Significance of clinical-immunological patterns and diagnostic yield of biopsies in microscopic polyangiitis and granulomatosis with polyangiitis.

BACKGROUND: Microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA) are the two major antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). OBJECTIVES: To characterize a homogenous AAV cohort and to assess the impact of clinicopathological profiles and ANCA serotypes on clinical presentation and prognosis. Clinical differences in GPA patients according to ANCA serotype and the diagnostic yield for vasculitis of biopsies in different territories were also investigated. RESULTS: This retrospective study (2000-2021) included 152 patients with AAV (77 MPA/75 GPA). MPA patients (96.1% myeloperoxidase [MPO]-ANCA and 2.6% proteinase 3 [PR3]-ANCA) presented more often with weight loss, myalgia, renal involvement, interstitial lung disease (ILD), cutaneous purpura, and peripheral nerve involvement. Patients with GPA (44% PR3-ANCA, 33.3% MPO, and 22.7% negative/atypical ANCA) presented more commonly with ear, nose, and throat and eye/orbital manifestations, more relapses, and higher survival than patients with MPA. GPA was the only independent risk factor for relapse. Poor survival predictors were older age at diagnosis and peripheral nerve involvement. ANCA serotypes differentiated clinical features in a lesser degree than clinical phenotypes. A mean of 1.5 biopsies were performed in 93.4% of patients in different territories. Overall, vasculitis was identified in 80.3% (97.3% in MPA and 61.8% in GPA) of patients. CONCLUSIONS: The identification of GPA presentations associated with MPO-ANCA and awareness of risk factors for relapse and mortality are important to guide proper therapeutic strategies in AAV patients. Biopsies of different affected territories should be pursued in difficult-to-diagnose patients based on their significant diagnostic yield.

Effect of supplementing a Bacillus subtilis-based probiotic on performance, intestinal integrity, and serum antioxidant capacity and metabolites concentrations of heat-stressed growing pigs.

Exposing pigs to heat stress (HS) seems to modify the intestinal microbiota which may compromise the integrity of the small intestine epithelia. Probiotics, live microorganisms, can help pigs to maintain a healthy intestinal environment. Eighty pigs (21.6 ±â€…3.4 kg body weight) exposed to HS or thermal neutral (TN) conditions were used to evaluate the effect of a Bacillus subtilis-based probiotic on performance, body temperature, and intestinal integrity. Treatments were: TN pigs fed a control diet without (TN-C) or with 1 × 106 CFU probiotic/g of feed (TN-P), and HS pigs fed a control without (HS-C) or with probiotic (HS-P). The control diet was formulated with wheat, soybean meal, and free amino acids (AA). Feed and water were freely available during the 21-d study. At completion, samples from duodenum, jejunum, and ileum were collected to analyze epithelial histology and tight junction protein expression; antioxidant activity, and free AA and metabolites in serum. Relative abundance of Lactobacillus, Bifidobacterium, Escherichia coli, and Bacillus in ileal content was analyzed. Ambient temperature in the TN room ranged from 19 to 25 °C, and in HS room from 30 to 38.5 °C. Intestinal temperature in HS-P pigs was lower than in HS-C pigs. Weight gain and feed intake reduced, but feed:gain and respiration rate increased in HS compared to TN pigs, regardless of diet (P < 0.01). Probiotic increased weight gain and improved feed:gain (P < 0.05) in both TN and HS pigs, but feed intake did not differ. Heat stress decreased villi height in jejunum and villi height:crypt depth in duodenum and jejunum (P < 0.05). Probiotic increased villi height in duodenum and ileum, and villi height:crypt depth in all small intestine segments (P < 0.05). Relative abundance of Lactobacillus and Bifidobacterium tended to reduce, and E. coli tended to increase (P < 0.10) in ileal content of HS-C pigs. Ileal relative abundance of Bacillus was higher (P < 0.01) in HS-P pigs than in HS-C and TN-C pigs. Cystathionine, homocysteine, hydroxylysine, α-amino-adipic acid, citrulline, α-amino-n-butyric acid, P-Ser, and taurine were higher in HS than in TN pigs (P < 0.05). These data confirm the negative effect of HS on performance, body temperature, and intestinal integrity of pigs. These data suggest that supplementing 1 × 106 CFU probiotic/g of feed based on Bacillus subtilis DSM 32540 may help to counteract the negative effects of HS on the performance and intestinal integrity of pigs.

High ambient temperature provokes heat stress in animals, and pigs are highly affected showing low performance, and intestinal integrity and microbiota compromised. Probiotics could help pigs to maintain a healthy intestinal environment. We analyzed the effect of a probiotic based on Bacillus subtilis on growth performance, intestinal integrity of small intestine, intestinal microbiota, antioxidant activity, and serum concentration of amino acids in pigs under heat stress (HS) and thermal neutral (TN) conditions. Ambient temperature under TN and HS conditions was 19­25 and 30­38.5 °C, respectively. Weight gain and feed intake reduced in HS pigs compared to TN pigs, but probiotic increased weight gain in both TN and HS pigs. Heat stress decreased villi size in duodenum and jejunum, and probiotic restored them. Relative abundance of Lactobacillus and Bifidobacterium reduced and Escherichia coli increased in the small intestine content of HS pigs; probiotic increased the abundance of Bacillus. The activity of antioxidant enzymes increased in HS pigs fed the probiotic diet. Serum concentration of amino acid metabolites was affected by HS. These data suggest that supplementing a Bacillus subtilis-based probiotic may help to counteract the negative effects of HS on the performance and intestinal integrity of pigs.

Iron accumulation drives fibrosis, senescence and the senescence-associated secretory phenotype.

Fibrogenesis is part of a normal protective response to tissue injury that can become irreversible and progressive, leading to fatal diseases. Senescent cells are a main driver of fibrotic diseases through their secretome, known as senescence-associated secretory phenotype (SASP). Here, we report that cellular senescence, and multiple types of fibrotic diseases in mice and humans are characterized by the accumulation of iron. We show that vascular and hemolytic injuries are efficient in triggering iron accumulation, which in turn can cause senescence and promote fibrosis. Notably, we find that senescent cells persistently accumulate iron, even when the surge of extracellular iron has subdued. Indeed, under normal conditions of extracellular iron, cells exposed to different types of senescence-inducing insults accumulate abundant ferritin-bound iron, mostly within lysosomes, and present high levels of labile iron, which fuels the generation of reactive oxygen species and the SASP. Finally, we demonstrate that detection of iron by magnetic resonance imaging might allow non-invasive assessment of fibrotic burden in the kidneys of mice and in patients with renal fibrosis. Our findings suggest that iron accumulation plays a central role in senescence and fibrosis, even when the initiating events may be independent of iron, and identify iron metabolism as a potential therapeutic target for senescence-associated diseases.

Estigma en mujeres de peso alto a través de un análisis fenomenológico interpretativo

Tener peso alto es una característica que ha sido devaluada y denigrada socialmente, convirtiendo a las personas de cuerpos grandes en víctimas de estereotipos, prejuicios y discriminación, lo que se ha denominado estigmatización por el peso, fenómeno que ocurre especialmente en mujeres. El objetivo de este estudio fue describir las experiencias de estigma de peso de mujeres con obesidad que viven en el sur de Chile. Participaron seis mujeres entre 20 y 57 años a través de entrevistas semi-estructuradas realizadas de manera remota. Mediante Análisis Fenomenológico Interpretativo se identificaron cuatro supratemas y diversos subtemas, los supratemas son: 1. La obesidad como parte de la persona. 2. Las experiencias de sentirse discriminada. 3. Todo gira en función del peso. 4. Lo que la sociedad piensa de la obesidad, los que en su conjunto permiten caracterizar la experiencia de vivir con obesidad y sufrir el estigma asociado al peso en distintos ámbitos de sus vidas, incluso en contextos sanitarios. Las consecuencias de esta experiencia son diversas y negativas, destacando el impacto que tiene en su autoestima y las constantes emociones negativas que derivan de las situaciones de discriminación. Estos resultados ponen de manifiesto la importancia de avanzar hacia la diversidad y aceptación corporal, lo que supone un desafío a la sociedad en general y en particular a los proveedores de salud, ya que se requiere de intervenciones libres de prejuicios y orientadas a la salud y el bienestar de las personas.

Carrying a high weight is a characteristic that has been devalued and socially denigrated, turning people with large bodies into victims of stereotypes, prejudice, or discrimination, which has been called weight stigmatisation, a phenomenon that occurs especially in women. The aim of this study was to describe the weight stigma experiences of women with obesity who live in southern Chile. Six women between 20 and 57 years of age participated in semi-structured interviews conducted remotely. Through Interpretative Phenomenological Analysis four supra-themes and several sub-themes were identified, the supra-themes are: 1. Obesity as part of the person. 2. Experiences of feeling discriminated. 3. Everything is about weight. 4. what society thinks of obesity, which together allow characterising the experience of living with obesity and suffering the weight stigma in different areas of their lives, including in health contexts. The consequences of this experience are diverse and negative, highlighting the impact it has on their self-esteem and the constant negative emotions that derive from discrimination situations. These results highlight the importance of moving toward body diversity and acceptance, which is a challenge for society in general and health care providers in particular, as it requires interventions free from prejudice and orientated to the health and well-being of individuals.

Revisión sobre intervenciones de enfermería exitosas en educación sexual en adolescentes

Introducción: En la adolescencia son frecuentes los comportamientos sexuales de riesgo asociados a desinformación y falta de asesoramiento de la familia y de los profesionales de enfermería, lo que constituye un problema de salud pública. Objetivo: Analizar las evidencias científicas que existen sobre intervenciones de enfermería exitosas en el marco de la educación sexual orientada a la población escolar adolescente. Método: Revisión bibliográfica en las bases de datos Dialnet, LILACS y Pubmed. Los criterios de inclusión consideraron documentos que contenían intervenciones de enfermería escolar en educación sexual en población adolescente. Respecto a la selección por calidad metodológica de los artículos, se recurrió a lectura crítica, mediante la aplicación de la lista de comprobación CASPe. Luego se emplearon técnicas de análisis de contenido y se presentaron los resultados en tablas. Resultados: Las intervenciones de enfermería en educación demostraron efectos positivos sobre la salud sexual de los adolescentes, al mejorar sus conocimientos en prevención de embarazo e infecciones de transmisión sexual y disminuir significativamente la probabilidad de cometer conductas de riesgo. Conclusión: Según la bibliografía seleccionada se concluye que la enfermera escolar es un recurso indispensable para padres y educadores, al implementar programas educativos que promueven un desarrollo sexual saludable en los adolescentes.

Introdução: Na adolescência, são frequentes os comportamentos sexuais de risco associados à desinformação e à falta de orientação da família e dos profissionais de enfermagem, o que constitui um problema de saúde pública. Objetivo: Analisar as evidências científicas sobre intervenções de enfermagem bem-sucedidas no âmbito da educação sexual voltada para a população escolar adolescente. Método: Revisão bibliográfica nas bases de dados Dialnet, LILACS e Pubmed. Os critérios de inclusão consideraram documentos que continham intervenções de enfermagem escolar em educação sexual na população adolescente. Para a seleção dos artigos quanto à qualidade metodológica, foi utilizada a leitura crítica, aplicando a lista de verificação CASPe. Foram empregadas técnicas de análise de conteúdo e os resultados foram apresentados em tabelas. Resultados: As intervenções de enfermagem na educação demonstraram efeitos positivos na saúde sexual dos adolescentes, melhorando seu conhecimento sobre gravidez e prevenção de infecções sexualmente transmissíveis e reduzindo significativamente a probabilidade de cometer comportamentos de risco. Conclusão: De acordo com a bibliografia selecionada, conclui-se que o enfermeiro escolar é um recurso indispensável para pais e educadores na implementação de programas educacionais que promovam o desenvolvimento sexual saudável em adolescentes.

Introduction: In adolescence, risky sexual behaviors associated with misinformation and lack of advice from the family and nursing professionals are frequent, which constitutes a public health problem. Objective: To analyze the scientific evidence on successful nursing interventions within the framework of sexual education oriented to the adolescent school population. Method: Bibliographic review in the Dialnet, LILACS and Pubmed databases. Inclusion criteria considered documents containing school nursing interventions in sex education in the adolescent population. Regarding the selection of articles for methodological quality, critical reading was used, by applying the CASP checklist. Content analysis techniques were then used and the results were presented in tables. Results: Nursing interventions in education showed positive effects on the sexual health of adolescents, improving their knowledge of pregnancy and sexually transmitted infection prevention and significantly reducing the probability of committing risky behaviors. Conclusion: According to the selected bibliography, it is concluded that the school nurse is an indispensable resource for parents and educators, implementing educational programs that promote healthy sexual development in adolescents.

Interculturalidad e infancia rural: trabajo y cuidado en La Araucanía, Chile / Interculturality and rural childhood: work and care in La Araucanía, Chile

(analítico) Desde una mirada intercultural, se exploraron los significados de infancia en la agricultura familiar campesina, así como sus implicaciones en términos de trabajo y provisión de cuidados a niños y niñas. A partir de la tensión entre los significados universales de infancia basados en un enfoque de derechos y el trabajo en el campo del cual participan las personas desde temprana edad, se realizó un estudio cualitativo con diseño de teoría fundamentada y aplicación de entrevistas a mujeres cuidadoras y profesionales de programas de desarrollo rural en Chile. Se evidenció que a medida que la infancia aumenta en actoría social, disminuyen las prácticas de trabajo y se profundizan las de cuidado. Los resultados alientan a pensar en la proyección de una ontología de la niñez rural.

(analytical) Using an intercultural perspective, this study explores the meanings of childhood in the rural peasant population, as well as the implications of these meanings on the allocation of tasks and providing care to boys and girls. Taking into account the tension between universal meanings of childhood that draw on rights-based perspectives and the traditional practice of children working in agriculture, we conducted a qualitative study using a grounded theory methodology. Interviews were conducted with women caregivers and staff who work in rural development programs in Chile. The study's results show that as childhood has had an increasing value with children becoming more and more recognized as social actors, traditional child work practices in agriculture have decreased and care practices have been strengthened. The author concludes that the results of the research have consequences when thinking about an ontology for rural children.

(analítico) A partir de uma perspectiva intercultural, exploramos os significados da infância entre famílias voltadas para agricultura familiar camponesa, bem como suas implicações em termos de trabalho e prestação de cuidados às meninos e meninas. Considerando a tensão existente entre os significados universais da infância a partir de uma abordagem de direitos e o trabalho no campo, no qual as pessoas se engajam desde muito cedo, realizamos um estudo qualitativo, com base na teoria fundamentada, onde realizamos entrevistas com mulheres cuidadoras e profissionais dos programas de desenvolvimento rural no Chile. Evidenciamos que à medida que a infância adquiriu um valor ao nível da atuação social, as práticas de trabalho diminuíram e as práticas de cuidado se aprofundaram. Conclui-se sobre as consequências dos resultados para pensar uma ontologia da infância rural.

Effects of dietary supplementation with L-arginine on the endogenous losses of amino acids in growing pigs exposed to heat stress.

Exposing pigs to heat stress (HS) provokes higher death of intestinal cells, resulting in elevated endogenous intestinal losses (EIL) of amino acids (AA) and damage to intestinal epithelia. Arginine (Arg) is precursor for the synthesis of polyamines, which are involved in proliferation of intestinal cells and restoration of the intestinal epithelia. Thus the effect of adding L-Arg to diets for HS pigs on the EIL of AA was analyzed. Twelve pigs (23.1 ± 1.1 kg body weight) implanted with T-type cannulas at the end of ileum were individually housed and allowed 15-days for surgery recovery under thermoneutral (TN) conditions (22 ± 2 °C). Following, the pigs were randomly assigned to one of three treatments: TN pigs fed a semi-purified, corn starch-3% casein basal diet (TN-B); HS pigs with the basal diet (HS-B); HS pigs consuming the basal diet supplemented with 0.20% L-Arg (HS-Arg). The experiment consisted of two 9-day periods; each period included 7-days of adaptation to their respective diet, followed by a 2-day ileal digesta collection period. Digesta was collected during 12 consecutive hours each day. The pigs were fed twice a-day. Ambient temperature (AT) inside the TN and HS rooms ranged from 18.6 to 27.6 °C and from 29.5 to 40.7 °C, respectively. Body temperature followed a pattern similar to that of AT. The daily EIL of indispensable AA increased (P < 0.01) in the HS-B pigs compared to both the TN-B and the HS-Arg pigs, however, there was no EIL difference between the TN-B and the HS-Arg pigs (P > 0.05). Likewise, with the exception of serine, daily losses of endogenous dispensable AA in the HS-B pigs were higher (P < 0.01) in comparison with those of TN-B and HS-Arg pigs. In summary, HS exposure compared to TN conditions increases the loss of endogenous AA, but dietary supplementation with L-Arg helped to counteract the negative HS effect.

COPI vesicle formation and N-myristoylation are targetable vulnerabilities of senescent cells.

Drugs that selectively kill senescent cells (senolytics) improve the outcomes of cancer, fibrosis and age-related diseases. Despite their potential, our knowledge of the molecular pathways that affect the survival of senescent cells is limited. To discover senolytic targets, we performed RNAi screens and identified coatomer complex I (COPI) vesicle formation as a liability of senescent cells. Genetic or pharmacological inhibition of COPI results in Golgi dispersal, dysfunctional autophagy, and unfolded protein response-dependent apoptosis of senescent cells, and knockdown of COPI subunits improves the outcomes of cancer and fibrosis in mouse models. Drugs targeting COPI have poor pharmacological properties, but we find that N-myristoyltransferase inhibitors (NMTi) phenocopy COPI inhibition and are potent senolytics. NMTi selectively eliminated senescent cells and improved outcomes in models of cancer and non-alcoholic steatohepatitis. Our results suggest that senescent cells rely on a hyperactive secretory apparatus and that inhibiting trafficking kills senescent cells with the potential to treat various senescence-associated diseases.

Uso de terapias complementarias para la disminución del índice de masa corporal en personas mayores con Diabetes Mellitus tipo 2 / Use of complementary therapies to reduce body mass indexin older people with type 2 Diabetes Mellitus

Las enfermedades cardiovasculares están determinadas por ciertos factores de riesgos, la prevalencia y sinergia de éstos genera un de-terminado riesgo cardiovascular que deteriora la calidad de vida de quienes lo padecen. La realización de actividad física es considerada como una herramienta útil para disminuir uno de los factores de riesgo más importantes, la obesidad, medida mediante el índice de masa corporal. Sin embargo, no todos los seres humanos poseen las mismas características y capacidades físicas, por ende, la realización de ejercicio está restringida a éstas. Es en este sentido que se desarrolla el siguiente informe, el cual contempla una revisión sistemática que enfrenta a dos terapias complementarias: Yoga v/s Tai Chi, buscando la evidencia que permita la recomendación de una de ellas para la disminución de IMC en personas mayores con DM2. Los artículos fueron extraídos desde la plataforma académica PubMed, sometidos a 3 cribados de búsqueda, y criterios de inclusión y exclusión, resultando en la obtención de 4 artículos para el análisis, a partir de esta observación se obtiene que la realización de yoga es beneficiosa para la disminución de el IMC al caso índice. Por ende, se recomienda el uso de la terapia complementaria yoga, puesto que esta favorece la reducción del IMC en pacientes con enfermedades crónicas no transmisibles en comparación a la terapia complementaria Tai Chi[AU]

Cardiovascular diseases are determined by certain risk factors, the prevalence and synergy of which generates a certain cardiovascular risk that deteriorates the quality of life of those who suffer from it. Physical activity is considered a useful tool for reducing one of the most important risk factors, obesity, measured by the body mass index. However, not all human beings have the same physical capacities, therefore, exercise is restricted to them. It is in this sense that the following report is developed, which contemplates a systematic review that confronts two complementary therapies: yoga v/s Tai Chi, looking for the evidence that allows the recommendation of one of them for the decrease of BMI in elderly people with DM2.The articles were extracted from the academic platform PubMed, subjected to 3 search screens, and inclusion and exclusion criteria, resulting in obtaining 4 articles for analysis, from this observation it is obtained that the performance of yoga is beneficial for the decrease of the BMI to the index case. Therefore, the use of yoga complementary therapy is recommended, since it favors the reduction of BMI in patients with chronic noncommunicable diseases compared to Cardiovascular diseases are determined by certain risk factors, the prevalence and synergy of which generates a certain cardiovascular risk that deteriorates the quality of life of those who suffer from it. Physical activity is considered a useful tool for reducing one of the most important risk factors, obesity, measured by the body mass index. However, not all human beings have the same physical capacities, therefore, exercise is restricted to them. It is in this sense that the following report is developed, which contemplates a systematic review that confronts two complementary therapies: yoga v/s Tai Chi, looking for the evidence that allows the recommendation of one of them for the decrease of BMI in elderly people with DM2.The articles were extracted from the academic platform PubMed, subjected to 3 search screens, and inclusion and exclusion criteria, resulting in obtaining 4 articles for analysis, from this observation it is obtained that the performance of yoga is beneficial for the decrease of the BMI to the index case. Therefore, the use of yoga complementary therapy is recommended, since it favors the reduction of BMI in patients with chronic noncommunicable diseases compared to Tai Chi complementary[AU]

As doenças cardiovasculares são determinadas por certos factores de risco, cuja prevalência e sinergia geram um certo risco cardio-vascular que deteriora a qualidade de vida das pessoas que delas sofrem. A atividade física é considerada uma ferramenta útil para reduzir um dos factores de risco mais importantes, a obesidade, medida pelo índice de massa corporal. No entanto, nem todos os seres humanos têm as mesmas características físicas e, por isso, o exercício é restrito a eles. É nesse sentido que se desenvolve o pre-sente relatório, que contempla uma revisão sistemática que con-fronta duas terapias complementares: yoga v/s Tai Chi, buscando as evidências que permitam a recomendação de uma delas para a diminuição do IMC em idosos com DM2. Os artigos foram ex-traídos da plataforma acadêmica Pubmed, submetidos a 3 telas de busca, e critérios de inclusão e exclusão, resultando na obtenção de 4 artigos para análise, a partir desta observação obtém-se que a realização do yoga é benéfica para a redução do IMC para o caso índice. Portanto, recomenda-se a utilização da terapia complemen-tar yoga, uma vez que favorece a redução do IMC em pacientes com doenças crónicas não transmissíveis em comparação com a terapia complementar Tai Chi[AU]

Blood Immunophenotypes of Idiopathic Pulmonary Fibrosis: Relationship with Disease Severity and Progression.

(1) The role of the immune response in the pathogenesis of idiopathic pulmonary fibrosis (IPF) remains controversial. We hypothesized that peripheral blood immune phenotypes will be different in IPF patients and may relate to the disease severity and progression. (2) Whole blood flow cytometry staining was performed at diagnosis in 32 IPF patients, and in 32 age- and smoking-matched healthy controls. Thirty-one IPF patients were followed up for one year and categorized as stable or progressors based on lung function, deterioration and/or death. At 18-60 months, immunophenotypes were characterized again. (3) The main results showed that: (1) compared to matched controls, at diagnosis, patients with IPF showed more neutrophils, CD8+HLA-DR+ and CD8+CD28- T cells, and fewer B lymphocytes and naïve T cells; (2) in IPF, circulating neutrophils, eosinophils and naïve T cells were associated with lung function abnormalities; (3) patients whose disease progressed during the 12 months of follow-up showed evidence of cytotoxic dysregulation, with increased CD8+CD28- T cells, decreased naïve T cells and an inverted CD4/CD8 ratio at baseline; and (4) blood cell alterations were stable over time in survivors. (4) IPF is associated with abnormalities in circulating immune cells, particularly in the cytotoxic cell domain. Patients with progressive IPF, despite antifibrotic therapy, present an over-activated and exhausted immunophenotype at diagnosis, which is maintained over time.

Lung immune signatures define two groups of end-stage IPF patients.

BACKGROUND: The role of the immune system in the pathobiology of Idiopathic Pulmonary Fibrosis (IPF) is controversial. METHODS: To investigate it, we calculated immune signatures with Gene Set Variation Analysis (GSVA) and applied them to the lung transcriptome followed by unbiased cluster analysis of GSVA immune-enrichment scores, in 109 IPF patients from the Lung Tissue Research Consortium (LTRC). Results were validated experimentally using cell-based methods (flow cytometry) in lung tissue of IPF patients from the University of Pittsburgh (n = 26). Finally, differential gene expression and hypergeometric test were used to explore non-immune differences between clusters. RESULTS: We identified two clusters (C#1 and C#2) of IPF patients of similar size in the LTRC dataset. C#1 included 58 patients (53%) with enrichment in GSVA immune signatures, particularly cytotoxic and memory T cells signatures, whereas C#2 included 51 patients (47%) with an overall lower expression of GSVA immune signatures (results were validated by flow cytometry with similar unbiased clustering generation). Differential gene expression between clusters identified differences in cilium, epithelial and secretory cell genes, all of them showing an inverse correlation with the immune response signatures. Notably, both clusters showed distinct features despite clinical similarities. CONCLUSIONS: In end-stage IPF lung tissue, we identified two clusters of patients with very different levels of immune signatures and gene expression but with similar clinical characteristics. Weather these immune clusters differentiate diverse disease trajectories remains unexplored.

Human senescent fibroblasts trigger progressive lung fibrosis in mice.

Cell senescence has recently emerged as a potentially relevant pathogenic mechanism in fibrosing interstitial lung diseases (f-ILDs), particularly in idiopathic pulmonary fibrosis. We hypothesized that senescent human fibroblasts may suffice to trigger a progressive fibrogenic reaction in the lung. To address this, senescent human lung fibroblasts, or their secretome (SASP), were instilled into the lungs of immunodeficient mice. We found that: (1) human senescent fibroblasts engraft in the lungs of immunodeficient mice and trigger progressive lung fibrosis associated to increasing levels of mouse senescent cells, whereas non-senescent fibroblasts do not trigger fibrosis; (2) the SASP of human senescent fibroblasts is pro-senescence and pro-fibrotic both in vitro when added to mouse recipient cells and in vivo when delivered into the lungs of mice, whereas the conditioned medium (CM) from non-senescent fibroblasts lacks these activities; and, (3) navitoclax, nintedanib and pirfenidone ameliorate lung fibrosis induced by senescent human fibroblasts in mice, albeit only navitoclax displayed senolytic activity. We conclude that human senescent fibroblasts, through their bioactive secretome, trigger a progressive fibrogenic reaction in the lungs of immunodeficient mice that includes the induction of paracrine senescence in the cells of the host, supporting the concept that senescent cells actively contribute to disease progression in patients with f-ILDs.

Skin basal cell carcinomas assemble a pro-tumorigenic spatially organized and self-propagating Trem2+ myeloid niche.

Cancer immunotherapies have revolutionized treatment but have shown limited success as single-agent therapies highlighting the need to understand the origin, assembly, and dynamics of heterogeneous tumor immune niches. Here, we use single-cell and imaging-based spatial analysis to elucidate three microenvironmental neighborhoods surrounding the heterogeneous basal cell carcinoma tumor epithelia. Within the highly proliferative neighborhood, we find that TREM2+ skin cancer-associated macrophages (SCAMs) support the proliferation of a distinct tumor epithelial population through an immunosuppression-independent manner via oncostatin-M/JAK-STAT3 signaling. SCAMs represent a unique tumor-specific TREM2+ population defined by VCAM1 surface expression that is not found in normal homeostatic skin or during wound healing. Furthermore, SCAMs actively proliferate and self-propagate through multiple serial tumor passages, indicating long-term potential. The tumor rapidly drives SCAM differentiation, with intratumoral injections sufficient to instruct naive bone marrow-derived monocytes to polarize within days. This work provides mechanistic insights into direct tumor-immune niche dynamics independent of immunosuppression, providing the basis for potential combination tumor therapies.

Outros modos de ensinar: a experiência de criar comunidade e movimentar o pensamento crítico a partir da curricularização da extensão / Other modes of teaching: the experience of creating a community and stimulating critical thinking through the curricularization of extension / Otros modos de enseñar: la experiencia de crear comunidad y mover el pensamiento crítico a partir de la curricularización de la extensión

O presente artigo traz o relato de uma experiência de curricularização da extensão na temática da alimentação e nutrição infantojuvenil, construído por uma equipe de docentes, graduandos em Nutrição e trabalhadores com formação em Saúde. Partindo da descentralização e partilha do lugar/função do educador; e da criação de uma comunidade de aprendizagem, a experiência apontou para o papel transformador da extensão no questionamento de concepções reducionistas de produção de conhecimento e de cuidado. A experiência reconhece a importância do pensamento crítico na superação dos olhares adultocêntricos, repensa a atuação do nutricionista e amplia os sentidos da comida e do comer para as diferentes infâncias, adolescências e juventudes. São desafios futuros a inclusão direta de crianças e adolescentes no processo, a sustentação de uma cultura político-participativa em parceria com segmentos da sociedade outrora distanciados e o enfrentamento da lógica produtivista nas instituições universitárias.(AU)

This article is an experience report of the curricularization of extension within the theme of child and youth eating habits and nutrition developed by a team of teachers, nutrition students and workers with a health degree. Through the decentralization and sharing of the place/role of the educator and creation of a learning community, the experience highlights the transformative role of extension in questioning reductionist concepts of knowledge generation and care. The experience recognizes the importance of critical thinking to overcome adult-centric perspectives, rethink the work of nutritionists and expand the sensory experience of food and eating in different children, adolescents and youth. Future challenges include the direct involvement of children and adolescents in the process, the promotion of a political-participatory culture among socially distanced segments of society and the confrontation of productivist logic in university institutions.(AU)

Se trata del relato de una experiencia de curricularización de la extensión en la temática de la alimentación y de la nutrición infanto-juvenil, construido por un equipo de docentes, alumnos de Nutrición y trabajadores con formación en salud. Partiendo de la descentralización y compartición del lugar/función del educador y de la creación de una comunidad de aprendizaje, la experiencia señaló hacia el papel transformador de la extensión en el cuestionamiento de concepciones reduccionistas de producción de conocimiento y de cuidado. La experiencia reconoce la importancia del pensamiento crítico en la superación de las miradas adulto-céntricas, repiensa la actuación del nutricionista y amplía los sentidos de la comida y del comer para las diferentes infancias, adolescencias y juventudes. Son desafíos futuros la inclusión directa de niños y adolescentes en el proceso, la sustentación de una cultura político-participativa con segmentos de la sociedad que antes estaban distanciados y el enfrentamiento de la lógica productivista en las instituciones universitarias.(AU)

LY6D marks pre-existing resistant basosquamous tumor subpopulations.

Improved response to canonical therapies requires a mechanistic understanding of dynamic tumor heterogeneity by identifying discrete cellular populations with enhanced cellular plasticity. We have previously demonstrated distinct resistance mechanisms in skin basal cell carcinomas, but a comprehensive understanding of the cellular states and markers associated with these populations remains poorly understood. Here we identify a pre-existing resistant cellular population in naive basal cell carcinoma tumors marked by the surface marker LY6D. LY6D+ tumor cells are spatially localized and possess basal cell carcinoma and squamous cell carcinoma-like features. Using computational tools, organoids, and spatial tools, we show that LY6D+ basosquamous cells represent a persister population lying on a central node along the skin lineage-associated spectrum of epithelial states with local environmental and applied therapies determining the kinetics of accumulation. Surprisingly, LY6D+ basosquamous populations exist in many epithelial tumors, such as pancreatic adenocarcinomas, which have poor outcomes. Overall, our results identify the resistant LY6D+ basosquamous population as an important clinical target and suggest strategies for future therapeutic approaches to target them.

Predictors and changes of physical activity in idiopathic pulmonary fibrosis.

BACKGROUND: Different clinical predictors of physical activity (PA) have been described in idiopathic pulmonary fibrosis (IPF), but studies are lacking evaluating the potential role of muscle strength and anxiety and depression symptoms in PA limitation. Moreover, little is known about the impact of changes in PA in the course of the disease. The aim of the present study was to investigate the relationship between baseline PA and a wide range of variables in IPF, to assess its longitudinal changes at 12 months and its impact on progression free-survival. METHODS: PA was assessed by accelerometer and physiological, clinical, psychological factors and health-related quality of life were evaluated in subjects with IPF at baseline and at 12 month follow-up. Predictors of PA were determined at baseline, evolution of PA parameters was described and the prognostic role of PA evolution was also established. RESULTS: Forty participants with IPF were included and 22 completed the follow-up. At baseline, subjects performed 5765 (3442) daily steps and spent 64 (44) minutes/day in moderate to vigorous PA. Multivariate regression models showed that at baseline, a lower six-minute walked distance, lower quadriceps strength (QMVC), and a higher depression score in the Hospital Anxiety and Depression scale were associated to lower daily step number. In addition, being in (Gender-Age-Physiology) GAP III stage, having a BMI ≥ 25 kg/m2 and lower QMVC or maximum inspiratory pressure were factors associated with sedentary behaviour. Adjusted for age, gender and forced vital capacity (FVC) (%pred.) a lower progression-free survival was evidenced in those subjects that decreased PA compared to those that maintained, or even increased it, at 12 months [HR 12.1 (95% CI, 1.9-78.8); p = 0.009]. CONCLUSION: Among a wide range of variables, muscle strength and depression symptoms have a predominant role in PA in IPF patients. Daily PA behaviour and its evolution should be considered in IPF clinical assessment and as a potential complementary indicator of disease prognosis.