modulating synaptic plasticity, nociception, affective states, appetite regulation, and immune responses. This scientific review delves into the intricate interconnections between these two systems, exploring their combined influence on brain health and disease. By elucidating the synergistic effects of glymphatic function and endocannabinoid signaling, this review aims to deepen our understanding of their implications for neurological disorders, immune responses, and cognitive well-being.

Nanoceria as Safe Contrast Agents for X-ray CT Imaging.

Cerium oxide nanoparticles (CeO2NPs) have exceptional catalytic properties, rendering them highly effective in removing excessive reactive oxygen species (ROS) from biological environments, which is crucial in safeguarding these environments against radiation-induced damage. Additionally, the Ce atom's high Z number makes it an ideal candidate for utilisation as an X-ray imaging contrast agent. We herein show how the injection of albumin-stabilised 5 nm CeO2NPs into mice revealed substantial enhancement in X-ray contrast, reaching up to a tenfold increase at significantly lower concentrations than commercial or other proposed contrast agents. Remarkably, these NPs exhibited prolonged residence time within the target organs. Thus, upon injection into the tail vein, they exhibited efficient uptake by the liver and spleen, with 85% of the injected dose (%ID) recovered after 7 days. In the case of intratumoral administration, 99% ID of CeO2NPs remained within the tumour throughout the 7-day observation period, allowing for observation of disease dynamics. Mass spectrometry (ICP-MS) elemental analysis confirmed X-ray CT imaging observations.

Epigenetic targets in B- and T-cell lymphomas: latest developments.

Non-Hodgkin's lymphomas (NHLs) comprise a diverse group of diseases, either of mature B-cell or of T-cell derivation, characterized by heterogeneous molecular features and clinical manifestations. While most of the patients are responsive to standard chemotherapy, immunotherapy, radiation and/or stem cell transplantation, relapsed and/or refractory cases still have a dismal outcome. Deep sequencing analysis have pointed out that epigenetic dysregulations, including mutations in epigenetic enzymes, such as chromatin modifiers and DNA methyltransferases (DNMTs), are prevalent in both B- cell and T-cell lymphomas. Accordingly, over the past decade, a large number of epigenetic-modifying agents have been developed and introduced into the clinical management of these entities, and a few specific inhibitors have already been approved for clinical use. Here we summarize the main epigenetic alterations described in B- and T-NHL, that further supported the clinical development of a selected set of epidrugs in determined diseases, including inhibitors of DNMTs, histone deacetylases (HDACs), and extra-terminal domain proteins (bromodomain and extra-terminal motif; BETs). Finally, we highlight the most promising future directions of research in this area, explaining how bioinformatics approaches can help to identify new epigenetic targets in B- and T-cell lymphoid neoplasms.

Weight bias internalization among adolescents in Spain: psychological correlates across gender diversity and weight status / La internalización de los prejuicios de peso entre los y las adolescentes en España: correlatos psicológicos en función del género y el estatus de peso

Weight bias internalization refers to the negative weight-related attributions applied to oneself, but it does not just occur in the highest weight statuses, but rather exists across the entire weight spectrum. There is a negative impact associated to increase psychological problems in adults, however, it has been less studied among the adolescent Spanish population. In this study, we assess the relationship between the internalization of weight bias, social attitudes towards appearance, body appreciation and self-esteem, and potential differences regarding gender and weight status. A community sample of 1258 Spanish adolescents between 12 and 18 years old (46.3% male gender; Mage = 15.58; SD = 1.59; 49.5% female gender; Mage = 15.59; SD = 1.67; and 4.1% non-binary gender; Mage = 14.86; SD = 2.86) participated in the study. The Modified Weight Bias Internalization Scale (WBIS-M), the Rosenberg Self-Esteem Scale (RSES), and the Sociocultural Attitudes Towards Appearance Questionnaire (SATAQ-4) were used. ANOVA’s test and bivariate correlations were performed. The results suggest that females (t = -.55; p ≤ .001) and non-binary adolescents (t = .64; p ≤ .01) have higher levels of WBI-M compared to males. Regarding weight status, the group with obesity (t = 1.39; p ≤ .001) and the group with overweight (t = -.81; p ≤ .001) have higher levels of WBI-M compared to the normal weight group. Significant correlations between WBI-M and the assessed psychological variables were found in the total sample, and across all-gender and weight categories, except for the underweight group. These results are a first approximation to the internalization of weight bias in a Spanish adolescent sample and highlight the need to introduce this concept in prevention and psychological interventions in school context. (AU)

La internalización de los prejuicios de peso hace referencia a las atribuciones negativas relacionadas con el peso aplicadas a uno mismo/a, lo cual no ocurre únicamente en las personas con un estatus de peso elevado, sino en todo el rango de pesos. En adultos, existe evidencia de su impacto negativoasociados a incrementar problemas psicológicos; aunque se ha estudiado en menor medida en la población adolescente. El objetivo de este estudio fue examinar la relación entre la internalización de prejuicios de peso, las actitudes socioculturales hacia la apariencia, la apreciación corporal y el nivel de autoestima, y analizar las posibles diferencias en función del género y del estatus de peso. Participaron 1.258 adolescentes españoles de una muestra comunitaria entre 12 y 18 años (46.3% género masculino; Medad = 15.58; DT = 1.59; 49,5% género femenino; Medad = 15.59; DT = 1.67; y 4.1% género no binario; Medad = 14.86; DT = 2.86). Se utilizaron la escala de internalización de prejuicios de peso modificado (WBIS-M), la escala de autoestima de Rosenberg (RSES) y el cuestionario de actitudes socioculturales hacia la apariencia (SATAQ-4). Se realizó la prueba ANOVA y correlaciones bivariadas. Los resultados sugieren que el grupo identificado con el género femenino (t = -.55; p ≤ .001) y con el no binario (t = .64; p ≤ .01) muestran niveles más altos de internalización del sesgo de peso en comparación con el género masculino. En cuanto al estado ponderal, el grupo con obesidad (t = 1.39; p ≤ .001) y el grupo con sobrepeso (t = -.81; p ≤ .001) presentan niveles más altos de internalización de prejuicios de peso en comparación con el grupo con normopeso. Se encontraron correlaciones significativas entre las puntuaciones del WBIS-M y las variables psicológicas evaluadas en la muestra total yen todas las categorías de género y peso, con la excepción del grupo de bajo peso. (AU)

Exploring the Long-Term Tissue Accumulation and Excretion of 3 nm Cerium Oxide Nanoparticles after Single Dose Administration.

Nanoparticle (NP) pharmacokinetics significantly differ from traditional small molecule principles. From this emerges the need to create new tools and concepts to harness their full potential and avoid unnecessary risks. Nanoparticle pharmacokinetics strongly depend on size, shape, surface functionalisation, and aggregation state, influencing their biodistribution, accumulation, transformations, and excretion profile, and hence their efficacy and safety. Today, while NP biodistribution and nanoceria biodistribution have been studied often at short times, their long-term accumulation and excretion have rarely been studied. In this work, 3 nm nanoceria at 5.7 mg/kg of body weight was intravenously administrated in a single dose to healthy mice. Biodistribution was measured in the liver, spleen, kidney, lung, brain, lymph nodes, ovary, bone marrow, urine, and faeces at different time points (1, 9, 30, and 100 days). Biodistribution and urinary and faecal excretion were also studied in rats placed in metabolic cages at shorter times. The similarity of results of different NPs in different models is shown as the heterogeneous nanoceria distribution in organs. After the expectable accumulation in the liver and spleen, the concentration of cerium decays exponentially, accounting for about a 50% excretion of cerium from the body in 100 days. Cerium ions, coming from NP dissolution, are most likely excreted via the urinary tract, and ceria nanoparticles accumulated in the liver are most likely excreted via the hepatobiliary route. In addition, nanoceria looks safe and does not damage the target organs. No weight loss or apathy was observed during the course of the experiments.

Interacción de los rasgos de personalidad de los padres con hijas adolescentes al inicio de la anorexia nerviosa: un estudio de casos y controles / Interaction of parental personality traits with adolescent daughters at the onset of anorexia nervosa: a case-control study

El objetivo del estudio fue examinar la relación entre los rasgos de personalidad de los padres y sus hijas con anorexia nerviosa (AN) mediante un estudio de casos y controles. Fueron evaluadas 50 chicas adolescentes con AN (G-AN) y 50 chicas sanas (GC), junto con sus padres, con el “Inventario de temperamento y carácter revisado” y el “Inventario de trastornos de la conducta alimentaria-2”. El G-AN y el GC no difirieron en los rasgos de personalidad. Los padres del G-AN mostraron diferencias significativas en los rasgos temperamentales y de carácter en comparación con los padres del GC. Se encontraron relaciones complementarias en la evitación del daño de las madres con la cooperación y la fantasía de las hijas en el G-AN, mientras que en los padres y las hijas se encontraron asociaciones entre la dependencia de la recompensa, la persistencia y la autodirección. La única escala que discriminó entre el G-AN y GC fue la obsesión por la delgadez (clasificación: 74,7%). La identificación de los rasgos de personalidad de padres y adolescentes al inicio de la AN permitirá mejorar la intervención. (AU)

Relationship between Dynamic and Isometric Strength, Power, Speed, and Average Propulsive Speed of Recreational Athletes.

The purpose of this study was to examine the type of relationship between measures of maximal force (dynamic and isometric), maximal power, and mean propulsive velocity. In total, 355 recreational athletes, 96 women (age 20.5 ± 2.5 years; height 158.2 ± 17.3 cm; weight 61.8 ± 48.4 kg) and 259 men (age 21.0 ± 2.6 years; height 170.5 ± 12.6 cm; weight 65.9 ± 9.2 kg) were evaluated in three sessions separated by 72 h each in isometric midthigh pull exercise (ISOS) (kg), bench press maximum strength (1RM MSBP) (kg), jump height (CMJ) (m), and maximum pedaling power (WT) the maximum squat strength (1RM MSS) (kg), the mean propulsive velocity in the bench press (MPVBP) (m·s-1), and the peak power (PPBP) (w), mean propulsive squat velocity (MPVS) (m·s-1), peak power (PP) (w), maximum handgrip force (ISOHG) (kg), and 30 m movement speed (V30) (s). Significant correlations (p ≤ 0.01) were identified between 95% of the various manifestations of force, and only 5% presented a significance of p ≤ 0.05; however, when the magnitude of these correlations is observed, there is great heterogeneity. In this sense, the dynamic strength tests present the best correlations with the other strength and power tests used in the present study, followed by PPBP and PP. The results of this study complement what is reported in the literature regarding the correlation between different types of force manifestations being heterogeneous and contradictory.

Role of Common Cell Culture Media Supplements on Citrate-Stabilized Gold Nanoparticle Protein Corona Formation, Aggregation State, and the Consequent Impact on Cellular Uptake.

Sodium citrate-stabilized gold nanoparticles (AuNPs) are destabilized when dispersed in cell culture media (CCMs). This may promote their aggregation and subsequent sedimentation, or under the proper conditions, their interaction with dispersed proteins can lead to the formation of a NP-stabilizing protein corona. CCMs are ionic solutions that contain growth substances which are typically supplemented, in addition to serum, with different substances such as dyes, antioxidants, and antibiotics. In this study, the impact of phenol red, penicillin-streptomycin, l-glutamine, and ß-mercaptoethanol on the formation of the NP-protein corona in CCMs was investigated. Similar protein coronas were obtained except in the presence of antibiotics. Under these conditions, the protein corona took more time to be formed, and its density and composition were altered, as indicated by UV-vis spectroscopy, Z potential, dynamic light scattering, and liquid chromatography-mass spectrometry analyses. As a consequence of these modifications, a significantly different AuNP cellular uptake was measured, showing that NP uptake increased as did the NP aggregate formation. AuNP uptake studies performed in the presence of clathrin- and caveolin-mediated endocytosis inhibitors showed that neither clathrin receptors nor lipid rafts were significantly involved in the internalization mechanism. These results suggest that in these conditions, NP aggregation is the main mechanism responsible for their cellular uptake.

Bar Load-Velocity Profile of Full Squat and Bench Press Exercises in Young Recreational Athletes.

The purpose of this study was to determine the mean propulsive velocity (MVP) at various percentages of one repetition maximum (1RM) in the full squat and chest press exercises. A total of 96 young women and 256 young men (recreational athletes) performed an incremental test (50−60−70−80% 1RM) comprising the bench press and full squat exercises in two different sessions. The individual load and velocity ratios were established through the MPV. Data were analyzed using SPSS software version 25.0, with the significance level set at 5%. The following findings were revealed: highly linear load-velocity relationships in the group of women (r = 0.806 in the squat, and r = 0.872 in the bench press) and in the group of men (r = 0.832 and r = 0.880, respectively); significant differences (p < 0.001) in the MPV at 50−70−80% 1RM between the bench press and the full squat in men and at 70−80% 1RM in women; and a high variability in the MPV (11.49% to 22.63) in the bench press and full squat (11.58% to 25.15%) was observed in women and men (11.31% to 21.06%, and 9.26% to 24.2%) at the different percentages of 1RM evaluated. These results suggest that the load-velocity ratio in non-strength-trained subjects should be determined individually to more precisely establish the relative load to be used in a full squat and bench press training program.

Multifaceted modes of action of the anticancer probiotic Enterococcus hirae.

A deviated repertoire of the gut microbiome predicts resistance to cancer immunotherapy. Enterococcus hirae compensated cancer-associated dysbiosis in various tumor models. However, the mechanisms by which E. hirae restored the efficacy of cyclophosphamide administered with concomitant antibiotics remain ill defined. Here, we analyzed the multifaceted modes of action of this anticancer probiotic. Firstly, E. hirae elicited emigration of thymocytes and triggered systemic and intratumoral IFNγ-producing and CD137-expressing effector memory T cell responses. Secondly, E. hirae activated the autophagy machinery in enterocytes and mediated ATG4B-dependent anticancer effects, likely as a consequence of its ability to increase local delivery of polyamines. Thirdly, E. hirae shifted the host microbiome toward a Bifidobacteria-enriched ecosystem. In contrast to the live bacterium, its pasteurized cells or membrane vesicles were devoid of anticancer properties. These pleiotropic functions allow the design of optimal immunotherapies combining E. hirae with CD137 agonistic antibodies, spermidine, or Bifidobacterium animalis. We surmise that immunological, metabolic, epithelial, and microbial modes of action of the live E. hirae cooperate to circumvent primary resistance to therapy.

Bone mineral density and low bone mass in severely burned patients: A retrospective cohort study.

INTRODUCTION: Severe burns can alter bone metabolism through different mechanisms. Despite prior published studies describing the association between burns and a decrease in bone mineral density (BMD), no clinical guidelines currently exist recommending the systematic evaluation of bone health in patients after severe burns. This study aims to describe the BMD of individuals with severe burn injuries and healthy controls and determine the frequency of low-to-normal bone mass (LNBM) and BMD below the expected range for age (BEA). MATERIALS AND METHODS: We conducted a retrospective cohort of patients with either severe thermal or electrical burns and healthy controls paired by gender and age. We performed a dual-energy X-ray absorptiometry at least 90 days after the burn and collected data from each patient's clinical evaluation and clinical file. RESULTS: A total of 77 patients (64 men and 13 women) and their paired controls were included in the study (age [mean ± standard deviation, SD]: 30.37 ± 8.66 years). Patients participated in the study an average of 315 ± 438 days after their burn. The BMD (grs/cm2) in total hip burned vs controls was: 0.998 ± 0.135 vs 1.059 ± 0.12 (p = 0.004); femoral neck 0.876 ± 0.121 vs 0.915 ± 0.097 (p = 0.031), spine 0.977 ± 0.127 vs 1.003 ± 0.076 (p = 0.132).The Z-scores for total hip were - 0.06 ± 1.05 vs 0.41 ± 0.80 (p = 0.002); for neck -0.39 ± 0.89 vs -0.01 ± 0.77 (p = 0.005); and for spine -0.75 ± 1.11 vs -0.32 ± 0.73 (p = 0.005). The proportion of subjects with BMD BEA in burns vs controls was 5.2 vs 1.2% (p = 0.05) in total hip, 3.9 vs 0% (p = 0.045) in the neck, and 18.2 vs 1.2% (p = 0.001) in the spine. The logistic regression model found-in burn patients vs controls-an OR of 9.83 for BMD BEA (CI 95%: 2.17-44.45, p = 003), OR = 4.05 for electrical burns (CI 95%: 1.72-20.89, p = 004) and OR = 15.16 for thermal burns (CI 95%: 2.91-79.00, p = 001). The model also found an OR = 2.48 for LNBM (CI 95%: 1.25-4.93, p = 0.009). The burn variables associated with BMD BEA at any site in the patients were BMI >25 Kg/m2 with an OR = 0.180 (CI 95%: 0.046-0.710, p = 0.014); and the lower limb amputation with an OR = 7.33 (CI 95%; 1.12-48.33, p = 0.038). Five burn patients had a fragility fracture. CONCLUSION: BMD was significantly lower in severely burned patients than in controls, and the proportion BMD BEA cases was significantly higher in the burn patient sample. Severe burns are a strong independent predictor of bone loss, and this risk is maintained for an extended period after the burn.

Publisher Correction: Immunoprophylactic and immunotherapeutic control of hormone receptor-positive breast cancer.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Immunoprophylactic and immunotherapeutic control of hormone receptor-positive breast cancer.

Hormone receptor (HR)+ breast cancer (BC) causes most BC-related deaths, calling for improved therapeutic approaches. Despite expectations, immune checkpoint blockers (ICBs) are poorly active in patients with HR+ BC, in part reflecting the lack of preclinical models that recapitulate disease progression in immunocompetent hosts. We demonstrate that mammary tumors driven by medroxyprogesterone acetate (M) and 7,12-dimethylbenz[a]anthracene (D) recapitulate several key features of human luminal B HR+HER2- BC, including limited immune infiltration and poor sensitivity to ICBs. M/D-driven oncogenesis is accelerated by immune defects, demonstrating that M/D-driven tumors are under immunosurveillance. Safe nutritional measures including nicotinamide (NAM) supplementation efficiently delay M/D-driven oncogenesis by reactivating immunosurveillance. NAM also mediates immunotherapeutic effects against established M/D-driven and transplantable BC, largely reflecting increased type I interferon secretion by malignant cells and direct stimulation of immune effector cells. Our findings identify NAM as a potential strategy for the prevention and treatment of HR+ BC.

Gut Bacteria Composition Drives Primary Resistance to Cancer Immunotherapy in Renal Cell Carcinoma Patients.

BACKGROUND: The development of immune checkpoint blockade (ICB) has revolutionized the clinical outcome of renal cell carcinoma (RCC). Nevertheless, improvement of durability and prediction of responses remain unmet medical needs. While it has been recognized that antibiotics (ATBs) decrease the clinical activity of ICB across various malignancies, little is known about the direct impact of distinct intestinal nonpathogenic bacteria (commensals) on therapeutic outcomes of ICB in RCC. OBJECTIVE: To evaluate the predictive value of stool bacteria composition for ICB efficacy in a cohort of advanced RCC patients. DESIGN, SETTING, AND PARTICIPANTS: We prospectively collected fecal samples from 69 advanced RCC patients treated with nivolumab and enrolled in the GETUG-AFU 26 NIVOREN microbiota translational substudy phase 2 trial (NCT03013335) at Gustave Roussy. We recorded patient characteristics including ATB use, prior systemic therapies, and response criteria. We analyzed 2994 samples of feces from healthy volunteers (HVs). In parallel, preclinical studies performed in RCC-bearing mice that received fecal transplant (FMT) from RCC patients resistant to ICB (NR-FMT) allowed us to draw a cause-effect relationship between gut bacteria composition and clinical outcomes for ICB. The influence of tyrosine kinase inhibitors (TKIs) taken before starting nivolumab on the microbiota composition has also been assessed. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Metagenomic data (MG) from whole genome sequencing (WGS) were analyzed by multivariate and pairwise comparisons/fold ratio to identify bacterial fingerprints related to ATB or prior TKI exposure and patients' therapeutic response (overall response and progression-free survival), and compared with the data from cancer-free donors. RESULTS AND LIMITATIONS: Recent ATB use (n = 11; 16%) reduced objective response rates (from 28% to 9%, p < 0.03) and markedly affected the composition of the microbiota, facilitating the dominance of distinct species such as Clostridium hathewayi, which were also preferentially over-represented in stools from RCC patients compared with HVs. Importantly, TKIs taken prior to nivolumab had implications in shifting the microbiota composition. To establish a cause-effect relationship between gut bacteria composition and ICB efficacy, NR-FMT mice were successfully compensated with either FMT from responding RCC patients or beneficial commensals identified by WGS-MG (Akkermansia muciniphila and Bacteroides salyersiae). CONCLUSIONS: The composition of the microbiota is influenced by TKIs and ATBs, and impacts the success of immunotherapy. Future studies will help sharpen the role of these specific bacteria and their potential as new biomarkers. PATIENT SUMMARY: We used quantitative shotgun DNA sequencing of fecal microbes as well as preclinical models of fecal or bacterial transfer to study the association between stool composition and (pre)clinical outcome to immune checkpoint blockade. Novel insights into the pathophysiological relevance of intestinal dysbiosis in the prognosis of kidney cancer may lead to innovative therapeutic solutions, such as supplementation with probiotics to prevent primary resistance to therapy.

Autolesiones online entre adolescentes españoles: análisis de la prevalencia y de las motivaciones / Digital self-harm among spanish adolescents: analysis of prevalence and motivations

Las autolesiones online ("digital self-harm") consisten en el uso de las tecnologías de la información y la comunicación, como Internet y el teléfono móvil, para colgar, enviar o compartir contenidos que incluyen autolesiones físicas o que resultan dañinos o humillantes para uno mismo. El primer objetivo de este estudio consistió en examinar la prevalencia de diferentes formas de autolesiones online entre adolescentes. El segundo objetivo fue el de analizar las motivaciones para implicarse en autolesiones online empleando, para ello, una metodología cualitativa de análisis de contenido. La muestra de este estudio estuvo compuesta por 794 participantes (50.6% mujeres) entre 12 y 18 años (M = 14.29 y DT = 1.64). El 7.9% de los adolescentes reconoció haberse provocado algún daño físico y contarlo en Internet y el 3.8% haber publicado las fotos de una autolesión en Internet. Las motivaciones más frecuentes para implicarse en autolesiones online fueron: 1) hacerlo como una expresión de malestar; 2) buscar desahogo o alivio; 3) buscar la atención y comprensión de otros; 4) ver la reacción de otros; 5) porque consideraban que era gracioso; y 6) porque otros lo hacen o es "una moda". Los resultados sugieren que nos encontramos ante un problema preocupante que requiere ser mejor investigado

Digital self-harm consists of the use of information and communication technologies, as Internet and mobile phone, to post, send or share content that is harmful or humiliating to oneself. The first objective of this study was to examine the prevalence of different forms of digital self-harm among adolescents. The second objective was to analyze the motivations to engage in digital self-harm using, to this end, a qualitative methodology of content analysis. The sample of this study was composed of 794 participants (50.6% women) between 12 and 18 years (M = 14.29 y DT = 1.64). The 7.9% of the adolescents recognized having caused some physical damage and posting it on the Internet and 3.8% having published the photos of the self-harm on the Internet. The main motivations for engaging in digital self-harm were: 1) doing it as an expression of distress; 2) seeking relief; 3) looking for others' attention and understanding; 4) see the reaction of others; 5) because they considered that it was funny; and 6) because others do it or it is "a fad". The results suggest that we are facing a worrying problem that needs to be better investigated

Fitness for health assessment in unilateral lower limb amputation: The Evam1 battery.

BACKGROUND: During the rehabilitation phase, physical exercise is a key element that requires an assessment of the best alternatives for application since the pre-prosthetic phase (PPF) for an accurate prescription. Therefore, the assessment of fitness for health (FFH) shall be included in the initial rehabilitation process. OBJECTIVE: To develop a FFH evaluation battery (Evam1) for pre-prosthetic unilateral lower-limb amputees (PPULLA). METHOD: A descriptive study of the theoretical construction and validation of a FFH evaluation battery based on a review of international literature for tests that measure amputee physical capability. RESULTS: During the scientific literature review, no batteries designed with this goal were found. We therefore designed a battery that was assembled of five tests for anthropometry, aerobic capacity, strength and flexibility. Combined leg and arm cycloergometrics, isokinetic dynamometry, and flexi test are the most reliable tests for the corresponding assessment of each component. CONCLUSIONS: PPF is of great importance, since the basic physical capabilities are altered due to long immobilization and hospitalization periods, inadequate postures, alteration of basic daily activities, and decrease in participation in sports, recreational, and work activities. This is a fundamental proposal, given that the procedures for FFH assessment of PPULLA have been rarely addressed, thus limiting the information on assessment methods, processes and/or tests established for these procedures.

GAPDH Overexpression in the T Cell Lineage Promotes Angioimmunoblastic T Cell Lymphoma through an NF-κB-Dependent Mechanism.

GAPDH is emerging as a key player in T cell development and function. To investigate the role of GAPDH in T cells, we generated a transgenic mouse model overexpressing GAPDH in the T cell lineage. Aged mice developed a peripheral Tfh-like lymphoma that recapitulated key molecular, pathological, and immunophenotypic features of human angioimmunoblastic T cell lymphoma (AITL). GAPDH induced non-canonical NF-κB pathway activation in mouse T cells, which was strongly activated in human AITL. We developed a NIK inhibitor to reveal that targeting the NF-κB pathway prolonged AITL-bearing mouse survival alone and in combination with anti-PD-1. These findings suggest the therapeutic potential of targeting NF-κB signaling in AITL and provide a model for future AITL therapeutic investigations.

Tumor lysis with LTX-401 creates anticancer immunity.

Local immunotherapies such as the intratumoral injection of oncolytic compounds aim at reinstating and enhancing systemic anticancer immune responses. LTX-315 is a first-in-class, clinically evaluated oncolytic peptide-based local immunotherapy that meets these criteria. Here, we show that LTX-401, yet another oncolytic compound designed for local immunotherapy, depicts a similar safety profile and that sequential local inoculation of LTX-401 was able to cure immunocompetent host from subcutaneous MCA205 and TC-1 cancers. Cured animals exhibited long-term immune memory effects that rendered them resistant to rechallenge with syngeneic tumors. Nevertheless, the local treatment with LTX-401 alone had only limited abscopal effects on secondary contralateral lesions. Anticancer effects resulting from single as well as sequential injections of LTX-401 were boosted in combination with PD-1 and CTLA-4 immune checkpoint blockade (ICB), and sequential LTX-401 treatment combined with double ICB exhibited strong abscopal antineoplastic effects on contralateral tumors underlining the potency of this combination therapy.

AIF-regulated oxidative phosphorylation supports lung cancer development.

Cancer is a major and still increasing cause of death in humans. Most cancer cells have a fundamentally different metabolic profile from that of normal tissue. This shift away from mitochondrial ATP synthesis via oxidative phosphorylation towards a high rate of glycolysis, termed Warburg effect, has long been recognized as a paradigmatic hallmark of cancer, supporting the increased biosynthetic demands of tumor cells. Here we show that deletion of apoptosis-inducing factor (AIF) in a KrasG12D-driven mouse lung cancer model resulted in a marked survival advantage, with delayed tumor onset and decreased malignant progression. Mechanistically, Aif deletion leads to oxidative phosphorylation (OXPHOS) deficiency and a switch in cellular metabolism towards glycolysis in non-transformed pneumocytes and at early stages of tumor development. Paradoxically, although Aif-deficient cells exhibited a metabolic Warburg profile, this bioenergetic change resulted in a growth disadvantage of KrasG12D-driven as well as Kras wild-type lung cancer cells. Cell-autonomous re-expression of both wild-type and mutant AIF (displaying an intact mitochondrial, but abrogated apoptotic function) in Aif-knockout KrasG12D mice restored OXPHOS and reduced animal survival to the same level as AIF wild-type mice. In patients with non-small cell lung cancer, high AIF expression was associated with poor prognosis. These data show that AIF-regulated mitochondrial respiration and OXPHOS drive the progression of lung cancer.