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El siguiente manuscrito nos menciona dando a conocer la baja productividad de los estudiantes y profesionales de la carrera de enfermeria en investigación, la atencion de enfermeria debe estar justificada por evidencia científica por ello es importante que respalden sus intervenciones. Teniendo como referencia tambien a Brasil un pilar en investigacion con sus trabajos de conocimiento con responsabilidad y compromiso ético, pese a ello se denota la bajas en cifras estadisticas relacionadas a investigacion con respecto a años anteriores en la producción científica en enfermería ha aumentado en los últimos años. Sin embargo, persisten desafíos en el desarrollo de talento investigador calificado.

IntroductionOur understanding of HIV-associated gut microbial dysbiosis in children perinatally-infected with HIV (CLWH) lags behind that of adults living with HIV. Childhood represents a critical window for the gut microbiota. Any disturbances, including prolonged exposure to HIV, antiretroviral drugs, and antibiotics are likely to have a significant impact on long-term health, resulting in a less resilient gut microbiome. The objective of our study was to characterize the gut microbiota in CLWH, and compare it with HIV-unexposed and -uninfected children.MethodsWe enrolled 31 children aged 3 to 15 years; 15 were CLWH and 16 were HUU. We assessed dietary patterns and quality; quantified soluble and cellular markers of HIV disease progression by flow cytometry, enzyme-linked immunosorbent and multiplex-bead assays, and profiled the gut microbiota by 16S rRNA sequencing. We explored relationships between the gut microbiota, antibiotic exposure, dietary habits, soluble and cellular markers and host metadata.ResultsChildren had a Western-type diet, their median health eating index score was 67.06 (interquartile range 58.76-74.66). We found no discernable impact of HIV on the gut microbiota. Alpha diversity metrics did not differ between CLWH and HUU. Sex impacted the gut microbiota (R-squared= 0.052, PERMANOVA p=0.024). Male children had higher microbial richness compared with female children. Two taxa were found to discriminate female from male children independently from HIV status: Firmicutes for males, and Bacteroides for females. Markers of HIV disease progression were comparable between CLWH and HUU, except for the frequency of exhausted CD4+ T cells (PD-1+) which was increased in CLWH (p=0.0024 after adjusting for confounders). Both the frequency of exhausted CD4+ and activated CD4+ T cells (CD38+ HLADR+) correlated positively with the relative abundance of Proteobacteria (rho=0.568. false discovery rate (FDR)-adjusted p= 0.029, and rho=0.62, FDR-adjusted p=0.0126, respectively).ConclusionThe gut microbiota of CLWH appears similar to that of HUU, and most markers of HIV disease progression are normalized with long-term ART, suggesting a beneficial effect of the latter on the gut microbial ecology. The relationship between exhausted and activated CD4+ T cells and Proteobacteria suggests a connection between the gut microbiome, and premature aging in CLWH.

Abstract Background The 2020 pandemic of SARS-CoV-2 causing COVID-19 disease is an unprecedented global emergency. COVID-19 appears to be a disease with an early phase where the virus replicates, coinciding with the first presentation of symptoms, followed by a later ‘inflammatory’ phase which results in severe disease in some individuals. It is known from other rapidly progressive infections such as sepsis and influenza that early treatment with antimicrobials is associated with a better outcome. The hypothesis is that this holds for COVID-19 and that early antiviral treatment may prevent progression to the later phase of the disease. Methods Trial design: Phase IIA randomised, double-blind, 2 × 2 design, placebo-controlled, interventional trial. Randomisation: Participants will be randomised 1:1 by stratification, with the following factors: gender, obesity, symptomatic or asymptomatic, current smoking status presence or absence of comorbidity, and if the participant has or has not been vaccinated. Blinding: Participants and investigators will both be blinded to treatment allocation (double-blind). Discussion We propose to conduct a proof-of-principle placebo-controlled clinical trial of favipiravir plus or minus nitazoxanide in health workers, their household members and patients treated at the Mexican Social Security Institute (IMSS) facilities. Participants with or without symptomatic COVID-19 or who tested positive will be assigned to receive favipiravir plus nitazoxanide or favipiravir plus nitazoxanide placebo. The primary outcome will be the difference in the amount of virus (‘viral load’) in the upper respiratory tract after 5 days of therapy. Secondary outcomes will include hospitalization, major morbidity and mortality, pharmacokinetics, and impact of antiviral therapy on viral genetic mutation rate. If favipiravir with nitazoxanide demonstrates important antiviral effects without significant toxicity, there will be a strong case for a larger trial in people at high risk of hospitalization or intensive care admission, for example older patients and/or those with comorbidities and with early disease. Trial registration ClinicalTrials.gov NCT04918927 . Registered on June 9, 2021.

El aprendizaje es un proceso complejo mediante el cual se convierte información y experiencia en conocimientos, habilidades, comportamientos y actitudes. Hay varias teorías de aprendizaje que ayudan a explicar cómo se aprende. Este artículo explora diferentes definiciones de aprendizaje, los temas fundamentales para las teorías de aprendizaje, el papel que desempeña la memoria, el papel de la motivación, como ocurre la trasferencia, los procesos de autorregulación, los tipos de aprendizaje significativo, y un análisis breve de distintos estilos y modelos de aprendizaje; Cada rol sirve como un medio para lograr resultados de aprendizaje. Algunos maestros utilizan una variedad de estilos de enseñanza (experto, formal, autoridad, facilitador y delegado de modelo personal), mientras que otros se basan en las mismas técnicas probadas y comprobadas. Sin embargo, el método de enseñanza más efectivo implica cambiar el estilo de enseñanza de los alumnos para adaptarlos a la situación y las necesidades individuales. Se ha demostrado la importancia del comportamiento de la enseñanza y los diversos estilos de enseñanza y los beneficios previstos en el aprendizaje de los estudiantes.

Inés Velázquez-Quesada,1,2 Angel J Ruiz-Moreno,1,3,4 Diana Casique-Aguirre,1 Charmina Aguirre-Alvarado,1 Fabiola Cortés-Mendoza,1,5 Marisol de la Fuente-Granada,6 Carlos García-Pérez,7 Sonia M Pérez-Tapia,2,8 Aliesha González-Arenas,6 Aldo Segura-Cabrera,9 Marco A Velasco-Velázquez1,10 1Department of Pharmacology, School of Medicine, Universidad Nacional Autónoma de México, Mexico City, Mexico; 2Research and Development in Bioprocess Unit, National School of Biological Sciences, Instituto Politécnico Nacional, Mexico City, Mexico; 3Graduate Program in Biomedical Sciences, Universidad Nacional Autónoma de México, Mexico City, Mexico; 4Department of Drug Design, Graduate School of Science and Engineering, University of Groningen (RUG), Groningen, The Netherlands; 5Graduate Program in Biochemical Sciences, Universidad Nacional Autónoma de México, Mexico City, Mexico; 6Department of Genomic Medicine and Environmental Toxicology, Institute for Biomedical Research, Universidad Nacional Autónoma de México, Mexico City, Mexico; 7Center for Genomic Biotechnology, Instituto Politécnico Nacional, Reynosa, Tamaulipas, Mexico; 8National Laboratory for Specialized Services of Investigation, Development and Innovation (I+D+i) for Pharma Chemicals and Biotechnological Products, LANSEIDI-FarBiotec-CONACyT, Mexico City, Mexico; 9European Molecular Biology Laboratory, European Bioinformatics Institute, Hinxton, UK; 10Peripherical Unit for Research in Translational Biomedicine, School of Medicine, Universidad Nacional Autónoma de México, Mexico City, MexicoCorrespondence: Marco A Velasco-VelázquezSchool of Medicine, Universidad Nacional Autónoma de México, Circuito Interno s/n, Mexico City 04510, MexicoTel/Fax +52 55 5623 2282Email marcovelasco@unam.mxIntroduction: Cancer stem cells (CSCs) drive the initiation, maintenance, and therapy response of breast tumors. CD49f is expressed in breast CSCs and functions in the maintenance of stemness. Thus, blockade of CD49f is a potential therapeutic approach for targeting breast CSCs. In the present study, we aimed to repurpose drugs as CD49f antagonists.Materials and Methods: We performed consensus molecular docking using a subdomain of CD49f that is critical for heterodimerization and a collection of pharmochemicals clinically tested. Molecular dynamics simulations were employed to further characterize drug-target binding. Using MDA-MB-231 cells, we evaluated the effects of potential CD49f antagonists on 1) cell adhesion to laminin; 2) mammosphere formation; and 3) cell viability. We analyzed the effects of the drug with better CSC-selectivity on the activation of CD49f-downstream signaling by Western blot (WB) and co-immunoprecipitation. Expressions of the stem cell markers CD44 and SOX2 were analyzed by flow cytometry and WB, respectively. Transactivation of SOX2 promoter was evaluated by luciferase reporter assays. Changes in the number of CSCs were assessed by limiting-dilution xenotransplantation.Results: Pranlukast, a drug used to treat asthma, bound to CD49f in silico and inhibited the adhesion of CD49f+ MDA-MB-231 cells to laminin, indicating that it antagonizes CD49f-containing integrins. Molecular dynamics analysis showed that pranlukast binding induces conformational changes in CD49f that affect its interaction with β 1-integrin subunit and constrained the conformational dynamics of the heterodimer. Pranlukast decreased the clonogenicity of breast cancer cells on mammosphere formation assay but had no impact on the viability of bulk tumor cells. Brief exposure of MDA-MB-231 cells to pranlukast altered CD49f-dependent signaling, reducing focal adhesion kinase (FAK) and phosphatidylinositol 3-kinase (PI3K) activation. Further, pranlukast-treated cells showed decreased CD44 and SOX2 expression, SOX2 promoter transactivation, and in vivo tumorigenicity, supporting that this drug reduces the frequency of CSC.Conclusion: Our results support the function of pranlukast as a CD49f antagonist that reduces the CSC population in triple-negative breast cancer cells. The pharmacokinetics and toxicology of this drug have already been established, rendering a potential adjuvant therapy for breast cancer patients.Keywords: CD49f, alpha6 integrin, breast cancer stem cells, pranlukast, drug repositioning, triple-negative breast cancer cells

Background: The 5α-reductase type 2 deficiency (5α-RD2) is a specific form of disorder of sexual development (DSD). Pathogenic variants in the SRD5A2 gene, which encodes this enzyme, are responsible for 46,XY DSD.Objective: The objective of the study was to investigate the genetic etiology of 46,XY DSD in two Mexican families with affected children.Materials and methods: The SRD5A2 gene of the parents and affected children was screened in both families via polymerase chain reaction amplification and DNA direct sequencing. The role of genetic variants in enzymatic activity was tested by site-directed mutagenesis.Results: Subject 1 presented two variants: p.Glu197Asp and p.Pro212Arg. Subject 2 was homozygous for the variant p.Glu197Asp. The two variants were reported in early studies. The directed mutagenesis study showed that the p.Glu197Asp and p.Pro212Arg variants lead to a total loss of enzymatic activity and, consequently, abnormal genitalia development in the patients.Conclusion: These results suggest that p.Glu197Asp and p.Pro212Arg are pathogenic variants that lead to the phenotypic expression of DSD. 5α-RD2 is of extreme importance not only because of its frequency (it is rare) but also because of its significance in understanding the mechanism of androgen action, the process of sexual differentiation, and the factors that influence normal sexual behavior.

The appearance of drug-resistant strains of Mycobacterium tuberculosis and the dramatic increase in infection rates worldwide evidences the urgency of developing new and effective compounds for treating tuberculosis. Benzimidazoles represent one possible source of new compounds given that antimycobacterial activity has already been documented for some derivatives, such as those bearing electron-withdrawing groups. The aim of this study was to synthesize two series of benzimidazoles, di- and trisubstituted derivatives, and evaluate their antimycobacterial activity. Accordingly, 5a and 5b were synthesized from hydroxymoyl halides 3a and 3b, and nitro-substituted o-phenylenediamine 4. Compound 11 was synthesized from an aromatic nitro compound, 4-chloro-1,2-phenylenediamine 9, mixed with 3-nitrobenzaldehyde 10, and bentonite clay. Although the synthesis of 11 has already been reported, its antimycobacterial activity is herein examined for the first time. 1,2,5-trisubstituted benzimidazoles 7a, 7b, and 12 were obtained from N-alkylation of 5a, 5b, and 11. All benzimidazole derivatives were characterized by FT-IR, NMR, and HR-MS, and then screened for their in vitro antimycobacterial effect against the M. tuberculosis H37Rv strain. The N-alkylated molecules (7a, 7b, and 12) generated very limited in vitro inhibition of mycobacterial growth. The benzimidazoles (5a, 5b, and 11) showed in vitro potency against mycobacteria, reflected in minimal inhibitory concentration (MIC) values in the range of 6.25–25 μg/mL. Consequently, only the 2,5-disubstituted benzimidazoles were assessed for biological activity on mouse macrophages infected with M. tuberculosis. A good effect was found for the three compounds. The cytotoxicity assay revealed very low toxicity for all the test compounds against the macrophage cell line. According to the docking study, 2,5-disubstituted benzimidazoles exhibit high affinity for an interdomain cleft that plays a key role in the GTP-dependent polymerization of the filamentous temperature-sensitive Z (FtsZ) protein. The ability of different benzimidazoles to impede FtsZ polymerization is reportedly related to their antimycobacterial activity. On the other hand, the 1,2,5-trisubstituted benzimidazoles docked to the N-terminal of the protein, close to the GTP binding domain, and did not show strong binding energies. Overall, 5a, 5b, and 11 proved to be good candidates for in vivo testing to determine their potential for treating tuberculosis.

Purpose: To describe the case of orbital subcutaneous emphysema who was successfully treated with hyperbaric oxygen therapy. Observations: Case report. Retrospective analysis of medical records and computer tomography images. A 40 years-old female, with retinal detachment who was seen at the emergency department, two weeks after undergoing a combined procedure of pars plana vitrectomy, scleral buckle and Sulfur hexafluoride tamponade. The patient complained of pain, decrease eye movement and edema of the upper eyelid. Clinical examination revealed periorbital crepitus. She was treated immediately with soft tissue decompression with small-gauge needle. Orbital emphysema recurred quickly, indicating possible gas trapped in the soft tissue. Using the US NAVY decompression protocol we were able to achieve fast clinical improvement. The protocol was repeated in several occasions until complete resolution. Conclusion and importance: Hyperbaric oxygen therapy is an effective treatment for orbital and periorbital emphysema, due to its property of helping accelerate N2 elimination from adipose tissue.

CATSPER1 gene encodes a pore-forming and pH-sensing subunit of the CatSper Ca2+- permeable channel, a protein in the flagellum essential for sperm hyperactivation. Previous studies have shown that the murine Catsper1 gene promoter is regulated by different Sox proteins. Likewise, it is acknowledged that the human CATSPER1 gene promoter sequence is enriched in potential interaction sites for the sex-determining region Y gene (SRY), which suggest a novel regulatory transcriptional mechanism for CatSper1 channel expression. Therefore, in this work, we sought to determine whether the human CATSPER1 gene expression is regulated by the SRY transcription factor. To this end, a series of deletions and mutations were introduced in the wild- type CATSPER1 gene promoter to eliminate the SRY sites, and the different constructs were tested for their ability to activate transcription in human embryonic kidney and murine spermatogonial germ cell lines (HEK-293 and GC1-spg, respectively) using luciferase assays. In addition, by using a strategy that combines electrophoretic mobility shift assays (EMSA) and chromatin immunoprecipitation (ChIP) we investigated whether the CATSPER1 gene expression is regulated by the SRY transcription factor both in vitro and in vivo. Our results show that the transcriptional factor SRY specifically binds to different sites in the promoter sequence and has the ability to control CATSPER1 gene transcription.

El presente artículo tiene por objetivo discutir en torno a la concepción de responsabilidad como criterio de calidad de las intervenciones con varones que ejercen violencia en contextos de pareja, a la luz de los aportes realizados por la sociología de Bourdieu y el psicoanálisis freudo-lacaniano. Se discute sobre la dimensión volitiva asignada al acto violento, por una parte, y la impronta kantiana con la que se concibe el ideal de asunción de responsabilidad, por otra; lo que tendería a desplazar y velar dimensiones que determinan y posicionan a los sujetos en sus relaciones genéricas. Asimismo, se promueve una concepción de responsabilidad amparada dentro de los marcos de la ética del cuidado, como una dimensión prioritaria en el trabajo con varones.