Transformer-based spatial-temporal detection of apoptotic cell death in live-cell imaging.

Intravital microscopy has revolutionized live-cell imaging by allowing the study of spatial-temporal cell dynamics in living animals. However, the complexity of the data generated by this technology has limited the development of effective computational tools to identify and quantify cell processes. Amongst them, apoptosis is a crucial form of regulated cell death involved in tissue homeostasis and host defense. Live-cell imaging enabled the study of apoptosis at the cellular level, enhancing our understanding of its spatial-temporal regulation. However, at present, no computational method can deliver robust detection of apoptosis in microscopy timelapses. To overcome this limitation, we developed ADeS, a deep learning-based apoptosis detection system that employs the principle of activity recognition. We trained ADeS on extensive datasets containing more than 10,000 apoptotic instances collected both in vitro and in vivo, achieving a classification accuracy above 98% and outperforming state-of-the-art solutions. ADeS is the first method capable of detecting the location and duration of multiple apoptotic events in full microscopy timelapses, surpassing human performance in the same task. We demonstrated the effectiveness and robustness of ADeS across various imaging modalities, cell types, and staining techniques. Finally, we employed ADeS to quantify cell survival in vitro and tissue damage in mice, demonstrating its potential application in toxicity assays, treatment evaluation, and inflammatory dynamics. Our findings suggest that ADeS is a valuable tool for the accurate detection and quantification of apoptosis in live-cell imaging and, in particular, intravital microscopy data, providing insights into the complex spatial-temporal regulation of this process.

Antigen recognition reinforces regulatory T cell mediated Leishmania major persistence.

Cutaneous Leishmania major infection elicits a rapid T cell response that is insufficient to clear residually infected cells, possibly due to the accumulation of regulatory T cells in healed skin. Here, we used Leishmania-specific TCR transgenic mice as a sensitive tool to characterize parasite-specific effector and immunosuppressive responses in vivo using two-photon microscopy. We show that Leishmania-specific Tregs displayed higher suppressive activity compared to polyclonal Tregs, that was mediated through IL-10 and not through disrupting cell-cell contacts or antigen presentation. In vivo expansion of endogenous Leishmania-specific Tregs resulted in disease reactivation that was also IL-10 dependent. Interestingly, lack of Treg expansion that recognized the immunodominant Leishmania peptide PEPCK was sufficient to restore robust effector Th1 responses and resulted in parasite control exclusively in male hosts. Our data suggest a stochastic model of Leishmania major persistence in skin, where cellular factors that control parasite numbers are counterbalanced by Leishmania-specific Tregs that facilitate parasite persistence.

Early antiviral CD4 and CD8 T cell responses are associated with upper respiratory tract clearance of SARS-CoV-2.

T cells are involved in protective immunity against numerous viral infections. Limited data have been available regarding roles of human T cell responses controlling SARS-CoV-2 viral clearance in primary COVID-19. Here, we examined longitudinal SARS-CoV-2 upper respiratory tract viral RNA levels and early adaptive immune responses from 95 unvaccinated individuals with acute COVID-19. Acute SARS-CoV-2-specific CD4 and CD8 T cell responses were evaluated in addition to antibody responses. Most individuals with acute COVID-19 developed rapid SARS-CoV-2-specific T cell responses during infection, and both early CD4 T cell and CD8 T cell responses correlated with reduced upper respiratory tract SARS-CoV-2 viral RNA, independent of neutralizing antibody titers. Overall, our findings indicate a distinct protective role for SARS-CoV-2-specific T cells during acute COVID-19.

A combined adjuvant approach primes robust germinal center responses and humoral immunity in non-human primates.

Adjuvants and antigen delivery kinetics can profoundly influence B cell responses and should be critically considered in rational vaccine design, particularly for difficult neutralizing antibody targets such as human immunodeficiency virus (HIV). Antigen kinetics can change depending on the delivery method. To promote extended immunogen bioavailability and to present antigen in a multivalent form, native-HIV Env trimers are modified with short phosphoserine peptide linkers that promote tight binding to aluminum hydroxide (pSer:alum). Here we explore the use of a combined adjuvant approach that incorporates pSer:alum-mediated antigen delivery with potent adjuvants (SMNP, 3M-052) in an extensive head-to-head comparison study with conventional alum to assess germinal center (GC) and humoral immune responses. Priming with pSer:alum plus SMNP induces additive effects that enhance the magnitude and persistence of GCs, which correlate with better GC-TFH cell help. Autologous HIV-neutralizing antibody titers are improved in SMNP-immunized animals after two immunizations. Over 9 months after priming immunization of pSer:alum with either SMNP or 3M-052, robust Env-specific bone marrow plasma cells (BM BPC) are observed. Furthermore, pSer-modification of Env trimer reduce targeting towards immunodominant non-neutralizing epitopes. The study shows that a combined adjuvant approach can augment humoral immunity by modulating immunodominance and shows promise for clinical translation.

Handgrip Strength Is Associated with Specific Aspects of Vascular Function in Individuals with Metabolic Syndrome.

BACKGROUND: Metabolic syndrome (MetS) is a disorder associated with an increased risk for the development of diabetes mellitus and its complications. Lower isometric handgrip strength (HGS) is associated with an increased risk of cardiometabolic diseases. However, the association between HGS and arterial stiffness parameters, which are considered the predictors of morbidity and mortality in individuals with MetS, is not well defined. OBJECTIVE: To determine the association between HGS and HGS asymmetry on components of vascular function in adults with MetS. METHODS: We measured handgrip strength normalized to bodyweight (HGS/kg), HGS asymmetry, body composition, blood glucose, lipid profile, blood pressure, pulse wave velocity (PWV), reflection coefficient (RC), augmentation index @75 bpm (AIx@75) and peripheral vascular resistance (PVR) in 55 adults with a diagnosis of MetS between 25 and 54 years old. RESULTS: Mean age was 43.1 ± 7.0 years, 56.3% were females. HGS/kg was negatively correlated with AIx@75 (r = -0.440), p < 0.05, but these associations were not significant after adjusting for age and sex. However, when interaction effects between sex, HGS/kg and age were examined, we observed an inverse relationship between HGS/kg and AIx@75 in the older adults in the sample, whereas in the younger adults, a weak direct association was found. We also found a significant association between HGS asymmetry and PVR (beta = 30, 95% CI = 7.02; 54.2; p <0.012). CONCLUSIONS: Our findings suggest that in people with MetS, maintaining muscle strength may have an increasingly important role in older age in the attenuation of age-related increases in AIx@75-a marker of vascular stiffness-and that a higher HGS asymmetry could be associated with a greater vascular resistance.

General Hospitalization and Intensive Care Unit-Related Factors of COVID-19 Patients in Northeastern Colombia: Baseline Characteristics of a Cohort Study.

Objective This study aims to describe demographic and clinical characteristics and the factors associated with the risk of COVID-19 general hospitalization and intensive care unit (ICU) care of patients who consulted in a third-level hospital in Santander, Colombia. Methods We used baseline data from an ambidirectional cohort study. We included all patients with positive real-time polymerase chain reaction (PCR) tests for COVID-19 who came to the emergency room (ER) for respiratory symptoms related to COVID-19. Information regarding patients' baseline characteristics and symptoms was collected through telephone interviews and review of medical records. Vital signs were extracted from medical records as well. Results We enrolled 3,030 patients, predominantly men, with a median age of 60 (interquartile range (IQR): 44-73). Symptoms of the acute phase varied between men and women. Men presented with more respiratory symptoms, and women had general symptoms. Hypertension, obesity, and diabetes were common risk factors for hospital admission. Antibiotic consumption may also play a role in hospital admission.  Conclusions Male sex, older age, hypertension, obesity, prior thrombotic events, and self-medicated antibiotics were associated with general hospitalization. Hypertension, obesity, diabetes, and cancer were associated with ICU admission. The Charlson comorbidity index (CCI) is a powerful tool for evaluate the impact of pre-existing health conditions on COVID-19 hospital admission. We highlight the importance of these findings as possible predictors in our region.

Nonoptimal bacteria species induce neutrophil-driven inflammation and barrier disruption in the female genital tract.

Neutrophil recruitment and activation within the female genital tract are often associated with tissue inflammation, loss of vaginal epithelial barrier integrity, and increased risk for sexually transmitted infections, such as HIV-1. However, the direct role of neutrophils on vaginal epithelial barrier function during genital inflammation in vivo remains unclear. Using complementary proteome and immunological analyses, we show high neutrophil influx into the lower female genital tract in response to physiological surges in progesterone, stimulating distinct stromal, immunological, and metabolic signaling pathways. However, despite the release of extracellular matrix-modifying proteases and inflammatory mediators, neutrophils contributed little to physiological mucosal remodeling events such as epithelial shedding or re-epithelialization during transition from diestrus to estrus phase. In contrast, the presence of bacterial vaginosis-associated bacteria resulted in a rapid and sustained neutrophil recruitment, resulting in vaginal epithelial barrier leakage and decreased cell-cell junction protein expression in vivo. Thus, neutrophils are important mucosal sentinels that rapidly respond to various biological cues within the female genital tract, dictating the magnitude and duration of the ensuing inflammatory response at steady state and during disease processes.

Factors associated with long COVID syndrome in a Colombian cohort.

Introduction: After acute phase of SARS-CoV-2 infection, some patients persist with clinical symptoms, a phenomenon known as Long COVID syndrome. It is necessary to understand the factors associated with the persistence of these symptoms to develop individualized preventive approaches and effectively address this challenge. Objective: To determine the factors associated with the persistence of symptoms six months after COVID-19 infection. Materials and methods: A ambidirectional cohort, single-center study, that included individuals previously diagnosed with COVID-19 by real-time polymerase chain reaction (PCR) positive test, who were followed for a period of six months. Univariate, bivariate and a multivariate binomial regression model were performed to determine risk factors associated with the persistence of COVID-19 symptoms at the six months of follow-up. Results: The prevalence of long COVID syndrome was 47%. Age demonstrated no significant association with Long COVID (RR 0.999 [95% CI 0.996-1.002]); however, female sex (RR 1.148 [95% CI 1.038-1.268]), requirement of mechanical ventilation (RR 1.278 [95% CI 1.050-1.555]), presence of Chronic Obstructive Pulmonary Disease (COPD) (RR 1.340 [95% CI 1.104-1.626]), Rheumatic Disease (RR 1.259 [95% CI 1.055-1.504]) and the Hospitalization Type: General Hospitalization (RR 1.247 [95% CI 1.090-1.427]) and ICU Hospitalization (RR 1.490 [95% CI 1.221-1.818]) were significantly associated with the persistence of symptoms at the six month of follow-up. Conclusion: Female sex, presence of COPD, rheumatic disease, hospitalization type and requirement of mechanical ventilation during index infection were identified as significant risk factors for the diagnosis of Long COVID. These findings emphasize the importance of addressing Long COVID syndrome in terms of prevention and management, taking these risk factors into consideration.

T cell migration potentiates HIV infection by enhancing viral fusion and integration.

T cells actively migrate along reticular networks within lymphoid organs in search for cognate antigen, but how these behaviors impact HIV entry and infection is unclear. Here, we show that migratory T cells in 3D collagen matrix display significantly enhanced infection and integration by cell-free R5-tropic lab adapted and transmitted/founder molecular HIV clones in the absence of exogenous cytokines or cationic polymers. Using two different collagen matrices that either support or restrict T cell migration, we observe high levels of HIV fusion in migratory T cells, whereas non-motile T cells display low viral entry and integration. Motile T cells were less sensitive to combination antiretroviral drugs and were able to freely migrate into regions with high HIV densities, resulting in high infection rates. Together, our studies indicate that the environmental context in which initial HIV-T cell encounters occur modulates HIV-1 entry and integration efficiencies.

Mouse Papillomavirus L1 and L2 Are Dispensable for Viral Infection and Persistence at Both Cutaneous and Mucosal Tissues.

Papillomavirus L1 and L2, the major and minor capsid proteins, play significant roles in viral assembly, entry, and propagation. In the current study, we investigate the impact of L1 and L2 on viral life cycle and tumor growth with a newly established mouse papillomavirus (MmuPV1) infection model. MmuPV1 L1 knockout, L2 knockout, and L1 plus L2 knockout mutant genomes (designated as L1ATGko-4m, L2ATGko, and L1-L2ATGko respectively) were generated. The mutants were examined for their ability to generate lesions in athymic nude mice. Viral activities were examined by qPCR, immunohistochemistry (IHC), in situ hybridization (ISH), and transmission electron microscopy (TEM) analyses. We demonstrated that viral DNA replication and tumor growth occurred at both cutaneous and mucosal sites infected with each of the mutants. Infections involving L1ATGko-4m, L2ATGko, and L1-L2ATGko mutant genomes generally resulted in smaller tumor sizes compared to infection with the wild type. The L1 protein was absent in L1ATGko-4m and L1-L2ATGko mutant-treated tissues, even though viral transcripts and E4 protein expression were robust. Therefore, L1 is not essential for MmuPV1-induced tumor growth, and this finding parallels our previous observations in the rabbit papillomavirus model. Very few viral particles were detected in L2ATGko mutant-infected tissues. Interestingly, the localization of L1 in lesions induced by L2ATGko was primarily cytoplasmic rather than nuclear. The findings support the hypothesis that the L2 gene influences the expression, location, transport, and assembly of the L1 protein in vivo.

Comparación del ángulo de la guía condílea sagital obtenida del registro radiográfico y clínico en pacientes dentados / Comparison of sagittal condylar guidance obtained from radiographic and and clinical records in dentate patients

Objetivo: Comparar el ángulo de la guía condílea sagital obtenida del registro radiográfico y clínico en pacientes dentados. Materiales y métodos: La muestra estuvo conformada por un grupo único de estudio de 32 pacientes, en el que se evaluó la radiografía lateral estricta y los registros posicionales: en relación céntrica, registro protrusivo a 5 mm en lateralidad derecha y registro protrusivo a 5 mm en lateralidad izquierda. Con el registro posicional del arco facial se articuló el modelo superior, con el registro posicional en relación céntrica se articuló el modelo inferior, con los registros laterales protrusivos de los lados derecho e izquierdo se obtuvo la medida del ángulo de la guía condílea sagital para la programación del articulador semiajustable. El plan estadístico en la presente investigación utilizó el programa SPSS versión 24, la normalidad fue evaluada usando el test de Shapiro-Wilk, también se realizaron las pruebas de T de Student y correlación de Pearson. Resultados: Se determinó estadísticamente que el género y la edad influyen en la medida del ángulo de la guía condílea sagital. El método radiográfico presentó un ángulo de guía condílea de 35,69 ±5,18 y con el método clínico fue 35,69 ± 5,16 (p > 0,05). La prueba de correlación de Pearson sí mostró una correlación importante entre ambos métodos r = 0,948, p < 0,001. Conclusiones: Existe alta correlación en las medidas obtenidas del ángulo de la guía condílea sagital con los registros radiográficos y clínicos; esta concordancia permitiría reemplazar un método por el otro. (AU)

Objective: To compare the angle of the sagittal condylar guidance obtained from the radiographic and clinical records of dentate patients. Materials and Methods: The sample consisted of 32 patients in whom strict lateral radiography and positional records were performed: in centric relation, protrusive recording 5 mm in right laterality and protrusive recording 5 mm in left laterality. With the positional registration of the facebow, the upper model was articulated, while the lower model was articulated with the positional registration in centric relation, and with the protrusive lateral registrations on the right and left side the condylar guidance was obtained for programming the semi-adjustable articulator. Statistics were performed with the SPSS program version 24 in Spanish. Normality was evaluated using the Shapiro-Wilk test, for data with normal distribution, and the Student's T test and Pearson's correlation were performed in descriptive statistics. Results: The statistical analyses showed that gender and age influence the angle measurement of the sagittal condylar guide. The radiographic method presented a condylar guide angle of 35.69 ± 5.18, being 35.69 ± 5.16 with the clinical method (p> 0.05). Pearson's correlation test showed an important correlation between the two methods (r = 0.948, p <0.001). Conclusions: There is a high correlation in the measurements obtained from the angle of the sagittal condylar guide and the radiographic and clinical records, indicating that both methods are effective. (AU)

An updated review of idiopathic osteosclerosis of the jaws / Una revisión actualizada de la osteoesclerosis idiopática en los maxilares

Objective: The aim of this study was to update the concepts of the diagnosis of idiopathic osteosclerosis (IO) of the jaws by digital panoramic radiographs and cone beam tomography and describe the impact of this disease on oral and general health. Methods: A search of the main databases of dental medical research was carried out using the search terms "osteosclerosis, panoramic radiography, cone beam computed tomography, jaws". Articles without language restriction until September 30, 2020 were identified. The prevalence and clinical and radiographic characteristics of IO of the jaws were examined in 2D and 3D imaging studies, as well as the interaction during treatments in the various dental specialties. Results: We analyzed the current situation regarding the diagnosis of IO, with an update of the diagnostic criteria used to accurately identify IO in the latest generation imaging studies, as well determine its possible interactions in oral an general health. Conclusions: It is important to have a clear differential diagnosis of IO and be able to distinguish different radiopacities in the maxilla. Accurate reporting and monitoring of the morphometric characteristics are necessary taking into account the impact the presence of IO of the jaws has on future dental treatments. (AU)

Objetivo: El propósito de esta investigación fue actualizar las consideraciones para el diagnóstico de la osteoesclerosis idiopática en radiografías panorámicas digitales y tomografías de haz cónico, a fin de determinar sus implicancias en la salud oral y general. Métodos: Se realizó las pesquisas en las principales bases de datos de investigación médica estomatológica, utilizando las palabras "osteoesclerosis", "radiografía panorámica", "tomografía computarizada de haz cónico" y "mandíbula". Se identificaron artículos sin restricción de idioma, desde las primeras publicaciones hasta el 30 de septiembre del 2020. Se examinaron la prevalencia, las características clínicas y radiográficas en estudios imagenológicos de dos y tres dimensiones, así como su interacción durante los tratamientos realizados en las diversas especialidades estomatológicas. Resultados: La información obtenida nos permitió analizar la situación actual con respecto al diagnóstico de la OI y actualizar los criterios diagnósticos para una identificación certera de la OI en los estudios imagenológicos de última generación, así como sus posibles interacciones en la salud oral y general. Conclusiones: Es importante tener un criterio diagnóstico diferencial claro al distinguir las diferentes radiopacidades como la OI, que se pueden presentar en los maxilares, mediante un registro preciso de sus características morfométricas y seguimiento en el tiempo, teniendo en cuenta su existencia y sus implicancias en los tratamientos dentales a futuro. (AU)

Ileal Intussusception in an Adult Caused by a Locally Invasive Inflammatory Fibroid Polyp: A Case Report.

Inflammatory fibroid polyps (IFPs) are rare mesenchymal neoplasms affecting the gastrointestinal tract which are considered benign and noninvasive. We present a case of an invasive IFP in a 46-year-old woman who presented with signs of intestinal obstruction due to ileal intussusception. A segment of the small intestine was resected and subsequently intestinal continuity was restored. A polypoid lesion was found obstructing the lumen. Histopathology revealed a mesenchymal proliferation of spindle and stellate cells, without cytological atypia, arranged in a fibromyxoid stroma. The tumor cells were located in the submucosa but also infiltrated the muscularis propria and the subserosa and were CD34 positive. The molecular study by PCR showed mutation in exon 12 of the PDGFRA gene. IFP is considered a true neoplasm and can also be considered as a potentially invasive lesion.

An updated review of idiopathic osteosclerosis of the jaws.

Objective: : The aim of this study was to update the concepts of the diagnosis of idiopathic osteosclerosis (IO) of the jaws by digital panoramic radiographs and cone beam tomography and describe the impact of this disease on oral and general health. Methods: A search of the main databases of dental medical research was carried out using the search terms "osteosclerosis, panoramic radiography, cone beam computed tomography, jaws". Articles without language restriction until September 30, 2020 were identified. The prevalence and clinical and radiographic characteristics of IO of the jaws were examined in 2D and 3D imaging studies, as well as the interaction during treatments in the various dental specialties. Results: We analyzed the current situation regarding the diagnosis of IO, with an update of the diagnostic criteria used to accurately identify IO in the latest generation imaging studies, as well determine its possible interactions in oral an general health. Conclusions: It is important to have a clear differential diagnosis of IO and be able to distinguish different radiopacities in the maxilla. Accurate reporting and monitoring of the morphometric characteristics are necessary taking into account the impact the presence of IO of the jaws has on future dental treatments.

Objetivo: El propósito de esta investigación fue actualizar las consideraciones para el diagnóstico de la osteoesclerosis idiopática en radiografías panorámicas digitales y tomografías de haz cónico, a fin de determinar sus implicancias en la salud oral y general. Métodos: Se realizó las pesquisas en las principales bases de datos de investigación médica estomatológica, utilizando las palabras "osteoesclerosis", "radiografía panorámica", "tomografía computarizada de haz cónico" y "mandíbula". Se identificaron artículos sin restricción de idioma, desde las primeras publicaciones hasta el 30 de septiembre del 2020. Se examinaron la prevalencia, las características clínicas y radiográficas en estudios imagenológicos de dos y tres dimensiones, así como su interacción durante los tratamientos realizados en las diversas especialidades estomatológicas. Resultados: La información obtenida nos permitió analizar la situación actual con respecto al diagnóstico de la OI y actualizar los criterios diagnósticos para una identificación certera de la OI en los estudios imagenológicos de última generación, así como sus posibles interacciones en la salud oral y general. Conclusiones: Es importante tener un criterio diagnóstico diferencial claro al distinguir las diferentes radiopacidades como la OI, que se pueden presentar en los maxilares, mediante un registro preciso de sus características morfométricas y seguimiento en el tiempo, teniendo en cuenta su existencia y sus implicancias en los tratamientos dentales a futuro.

[Prevalence of idiopathic osteosclerosis in patients cared for at a radiological center in Ayacucho from 2016-2018]. / Prevalencia de osteoesclerosis idiopática de pacientes atendidos en un centro radiológico de Ayacucho entre los años 2016 y 2018.

Objective: The objective of this study was to determine, describe and identify the prevalence of radiopaque images compatible with idiopathic osteosclerosis in digital panoramic radiographs taken in patients between the ages of 18 and 50. Materials and methods: The study design was descriptive, cross-sectional and retrospective. The sample consisted of 500 digital panoramic radiographs taken between January 1, 2016 and December 31, 2018, in the target population aged between 18 and 50 years from Ayacucho - Peru, attended at a private radiological center. The radiographs obtained were analyzed using the Romexis viewer version 5.3 program, and the results were recorded on a data collection sheet. The Chi-square test was used to establish associations among the variables evaluated. A P <0.05 was considered significant. Results: 500 digital panoramic radiographs were analyzed, showing a prevalence of idiopathic osteosclerosis of 17.4%, of which 12% were female and 5.4% male, and according to age, the presence of idiopathic osteosclerosis was more prevalent in the second decade of life. Conclusions: It is important to have a clear differential diagnostic criterion when distinguishing the different radiopacities such as idiopathic osteosclerosis, which can occur in the jaws, making a precise record of the morphometric characteristics and monitoring over time, taking into account their existence and implication in dental treatments.

[Comparison of sagittal condylar guidance obtained from radiographic and clinical records in dentate patients]. / Comparación del ángulo de la guía condílea sagital obtenida del registro radiográfico y clínico en pacientes dentados.

Objective: To compare the angle of the sagittal condylar guidance obtained from the radiographic and clinical records of dentate patients. Materials and Methods: The sample consisted of 32 patients in whom strict lateral radiography and positional records were performed: in centric relation, protrusive recording 5 mm in right laterality and protrusive recording 5 mm in left laterality. With the positional registration of the facebow, the upper model was articulated, while the lower model was articulated with the positional registration in centric relation, and with the protrusive lateral registrations on the right and left side the condylar guidance was obtained for programming the semi-adjustable articulator. Statistics were performed with the SPSS program version 24 in Spanish. Normality was evaluated using the Shapiro-Wilk test, for data with normal distribution, and the Student's T test and Pearson's correlation were performed in descriptive statistics. Results: The statistical analyses showed that gender and age influence the angle measurement of the sagittal condylar guide. The radiographic method presented a condylar guide angle of 35.69 ± 5.18, being 35.69 ± 5.16 with the clinical method (p> 0.05). Pearson's correlation test showed an important correlation between the two methods (r = 0.948, p <0.001). Conclusions: There is a high correlation in the measurements obtained from the angle of the sagittal condylar guide and the radiographic and clinical records, indicating that both methods are effective.

Visualizing Cellular Dynamics and Protein Localization in 3D Collagen.

Immune cells migrate and communicate through cell-to-cell interactions and cytokines to coordinate the specificity and timing of the immune response. While studying these events in cell culture are standard procedure, spatiotemporal dynamics of cell-to-cell interactions within three-dimensional (3D) environments are critical in generating appropriate effector functions. Here, we present a detailed protocol to study cells within an all-in-one 3D collagen matrix that is amenable to live-cell microscopy and immunohistochemistry. This approach facilitates analyses of dynamic cellular events in 3D settings. For complete details on the use and execution of this protocol, please refer to Koh et al. (2020).

Hidroxicloroquina para manejo de infección por SARS-CoV-2 Una revisión exploratoria / Hydroxychloroquine for treatment of SARS-CoV-2 infection An exploratory review

Resumen Introducción: la hidroxicloroquina se ha venido postulando en estos tiempos de pandemia como posible tratamiento eficaz frente a COVID-19. Esto ya que se ha demostrado por expertos chinos su capacidad para inhibir la replicación viral usando distintos mecanismos. En este momento es de vital importancia tener conocimiento acerca de las últimas investigaciones y ensayos clínicos en lo que respecta a un esquema de tratamiento efectivo que ayude a un mejor manejo de pacientes con infección por SARS-CoV-2. Objetivo: presentar la información disponible sobre el uso de hidroxicloroquina como opción de manejo para pacientes infectados por SARS-CoV-2. Material y métodos: se realizó una revisión siguiendo el marco metodológico sugerido por Arksey y O'Malley. Las bases de datos utilizadas fueron: PubMed, MedLine, Lilacs, Scopus, Clinical Trials, Cochrane y CNKI. Se incluyeron únicamente textos en español e inglés, finalmente se realizó una caracterización y resumen de los estudios pertinentes para esta revisión. Resultados: se incluyeron en la revisión 87 artículos académicos incluyendo estudios experimentales y no experimentales; todos con evidencia sobre el uso de hidroxicloroquina en COVID-19. Conclusiones: A la fecha no hay información científica disponible que sustente y tenga la suficiente evidencia para soportar el uso de la hidroxicloroquina como tratamiento farmacológico en la pandemia actual. Dos ensayos clínicos aleatorizados se contradicen en cuanto a la efectividad de la hidroxicloroquina; sin embargo, ambos comparten errores metodológicos y tamaños de muestra limitados; y un único ensayo no aleatorizado con los mismos errores demuestra efectividad de la hidroxicloroquina. En cuanto al perfil de seguridad se cuenta con información que evidencia una menor tasa de efectos adversos de la hidroxicloroquina frente a la cloroquina por lo que se preferiría su uso en caso de demostrar efectividad frente a COVID-19. Existen varios ensayos clínicos aleatorizados en curso que se espera esclarezcan las dudas que surgen al revisar la literatura.(Acta Med Colomb 2020; 45. DOI:https://doi.org/10.36104/amc.2020.1880).

Abstract Introduction: hydroxychloroquine has been recommended in this pandemic as a possible effective treatment for COVID-19. This is because Chinese experts have demonstrated its ability to inhibit viral replication through various mechanisms. At this juncture, it is vitally important to understand the latest research and clinical trials regarding an effective treatment regimen which would help improve the treatment of patients with SARS-CoV-2 infection. Objective: to present the available information regarding the use of hydroxychloroquine as a treatment option for patients infected with SARS-CoV-2. Material and methods: a review was carried out following the methodological framework proposed by Arksey and O'Malley. The data bases used were: PubMed, MedLine, Lilacs, Scopus, Clinical Trials, Cochrane and CNKI. Only texts in Spanish and English were included. Finally, the pertinent studies for this review were described and summarized. Results: a total of 87 academic articles were included in the review, including experimental and non-experimental studies, all containing evidence regarding the use of hydroxychloroquine in COVID-19. Conclusions: To date, there is no available substantiating scientific data with enough evidence to support the use of hydroxychloroquine as a pharmacological treatment for the current pandemic. Two randomized clinical trials contradict each other regarding the efficacy of hydroxychloroquine. However, they both share methodological errors and have small sample sizes. A single nonrandomized trial with the same errors shows efficacy of hydroxychloroquine. As far as the safety profile, there is data showing a lower rate of adverse effects for hydroxychloroquine compared with chloroquine, so its use would be preferred if it were to be proven effective against COVID-19. There are several randomized clinical trials underway which, it is hoped, will answer the questions raised by the literature review.(Acta Med Colomb 2020; 45. DOI:https://doi.org/10.36104/amc.2020.1880).

HIV-Captured DCs Regulate T Cell Migration and Cell-Cell Contact Dynamics to Enhance Viral Spread.

Trafficking of cell-associated HIV-1 from the genital mucosa to lymphoid organs represents a critical first step toward systemic infection. Mature DCs capture and transmit HIV-1 to T cells, but insights into DC-to-T cell viral spread dynamics within a 3-dimensional environment is lacking. Using live-cell imaging, we show that mature DCs rapidly compartmentalize HIV-1 within surface-accessible invaginations near the uropod. HIV-1 capture did not interfere with DC migration toward lymph node homing chemo-attractants and their ability to enter lymphatic vessels. However, HIV-captured DCs engaged in prolonged contacts with autologous CD4+ T cells, which led to high T cell infection. Interestingly, we show that surface bound, virion-associated Env induced signal transduction in motile T cells that facilitated prolonged DC:T cell interactions, partially through high-affinity LFA-1 expression. Together, we describe a mechanism by which surface bound HIV-1 particles function as signaling receptors that regulate T cell motility, cell-cell contact dynamics, and productive infection.

Facilitadores y barreras percibidos en la práctica de la actividad física en adolescentes escolarizados en Piedecuesta (Santander), en 2016: análisis cualitativo / Perceived facilitators and barriers to physical activity in adolescents in Piedecuesta (Santander), in 2016: qualitative analysis / Facilitadores e barreiras evidentes na prática da atividade física nos adolescentes em idade escolar em Piedecuesta Santander, em 2016: Análise qualitativa

Resumen Objetivo: Describir la percepción que tienen adolescentes escolarizados entre 12 y 16 años, en Piedecuesta (Santander), en 2016, sobre los facilitadores y las barreras que influyen en la práctica de la actividad física. Metodología: Análisis cualitativo desde un enfoque fenomenológico, con la participación de 20 adolescentes escolarizados que, mediante entrevistas semiestructuradas y un grupo focal, conversaron sobre la práctica, los beneficios, los entornos y la influencia y la compañía en relación con la actividad física, para identificar barreras y facilitadores. Resultados: La práctica de la actividad física se limitaba a las clases de educación física en la mayoría de los casos. El compañero principal en la práctica extracurricular era el padre del mismo sexo. La actividad física representaba una oportunidad para el disfrute, mejorar la salud física y mental, así como la contextura corporal, y para romper con la rutina diaria. La falta de tiempo por compromisos académicos fue la razón principal para no realizar actividad física. Los lugares públicos no siempre estaban disponibles, a menudo no se consideraban seguros. En la escuela, el espacio y las instalaciones eran inadecuados, y el uso estaba restringido. Conclusiones: La escuela es un punto de convergencia importante para la práctica de la actividad física, lo que sugiere la necesidad de fortalecer el plan de estudios al respecto; este entorno es un facilitador potencial para aumentar el nivel de actividad física en adolescentes. También se percibe como barrera, dado que la práctica interfiere con las actividades académicas. Las mejoras en la seguridad y el atractivo estético en el entorno comunitario se visibilizan como un facilitador para promover la actividad física.

Abstract Objective: Describe the perception of adolescents aged between 12 and 16 years, in Piedecuesta (Santander), in 2016, about the facilitators and barriers that influence physical activity. Methodology: Qualitative analysis from a phenomenological approach, with the participation of 20 adolescents who talked about the practice, benefits, environments, influence and company in connection with physical activity , to identify barriers and facilitators, through semi-structured interviews and a focus group. Results: Physical activity was limited to physical education classes in most cases. The main companion in extracurricular physical activity was the parent of the same sex. Physical activity represented an opportunity for enjoyment, improvement of physical and mental health, as well as body composition, and to have a break in their daily routine. Lack of time due to academic commitments was the main reason for not doing physical activity. Public places were not always available and they were often not considered to be safe. Space and facilities at school were inadequate, and their use was restricted.. Conclusions: The school is an important point of convergence for doing physical activity, suggesting the need to strengthen the curriculum in this respect; this environment is a potential facilitator to increasing the level of physical activity in adolescents. It can also be seen as a barrier, given that the practice interferes with academic activities. Improvements in safety and aesthetic appeal in the surrounding community are seen as a facilitator to promoting physical activity.

Resumo Objetivo: Descrever a percepção que os adolescentes entre 12 e 17 anos de Piedecuesta em Santander, tiveram em 2016 sobre os facilitadores e as barreiras que influenciaram na prática da atividade física. Metodologia: Análise qualitativa partindo de um foco fenomenológico, com a participação de 20 adolescentes em idade escolar que, através de entrevistas semiestruturadas e um grupo focal, conversaram sobre a prática, os benefícios, os entornos, a influência e o acompanhamento relacionados com a atividade física, para identificar barreiras e facilitadores. Resultados: Na maioria dos casos, a prática da atividade física limitava-se às aulas de educação física. O companheiro principal na prática extracurricular era o genitor ou genitora do mesmo sexo. A atividade física representava uma oportunidade para disfrutar, melhorar a saúde física e mental, além da estrutura corporal e para sair da rotina diária. A falta de tempo devido às responsabilidades escolares foi a principal razão para não realizarem atividade física. Os lugares públicos nem sempre estavam disponíveis e geralmente não são considerados seguros. Na escola, o espaço e as instalações eram inadequados e o uso estava restrito. Conclusões: A escola é um importante ponto de convergência para a prática da atividade física, o que determina a necessidade de fortalecer o currículo relacionado; esse ambiente é um facilitador potencial para aumentar o nível de atividade física nos adolescentes. Também se percebe como barreira, já que a prática interfere com as atividades escolares. As melhorias na segurança e um espaço comunitário mais atraente do ponto de vista estético são determinantes como facilitadores para a promoção da atividade física.