Biocompatibility of Brazilian native yeast-derived sophorolipids and Trichoderma harzianum as plant-growth promoting bioformulations.

The replacement of agrochemicals by biomolecules is imperative to mitigate soil contamination and inactivation of its core microbiota. Within this context, this study aimed at the interaction between a biological control agent such as Trichoderma harzianum CCT 2160 (BF-Th) and the biosurfactants (BSs) derived from the native Brazilian yeast Starmerella bombicola UFMG-CM-Y6419. Thereafter, their potential in germination of Oryza sativa L. seeds was tested. Both bioproducts were produced on site and characterized according to their chemical composition by HPLC-MS and GC-MS for BSs and SDS-PAGE gel for BF-Th. The BSs were confirmed to be sophorolipids (SLs) which is a well-studied compound with antimicrobial activity. The biocompatibility was examined by cultivating the fungus with SLs supplementation ranging from 0.1 to 2 g/L in solid and submerged fermentation. In solid state fermentation the supplementation of SLs enhanced spore production, conferring the synergy of both bioproducts. For the germination assays, bioformulations composed of SLs, BF-Th and combined (SLT) were applied in the germination of O. sativa L seeds achieving an improvement of up to 30% in morphological aspects such as root and shoot size as well as the presence of lateral roots. It was hypothesized that SLs were able to regulate phytohormones expression such as auxins and gibberellins during early stage of growth, pointing to their novel plant-growth stimulating properties. Thus, this study has pointed to the potential of hybrid bioformulations composed of biosurfactants and active endophytic fungal spores in order to augment the plant fitness and possibly the control of diseases.

Kv1.3 in the spotlight for treating immune diseases.

INTRODUCTION: Kv1.3 is the main voltage-gated potassium channel of leukocytes from both the innate and adaptive immune systems. Channel function is required for common processes such as Ca2+ signaling but also for cell-specific events. In this context, alterations in Kv1.3 are associated with multiple immune disorders. Excessive channel activity correlates with numerous autoimmune diseases, while reduced currents result in increased cancer prevalence and immunodeficiencies. AREAS COVERED: This review offers a general view of the role of Kv1.3 in every type of leukocyte. Moreover, diseases stemming from dysregulations of the channel are detailed, as well as current advances in their therapeutic research. EXPERT OPINION: Kv1.3 arises as a potential immune target in a variety of diseases. Several lines of research focused on channel modulation have yielded positive results. However, among the great variety of specific channel blockers, only one has reached clinical trials. Future investigations should focus on developing simpler administration routes for channel inhibitors to facilitate their entrance into clinical trials. Prospective Kv1.3-based treatments will ensure powerful therapies while minimizing undesired side effects.

Routing of Kv7.1 to endoplasmic reticulum plasma membrane junctions.

AIM: The voltage-gated Kv7.1 channel, in association with the regulatory subunit KCNE1, contributes to the IKs current in the heart. However, both proteins travel to the plasma membrane using different routes. While KCNE1 follows a classical Golgi-mediated anterograde pathway, Kv7.1 is located in endoplasmic reticulum-plasma membrane junctions (ER-PMjs), where it associates with KCNE1 before being delivered to the plasma membrane. METHODS: To characterize the channel routing to these spots we used a wide repertoire of methodologies, such as protein expression analysis (i.e. protein association and biotin labeling), confocal (i.e. immunocytochemistry, FRET, and FRAP), and dSTORM microscopy, transmission electron microscopy, proteomics, and electrophysiology. RESULTS: We demonstrated that Kv7.1 targeted ER-PMjs regardless of the origin or architecture of these structures. Kv2.1, a neuronal channel that also contributes to a cardiac action potential, and JPHs, involved in cardiac dyads, increased the number of ER-PMjs in nonexcitable cells, driving and increasing the level of Kv7.1 at the cell surface. Both ER-PMj inducers influenced channel function and dynamics, suggesting that different protein structures are formed. Although exhibiting no physical interaction, Kv7.1 resided in more condensed clusters (ring-shaped) with Kv2.1 than with JPH4. Moreover, we found that VAMPs and AMIGO, which are Kv2.1 ancillary proteins also associated with Kv7.1. Specially, VAP B, showed higher interaction with the channel when ER-PMjs were stimulated by Kv2.1. CONCLUSION: Our results indicated that Kv7.1 may bind to different structures of ER-PMjs that are induced by different mechanisms. This variable architecture can differentially affect the fate of cardiac Kv7.1 channels.

Functional pri-miR-34b/c rs4938723 and KRAS 3'UTR rs61764370 SNPs: Novel phenotype modifiers in Li-Fraumeni Syndrome?

PURPOSE: Li-Fraumeni Syndrome (LFS) is a rare cancer predisposing condition caused by germline pathogenic TP53 variants, in which core tumors comprise sarcomas, breast, brain and adrenocortical neoplasms. Clinical manifestations are highly variable in carriers of the Brazilian germline founder variant TP53 p.R337H, possibly due to the influence of modifier genes such as miRNA genes involved in the regulation of the p53 pathway. Herein, we investigated the potential phenotypic effects of two miRNA-related functional SNPs, pri-miR-34b/c rs4938723 and 3'UTR KRAS rs61764370, in a cohort of 273 LFS patients from Southern and Southeastern Brazil. METHODS: The genotyping of selected SNPs was performed by TaqMan® allelic discrimination and subsequently custom TaqMan® genotyping results were confirmed by Sanger sequencing in all SNP-positive LFS patients. RESULTS: Although the KRAS SNP showed no effect as a phenotype modulator, the rs4938723 CC genotype was significantly associated with development of LFS non-core tumors (first tumor diagnosis) in p.R337H carriers (p = 0.039). Non-core tumors were also more frequently diagnosed in carriers of germline TP53 DNA binding domain variants harboring the rs4938723 C variant allele. Previous studies described pri-miR-34b/c rs4938723 C as a risk allele for sporadic occurrence of thyroid and prostate cancers (non-core tumors of the LFS spectrum). CONCLUSION: With this study, we presented additional evidence about the importance of analyzing miRNA genes that could indirectly regulate p53 expression, and, therefore, may modulate the LFS phenotype, such as those of the miR-34 family.

In-Hospital influenza vaccination to prevent cardiorespiratory events in the first 45 days after acute coronary syndrome: A prespecified analysis of the VIP-ACS trial.

BACKGROUND: Influenza vaccination prevents major cardiovascular events in individuals presenting a recent acute coronary syndrome (ACS), however the early effect of an in-hospital double-dose vaccination strategy remains uncertain. METHODS: The VIP-ACS was a randomized, pragmatic, multicenter, open-label trial with a blinded-adjudication endpoint. Patients with ACS ≤ 7 days of hospitalization were randomized to an in-hospital double-dose quadrivalent inactivated influenza vaccine (double-dose) or a standard-dose influenza vaccine at 30 days post-randomization. The primary endpoint was a hierarchical composite of death, myocardial infarction, stroke, hospitalization for unstable angina, hospitalization for heart failure, urgent coronary revascularization, and hospitalization for respiratory infections, analyzed with the win ratio (WR) method in short-term follow-up (45-days after randomization). RESULTS: The trial enrolled 1,801 patients (≥18 years old). Median participant age was 57 years, 70 % were male. There were no significant differences between groups on the primary hierarchical endpoint: there were 5.7 % wins in the double-dose in-hospital group and 5.5 % wins in the standard-dose delayed vaccination group (WR: 1.03; 95 % CI: 0.70---1.53; P = 0.85). In a sensitivity analysis including COVID-19 infection in the hospitalizations for respiratory infections endpoint, overall results were maintained (WR: 1.03; 95 % CI 0.71---1.51; P = 0.87). Results were consistent for major cardiovascular events only (WR: 0.82; 95 % CI: 0.48---1.39; P = 0.46). No serious adverse events were observed. CONCLUSION: In patients with recent ACS, in-hospital double-dose influenza vaccination did not significantly reduce cardiorespiratory events at 45 days compared with standard-dose vaccination at 30 days post-randomization.

Reduced mobility is associated with adverse outcomes after in-hospital cardiac arrest.

OBJECTIVE: In-hospital cardiac arrest is a critical medical emergency. Knowledge of prognostic factors could assist in cardiopulmonary resuscitation decision-making. Frailty and functional status are emerging risk factors and may play a role in prognostication. The objective was to evaluate the association between reduced mobility and in-hospital cardiac arrest outcomes. METHODS: This retrospective cohort study included patients over 18 years of age with in-hospital cardiac arrest in Botucatu, Brazil, from April 2018 to December 2021. Exclusion criteria were patients with a do-not-resuscitate order or patients with recurrent in-hospital cardiac arrest. Reduced mobility was defined as the need for a bed bath 48 h before in-hospital cardiac arrest. The outcomes of no return of spontaneous circulation and in-hospital mortality were evaluated. RESULTS: A total of 387 patients were included in the analysis. The mean age was 65.4±14.8 years; 53.7% were males and 75.4% had reduced mobility. Among the evaluated outcomes, the no return of spontaneous circulation rate was 57.1%, and in-hospital mortality was 94.3%. In multivariate analysis, reduced mobility was associated with no return of spontaneous circulation when adjusted by age, gender, initial shockable rhythm, duration of cardiopulmonary resuscitation, and epinephrine administration. However, in multiple logistic regression, there was no association between reduced mobility and in-hospital mortality. CONCLUSION: In patients with in-hospital cardiac arrest, reduced mobility is associated with no return of spontaneous circulation. However, there is no relation to in-hospital mortality.

High frequency of WNT-activated medulloblastomas with CTNNB1 wild type suggests a higher proportion of hereditary cases in a Latin-Iberian population.

Purpose: Medulloblastomas are the most common primary malignant brain tumors in children. They are divided into molecular subgroups: WNT-activated, SHH-Activated, TP53 mutant or wild type, and non-WNT/non-SHH (Groups 3 and 4). WNT-activated medulloblastomas are usually caused by mutations in the CTNNB1 gene (85%-90%), and most remaining cases of CTNNB1 wild type are thought to be caused by germline mutations in APC. So far, the frequencies of CTNNB1 have been reported mainly in North American and European populations. The aim of this study was to report the frequency of CTNNB1 mutations in WNT-activated medulloblastomas in a Latin-Iberian population and correlate with their clinicopathological characteristics. Methods: A total of 266 medulloblastomas from seven different institutions from Brazil (n=211), Portugal (n=38), and Argentina (n=17) were evaluated. Following RNA and DNA isolation from formalin-fixed, paraffin-embedded (FFPE) tumor tissues, the molecular classification and CTNNB1 mutation analysis were performed by nCounter and Sanger sequencing, respectively. Results: WNT-activated medulloblastomas accounted for 15% (40/266) of the series. We observed that 73% of WNT-activated medulloblastomas harbored CTNNB1 mutations. CTNNB1 wild-type cases (27%) were more prevalent in female individuals and suggested to be associated with a worse outcome. Among the CTNNB1 wild-type cases, the available analysis of family history revealed two cases with familiar adenomatous polyposis, harboring APC germline variants. Conclusion: We observed a lower incidence of CTNNB1 mutations in WNT-activated medulloblastomas in our Latin-Iberian cohort compared to frequencies previously described in other populations. Considering that CTNNB1 wild-type cases may exhibit APC germline mutations, our study suggests a higher incidence (~30%) of hereditary WNT-activated medulloblastomas in the Latin-Iberian population.

Dynamics and spatial organization of Kv1.3 at the immunological synapse of human CD4+ T cells.

Formation of the immunological synapse (IS) is a key event during initiation of an adaptive immune response to a specific antigen. During this process, a T cell and an antigen presenting cell form a stable contact that allows the T cell to integrate both internal and external stimuli in order to decide whether to activate. The threshold for T cell activation depends on the strength and frequency of the calcium (Ca2+) signaling induced by antigen recognition, and it must be tightly regulated to avoid undesired harm to healthy cells. Potassium (K+) channels are recruited to the IS to maintain the negative membrane potential required to sustain Ca2+ entry. However, the precise localization of K+ channels within the IS remains unknown. Here, we visualized the dynamic subsynaptic distribution of Kv1.3, the main voltage-gated potassium channel in human T cells. Upon T cell receptor engagement, Kv1.3 polarized toward the synaptic cleft and diffused throughout the F-actin rich distal compartment of the synaptic interface-an effect enhanced by CD2-CD58 corolla formation. As the synapse matured, Kv1.3 clusters were internalized at the center of the IS and released in extracellular vesicles. We propose a model in which specific distribution of Kv1.3 within the synapse indirectly regulates the channel function and that this process is limited through Kv1.3 internalization and release in extracellular vesicles.

Production and applications of pullulan from lignocellulosic biomass: Challenges and perspectives.

Pullulan is an exopolysaccharide produced by Aureobasidium pullulans, with interesting characteristics which lead to its application in industries such as pharmaceuticals, cosmetics, food, and others. To reduce production costs for industrial applications, cheaper raw materials such as lignocellulosic biomass can be utilized as a carbon and nutrient source for the microbial process. In this study, a comprehensive and critical review was conducted, encompassing the pullulan production process and the key influential variables. The main properties of the biopolymer were presented, and different applications were discussed. Subsequently, the utilization of lignocellulosics for pullulan production within the framework of a biorefinery concept was explored, considering the main published works that deal with materials such as sugarcane bagasse, rice husk, corn straw, and corn cob. Next, the main challenges and future prospects in this research area were highlighted, indicating the key strategies to favor the industrial production of pullulan from lignocellulosic biomasses.

Bleeding hepatocellular adenoma: historical series and outcomes.

INTRODUCTION: hepatocellular adenoma - AHC - is a rare benign neoplasm of the liver more prevalent in women at reproductive age and its main complication is hemorrhage. In the literature, case series addressing this complication are limited. METHODS: between 2010 and 2022, 12 cases of bleeding AHC were attended in a high-complexity university hospital in southern Brazil, whose medical records were retrospectively evaluated. RESULTS: all patients were female, with a mean age of 32 years and a BMI of 33kg/m2. The use of oral contraceptives was identified in half of the sample and also half of the patients had a single lesion. The mean diameter of the largest lesion was 9.60cm and the largest lesion was responsible for bleeding in all cases. The presence of hemoperitoneum was documented in 33% of the patients and their age was significantly higher than the patients who did not have hemoperitoneum - 38 vs 30 years, respectively. Surgical resection of the bleeding lesion was performed in 50% of the patients and the median number of days between bleeding and resection was 27 days. In only one case, embolization was used. The relation between ingrowth of the lesions and the time, in months, was not obtained in this study. CONCLUSION: it is concluded that the bleeding AHC of the present series shows epidemiological agreement with the literature and may suggest that older patients trend to have hemoperitoneum more frequently, a fact that should be investigated in further studies.

The Phosphorylation of Kv1.3: A Modulatory Mechanism for a Multifunctional Ion Channel.

The voltage-gated potassium channel Kv1.3 plays a pivotal role in a myriad of biological processes, including cell proliferation, differentiation, and apoptosis. Kv1.3 undergoes fine-tuned regulation, and its altered expression or function correlates with tumorigenesis and cancer progression. Moreover, posttranslational modifications (PTMs), such as phosphorylation, have evolved as rapid switch-like moieties that tightly modulate channel activity. In addition, kinases are promising targets in anticancer therapies. The diverse serine/threonine and tyrosine kinases function on Kv1.3 and the effects of its phosphorylation vary depending on multiple factors. For instance, Kv1.3 regulatory subunits (KCNE4 and Kvß) can be phosphorylated, increasing the complexity of channel modulation. Scaffold proteins allow the Kv1.3 channelosome and kinase to form protein complexes, thereby favoring the attachment of phosphate groups. This review compiles the network triggers and signaling pathways that culminate in Kv1.3 phosphorylation. Alterations to Kv1.3 expression and its phosphorylation are detailed, emphasizing the importance of this channel as an anticancer target. Overall, further research on Kv1.3 kinase-dependent effects should be addressed to develop effective antineoplastic drugs while minimizing side effects. This promising field encourages basic cancer research while inspiring new therapy development.

Membrane Channels in Health and Diseases.

The goal of this Special Issue, entitled "Membrane Channels in Health and Diseases (https://www [...].

Phenolic Content and Bioactivity as Geographical Classifiers of Propolis from Stingless Bees in Southeastern Mexico.

Propolis collected by stingless bees is a valuable biocultural resource and a source of bioactive compounds. Methodologies to establish both the geographic origin and the potential pharmacological activity of propolis of stingless bees are required to regulate their sustainable use. The aim of this study was to classify Melipona beecheii propolis according to its phenolic compound content and potential pharmacological activity, using in vitro assays and statistical methodologies of multivariate analysis, hierarchical cluster analysis, and principal component analysis. Propolis samples were collected from seven states in southeastern Mexico. Total phenolic content and flavonoids were determined spectrophotometrically, and antioxidant, anti-inflammatory, and antimicrobial activities were evaluated. Both total phenolic content and flavonoids, and in vitro bioactivity potential of propolis extracts showed significant variations. Multivariate analysis, hierarchical cluster analysis, and principal component analysis enabled us to distinguish and classify propolis produced by M. beecheii according to similarity in terms of total phenolic content, in vitro bioactivity potential, and geographical origin. This strategy could be used to establish regulations for sustainable use, marketing, and industrial applications.

Genomic profile of two Brazilian choroid plexus tumors by whole-exome sequencing.

Choroid plexus tumors (CPTs) are rare intracranial neoplasms, representing <1% of all brain tumors, yet they represent 20% of first-year pediatric brain tumors. Although these tumors have been linked to TP53 germline mutations in the context of Li-Fraumeni syndrome, their somatic driver alterations remain poorly understood. In this study, we report two cases of lateral ventricle tumors: 3-yr-old male diagnosed with an atypical choroid plexus papilloma (aCPP), and a 6-mo-old female diagnosed with a choroid plexus carcinoma (CPC). We performed whole-exome sequencing of paired blood and tumor tissue in both patients, categorized somatic variants, and determined copy-number alterations. Our analysis revealed a tier II variant (Association for Molecular Pathology [AMP] criteria) in BRD1, a H3 and TP53 acetylation agent, in the aCPP. In addition, we detected copy-number gains on Chromosomes 12, 18, and 20 and copy-number losses on Chromosomes 13q and 22q (BRD1 locus) in this tumor. The CPC tumor had only a pathogenic germline TP53 variant, based on American College of Medical Genetics (ACMG) criteria, with a clinical and familiar history of Li-Fraumeni syndrome. The CPC patient presented loss of heterozygosity (LoH) of TP53 loci and hyperdiploid genome. Both tumors were microsatellite-stable. This is the first study performing whole-exome sequencing in Brazilian choroid plexus tumors, and in line with the literature, we corroborate the absence of recurrent somatic mutations in these tumors. Further studies with larger sample sizes are necessary to confirm our findings and better understand the underlying biology of these tumors.

Formación universitaria a distancia para la inserción laboral de personas con discapacidad intelectualUna experiencia en la UNED / University Distance Learning for the Labor Market Integration of People with Intellectual Disabilities: An Experience at UNED

El presente artículo describe una experiencia de formación universitaria a distancia, la cual se ha basado en los principios del diseño universal para el aprendizaje y la accesibilidad cognitiva para promover la inserción laboral de personas con discapacidad intelectual. El principal objetivo de esta experiencia formativa fue contribuir al desarrollo de competencias que ayudaran a estudiantes con discapacidad intelectual a avanzar en su actualización profesional para la inserción laboral en la Administración Pública española. Participaron 179 personas con discapacidad intelectual. Los resultados mostraron una tasa de éxito del 89 % y una tasa de abandono del 11 %. A través de un cuestionario ad hoc, se evaluó el grado de satisfacción de los diferentes elementos del diseño curricular de esta experiencia de aprendizaje a distancia. En particular, los participantes mostraron índices de satisfacción elevada con los contenidos seleccionados, los materiales y recursos multimedia disponibles en el aula virtual, así como con los posibles beneficios de la instrucción de estrategias de autorregulación emocional. Cabe concluir que el diseño curricular implementado ha sido muy satisfactorio y ha mejorado las habilidades para el empleo que propicien la inserción laboral de los estudiantes. (AU)

This paper focuses on the description of an experience carried out in a Spanish distance university, which was based on the principles of universal design for learning and cognitive accessibility to promote the labour insertion of people with intellectual disabilities. The main objective of the training proposal was to contribute to the development of some competencies that would help students with intellectual disabilities to improve their professional updating for job placement in the Spanish Public Administration. A total of 179 people with intellectual disabilities participated in the course. The results evidenced a high success rate of 89% and a low dropout rate of 11%. Through an ad hoc questionnaire, we evaluated the degree of learners´ satisfaction with different elements of the curricular design for this online learning experience. Particularly, participants reported high satisfaction rates with the selected contents, educational materials and multimedia resources available in the virtual classroom, as well as with the possible benefits of the instruction of emotional self-regulation strategies. It can be concluded that the instructional design has led to high satisfaction and improved the employability abilities of the students to deal with the labour market. (AU)

Reduced mobility is associated with adverse outcomes after in-hospital cardiac arrest

SUMMARY OBJECTIVE: In-hospital cardiac arrest is a critical medical emergency. Knowledge of prognostic factors could assist in cardiopulmonary resuscitation decision-making. Frailty and functional status are emerging risk factors and may play a role in prognostication. The objective was to evaluate the association between reduced mobility and in-hospital cardiac arrest outcomes. METHODS: This retrospective cohort study included patients over 18 years of age with in-hospital cardiac arrest in Botucatu, Brazil, from April 2018 to December 2021. Exclusion criteria were patients with a do-not-resuscitate order or patients with recurrent in-hospital cardiac arrest. Reduced mobility was defined as the need for a bed bath 48 h before in-hospital cardiac arrest. The outcomes of no return of spontaneous circulation and in-hospital mortality were evaluated. RESULTS: A total of 387 patients were included in the analysis. The mean age was 65.4±14.8 years; 53.7% were males and 75.4% had reduced mobility. Among the evaluated outcomes, the no return of spontaneous circulation rate was 57.1%, and in-hospital mortality was 94.3%. In multivariate analysis, reduced mobility was associated with no return of spontaneous circulation when adjusted by age, gender, initial shockable rhythm, duration of cardiopulmonary resuscitation, and epinephrine administration. However, in multiple logistic regression, there was no association between reduced mobility and in-hospital mortality. CONCLUSION: In patients with in-hospital cardiac arrest, reduced mobility is associated with no return of spontaneous circulation. However, there is no relation to in-hospital mortality.

Rasgos de profesionalidad médica en el ámbito de la atención primaria: respeto por la autonomía / Traits of medical professionalism in the field of primary care: respect for autonomy

Fundamento: el respeto por la autonomía del paciente y una conducta respetuosa en general son rasgos centrales de la profesionalidad médica. Objetivo: indagar la presencia de los rasgos profesionales de respeto por la autonomía de los pacientes y de respeto en general en las expresiones verbales de profesionales del ámbito de atención primaria de la salud durante su interacción con pacientes y estudiantes del último año de la carrera de Medicina. Métodos: se efectuó una investigación cualitativa de carácter exploratorio en contextos de prácticas finales obligatorias en dos Centros de Atención Primaria de la Salud de la ciudad de Tandil, República de Argentina, durante el año 2019. Como métodos teóricos se emplearon: análisis-síntesis, inductivo-deductivo y método de revisión crítica de la literatura y empírico: se realizó el registro grabado de 28 encuentros entre expertos, estudiantes y pacientes. Las sesiones se analizaron mediante triangulación de investigadores. Resultados: las expresiones verbales de los expertos permitieron identificar enunciados relacionados con rasgos de respeto en general y respeto por la autonomía de los pacientes. Estos se evidenciaron en enunciados para construir un ambiente de confianza y confidencialidad, el esfuerzo por brindar explicaciones de forma clara y sencilla, la atención a las dudas de los pacientes y la formulación de explicaciones sobre cómo proceder, en un lenguaje accesible. Conclusiones: se identificó la presencia de los rasgos profesionales de respeto por la autonomía de los pacientes y de respeto en general, tanto en las interacciones con pacientes como con los estudiantes.

Background: respect for the autonomy of the patient and a respectful behavior in general are key features of medical professionalism. Objective: to investigate the presence of professional traits of respect for the autonomy of patients and of respect in general in the verbal expressions of professionals in the field of primary health care during their interaction with patients and students in the last year of the Medicine degree. Methods: a qualitative research of an exploratory nature was carried out in the context of mandatory final practices in two Primary Health Care Centers in the city of Tandil, Republic of Argentina, during the year 2019. The following theoretical methods were used: analysis-synthesis, inductive-deductive and method of critical review of the literature and empirical ones: the recorded record of 28 meetings between experts, students and patients was made. The sessions were analyzed by opposing sources of researchers. Results: the verbal expressions of the experts made it possible to identify statements related to traits of respect in general and respect for the autonomy of the patients. These were evidenced in statements to build an environment of trust and confidentiality, the effort to provide explanations in a clear and simple way, the attention to the patients' doubts and the formulation of explanations on how to proceed, in an accessible language. Conclusions: the presence of professional traits of respect for the autonomy of patients and respect in general was identified, both in interactions with patients and with students.

Bleeding hepatocellular adenoma: historical series and outcomes / Adenoma hepatocelular sangrante: série histórica e desfechos

ABSTRACT Introduction: hepatocellular adenoma - AHC - is a rare benign neoplasm of the liver more prevalent in women at reproductive age and its main complication is hemorrhage. In the literature, case series addressing this complication are limited. Methods: between 2010 and 2022, 12 cases of bleeding AHC were attended in a high-complexity university hospital in southern Brazil, whose medical records were retrospectively evaluated. Results: all patients were female, with a mean age of 32 years and a BMI of 33kg/m2. The use of oral contraceptives was identified in half of the sample and also half of the patients had a single lesion. The mean diameter of the largest lesion was 9.60cm and the largest lesion was responsible for bleeding in all cases. The presence of hemoperitoneum was documented in 33% of the patients and their age was significantly higher than the patients who did not have hemoperitoneum - 38 vs 30 years, respectively. Surgical resection of the bleeding lesion was performed in 50% of the patients and the median number of days between bleeding and resection was 27 days. In only one case, embolization was used. The relation between ingrowth of the lesions and the time, in months, was not obtained in this study. Conclusion: it is concluded that the bleeding AHC of the present series shows epidemiological agreement with the literature and may suggest that older patients trend to have hemoperitoneum more frequently, a fact that should be investigated in further studies.

RESUMO Introdução: o Adenoma Hepatocelular - AHC - é uma neoplasia benigna rara do fígado associada a mulheres com idade reprodutiva. Sua principal complicação é o sangramento,mas as séries de casos direcionadas a esta intercorrência são limitadas. Métodos: entre os anos de 2010 e 2022 foram registrados 12 casos de AHC sangrante em um hospital universitário de alta complexidade no sul do Brasil, cujos prontuários foram retrospectivamente avaliados. Resultados: todos os pacientes eram do sexo feminino, com média de idade de 32 anos e de IMC de 33kg/m2. O uso de anticoncepcionais foi identificado em metade da amostra e também metade das pacientes apresentava lesão única. O diâmetro médio da maior lesão foi de 9,60cm e a maior lesão foi responsável pelo sangramento em todos os casos. Hemoperitôneo foi documentado em 33% das pacientes e a idade destas foi significativamente maior do que as pacientes que não apresentaram hemoperitôneo - 38 vs 30 anos, respectivamente. A ressecção cirúrgica da lesão sangrante foi realizada em 50% das pacientes e a mediana de dias entre o sangramento e a ressecção foi de 27 dias. Em apenas um caso foi lançado mão da embolização da lesão. Não se demonstrou correlação entre a taxa de redução das lesões e o passar dos meses, nos casos em que foi adotado tratamento conservador. Conclusão: conclui-se que aos AHC sangrantes da presente série apresentam concordância epidemiológica com a literatura e pode sugerir que as pacientes com maior idade tendem a apresentar hemoperitôneo mais frequentemente, fato que deve ser investigado em maiores estudos.

Insights on variant analysis in silico tools for pathogenicity prediction.

Molecular biology is currently a fast-advancing science. Sequencing techniques are getting cheaper, but the interpretation of genetic variants requires expertise and computational power, therefore is still a challenge. Next-generation sequencing releases thousands of variants and to classify them, researchers propose protocols with several parameters. Here we present a review of several in silico pathogenicity prediction tools involved in the variant prioritization/classification process used by some international protocols for variant analysis and studies evaluating their efficiency.