CoVAMPnet: Comparative Markov State Analysis for Studying Effects of Drug Candidates on Disordered Biomolecules.

Computational study of the effect of drug candidates on intrinsically disordered biomolecules is challenging due to their vast and complex conformational space. Here, we developed a comparative Markov state analysis (CoVAMPnet) framework to quantify changes in the conformational distribution and dynamics of a disordered biomolecule in the presence and absence of small organic drug candidate molecules. First, molecular dynamics trajectories are generated using enhanced sampling, in the presence and absence of small molecule drug candidates, and ensembles of soft Markov state models (MSMs) are learned for each system using unsupervised machine learning. Second, these ensembles of learned MSMs are aligned across different systems based on a solution to an optimal transport problem. Third, the directional importance of inter-residue distances for the assignment to different conformational states is assessed by a discriminative analysis of aggregated neural network gradients. This final step provides interpretability and biophysical context to the learned MSMs. We applied this novel computational framework to assess the effects of ongoing phase 3 therapeutics tramiprosate (TMP) and its metabolite 3-sulfopropanoic acid (SPA) on the disordered Aß42 peptide involved in Alzheimer's disease. Based on adaptive sampling molecular dynamics and CoVAMPnet analysis, we observed that both TMP and SPA preserved more structured conformations of Aß42 by interacting nonspecifically with charged residues. SPA impacted Aß42 more than TMP, protecting α-helices and suppressing the formation of aggregation-prone ß-strands. Experimental biophysical analyses showed only mild effects of TMP/SPA on Aß42 and activity enhancement by the endogenous metabolization of TMP into SPA. Our data suggest that TMP/SPA may also target biomolecules other than Aß peptides. The CoVAMPnet method is broadly applicable to study the effects of drug candidates on the conformational behavior of intrinsically disordered biomolecules.

Cryotherapy versus radiofrequency ablation in the treatment of dysplastic Barrett's esophagus with or without early esophageal neoplasia: a systematic review and meta-analysis.

BACKGROUND/AIMS: Radiofrequency ablation (RFA) is the first-line therapy for dysplastic Barrett's esophagus (BE). Therefore, cryotherapy has emerged as an alternative treatment option. This study aimed to compare the efficacies of these two techniques based on the rates of complete eradication of intestinal metaplasia (CE-IM) and dysplasia (CE-D). Adverse events and recurrence have also been reported. METHODS: An electronic search was conducted using the Medline (PubMed), Embase, LILACS, and Google Scholar databases until December 2022. Studies were included comparing cryotherapy and RFA for treating dysplastic BE with or without early esophageal neoplasia. This study was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. RESULTS: Three retrospective cohort studies involving 627 patients were included. Of these, 399 patients underwent RFA, and 228 were treated with cryotherapy. There was no difference in CE-IM (risk difference [RD], -0.03; 95% confidence interval [CI], -0.25 to 0.19; p=0.78; I2=86%) as well as in CE-D (RD, -0.03; 95% CI, -0.15 to 0.09; p=0.64; I2=70%) between the groups. The absolute number of adverse events was low, and there was no difference in the recurrence rate. CONCLUSION: Cryotherapy and RFA were equally effective in treating dysplastic BE, with or without early esophageal neoplasia.

InVADo: Interactive Visual Analysis of Molecular Docking Data.

Molecular docking is a key technique in various fields like structural biology, medicinal chemistry, and biotechnology. It is widely used for virtual screening during drug discovery, computer-assisted drug design, and protein engineering. A general molecular docking process consists of the target and ligand selection, their preparation, and the docking process itself, followed by the evaluation of the results. However, the most commonly used docking software provides no or very basic evaluation possibilities. Scripting and external molecular viewers are often used, which are not designed for an efficient analysis of docking results. Therefore, we developed InVADo, a comprehensive interactive visual analysis tool for large docking data. It consists of multiple linked 2D and 3D views. It filters and spatially clusters the data, and enriches it with post-docking analysis results of protein-ligand interactions and functional groups, to enable well-founded decision-making. In an exemplary case study, domain experts confirmed that InVADo facilitates and accelerates the analysis workflow. They rated it as a convenient, comprehensive, and feature-rich tool, especially useful for virtual screening.

Social representation of young people in higher education about sexually transmitted infections.

OBJECTIVE: to analyze the social representations about sexually transmitted infections elaborated by undergraduate students. METHODS: a descriptive, qualitative study, in the light of the structural approach of Social Representation Theory, carried out with 160 young undergraduate students, in the second half of 2019, in the city of Rio de Janeiro. Data were collected using a sociodemographic characterization questionnaire, knowledge and practices for preventing sexually transmitted infections, analyzed using descriptive statistics and a form of free evocations with the inducing term STD, analyzed using prototypical and similarity analysis. RESULTS: the representation's possible central nucleus is composed of lexicons aids, disease and HIV; the peripheral system by syphilis, sex, condoms, gonorrhea, prevention, infection, carelessness, HPV, herpes, ignorance, treatment, fear, unprotected-sex and danger. FINAL CONSIDERATIONS: social thinking about sexually transmitted infections is characterized by their recognition as diseases, which require barrier prevention measures, associating with unsafe sexual practices that arouse fear.

Social representation of spiritual surgeries in Umbanda: culture, religion and contributions of nursing theory.

OBJECTIVE: to analyze the social representation of spiritual surgeries in Umbanda for Bantu-Amerindian ritual mediums and their contributions to the cross-cultural care proposed by Madeleine Leininger. METHODS: a descriptive-exploratory, qualitative study, supported by the procedural approach of Social Representation Theory and Transcultural Nursing Theory, carried out with 30 Umbanda mediums of the Bantu-Amerindian ritual through interviews, submitted to the Iramuteq software for lexical analysis. RESULTS: mostly women, white, with an average of 46 years old and approximately 14 years of practice in Umbanda participated. The social representation of spiritual surgeries in Umbanda is objectified and anchored through a biomedical vision of care, encompassing a set of beliefs, values and practices as religious treatments, through faith, whose main objective is healing. FINAL CONSIDERATIONS: spiritual surgeries are a form of transcultural care, according to Madeleine Leininger's propositions, as they integrate the culture of a group through health care in Umbanda.

Illuminating the mechanism and allosteric behavior of NanoLuc luciferase.

NanoLuc, a superior ß-barrel fold luciferase, was engineered 10 years ago but the nature of its catalysis remains puzzling. Here experimental and computational techniques are combined, revealing that imidazopyrazinone luciferins bind to an intra-barrel catalytic site but also to an allosteric site shaped on the enzyme surface. Structurally, binding to the allosteric site prevents simultaneous binding to the catalytic site, and vice versa, through concerted conformational changes. We demonstrate that restructuration of the allosteric site can boost the luminescent reaction in the remote active site. Mechanistically, an intra-barrel arginine coordinates the imidazopyrazinone component of luciferin, which reacts with O2 via a radical charge-transfer mechanism, and then it also protonates the resulting excited amide product to form a light-emitting neutral species. Concomitantly, an aspartate, supported by two tyrosines, fine-tunes the blue color emitter to secure a high emission intensity. This information is critical to engineering the next-generation of ultrasensitive bioluminescent reporters.

Atypical homodimerization revealed by the structure of the (S)-enantioselective haloalkane dehalogenase DmmarA from Mycobacterium marinum.

Haloalkane dehalogenases (HLDs) are a family of α/ß-hydrolase fold enzymes that employ SN2 nucleophilic substitution to cleave the carbon-halogen bond in diverse chemical structures, the biological role of which is still poorly understood. Atomic-level knowledge of both the inner organization and supramolecular complexation of HLDs is thus crucial to understand their catalytic and noncatalytic functions. Here, crystallographic structures of the (S)-enantioselective haloalkane dehalogenase DmmarA from the waterborne pathogenic microbe Mycobacterium marinum were determined at 1.6 and 1.85 Šresolution. The structures show a canonical αßα-sandwich HLD fold with several unusual structural features. Mechanistically, the atypical composition of the proton-relay catalytic triad (aspartate-histidine-aspartate) and uncommon active-site pocket reveal the molecular specificities of a catalytic apparatus that exhibits a rare (S)-enantiopreference. Additionally, the structures reveal a previously unobserved mode of symmetric homodimerization, which is predominantly mediated through unusual L5-to-L5 loop interactions. This homodimeric association in solution is confirmed experimentally by data obtained from small-angle X-ray scattering. Utilizing the newly determined structures of DmmarA, molecular modelling techniques were employed to elucidate the underlying mechanism behind its uncommon enantioselectivity. The (S)-preference can be attributed to the presence of a distinct binding pocket and variance in the activation barrier for nucleophilic substitution.

Advancing Enzyme's Stability and Catalytic Efficiency through Synergy of Force-Field Calculations, Evolutionary Analysis, and Machine Learning.

Thermostability is an essential requirement for the use of enzymes in the bioindustry. Here, we compare different protein stabilization strategies using a challenging target, a stable haloalkane dehalogenase DhaA115. We observe better performance of automated stabilization platforms FireProt and PROSS in designing multiple-point mutations over the introduction of disulfide bonds and strengthening the intra- and the inter-domain contacts by in silico saturation mutagenesis. We reveal that the performance of automated stabilization platforms was still compromised due to the introduction of some destabilizing mutations. Notably, we show that their prediction accuracy can be improved by applying manual curation or machine learning for the removal of potentially destabilizing mutations, yielding highly stable haloalkane dehalogenases with enhanced catalytic properties. A comparison of crystallographic structures revealed that current stabilization rounds were not accompanied by large backbone re-arrangements previously observed during the engineering stability of DhaA115. Stabilization was achieved by improving local contacts including protein-water interactions. Our study provides guidance for further improvement of automated structure-based computational tools for protein stabilization.

Domino-like effect of C112R mutation on ApoE4 aggregation and its reduction by Alzheimer's Disease drug candidate.

BACKGROUND: Apolipoprotein E (ApoE) ε4 genotype is the most prevalent risk factor for late-onset Alzheimer's Disease (AD). Although ApoE4 differs from its non-pathological ApoE3 isoform only by the C112R mutation, the molecular mechanism of its proteinopathy is unknown. METHODS: Here, we reveal the molecular mechanism of ApoE4 aggregation using a combination of experimental and computational techniques, including X-ray crystallography, site-directed mutagenesis, hydrogen-deuterium mass spectrometry (HDX-MS), static light scattering and molecular dynamics simulations. Treatment of ApoE ε3/ε3 and ε4/ε4 cerebral organoids with tramiprosate was used to compare the effect of tramiprosate on ApoE4 aggregation at the cellular level. RESULTS: We found that C112R substitution in ApoE4 induces long-distance (> 15 Å) conformational changes leading to the formation of a V-shaped dimeric unit that is geometrically different and more aggregation-prone than the ApoE3 structure. AD drug candidate tramiprosate and its metabolite 3-sulfopropanoic acid induce ApoE3-like conformational behavior in ApoE4 and reduce its aggregation propensity. Analysis of ApoE ε4/ε4 cerebral organoids treated with tramiprosate revealed its effect on cholesteryl esters, the storage products of excess cholesterol. CONCLUSIONS: Our results connect the ApoE4 structure with its aggregation propensity, providing a new druggable target for neurodegeneration and ageing.

Quality of life from women's perspective in the exercise of sex work: a study of social representations.

OBJECTIVES: to analyze the social representations elaborated by sex workers from Alto Sertão Produtivo Baiano about quality of life. METHODS: a qualitative study, based on the Social Representation Theory, carried out in the region of Alto Sertão Produtivo Baiano, with 30 sex workers. Individual in-depth interview was carried out, with speeches organized in a corpus and treated in IRAMUTEQ, enabling lexical analysis for Descending Hierarchical Classification. RESULTS: four thematic classes emerged, in which social representations of quality of life pervade: money earned to supply needs; association with healthy living and obtaining health (physical and mental); balance of emotions (although there are some negative sensations such as fear and anxiety); and faith in a deity. FINAL CONSIDERATIONS: the social representations elaborated by sex workers about quality of life are anchored in concepts, subjective and practical, punctuated by the World Health Organization.

Endoscopic Imaging for the Diagnosis of Neoplastic and Pre-Neoplastic Conditions of the Stomach.

Gastric cancer is an aggressive disease with low long-term survival rates. An early diagnosis is essential to offer a better prognosis and curative treatment. Upper gastrointestinal endoscopy is the main tool for the screening and diagnosis of patients with gastric pre-neoplastic conditions and early lesions. Image-enhanced techniques such as conventional chromoendoscopy, virtual chromoendoscopy, magnifying imaging, and artificial intelligence improve the diagnosis and the characterization of early neoplastic lesions. In this review, we provide a summary of the currently available recommendations for the screening, surveillance, and diagnosis of gastric cancer, focusing on novel endoscopy imaging technologies.

sMolBoxes: Dataflow Model for Molecular Dynamics Exploration.

We present sMolBoxes, a dataflow representation for the exploration and analysis of long molecular dynamics (MD) simulations. When MD simulations reach millions of snapshots, a frame-by-frame observation is not feasible anymore. Thus, biochemists rely to a large extent only on quantitative analysis of geometric and physico-chemical properties. However, the usage of abstract methods to study inherently spatial data hinders the exploration and poses a considerable workload. sMolBoxes link quantitative analysis of a user-defined set of properties with interactive 3D visualizations. They enable visual explanations of molecular behaviors, which lead to an efficient discovery of biochemically significant parts of the MD simulation. sMolBoxes follow a node-based model for flexible definition, combination, and immediate evaluation of properties to be investigated. Progressive analytics enable fluid switching between multiple properties, which facilitates hypothesis generation. Each sMolBox provides quick insight to an observed property or function, available in more detail in the bigBox View. The case studies illustrate that even with relatively few sMolBoxes, it is possible to express complex analytical tasks, and their use in exploratory analysis is perceived as more efficient than traditional scripting-based methods.

Ancestry estimation in forensic anthropology: accuracy of the AncesTrees software in a Brazilian sample.

The objective of this study is to analyze the accuracy and applicability of the AncesTrees software with respect to a set of cranial measurements of a Brazilian sample consisting of 114 identified skulls from two osteological collections, predominantly composed of European (n = 59), African (n = 35), and admixed individuals (n = 20). Twenty-four different craniometric measurements are performed and input to AncesTrees via two algorithms, one of which is used in three configurations, with different ancestral groups integrated in the model. The software exhibits superior performance in the estimation of European individuals, reaching 73% accuracy, compared with 66% in the African individuals. Those individuals classified as admixed produce a variety of ancestral classifications, mainly European. Overall, the most accurate combination of AncesTrees is obtained using ancestralForest with only the European and African groups integrated into the algorithm, where the accuracy reaches 70%. The applicability of this software to a specific population is fragile because of the high admixing load, making it necessary to create a more representative anthropometric database of the Brazilian people. Key points: Ancestry estimation methods are seldom validated in Brazil.AncesTrees performed poorly on our sample, with a maximum accuracy of 70%.Brazil's highly mixed population hinders ancestry estimation.Mixed individuals (pardos) are predominantly classified as Europeans.The insertion of Brazilian metric data into the AncesTrees database would produce better results.

Social representation of young people in higher education about sexually transmitted infections / Representación social de jóvenes en educación superior sobre las infecciones de transmisión sexual / Representação social de jovens da educação superior sobre infecções sexualmente transmissíveis

ABSTRACT Objective: to analyze the social representations about sexually transmitted infections elaborated by undergraduate students. Methods: a descriptive, qualitative study, in the light of the structural approach of Social Representation Theory, carried out with 160 young undergraduate students, in the second half of 2019, in the city of Rio de Janeiro. Data were collected using a sociodemographic characterization questionnaire, knowledge and practices for preventing sexually transmitted infections, analyzed using descriptive statistics and a form of free evocations with the inducing term STD, analyzed using prototypical and similarity analysis. Results: the representation's possible central nucleus is composed of lexicons aids, disease and HIV; the peripheral system by syphilis, sex, condoms, gonorrhea, prevention, infection, carelessness, HPV, herpes, ignorance, treatment, fear, unprotected-sex and danger. Final considerations: social thinking about sexually transmitted infections is characterized by their recognition as diseases, which require barrier prevention measures, associating with unsafe sexual practices that arouse fear.

RESUMEN Objetivo: analizar las representaciones sociales sobre las infecciones de transmisión sexual elaboradas por estudiantes universitarios. Métodos: estudio descriptivo, cualitativo, a la luz del enfoque estructural de la Teoría de las Representaciones Sociales, realizado con 160 jóvenes universitarios, en el segundo semestre de 2019, en la ciudad de Río de Janeiro. Los datos fueron recolectados mediante un cuestionario de caracterización sociodemográfica, conocimientos y prácticas para la prevención de infecciones de transmisión sexual, analizados mediante estadística descriptiva y un formulario de evocaciones libres con el término inductor de ETS, analizados mediante análisis prototípico y de similitud. Resultados: el posible núcleo central de la representación está compuesto por los léxicos sida, enfermedad y VIH; el sistema periférico, por sífilis, sexo, condones, gonorrea, prevención, infección, descuido, VPH, herpes, desconocimiento, tratamiento, miedo, sexo sin protección y peligro. Consideraciones finales: el pensamiento social sobre las infecciones de transmisión sexual se caracteriza por su reconocimiento como enfermedades que requierendo medidas de prevención de barrera, se asociando a prácticas sexuales inseguras que despiertan miedo.

RESUMO Objetivo: analisar as representações sociais sobre as infecções sexualmente transmissíveis elaboradas por jovens universitários. Métodos: estudo descritivo, qualitativo, à luz da abordagem estrutural da Teoria das Representações Sociais, realizado com 160 jovens universitários, no segundo semestre de 2019, na cidade do Rio de Janeiro. Os dados foram coletados por questionário de caracterização sociodemográfica, conhecimentos e práticas de prevenção das infecções sexualmente transmissíveis, analisados pela estatística descritiva e por formulário de evocações livres com o termo indutor DST, analisadas pela análise prototípica e de similitude. Resultados: o possível núcleo central da representação é composto pelos léxicos aids, doença e HIV; o sistema periférico, por sífilis, sexo, camisinha, gonorreia, prevenção, infecção, descuido, HPV, herpes, desconhecimento, tratamento, medo, sexo-sem-proteção e perigo. Considerações finais: o pensamento social sobre as infecções sexualmente transmissíveis caracteriza-se pelo seu reconhecimento como doenças que requerem medidas de prevenção de barreira, e associam-se a práticas sexuais inseguras que despertam medo.

Social representation of spiritual surgeries in Umbanda: culture, religion and contributions of nursing theory / Representación social de las cirugías espirituales en Umbanda: cultura, religión y aportes de la teoría de enfermería / Representação social das cirurgias espirituais na Umbanda: cultura, religião e contribuições da teoria de enfermagem

ABSTRACT Objective: to analyze the social representation of spiritual surgeries in Umbanda for Bantu-Amerindian ritual mediums and their contributions to the cross-cultural care proposed by Madeleine Leininger. Methods: a descriptive-exploratory, qualitative study, supported by the procedural approach of Social Representation Theory and Transcultural Nursing Theory, carried out with 30 Umbanda mediums of the Bantu-Amerindian ritual through interviews, submitted to the Iramuteq software for lexical analysis. Results: mostly women, white, with an average of 46 years old and approximately 14 years of practice in Umbanda participated. The social representation of spiritual surgeries in Umbanda is objectified and anchored through a biomedical vision of care, encompassing a set of beliefs, values and practices as religious treatments, through faith, whose main objective is healing. Final considerations: spiritual surgeries are a form of transcultural care, according to Madeleine Leininger's propositions, as they integrate the culture of a group through health care in Umbanda.

RESUMEN Objetivo: analizar la representación social de las cirugías espirituales en Umbanda para médiums rituales bantú-amerindios y sus aportes al cuidado transcultural propuesto por Madeleine Leininger. Métodos: estudio descriptivo-exploratorio, cualitativo, sustentado en el enfoque procedimental de la Teoría de las Representaciones Sociales y la Teoría del Cuidado Transcultural, realizado con 30 médiums Umbanda del ritual Bantú-Amerindio a través de entrevistas, sometidos al software Iramuteq para análisis léxico. Resultados: participaron en su mayoría mujeres, blancas, con una edad promedio de 46 años y aproximadamente 14 años de práctica en Umbanda. La representación social de las cirugías espirituales en Umbanda se objetiva y ancla a través de una visión biomédica del cuidado, englobando un conjunto de creencias, valores y prácticas como tratamientos religiosos, a través de la fe, cuyo principal objetivo es la sanación. Consideraciones finales: las cirugías espirituales son una forma de cuidado transcultural según las proposiciones de Madeleine Leininger, en tanto integran la cultura de un grupo a través del cuidado de la salud en Umbanda.

RESUMO Objetivo: analisar a representação social das cirurgias espirituais na Umbanda para médiuns do ritual bantu-ameríndio e suas contribuições para o cuidado transcultural proposto por Madeleine Leininger. Métodos: estudo descritivo-exploratório, qualitativo, apoiado na abordagem processual da Teoria das Representações Sociais e na Teoria do Cuidado Transcultural, realizado com 30 médiuns umbandistas do ritual bantu-ameríndio por meio de entrevistas, submetidas ao software Iramuteq para análise lexical. Resultados: participaram, majoritariamente, mulheres, brancas, na média dos 46 anos e aproximadamente 14 anos de prática na Umbanda. A representação social das cirurgias espirituais na Umbanda é objetivada e ancorada mediante uma visão biomédica do cuidado, englobando um conjunto de crenças, valores e práticas enquanto tratamentos religiosos, por meio da fé, cujo objetivo principal é a cura. Considerações finais: cirurgias espirituais são uma forma de cuidado transcultural, segundo proposições de Madeleine Leininger, por integrarem a cultura de um grupo através dos cuidados em saúde na Umbanda.

Representação social da qualidade de vida de pessoas com HIV residentes em municípios de pequeno porte / Social representation of quality of life among people with HIV residing in small towns / Representación social de la calidad de vida de las personas con VIH residentes en pequeños municípios

Objetivo: compreender a representação social da qualidade de vida de pessoas que vivem com HIV/Aids residentes em municípios de pequeno porte do estado do Rio de Janeiro. Método: estudo descritivo, qualitativo, apoiado na Teoria das Representações Sociais, em sua abordagem estrutural. Participaram 80 pessoas vivendo com HIV. Os dados foram coletados por questionário e evocação livre de palavras. Resultado: a análise prototípica evidenciou que os conteúdos centrais da representação social são: boa alimentação, saúde e estado psicológico, expressando as dimensões corporal, processo saúde-doença e psicológica. A análise de similitude retratou que os elementos com maior conexão são boa alimentação, atividade física e lazer. Conclusão: o estudo permitiu compreender a representação social da qualidade de vida e, ainda, colocou em destaque as dimensões nas quais os participantes se apoiam na busca por esta qualidade. É relevante por propiciar a adequação de serviços de apoio interdisciplinares a esta clientela.

Objective: to understand social representations of quality of life among people living with HIV/AIDS living in small towns in Rio de Janeiro State. Method: this qualitative, descriptive study of 80 people living with HIV was supported by the structural approach of Social Representations Theory. Data were collected by sociodemographic questionnaire and free word evocation. Result: prototype analysis showed that the core contents of the social representation were: good food, health, and psychological state, expressing the body, health-disease, and psychological process dimensions. Similarity analysis showed that the most strongly connected elements were good food, physical activity, and leisure. Conclusion: the study made it possible to understand participants' social representations of quality of life and also highlighted the dimensions on which they relied in striving for that quality. It was important in fostering alignment by interdisciplinary support services for this clientele.

Objetivo: comprender la representación social de la calidad de vida de personas que viven con el VIH/SIDA residentes en pequeñas ciudades del estado de Río de Janeiro. Método: estudio descriptivo, cualitativo, apoyado en la Teoría de las Representaciones Sociales, en su enfoque estructural. Participaron 80 personas que viven con el VIH. Se recogieron los datos a través de un cuestionario y de técnica de evocación libre de palabras. Resultado: el análisis prototípico mostró que los contenidos centrales de la representación social son: buena alimentación, salud y estado psicológico, expresando las dimensiones corporales, salud-enfermedad y psicológica. El análisis de similitud mostró que los elementos con mayor conexión son la buena alimentación, la actividad física y el ocio. Conclusión: el estudio permitió comprender la representación social de la calidad de vida y también destacó las dimensiones en las que se basan los participantes al buscar esta calidad. Es relevante para brindar la adecuación de los servicios de apoyo interdisciplinarios a esta clientela.

Fatores que influenciam o uso inadequado do preservativo na perspetiva de jovens universitários / Factors influencing condom misuse from the perspective of young university students / Factores que influyen en el uso inadecuado del preservativo desde la perspectiva de los jóvenes universitarios

Resumo Enquadramento: O comportamento de risco sexual de jovens relacionado com as infeções sexualmente transmissíveis envolve o início da vida sexual, variabilidade de parceiros, práticas casuais, (des)uso de preservativos e consumo de substâncias psicoativas. Objetivo: Identificar os fatores que influenciam o uso inadequado do preservativo na perspetiva de jovens universitários. Metodologia: Estudo descritivo, qualitativo, realizado numa universidade privada carioca brasileira com 30 jovens universitários, que integraram três grupos focais. Análise de dados utilizando a técnica de análise lexical e do IRaMuTeQ. Resultados: Emergiram cinco classes, entre elas: o uso de álcool como determinante do comportamento de risco; uso inadequado de preservativos, associado ao risco de infeção; pouca informação sobre a prevenção dessas doenças; e uso de preservativos. Nas práticas sexuais, os participantes faziam uso descontinuado do preservativo e preocupavam-se mais com a ocorrência de uma gravidez não planeada. Conclusão: A assunção dos comportamentos sexuais de risco pelos universitários denota vulnerabilidades nos âmbitos individual-social evidenciando-se a necessidade de se desenvolver estratégias efetivas de educação para a saúde e de intervenções terapêuticas.

Abstract Background: The sexual risk-taking behaviors of young people regarding Sexually Transmitted Infections (STIs) are associated with sexual debut, partner variability, casual sex activities, (lack of) use of condoms, and substance abuse. Objective: To identify the factors influencing condom misuse from the perspective of young university students. Methodology: A descriptive qualitative study was conducted at a private university in Rio de Janeiro, Brazil, with 30 young university students participating in three focus groups. Data were analyzed using the lexical analysis technique and IRaMuTeQ software. Results: The following five classes emerged: alcohol use as a determinant of risky behaviors; condom misuse associated with the risk of infection; lack of information on STI prevention; and condom use. Participants reported using condoms inconsistently and being more concerned about the occurrence of an unplanned pregnancy. Conclusion: University students' sexual risk-taking behaviors reveal individual and social vulnerabilities and highlight the need to develop efficient health education and therapeutic interventions strategies.

Resumen Marco contextual: El comportamiento sexual de riesgo de los jóvenes relacionado con las infecciones de transmisión sexual implica el inicio de la vida sexual, la variabilidad de las parejas, las prácticas casuales, el (no) uso de preservativos y el consumo de sustancias psicoactivas. Objetivo: Identificar los factores que influyen en el uso inadecuado del preservativo desde la perspectiva de los jóvenes universitarios. Metodología: Estudio descriptivo y cualitativo, realizado en una universidad privada de Río de Janeiro, Brasil, con 30 jóvenes universitarios que participaron en tres grupos focales. El análisis de datos se llevó a cabo mediante la técnica del análisis léxico y del IRAMUTEC. Resultados: Surgieron cinco clases, entre ellas, el consumo de alcohol como determinante del comportamiento de riesgo; el uso inadecuado del preservativo, asociado al riesgo de infección; la poca información sobre la prevención de estas enfermedades, y el uso del preservativo. En las prácticas sexuales, los participantes hacían un uso discontinuo del preservativo y se mostraban más preocupados por la aparición de un embarazo no planificado. Conclusión: La adopción de conductas sexuales de riesgo por parte de los estudiantes universitarios denota vulnerabilidades en el ámbito individual y social, lo que pone de manifiesto la necesidad de desarrollar estrategias eficaces de educación sanitaria e intervenciones terapéuticas.

Effects of Eucalypt ashes from moderate and high severity wildfires on the skin microbiome of the Iberian frog (Rana iberica).

Forest fires can threaten amphibians because ash-associated contaminants transported by post-fire runoff impact both terrestrial and aquatic ecosystems. Still, the effects of these contaminants on the skin microbiome of amphibians have been overlooked. Thus, the main objective of this study was to assess the effects of ash from different severity wildfires (moderate and high) on the skin microbiome of the Iberian frog (Rana iberica). Bacterial isolates sampled from R. iberica skin microbiome were tested for their antimicrobial activity against the pathogen Aeromonas salmonicida. The isolates with antimicrobial activity were identified and further exposed to several concentrations (0, 6.25, 12.5, 25, 50, 75, and 100%) of Eucalypt (Eucalyptus globulus) aqueous extracts (AAEs) of ash from both a moderate and a high severity wildfire. The results showed that 53% of the bacterial isolates presented antimicrobial activity, with Pseudomonas being the most common genus. Exposure to AAEs had diverse effects on bacterial growth since a decrease, an increase or no effects on growth were observed. For both ash types, increasing AAEs concentrations led to an increase in the number of bacteria whose growth was negatively affected. Ash from the high severity fire showed more adverse effects on bacterial growth than those from moderate severity, likely due to the higher metal concentrations of the former. This study revealed that bacteria living in Iberian frogs' skin could be impaired by ash-related contaminants, potentially weakening the individual's immune system. Given the foreseen increase in wildfires' frequency and severity under climate change, this work raises awareness of the risks faced by amphibian communities in fire-prone regions, emphasising the importance of a rapid implementation of post-fire emergency measures for the preservation and conservation of this group of animals.

Microsurgical Anatomy of the Cerebellar Interpeduncular Entry Zones.

OBJECTIVE: The cerebellar interpeduncular region, particularly the middle cerebellar peduncle (MCP) and interpeduncular sulcus (IPS) are significant surgical relevance areas due to the high prevalence of vascular and tumoral pathologies, such as cavernomas, arteriovenous malformations, and gliomas. We defined safer access areas of the MCP and the IPS, according to the surface anatomy, involved vessels, and fiber tracts of the cerebellar interpeduncular region. METHODS: Fifteen formalin-fixed and silicone-injected cadaveric heads and 23 human brainstems with attached cerebellums prepared with the Klingler's technique were bilaterally dissected to study the vascular and intrinsic anatomy. RESULTS: Surface anatomy: The mean length of the IPS was 12.73 mm (standard deviation [SD],2.15 mm), and the average measured angle formed by the IPS and the lateral mesencephalic sulcus was 144.53°. The mean distance from the uppermost point of the IPS to cranial nerve IV was 2.63 mm (SD, 2.84 mm). Vascular anatomy: The perforating branches of the superior cerebellar peduncle, IPS, and MCP originated predominantly from the caudal trunk of the superior cerebellar artery. The inferior third of the superior cerebellar peduncle and IPS was the third most pierced by perforating arteries, and for the MCP, was its superior third. Crossing vessels: The branches of the pontotrigeminal vein and the caudal trunk of the superior cerebellar artery crossed the IPS mostly. The superior third of the IPS was the most crossed by arteries and veins. CONCLUSIONS: The middle thirds of the IPS and MCP as entry zones might be safer than their superior and inferior thirds due to fewer perforating branches, arterial trunks, and veins crossing the sulcus as fewer eloquent tracts.

Mechanism-Based Strategy for Optimizing HaloTag Protein Labeling.

HaloTag labeling technology has introduced unrivaled potential in protein chemistry and molecular and cellular biology. A wide variety of ligands have been developed to meet the specific needs of diverse applications, but only a single protein tag, DhaAHT, is routinely used for their incorporation. Following a systematic kinetic and computational analysis of different reporters, a tetramethylrhodamine- and three 4-stilbazolium-based fluorescent ligands, we showed that the mechanism of incorporating different ligands depends both on the binding step and the efficiency of the chemical reaction. By studying the different haloalkane dehalogenases DhaA, LinB, and DmmA, we found that the architecture of the access tunnels is critical for the kinetics of both steps and the ligand specificity. We showed that highly efficient labeling with specific ligands is achievable with natural dehalogenases. We propose a simple protocol for selecting the optimal protein tag for a specific ligand from the wide pool of available enzymes with diverse access tunnel architectures. The application of this protocol eliminates the need for expensive and laborious protein engineering.