Shedding light on ai in radiology: A systematic review and taxonomy of eye gaze-driven interpretability in deep learning.

X-ray imaging plays a crucial role in diagnostic medicine. Yet, a significant portion of the global population lacks access to this essential technology due to a shortage of trained radiologists. Eye-tracking data and deep learning models can enhance X-ray analysis by mapping expert focus areas, guiding automated anomaly detection, optimizing workflow efficiency, and bolstering training methods for novice radiologists. However, the literature shows contradictory results regarding the usefulness of eye-tracking data in deep-learning architectures for abnormality detection. We argue that these discrepancies between studies in the literature are due to (a) the way eye-tracking data is (or is not) processed, (b) the types of deep learning architectures chosen, and (c) the type of application that these architectures will have. We conducted a systematic literature review using PRISMA to address these contradicting results. We analyzed 60 studies that incorporated eye-tracking data in a deep-learning approach for different application goals in radiology. We performed a comparative analysis to understand if eye gaze data contains feature maps that can be useful under a deep learning approach and whether they can promote more interpretable predictions. To the best of our knowledge, this is the first survey in the area that performs a thorough investigation of eye gaze data processing techniques and their impacts in different deep learning architectures for applications such as error detection, classification, object detection, expertise level analysis, fatigue estimation and human attention prediction in medical imaging data. Our analysis resulted in two main contributions: (1) taxonomy that first divides the literature by task, enabling us to analyze the value eye movement can bring for each case and build guidelines regarding architectures and gaze processing techniques adequate for each application, and (2) an overall analysis of how eye gaze data can promote explainability in radiology.

Peri-implant Parameters of Dental Implants Inserted in Prefabricated Microvascular Fibular Flaps: A Retrospective Study.

PURPOSE: To assess the peri-implant and flap parameters of the prefabricated microvascular fibula flap and determine the dental implant survival rate. MATERIALS AND METHODS: This retrospective study investigated a cohort of subjects who received prefabricated microvascular fibula flaps at two highly specialized tumor reconstruction centers. The subjects had all suffered atrophy or a large segmental defect of the jaws due to tumor resection or injury. Two independent surgeons determined the dental implant survival rate and assessed the peri-implant parameters and flap parameters during clinical follow-up. RESULTS: In total, 41 subjects were treated with a prefabricated fibula flap between 1999 and 2012. Of these, 17 subjects (10 male, 7 female) with a total of 62 dental implants were examined. The other 24 subjects were unavailable for assessment and had to be excluded. Ten of the 62 dental implants (16.1%) had to be removed due to peri-implantitis before the follow-up assessment. Follow-up assessments were performed at intervals ranging from 2 to 12 years (mean: 7.2 years) after fibula flap transplantation. The dental implant survival rate was found to be 83.9%. A total of 208 dental surfaces were assessed. Overall, 96% of all surfaces had a pocket depth (PD) of ≤ 4 mm and 4% had a pocket depth of > 5 mm. An attachment level (AL) of 3 mm was measured in 48.5% of implants and ≥ 5 mm was measured in 15.9% of implants. Dental implants with a PD > 4 mm showed a significantly higher plaque index (PI) (75%; P = .0057), papillary bleeding index (PBI) (62.5%; P = .0094), and radiologic bone loss (P = .0014) compared to dental implants with a PD ≤ 4 mm. CONCLUSIONS: Reconstructive surgery using microvascular fibula flaps represents an alternative tool for oral rehabilitation in subjects suffering from a large segmental defect in the maxillary or mandibular bone compared to the conventional method. However, it appears that the different ossification processes that develop the fibula and the jawbones affect dental implant survival.

MDF-Net for abnormality detection by fusing X-rays with clinical data.

This study investigates the effects of including patients' clinical information on the performance of deep learning (DL) classifiers for disease location in chest X-ray images. Although current classifiers achieve high performance using chest X-ray images alone, consultations with practicing radiologists indicate that clinical data is highly informative and essential for interpreting medical images and making proper diagnoses. In this work, we propose a novel architecture consisting of two fusion methods that enable the model to simultaneously process patients' clinical data (structured data) and chest X-rays (image data). Since these data modalities are in different dimensional spaces, we propose a spatial arrangement strategy, spatialization, to facilitate the multimodal learning process in a Mask R-CNN model. We performed an extensive experimental evaluation using MIMIC-Eye, a dataset comprising different modalities: MIMIC-CXR (chest X-ray images), MIMIC IV-ED (patients' clinical data), and REFLACX (annotations of disease locations in chest X-rays). Results show that incorporating patients' clinical data in a DL model together with the proposed fusion methods improves the disease localization in chest X-rays by 12% in terms of Average Precision compared to a standard Mask R-CNN using chest X-rays alone. Further ablation studies also emphasize the importance of multimodal DL architectures and the incorporation of patients' clinical data in disease localization. In the interest of fostering scientific reproducibility, the architecture proposed within this investigation has been made publicly accessible( https://github.com/ChihchengHsieh/multimodal-abnormalities-detection ).

Peri-implant Parameters of Dental Implants Inserted in Prefabricated Microvascular Fibular Flaps: A Retrospective Study.

PURPOSE: To assess the peri-implant and flap parameters of the prefabricated microvascular fibula flap and determine the dental implant survival rate. MATERIALS AND METHODS: This retrospective study investigated a cohort of subjects who received prefabricated microvascular fibula flaps at two highly specialized tumor reconstruction centers. The subjects had all suffered atrophy or a large segmental defect of the jaws due to tumor resection or injury. Two independent surgeons determined the dental implant survival rate and assessed the peri-implant parameters and flap parameters during clinical follow-up. RESULTS: In total, 41 subjects were treated with a prefabricated fibula flap between 1999 and 2012. Of these, 17 subjects (10 male, 7 female) with a total of 62 dental implants were examined. The other 24 subjects were unavailable for assessment and had to be excluded. Ten of the 62 dental implants (16.1%) had to be removed due to peri-implantitis before the follow-up assessment. Follow-up assessments were performed at intervals ranging from 2 to 12 years (mean: 7.2 years) after fibula flap transplantation. The dental implant survival rate was found to be 83.9%. A total of 208 dental surfaces were assessed. Overall, 96% of all surfaces had a pocket depth (PD) of ≤ 4 mm and 4% had a pocket depth of > 5 mm. An attachment level (AL) of 3 mm was measured in 48.5% of implants and ≥ 5 mm was measured in 15.9% of implants. Dental implants with a PD > 4 mm showed a significantly higher plaque index (PI) (75%; P = .0057), papillary bleeding index (PBI) (62.5%; P = .0094), and radiologic bone loss (P = .0014) compared to dental implants with a PD ≤ 4 mm. CONCLUSIONS: Reconstructive surgery using microvascular fibula flaps represents an alternative tool for oral rehabilitation in subjects suffering from a large segmental defect in the maxillary or mandibular bone compared to the conventional method. However, it appears that the different ossification processes that develop the fibula and the jawbones affect dental implant survival.

Children with extended oligoarticular and polyarticular juvenile idiopathic arthritis have alterations in B and T follicular cell subsets in peripheral blood and a cytokine profile sustaining B cell activation.

OBJECTIVES: The main goal of this study was to characterise the frequency and phenotype of B, T follicular helper (Tfh) and T follicular regulatory (Tfr) cells in peripheral blood and the cytokine environment present in circulation in children with extended oligoarticular juvenile idiopathic arthritis (extended oligo JIA) and polyarticular JIA (poly JIA) when compared with healthy controls, children with persistent oligoarticular JIA (persistent oligo JIA) and adult JIA patients. METHODS: Blood samples were collected from 105 JIA patients (children and adults) and 50 age-matched healthy individuals. The frequency and phenotype of B, Tfh and Tfr cells were evaluated by flow cytometry. Serum levels of APRIL, BAFF, IL-1ß, IL-2, IL-4, IL-6, IL-10, IL-17A, IL-21, IL-22, IFN-γ, PD-1, PD-L1, sCD40L, CXCL13 and TNF were measured by multiplex bead-based immunoassay and/or ELISA in all groups included. RESULTS: The frequency of B, Tfh and Tfr cells was similar between JIA patients and controls. Children with extended oligo JIA and poly JIA, but not persistent oligo JIA, had significantly lower frequencies of plasmablasts, regulatory T cells and higher levels of Th17-like Tfh cells in circulation when compared with controls. Furthermore, APRIL, BAFF, IL-6 and IL-17A serum levels were significantly higher in paediatric extended oligo JIA and poly JIA patients when compared with controls. These immunological alterations were not found in adult JIA patients in comparison to controls. CONCLUSIONS: Our results suggest a potential role and/or activation profile of B and Th17-like Tfh cells in the pathogenesis of extended oligo JIA and poly JIA, but not persistent oligo JIA.

Src-Dependent NM2A Tyrosine Phosphorylation Regulates Actomyosin Remodeling.

Non-muscle myosin 2A (NM2A) is a key cytoskeletal enzyme that, along with actin, assembles into actomyosin filaments inside cells. NM2A is fundamental for cell adhesion and motility, playing important functions in different stages of development and during the progression of viral and bacterial infections. Phosphorylation events regulate the activity and the cellular localization of NM2A. We previously identified the tyrosine phosphorylation of residue 158 (pTyr158) in the motor domain of the NM2A heavy chain. This phosphorylation can be promoted by Listeria monocytogenes infection of epithelial cells and is dependent on Src kinase; however, its molecular role is unknown. Here, we show that the status of pTyr158 defines cytoskeletal organization, affects the assembly/disassembly of focal adhesions, and interferes with cell migration. Cells overexpressing a non-phosphorylatable NM2A variant or expressing reduced levels of Src kinase display increased stress fibers and larger focal adhesions, suggesting an altered contraction status consistent with the increased NM2A activity that we also observed. We propose NM2A pTyr158 as a novel layer of regulation of actomyosin cytoskeleton organization.

[Evaluation of the Knowledge of Women of Childbearing Age with Epilepsy about the Impact of Their Disease in Contraception, Pregnancy and Breastfeeding: A Multicenter Cross-Sectional Study]. / Avaliação do Conhecimento das Mulheres com Epilepsia em Idade Fértil sobre o Impacto da sua Doença na Contraceção, Gravidez e Amamentação: Um Estudo Transversal Multicêntrico.

INTRODUCTION: The interaction of antiseizure medication with contraceptives, its potential teratogenicity and implications in pregnancy and breastfeeding are aspects to consider in the neurological care of women with epilepsy of childbearing age. To ensure the commitment in therapeutic decisions and the appropriate planning of maternity, it is essential that women are informed about the implications of their disease in these domains. The main aim of this study was to assess the knowledge of women of childbearing age with epilepsy concerning the impact of epilepsy in contraception, pregnancy and breastfeeding. As secondary aims we defined (1) the demographic, clinical and therapeutic characterization of this group of patients, (2) the identification of variables that correlated with the level of knowledge of women with epilepsy, and (3) the identification of preferential methods to acquire new knowledge about epilepsy. MATERIAL AND METHODS: The study was observational, cross-sectional and multicentric, and was carried out in five hospitals of the Lisbon metropolitan area. After identifying all women of childbearing age with epilepsy followed in the epilepsy clinic of each center, we applied an electronic questionnaire based on a non-systematic review of the literature. RESULTS: One hundred and fourteen participants were validated, with a median age of 33 years. Half of the participants were on monotherapy, and the majority had no seizures in the last six months. We identified important gaps in the participants' knowledge. Sections about complications and administration of antiseizure medication during pregnancy were the ones with the worst results. None of the clinical and demographic variables correlated with the final questionnaire score. Having had a previous pregnancy and the desire to breastfeed in a future pregnancy were positively correlated with the performance in breastfeeding section. Face-to-face discussion during medical outpatient visits was selected as the preferential method to learn about epilepsy, and the internet and social media were the least preferred ones. CONCLUSION: The knowledge of women of childbearing age with epilepsy in the Lisbon metropolitan area concerning the impact of epilepsy in contraception, pregnancy and breastfeeding seems to have significant gaps. Medical teams should consider engaging in patient education particularly during outpatient clinics.

Introdução: A interação dos fármacos anticrise epilética com os métodos contracetivos, a sua potencial teratogenicidade e as implicações na gravidez e amamentação são aspetos a considerar no acompanhamento de mulheres com epilepsia em idade fértil. Para o seu desejado envolvimento nas decisões terapêuticas e o adequado planeamento da maternidade, é essencial que as mulheres estejam corretamente informadas acerca das implicações da sua doença. O objetivo principal do presente estudo foi avaliar o conhecimento das mulheres com epilepsia em idade fértil sobre o impacto da epilepsia na contraceção, gravidez e amamentação. Como objetivos secundários definiram-se (1) a caracterização demográfica, clínica e terapêutica deste grupo de doentes, (2) a identificação de variáveis correlacionadas com o nível de conhecimento das mulheres com epilepsia, e (3) a identificação de meios e suportes preferenciais para aquisição de novos conhecimentos sobre epilepsia. Material e Métodos: O estudo foi observacional, transversal e multicêntrico, tendo decorrido em cinco centros hospitalares da região metropolitana de Lisboa. Após identificação das mulheres com epilepsia em idade fértil seguidas na Consulta de Epilepsia de cada centro, aplicou-se um questionário eletrónico construído após revisão não sistemática da literatura. Resultados: Foram validadas 114 participantes, com uma idade mediana de 33 anos. Metade das participantes apresentavam-se sob monoterapia, tendo a maioria a epilepsia controlada há pelo menos seis meses. Identificaram-se importantes lacunas no conhecimento das participantes. Conceitos sobre complicações dos fármacos anticrise epilética e a sua administração durante a gravidez motivaram piores resultados. Não houve correlação entre variáveis clinico-demográficas e o resultado no questionário. A ocorrência de gravidez prévia e o desejo de amamentar numa gravidez futura correlacionaram-se com o desempenho na secção sobre amamentação. A discussão oral na consulta foi a forma preferencial para aquisição de novos conhecimentos sobre epilepsia, tendo a internet e as redes sociais sido os meios menos escolhidos. Conclusão: O conhecimento das mulheres com epilepsia em idade fértil na área metropolitana de Lisboa sobre o impacto da sua doença na contraceção, gravidez e amamentação parece apresentar lacunas importantes. A educação para a saúde deste grupo deverá constituir uma preocupação por parte das equipas médicas, devendo privilegiar-se a consulta como local de ensino.

Immune and spermatogenesis-related loci are involved in the development of extreme patterns of male infertility.

We conducted a genome-wide association study in a large population of infertile men due to unexplained spermatogenic failure (SPGF). More than seven million genetic variants were analysed in 1,274 SPGF cases and 1,951 unaffected controls from two independent European cohorts. Two genomic regions were associated with the most severe histological pattern of SPGF, defined by Sertoli cell-only (SCO) phenotype, namely the MHC class II gene HLA-DRB1 (rs1136759, P = 1.32E-08, OR = 1.80) and an upstream locus of VRK1 (rs115054029, P = 4.24E-08, OR = 3.14), which encodes a protein kinase involved in the regulation of spermatogenesis. The SCO-associated rs1136759 allele (G) determines a serine in the position 13 of the HLA-DRß1 molecule located in the antigen-binding pocket. Overall, our data support the notion of unexplained SPGF as a complex trait influenced by common variation in the genome, with the SCO phenotype likely representing an immune-mediated condition.

Assessment of the outcomes of SARS-CoV-2 infection in children and young people followed at Portuguese pediatric rheumatology clinics.

INTRODUCTION: Coronavirus Disease 2019 (COVID-19) generally appears to have milder clinical symptoms and fewer laboratory abnormalities in children. It remains unknown whether children and young people with inflammatory chronic diseases who acquire SARS-CoV-2 infection have a more severe course, due to either underlying disease or immunosuppressive treatments. OBJECTIVES: To assess the epidemiological features and clinical outcomes of children and young people with inflammatory chronic diseases followed at Pediatric Rheumatology Clinics who were infected with SARS-CoV-2. METHODS: A multicentric prospective observational study was performed. Data on demographic variables, clinical features and treatment were collected between March 2020 and September 2021, using the Rheumatic Diseases Portuguese Register (Reuma.pt) and complemented with data from the hospital clinical records. RESULTS: Thirty-four patients were included, 62% were female, with a median age of 13 [8-16] years and a median time of inflammatory chronic disease of 6 [3-10] years. The most common diagnoses were juvenile idiopathic arthritis (n=22, 64.7%), juvenile dermatomyositis (n=3, 8.8%) and idiopathic uveitis (n=3, 8.8%). Twenty patients were on conventional synthetic disease modifying drugs (csDMARDs) and 10 on biologic DMARDs (bDMARDs). Five patients had an active inflammatory disease at the time of infection (low activity). Seven patients had an asymptomatic infection while 27 patients (79%) had symptoms: cough (n=12), fever (n=11), rhinorrhea (n=10), headache (n=8), malaise (n=8), fatigue (n=7), anosmia (n=5), myalgia (n=5),dysgeusia (n=4), odynophagia (n=4), chest pain (n=2), diarrhea (n=2), arthralgia (n=1), vomiting (n=1) and conjunctivitis (n=1). No patient required hospitalization or directed treatment, and all recovered without sequelae. In 8 patients there was a change in the baseline medication during the infection: suspension of bDMARDs (n=4), reduction of bDMARDs (n=1), suspension of csDMARDs (n=4) and reduction of csDMARDs (n=2). Only in one patient with juvenile dermatomyositis (who discontinued bDMARDs and csDMARDs), the underlying disease worsened. CONCLUSIONS: This is the first study involving children with inflammatory chronic diseases followed at Rheumatology Clinics and SARS-CoV-2 infection in Portugal. In our cohort, mild illness was predominant, which is consistent with the literature. There was no need for hospitalization or specific treatment, and, in most cases, no worsening of the underlying disease was identified.

Effectiveness of a hybrid digital substance abuse prevention approach combining e-Learning and in-person class sessions.

Background: Effective school-based programs for preventing substance abuse offer considerable public health potential. Yet limited class time and uneven implementation fidelity can be barriers to widespread adoption and high-quality implementation. A hybrid digital approach may be effective and help address these barriers. Objective: To evaluate the effectiveness of a hybrid substance abuse prevention program for middle school students consisting of e-learning modules and in-person class sessions. Design: Twenty-three United States (U.S.) middle schools were randomly assigned either to an intervention condition (13 schools) or a treatment-as-usual control condition (10 schools) where standard health education material was delivered. There were 1,447 participants who completed the pre-test and post-test assessments, of which 48.3% were male and 51.7% female. Intervention: The hybrid digital intervention consisted of 14 brief e-learning modules and six classroom sessions adapted from an evidence-based program designed for classroom implementation to increase knowledge of adverse consequences of substance use and improve social skills, personal coping skills, and skills for resisting social influences to smoke, drink, or use drugs. Measures: Participating students completed online pre-test and post-test surveys to assess substance use, knowledge, and life skills. Results: There were significant reductions in substance use for the hybrid digital condition compared to the control condition as well as significant increases in health knowledge, skills knowledge, and life skills. Conclusions: A hybrid digital approach to substance abuse prevention is effective and offers potential for overcoming common barriers to widespread adoption and high-quality implementation.

Effects of Early Weaning Associated with Alimentary Stress on Emotional and Feeding Behavior of Female Adult Wistar Rats.

Maternal lactation proves crucial for mammals' nutrition during their early development, influencing the development of adult physiological mechanisms. Its premature termination has been associated with several disorders, but these have been primarily documented in males, when they are most prevalent in women. Therefore, we subjected adult female Wistar rats to Early Weaning through maternal separation at age 15 days to acute alimentary stress in the form of visual and olfactory exposition to a cafeteria diet sans consumption for 22 days. We measured standard diet intake and water intake daily and cafeteria diet intake every 7 days. Additionally, we evaluated anxiety using the elevated plus maze and measured body weight in similar intervals. Results showed less consumption of the cafeteria diet among Early Weaning rats on day 2 and more time spent in the maze's central area by the Early Weaning rats during the basal evaluation and in the maze's open arms by control rats on day 7 when compared to the same group's basal time. No other significant differences were found. These results show the importance of determining the impact that female steroidal gonadal hormones such as estradiol have upon feeding behavior and anxiety and determining to what degree these parameters are influenced by hormonal action.

The Yin and Yang of Pneumolysin During Pneumococcal Infection.

Pneumolysin (PLY) is a pore-forming toxin produced by the human pathobiont Streptococcus pneumoniae, the major cause of pneumonia worldwide. PLY, a key pneumococcal virulence factor, can form transmembrane pores in host cells, disrupting plasma membrane integrity and deregulating cellular homeostasis. At lytic concentrations, PLY causes cell death. At sub-lytic concentrations, PLY triggers host cell survival pathways that cooperate to reseal the damaged plasma membrane and restore cell homeostasis. While PLY is generally considered a pivotal factor promoting S. pneumoniae colonization and survival, it is also a powerful trigger of the innate and adaptive host immune response against bacterial infection. The dichotomy of PLY as both a key bacterial virulence factor and a trigger for host immune modulation allows the toxin to display both "Yin" and "Yang" properties during infection, promoting disease by membrane perforation and activating inflammatory pathways, while also mitigating damage by triggering host cell repair and initiating anti-inflammatory responses. Due to its cytolytic activity and diverse immunomodulatory properties, PLY is integral to every stage of S. pneumoniae pathogenesis and may tip the balance towards either the pathogen or the host depending on the context of infection.

Oportunidades e barreiras à comunicação interprofissional no contexto da Covid-19: protocolo de revisão de escopo / Opportunities and barriers to interprofessional communication in the Covid-19 context: scoping review protocol

OBJETIVO: Mapear, na literatura, evidências de oportunidades e barreiras que influenciam a comunicação interprofissional no cotidiano das equipes da Atenção Primária à Saúde e interferem na produção do cuidado do paciente ante a pandemia da Covid-19. MÉTODO: Revisão de escopo, conduzida em conformidade com as recomendações do Joanna Briggs Institute e a extensão PRISMA-ScR, cujo procedimento da estratégia de busca acontecerá a partir da definição dos vocabulários controlados e correspondentes, em combinações com operadores booleanos. RESULTADOS: Serão extraídos dados que constituem características bibliográficas e aspectos metodológicos dos estudos, além de elementos, atividades ou recursos empregados que oportunizam ou bloqueiam a comunicação interprofissional. As evidências mapeadas serão apresentadas em formato de diagramas, gráficos e síntese narrativa. CONCLUSÃO: Pressupõe-se que profissionais de diferentes núcleos de conhecimento assumam compromisso em menor ou maior grau dentro dos serviços. Outrossim, comunicação interprofissional torna-se ferramenta essencial à melhoria do cuidado, especialmente ao enfrentamento de situações pandêmicas. Descritores: Pessoal de Saúde; Relações Interprofissionais; Comunicação; Infecções por Coronavírus.

OBJECTIVE: To map, in the literature, evidence of opportunities and barriers that influence interprofessional communication in the daily lives of Primary Health Care teams and interfere in the production of patient care in the face of the Covid-19 pandemic. METHOD: Scoping review, conducted under the recommendations from the Joanna Briggs Institute and the PRISMA-ScR extension, whose search strategy will take place from the definition of the controlled and corresponding vocabularies in combinations with Boolean operators. RESULTS: Data on the bibliographic characteristics and methodological aspects of the studies will be extracted, in addition to elements, activities, or resources used that provide or restrain interprofessional communication. The mapped evidence will be presented in the form of diagrams, graphs, and narrative synthesis. CONCLUSION: It is assumed that professionals from different knowledge centers assume the commitment to a lesser or greater degree within the services. Furthermore, interprofessional communication becomes essential for improving care, especially when dealing with pandemic situations.

Patients' related sexual outcomes in colorectal surgery.

Background: Patients undergoing colorectal surgery (CRS) have an increased risk of developing sexual disorders, attributed to different mechanisms. In this context, sexual function (SF) assessment of patients before and after surgery is essential: to identify risk factors for sexual disorders as well as to minimize their impact on overall quality of life (QoL), allowing them a satisfying relationship and sexual life. Material and methods: Patients over 18 years of age who underwent a CRS in the University Hospital of Geneva, Switzerland, between June 2014 and February 2016 were included. Our main objective was to compare and analyze the evolution of SF, QoL, and marital satisfaction (MS) before and after CRS. Specific and standardized tests were used. Results: A cohort of 72 patients with a median age of 58.73 was analyzed. The majority of CRS was elective (91.5%). A percentage of 52.8% of patients underwent surgery for oncological reasons. There was no statistical difference in SF, sexual QoL, and MS before and after elective or emergency CRS for men. Interestingly, a significant decrease in women's SF (FSFI) as well as their satisfaction within their couple (Locke-Wallace) until 12 months after surgery was found (p = 0.021). However, they showed a steady SF (GRISS) within their couple until 12 months after surgery. Conclusion: Regarding knowledge about difficulties to talk about this intimate topic and gender differences, this general overview raises the question of the necessity to introduce in a long-course follow-up different methods of sexual health assessment with specific stakeholders.

Inhibition of extracellular traps by spores of Trichoderma stromaticum on neutrophils obtained from human peripheral blood.

Although the genus Trichoderma is widely used as a biocontrol agent in crops, little is known about its potential impact on the human immune system. In mice, our group has shown that exposition to T. asperelloides spores lead to reduced neutrophil counts in the peripheral blood and in the peritoneal cavity. In addition, T. stromaticum spores produced an inflammatory infiltrate on mice lungs, reducing the levels of IFN-γ and IL-10 cytokines, reactive oxygen species, and receptors of microbial patterns. Here we demonstrate that the interaction of human peripheral neutrophils with T. stromaticum spores also leads to a reduced release of neutrophil extracellular traps (NETs) after induction with the NET-inducer agent phorbol 12-myristate 13-acetate. This interaction also reduced the expression levels of multiple microRNAs, such as miR-221, miR-222, miR-223 and miR-27a, as well as genes related to NETs, such as ELANE, MPO and PADI4. Furthermore, T. stromaticum spores affected the expression of the genes SOCS3, TLR4, CSNK2A1, GSDMD, and NFFKBIA, related to the activation of inflammatory immune responses in neutrophils. Overall, our results suggest T. stromaticum as a potential NET inhibitor and as an immunomodulatory agent. Since this fungus is used as biocontrol in crops, our findings point to the importance of advancing our knowledge on the effects of this bioagent on the human immune system. Finally, the study of the active compounds produced by the fungus is also important for the prospection of new drugs that could be used to block the exacerbation of inflammatory immune responses present in several human diseases.

Cells Responding to Closely Related Cholesterol-Dependent Cytolysins Release Extracellular Vesicles with a Common Proteomic Content Including Membrane Repair Proteins.

The plasma membrane (PM) protects cells from extracellular threats and supports cellular homeostasis. Some pathogens produce pore-forming toxins (PFTs) that disrupt PM integrity by forming transmembrane pores. High PFT concentrations cause massive damage leading to cell death and facilitating infection. Sub-lytic PFT doses activate repair mechanisms to restore PM integrity, support cell survival and limit disease. Shedding of extracellular vesicles (EVs) has been proposed as a key mechanism to eliminate PFT pores and restore PM integrity. We show here that cholesterol-dependent cytolysins (CDCs), a specific family of PFTs, are at least partially eliminated through EVs release, and we hypothesize that proteins important for PM repair might be included in EVs shed by cells during repair. To identify new PM repair proteins, we collected EVs released by cells challenged with sub-lytic doses of two different bacterial CDCs, listeriolysin O and pneumolysin, and determined the EV proteomic repertoire by LC-MS/MS. Intoxicated cells release similar EVs irrespectively of the CDC used. Also, they release more and larger EVs than non-intoxicated cells. A cluster of 70 proteins including calcium-binding proteins, molecular chaperones, cytoskeletal, scaffold and membrane trafficking proteins, was detected enriched in EVs collected from intoxicated cells. While some of these proteins have well-characterized roles in repair, the involvement of others requires further study. As proof of concept, we show here that Copine-1 and Copine-3, proteins abundantly detected in EVs released by intoxicated cells, are required for efficient repair of CDC-induced PM damage. Additionally, we reveal here new proteins potentially involved in PM repair and give new insights into common mechanisms and machinery engaged by cells in response to PM damage.

O processo de trabalho de um ambulatório de oncologia em análise / The work process of an oncology outpatient clinic under analysis

O alto índice do câncer é algo preocupante em todo o mundo. A modalidade de tratamento mais utilizada em oncologia são os quimioterápicos, que, por sua vez, trazem o desconforto por seus efeitos colaterais tão temidos, como náuseas, vômitos, alopecia, entre outros. Se, por um lado, lidar com a dor e o sofrimento faz parte do trabalho em saúde, por outro, isso não pode significar que o trabalhador tenha que carregar as consequências como uma carga de sofrimento individual inerente às suas escolhas profissionais. Afinal, lidar com a dor e o sofrimento é uma necessidade e um bem social inestimável, que precisa ser reconhecido e valorizado nas instituições. Os objetivos deste estudo consistem conhecer os processos de trabalho junto da equipe de enfermagem no ambulatório de oncologia; promover o diálogo e a reflexão da atividade desenvolvida pela equipe de enfermagem no ambulatório de oncologia a partir do método de Instrução ao Sósia; analisar os processos de trabalho da equipe de enfermagem do ambulatório de oncologia por meio do método de Instrução ao Sósia; propor a implantação de supervisão/de reuniões de equipe com o intuito de produção coletiva do trabalho. O cenário foi o ambulatório de oncologia de um hospital público federal do estado do Rio de Janeiro; os participantes foram os integrantes da equipe de enfermagem que atuam na sala de terapia na qual se administram os quimioterápicos. Nos resultados: a dificuldade de instruir o outro na terceira pessoa trata da complexidade que é falar de sua atividade como algo fora de si; o reconhecimento de que o trabalho na quimioterapia é muito focado na técnica, e que, muitas vezes, o trabalhador esquece o poder que existe a cada encontro com o usuário e suas singularidades, mostrando aí que, frequentemente, o trabalhador é capturado pelo "trabalho morto" em detrimento do "trabalho vivo"; a falta de espaço para discussões diárias para trocas e reflexões da prática, trazendo a necessidade de reuniões; e a falta de atendimento psicológico aos profissionais do ambulatório de oncologia. Esta pesquisa traz à luz assuntos que, de fato, precisam ser vistos pelos gestores, líderes que atuam no setor referido: do quanto investimentos com espaços de Educação Permanente em Saúde, para reflexões e resoluções sobre a prática do cuidado em saúde, são essenciais; a atenção à saúde do trabalhador do ambulatório em oncologia deve ser vista e, assim, considerar que se um profissional é bem assistido, o paciente também o será. Cuidando de quem cuida, certamente reverberará em seu cuidado ao usuário.

The high rate of cancer is something worrisome around the world. The most used treatment modality in oncology is chemotherapy, which in turn brings discomfort due to its feared side effects such as nausea, vomiting, alopecia, among others. If, on the one hand, dealing with pain and suffering is part of health workers, on the other hand, this cannot mean that workers have to bear the consequences as a burden of individual suffering inherent to their professional choices. After all, dealing with pain and suffering is an invaluable need and social good that needs to be recognized and valued in institutions. The objectives of this study are: to know the work processes with the nursing team in the oncology outpatient clinic from the use of the method of instruction to the double and thus expand the resources for the action of their activities; to identify the challenges encountered in practice for the care of people using chemotherapy; and to promote transformations in the work processes. This is a qualitative study, which used the method of instruction to the double, promoting dialogue and reflection among workers. The scenario was the oncology outpatient clinic of a federal public hospital in the state of Rio de Janeiro, the participants were the members of the nursing team working in the therapy room where chemotherapy is administered. Results: the difficulty of instructing the other in the 3rd person addresses the difficulty that is to speak of their activity as something outside of themselves; the recognition that the work in chemotherapy is very focused on the technique, and that often the worker forgets the power that exists at each meeting with the user and its singularities, showing that the worker is often captured by "dead work" to the detriment of "living work"; the lack of space for daily discussions for exchanges and reflections of practice, bringing the need for meetings; the lack of psychological care for the professionals of the oncology outpatient clinic. Final considerations: this research brings to light issues that need to be seen by managers, leaders working in the referred sector, of how much investment with spaces of Permanent Education in Health are essential for reflections and resolutions on the practice of health care, the health care of the outpatient worker in oncology should be seen and thus it should be considered that if the professional is well-attended, the patient will be, too. Taking care of those who care will certainly reverberate in their care towards the user.