Motor adaptation to continuous lateral trunk support force during walking improves trunk postural control and walking in children with cerebral palsy: A pilot study.

PURPOSE: To determine whether the application of continuous lateral trunk support forces during walking would improve trunk postural control and improve gait performance in children with CP. MATERIALS AND METHODS: Nineteen children with spastic CP participated in this study (8 boys; mean age 10.6 ± 3.4 years old). Fourteen of them were tested in the following sessions: 1) walking on a treadmill without force for 1-min (baseline), 2) with lateral trunk support force for 7-min (adaptation), and 3) without force for 1-min (post-adaptation). Overground walking pre/post treadmill walking. Five of them were tested using a similar protocol but without trunk support force (i.e., control). RESULTS: Participants from the experimental group showed enhancement in gait phase dependent muscle activation of rectus abdominis in late adaptation period compared to baseline (P = 0.005), which was retained during the post-adaptation period (P = 0.036), reduced variability of the peak trunk oblique angle during the late post-adaptation period (P = 0.023), and increased overground walking speed after treadmill walking (P = 0.032). Participants from the control group showed modest changes in kinematics and EMG during treadmill and overground walking performance. These results suggest that applying continuous lateral trunk support during walking is likely to induce learning of improved trunk postural control in children with CP, which may partially transfer to overground walking, although we do not have a firm conclusion due to the small sample size in the control group.

Decoding functional proteome information in model organisms using protein language models.

Protein language models have been tested and proved to be reliable when used on curated datasets but have not yet been applied to full proteomes. Accordingly, we tested how two different machine learning-based methods performed when decoding functional information from the proteomes of selected model organisms. We found that protein language models are more precise and informative than deep learning methods for all the species tested and across the three gene ontologies studied, and that they better recover functional information from transcriptomic experiments. The results obtained indicate that these language models are likely to be suitable for large-scale annotation and downstream analyses, and we recommend a guide for their use.

Single-dose high-dose-rate brachytherapy versus two and three fractions for locally advanced prostate cancer.

BACKGROUND: Single-dose high-dose-rate brachytherapy (SD-HDR-BT) was compared to two or three fraction HDR BT in intermediate and high-risk localized prostate cancer with median follow-up of 10 years. MATERIALS AND METHODS: 293 patients received 1 × 19Gy or 1 × 20Gy (Group A = 49), 2 × 13Gy (Group B = 138), or 3 × 10.5 Gy (Group C = 106) HDR BT. The primary endpoint was biochemical relapse-free interval (bRFI). Late genitourinary (GU) and gastrointestinal (GI) morbidity used RTOG scales and the International Prostate Symptom Score (IPSS). Freedom from biochemical relapse (bRFI), overall survival (OS) and GU, GI and IPSS morbidity were calculated using Kaplan-Meier (K-M) method and log-rank test. Univariate and multivariate hazard ratios (HR) were obtained using Cox's proportional hazard. RESULTS: At 10 years, K-M estimates of bRFI were 64 % (Group A), 72 % (Group B), and 76 % (Group C) (p = 0.2). No statistically significant difference was seen in OS. In multivariate analysis risk-category and ADT administration, but not dose, were significant predictors of relapse (p = 0.0003 and 0.03, respectively). At ten years, GU grade 3 events were 8 % (A), 2 % (B) and 13 % (C); (p = 0.01). IPSS ≥ 20 was 31 % (A), 20 % (B) and 23 % (C); (p = 0.6) and grade 3 GI was 0 % in groups A and B and 2 % in C; (p = 0.3). No GU or GI grade-4 events were observed. Pre-treatment IPSS was a highly significant predictor of failure in multivariate analysis. CONCLUSIONS: Long-term outcome data show reduced but not statistically significant difference in PSA control, and no difference in overall survival, between SD-HDR-BT and 2 or 3 fractions of HDR-BT.

Structure and rheology of the polysaccharides from Schizymenia dubyi: Isolation of an unusual glucurono-carrageenan.

The system of polysaccharides from Schizymenia dubyi (Nemastomatales) was investigated. It contains a mixture of hybrid dl galactans (SH-S) and carrageenan-like polysaccharides, which were separated by means of precipitation with KCl at high concentrations. The structural features of the carrageenan-like fraction (SH-I) were investigated by methylation analysis, desulfation, uronic acid reduction, and NMR spectroscopy. It was concluded that the structure has the typical alternance α-(1 â†’ 3), ß-(1 â†’ 4) of d-galactose units, with most of the 3-linked units sulfated in O-2 (and some in O-4), and most of the 4-linked units sulfated in O-3, and substituted in O-2 by single stubs of ß-d-glucuronic acid (partly sulfated in each of the three available positions). This substituent has been only seldom found in red seaweed galactans. Rheological studies of 5 % and 10 % w/v SH, SH-S and SH-I aqueous systems, either without ions, or in KCl or CaCl2 solution gave thickening behaviors. Their random coil conformations justify the pseudoplastic behavior observed in the viscosity versus shear rate curves. As SH-S and SH-I are both contained in SH, an interpenetrating network could form in SH between the glucurono-carrageenan and the agaran, as inferred from the mechanical spectra recorded in water, especially with potassium ion.

Case-based explanation of standard work tools for selective dorsal rhizotomy for cerebral palsy.

OBJECTIVE: Spasticity is a challenging feature of cerebral palsy (CP) that may be managed with selective dorsal rhizotomy (SDR). Although standard work tools (SWTs) have recently been utilized to inform a standard of care for neurosurgical procedures, no SWTs for SDR have been previously described. The authors present the multidisciplinary approach SWTs for SDR used at their institutions to promote consistency in the field and minimize complication rates. METHODS: A multidisciplinary approach was used to define all steps in the SDR pathway. Preoperative, intraoperative, and postoperative workflows were synthesized, with specific efforts to improve mobility through inpatient rehabilitation and minimize infection. RESULTS: The SWTs have been implemented at two institutions for 7 years. An illustrative case of a patient aged 3 years 10 months with a history of premature birth at 29 weeks, spastic-diplegic CP, right-sided periventricular leukomalacia, and developmental delay who underwent L2-S1 SDR is presented. CONCLUSIONS: The authors detail SWTs for SDR developed by a multidisciplinary team with specific steps at all points in the patient pathway. The illustrative case emphasizes that SWTs may help ensure the safety of SDR while maximizing its long-term efficacy for individuals with CP.

Calidad de vida y factores condicionantes en personas con Labio Fisurado y Paladar Hendido No Sindrómico (LPHNs): experiencias de familiares, pacientes, y personal de salud / Quality of life and conditioning factors in people with Non-syndromic Cleft Lip and Palate (NSCLP): experiences of family members, patients, and health personnel

Objetivo: comprender las percepciones sobre calidad de vida (CV) y sus factores condicionantes en personas con Labio Fisurado y Paladar Hendido No Sindrómico (LPHNs), desde la experiencia de las personas con esta condición, y desde sus familias y equipo de salud. Métodos: estudio cualitativo con perspectiva fenomenológica. Se realizaron entrevistas semiestructuradas a seis individuos que cumplían los criterios de participación (4 mujeres) y seis familiares (esposos, hermanos, padre/madre) mediante un guion estructurado. Esta información se complementó con una entrevista a un ortodoncista con experiencia en atención a estos individuos y un grupo focal con laparticipación de profesionales de la salud. Se realizó análisis de contenido cualitativo y estrategias de reducción fenomenológica desde los discursos experienciales de la población participante. Se contó con aprobación ética e institucional. Resultados: se encontraron cuatro categorías principales desde la experiencia de las personas con LPHNs que involucran diferentes perspectivas de los participantes del estudio: 1) concepto de CV y sus factores condicionantes, 2) experiencia de vida con la condición de LPHNs; 3) experiencia durante el tratamiento integral para la condición de LPHNs; y 4) expectativas generales. Todas estas categorías reflejan la historia de vida, los elementos individuales y sociales, y las dificultades propias de su condición. Conclusiones: existen factores individuales, sociales y contextuales que inciden en la CV de los pacientes con LPHNs. Esto implica un abordaje intersectorial y multidisciplinario que permita la generación de políticas en salud y estrategias de tratamiento acordes a las necesidades individuales y colectivas de estas personas.

Objective: Understand the perceptions and experiences about quality of life (QOL) and their conditionants in people with Non-syndromic Cleft Lip and Palate (NSCLP), from the experience of people living with this condition, and from their families and health personnel. Methods: A qualitative study with phenomenological perspective was conducted. Six individuals and relatives (partner, siblings, parents) were interviewed. This information was complemented by an interview with an orthodontist who works with people with NSCLP and a Focus Group with the participation of health personnel working in a Specialized Foundation focused on these individuals. Qualitative content analysis and phenomenological reduction strategies were carried out to address the main themes extracted from the discourses of the participating population. Ethical and institutional approval was obtained. Results: Four main categories of the experience of people with NSCLP were found that involve the different perspectives of the study participants: 1) concept of QOL and its conditioning factors, 2) life experience with the condition of NSCLP; 3) experience during comprehensive treatment for NSCLP condition; and 4) general expectations. All these categories reflect the life history, the individual and social elements, and the difficulties inherent to their condition. Conclusions: there are individual, social, and contextual factors that affect the QOL of people living with NSCLP. This situation implies an intersectoral and multidisciplinary approach that allows the generation of health policies and treatment strategies according to the individual and collective people's needs.

Amidation of arabinoglucuronoxylans to modulate their flow behavior.

Arabinoglucuronoxylans obtained from the exudate of Cercidium praecox (Brea gum) were subjected to an amidation reaction to modulate their flow behavior to obtain a product with similar behavior to gum Arabic. The amidation reaction of the uronic acids present in this exudate was studied using the 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC) and N-hydroxysuccinimide (NHS) system with the aim of maximizing product yield and minimizing by-product. An analysis of the significant factors involved in the reaction was carried out and a response surface methodology was conducted to optimize the stoichiometry of the reagents used. It was possible to obtain models for predicting the degree of amidation (DA) of arabinoglucuronoxylans and the formation of by-products. The formation of a secondary product derived from the amino acid ß-alanine which has not been reported previously in the reaction with polysaccharides, was described. The flow behavior of an amidated product (DA = 52 %) was determined, showing a pseudoplastic behavior and a decreased Newtonian viscosity (η0 = 36.2 Pa s) at the lowest shear rate range with respect to native product solution (η0 = 115 Pa s). Amidated arabinoglucuronoxylans had a flow behavior more similar to that of gum Arabic.

Mexican consensus on cow's milk protein allergy.

BACKGROUND: The aim of this study is to present the current views of a diverse group of experts on the diagnosis and treatment of Cow's Milk Protein Allergy (CMPA) in children under 2 years of age in Mexico. MATERIAL AND METHODS: The study, led by a scientific committee of five experts in CMPA, was divided into six phases, including a modified Delphi process. A total of 20 panelists, all of whom were pediatric specialists, participated in administering a comprehensive 38-item questionnaire. The questionnaire was divided into two blocks: Diagnosis and Treatment (20 items each). RESULTS: Consensus was reached on all the proposed items, with an agreement rate of over 70% for each of them. As a result, a diagnostic and treatment algorithm was developed that emphasized the reduction of unnecessary diagnostic studies and encouraged breastfeeding whenever possible. In cases where breast milk is not available, appropriate use of hypoallergenic formulas was recommended. In addition, recommendations on treatment duration and gradual reintroduction of cow's milk protein were provided. CONCLUSIONS: The recommendations endorsed by 20 Mexican pediatricians through this study are applicable to everyday clinical practice, thereby enhancing the diagnosis and treatment of children under 2 years of age with CMPA. This, in turn, will foster improved health outcomes and optimize the utilization of healthcare resources.

Trunk postural reactions to the force perturbation intensity and frequency during sitting astride in children with cerebral palsy.

The purpose of this study was to examine kinematic and neuromuscular responses of the head and body to pelvis perturbations with different intensities and frequencies during sitting astride in children with CP. Sixteen children with spastic CP (mean age 7.4 ± 2.4 years old) were recruited in this study. A custom designed cable-driven robotic horse was used to apply controlled force perturbations to the pelvis during sitting astride. Each participant was tested in four force intensity conditions (i.e., 10%, 15%, 20%, and 25% of body weight (BW), frequency = 1 Hz), and six force frequency conditions (i.e., 0.5 Hz, 1 Hz, 1.5 Hz, 2 Hz, 2.5 Hz, and 3 Hz, intensity = 20% of BW). Each testing session lasted for one minute with a one-minute rest break inserted between two sessions. Kinematic data of the head, trunk, and legs were recorded using wearable sensors, and EMG signals of neck, trunk, and leg muscles were recorded. Children with CP showed direction-specific trunk and neck muscle activity in response to the pelvis perturbations during sitting astride. Greater EMG activities of trunk and neck muscles were observed for the greater intensities of force perturbations (P < .05). Participants also showed enhanced activation of antagonistic muscles rather than direction-specific trunk and neck muscle activities for the conditions of higher frequency perturbations (P < .05). Children with CP may modulate trunk and neck muscle activities in response to greater changes in intensity of pelvis perturbation during sitting astride. Perturbations with too high frequency may be less effective in inducing direction-specific trunk and neck muscle activities.

El estudio de la cognición: hacia una perspectiva corporizada / O estudo da cognição: em direção a uma perspectiva incorporada / The study of cognition: towards an embodied perspective / L'étude de la cognition: vers une perspective incarnée

Resumen El campo de la cognición ha tenido una larga historia en la que los modelos formales, el cuerpo y la interacción con el mundo físico y social han tenido significados y papeles variados. En los últimos años, las propuestas han intentado reintroducir el cuerpo y la variabilidad cognitiva resultante de la sensibilidad a contextos ricos e impredecibles. Este artículo presenta el enactivismo autopoiético, una de las versiones esenciales de las teorías encarnadas dentro de las ciencias cognitivas, señalando algunas limitaciones de las teorías clásicas de procesamiento de la información y sus nociones de representación. En este distanciamiento, las ciencias cognitivas han recuperado el cuerpo, la sensibilidad y flexibilidad de los procesos cognitivos, la naturaleza dinámica de la experiencia y el valor de los sistemas culturales que sustentan la actividad cognitiva.

Resumo O campo da cognição tem uma longa história na qual modelos formais, o corpo, e a interação com o mundo físico e social tiveram significados e papéis variados. Nos últimos anos, as propostas tentaram reintroduzir o corpo e a variabilidade cognitiva resultante da sensibilidade a contextos ricos e imprevisíveis. Este artigo apresenta o enativismo autopoiético, uma das versões essenciais das teorias corporizadas dentro das ciências cognitivas, apontando algumas limitações das teorias clássicas de processamento de informação e as suas noções de representação. Nesse distanciamento, as ciências cognitivas recuperaram o corpo, a sensibilidade e flexibilidade dos processos cognitivos, a natureza dinâmica da experiência e o valor dos sistemas culturais que sustentam a atividade cognitiva.

Abstract The field of cognition has had a long history where formal models, the body, and interaction with the physical and social world have had varied meanings and roles. In recent years, proposals have tried to reintroduce the body and the cognitive variability resulting from sensitivity to rich and unpredictable contexts. This article presents the autopoietic enactivism, one of the essential versions of embodied theories within the cognitive sciences, pointing out some limitations of classical information processing theories and their notions of representation. In this distancing, cognitive sciences have recovered the body, the sensitivity and flexibility of cognitive processes, the dynamic nature of experience, and the value of the cultural systems that support cognitive activity.

Résumé Le domaine de la cognition a connu une longue histoire dans laquelle les modèles formels, le corps et l'interaction avec le monde physique et social ont eu des significations et des rôles variés. Ces dernières années, des propositions ont tenté de réintroduire le corps et la variabilité cognitive résultant de la sensibilité à des contextes riches et imprévisibles. Cet article présente l'enactivisme autopoïétique, l'une des versions essentielles des théories incarnées au sein des sciences cognitives, en soulignant certaines limites des théories classiques du traitement de l'information et de leurs notions de représentation. Avec cet écartement, les sciences cognitives ont récupéré le corps, la sensibilité et la flexibilité des processus cognitifs, la nature dynamique de l'expérience et la valeur des systèmes culturels qui soutiennent l'activité cognitive.

Environmental surface monitoring as a noninvasive method for SARS-CoV-2 surveillance in community settings: Lessons from a university campus study.

Environmental testing of high-touch objects is a potential noninvasive approach for monitoring population-level trends of SARS-CoV-2 and other respiratory viruses within a defined setting. We aimed to determine the association between SARS-CoV-2 contamination on high-touch environmental surfaces, community level case incidence, and university student health data. Environmental swabs were collected from January 2022 to November 2022 from high-touch objects and surfaces from five locations on a large university campus in Florida, USA. RT-qPCR was used to detect and quantify viral RNA, and a subset of positive samples was analyzed by viral genome sequencing to identify circulating lineages. During the study period, we detected SARS-CoV-2 viral RNA on 90.7 % of 162 tested samples. Levels of environmental viral RNA correlated with trends in community-level activity and case reports from the student health center. A significant positive correlation was observed between the estimated viral gene copy number in environmental samples and the weekly confirmed cases at the university. Viral sequencing data from environmental samples identified lineages concurrently circulating in the local community and state based on genomic surveillance data. Further, we detected emerging variants in environmental samples prior to their identification by clinical genomic surveillance. Our results demonstrate the utility of viral monitoring on high-touch environmental surfaces for SARS-CoV-2 surveillance at a community level. In communities with delayed or limited testing facilities, immediate environmental surface testing may considerably inform epidemic dynamics.

Free Energy Perturbation Approach for Accurate Crystalline Aqueous Solubility Predictions.

Early assessment of crystalline thermodynamic solubility continues to be elusive for drug discovery and development despite its critical importance, especially for the ever-increasing fraction of poorly soluble drug candidates. Here we present a detailed evaluation of a physics-based free energy perturbation (FEP+) approach for computing the thermodynamic aqueous solubility. The predictive power of this approach is assessed across diverse chemical spaces, spanning pharmaceutically relevant literature compounds and more complex AbbVie compounds. Our approach achieves predictive (RMSE = 0.86) and differentiating power (R2 = 0.69) and therefore provides notably improved correlations to experimental solubility compared to state-of-the-art machine learning approaches that utilize quantum mechanics-based descriptors. The importance of explicit considerations of crystalline packing in predicting solubility by the FEP+ approach is also highlighted in this study. Finally, we show how computed energetics, including hydration and sublimation free energies, can provide further insights into molecule design to feed the medicinal chemistry DMTA cycle.

Simulation-based mastery learning for intrathecal baclofen pump management in physical medicine and rehabilitation: A pilot study.

BACKGROUND: Simulation-based mastery learning (SBML) has demonstrated superiority as a procedural learning method. Implementation of SBML in Physical Medicine and Rehabilitation (PM&R) education has not been described and there is a paucity of literature regarding standardized procedural learning in this specialty. OBJECTIVE: To evaluate if implementation of intrathecal baclofen pump management SBML affects knowledge, attitudes, and skills in PM&R residents. DESIGN: Pretest-posttest design. SETTING: Academic rehabilitation hospital. PARTICIPANTS: Twenty-two PM&R residents. INTERVENTIONS: Participants engaged in SBML steps: pre-test, demonstration of proper technique, deliberate practice, and a post-test. MAIN OUTCOME MEASURES: Ability to achieve minimum passing score, quiz scores, and survey scores. Pre- and post-test results were compared using Wilcoxon signed-rank tests. Post graduate year (PGY)-3 and PGY-4 resident results were compared using Mann-Whitney U tests. RESULTS: Based on institutional expert consensus, a simulation procedural checklist was created with a minimum passing score set at correctly performing 30 of 31 items. On pre-test, no learners achieved the minimum passing score (22.5, interquartile range [IQR] 17.0-23.0). Initial post-test score for all learners was 30 (IQR 29.8-31.0). Six learners required additional attempts to reach mastery as defined by reaching the minimum passing score. Quiz scores significantly improved from 9 to 11 (pre-test IQR 9-10; post-test IQR 10-11; p < .05). Confidence in procedure significantly improved (pre-test 2.7/5.9, IQR 2.2-3.8; post-test 4.1/5.0, IQR 3.7-4.5; p < .01). Likelihood to perform procedure in future practice did not change (pre-test 2.2, IQR 1.0-3.8; post-test 3.0, IQR 1.0-4.0; p = .89). CONCLUSION: SBML is an effective tool to improve multiple domains of learning in PM&R residents.

Expression of ERG11, ERG3, MDR1 and CDR1 genes in Candida tropicalis / Expresión de los genes ERG11, ERG3, MDR1 y CDR1 en Candida tropicalis

INTRODUCTION: Drug resistance to azoles is a growing problem in the Candida genus. OBJECTIVE: To analyze molecularly the genes responsible for fluconazole resistance in Candida tropicalis strains. MATERIALS AND METHODS: Nineteen strains, with and without exposure to fluconazole, were selected for this study. The expression of MDR1, CDR1, ERG11, and ERG3 genes was analyzed in sensitive, dose-dependent sensitive, and resistant strains exposed to different concentrations of the antifungal drug. RESULTS: MDR1, ERG11 and ERG3 genes were significantly overexpressed in the different sensitivity groups. CDR1 gene expression was not statistically significant among the studied groups. Seven of the eight fluconazole-resistant strains showed overexpression of one or more of the analyzed genes. In some dose-dependent sensitive strains, we found overexpression of CDR1, ERG11, and ERG3. CONCLUSION: The frequency of overexpression of ERG11 and ERG3 genes indicates that they are related to resistance. However, the finding of dose-dependent resistant/sensitive strains without overexpression of these genes suggests that they are not exclusive to this phenomenon. More basic research is needed to study other potentially involved genes in the resistance mechanism to fluconazole.

Introducción: La farmacorresistencia a los azoles es un problema creciente en el género Candida. Objetivo: Analizar molecularmente los genes responsables de la resistencia a fluconazol en cepas de Candida tropicalis. Materiales y métodos: Para este estudio, se seleccionaron 19 cepas, con exposición a fluconazol y sin ella. Se analizó la expresión de los genes MDR1, CDR1, ERG11 y ERG3 en cepas sensibles, sensibles dependiente de la dosis, y resistentes, previamente expuestas a diferentes concentraciones del fármaco antifúngico. Resultados: Se encontró que los genes MDR1, ERG11 y ERG3 estaban significativamente sobreexpresados en los diferentes grupos de sensibilidad. La expresión del gen CDR1 no fue estadísticamente significativa entre los grupos estudiados. Siete de las ocho cepas resistentes a fluconazol mostraron sobreexpresión de uno o más de los genes analizados. En algunas cepas sensibles dependientes de la dosis, se encontró sobreexpresión de CDR1, ERG11 y ERG3. Conclusión: La sobreexpresión de los genes ERG11 y ERG3 indica que están relacionados con la resistencia de las cepas de Candida. Sin embargo, el hallazgo de cepas resistentes o sensibles según la dosis, sin sobreexpresión de estos genes, sugiere que pueden existir otros genes involucrados en este fenómeno. Se necesitan más investigaciones básicas que contribuyan al estudio de otros genes potencialmente involucrados en el mecanismo de resistencia al fluconazol.

Experiencias de docentes y estudiantes en la educación remota de emergencia: oportunidades para mejorar la educación del pregrado en medicina / Faculty and student experience during remote emergency education: opportunities for improving undergraduate medical education

Introducción: Los ciclos clínicos de pregrado representan los escenarios principales en los que los estudiantes de medicina consolidan los conocimientos. Sin embargo, a principios de 2020, la mayoría de los estudiantes fue confinada en sus domicilios debido a la pandemia por el SARS-CoV-2. Los procesos formativos continuaron desde los hogares por medio de la educación remota de emergencia, una modalidad de enseñanza basada en el uso intensivo de la tecnología que, a pesar de hacerse de manera improvisada, respondió a la situación educativa de urgencia. El propósito de este estudio fue indagar la experiencia educativa de estudiantes y docentes que se encontraban en los años clínicos de pregrado de la carrera de medicina con el fin de identificar las oportunidades de mejora en la enseñanza a partir de la crisis sanitaria vivida. Sujetos y métodos: Se realizó un estudio cualitativo de carácter descriptivo con la técnica de grupos focales. El análisis se basó en la reducción de datos, en la triangulación entre estamentos y en la bibliografía del tema. Resultados: Se realizaron 16 grupos focales con un total de 148 participantes. Se identificaron cuatro categorías generales: a) enseñanza y aprendizaje; b) evaluación de la práctica clínica; c) identidad profesional, y d) sugerencias en busca de mejoras en la formación de los médicos Conclusiones: Las reflexiones reconocen la necesidad de incorporar las tecnologías digitales de una manera planeada y diseñada en conjunto por expertos y docentes para adaptarlas a las necesidades de los contextos educativos, y continuar con modelos híbridos o combinados para mejorar la educación médica.(AU)

Introduction: During medical education, undergraduate clinical cycles represent the main scenarios where students consolidate knowledge. However, in the early 2020s, most students were confined to their homes due to the SARS-Cov-2 pandemic. In this situation, the digital network allowed the educational processes to continue from their homes through remote emergency education (REE), a teaching modality based on the intensive use of technology that, despite having been improvised, responded to the emergency educational situation. Therefore, this study aimed to investigate the educational experience of students and teachers in the undergraduate clinical years of the medical degree in order to identify opportunities for improvement in teaching after the health crisis. Subjects and methods: A descriptive qualitative study was carried out with a phenomenological approach through the focus group technique. The qualitative analysis was based on data reduction and triangulation between strata and subject literature. Results: Sixteen focus groups were integrated with a total of 148 participants. Four categories were identified: a) teaching and learning; b) evaluation of clinical practice; c) professional identity, and d) suggestions for improvement in the training of physicians. Conclusions: The reflections lead to recognizing the need to incorporate digital technology designed by experts and teachers to adapt them to the real needs of the educational contexts and to continue with a hybrid or combined model that supports the improvement of medical education.(AU)

Rapid population growth and high management costs have created a narrow window for control of introduced hippos in Colombia.

The introduction of hippos into the wild in Colombia has been marked by their rapid population growth and widespread dispersal on the landscape, high financial costs of management, and conflicting social perspectives on their management and fate. Here we use population projection models to investigate the effectiveness and cost of management options under consideration for controlling introduced hippos. We estimate there are 91 hippos in the middle Magdalena River basin, Colombia, and the hippo population is growing at an estimated rate of 9.6% per year. At this rate, there will be 230 hippos by 2032 and over 1,000 by 2050. Applying the population control methods currently under consideration will cost at least 1-2 million USD to sufficiently decrease hippo population growth to achieve long-term removal, and depending on the management strategy selected, there may still be hippos on the landscape for 50-100 years. Delaying management actions for a single decade will increase minimum costs by a factor of 2.5, and some methods may become infeasible. Our approach illustrates the trade-offs inherent between cost and effort in managing introduced species, as well as the importance of acting quickly, especially when dealing with species with rapid population growth rates and potential for significant ecological and social impacts.

Chemoinformatic modelling of the antioxidant activity of phenolic compounds.

BACKGROUND: Antioxidants are chemicals used to protect foods from deterioration by neutralizing free radicals and inhibiting the oxidative process. One approach to investigate the antioxidant activity is to develop quantitative structure-activity relationships (QSARs). RESULTS: A curated database of 165 structurally heterogeneous phenolic compounds with the Trolox equivalent antioxidant capacity (TEAC) was developed. Molecular geometries were optimized by means of the GFN2-xTB semiempirical method and diverse molecular descriptors were obtained afterwards. For model development, V-WSP unsupervised variable reduction was used before performing the genetic algorithms-variable subset selection (GAs-VSS) to construct the best five-descriptor multiple linear regression model. The coefficient of determination and the root mean square error were used to measure the performance in calibration (R2 = 0.789 and RMSEC = 0.381), and test set prediction (Q2 = 0.748 and RMSEP = 0.416), along several cross-validation criteria. To thoroughly understand the TEAC prediction, a fully explained mechanism of action of the descriptors is provided. In addition, the applicability domain of the model defined a theoretical chemical space for reliable predictions of new phenolic compounds. CONCLUSION: This in silico model conforms to the five principles stated by the Organisation for Economic Co-operation and Development. The model might be useful for virtual screening of the antioxidant chemical space and for identifying the most potent molecules related to an experimental measurement of TEAC activity. In addition, the model could assist chemists working on computer-aided drug design for the synthesis of new targets with improved activity and potential uses in food science. © 2023 Society of Chemical Industry.

A hotspot for posttranslational modifications on the androgen receptor dimer interface drives pathology and anti-androgen resistance.

Mutations of the androgen receptor (AR) associated with prostate cancer and androgen insensitivity syndrome may profoundly influence its structure, protein interaction network, and binding to chromatin, resulting in altered transcription signatures and drug responses. Current structural information fails to explain the effect of pathological mutations on AR structure-function relationship. Here, we have thoroughly studied the effects of selected mutations that span the complete dimer interface of AR ligand-binding domain (AR-LBD) using x-ray crystallography in combination with in vitro, in silico, and cell-based assays. We show that these variants alter AR-dependent transcription and responses to anti-androgens by inducing a previously undescribed allosteric switch in the AR-LBD that increases exposure of a major methylation target, Arg761. We also corroborate the relevance of residues Arg761 and Tyr764 for AR dimerization and function. Together, our results reveal allosteric coupling of AR dimerization and posttranslational modifications as a disease mechanism with implications for precision medicine.

Improving Trunk Postural Control Facilitates Walking in Children With Cerebral Palsy: A Pilot Study.

OBJECTIVE: The aim of this study is to determine the effects of bilateral trunk support during walking on trunk and leg kinematics and neuromuscular responses in children with cerebral palsy. DESIGN: Fourteen children with spastic cerebral palsy (Gross Motor Function Classification System level I to III) participated in this study. Children walked on a treadmill under four different conditions, that is, without support (Baseline), with bilateral support applied to the upper trunk (upper trunk support), the lower trunk (lower trunk support), and combined upper and lower trunk (combined trunk support). The trunk and leg kinematics and muscle activity were recorded. RESULTS: Providing bilateral support to the trunk had a significant impact on the displacement of the pelvis and trunk ( P < 0.003) during walking. Children's weaker leg showed greater step length ( P = 0.032) and step height ( P = 0.012) in combined trunk support compared with baseline and greater step length in upper trunk support ( P = 0.02) and combined trunk support ( P = 0.022) compared with lower trunk support. Changes in soleus electromyographic activity during stance phase of gait mirrored the changes in step length across all conditions. CONCLUSIONS: Providing bilateral upper or combined upper and lower trunk support during walking may induce improvements in gait performance, which may be due to improved pelvis kinematics. Improving trunk postural control may facilitate walking in children with cerebral palsy.

Structure-Based Design of Potent Iminosugar Inhibitors of Endoplasmic Reticulum α-Glucosidase I with Anti-SARS-CoV-2 Activity.

Enveloped viruses depend on the host endoplasmic reticulum (ER) quality control (QC) machinery for proper glycoprotein folding. The endoplasmic reticulum quality control (ERQC) enzyme α-glucosidase I (α-GluI) is an attractive target for developing broad-spectrum antivirals. We synthesized 28 inhibitors designed to interact with all four subsites of the α-GluI active site. These inhibitors are derivatives of the iminosugars 1-deoxynojirimycin (1-DNJ) and valiolamine. Crystal structures of ER α-GluI bound to 25 1-DNJ and three valiolamine derivatives revealed the basis for inhibitory potency. We established the structure-activity relationship (SAR) and used the Site Identification by Ligand Competitive Saturation (SILCS) method to develop a model for predicting α-GluI inhibition. We screened the compounds against SARS-CoV-2 in vitro to identify those with greater antiviral activity than the benchmark α-glucosidase inhibitor UV-4. These host-targeting compounds are candidates for investigation in animal models of SARS-CoV-2 and for testing against other viruses that rely on ERQC for correct glycoprotein folding.