Restoring retinal polyunsaturated fatty acid balance and retina function by targeting ceramide in AdipoR1 deficient mice.

Mutations in the adiponectin receptor 1 gene (AdipoR1) lead to retinitis pigmentosa and are associated with age-related macular degeneration (AMD). This study explores the effects of AdipoR1 gene deficiency in mice, revealing a striking decline in ω3 polyunsaturated fatty acids (PUFA), an increase in ω6 FAs, and elevated ceramides in the retina. The AdipoR1 deficiency impairs peroxisome proliferator-activated receptor α (PPARα) signaling, which is crucial for FA metabolism, particularly affecting proteins associated with FA transport and oxidation in the retina and retinal pigmented epithelium (RPE). Our lipidomic and proteomic analyses indicate changes that could affect membrane composition and viscosity through altered ω3 PUFA transport and synthesis, suggesting a potential influence of AdipoR1 on these properties. Furthermore, we noted a reduction in the Bardet-Biedl syndrome (BBS) proteins, which are crucial for forming and maintaining photoreceptor outer segments that are PUFA-enriched ciliary structures. Diminution in BBS-proteins content combined with our electron microscopic observations raises the possibility that AdipoR1 deficiency might impair ciliary function. Treatment with inhibitors of ceramide synthesis led to substantial elevation of ω3 LC-PUFAs, alleviating photoreceptor degeneration and improving retinal function. These results serve as the proof of concept for a ceramide-targeted strategy to treat retinopathies linked to PUFA deficiency, including AMD.

The role of dendritic cells in MASH: friends or foes?

Dendritic cells (DCs) are major antigen-presenting cells that connect innate and adaptive immunity. Hepatic DCs are less activated and contribute to maintain the tolerogenic environment of the liver under steady state. Several studies indicated DCs in metabolic dysfunction-associated steatohepatitis (MASH), representing a substantial burden on healthcare systems due to its association with liver-related morbidity and mortality. Studies highlighted the potential disease-promoting role of liver DCs in the development of MASH while other experimental systems suggested their protective role. This review discusses this controversy and the current understanding of how DCs affect the pathogenesis of MASH.

A fast-acting lipid checkpoint in G1 prevents mitotic defects.

Lipid synthesis increases during the cell cycle to ensure sufficient membrane mass, but how insufficient synthesis restricts cell-cycle entry is not understood. Here, we identify a lipid checkpoint in G1 phase of the mammalian cell cycle by using live single-cell imaging, lipidome, and transcriptome analysis of a non-transformed cell. We show that synthesis of fatty acids in G1 not only increases lipid mass but extensively shifts the lipid composition to unsaturated phospholipids and neutral lipids. Strikingly, acute lowering of lipid synthesis rapidly activates the PERK/ATF4 endoplasmic reticulum (ER) stress pathway that blocks cell-cycle entry by increasing p21 levels, decreasing Cyclin D levels, and suppressing Retinoblastoma protein phosphorylation. Together, our study identifies a rapid anticipatory ER lipid checkpoint in G1 that prevents cells from starting the cell cycle as long as lipid synthesis is low, thereby preventing mitotic defects, which are triggered by low lipid synthesis much later in mitosis.

Breakthrough in Blastic Plasmacytoid Dendritic Cell Neoplasm Cancer Therapy Owing to Precision Targeting of CD123.

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and aggressive hematologic cancer originating from the malignant transformation of plasmacytoid dendritic cell precursors. This malignancy progresses rapidly, with frequent relapses and a poor overall survival rate, underscoring the urgent need for effective treatments. However, diagnosing and treating BPDCN have historically been challenging due to its rarity and the lack of standardized approaches. The recognition of BPDCN as a distinct disease entity is recent, and standardized treatment protocols are yet to be established. Traditionally, conventional chemotherapy and stem cell transplantation have been the primary methods for treating BPDCN patients. Advances in immunophenotyping and molecular profiling have identified potential therapeutic targets, leading to a shift toward CD123-targeted immunotherapies in both clinical and research settings. Ongoing developments with SL-401, IMGN632, CD123 chimeric antigen receptor (CAR) T-cells, and bispecific antibodies (BsAb) show promising advancements. However, the therapeutic effectiveness of CD123-targeting treatments needs improvement through innovative approaches and combinations of treatments with other anti-leukemic drugs. The exploration of combinations such as CD123-targeted immunotherapies with azacitidine and venetoclax is suggested to enhance antineoplastic responses and improve survival rates in BPDCN patients. In conclusion, this multifaceted approach offers hope for more effective and tailored therapeutic interventions against this challenging hematologic malignancy.

Changes in saliva protein profile throughout Rhipicephalus microplus blood feeding.

BACKGROUND: When feeding on a vertebrate host, ticks secrete saliva, which is a complex mixture of proteins, lipids, and other molecules. Tick saliva assists the vector in modulating host hemostasis, immunity, and tissue repair mechanisms. While helping the vector to feed, its saliva modifies the site where pathogens are inoculated and often facilitates the infection process. The objective of this study is to uncover the variation in protein composition of Rhipicephalus microplus saliva during blood feeding. METHODS: Ticks were fed on calves, and adult females were collected, weighed, and divided in nine weight groups, representing the slow and rapid feeding phases of blood feeding. Tick saliva was collected, and mass spectrometry analyses were used to identify differentially secreted proteins. Bioinformatic tools were employed to predict the structural and functional features of the salivary proteins. Reciprocal best hit analyses were used to identify conserved families of salivary proteins secreted by other tick species. RESULTS: Changes in the protein secretion profiles of R. microplus adult female saliva during the blood feeding were observed, characterizing the phenomenon known as "sialome switching." This observation validates the idea that the switch in protein expression may serve as a mechanism for evading host responses against tick feeding. Cattle tick saliva is predominantly rich in heme-binding proteins, secreted conserved proteins, lipocalins, and protease inhibitors, many of which are conserved and present in the saliva of other tick species. Additionally, another remarkable observation was the identification of host-derived proteins as a component of tick saliva. CONCLUSIONS: Overall, this study brings new insights to understanding the dynamics of the proteomic profile of tick saliva, which is an important component of tick feeding biology. The results presented here, along with the disclosed sequences, contribute to our understanding of tick feeding biology and might aid in the identification of new targets for the development of novel anti-tick methods.

Intergeracionalidade e promoção da saúde: reflexões e desafios na atenção à pessoa idosa / Intergenerationality and Health Promotion: Reflections and Challenges in the Care of Older Adults

Resumo Objetivo Discutir sobre a promoção da saúde da pessoa idosa por meio da intergeracionalidade, com ênfase na educação intergeracional nos Programas Intergeracionais, como uma proposta de educação para o protagonismo da pessoa idosa e o envelhecimento bem-sucedido. Método Ensaio teórico, de cunho reflexivo com abordagem qualitativa. Embasando-se na leitura de documentos que reforçam o aumento da longevidade e a preocupação com a promoção da saúde para a pessoa idosa no Brasil, a fim de refletir sobre a intergeracionalidade na promoção da saúde e a utilização da educação intergeracional para promover o envelhecimento bem-sucedido, por meio dos Programas Intergeracionais. Resultados Organizaram-se em três tópicos: Promoção da saúde da pessoa idosa: desafios para o seu protagonismo; Compreensão sobre envelhecimento para a aprendizagem intergeracional; Programa intergeracional: protagonismo para a promoção da saúde da pessoa idosa. Conclusão Experiências exitosas na saúde, especificamente nos espaços ocupados pela Atenção Primária à Saúde ainda se mostram restritas ou pouco visualizadas para a construção de uma educação transformadora para a promoção da saúde da pessoa idosa. O desafio é fomentar pesquisas científicas, para que os profissionais, a partir da educação permanente, possam potencializar os momentos de educação em saúde a partir da educação intergeracional, sendo assim, a construção e implementação de Programas Intergeracionais podem representar essa possibilidade.

Abstract Objective To discuss the promotion of health for older adults through intergenerationality, with an emphasis on intergenerational education within Intergenerational Programs, as a proposal for education fostering the protagonism of older adults and successful aging. Method Theoretical essay, reflective in nature with a qualitative approach. Grounded in the examination of documents emphasizing the increase in longevity and the concern for health promotion among older adults in Brazil, the aim is to contemplate intergenerationality in health promotion and the utilization of intergenerational education to foster successful aging through Intergenerational Programs. Results Organized into three topics: Health promotion for older adults: challenges for their protagonism; Understanding aging for intergenerational learning; Intergenerational program: protagonism for the health promotion of older adults. Conclusion Successful experiences in health, specifically within the realms of Primary Health Care, still appear to be limited or insufficiently recognized for the development of transformative education in health promotion for older adults. The challenge lies in fostering scientific research so that professionals, through continuous education, can enhance health education moments through intergenerational education. Thus, the establishment and implementation of Intergenerational Programs may represent this promising possibility.

Inhibiting stromal Class I HDACs curbs pancreatic cancer progression.

Oncogenic lesions in pancreatic ductal adenocarcinoma (PDAC) hijack the epigenetic machinery in stromal components to establish a desmoplastic and therapeutic resistant tumor microenvironment (TME). Here we identify Class I histone deacetylases (HDACs) as key epigenetic factors facilitating the induction of pro-desmoplastic and pro-tumorigenic transcriptional programs in pancreatic stromal fibroblasts. Mechanistically, HDAC-mediated changes in chromatin architecture enable the activation of pro-desmoplastic programs directed by serum response factor (SRF) and forkhead box M1 (FOXM1). HDACs also coordinate fibroblast pro-inflammatory programs inducing leukemia inhibitory factor (LIF) expression, supporting paracrine pro-tumorigenic crosstalk. HDAC depletion in cancer-associated fibroblasts (CAFs) and treatment with the HDAC inhibitor entinostat (Ent) in PDAC mouse models reduce stromal activation and curb tumor progression. Notably, HDAC inhibition (HDACi) enriches a lipogenic fibroblast subpopulation, a potential precursor for myofibroblasts in the PDAC stroma. Overall, our study reveals the stromal targeting potential of HDACi, highlighting the utility of this epigenetic modulating approach in PDAC therapeutics.

Essential role of MFSD1-GLMP-GIMAP5 in lymphocyte survival and liver homeostasis.

We detected ENU-induced alleles of Mfsd1 (encoding the major facilitator superfamily domain containing 1 protein) that caused lymphopenia, splenomegaly, progressive liver pathology, and extramedullary hematopoiesis (EMH). MFSD1 is a lysosomal membrane-bound solute carrier protein with no previously described function in immunity. By proteomic analysis, we identified association between MFSD1 and both GLMP (glycosylated lysosomal membrane protein) and GIMAP5 (GTPase of immunity-associated protein 5). Germline knockout alleles of Mfsd1, Glmp, and Gimap5 each caused lymphopenia, liver pathology, EMH, and lipid deposition in the bone marrow and liver. We found that the interactions of MFSD1 and GLMP with GIMAP5 are essential to maintain normal GIMAP5 expression, which in turn is critical to support lymphocyte development and liver homeostasis that suppresses EMH. These findings identify the protein complex MFSD1-GLMP-GIMAP5 operating in hematopoietic and extrahematopoietic tissues to regulate immunity and liver homeostasis.

"São tantas orientações": práticas de enfermeiros na atenção pré-natal durante o terceiro trimestre gestacional / "So many guidelines": practices of nurses in prenatal care during the third quarter of pregnancy / "Tantas directrices: prácticas de enfermeras en la atención prenatal durante el tercer trimestre del embarazo

Objetivo: analisar práticas de enfermeiros da Estratégia Saúde da Família no pré-natal durante o terceiro trimestre gestacional. Método: trata-se de um estudo descritivo com abordagem qualitativa com 24 enfermeiros da Estratégia Saúde da Família em Iguatu, Ceará, entre agosto e dezembro de 2021. A coleta incluiu levantamento territorial e entrevistas, interpretadas por análise de conteúdo. Resultados: evidenciaram-se temas relacionados àatuação do enfermeiro nesta etapa da gestação: orientações no acompanhamento clínico no terceiro trimestre gestacional e desafios na assistência pré-natal enfrentados pelos enfermeiros. Conclusão: entre osavanços, desvelaram-se as orientações prestadas às gestantes no final da gestação relacionadas ao aleitamento materno e tipos de parto; e, entre os desafios, a sobrecarga administrativa, pois dificulta àassistência.

Objective:to analyze the practices of nurses from the Family Health Strategy in prenatal care during the third trimester of pregnancy. Method:this is a descriptive study with a qualitative approach with 24 nurses from the Family Health Strategy in Iguatu, Ceará, between August and December 2021. Collection included a territorial survey and interviews, interpreted using content analysis. Results:themes related to the role of nurses at this stage of pregnancy were highlighted: guidelines for clinical monitoring in the third trimester of pregnancy and challenges in prenatal care faced by nurses. Conclusion:among the advances, guidance provided to pregnant women at the end of pregnancy related to breastfeeding and types of birth were revealed; and, among the challenges, administrative overload, as it makes assistance difficult.

Objetivo:analizar las prácticas de los enfermeros de la Estrategia Salud de la Familia en la atención prenatal durante el tercer trimestre del embarazo. Método:se trata de un estudio descriptivo, con enfoque cualitativo, con 24 enfermeros de la Estrategia de Salud de la Familia en Iguatu, Ceará, entre agosto y diciembre de 2021. La recolección incluyó encuesta territorial y entrevistas, interpretadas mediante análisis de contenido. Resultados:se destacaron temas relacionados al papel del enfermero en esta etapa del embarazo: directrices para el seguimiento clínico en el tercer trimestre del embarazo y desafíos en el cuidado prenatal que enfrentan los enfermeros. Conclusión: entre los avances, se revelaron orientaciones brindadas a las gestantes al final del embarazo relacionadas con la lactancia materna y tipos de parto; y, entre los desafíos, la sobrecarga administrativa, ya que dificulta la asistencia.

Efeito do relaxamento muscular progressivo em adultos com sintomas de ansiedade / Effect of progressive muscle relaxation in adults with anxiety symptoms / Efecto de la relajación muscular progresiva en adultos con síntomas de ansiedad

Objetivo: avaliar a efetividade da aplicação da técnica de relaxamento muscular progressivo de Jacobson na redução de sintomas de ansiedade leves e moderados em adultos. Método: estudo quase-experimental, com amostra de 108 adultos usuários da Estratégia Saúde da Família, realizado entre março e agosto de 2019. Para análise estatística descritiva e inferencial, foram utilizados: medidas de tendência central, Teste Qui-Quadrado de Pearson, Exato de Fisher, Mann-Whitney e Wilcoxon (nível de significância de 5%). Resultados: no primeiro momento, os grupos apresentaram homogeneidade em relação às características (p= 0,707) e aos escores dos níveis de ansiedade (p=0,463). No segundo momento, mostraram heterogeneidade e independência relacionados às características (p=0,001) e aos escores (p=0,001). Conclusão: a aplicação da técnica demonstrou melhoria dos sintomas ansiosos do grupo experimental (p=0,001), com maior efetividade nos participantes com sintomas leves (p 0,010), sexo feminino, adulto jovem, histórico de situação estressora recente e com problemas com o sono (p<0,001).

Objective: to evaluate the effectiveness of applying Jacobson's progressive muscle relaxation technique in reducing mild and moderate anxiety symptoms in adults. Method: quasi-experimental study, with a sample of 108 adult users of the Family Health Strategy, carried out from March to August 2019. For descriptive and inferential statistical analysis, the following were used: measures of central tendency, Pearson's Chi-Square Test, Exact Fisher, Mann-Whitney and Wilcoxon (5% significance level). Results: at first, the groups were homogeneous in terms of characteristics (p=0.707) and anxiety levels scores (p=0.463). In the second moment, they showed heterogeneity and independence related to characteristics (p=0.001) and scores (p=0.001). Conclusion: the application of the technique showed an improvement in anxiety symptoms in the experimental group (p=0.001), with greater effectiveness in participants with mild symptoms (p=0.010), female, young adult, history of recent stressful situation and with problems with sleep (p<0.001).

Objetivo: evaluar la efectividad de la aplicación de la técnica de relajación muscular progresiva de Jacobson en la reducción de los síntomas de ansiedad leve y moderada en adultos. Método: estudio cuasiexperimental, con una muestra de 108 adultos usuarios de la Estrategia Salud de la Familia, realizado de marzo a agosto de 2019. Para el análisis estadístico descriptivo e inferencial se utilizaron: medidas de tendencia central, test Chi-Cuadrado de Pearson, Exacto de Fisher, Mann-Whitney y Wilcoxon (nivel de significancia del 5%). Resultados: en un principio, los grupos fueron homogéneos en cuanto a las características (p=0,707) y a los puntajes de niveles de ansiedad (p=0,463). En el segundo momento, mostraron heterogeneidad e independencia respecto a las características (p=0,001) y puntajes (p=0,001). Conclusión: la aplicación de la técnica mostró una mejoría en los síntomas de ansiedad en el grupo experimental (p=0,001), con mayor efectividad en los participantes con síntomas leves (p=0,010), sexo femenino, adulto joven, antecedente de situación estresante reciente y con tratornos de sueño (p<0,001).

Time-motion analysis in men's breaking: A longitudinal study.

Quantifying the effort of a sport confrontation by determining its temporal structure is of concern to the scientific community. In breaking this has not yet been sufficiently studied. The objectives of the study were to longitudinally analyze the temporal and sequential parameters of male breaking battles to determine the evolution of these parameters and to establish a model of temporal structure. All Red Bull BC One dancers from 2011 to 2021 (n = 152 dancers) participated. By using observational methodology, all battles were analyzed (n = 142). To obtain the results, we employed different analysis techniques: descriptive, normality tests, Student's t-test or Mann-Whitney, one factor ANOVA or Kruskall-Wallis and effect size (Cohen's d or Hedges' g). The significance level established for the study was ρ ≤ 0.05. The results define the temporal and sequential structure of the battles. With these, breaking professionals will be able to develop precise and adequate training for these athletes. We conclude that approaches to dancing and battling have evolved. The effort that the athlete must exert is increasing and will therefore require better preparation to cope with the physical demands required for a sport that will be incorporated into the Olympics program in 2024.

Impact of a heart failure multidisciplinary clinic on the reduction of healthcare-related events and costs: the GEstIC study.

Introduction: Heart failure (HF) is the leading cause of hospitalization in the elderly in developed countries and significantly impacts public health expenditures. Patients with HF usually have associated comorbidities that require multidisciplinary management. This study aims to demonstrate the benefits of a multidisciplinary clinic in reducing all-cause hospitalizations and HF events (HF hospitalizations and urgent HF visits) in a real-world setting. Finally, the study evaluates the associated costs of HF events. Methods: This observational study included patients admitted to GEstIC, a multidisciplinary Portuguese HF clinic, from January 2013 to February 2019, who had one-year follow-up. Hospitalizations and HF events, total days spent in the hospital during HF hospitalizations, and HF events-related costs, in the year before and the year after GEstIC admission, were compared. Results: Of the 487 patients admitted to the GEstIC, 287 were eligible for the study sample. After one year of HF patients' multidisciplinary management at GEstIC, there was a 53.7% reduction in all-cause hospitalizations (462 vs. 214), a 71.7% reduction in HF hospitalizations (392 vs. 111), and a 39.1% reduction in urgent HF visits (87 vs. 53). As a result, there was a significant decrease of 12.6 days in the length of hospital stay due to HF per patient (15.6 vs. 3.0, p < 0.001). This translated into the release of 9.9 hospital beds in the year following admission to GEstIC. The average total savings associated with the reduction of HF events was €5,439.77 per patient (6,774.15 vs. 1,334.38, p < 0.001), representing a total cost reduction of €1,561,213. Furthermore, the significant reduction in the number of all events was independent of the patient's left ventricular ejection fraction (LVEF). Discussion: Significant reductions in all-cause and HF hospitalizations and urgent HF visits were observed with the implementation of this multidisciplinary clinic for HF patients' management. This was particularly important for patients with LVEF >40%. Before GEstIC, there was no medical intervention to improve the prognosis of these patients. The reduction of over one million euros in health-related costs after only one year of person-centered multidisciplinary management highlights the need to replicate this approach in other national healthcare institutions.

Inhibiting Stromal Class I HDACs Curbs Pancreatic Cancer Progression.

Oncogenic lesions in pancreatic ductal adenocarcinoma (PDAC) hijack the epigenetic machinery in stromal components to establish a desmoplastic and therapeutic resistant tumor microenvironment (TME). Here we identify Class I histone deacetylases (HDACs) as key epigenetic factors facilitating the induction of pro-desmoplastic and pro-tumorigenic transcriptional programs in pancreatic stromal fibroblasts. Mechanistically, HDAC-mediated changes in chromatin architecture enable the activation of pro-desmoplastic programs directed by serum response factor (SRF) and forkhead box M1 (FOXM1). HDACs also coordinate fibroblast pro-inflammatory programs inducing leukemia inhibitory factor (LIF) expression, supporting paracrine pro-tumorigenic crosstalk. HDAC depletion in cancer-associated fibroblasts (CAFs) and treatment with the HDAC inhibitor entinostat (Ent) in PDAC mouse models reduce stromal activation and curb tumor progression. Notably, HDAC inhibition (HDACi) enriches a lipogenic fibroblast subpopulation, a potential precursor for myofibroblasts in the PDAC stroma. Overall, our study reveals the stromal targeting potential of HDACi, highlighting the utility of this epigenetic modulating approach in PDAC therapeutics.

Nursing care management in substitutive renal therapy in patients with COVID-19: integrative review / Gestión de Cuidados de Enfermería en Terapia Renal Sustitutiva en Pacientes con COVID-19: Revisión Integradora

Introducción: Among the systems most affected by COVID-19, the renal system stands out, which leads to challenges in the management of nursing care for these patients. Objetives: To describe the scientific evidence on nursing care management in patients diagnosed with COVID-19 undergoing Renal Replacement Therapy. Methodology: Articles were searched in PubMed, SCOPUS, Web of Science, LILACS, BDENF, EMBASE, IBECS, CINAHL, COCHRANE LIBRARY, and Scielo databases, using the following cross-references: “renal therapy” AND “nursing care” AND “covid-19”. To systematize the searches, the Boolean operator “AND” was used. Initially, 167 primary references were identified in the selected databases/virtual library, and as a final sample, 14 articles were included. Results: It was found that among the contributions to nursing care management in hemodialysis patient care in the context of the COVID-19 pandemic, the use of health technologies (examples: use of telehealth and the development of new protocols), development of new methods in nursing care management and continuing education are described in the literature. These tools were essential for the continuity of nursing care. Conclusion: Among the tools used for nursing care management in the context of the pandemic of COVID-19 in hemodialysis patients, health technologies and continuing education in health are included, enabling qualified care management. (AU)

Introducción: Entre los sistemas más afectados por la pandemia COVID-19, destaca el sistema renal, circunstancia que conlleva desafíos en la gestión de cuidados de enfermería en los pacientes. Objetivo: Describir la evidencia científica sobre la gestión de cuidados de enfermería en pacientes diagnosticados con COVID-19 sometidos a terapia renal sustitutiva. Metodología: Se buscaron artículos en las bases de datos PubMed, SCOPUS, Web Of Science, LILACS, BDENF, EMBASE, IBECS, CINAHL, COCHRANE LIBRARY y Scielo, utilizando las siguientes palabras clave cruzadas: “renal therapy” AND “nursing care” AND “covid-19”. Para sistematizar las búsquedas, se utilizó el operador booleano “AND”. Inicialmente, se identificaron 167 referencias primarias en las bases de datos seleccionadas, y como muestra final, se incluyeron 14 artículos. Resultados: Se encontró que entre las contribuciones a la gestión de cuidados de enfermería en la atención de pacientes en hemodiálisis en el contexto de la pandemia de COVID-19, se describen el uso de tecnologías de la salud (ejemplos: el uso de telemedicina y el desarrollo de nuevos protocolos), el desarrollo de nuevos métodos en la gestión de cuidados de enfermería y la educación continua. Estas herramientas fueron esenciales para la continuidad de los cuidados de enfermería. Conclusión: Entre las herramientas utilizadas para la gestión de cuidados de enfermería en el contexto de la pandemia de COVID-19 en pacientes en hemodiálisis, se incluyen las tecnologías de la salud y la educación continua en salud, lo que permite una gestión de cuidados calificada. (AU)

Differential Precipitation of Proteins: A Simple Protein Fractionation Strategy to Gain Biological Insights with Proteomics.

Differential precipitation of proteins (DiffPOP) is a simple technique for fractionating complex protein mixtures. Using stepwise addition of acidified methanol, ten distinct subsets of proteins can be selectively precipitated by centrifugation and identified by mass spectrometry-based proteomics. We have previously shown that the ability of a protein to resist precipitation can be altered by drug binding, which enabled us to identify a novel drug-target interaction. Here, we show that the addition of DiffPOP to a standard LC-MS proteomics workflow results in a three-dimensional separation of peptides that increases protein coverage and peptide identifications. Importantly, DiffPOP reveals solubility differences between proteoforms, potentially providing valuable insights that are typically lost in bottom-up proteomics.

Listening and valuing clients: conceptions and practices in the care management in the Family Health Strategy. / Escuta e valorização dos usuários: concepções e práticas na gestão do cuidado na Estratégia Saúde da Família.

We aimed to analyze the practices of receiving, bonding, and shared responsibility in producing care in the Family Health Strategy. This qualitative, exploratory study in the dimension of hermeneutics-dialectics was conducted from August and November 2021 in Iguatu, Ceará, with 25 professional coordinators of the Family Health Strategy teams. A semi-structured interview was adopted to collect data. We identified different conceptions among the coordinators about reception and bonding. We shared responsibility: conceptual aspects linked to the experimental care practice mode the team experienced, the aspects that intervened in these processes, and the relationships built through care management and production. We evidenced contributions to evaluating and improving care management and production in the Family Health Strategy and the Unified Health System (SUS). Reception, bonding, and shared responsibility were proven potential tools in qualifying care management in the Family Health Strategy. Improving professional skills and investing in relational technologies are required for humanized health practice.

Objetivou-se analisar as práticas de acolhimento, vínculo e corresponsabilização na produção do cuidado da Estratégia Saúde da Família. Estudo exploratório de natureza qualitativa, na dimensão da hermenêutica-dialética, realizado entre agosto e novembro de 2021, em Iguatu, Ceará. Participaram 25 profissionais coordenadores das equipes da Estratégia Saúde da Família. Utilizou-se entrevista semiestruturada para coleta de dados. Identificaram-se diferentes concepções entre os coordenadores sobre acolhimento, vínculo e corresponsabilização, sendo eles: aspectos conceituais ligados ao modo de experienciação das práticas de cuidado vivenciadas pela equipe, e os aspectos intervenientes nesses processos e nas relações construídas na gestão e produção do cuidado. Evidenciaram-se contribuições para a avaliação e o aprimoramento da gestão e produção do cuidado na Estratégia Saúde da Família e no Sistema Único de Saúde. As práticas de acolhimento, vínculo e corresponsabilização mostraram-se como ferramentas potenciais na qualificação da gestão do cuidado na Estratégia Saúde da Família. Considera-se que o aperfeiçoamento das habilidades profissionais e o investimento nas tecnologias relacionais são exigências para a prática humanizada em saúde.

Infarct-like versus Non-Infarct-like Clinical Presentation of Acute Myocarditis: Comparison of Cardiac Magnetic Resonance (CMR) Findings.

BACKGROUND: The clinical presentation of acute myocarditis (AM) is widely variable, ranging from a subclinical disease to an infarct-like syndrome. Cardiac magnetic resonance (CMR) has become the reference non-invasive diagnostic tool for suspected AM, allowing the identification of the various hallmarks of myocardial inflammation (edema, fibrosis, and hyperemia). The aim of the study was to investigate any differences in morphological, functional, and tissue characterization CMR parameters between infarct-like AM in patients with unobstructed coronary arteries and non-infarct-like AM, diagnosed according to the original Lake-Louise Criteria (LLC); Methods: We retrospectively selected 39 patients diagnosed with AM according to LLC, divided into 2 groups according to the clinical presentation: infarct-like in group 1 patients and non-infarct-like in group 2 patients. CMR morphologic, functional, and tissue characterization parameters were analyzed and compared. RESULTS: In group 1, CMR tissue characterization parameters were mainly altereda in septal location with mesocardial myocardial involvement; in group 2, CMR tissue characterization parameters were mainly altered in a lateral location with subepicardial myocardial involvement mainly at the mid-cavity. No significant differences in morphological or functional parameters were observed between the two study groups. CONCLUSIONS: Our results showed differences in the localization and distribution of myocardial tissue damage assessed by CMR among forms of AM accompanied by an infarct-like clinical presentation compared with non-infarct-like presentations of AM. The mechanisms underlying the different preferential sites of damage observed in our study are not known, and we do not exclude the possibility of their prognostic implications.

Potential clinical implications of CD4+CD26high T cells for nivolumab treated melanoma patients.

BACKGROUND: Nivolumab is an anti-PD1 antibody that has dramatically improved metastatic melanoma patients' outcomes. Nevertheless, many patients are resistant to PD-1 inhibition, occasionally experiencing severe off-target immune toxicity. In addition, no robust and reproducible biomarkers have yet been validated to identify the correct selection of patients who will benefit from anti-PD-1 treatment avoiding unwanted side effects. However, the strength of CD26 expression on CD4+ T lymphocytes permits the characterization of three subtypes with variable degrees of responsiveness to tumors, suggesting that the presence of CD26-expressing T cells in patients might be a marker of responsiveness to PD-1-based therapies. METHODS: The frequency distribution of peripheral blood CD26-expressing cells was investigated employing multi-parametric flow cytometry in 69 metastatic melanoma patients along with clinical characteristics and blood count parameters at baseline (W0) and compared to 20 age- and sex-matched healthy controls. Percentages of baseline CD4+CD26high T cells were correlated with the outcome after nivolumab treatment. In addition, the frequency of CD4+CD26high T cells at W0 was compared with those obtained after 12 weeks (W1) of therapy in a sub-cohort of 33 patients. RESULTS: Circulating CD4+CD26high T cells were significantly reduced in melanoma patients compared to healthy subjects (p = 0.001). In addition, a significant association was observed between a low baseline percentage of CD4+CD26high T cells (< 7.3%) and clinical outcomes, measured as overall survival (p = 0.010) and progression-free survival (p = 0.014). Moreover, patients with clinical benefit from nivolumab therapy had significantly higher frequencies of circulating CD4+CD26high T cells than patients with non-clinical benefit (p = 0.004) at 12 months. Also, a higher pre-treatment proportion of circulating CD4+CD26high T cells was correlated with Disease Control Rate (p = 0.014) and best Overall Response Rate (p = 0.009) at 12 months. Interestingly, after 12 weeks (W1) of nivolumab treatment, percentages of CD4+CD26high T cells were significantly higher in comparison with the frequencies measured at W0 (p < 0.0001), aligning the cell counts with the ranges seen in the blood of healthy subjects. CONCLUSIONS: Our study firstly demonstrates that peripheral blood circulating CD4+CD26high T lymphocytes represent potential biomarkers whose perturbations are associated with reduced survival and worse clinical outcomes in melanoma patients.

DNA aneuploidy identifies a subset of Luminal subtype breast carcinoma patients with worse clinical outcome.

AIM: In breast carcinoma (BC), the relationship between the ploidy pattern and molecular subtyping is still unknown. We aim to investigate the prognostic impact of DNA ploidy within molecular subtypes of a large cohort of BC patients. METHODS: The series involved 520 BC patients with no neoadjuvant therapy and a median follow-up of 115.5 months. Immunohistochemical assessment of hormonal receptors, ERBB2 (HER2) status and Ki67 proliferative activity was the basis of the surrogate molecular subtyping. Ploidy was evaluated by DNA flow cytometry in fresh/frozen tumour samples. Kaplan-Meier (K-M) survival estimation was used for prognostic statistical analysis. RESULTS: Luminal A subtype had the lowest prevalence of disease recurrences (23.6 %) and deaths from disease (18.3 %), while Luminal B (42.2 %/37.9 %), Triple-negative (46.4 %/40.6 %), and HER2-positive (55.9 %/50.0 %) subtypes had the highest. The Triple-positive subtype shows an intermediate/low frequency of adverse events (29.4 % of disease recurrences and 17.6 % of deaths from disease). Luminal A tumours were mostly diploid (55.3 %), while Triple-negative and HER2-positive tumours showed a high incidence of aneuploidy (82.6 % and 88.2 %, respectively). Luminal B and Triple-positive tumours had an intermediate percentage of aneuploidy (63.8 % and 70.6 %, respectively). K-M survival curves showed that DNA aneuploidy is significantly associated with shorter disease-free survival and overall survival in Luminal A and Luminal B molecular subtypes. CONCLUSION: DNA aneuploidy identifies a subset of Luminal BC patients with worse clinical outcome, potentially eligible for more aggressive adjuvant therapy.