Engineering and evaluation of FXa bypassing agents that restore hemostasis following Apixaban associated bleeding.

Direct oral anticoagulants (DOACs) targeting activated factor Xa (FXa) are used to prevent or treat thromboembolic disorders. DOACs reversibly bind to FXa and inhibit its enzymatic activity. However, DOAC treatment carries the risk of anticoagulant-associated bleeding. Currently, only one specific agent, andexanet alfa, is approved to reverse the anticoagulant effects of FXa-targeting DOACs (FXaDOACs) and control life-threatening bleeding. However, because of its mechanism of action, andexanet alfa requires a cumbersome dosing schedule, and its use is associated with the risk of thrombosis. Here, we present the computational design, engineering, and evaluation of FXa-variants that exhibit anticoagulation reversal activity in the presence of FXaDOACs. Our designs demonstrate low DOAC binding affinity, retain FXa-enzymatic activity and reduce the DOAC-associated bleeding by restoring hemostasis in mice treated with apixaban. Importantly, the FXaDOACs reversal agents we designed, unlike andexanet alfa, do not inhibit TFPI, and consequently, may have a safer thrombogenic profile.

Ecoepidemiology of Chagas Disease in a Biological Corridor in Southeastern Mexico: A Promising Approach to Understand the Risk of Chagas Disease.

Ecoepidemiology is an emerging field that attempts to explain how biotic, environmental, and even social factors influence the dynamics of infectious diseases. Particularly in vector-borne diseases, the study under this approach offers us an overview of the pathogens, vectors, and hosts that coexist in a given region and their ecological determinants. As a result of this, risk predictions can be established in a changing environment and how it may impact human populations. This paper is aimed at evaluating some ecoepidemiological characteristics of Chagas disease in a natural reserve in southeastern Mexico that borders human settlements. We carry out a cross-sectional study in 2022 where we search insects manually and with light traps. We set traps for small mammals and bats and conducted interviews with the inhabitants living around the study site. We identified the presence of Triatoma dimidiata and T. huehuetenanguensis species with a percentage of TcI T. cruzi infection of 68.4% (95% CI: 66.9-69.9). Temperature and humidity were not determining factors for the probability of insect capture. Of the 108 wild mammals (Chiroptera, Rodentia, and Didelphimorphia), none was infected with T. cruzi. Knowledge about Chagas disease in nearby inhabitants is poor, and some characteristics were found on the periphery of dwellings that could offer a refuge for insect vectors. With this information, surveillance strategies can be generated in the study area that reduce the risk of transmission of T. cruzi parasite to humans, and it is expected to motivate the use of this field in future research.

Identification of Discrete Typing Units of Trypanosoma cruzi Isolated from Domestic Environments in Southeastern Mexico.

Background: The Trypanosoma cruzi parasite is the causal agent of Chagas disease, recognized by the World Health Organization as a neglected tropical disease. Currently there are seven discrete typing units (DTUs) of T. cruzi distributed in America, but there are still gaps about its distribution in some endemic regions. Materials and Methods: Seventeen units isolated from Chiapas and Oaxaca in Mexico were identified by amplification of the C-5 sterol desaturase gene. Results: Three DTUs of T. cruzi, TcI (6), TcII (10), and TcIV (1) were detected by comparing polymorphic sites in specific regions. Conclusions: New DTUs are reported for both states, where TcII was the most common DTU. The genetic characterization of the isolates can help to understand the epidemiology of Chagas disease.

Corrigendum to "Computational design of nanomolar-binding antibodies specific to multiple SARS-CoV-2 variants by engineering a specificity switch of antibody 80R using RosettaAntibodyDesign (RAbD) results in potential generalizable therapeutic antibodies for novel SARS-CoV-2 virus" [Heliyon 9(4) (April 2023) e15032].

[This corrects the article DOI: 10.1016/j.heliyon.2023.e15032.].

What Do You Need to Know before Studying Chagas Disease? A Beginner's Guide.

Chagas disease is one of the most important tropical infections in the world and mainly affects poor people. The causative agent is the hemoflagellate protozoan Trypanosoma cruzi, which circulates among insect vectors and mammals throughout the Americas. A large body of research on Chagas disease has shown the complexity of this zoonosis, and controlling it remains a challenge for public health systems. Although knowledge of Chagas disease has advanced greatly, there are still many gaps, and it is necessary to continue generating basic and applied research to create more effective control strategies. The aim of this review is to provide up-to-date information on the components of Chagas disease and highlight current trends in research. We hope that this review will be a starting point for beginners and facilitate the search for more specific information.

Computational design of nanomolar-binding antibodies specific to multiple SARS-CoV-2 variants by engineering a specificity switch of antibody 80R using RosettaAntibodyDesign (RAbD) results in potential generalizable therapeutic antibodies for novel SARS-CoV-2 virus.

The human infectious disease COVID-19 caused by the SARS-CoV-2 virus has become a major threat to global public health. Developing a vaccine is the preferred prophylactic response to epidemics and pandemics. However, for individuals who have contracted the disease, the rapid design of antibodies that can target the SARS-CoV-2 virus fulfils a critical need. Further, discovering antibodies that bind multiple variants of SARS-CoV-2 can aid in the development of rapid antigen tests (RATs) which are critical for the identification and isolation of individuals currently carrying COVID-19. Here we provide a proof-of-concept study for the computational design of high-affinity antibodies that bind to multiple variants of the SARS-CoV-2 spike protein using RosettaAntibodyDesign (RAbD). Well characterized antibodies that bind with high affinity to the SARS-CoV-1 (but not SARS-CoV-2) spike protein were used as templates and re-designed to bind the SARS-CoV-2 spike protein with high affinity, resulting in a specificity switch. A panel of designed antibodies were experimentally validated. One design bound to a broad range of variants of concern including the Omicron, Delta, Wuhan, and South African spike protein variants.

Assessing the Larvicidal Properties of Endemic Campeche, Mexico Plant Piper cordoncillo var. apazoteanum (Piperaceae) against Aedes aegypti (Diptera: Culicidae) Mosquitoes.

The research aims to investigate the mortality effect of essential oil from Piper cordoncillo var. apazoteanum, an endemic plant from Campeche, Mexico, on early second-instar Aedes aegypti larvae; it also aims to identify the volatile compounds present in the fresh leaves of the plant. To test the effectiveness of the essential oil, we followed World Health Organization Standard Procedures. Larvae were observed for 17 consecutive days after treatment to determine the mortality and growth-inhibitory effect exerted by the essential oil. The results showed that the essential oil was effective in controlling mosquito populations. At a concentration of 800 ppm, the oil achieved an effectiveness rate of 70.00 ± 8.16% after 24 h, increasing to 100.00 ± 0.01% mortality after 72 h. With a concentration of 400 ppm, the effectiveness was 98.33 ± 0.17% by the end of the experiment. Furthermore, the obtained results demonstrated that the LC50 value was 61.84 ± 6.79 ppm, while the LC90 value was 167.20 ± 11.49 ppm. Essential oil concentrations inhibited the growth of immature insect stages, with concentrations between 800-100 ppm demonstrating very high inhibitory activity, and the lowest concentration of 50 ppm showing high inhibitory activity. The study also identified 24 chemical compounds representing 86.71% of the volatile compound composition of the fresh leaves of P. cordoncillo; the most abundant compounds were Safrole, Caryophyllene oxide, E-Nerolidol, and Calarene epoxide. The method used to extract the volatile compounds, solvent-free microwave extraction (SFME), is a promising alternative to traditional methods that avoids the use of potentially harmful solvents, making it more ecologically friendly and potentially safer for professionals handling the extracted compounds. Overall, the study demonstrates the potential of P. cordoncillo essential oil as an effective means of controlling mosquito populations, and provides valuable information on the chemical composition of the plant.Moreover, our study is the first to report on the biological activity and chemical composition of P. cordoncillo worldwide.

Producción científica sobre Ortodoncia publicada en revistas biomédicas pertenecientes a universidades médicas cubanas / Scientific production on Orthodontics published in biomedical journals belonging to Cuban medical universities

La necesidad de impulsar la investigación en Ortodoncia y realizar un análisis de los artículos publicados en la web cubana, con la finalidad de conocer sus características bibliométricas, es cada vez mayor. El presente estudio tuvo como objetivo caracterizar la producción científica sobre Ortodoncia, publicada en revistas biomédicas profesionales patrocinadas por las universidades médicas cubanas entre enero del 2015 y agosto del 2021. Se realizó un estudio bibliométrico, observacional, descriptivo, longitudinal de la productividad científica acerca de Ortodoncia publicada en dichas revistas. Se empleó el gestor de referencias Zotero para procesar los metadatos y VOSviewer para analizar las redes de coautoría. Se constataron 158 artículos; el 15,19 por ciento se publicó en Medisan y el año más productivo fue el 2015. Predominaron los artículos originales (67,72 por ciento), con autoría múltiple (cinco autores), el sexo femenino (76,41 por ciento), los autores de nacionalidad cubana (98,38 por ciento) y procedentes de Santiago de Cuba/Cuba (15,19 por ciento). Se emplearon 2665 referencias con un índice de Price de 0,53. El área temática más abordada fue la Ortodoncia interceptiva (33,54 por ciento). Los artículos recibieron un total de 1041 citas en el Google Académico. El análisis de la red de coautoría permitió establecer 13 clústeres, donde fueron visualizados 106 autores, con 282 links y una fuerza de atracción total entre ellos de 97. Se concluye que la producción científica sobre Ortodoncia, por lo general, es baja. Es necesario lograr la indexación de estas revistas en las grandes bases de datos para así aumentar la visibilidad e impacto de los artículos(AU)

The need to promote research in orthodontics and to carry out an analysis of the articles published in the Cuban web, with the purpose of knowing their bibliometric characteristics, is increasing. The present study aimed at characterizing the scientific production on orthodontics, published in professional biomedical journals sponsored by Cuban medical universities between January 2015 and August 2021. A bibliometric, observational, descriptive, longitudinal, descriptive study of the scientific productivity about Orthodontics published in these journals was carried out. The reference manager Zotero was used to process the metadata and VOSviewer to analyze the co-authorship networks. A total of 158 articles were ascertained; 15.19percent ere published in Medisan and the most productive year was 2015. Original articles predominated (67.72percent), with multiple authorship (five authors), female gender (76.41percent), authors of Cuban nationality (98.38percent) and from Santiago de Cuba/Cuba (15.19percent). A total of 2665 references were used with a Price index of 0.53. Interceptive orthodontics (33.54percent) was the most common subject area. The articles received a total of 1041 citations in Google Scholar. The analysis of the co-authorship network made it possible to establish 13 clusters, where 106 authors were visualized, with 282 links and a total strength of attraction among them of 97. It is necessary to achieve the indexing of these journals in large databases in order to increase the visibility and impact of the articles(AU)

Protocol to identify host-viral protein interactions between coagulation-related proteins and their genetic variants with SARS-CoV-2 proteins.

Here, we describe a bioinformatics pipeline that evaluates the interactions between coagulation-related proteins and genetic variants with SARS-CoV-2 proteins. This pipeline searches for host proteins that may bind to viral protein and identifies and scores the protein genetic variants to predict the disease pathogenesis in specific subpopulations. Additionally, it is able to find structurally similar motifs and identify potential binding sites within the host-viral protein complexes to unveil viral impact on regulated biological processes and/or host-protein impact on viral invasion or reproduction. For complete details on the use and execution of this protocol, please refer to Holcomb et al. (2021).

Factores de riesgos heredofamiliares, prenatales y perinatales en niños cubanos con autismo primario / Family inherited, prenatal and perinatal risk factors in Cuban children with primary autism

Introducción: El autismo primario es una heterogénea alteración neuroconductual, de causa no precisa, en la que tanto los genes como el ambiente contribuyen a la patogenia del trastorno. Objetivo: Identificar factores de riesgos heredofamiliares, prenatales y perinatales en niños cubanos con autismo primario. Material y Métodos: Se realizó una investigación observacional tipo casos y controles (1:1) en niños con autismo primario, atendidos en el Hospital Pediátrico "Juan Manuel Márquez", La Habana; en el período de octubre de 2014 a septiembre de 2019. La muestra quedó conformada por 126 casos y 126 controles. Se recolectaron los datos sobre la historia de enfermedades neuropsiquiátricas de tres generaciones, antecedentes prenatales y perinatales. Se realizó una regresión logística multivariada para identificar factores de riesgos relacionados con el autismo primario. Resultados: El odds de presentar autismo primario fue aproximadamente siete y cuatro veces superior en hijos de madres y padres con edad avanzada, respectivamente. Los antecedentes de trastornos del lenguaje y epilepsia en familiares de primer grado, confirió un odds de presentar autismo 27 y 24 veces mayor, respectivamente. El odds de presentar autismo fue aproximadamente diez veces mayor en los hijos de gestantes con anemia, ocho veces en hijos de gestantes que tuvieron gestorragias y 18 veces para los nacidos de madres con antecedentes de diabetes mellitus pregestacional. Conclusiones: Los antecedentes de enfermedades heredofamiliares neuropsiquiátricas y de factores ambientales prenatales y perinatales relacionados con eventos hipoxémicos constituyen factores de riesgo para el autismo primario en la muestra de niños cubanos estudiados(AU)

Introduction: Primary autism is a heterogeneous neurobehavioral disorder of uncertain etiology in which both genes and the environment contribute to the pathogenesis of the disorder. Objective: To identify family inherited, prenatal and perinatal risk factors in Cuban children with primary autism. Material and Methods: An observational case-control study (1:1) was carried out in children with primary autism, treated at "Juan Manuel Márquez" Pediatric Hospital, Havana, in the period from October of 2014 to September of 2019. The sample was made up of 126 cases and 126 controls. Data on neuropsychiatric diseases, prenatal and perinatal history of three generations were collected. Multivariate logistic regression was performed to identify risk factors related to primary autism. Results: The odds of presenting primary autism were approximately seven and four times higher in children of mothers and fathers of advanced ages, respectively. A history of language disorders and epilepsy in first-degree relatives conferred 27- and 24-fold higher odds of presenting with autism, respectively. The odds of presenting autism were approximately ten times greater in children born to pregnant women with anemia, eight times in children born to pregnant women who had bleeding during pregnancy, and 18 times in those born to mothers with a history of pregestational diabetes mellitus. Conclusions: The history of inherited neuropsychiatric diseases and prenatal and perinatal environmental factors related to hypoxemic events are risk factors for primary autism in the sample of Cuban children studied(AU)

A structural homology approach to identify potential cross-reactive antibody responses following SARS-CoV-2 infection.

The emergence of the novel SARS-CoV-2 virus is the most important public-health issue of our time. Understanding the diverse clinical presentations of the ensuing disease, COVID-19, remains a critical unmet need. Here we present a comprehensive listing of the diverse clinical indications associated with COVID-19. We explore the theory that anti-SARS-CoV-2 antibodies could cross-react with endogenous human proteins driving some of the pathologies associated with COVID-19. We describe a novel computational approach to estimate structural homology between SARS-CoV-2 proteins and human proteins. Antibodies are more likely to interrogate 3D-structural epitopes than continuous linear epitopes. This computational workflow identified 346 human proteins containing a domain with high structural homology to a SARS-CoV-2 Wuhan strain protein. Of these, 102 proteins exhibit functions that could contribute to COVID-19 clinical pathologies. We present a testable hypothesis to delineate unexplained clinical observations vis-à-vis COVID-19 and a tool to evaluate the safety-risk profile of potential COVID-19 therapies.

Atención estomatológica integral a niños con trastorno del espectro autista / Comprehensive dental care for children with autism spectrum disorder

RESUMEN Introducción: los trastornos del espectro autista consisten en un grupo de discapacidades del desarrollo nervioso que afecta la interacción social. El niño autista se considera un paciente especial en Estomatología. Objetivo: evaluar la efectividad de una intervención estomatológica en niños autistas, de la escuela especial "Héroes del Moncada" del municipio Camagüey, de septiembre 2018 a junio 2019. Métodos: se realizó un estudio cuasi experimental, antes-después sin grupo control, de septiembre 2018 a junio 2019. El universo y la muestra coincidieron con 26 pacientes, matrícula total de la escuela especial. Se estudiaron variables: tipos de enfermedades bucodentales, factores de riesgo, clasificación epidemiológica, índice COP-D. Se diseñó un protocolo de actuación escalonada, reforzado por técnicas de modificación de la conducta para la familiarización, el acondicionamiento y las posteriores acciones curativas. Resultados: se observó la prevalencia de enfermedad periodontal (80,8 %) y caries dental (57,7 %), cifras que disminuyeron a 15,4 % y 7,7 % después de la intervención. Existió una frecuencia elevada de anomalías dento-maxilo-faciales (61,5 %), tributarias al segundo nivel de atención. El 96,2 % de los pacientes presentaron una mala higiene bucal y presencia de placa dentobacteriana (PDB), lo cual disminuyó notablemente (26,9 % para ambas variables) una vez tratados. Conclusiones: la intervención estomatológica desarrollada fue efectiva y aplicable, con un aporte educativo, preventivo-curativo y social. Desarrolló en los niños con TEA, hábitos correctos y conocimientos básicos de higiene bucal. Se redujeron las afecciones bucales, se garantizó el seguimiento y evolución a través de nexos afectivos que se establecieron.

ABSTRACT Introduction: autism spectrum disorders consist of a group of neuro-developmental disabilities that affect social interaction. The autistic child is considered a special patient in dentistry. Objective: to evaluate the effectiveness of a dentistry intervention in autistic children, from Heroes del Moncada Special School in Camagüey municipality, September 2018 to June 2019. Methods: a quasi-experimental study was conducted, before-after without control group from September 2018 to June 2019.The target group and the sample matched (26 patients), the total registration of the special school. The variables studied were: types of oral diseases, risk factors, epidemiological classification, and DMFT index. A stepwise action protocol was designed, reinforced by behavior modification techniques for familiarization, conditioning and subsequent healing actions. Results: the prevalence of periodontal disease (80,8 %) and dental caries (57,7 %) was observed, figures that decreased to 15,4 % and 7,7 % respectively after the intervention. There was a high frequency of dento-maxillofacial anomalies (61,5 %), responding to the second level of care. The 96,2 % of patients presented poor oral hygiene and presence of dentobacterial plaque (DBP), which decreased significantly (26,9 % for both variables) after treatment. Conclusions: the dentistry intervention developed was effective and applicable, with an educational, preventive-healing and social contribution. It developed correct habits and basic knowledge of oral hygiene in children with ASD. Oral disorders were reduced and follow-up along with evolution were guaranteed all through the affective bonds developed.

Growth of the Black Soldier Fly Hermetia illucens (Diptera: Stratiomyidae) on Organic-Waste Residues and Its Application as Supplementary Diet for Nile Tilapia Oreochromis niloticus (Perciformes: Cichlidae).

The black soldier fly, Hermetia illucens (BSF, Diptera: Stratiomyidae) is an insect with high protein value and a potential feed agent for animals aimed for human consumption. The growth parameters of BSF larvae reared on four substrates-restaurant-waste, fruit-waste, fish-waste, and commercial tilapia food-for 41 days before processing for inclusion into Oreochromis niloticus (Perciformes: Cichlidae, Nile tilapia) commercial fry diets at 30% (70:30) were determined. On fly larvae, the food substrate based on restaurant waste yielded the greatest larval weight and length. BSF larvae fed a fish-waste diet showed the shortest developmental time. The fruit-waste diet induced the lowest weight and length in the fly larvae/pre-pupae (immature stage). The pre-pupal protein values were similar to commercial food. On fry-fish, the diets with pre-pupae grown on fish waste showed the greatest yields regarding weight (biomass), length, and nutritional content. These results suggest the BSF has the potential to be used in fish feed and provides an alternative for commercial cultivation.

Mini-exon gene reveals circulation of TcI Trypanosomacruzi (Chagas, 1909) (Kinetoplastida, Trypanosomatidae) in bats and small mammals in an ecological reserve in southeastern Mexico.

A wide variety of mammals are involved in the sylvatic cycle of Trypanosomacruzi, the causative agent of Chagas disease. In many areas in Latin America where T.cruzi is endemic, this cycle is poorly known, and its main reservoirs have not been identified. In this study we analyzed T.cruzi infection in bats and other small mammals from an Ecological Reserve in southeastern Mexico. From January through March 2021, we captured wild individuals to extract cardiac and peripheral blood, and infection was detected by PCR of the mini-exon gene. In bats, the prevalence of infection was 16.36%, while in small mammals the prevalence was 28.57%. All of the samples that were positive for T.cruzi were identified as the TCI genotype. Our findings suggest that this zone, situated at the periphery of urban zones might have epidemiological relevance in the sylvatic cycle of T.cruzi and needs to be monitored. The infection of bats in this area is particularly concerning since the flight pattern of this populations overlaps with human settlements. Despite being subject to conservation protections, there continue to be anthropogenic actions that disturb the study area, which could exacerbate risks to public health.

Uso del yo como herramienta terapéutica: una experiencia formativa de terapia ocupacional en pregrado / Uso de si como ferramenta terapêutica: uma experiência formativa na graduação em terapia ocupacional / Use of the self as a therapeutic tool: a formative experience of occupational therapy in an undergraduate course

Resumen Introducción El uso del yo como herramienta terapéutica es una práctica centrada en el cliente y el pilar disciplinar con menor evidencia pedagógica en terapia ocupacional. En Chile, surgen asignaturas vivenciales, ligadas a métodos artísticos/lúdicos que buscan incidir en competencias del estudiante de pregrado para su desarrollo. Objetivo Analizar la experiencia de las estudiantes en relación a los aprendizajes, características y contribuciones de las asignaturas que aportan a la formación del uso del yo como herramienta terapéutica, en carreras de terapia ocupacional de universidades al sur de Chile. Método Investigación cualitativa, con diseño en teoría fundamentada de alcance exploratorio. El muestreo fue no probabilístico, intencionado, por criterio, conformado por quince estudiantes en etapa de internado profesional. La recolección de datos fue mediante dos grupos focales, previa firma de consentimiento informado. El análisis se realizó por método de comparación constante de Glaser y Strauss, utilizando el programa Atlas Ti para sistematizar la información. La rigurosidad científica fue cautelada por los criterios de Guba y Lincoln. Resultados Se identifican 530 unidades de significado, 30 códigos abiertos descriptivos, agrupados en ocho categorías axiales, emergiendo dos núcleos temáticos que abordan el "Proceso de enseñanza aprendizaje en la formación del Uso del Yo" y el "Desarrollo profesional para el Uso del Yo". Conclusión Para los estudiantes las metodologías utilizadas contribuyen de manera relevante al desarrollo del autoconocimiento y competencias genéricas clave para el "Uso del Yo". Esta pedagogía se podría complementar con otras estrategias activas para asegurar la centralidad del usuario en la terapia ocupacional.

Resumo Introdução O uso de si como ferramenta terapêutica é uma prática centrada no cliente e o pilar disciplinar com menor evidência pedagógica em terapia ocupacional. No Chile, surgem disciplinas vivenciais, vinculadas a métodos artísticos/lúdicos que buscam contribuir as habilidades do aluno de graduação para seu desenvolvimento. Objetivo Analisar a experiência dos alunos em relação à aprendizagem, características e contribuições das disciplinas que auxiliam para a formação do uso de si como ferramenta terapêutica, nos cursos de terapia ocupacional em universidades ao sul do Chile. Método Pesquisa qualitativa, com delineamento da teoria fundamentada de alcance exploratório. A amostragem foi não probabilística, intencional, por critério, composta por quinze alunos em etapa de estágio profissional. A coleta de dados se deu por meio de dois grupos focais, após assinatura do consentimento informado. A análise foi realizada pelo método de comparação constante de Glaser e Strauss, utilizando o programa Atlas Ti para sistematizar as informações. O rigor científico foi resguardado pelos critérios de Guba e Lincoln. Resultados Foram identificadas 530 unidades de sentido, 30 códigos abertos descritivos, agrupados em oito categorias axiais, emergindo dois núcleos temáticos que abordam o "Processo de ensino-aprendizagem na formação do Uso de Si" e o "Desenvolvimento profissional para o uso de Si". Conclusão Para os alunos, as metodologias utilizadas contribuem de forma relevante para o desenvolvimento do autoconhecimento e das competências genéricas chave para o "Uso de Si". Essa pedagogia poderia ser complementada com outras estratégias ativas para garantir a centralidade do usuário na terapia ocupacional.

Abstract Introduction The use of the self as a therapeutic tool is a client-centered practice with the least evidence in the pedagogy of occupational therapy. In Chile, experiential subjects arise, linked to artistic/playful methods that seek to influence the skills of the undergraduate student for their development. Objective To analyze the experience of the students in relation to the learning, characteristics, and contributions of the subjects that contribute to the development of the use of the self as a therapeutic tool, in occupational therapy careers at universities in the south of Chile. Method Qualitative research, exploratory with a grounded theory design. The sampling was non-probabilistic, intentional, by criteria, of fifteen students in the professional internship stage. Data collection was through two focus groups, after signing informed consent. The analysis was carried out using the constant comparison method of Glaser and Strauss, using the Atlas Ti program to systematize the information. Scientific rigor was guarded by the criteria of Guba and Lincoln. Results 530 units of meaning are identified, 30 descriptive open codes, grouped into eight axial categories, emerging two thematic nuclei that address the "Teaching-learning process in the formation of the Use of the Self" and the "Professional Development for the Use of the Self". Conclusion For the students, the methodologies used to contribute in a relevant way to the development of self-knowledge and key generic competences for the "Use of the Self". This pedagogy could be complemented with other active strategies to ensure the centrality of the user in occupational therapy.

Effect of climate change on the potential distribution of Helodermaalvarezi (Squamata, Helodermatidae).

Climate change represents a real threat to biodiversity conservation worldwide. Although the effects on several species of conservation priority are known, comprehensive information about the impact of climate change on reptile populations is lacking. In the present study, we analyze outcomes on the potential distribution of the black beaded lizard (Helodermaalvarezi Bogert & Martin del Campo, 1956) under global warming scenarios. Its potential distribution, at present and in projections for the years 2050 and 2070, under both optimistic and pessimistic climate change forecasts, were computed using current data records and seven bioclimatic variables. General results predict a shift in the future potential distribution of H.alvarezi due to temperature increase. The optimistic scenario (4.5 W/m2) for 2070 suggests an enlargement in the species' distribution as a response to the availability of new areas of suitable habitat. On the contrary, the worst-case scenario (7 W/m2) shows a distribution decrease by 65%. Moreover, the range distribution of H.alvarezi is directly related to the human footprint, which consequently could magnify negative outcomes for this species. Our research elucidates the importance of conservation strategies to prevent the extinction of the black beaded lizard, especially considering that this species is highly threatened by aversive hunting.

A conserved epitope III on hepatitis C virus E2 protein has alternate conformations facilitating cell binding or virus neutralization.

Epitope III, a highly conserved amino acid motif of 524APTYSW529 on the hepatitis C virus (HCV) E2 glycoprotein, resides in the critical loop that binds to the host receptor CD81, thus making it one of the most important antibody targets for blocking HCV infections. Here, we have determined the X-ray crystal structure of epitope III at a 2.0-Å resolution when it was captured by a site-specific neutralizing antibody, monoclonal antibody 1H8 (mAb1H8). The snapshot of this complex revealed that epitope III has a relatively rigid structure when confined in the binding grooves of mAb1H8, which confers the residue specificity at both ends of the epitope. Such a high shape complementarity is reminiscent of the "lock and key" mode of action, which is reinforced by the incompatibility of an antibody binding with an epitope bearing specific mutations. By subtly positioning the side chains on the three residues of Tyr527, Ser528, and Trp529 while preserving the spatial rigidity of the rest, epitope III in this cocrystal complex adopts a unique conformation that is different from previously described E2 structures. With further analyses of molecular docking and phage display-based peptide interactions, we recognized that it is the arrangements of two separate sets of residues within epitope III that create these discrete conformations for the epitope to interact selectively with either mAb1H8 or CD81. These observations thus raise the possibility that local epitope III conformational dynamics, in conjunction with sequence variations, may act as a regulatory mechanism to coordinate "mAb1H8-like" antibody-mediated immune defenses with CD81-initiated HCV infections.

Molecular chaperone RAP interacts with LRP1 in a dynamic bivalent mode and enhances folding of ligand-binding regions of other LDLR family receptors.

The low-density lipoprotein receptor (LDLR) family of receptors are cell-surface receptors that internalize numerous ligands and play crucial role in various processes, such as lipoprotein metabolism, hemostasis, fetal development, etc. Previously, receptor-associated protein (RAP) was described as a molecular chaperone for LDLR-related protein 1 (LRP1), a prominent member of the LDLR family. We aimed to verify this role of RAP for LRP1 and two other LDLR family receptors, LDLR and vLDLR, and to investigate the mechanisms of respective interactions using a cell culture model system, purified system, and in silico modelling. Upon coexpression of RAP with clusters of the ligand-binding complement repeats (CRs) of the receptors in secreted form in insect cells culture, the isolated proteins had increased yield, enhanced folding, and improved binding properties compared with proteins expressed without RAP, as determined by circular dichroism and surface plasmon resonance. Within LRP1 CR-clusters II and IV, we identified multiple sites comprised of adjacent CR doublets, which provide alternative bivalent binding combinations with specific pairs of lysines on RAP. Mutational analysis of these lysines within each of isolated RAP D1/D2 and D3 domains having high affinity to LRP1 and of conserved tryptophans on selected CR-doublets of LRP1, as well as in silico docking of a model LRP1 CR-triplet with RAP, indicated a universal role for these residues in interaction of RAP and LRP1. Consequently, we propose a new model of RAP interaction with LDLR family receptors based on switching of the bivalent contacts between molecules over time in a dynamic mode.

Gene variants of coagulation related proteins that interact with SARS-CoV-2.

Thrombosis is a recognized complication of Coronavirus disease of 2019 (COVID-19) and is often associated with poor prognosis. There is a well-recognized link between coagulation and inflammation, however, the extent of thrombotic events associated with COVID-19 warrants further investigation. Poly(A) Binding Protein Cytoplasmic 4 (PABPC4), Serine/Cysteine Proteinase Inhibitor Clade G Member 1 (SERPING1) and Vitamin K epOxide Reductase Complex subunit 1 (VKORC1), which are all proteins linked to coagulation, have been shown to interact with SARS proteins. We computationally examined the interaction of these with SARS-CoV-2 proteins and, in the case of VKORC1, we describe its binding to ORF7a in detail. We examined the occurrence of variants of each of these proteins across populations and interrogated their potential contribution to COVID-19 severity. Potential mechanisms, by which some of these variants may contribute to disease, are proposed. Some of these variants are prevalent in minority groups that are disproportionally affected by severe COVID-19. Therefore, we are proposing that further investigation around these variants may lead to better understanding of disease pathogenesis in minority groups and more informed therapeutic approaches.