Coat Protein Mutations That Alter the Flux of Morphogenetic Intermediates through the ϕX174 Early Assembly Pathway.

Two scaffolding proteins orchestrate ϕX174 morphogenesis. The internal scaffolding protein B mediates the formation of pentameric assembly intermediates, whereas the external scaffolding protein D organizes 12 of these intermediates into procapsids. Aromatic amino acid side chains mediate most coat-internal scaffolding protein interactions. One residue in the internal scaffolding protein and three in the coat protein constitute the core of the B protein binding cleft. The three coat gene codons were randomized separately to ascertain the chemical requirements of the encoded amino acids and the morphogenetic consequences of mutation. The resulting mutants exhibited a wide range of recessive phenotypes, which could generally be explained within a structural context. Mutants with phenylalanine, tyrosine, and methionine substitutions were phenotypically indistinguishable from the wild type. However, tryptophan substitutions were detrimental at two sites. Charged residues were poorly tolerated, conferring extreme temperature-sensitive and lethal phenotypes. Eighteen lethal and conditional lethal mutants were genetically and biochemically characterized. The primary defect associated with the missense substitutions ranged from inefficient internal scaffolding protein B binding to faulty procapsid elongation reactions mediated by external scaffolding protein D. Elevating B protein concentrations above wild-type levels via exogenous, cloned-gene expression compensated for inefficient B protein binding, as did suppressing mutations within gene B. Similarly, elevating D protein concentrations above wild-type levels or compensatory mutations within gene D suppressed faulty elongation. Some of the parental mutations were pleiotropic, affecting multiple morphogenetic reactions. This progressively reduced the flux of intermediates through the pathway. Accordingly, multiple mechanisms, which may be unrelated, could restore viability.IMPORTANCE Genetic analyses have been instrumental in deciphering the temporal events of many biochemical pathways. However, pleiotropic effects can complicate analyses. Vis-à-vis virion morphogenesis, an improper protein-protein interaction within an early assembly intermediate can influence the efficiency of all subsequent reactions. Consequently, the flux of assembly intermediates cumulatively decreases as the pathway progresses. During morphogenesis, ϕX174 coat protein participates in at least four well-defined reactions, each one characterized by an interaction with a scaffolding or structural protein. In this study, genetic analyses, biochemical characterizations, and physiological assays, i.e., elevating the protein levels with which the coat protein interacts, were used to elucidate pleiotropic effects that may alter the flux of intermediates through a morphogenetic pathway.

Spinal meningioma and factors predictive of post-operative deterioration.

PURPOSE: Spinal meningiomas are slow-growing intradural-extramedullary tumors. They are usually associated with good outcomes. However, there are few descriptions of factors predictive of impaired evolution. Our objective was to identify predictive factors of post-operative deterioration as well as outcomes at follow-up. METHODS: Between 2009 and 2016, 87 patients had surgery for spinal meningioma in our referral center. Clinical presentation, management and outcomes were reported during the post-operative period and at 3-month follow-up. Evaluation was based on post-operative neurological deterioration defined as an increase of at least one point in the McCormick score compared to the status at admission. RESULTS: During the study period, post-operative deterioration occurred in 17 patients (19.5%). Risk factors associated with this deterioration were the absence of pre-operative neurological signs (Relative Risk; RR = 2.38, p = 0.04), an anterior location of the meningioma and a grade 2 meningioma on WHO classification score (RR = 6, p ≤ 0.01). At 3-month follow-up, in patients who initially presented with a motor deficit, partial recovery was found in 75%, stability in 20% and a deterioration of their clinical status in 5%. After a mean follow-up of 92.4 ± 51.9 months, the recurrence rate was 8%. CONCLUSIONS: Spinal meningiomas are usually benign tumors whose treatment is based on complete surgical resection. Progress in surgical techniques has resulted in lower morbidity rates and improvement in post-operative recovery. In this study, we observed several factors associated with clinical deterioration. Before surgery, patients should be fully informed of these predictive factors of post-operative deterioration and their association with surgical morbidity.

Enhancing the referral process for surgical management of spinal metastases: insights from a 12-year, bi-institutional study of 533 patients.

Introduction: Delayed surgical management of spinal metastases (SMs) can have detrimental effects on patient survival and quality of life, leading to pain and potential neurological impairment. This study aimed to assess the impact of delayed referral for SMs on clinical outcomes by analyzing patients managed in emergency situations. Methods: We retrospectively reviewed the data of all patients admitted on either emergency or elective basis who underwent surgery for the treatment of neoplastic spine lesions at our two institutions (tertiary referral neurosurgical units) between January 2008 and December 2019. Results: We analyzed 210 elective (EGp) and 323 emergency patients (UGp); emergencies increased significantly over the 12-year period, with a Friday peak (39.3%) and frequent neurological impairment (61.6% vs. 20%). Among the UGp patients, 186 (7.5%) had a previously monitored primitive cancer, including 102 (31.6%) with known SMs. On admission, 71 of the 102 (69.9%) patients presented with neurological deficits. UGp patients were more likely to undergo a single decompression without fixation. Outcomes at the 3-month follow-up were significantly worse for UGp patients ([very] poor, 29.2 vs. 13.8%), and the median overall survival for UGp patients was statistically lower. Risk factors for patients with SM undergoing emergency management included short delay between onset of symptoms and first contact with a spine surgeon, and an initial motor deficit. Conclusion: Many patients with previously identified metastases, including those with neurological deficits, are urgently referred. Optimization is needed in the oncology pathway, and all stakeholders must be made aware of the factors contributing to the improvement in the clinical and radiological identification of potential complications affecting patient survival and quality of life.

Elucidation of the molecular mechanism of the breakage-fusion-bridge (BFB) cycle using a CRISPR-dCas9 cellular model.

Chromosome instability (CIN) is frequently observed in many tumors. The breakage-fusion-bridge (BFB) cycle has been proposed to be one of the main drivers of CIN during tumorigenesis and tumor evolution. However, the detailed mechanisms for the individual steps of the BFB cycle warrants further investigation. Here, we demonstrated that a nuclease-dead Cas9 (dCas9) coupled with a telomere-specific single-guide RNA (sgTelo) can be used to model the BFB cycle. First, we showed that targeting dCas9 to telomeres using sgTelo impeded DNA replication at telomeres and induced a pronounced increase of replication stress and DNA damage. Using Single-Molecule Telomere Assay via Optical Mapping (SMTA-OM), we investigated the genome-wide features of telomeres in the dCas9/sgTelo cells and observed a dramatic increase of chromosome end fusions, including fusion/ITS+ and fusion/ITS-.Consistently, we also observed an increase in the formation of dicentric chromosomes, anaphase bridges, and intercellular telomeric chromosome bridges (ITCBs). Utilizing the dCas9/sgTelo system, we uncovered many novel molecular and structural features of the ITCB and demonstrated that multiple DNA repair pathways are implicated in the formation of ITCBs. Our studies shed new light on the molecular mechanisms of the BFB cycle, which will advance our understanding of tumorigenesis, tumor evolution, and drug resistance.

Targeting the BRCA1/2 deficient cancer with PARP inhibitors: Clinical outcomes and mechanistic insights.

BRCA1 and BRCA2 play a critical role in a variety of molecular processes related to DNA metabolism, including homologous recombination and mediating the replication stress response. Individuals with mutations in the BRCA1 and BRCA2 (BRCA1/2) genes have a significantly higher risk of developing various types of cancers, especially cancers of the breast, ovary, pancreas, and prostate. Currently, the Food and Drug Administration (FDA) has approved four PARP inhibitors (PARPi) to treat cancers with BRCA1/2 mutations. In this review, we will first summarize the clinical outcomes of the four FDA-approved PARPi in treating BRCA1/2 deficient cancers. We will then discuss evidence supporting the hypothesis that the cytotoxic effect of PARPi is likely due to inducing excessive replication stress at the difficult-to-replicate (DTR) genomic regions in BRCA1/2 mutated tumors. Finally, we will discuss the ongoing preclinical and clinical studies on how to combine the PARPi with immuno-oncology drugs to further improve clinical outcomes.

Mustn1 ablation in skeletal muscle results in increased glucose tolerance concomitant with upregulated GLUT expression in male mice.

Glucose homeostasis is closely regulated to maintain energy requirements of vital organs and skeletal muscle plays a crucial role in this process. Mustn1 is expressed during embryonic and postnatal skeletal muscle development and its function has been implicated in myogenic differentiation and myofusion. Whether Mustn1 plays a role in glucose homeostasis in anyway remains largely unknown. As such, we deleted Mustn1 in skeletal muscle using a conditional knockout (KO) mouse approach. KO mice did not reveal any specific gross phenotypic alterations in skeletal muscle. However, intraperitoneal glucose tolerance testing (IPGTT) revealed that 2-month-old male KO mice had significantly lower glycemia than their littermate wild type (WT) controls. These findings coincided with mRNA changes in genes known to be involved in glucose metabolism, tolerance, and insulin sensitivity; 2-month-old male KO mice had significantly higher expression of GLUT1 and GLUT10 transporters, MUP-1 while OSTN expression was lower. These differences in glycemia and gene expression were statistically insignificant after 4 months. Identical experiments in female KO and WT control mice did not indicate any differences at any age. Our results suggest a link between Mustn1 expression and glucose homeostasis during a restricted period of skeletal muscle development/maturation. While this is an observational study, Mustn1's relationship to glucose homeostasis appears to be more complex with a possible connection to other key proteins such as GLUTs, MUP-1, and OSTN. Additionally, our data indicate temporal and sex differences. Lastly, our findings strengthen the notion that Mustn1 plays a role in the metabolic capacity of skeletal muscle.

The Molecular and Cellular Basis of Hutchinson-Gilford Progeria Syndrome and Potential Treatments.

Hutchinson-Gilford progeria syndrome (HGPS) is a rare, autosomal-dominant, and fatal premature aging syndrome. HGPS is most often derived from a de novo point mutation in the LMNA gene, which results in an alternative splicing defect and the generation of the mutant protein, progerin. Progerin behaves in a dominant-negative fashion, leading to a variety of cellular and molecular changes, including nuclear abnormalities, defective DNA damage response (DDR) and DNA repair, and accelerated telomere attrition. Intriguingly, many of the manifestations of the HGPS cells are shared with normal aging cells. However, at a clinical level, HGPS does not fully match normal aging because of the accelerated nature of the phenotypes and its primary effects on connective tissues. Furthermore, the epigenetic changes in HGPS patients are of great interest and may play a crucial role in the pathogenesis of HGPS. Finally, various treatments for the HGPS patients have been developed in recent years with important effects at a cellular level, which translate to symptomatic improvement and increased lifespan.

Mad3 modulates the G1 Cdk and acts as a timer in the Start network.

Cells maintain their size within limits over successive generations to maximize fitness and survival. Sizer, timer, and adder behaviors have been proposed as possible alternatives to coordinate growth and cell cycle progression. Regarding budding yeast cells, a sizer mechanism is thought to rule cell cycle entry at Start. However, while many proteins controlling the size of these cells have been identified, the mechanistic framework in which they participate to achieve cell size homeostasis is not understood. We show here that intertwined APC and SCF degradation machineries with specific adaptor proteins drive cyclic accumulation of the G1 Cdk in the nucleus, reaching maximal levels at Start. The mechanism incorporates Mad3, a centromeric-signaling protein that subordinates G1 progression to the previous mitosis as a memory factor. This alternating-degradation device displays the properties of a timer and, together with the sizer device, would constitute a key determinant of cell cycle entry.

POLDIP3: At the Crossroad of RNA and DNA Metabolism.

POLDIP3 was initially identified as a DNA polymerase delta (Pol δ) interacting protein almost twenty years ago. Intriguingly, it also interacts with proteins involved in a variety of RNA related biological processes, such as transcription, pre-mRNA splicing, mRNA export, and translation. Studies in recent years revealed that POLDIP3 also plays critical roles in disassembling genome wide R-loop formation and activating the DNA damage checkpoint in vivo. Here, we review the functions of POLDIP3 in various RNA and DNA related cellular processes. We then propose a unified model to illustrate how POLDIP3 plays such a versatile role at the crossroad of the RNA and DNA metabolism.

Involvement of transmembrane protein 184a during angiogenesis in zebrafish embryos.

Angiogenesis, the outgrowth of new blood vessels from existing vasculature, is critical during development, tissue formation, and wound healing. In response to vascular endothelial growth factors (VEGFs), endothelial cells are activated to proliferate and move towards the signal, extending the vessel. These events are directed by VEGF-VEGF receptor (Vegfr2) signal transduction, which in turn is modulated by heparan sulfate proteoglycans (HSPGs). HSPGs are glycoproteins covalently attached to HS glycosaminoglycan chains. Transmembrane protein 184a (Tmem184a) has been recently identified as a heparin receptor, which is believed to bind heparan sulfate chains in vivo. Therefore, Tmem184a has the potential to fine-tune interactions between VEGF and HS, modulating Vegfr2-dependent angiogenesis. The function of Tmem184a has been investigated in the regenerating zebrafish caudal fin, but its role has yet to be evaluated during developmental angiogenesis. Here we provide insights into how Tmem184a contributes to the proper formation of the vasculature in zebrafish embryos. First, we find that knockdown of Tmem184a causes a reduction in the number of intact intersegmental vessels (ISVs) in the zebrafish embryo. This phenotype mimics that of vegfr2b knockout mutants, which have previously been shown to exhibit severe defects in ISV development. We then test the importance of HS interactions by removing the binding domain within the Tmem184a protein, which has a negative effect on angiogenesis. Tmem184a is found to act synergistically with Vegfr2b, indicating that the two gene products function in a common pathway to modulate angiogenesis. Moreover, we find that knockdown of Tmem184a leads to an increase in endothelial cell proliferation but a decrease in the amount of VE-cadherin present. Together, these findings suggest that Tmem184a is necessary for ISVs to organize into mature, complete vessels.

Application of a Non-Isothermal Numerical-Analytical Model to Determine the Kinetics of Austenite Formation in a Silicon Alloyed Steel.

A non-isothermal transformation model was proposed to determine the austenite formation kinetics in a steel alloyed with 2.6% wt. Si by dilatometric analysis, considering that the nucleation mechanism does not change with the heating rate. From the dilatometric analysis, it was observed that the austenite formation occurs in two stages; critical temperatures, degree and austenite formation rate were determined. The activation energies associated with each of the stages were obtained employing the Kissinger method (226.67 and 198.37 kJ·mol-1 for the first and second stage) which was used in concert with the austenite formation rate in the non-isothermal model as a first approximation, with acceptable results in the second stage, but not in the first due to the activation energies magnitude. Then, the activation energies were adjusted by minimizing the minimal squares error between estimated and experimental austenite formation degree, obtaining values of 158.50 kJ·mol-1 for the first and 165.50 kJ·mol-1 for the second stage. These values are consistent with those reported for the diffusion of carbon in austenite-FCC in silicon steels. With these activation energies it was possible to predict the austenite formation degree with a better level of convergence when implementing the non-isothermal model.

Stress granules display bistable dynamics modulated by Cdk.

Stress granules (SGs) are conserved biomolecular condensates that originate in response to many stress conditions. These membraneless organelles contain nontranslating mRNAs and a diverse subproteome, but our knowledge of their regulation and functional relevance is still incipient. Here, we describe a mutual-inhibition interplay between SGs and Cdc28, the budding yeast Cdk. Among Cdc28 interactors acting as negative modulators of Start, we have identified Whi8, an RNA-binding protein that localizes to SGs and recruits the mRNA of CLN3, the most upstream G1 cyclin, for efficient translation inhibition and Cdk inactivation under stress. However, Whi8 also contributes to recruiting Cdc28 to SGs, where it acts to promote their dissolution. As predicted by a mutual-inhibition framework, the SG constitutes a bistable system that is modulated by Cdk. Since mammalian cells display a homologous mechanism, we propose that the opposing functions of specific mRNA-binding proteins and Cdk's subjugate SG dynamics to a conserved hysteretic switch.

Overarching themes from ACS-AEI accreditation survey best practices 2011-2019.

The American College of Surgeons launched the Accredited Education Institutes (ACS-AEIs) in 2005 to create a network of simulation centers to offer the highest-quality surgical education and training and to pursue cutting-edge scholarship. Specific standards and criteria were developed to accredit simulation centers, and decisions made based on the application, site surveyor visit, and ACS-AEI Accreditation Committee review. In addition to granting accreditation and providing recommendations for improvement, site surveyors and the Accreditation Committee identified best practices defined as areas far exceeding the accreditation standards or novel methods of advancing high-quality, impactful education. Best practices were compiled into a list starting in 2011 for dissemination to all members of the ACS-AEI Consortium through on-line videos, newsletters, and workshops at the Annual ACS Surgical Simulation Summit. Using thematic analysis, the authors classified common themes from the 337 best practices identified during 247 accreditation reviews between June 2011 and June 2019. As best practices were extracted, the authors compiled them into a single database. Eight overarching themes were identified, including approaches to faculty development, scholarly activity, development of curricula, use of resources, delivery of educational content, assessment of learners, and collaboration between centers. The authors discuss themes in the context of their practical relevance and highlight strategies used at different centers, with an emphasis on the importance of each theme in developing a successful simulation program.

Impact of assessment of bone status before corrective surgery of lumbar spine in patients over 50 years old.

Background and objective: There is absence of data on the prevalence of osteoporosis before corrective surgery of the lumbar spine. We do not know the impact of bone assessment before corrective spine surgery, regarding the prevalence of osteoporosis, risk factors for osteoporosis, and prescription of osteoporotic treatment. Our objective was to evaluate the impact of assessment of bone status before corrective surgery of the lumbar spine. Methods: This retrospective study was conducted over a period of 30 months. Patients included were over 50 years old and had been referred to rheumatology consultation prior to corrective surgery of the lumbar spine with osteosynthesis, for scoliosis or spondylolisthesis. Assessment of bone status consisted in looking for risk factors for osteoporotic fracture, performing bone densitometry with the calculation of TBS (trabecular bone score) and the possible introduction of treatment for osteoporosis. Data were collected on complications related to bone fragility during follow-up. Results: Twenty-eight patients with a median age of 71.2 years (55.5-84.8) were included; 89% were women. T score was <-2.5 in 14.3% (4/28) and -1 to -2.5 in 42.9% (12/28) on at least one of the three sites analyzed. Fifty percent of patients had a TBS <1.2, a history of more than four falls per year, a duration of more than 20 s in the Timed Up and Go Test, and/or sedation treatment. Vitamin-calcium supplementation and treatment for osteoporosis were prescribed in 71.4% and 17.8% of cases, respectively. During follow-up, 3 patients had one or more osteoporotic vertebral fractures and 4 patients had loosening of implanted devices. Conclusion: Despite a low prevalence of densitometric osteoporosis and therapeutic management, one in four patients had a bone complication, suggesting the superiority of TBS as an indicator of bone status.

Posterior C1C2 harms fusion with 3D surgical navigation.

Several types of atlantoaxial instability can justify surgical fixation. The instrumented fusion procedure described by Harms with screw fixation of the C1 lateral masses and C2 pedicles is a demanding technique that provides lasting stabilization. However, it has been associated with nerve and vascular complications due to the local anatomical configuration. Surgical navigation systems can help improve the procedure's accuracy. We describe a series of 11 cases of C1C2 Harms fusion performed with surgical navigation and intraoperative 3D imaging checks. All procedures were carried out completely with satisfactory implant placement. There were no adverse events related to the procedure during the peri-operative period. No cortical breach was detected using cone-beam CT at the end of the procedure. The technical challenges and risks associated with C1C2 Harms fusion have led to the use of 3D intraoperative imaging systems, when available.

Terapia antiviral de acción directa para infección del virus de hepatitis C en pacientes en hemodiálisis

Introducción: La infección por el virus C de la hepatitis resulta común en pacientes en hemodiálisis y se considera endémica en estas unidades. El tratamiento utilizado lo componían el interferón pegilado y la ribavirina, combinación que presentaba niveles de toxicidad y baja respuesta. Las drogas actuales aportan mejores resultados. Objetivos: Determinar la eficacia y seguridad de la terapia antiviral de acción directa para la infección del virus de la hepatitis C en pacientes con insuficiencia renal crónica en hemodiálisis. Métodos: Estudio descriptivo prospectivo en 19 pacientes en régimen de hemodiálisis y con infección por virus C, pertenecientes al Hospital General Docente "Dr. Mario Muñoz Monroy", desde diciembre de 2020 hasta septiembre de 2021," A todos se les prescribió durante 12 semanas Sofosbuvir® 400 mg más Daclatasvir® 60 mg diarios. Se caracterizaron las variables edad, sexo, fibrosis hepática por el índice aspartato-aminotransferasa/plaquetas, reacciones adversas y respuesta viral 12 semanas después del tratamiento. Resultados: La infección predominó en el grupo de 51 a 60 años (36,84 %). La mayoría de los pacientes mostró un índice aspartato-aminotransferasa/plaquetas ≤ 0,5, lo que correspondió con ausencia de fibrosis hepática significativa (14 pacientes). Una minoría de pacientes registró reacciones adversas. No se demostró toxicidad cardiovascular ni hepática. La totalidad de los pacientes manifestaron carga viral no detectable 12 semanas después del tratamiento. Conclusiones: La combinación de Sofosbuvir® con Daclatasvir® para el tratamiento de la infección por virus de la hepatitis C en pacientes con insuficiencia renal crónica en tratamiento de hemodiálisis resultó eficaz, bien tolerada y segura.

Introduction: Hepatitis C virus infection is common in hemodialysis patients and is considered endemic in these units. The treatment used consisted of pegylated interferon and ribavirin, a combination that presented levels of toxicity and low response. Current drugs bring better results. Objectives: To determine the efficacy and safety of direct-acting antiviral therapy for hepatitis C virus infection in patients with chronic renal failure on hemodialysis. Methods: Prospective descriptive study in 19 patients on hemodialysis and with virus C infection, belonging to "Dr. Mario Muñoz Monroy" Teaching General Hospital, from December 2020 to September 2021. All were prescribed for 12 weeks with Sofosbuvir® 400 mg plus Daclatasvir® 60 mg daily. The variables age, sex, liver fibrosis were characterized by the aspartate aminotransferase/platelet index, adverse reactions and viral response 12 weeks after treatment. Results: Infection predominated in the group of 51 to 60 years (36.84%). Most patients showed an aspartate aminotransferase/platelet ratio ≤ 0.5, corresponding to the absence of significant liver fibrosis (14 patients). A minority of patients reported adverse reactions. No cardiovascular or hepatic toxicity was demonstrated. All patients had an undetectable viral load 12 weeks after treatment. Conclusions: The combination of Sofosbuvir® with Daclatasvir® for the treatment of hepatitis C virus infection in patients with chronic renal failure undergoing hemodialysis was effective, well tolerated and safe.

Conocimiento sobre primeros auxilios en estudiantes de la carrera Profesor de Educación Física de la Universidad de Tarapacá / Knowledge about first aid in students of the Professor of Physical Education career at the University of Tarapacá / Conhecimento de primeiros socorros nos alunos do curso de Professor de Educação Física da Universidade de Tarapacá, Chile

Resumen: Introducción: Evaluar el conocimiento (saber) sobre primeros auxilios (PA) en estudiantes de la carrera Profesor de Educación Física de la Universidad de Tarapacá, comparando el centro de estudios de procedencia y el género del alumnado. Metodología: Se efectuó un estudio mixto, con variables cualitativas y cuantitativas, en el que se indagó sobre el conocimiento en primeros auxilios en estudiantes de la carrera Profesor de Educación Física de la Universidad de Tarapacá. Se evaluó a 169 estudiantes, 99 con ingresos procedentes del Centro de Formación Técnica Tarapacá y 70 con incorporación a partir de la Prueba de Selección Universitaria. Se aplicó una encuesta, validada por criterio experto, que investigó sobre el conocimiento (saber) en relación con primeros auxilios. Se utilizó un pretest y, posteriormente, se intervino con un curso formativo teórico-práctico en primeros auxilios. Al finalizar el curso, se efectuó un postest, que tuvo como finalidad comprobar los conocimientos adquiridos sobre primeros auxilios. Resultados: Se observó que los hombres mostraron mayor conocimiento durante el pretest y el postest, con un 95.1 % y un 100 %, respectivamente, mientras que las mujeres registraron un 75 % en el pretest y 90.1 % en el postest. Por otro lado, el alumnado procedente del Centro de Formación Técnica mantuvo indicadores superiores en ambos análisis. Conclusiones: Los conocimientos adquiridos en enseñanza intermedia, así como la realización de cursos iniciales relacionados con primeros auxilios, favorecen la preparación del futuro profesorado de educación física, lo que conlleva un mejor accionar ante situaciones de emergencia, tanto en las escuelas como en la vida cotidiana.

Abstract: Introduction: To evaluate the knowledge (knowledge) about first aid (PA) in students of the Physical Education Professor career at the University of Tarapacá, comparing the study center of origin and the gender of the students. Methodology: A mixed study was carried out, with qualitative and quantitative variables, inquiring about knowledge in first aid in students of the Physical Education Professor Career, University of Tarapacá. 169 students were evaluated, 99 with income from the Tarapacá Technical Training Center and 70 incorporated from the University Selection Test. A survey was applied, validated by expert criteria, inquiring about knowledge (knowledge) in relation to first aid. A pre-test was used and subsequently a theoretical-practical training course in first aid was intervened. At the end of the course, a post-test was carried out, which the purpose of verifying the knowledge had acquired about first aid. Results: It was observed that the men showed greater knowledge during the pre-test and the post-test, with 95.1% and 100% respectively, while the women showed 75% in the pre-test and 90.1% in the post-test. On the other hand, students from the Technical Training Center maintained higher indicators in both analyses. Conclusions: The knowledge acquired in intermediate education, as well as the completion of initial courses related to first aid, favor the preparation of future Physical Education teachers, which leads to better actions in emergency situations, both in schools and in life everyday.

Resumo: Introdução: Avaliar o conhecimento sobre primeiros socorros (PS) dos estudantes da carreira de Professor de Educação Física da Universidade de Tarapacá, Chile, comparando o centro de estudos de origem e o gênero dos estudantes. Metodologia: Foi realizado um estudo misto, com variáveis qualitativas e quantitativas, no qual foram investigados conhecimentos sobre primeiros socorros em estudantes da carreira de Professor de Educação Física da Universidade de Tarapacá. O estudo avaliou 169 alunos, 99 provenientes do Centro de Treinamento Técnico de Tarapacá, e 70 que passaram no exame de admissão. Foi realizada uma pesquisa validada por especialistas, perguntando sobre os conhecimentos em relação aos primeiros socorros. Um pré-teste foi aplicado e, posteriormente, um curso teórico-prático de treinamento em primeiros socorros foi ministrado. Ao final do curso, foi realizado um pós-teste com o objetivo de verificar os conhecimentos adquiridos nos primeiros socorros. Resultados: Foi observado que os homens mostraram maiores conhecimentos durante o pré-teste e o pós-teste, com 95,1% e 100% respectivamente, enquanto as mulheres mostraram 75% no pré-teste e 90,1% no pós-teste. Por outro lado, os estudantes do Centro de Treinamento Técnico mantiveram indicadores mais elevados em ambas as análises. Conclusões: Os conhecimentos adquiridos no ensino médio, assim como a conclusão dos cursos iniciais de primeiros socorros, favorecem a preparação dos futuros professores de Educação Física, o que leva a melhores ações em situações de emergência, tanto nas escolas como na vida cotidiana.

Dilemas bioéticos en el desempeño del médico de la familia en la pesquisa del cáncer colorrectal

Introducción: La calidad del desempeño profesional determina la resolución de problemas de salud pública como el cáncer colorrectal a través de su pesquisa poblacional, en cuya realización, como en toda práctica médica, surgen dilemas bioéticos. Objetivo: Caracterizar los principales dilemas bioéticos en la realización de la pesquisa poblacional del cáncer colorrectal en la atención primaria. Materiales y métodos: Estudio descriptivo transversal en 19 médicos de la familia, seleccionados por muestreo simple aleatorio mediante la aplicación de un cuestionario en proceso de validación a través de criterio de expertos y coeficiente alfa de Cronbach. La variable estudiada fue "dilemas bioéticos en la realización de la pesquisa poblacional del cáncer colorrectal", parametrizada en dos dimensiones: valorativa y cognitiva, con cinco y tres indicadores respectivamente. Resultados: El "dilema por temor a realizarse la colonoscopia" fue considerado el de mayor peso, al ser evaluado por 13 médicos (68,4 %) como Muy Importante. El indicador "conocimiento profesional sobre bioética" fue evaluado por la mayoría de los profesionales dentro de los dos niveles superiores de la escala de Likert: cinco médicos (26,3 %) eligieron la categoría Importante, e igual número la de Muy Importante. Conclusiones: Los principales dilemas bioéticos a que se enfrentan los médicos de la familia en su desempeño profesional durante la realización de la pesquisa poblacional del cáncer colorrectal, están caracterizados por las actitudes que asumen los pacientes en relación con la disyuntiva que presupone la realización de la colonoscopia, con sus potenciales riesgos ante un resultado positivo.

Introduction: The quality of professional performance determines the resolution of public health problems such as colorectal cancer through population screening, in whose implementation, as in every medical practice, bioethical dilemmas arise. Objective: To characterize the main bioethical dilemma in carrying out population screening for colorectal cancer in primary care. Materials and methods: Cross-sectional, descriptive study in 19 family physicians, selected by simple random sampling, by application of a questionnaire in the process of validation through expert criteria and Cronbach alpha coefficient. The variable studied was "bioethical dilemmas in carrying out population screening for colorectal cancer" parameterized in two dimensions: evaluative and cognitive, with 5 and 3 indicators respectively. Results: The "dilemma for fear of having a colonoscopy" was considered the most important, being evaluated by 13 doctors/68.4% as Very Important; The indicator "professional knowledge about bioethics" was evaluated by the majority of professionals within the two upper levels of the Likert scale, 5 doctors (26.3%) chose the category of Important and an equal number the category of Very Important. Conclusions: The main bioethical dilemmas that family doctors face in their professional performance during population screening for colorectal cancer are characterized by the attitudes that patients assume in relation to the dilemma that presupposes performing colonoscopy with its potential risks to a positive result.

Nivelación propedéutica y rendimiento académico en la Universidad Bernardo O'Higgins de Chile / Preparatory leveling and academic performance in Bernardo O'Higgins University of Chile

Introducción: Esta investigación presenta los resultados preliminares del plan de Nivelación académica de la Universidad Bernardo O´Higgins, realizado en 2018 y denominado Nivelación Cero. Este proyecto es parte de la estrategia institucional, diseñada como una extensión del programa de nivelación de la universidad, para apoyar a los estudiantes nuevos en el repaso de contenidos escolares y estrategias de autogestión, para afrontar las exigencias del primer año de estudios. Objetivo: Exponer en qué medida un plan de acompañamiento propedéutico contribuye con la mejora del rendimiento en los estudiantes de nuevo ingreso. Métodos: En marzo de 2018 se llevó a cabo un estudio comparativo basado en un análisis estadístico multivariado (hj-Biplot), sobre los resultados obtenidos en la aprobación semestral general y en las asignaturas críticas de la formación, situados en el primer semestre de carrera. Resultado: La aplicación del programa de Nivelación Cero en el primer semestre de 2018 determinó de forma positiva la cantidad de aprobación en materias críticas de la carrera elegida. Conclusiones: Esta experiencia da cuenta de la importancia que tiene la realización de procesos de nivelación, tendientes a hacer del sistema universitario un espacio que promueva la equidad(AU)

ABSTRACT Introduction: This research presents the preliminary results of Bernardo O'Higgins University's academic leveling plan, carried out in 2018 and called "Nivelación Cero" [Zero Leveling]. This project is part of the institutional strategy designed as an extension of the university's leveling program, in order to support new students in reviewing school content and regarding self-management strategies, to face the demands of the first academic year. Objective: To expose to what extent a preparatory support plan contributes to improving the performance of new students. Methods: In March 2018, a comparative study was carried out based on a multivariate statistical analysis (hj-Biplot), on the results obtained in the general semester completion qualification as well as in the critical subjects of the training, located in the first semester of the major. Results: The application of the "Nivelación Cero" program in the first semester of 2018 positively determined the amount of completion qualification in critical subjects of the chosen major. Conclusions: This experience shows the importance of carrying out leveling processes, aimed at making the university system a space that promotes equity.

A monoclonal antibody against NeuGc-containing gangliosides contains a regulatory idiotope involved in the interaction with B and T cells.

P3 (IgM-kappa) is a monoclonal antibody (mAb) reacting with N-glycolyl neuraminic acid (NeuGc)-containing gangliosides and sulfated glycolipids. To explore the nature of the idiotope defined by 1E10, we used a phage-displayed random peptide library. After three rounds of selection, seven different phagotopes were isolated. Noteworthy, all the sequences were found to bear the basic amino acid-rich motifs KPPR (3) or RRPR/K (4). This recursive selection of basic sequences by 1E10 mAb confirmed previous suggestions of the involvement of charged residues in the interaction between gamma-type Ab2 and P3 mAb. The binding of 1E10 to phage peptides representing each group was completely inhibited by P3 mAb. In addition, other Ab2 to P3 were able to recognize these peptides. Thus, phage peptides seem to be mimotopes of the idiotope recognized by anti-idiotypic antibodies in P3. Phage motifs were represented in the lineal sequence of P3's heavy chain H-CDR3 and a 14-mer peptide representing this region was able to specifically inhibit 1E10 binding to P3. Previous studies showed that P3's idiotype was autoimmunogenic and shared by antibodies with different specificities. Now, we demonstrated that P3 mAb is able to activate a network cascade involving autologous anti-idiotypic and anti-anti-idiotypic T cells. Thus, P3's idiotype fulfill the three criteria previously established to define a "regulatory idiotype". Particularly, data presented here revealed the immunodominance of the H-CDR3 of this mAb as a T cell epitope. Thus, H-CDR3 is simultaneously involved in the interaction of P3 mAb with anti-idiotypic B and T cells, behaving as a potential regulatory idiotope.