Search

Abstract Background Non-Small Cell Lung Cancer (NSCLC) is the leading cause of cancer death worldwide. Although immune checkpoint inhibitors (ICIs) have shown remarkable clinical efficacy, they can also induce a paradoxical cancer acceleration, known as hyperprogressive disease (HPD), whose causative mechanisms are still unclear. Methods This study investigated the mechanisms of ICI resistance in an HPD-NSCLC model. Two primary cell cultures were established from samples of a NSCLC patient, before ICI initiation (“baseline”, NSCLC-B) and during HPD (“hyperprogression”, NSCLC-H). The cell lines were phenotypically and molecularly characterized through immunofluorescence, Western Blotting and RNA-Seq analysis. To assess cell plasticity and aggressiveness, cellular growth patterns were evaluated both in vitro and in vivo through 2D and 3D cell growth assays and patient-derived xenografts establishment. In vitro investigations, including the evaluation of cell sensitivity to interferon-gamma (IFN-γ) and cell response to PD-L1 modulation, were conducted to explore the influence of these factors on cell plasticity regulation. Results NSCLC-H exhibited increased expression of specific CD44 isoforms and a more aggressive phenotype, including organoid formation ability, compared to NSCLC-B. Plastic changes in NSCLC-H were well described by a deep transcriptome shift, that also affected IFN-γ–related genes, including PD-L1. IFN-γ–mediated cell growth inhibition was compromised in both 2D-cultured NSCLC-B and NSCLC-H cells. Further, the cytokine induced a partial activation of both type I and type II IFN-pathway mediators, together with a striking increase in NSCLC-B growth in 3D cell culture systems. Finally, low IFN-γ doses and PD-L1 modulation both promoted plastic changes in NSCLC-B, increasing CD44 expression and its ability to produce spheres. Conclusions Our findings identified plasticity as a relevant hallmark of ICI-mediated HPD by demonstrating that ICIs can modulate the IFN-γ and PD-L1 pathways, driving tumor cell plasticity and fueling HPD development.

Summary: Voltage-dependent anion channel 1 (VDAC1) is a key protein in cellular metabolism and apoptosis. Here, we present a protocol to express and purify milligram amounts of recombinant VDAC1 in Escherichia coli. We detail steps for a fluorescence polarization-based high-throughput screening assay using NADH displacement, along with procedures for thermostability, fluorescence polarization, and X-ray crystallography. In this context, we demonstrate how 2-methyl-2,4-pentanediol (MPD), a crystallization reagent, interferes with VDAC1 small-molecule binding, hindering the detection of these ligands in the crystal.For complete details on the use and execution of this protocol, please refer to Conti Nibali et al.1 : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

BackgroundRecent literature has shown the presence of B cells and autoantibodies in idiopathic pulmonary fibrosis (IPF) which would imply the presence of tertiary lymphoid structures (TLS, sites where the immune response is triggered), yet TLS are not considered features of the histological characteristics of IPF.AimThis study aims to quantify the presence, size, and degree of activation of TLS in biopsied and explanted lungs from patients with early- and late-IPF, never treated with antifibrotics, and relate their presence and activity to the clinical course, disease progression, and lung inflammation.MethodsImmunohistochestry for B cells and CD4, CD8, and CD45 cells was performed in lung tissue from IPF patients: 18 at diagnosis (early), 39 explanted (end-stage), and 12 smoking controls. TLS activation was assessed by CD40 expression. Spirometry along 31 (12–72) months of follow-up was used to characterize end-stage IPF as slow progressors or rapid progressors.ResultsB cells, along with other inflammatory cells, were higher in early- and end-stage IPF than in controls (p < 0.001). In rapid progressors, all inflammatory cells were higher than in slow progressors (p < 0.05). TLS were present in 100% of early- and end-stage IPF and in 50% of controls. In end-stage IPF, the TLS area and activation score were higher than in early IPF (p < 0.0001; p = 0.005) and controls (p < 0.04; p < 0.002). TLS activation score correlated with FVC decline during follow-up in rapid progressors (r = 0.73; p = 0.007) but not in slow progressors.ConclusionsA prominent B-cell infiltration, along with the presence of TLS, the activity of which correlates with FVC decline, is an important component of IPF from the beginning of the disease, likely playing an important role on its mechanism and progression.

The microbiota performs multiple functions vital to host fitness, including defense against pathogens and adaptation to dietary changes. Yet, how environmental challenges shape microbiota resilience to nutrient fluctuation remains largely unexplored. Here, we show that transient gut infection can optimize host metabolism toward the usage of carbohydrates. Following acute infection and clearance of the pathogen, mice gained more weight as a result of white adipose tissue expansion. Concomitantly, previously infected mice exhibited enhanced carbohydrate (glucose) disposal and insulin sensitivity. This metabolic remodeling depended on alterations to the gut microbiota, with infection-elicited Betaproteobacteria being sufficient to enhance host carbohydrate metabolism. Further, infection-induced metabolic alteration protected mice against stunting in the context of limited nutrient availability. Together, these results propose that alterations to the microbiota imposed by acute infection may enhance host fitness and survival in the face of nutrient restriction, a phenomenon that may be adaptive in settings where both infection burden and food precarity are prevalent.

Idiopathic pulmonary fibrosis (IPF) is associated with a significantly increased risk of thrombotic events and mortality. This review explores the complex bidirectional relationship between pulmonary fibrosis and thrombosis, discussing epidemiological evidence, pathogenetic mechanisms, and therapeutic implications, with a particular focus on the emerging role of extracellular vesicles (EVs) as crucial mediators linking fibrosis and coagulation. Coagulation factors directly promote fibrosis, while fibrosis itself activates thrombotic pathways. Retrospective studies suggest the benefits of anticoagulants in IPF, but prospective trials have faced challenges. Novel anticoagulants, profibrinolytic therapies, and agents targeting protease-activated receptors (PARs) show promise in preclinical studies and early clinical trials. EVs have emerged as key players in the pathogenesis of interstitial lung diseases (ILDs), serving as vehicles for intercellular communication and contributing to both fibrosis and coagulation. EV-based approaches, such as EV modulation, engineered EVs as drug delivery vehicles, and mesenchymal stem cell-derived EVs, represent promising therapeutic strategies. Ongoing research should focus on optimizing risk–benefit profiles, identifying predictive biomarkers, evaluating combination strategies targeting thrombotic, fibrotic, and inflammatory pathways, and advancing the understanding of EVs in ILDs to develop targeted interventions.

Summary: The voltage-dependent anion-selective channel isoform 1 (VDAC1) is a pivotal component in cellular metabolism and apoptosis with a prominent role in many cancer types, offering a unique therapeutic intervention point. Through an in-silico-to-in-vitro approach we identified a set of VA molecules (VDAC Antagonists) that selectively bind to VDAC1 and display specificity toward cancer cells. Biochemical characterization showed that VA molecules can directly interact with VDAC1 with micromolar affinity by competing with the endogenous ligand NADH for a partially shared binding site. NADH displacement results in mitochondrial distress and reduced cell proliferation, especially when compared to non-cancerous cells. Experiments performed on organoids derived from intrahepatic cholangiocarcinoma patients demonstrated a dose-dependent reduction in cell viability upon treatment with VA molecules with lower impact on healthy cells than conventional treatments like gemcitabine. VA molecules are chemical entities representing promising candidates for further optimization and development as cancer therapy strategies through precise metabolic interventions.

Introduction What topics from their personal lives do patients bring to talk to the clinical team, in addition to reporting their health-illness complaints, being examined, and receiving medical and nursing guidance? Knowing the symbolic aspects of the professional-patient relationship allows for care with more empathy and greater adherence to outpatient service follow-ups. The sociocultural contexts of vulnerable adolescents amplify the importance of reproductive health care and understanding perceptions about romantic relationships and sexuality. During adolescence, risky behaviours can interfere with life opportunities and the future. The lack of care for adolescents’ reproductive health is associated with irreparable physical and psychosocial consequences. In Brazil, the Unified Health System functions as an important support for the community. Objectives To interpret the symbolic meanings attributed by pregnant teenagers regarding the possible experience of talking and receiving guidance about romantic relations and sexuality from the clinical team of public primary attention (in the EPA-2023, we presented the work “on family relationships”, another branch belonging to the same PhD research). Methods We used the Clinical-Qualitative Method (Turato. Portuguese Psychos. J, 2000 2(1): 93-108). For data collection, the main researcher used the Semi-Directed Interview with Open-ended Questions In-Depth and Field Notes, fully transcript. The employ of the Seven Steps of the Clinical-Qualitative Content Analysis (Faria-Schützer et al. Cien Saude Colet. 2021; 26(1): 265-274) permits the solid discussion categories. Sample closed by saturation information criterion (Fontanella et al. Cad Saude Publica. 2008; 24(1): 17-27). Results Sample of 10 adolescents, from 15 to 19 years. Interviewed by the first author, a female psychologist, online from September 2020 to June 2022. Findings validated by peer reviewers from Lab of Clinical-Qualitative Research. Categories to this congress: 1) maternal figure referred to as the axis of orientations on sexuality. This seems to empty the opportunity or the need to discuss these aspects in clinical consultations; 2) interviewees do not cite teenage pregnancy in its new emotional status as present in the prenatal consultation protocol; 3) there is a discourse of the re-signification of relationship with a loving partner by assuming also symbolically the pregnancy by both. Conclusions Professionals that the teenagers access in clinical consultations at primary attention are not perceived psychoanalytically as transferential figures for conversations about romantic relationships and/or sexuality. It is opportune to rediscuss the expected and/or desired roles of the clinical team in that studied context from the psychic and cultural symbolic universe. Disclosure of Interest None Declared

Introduction To handle well clinical treatments, it is crucial to know the expectations of patients who seek help. We need to ask ourselves: how do patients interpret subjectively their diagnosis, treatments, and self-care? Medical Psychology brings us theories for this understanding. Grave’s Disease is an autoimmune disorder, a form of hyperthyroidism with a goitre, affecting also the eyes and the skin, as well as emotional manifestations. Weight loss, sometimes psychologically welcome, although due to a disease, can mean a psychoanalytic secondary gain. So, the medicine that leads to clinical improvement can be taken with ambivalence and bad adherence to treatment. It is important to differentiate between disease, a scientific entity explained by the clinical professional, and illness as a patient’s subjective perception of an un-health. Objectives To understand psychodynamically the fantasies, desires, and views related to Graves’ Disease as reported by patients in hyperthyroidism but without ophthalmopathy interviewed at an endocrinology-specialized outpatient clinic. (in the EPA-2023, it was presented the qualitative results of a sample in hyperthyroidism, with ophthalmopathy, studied at the same service). Methods Clinical-Qualitative Method designed by Turato. Data collected through Semi-Directed Interviews with Open-ended Questions in-Depth; and Field Notes, transcript fully. Treated by the Seven Steps of Clinical-Qualitative Content Analysis of Faria-Schützer, using psychodynamic concepts from Balintian Medical Psychology. Although we have extracted categories that permit us interesting discussions, we intend to close the sample (through the information saturation criterion by Fontanella) when we obtain other categories. The interviewer, a male psychologist, is the first author. The findings are validated by peer-reviewers of the Lab of Clinical Qualitative Research of the State University of Campinas. Results Three categories were chosen for this presentation: 1) “An atomic bomb in my life”: How drastic changes of a hormonal disease re-symbolize the patient’s life; 2) “I didn’t think the thyroid did that much”: the disease seen as a metaphor in a psychological blaming language to own disease and to himself as a sick person. 3) “I have so much medicine!”: a mode of referring to treatment that would justify an undisciplined use of medications. Conclusions Our findings can help clinical professionals to have a better understanding of some psychological meanings which have sense in the patients’ conscience, often not verbalized clearly in the conversation, and so to handle better the patients and relatives. In this way, it can reduce the patient’s resistance to recommended treatment, as well as encourage the clinical team to construct empathy with them. Disclosure of Interest None Declared

Introduction “What can and what cannot I do in a sexual relationship?” |In this way, a middle-aged man with HNC - Head and Neck Cancer, under chemotherapy or radiotherapy, asks. This doubt is raised to the oncologist, radiotherapist, nurse or psychotherapist. Apparently, his concern is objective, considering he has a severe diagnosis and important treatments. However, underlying the manifest doubt, there are symbolic constructions in his mind that generate anguish. The health professionals’ response must go beyond information. They also must understand the symbolic emotional meanings associated with the patient’s speech. This attitude will bring a psychotherapeutic effect to the ill man. Objectives To interpret symbolically sexual and emotional experiences reported by male patients diagnosed with HNC under outpatient treatment in a public specialized clinical unit. Methods We used the CQM - Clinical-Qualitative Method (Turato. Portuguese Psychos. J, 2000 2(1): 93-108). For data collection, the main researcher used the Semi-Directed Interview with Open-ended Questions In-Depth and Field Notes. The employ of the Seven Steps of the CQCA - Clinical-Qualitative Content Analysis (Faria-Schützer et al. Cien Saude Colet. 2021; 26(1): 265-274) brings us to discussion categories. The sample was closed with 12 patients according to the information saturation strategy (Fontanella et al. Cad Saude Publica. 2008; 24(1): 17-27). The interviews were conducted by the first author of this abstract, a male nurse, as part of his master’s research at a postgraduate course in Oncology. The findings were validated by peer reviewers from the Lab of Clinical-Qualitative Research at the State University of Campinas. Results Two categories were chosen for this presentation: ‘The dyad perceived in the felt body and the experienced body’, and ‘The body re-signified between the sexual and affective dimensions’. The body symbolized before and after the illness experiences a movement in phenomenological consciousness that leads to external changes in its attitudes. The patient needs now to ask himself and others what this body can - or cannot - do. The severely ill body imposes new meanings for life and sexuality. It does not cancel the wish but asks for a new channelling of your psychic/sexual energies. Conclusions These findings indicate that patients with HNC want to talk about sexuality and ask about the risks of sexual activity, contrary to what the common view supposes. Traditional Balint groups met with the multidisciplinary team can be beneficial for doctors and nurses to deal with their own emotional limitations. Furthermore, the Consultation-Liaison Psychiatry, under the approach of psychosomatic medicine, focuses on the care of patients with behavioural and emotional manifestations, together with the work of the oncologists. Disclosure of Interest None Declared

Introduction Health Psychology is aggregated to clinical studies providing physicians, nurses, and psychotherapists with psychodynamics of sick persons, facilitating interpersonal relationships and greater adherence to treatments. How do people deal with illness and treatment from what they symbolize in experiences of becoming ill? Watch & Wait Protocol for patients with rectal cancer is an active surveillance as an alternative approach in surgical medical management. Patients are followed with physical examinations, endoscopy, and imaging. Observation carried out through periodic examinations aims to avoid surgery stage while rectal cancer is maintained. Objectives To interpret emotional meanings attributed by patients, after adhering to the W&W protocol for rectal cancer, to life experiences of watching and waiting for the disease course. Methods Clinical-Qualitative Method (Turato. Portuguese Psychos. J, 2000 2(1): 93-108). For data collection, the first author used Semi-Directed Interview with Open-ended Questions In-Depth and Field Notes, after acculturation. Sample closed by information saturation (Fontanella et al. Cad Saude Publica. 2008; 24(1): 17-27). Interviews conducted by the first author, a female psychologist. We employed the Seven Steps of the Clinical-Qualitative Content Analysis (Faria-Schützer et al. Cien Saude Colet. 2021; 26(1): 265-274) to construct categories. Theoretical framework was the Balintian Medical Psychology. Findings were validated by peer reviewers from Lab of Clinical-Qualitative Research. Results Sample had 10 patients, 3 female and 7 male, from 52 to 77 years. Interviews carried out from October 2022 to March 2023. We constructed 03 categories: 1) Fate out of hands - “I get sick just coming in here.” There is an apprehension experienced in each medical evaluation to check the clinical condition because the symbol of waiting is not having the own destiny in the hands. 2) Psychic defence - “Sometimes I even thought if I had to live on a grant for the rest of my life or die!” Imagining the worst is a psychic defence because if this probability occurs, the mind has already begun its elaboration. 3) Life upside down - “I was going to have the surgery, use a bag, my life was going to be upside down.” Anxiety generated by waiting is a mental disorganizing. Conclusions Attitudes of observing and waiting carry different symbolisms to those who work with scientific thinking and who experience the observation of their own disease and the wait for what conduct they will receive. Observing oneself in illness requires acceleration of changes in ego identity. Waiting in front of illness asks the ego to think the worst. It is not a volitional choice. Preparing for the worst is a defensive necessity in the emotional sphere to avoid surprises that take to mental rupture. Disclosure of Interest None Declared

Introduction Humanistic studies applied to the health-illness clinic go beyond explaining cause-effect relationships among disease phenomena, treatments, and preventions. Qualitative research aims to understand symbolic relationships built in life experiences among the manifestations and the people. How to act in front of a person whose physical appearance and odour can be unpleasant, such as in the HNC - Head Neck Cancer? Or whose life history may have been marked by deviant behaviours and negligence in self-care? Objectives To interpret emotional meanings attributed through open interviews conducted with relatives about the domestic care of patients with HNC under clinical treatment. Methods Sample composed of family caregivers of patients with HNC, sent sequentially by colleagues from the clinical service who were informed of the research. The study used the Clinical-Qualitative Method (Turato. Portuguese Psychos. J, 2000 2(1): 93-108). Semi-Directed Interview with Open-ended Questions In-Depth and Field Notes was used for data collection. The employ of the Seven Steps of the Clinical-Qualitative Content Analysis (Faria-Schützer et al. Cien Saude Colet. 2021; 26(1): 265-274) has permitted the understanding of the topics. Sample closed with 12 persons according to the information saturation strategy (Fontanella et al. Cad Saude Publica. 2008; 24(1): 17-27), conducted by the first author, a female psychologist. To interpret the empirical material, we use Medical/Health Psychology, the psychodynamics of relationships of the Balintian framework, disease and illness while modes of un-health, psychic defence mechanisms against anguish. Validation by peers from the Lab of Clinical-Qualitative Research Laboratory, at the State University of Campinas. Results For this presentation, we listed three categories from the free-floating re-readings: (1) Certain need to recognize the care provided as a handling strategy with effort, putting in this ‘validation’ their relief regarding natural suffering of the care process; (2) Caregiver’s psychological fantasies of omnipotence in the care process, frequently perceiving the reality a phenomenologically and necessarily distorted by the caregiver. (3) Moments of impotence feeling in front of the finitude reality that it knows will arrive. Conclusions The family caregivers can present certain emotional defences, such as subtle magical thinking, in which they distort the reality experienced as a management strategy and validation of their care. They act so to alleviate their psychological and existential suffering. Group meetings with family members to talk openly about the difficulties on the psychological management of patients with HNC, coordinated by a psychotherapist, are effective as a space for creativity in daily management at home and a space for catharsis. Disclosure of Interest None Declared

BackgroundThe family of Suppressor of Cytokine Signaling (SOCS) acts as a controller of the duration and intensity of cytokine function by negatively regulating the JAK-STAT signaling pathway. SOCS’ role in inflammatory diseases in animal models is well demonstrated. However, its role in the development of human disease is still under investigation. SOCS3 plays an important role in tumor development where its downregulation has been implicated in the pathogenesis of various solid tumors such as triple-negative breast cancer.AimThe aim of this work was to study (1) the expression of SOCS3 in smokers’ lungs and its relation to the degree of inflammation and (2) SOCS3 regulation by microRNA (miRNA) in alveolar-macrophage (AM)-derived extracellular vesicles (EVs) in bronchoalveolar lavage (BAL).MethodsGroup A: 35 smokers’ [19 with COPD (SC) and 16 without COPD (S)] and 9 nonsmokers (NS); SOCS3, TNFα in AM, and CD8+ T cells were quantified by immunohistochemistry, in lung tissue. Group B: additional 9 SC, 11 S, and 5 NS; AM-EVs expressing SOCS3 (CD14+SOCS3+) and SOCS3 suppressors miRNA-19a-3p and 221-3p in EVs were quantified by flow cytometry and PCR, in BAL.ResultsThe percentage of SOCS3+ AM was higher in SC [68 (6.6–99)%] and S [48 (8–100)%] than in NS [9.6 (1.9–61)%; p = 0.002; p = 0.03] and correlated with % of TNFα+AM (r = 0.48; p = 0.0009) and CD8+ T cells (r = 0.44; p = 0.0029). In BAL, the CD14+SOCS3+ EVs/μL were increased in SC [33 (21–74)] compared to S [16 (8–37); p = 0.03] and NS [9 (7–21); p = 0.003]. Conversely, miRNA-19a-3p and miRNA-221-3p expression were increased in S when compared to SC [19 (2–53) vs. 3 (0.6–8); p = 0.03 and 3 (0.005–9.6) vs. 0.2 (0.08–0.7); p = 0.05].ConclusionsThe suppressor function of SOCS3 in COPD seems to be overridden by other factors and does not follow the animal-model paradigm. Expression of SOCS3 in BAL macrophage-derived EVs might be useful to assess the degree of inflammation and possible progression of COPD. Downregulation of SOCS3, by miRNA, in smokers without COPD might contribute to the risk of developing cancer in these patients.

From the discussion on the insertion of computational concepts in Basic Education in Brazil, there has been a growing demand for support to these teachers in the form of training courses in computing, whether offered by formal bodies or even by independent projects such as the university extension. If, on the one hand, the offer of these courses fulfills the role of helping Basic Education teachers in this challenge of integrating computational concepts in their classroom practice, on the other hand, these training courses also have the potential to engage teachers to attract their students to the area of ​​computing as a profession. We argue that because many girls are rarely exposed to content in this area in particular, and hearing quality clarifications from their teachers can spark previously unexplored curiosities. However, in order to fulfill this second role, it is necessary to discuss how these courses are approached in order to break with certain stereotypes, such as gender, which have long been perceived in this area. In this sense, this article highlights this demand for training courses in computing free of stereotypes, since it identifies a perception that is still stereotyped, a possible reflection of a clear lack of basic education teachers in training courses offered by the TIChers extension project.

This qualitative research aimed to understand the experiences of a fourth-year medical class during two clinical simulation scenarios of type 2 diabetes management in Primary Care. Ten simulated students were interviewed. The results describe the symbolic conception of diabetes and its treatment as anguish, damage, condemnation and an unpleasant sentence that affects the appropriation and performance of the medical role by students. Considering Medical Psychology, we suggest that such subjective factors should be addressed in teaching-learning in addition to commonly cognitive aspects mentioned in the medical education literature in order for students to develop the work profile to cope with diabetes in Primary Care. Clinical simulation facilitates the subjective approach through its group support component to promote reflection, insights and self-awareness.

Buscamos neste ensaio apresentar algumas das principais transformações pelas quais passou a psicanálise no seu desenvolvimento histórico. Nesse movimento, os chamados paradigmas pulsional e objetal foram se estabelecendo como principais referências ao campo psicanalítico. Nossa intenção principal foi conhecer como a relação de objeto está presente na teoria pulsional de Freud, sobretudo na primeira tópica. Ademais, saber como a dinâmica pulsional e o objeto se apresentam no pensamento de um dos principais psicanalistas da primeira geração, Karl Abraham. Como desdobramento deste estudo, apresentamos alguns dos efeitos de como a noção de objeto, presente nas teorias desses paradigmas, pode fundamentar diferentes noções de desenvolvimento, de psicopatologia e de manejo clínico em nossa contemporaneidade.

Resumo Objetivo Compreender os significados atribuídos pela pessoa idosa com Doença Pulmonar Obstrutiva Crônica (DPOC) em uso da Oxigenoterapia Domiciliar Prolongada (ODP) referente ao relacionamento amoroso e a prática sexual. Método Estudo qualitativo, no qual foram realizadas sete entrevistas semidirigidas com pacientes com diagnóstico confirmado de DPOC e em uso de ODP, atendidos em serviço ambulatorial. A técnica de análise de conteúdo foi aplicada com o apoio do software WebQDA 2.0®. Os critérios COREQ foram usados para relatar o método e o resultado. Resultados Duas categorias emergiram: 1- Desestabilização no relacionamento amoroso e na vida sexual do usuário de ODP: revelou que a terapia causa perturbação nos relacionamentos, mudança de parceiro depois que foi prescrita a ODP ou até a ideia de procurar uma pessoa extraconjugal. 2- Vivência e significados da DPOC e da oxigenoterapia durante a relação sexual: o sofrimento com as questões fisiológicas, o quanto o paciente sente falta de ar para ter relação sexual e o impacto disso no desempenho e na frequência, diminuindo esses momentos com o parceiro Conclusão A percepção da pessoa idosa com DPOC em uso da ODP indica que a oxigenoterapia impactou sobre a prática sexual e nos relacionamentos amorosos. Ter boa qualidade nos relacionamentos e na prática sexual é condição fundamental para promover a saúde.

Background: Non-Small Cell Lung Cancer (NSCLC) is the leading cause of cancer death worldwide. Although immune checkpoint inhibitors (ICIs) have shown remarkable clinical efficacy, they can also induce a paradoxical cancer acceleration, known as hyperprogressive disease (HPD), whose causative mechanisms are still unclear. Methods: This study investigated the mechanisms of ICI resistance in an HPD-NSCLC model. Two primary cell cultures were established from samples of a NSCLC patient, before ICI initiation ("baseline", NSCLC-B) and during HPD ("hyperprogression", NSCLC-H). The cell lines were phenotypically and molecularly characterized through immunofluorescence, Western Blotting and RNA-Seq analysis. To assess cell plasticity and aggressiveness, cellular growth patterns were evaluated both in vitro and in vivo through 2D and 3D cell growth assays and patient-derived xenografts establishment. In vitro investigations, including the evaluation of cell sensitivity to interferon-gamma (IFN-γ) and cell response to PD-L1 modulation, were conducted to explore the influence of these factors on cell plasticity regulation. Results: NSCLC-H exhibited increased expression of specific CD44 isoforms and a more aggressive phenotype, including organoid formation ability, compared to NSCLC-B. Plastic changes in NSCLC-H were well described by a deep transcriptome shift, that also affected IFN-γ–related genes, including PD-L1. IFN-γ–mediated cell growth inhibition was compromised in both 2D-cultured NSCLC-B and NSCLC-H cells. Further, the cytokine induced a partial activation of both type I and type II IFN-pathway mediators, together with a striking increase in NSCLC-B growth in 3D cell culture systems. Finally, low IFN-γ doses and PD-L1 modulation both promoted plastic changes in NSCLC-B, increasing CD44 expression and its ability to produce spheres. Conclusions: Our findings identified plasticity as a relevant hallmark of ICI-mediated HPD by demonstrating that ICIs can modulate the IFN-γ and PD-L1 pathways, driving tumor cell plasticity and fueling HPD development. [ABSTRACT FROM AUTHOR]

Idiopathic pulmonary fibrosis (IPF) is associated with a significantly increased risk of thrombotic events and mortality. This review explores the complex bidirectional relationship between pulmonary fibrosis and thrombosis, discussing epidemiological evidence, pathogenetic mechanisms, and therapeutic implications, with a particular focus on the emerging role of extracellular vesicles (EVs) as crucial mediators linking fibrosis and coagulation. Coagulation factors directly promote fibrosis, while fibrosis itself activates thrombotic pathways. Retrospective studies suggest the benefits of anticoagulants in IPF, but prospective trials have faced challenges. Novel anticoagulants, profibrinolytic therapies, and agents targeting protease-activated receptors (PARs) show promise in preclinical studies and early clinical trials. EVs have emerged as key players in the pathogenesis of interstitial lung diseases (ILDs), serving as vehicles for intercellular communication and contributing to both fibrosis and coagulation. EV-based approaches, such as EV modulation, engineered EVs as drug delivery vehicles, and mesenchymal stem cell-derived EVs, represent promising therapeutic strategies. Ongoing research should focus on optimizing risk–benefit profiles, identifying predictive biomarkers, evaluating combination strategies targeting thrombotic, fibrotic, and inflammatory pathways, and advancing the understanding of EVs in ILDs to develop targeted interventions. [ABSTRACT FROM AUTHOR]

Human bacterial infections significantly contribute to the increase in healthcare-related burdens. This scenario drives the study of novel techniques for the early and precise diagnosis of infectious processes. Some alternatives include Nuclear Medicine- and Molecular Imaging-based strategies. However, radiopharmaceuticals that are available for routine assessments are not specific to differentiating infectious from aseptic inflammatory processes. In this context, [68Ga]Ga-DOTA-Ubiquicidin29-41 was synthesized using an automated module and radiochemical; in vivo and in vitro studies were performed. The radiopharmaceutical remained stable in saline (up to 180 min) and in rodent serum (up to 120 min) with radiochemical purities > 99 and 95%, respectively. Partition coefficient and serum protein binding at 60 min were determined (−3.63 ± 0.17 and 44.06 ± 1.88%, respectively). Ex vivo biodistribution, as well as in vivo microPET/CT images in mice, showed rapid blood clearance with renal excretion and reduced uptake in other organs in Staphylococcus aureus-infected animals. Higher uptake was observed in the target as compared to the non-target tissue (p < 0.0001) at 60 min post administration. The presented in-human clinical case demonstrates uptake of the radiopharmaceutical by Staphyloccocus aureus bacteria. These results indicate the potential of [68Ga]Ga-DOTA-Ubiquicidin29-41 as a radiopharmaceutical that can be obtained in a hospital radiopharmacy for the diagnosis of infectious processes using PET/CT.

Abstract Background Elderly people are more likely to suffer severe chronic obstructive pulmonary disease (COPD) and require long-term home oxygen therapy (LTOT) as part of their treatment. LTOT has advantages such as improvement in symptoms, but there are also disadvantages such as physical barriers, psychosocial barriers and emotional challenges. The aim of this study is to understand the experiences of elderly people with COPD using LTOT with respect to their feelings attributed to therapy. Methods Qualitative study. Seven semidirected interviews were conducted with patients with a confirmed COPD diagnosis who used LTOT and were treated at an outpatient service. The content analysis technique was applied with the support of WebQDA software 2.0. Results Three categories emerged that were associated with the use of LTOT: (1) poor self-image; (2) feelings of sadness and (3) the impact of LTOT on others such as family and friends. Conclusions LTOT in elderly people with COPD was associated with a poor self-image, feelings of sadness and impacted on others apart from the patient. When LTOT is prescribed, healthcare practitioners should proactively address these concerns to minimise the negative biopsychosocial experiences caused by LTOT.

BackgroundThe local, extravascular, activation of the coagulation system in response to injury is a key factor mediating the resulting inflammatory response. Coagulation Factor XIIIA (FXIIIA) found in alveolar macrophages (AM) and dendritic cells (DC), by influencing fibrin stability, might be an inflammatory modifier in COPD.AimsTo study the expression of FXIIIA in AM and Langerin+DC (DC-1) and their relation to the inflammatory response and disease progression in COPD.MethodsIn 47 surgical lungs, 36 from smokers (22 COPD and 14 no-COPD) and 11 from non-smokers we quantified by immunohistochemistry FXIIIA expression in AM and DC-1 along with numbers of CD8+Tcells and CXCR3 expression in lung parenchyma and airways. Lung function was measured prior to surgery.ResultsThe percentage of AM expressing FXIII (%FXIII+AM) was higher in COPD than no-COPD and non-smokers. DC-1 expressed FXIIIA and their numbers were higher in COPD than no-COPD and non-smokers. DC-1 positively correlated with %FXIII+AM (r=0.43; p

Introduction Knowing mental representations about the phenomenon of illness and medical care allows the clinical team to have better emotional handling of their patients, with gains in greater adherence to treatments. Graves’ Ophthalmopathy is an inflammatory disease with primary involvement of the extraocular muscles and orbit, being the most frequent extrathyroidal manifestation of Graves’ Disease. Many patients have psychological status changes even after successful treatment of hyperthyroidism, especially when the disfiguring signs of ophthalmopathy are predominant. An understanding of the symbolic aspects linked to this condition help doctors and nurses to have a relationship more harmonious with them. Objectives To interpret emotional meanings in reports of patients with euthyroidism and with ophthalmopathy under follow-up at a specialized university endocrinology outpatient follow-up, discussing contradictions perceived between a stigmatized body and clinical-laboratory euthyroidism. Methods Clinical-Qualitative design of Turato. Data was collected using Semi-directed interviews with open-ended questions in-depth, carried out with patients at a university hospital specialized outpatient service in South-eastern Brazil. The interview material was audio-recorded and fully transcribed. The interviews were treated by Clinical-Qualitative Content Analysis described by Seven Steps’ Faria-Schützer. It is based on psychodynamic concepts from the Medical Psychology theoretical framework, whose main author is Michael Balint. The sample was closed by the Theoretical Saturation of Information studied by Fontanella and cols. The finding validation has occurred by peers at the Laboratory of Clinical-Qualitative Research, State University of Campinas, San Paolo. Results The sample was composed by 10 patients. From the search of nuclei of meanings in the reports, four categories of analysis were constructed: 1) “No, this is not normal, I must have cancer”: psychodynamics of the doctor-patient relationship in Graves’ Disease; 2) Types of illness according to their manifestations and auto-perception: silent illness and non-silent ones; 3) “The eyes are everything”: the impacts of the disfiguring alterations of ophthalmopathy; 4) The contradiction perception between clinical and laboratory normality the stigmas of ophthalmopathy. Conclusions The patients with severe exophthalmos, maintained emotional distress despite being euthyroid, manifested by various emotional meanings reported in the interviews. The clinical-laboratory diagnosis of Graves’ Disease alone is not sufficiently capable of responding to the psychological demands of the patients. Proper listening to emotional symbolic meanings attributed by patients can help physicians and nurses in handling this setting Disclosure of Interest None Declared

Introduction In prenatal clinical consultations, what do adolescents talk about, in addition to physical and affective conditions and acquiring information about the general state of the evolution of pregnancy? The symbolic psychological elements that emerge during consultations are important for the handling of family guidelines with the clinical team. Objectives To interpret emotional meanings attributed by pregnant adolescents, with the possibility of accessing public health care service in a Brazilian metropolitan city, about talking and listening about Family relationships with the clinical team in prenatal consultations. Methods Clinical-qualitative design by Turato. Semi-directed interviews with open-ended questions in-depth conducted online during the pandemic. Sample closed by theoretical information saturation according to Fontanella. Interview material, fully transcribed, was treated by Clinical-Qualitative Content Analysis of Faria-Schützer, with Balintian psychodynamic concepts from Medical Psychology to generate categories of discussion after free-floating readings. Findings were validated by peers from the Laboratory of Clinical-Qualitative Research, at the State University of Campinas. Results The sample was closed with 10 pregnant adolescents. Three categories emerged from the analysis: (1) emotional meanings of the non-use the access to health service as a listening space: affective obstacles and social shame; (2) the relationship of complicity with the maternal figure in “competition” with a possible broad psychological relationship with the clinical team; (3) recurrence of teenage pregnancy in the family as a possible obstacle. Conclusions The finding so far that the adolescent’s personal reference is reported as the mother figure is also accentuated because the affective relationship with the doctor figure is more fragile. The bond of adolescents is established with the health institution and not with the reference health team. There is a mismatch between the psychic maturation, still evolving, to the adult identity and the demands of social roles of the pregnant teenager already demanded as an adult. The teenager captures it, and the medical consultation becomes an act that occurs by inertial force. There is a perception of access to the health service and not access to the doctor as someone qualified for the adolescent to talk about relevant personal matters. Disclosure of Interest None Declared

Introduction The care relationships of physicians and nurses with patients with Covid-19 had pointed to a scenario explorable from a psychological point of view due to the peculiarities of this pandemic. How do clinicians feel, when caring for their co-workers, in a context that was not so common to see colleagues occupy the patient’s place? What emotional experiences arise from this reality? The results of the present study sought to point out how to handle this caring relationship, in an exceptional context. Objectives To interpret emotional meanings reported by physicians and nurses on their experiences of working at COVID-19 intensive care units during the height of the pandemic. Methods Clinical-qualitative design of Turato. Data collection with semi-directed interviews with open-ended questions in-depth applied to a sample of six professionals, closed by theoretical information saturation according to Fontanella, in a Brazilian university general hospital. Trigger question: “Talk about the psychological meanings of your experience in face of management of patients with COVID-19 at ICU”. Data treatment by the Seven Steps of the Clinical-Qualitative Content Analysis of Faria-Schützer. Theoretical framework from Medical Psychology using Balintian concepts. Results We raised initially 4 categories. Three categories were presented preliminarily in this congress, version last year. In this opportunity, we show this special category of analysis that emerged during the deepened discussion of the final results: “The feeling of insecurity: from technique to affective dimension”. Conclusions The care relationships between the health professional and the patient hospitalized in the Covid-19 ICU pointed to peculiar transference and countertransference psychodynamic mechanisms between both. Before the pandemic, the care relationship seemed pragmatic and protocolar. During the pandemic, this relationship seemed “more subjective”, building a strongly emotional dimension, as health professionals also began to care for their colleagues in the profession. The egoic defense mechanisms, such as projective and introjective identification were reported as intense. Disclosure of Interest None Declared

Introduction Knowing what “kind of patient” search the doctor is relevant to handle his/her treatment and care. What emotional meanings do people attach to their diagnosis, therapy, and care in general? Graves’ Disease has an impact on the metabolism, which directly affects behavior. Patients can be affected by Graves’ Ophthalmopathy at any stage of the disease. This usually leads to greater changes in facial physiognomy which may or may not be accompanied by typical symptoms of hyperthyroidism. Changes in appearance and visual symptoms often lead to a rapid search for treatment. Understanding the symbolic aspects of the condition can help clinicians to manage emotionally, leading to substantial improvements such as the adhesion to the treatment. Objectives To understand and interpret psychodynamically the perceptions and emotional meanings related to Graves’ Disease with Ophthalmopathy and hyperthyroidism as reported by patients at an endocrinology-specialized outpatient service. Methods Clinical-qualitative design of Turato. Data is collected using Semi-directed interviews with open-ended questions in-depth carried out with patients at an specialized outpatient service. Interview material was audio-recorded and fully transcribed. The material was treated by Clinical-Qualitative Content Analysis of Faria-Schützer. It is based on psychodynamic concepts from the Medical Psychology theoretical framework, and which main author is Michael Balint. The sample will be closed by the Theoretical Saturation of Information criterion according Fontanella. The interviewer was a male psychologist and doctoral student in the Health Mental Area. The finding validation has occurred by peers at the Laboratory of Clinical-Qualitative Research, State University of Campinas. Results This presentation refers to partial findings from a sample of a total of three participants as part of the doctoral project by the first author. The analysis of data collected so far indicates three designed categories of analysis: 1) “I wasn’t like that before”: impacts on physiognomy - the perception of social stigma and the difficulty of managing the illness. 2) “This disease is a mess”: the symptoms affect all aspects of the patient’s life. 3) Problematic emotions management: double anxiety in hyperthyroidism - hormonally based anxiety and psychological anxiety related to the impact of the medical diagnosis. Conclusions The findings shall aid medical personnel in better grasping patients’ emotional perceptions of their illness and medical care. The level of communication between the professional and the patient can be improved by involving the patient as an active protagonist in the well-being process. This could also lead to more effective management and greater adherence to the therapeutic process. Disclosure of Interest None Declared

Introduction Understanding the psychological meanings of a rigorous protocol for introducing a drug to patients is a challenge of emotional management for clinical professionals. Clozapine is an effective drug for patients with schizophrenia resistant to treatment with first and second-generation antipsychotics. This medication has agranulocytosis as an important side effect. The medication protocol requires frequent blood draws to monitor any effect on blood cells. Investigating patients’ emotional perceptions about the experience with this procedure was the triggering question of our study. Objectives To interpret emotional/symbolic meanings attributed by patients with schizophrenia to the protocol of introduction of clozapine in follow-up at a specialized university service. Methods Clinical-qualitative design of Turato. Semi-directed interviews with open-ended questions in-depth were conducted face-to-face with participants using clozapine. Closed sample by the theoretical information saturation criterion described by Fontanella. Data were treated by Faria-Schutzer’s Clinical-Qualitative Content Analysis, employing psychodynamic concepts of the theoretical framework of Medical Psychology. Results From the analysis of nine patients, three categories emerged: 1) “Anyway, I come here to stay alive”: frequent blood collections of the protocol seem to have a good impact on patient’s adherence to treatment; 2) To re-signify a psychiatric illness: the protocol reinforcing an embodiment of a medical diagnosis; 3) “It is a very big precaution”: the protocol as real and emotional support to deal with the possibility of serious side effects. Conclusions Although blood collection is a repetitive experience for patients, such a routine does not mean that the procedure brings symbolizations that are more charged than the disease itself. Patients can benefit from the commitment to attend blood collection frequently, as it removes them from possible social isolation, allowing social interaction; it brings the perception of emotional security due to the commitment to the clinical team. These benefits can lead the patient to develop new meanings for their life condition. Future qualitative research can be conducted to study the meanings of medical protocols in other diagnostic situations. Disclosure of Interest None Declared

Persons with severe mental disorders have higher chances of presenting oral health problems than persons in the general population. Mental disorders are considered public-health problems worldwide. Interpreting statements on oral health made by medical students receiving instruction in psychiatry is essential to provide elements for reflection on their difficulties, barriers or limited knowledge in managing their patients' oral health. Based on the presupposition that doctors provide their patients with no instruction or support concerning oral complaints, because these do not symbolize the same challenges as those emerging from severe mental disorders. The aim of this study was to interpret symbolic meanings of statements expressed by medical residents in psychiatry at a specialized university outpatient clinic, about their patients' oral health. Qualitative research using the Qualitative-Clinical method was conducted, adopting the theoretical reference of medical psychology. Data were analyzed by the Clinical-Qualitative Content method and the Seven-Step technique. Based on 06 interviews analyzed, the following categories emerged: "What do I do? Psychiatrists' dilemmas about not understanding their role in patients' oral health; and "Dentists do not participate in Balint' so-called "collusion in anonymity". It was concluded that among others, the paradigm consisted of a sociological composition, therefore it was stronger than personal decisions that might eventually oppose the barriers to interdisciplinary work posed by the institutional model, which were intertwined with paradigmatic barriers. Thus, specialist training should include a dental perspective, so that oral examinations would always be included in the physical examinations, from an interdisciplinary perspective of the integrity of health-care.

We have investigated the change in SerpinB3 during hepatic ischemia and the potential role of its antiprotease activity in cell protection by the administration of wild-type SerpinB3 (SerpinB3-WT) or active loop-deleted recombinant SerpinB3 protein (SerpinB3-D) in a rat model of ischemia (60 min)/reperfusion (60 min) (I/R). A time-dependent increase of SerpinB3, both at transcription and protein level, was found in ischemic livers after 60, 120 and 180 min. SerpinB3-WT decreased polymorphonuclear cell infiltration and serum enzymes and increased ATP when compared with I/R group. These events were not obtained using SerpinB3-D. No significant changes in both liver SerpinB3 mRNA and protein were found in all I/R groups considered. The present data show that the administration of SerpinB3-WT reduced the I/R injury and this effect appears to be dependent on its anti-protease activity.

Abstract Background Differential diagnosis of interstitial lung diseases (ILDs) during the COVID-19 pandemic is difficult, due to similarities in clinical and radiological presentation between COVID-19 and other ILDs on the one hand, and frequent false-negative swab results on the other. We describe a rare form of interstitial and organizing pneumonia resembling COVID-19, emphasizing some key aspects to focus on to get the right diagnosis and treat the patient properly. Case presentation A 76-year-old man presented with short breath and dry cough in the midst of the COVID-19 outbreak. He showed bilateral crackles and interstitial-alveolar opacities on X-ray, corresponding on computed tomography (CT) to extensive consolidations with air bronchograms, surrounded by ground glass opacities (GGO). Although his throat-and-nasopharyngeal swab tested negative, the picture was overall compatible with COVID-19. On the other hand, he showed subacute, rather than hyperacute, clinical onset; few and stable parenchymal consolidations, rather than patchy and rapidly evolving GGO; pleural and pericardial thickening, pleural effusion, and lymph node enlargement, usually absent in COVID-19; and peripheral eosinophilia, rather than lymphopenia, suggestive of hypersensitivity. In the past year, he had been taking amiodarone for a history of ventricular ectopic beats. CT scans, in fact, highlighted hyperattenuation areas suggestive of amiodarone pulmonary accumulation and toxicity. Bronchoalveolar lavage fluid (BALF) investigation confirmed the absence of coronavirus genome in the lower respiratory tract; conversely, high numbers of foamy macrophages, eosinophils, and cytotoxic T lymphocytes with low CD4/CD8 T-cell ratio were detected, confirming the hypothesis of amiodarone-induced cryptogenic organizing pneumonia. Timely discontinuation of amiodarone and initiation of steroid therapy led to resolution of respiratory symptoms, systemic inflammation, and radiographic opacities. Conclusions A comprehensive analysis of medical and pharmacological history, clinical onset, radiologic details, and peripheral and BALF cellularity, is required for a correct differential diagnosis and management of ILDs in the COVID-19 era.

Endobronchial Ultrasound (EBUS) has been widely used to stage lung tumors and to diagnose mediastinal diseases. In the last decade, this procedure has evolved in several technical aspects, with new tools available to optimize tissue sampling and to increase its diagnostic yield, like elastography, different types of needles and, most recently, miniforceps and cryobiopsy. Accordingly, the indications for the use of the EBUS scope into the airways to perform the Endobronchial Ultrasound–TransBronchial Needle Aspiration (EBUS-TBNA) has also extended beyond the endobronchial and thoracic boundaries to sample lesions from the liver, left adrenal gland and retroperitoneal lymph nodes via the gastroesophageal tract, performing the Endoscopic UltraSound with Bronchoscope-guided Fine Needle Aspiration (EUS-B-FNA). In this review, we summarize and critically discuss the main indication for the use of the EBUS scope, even the more uncommon, to underline its utility and versatility in clinical practice.

Background: Recent literature has shown the presence of B cells and autoantibodies in idiopathic pulmonary fibrosis (IPF) which would imply the presence of tertiary lymphoid structures (TLS, sites where the immune response is triggered), yet TLS are not considered features of the histological characteristics of IPF. Aim: This study aims to quantify the presence, size, and degree of activation of TLS in biopsied and explanted lungs from patients with early- and late-IPF, never treated with antifibrotics, and relate their presence and activity to the clinical course, disease progression, and lung inflammation. Methods: Immunohistochestry for B cells and CD4, CD8, and CD45 cells was performed in lung tissue from IPF patients: 18 at diagnosis (early), 39 explanted (end-stage), and 12 smoking controls. TLS activation was assessed by CD40 expression. Spirometry along 31 (12-72) months of follow-up was used to characterize end-stage IPF as slow progressors or rapid progressors. Results: B cells, along with other inflammatory cells, were higher in early- and end-stage IPF than in controls (p < 0.001). In rapid progressors, all inflammatory cells were higher than in slow progressors (p < 0.05). TLS were present in 100% of early- and end-stage IPF and in 50% of controls. In end-stage IPF, the TLS area and activation score were higher than in early IPF (p < 0.0001; p = 0.005) and controls (p < 0.04; p < 0.002). TLS activation score correlated with FVC decline during follow-up in rapid progressors (r = 0.73; p = 0.007) but not in slow progressors. Conclusions: A prominent B-cell infiltration, along with the presence of TLS, the activity of which correlates with FVC decline, is an important component of IPF from the beginning of the disease, likely playing an important role on its mechanism and progression. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic and the Russian invasion of Ukraine have had significant consequences for various aspects of global society, including the relationship between citizens and politics. This article explores how the COVID-19 crisis has impacted civic and political participation in Italy. To investigate this topic and provide insights, the two authors utilize data from the 'Italians and the State' survey conducted by the University of Urbino Carlo Bo's Lapolis, in addition to data from the Ministry of the Interior. The analysis reveals that the decline in electoral participation is part of a long-term trend that remained unaffected by the pandemic. While other forms of participation underwent a predictable drop during the most acute phase of the pandemic, they subsequently showed signs of recovery, indicating a general resurgence of participation in Italy. However, activities conducted exclusively online appear to have reached a plateau. This might suggest a growing disillusionment with the Internet itself among citizens. In conclusion, COVID-19 was not a decisive turning point but rather an event that intersected with existing long-term trends. [ABSTRACT FROM AUTHOR]

Non-alcoholic fatty liver disease (NAFLD) is becoming the most common chronic liver disease worldwide. In 20-30% of patients, NAFLD can progress into non-alcoholic steatohepatitis (NASH), eventually leading to fibrosis, cirrhosis and hepatocellular carcinoma development. SerpinB3 (SB3), a hypoxia-inducible factor-2α dependent cysteine protease inhibitor, is up-regulated in hepatocytes during progressive NAFLD and proposed to contribute to disease progression. In this study we investigated the pro-inflammatory role of SB3 by employing phorbol-myristate acetate-differentiated human THP-1 macrophages exposed in vitro to human recombinant SB3 (hrSB3) along with mice overexpressing SB3 in hepatocytes (TG/SB3) or knockout for SB3 (KO/SB3) in which NASH was induced by feeding methionine/choline deficient (MCD) or a choline-deficient, L-amino acid defined (CDAA) diets. In vivo experiments showed that the induction of NASH in TG/SB3 mice was characterized by an impressive increase of liver infiltrating macrophages that formed crown-like aggregates and by an up-regulation of hepatic transcript levels of pro-inflammatory cytokines. All these parameters and the extent of liver damage were significantly blunted in KO/SB3 mice. In vitro experiments confirmed that hrSB3 stimulated macrophage production of M1-cytokines such as TNFα and IL-1β and reactive oxygen species along with that of TGFβ and VEGF through the activation of the NF-kB transcription factor. The opposite changes in liver macrophage activation observed in TG/SB3 or KO/SB3 mice with NASH were associated with a parallel modulation in the expression of triggering receptor expressed on myeloid cells-2 (TREM2), CD9 and galectin-3 markers, recently detected in NASH-associated macrophages. From these results we propose that SB3, produced by activated/injured hepatocytes, may operate as a pro-inflammatory mediator in NASH contributing to the disease progression.

Background COPD is a major health problem, mainly due to cigarette smoking. Most studies in COPD are dedicated to fully developed COPD in older subjects, even though development of COPD may start soon after smoking initiation. Therefore, there is a need to diagnose this “early disease” by detecting the initial events responsible for ultimate development of COPD. Methods Measurement of maximum mid expiratory flow between 25 and 75% of vital capacity (MMEF) in a routine spirometry, which detects small airways disease, was used to investigate if MMEF abnormalities in smokers without COPD (noCOPD) would relate to respiratory symptoms and identify smokers that might progress to COPD. For this purpose we studied 511 smokers, 302 COPD and 209 noCOPD, followed long term with spirometry including MMEF, diffusing capacity of the lung for carbon monoxide (DLCO), 6-min walk test (6MWT), Medical Research Council Dyspnoea Scale and COPD Assessment Test. Three spirometries V1,V2 and V3 (5±2.5 and 10±4 years apart from V1) were performed to assess functional decline and development of COPD. Results 65% of noCOPD had an abnormal MMEF (80% group (p=0.04). 21% of noCOPD with MMEF 80% developed COPD by V3 (p=0.0004). Conclusions The MMEF, a functional test available in a routine spirometry, can detect early lung abnormalities and identify the subset of symptomatic smokers with pathological changes that might lead to COPD.

Introduction What does the physician think in his/her intimacy about clinical care for when his/her death would be near? Living Will is a type of advance directive with the aim to guarantee the testator’s autonomy when faced with death. Particularly oncologists are often faced with human finitude. Their delicate work does not protect them from the possible anguish of thinking and preparing for their own death. It is pertinent to know the psychic mechanisms normally present in the management of this expectation. Objectives To explore symbolic representations of oncologists such as referred to the possible elaboration of their own Living Will. Methods Qualitative design. Eight participants, clinicians, sample closed by theoretical saturation of information. Semidirected interviews in-depth were conducted online during the pandemic, fully transcribed. Technique of Clinical-Qualitative Content Analysis used for data treatment to generate categories of discussion. The authors search for core meanings in the corpus of interviews, after free-floating readings. Results Three categories emerged from the material: Living Will: postponing the decision in order to not anticipate death; From Rationalization Mechanism to Intellectualization: a more sophisticated defensive strategy; Loss of Autonomy: the doctor’s belief while to feel him/herself patient. Conclusions (1) Even with all scientific knowledge, respondents have archaic thoughts on defining advance directives as healthy individuals would mean rushing time of their death. (2) Resistance of these professionals to an imagined scenario of end reveals underlying anguish in writing of living will. (3) There is fear of losing autonomy when they do not know how their Living Will can be seen. Disclosure No significant relationships.

Introduction According to the Medical Subject Headings, the vocabulary used by PubMed, procrastination is ‘the deferment of actions or tasks to a later time, or to infinity’. Studies on procrastination are increasing, especially among university students, gaining prominence in academic literature. However, studies on the procrastination phenomenon have been mainly quantitative, correlating such experiences with clinical and behavioral manifestations. Specific research with occupational therapy students is lacking in the literature. Objectives To interpret symbolic meanings related to life experiences of the procrastination phenomenon of school tasks as reported by occupational therapy undergraduate students, self-referred as procrastinators. Methods Clinical-qualitative design. Data collected through semi-directed interviews with open-ended questions in-depth. Clinical-Qualitative Content Analysis generated categories discussed in the light of the psychodynamic theoretical framework. This study was carried out in a private Brazilian university. The sample was closed by the information saturation criterion. Results Seven students were interviewed. Procrastination comes associated with anxiety as productivity, but not reported as an “executive drive”, that would imprison the individual in a vicious cycle. There are defense mechanisms referred to as self-preservation for not assume responsibilities for tasks. Ineffective strategies seem to be experienced by the students to avoid procrastination, but without resolving possible psychodynamic conflicts related to the task. Conclusions Students’ procrastination ambivalently affects their daily lives, although they can report the phenomenon as negative. It is suggested further qualitative studies that explore specifically meanings of procrastinating personal activities, in general, considering these individuals will work precisely in a therapeutic approach in the field of occupations of the people. Disclosure No significant relationships.