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Abstract Isogenic cells respond in a heterogeneous manner to interferon. Using a micropatterning approach combined with high-content imaging and spatial analyses, we characterized how the population context (position of a cell with respect to neighboring cells) of epithelial cells affects their response to interferons. We identified that cells at the edge of cellular colonies are more responsive than cells embedded within colonies. We determined that this spatial heterogeneity in interferon response resulted from the polarized basolateral interferon receptor distribution, making cells located in the center of cellular colonies less responsive to ectopic interferon stimulation. This was conserved across cell lines and primary cells originating from epithelial tissues. Importantly, cells embedded within cellular colonies were not protected from viral infection by apical interferon treatment, demonstrating that the population context-driven heterogeneous response to interferon influences the outcome of viral infection. Our data highlights that the behavior of isolated cells does not directly translate to their behavior in a population, placing the population context as one important factor influencing heterogeneity during interferon response in epithelial cells.

This study applies a forensic examination to six distinct Android fitness applications centered around monitoring running activities. The applications are Adidas Running, MapMyWalk, Nike Run Club, Pumatrac, Runkeeper and Strava. Specifically, we perform a post mortem analysis of each application to find and document artifacts such as timelines and Global Positioning System (GPS) coordinates of running workouts that could prove helpful in digital forensic investigations. First, we focused on the Nike Run Club application and used the gained knowledge to analyze the other applications, taking advantage of their similarity. We began by creating a test environment and using each application during a fixed period. This procedure allowed us to gather testing data, and, to ensure access to all data generated by the apps, we used a rooted Android smartphone. For the forensic analysis, we examined the data stored by the smartphone application and documented the forensic artifacts found. To ease forensic data processing, we created several Python modules for the well-known Android Logs Events And Protobuf Parser (ALEAPP) digital forensic framework. These modules process the data sources, creating reports with the primary digital artifacts, which include the workout activities and related GPS data.

Introduction Oocyte vitrification is a scientific advance that has changed the reproductive perspective of human society. This procedure has been offered as an alternative to the voluntary postponement of pregnancy, giving women a new perspective on their reproductive autonomy. The number of women who consult and then choose to freeze oocytes has increased almost exponentially in Chile and throughout the world. There is little knowledge about the motivation, experience, and results of elective oocyte cryopreservation in Chile. The objective was to know the motivation, experience, and future reproductive desire of the women who underwent this technique. Methods Cross-sectional descriptive study based on a questionnaire sent by e-mail in which females who had previously undergone elective oocyte cryopreservation between January 2011 and December 2019 at Clínica Alemana, Santiago, Chile, participated. Results Of 342 women who had completed a cycle of elective oocyte cryopreservation, 193 agreed to participate, and of these, 98 (51%) answered the survey satisfactorily. Women who underwent this procedure for medical indication, including endometriosis, cancer, and low ovarian reserve, were excluded. The most frequent reason for the procedure was age (44%). Concerning the procedure: 94% do not regret having it done, and 74% of the women believe that they will use their oocytes at some point in their lives. Finally, from the time of oocyte cryopreservation to date, 11% of the surveyed women have used their vitrified oocytes, and 27% have become pregnant. Conclusions Women who undergo elective oocyte cryopreservation for social reasons are mainly women without a partner whose main motivation is their reproductive age. The vast majority do not regret doing so.

Master Regulator proteins, controlling the transcriptional identity of infected cells, can serve as drug targets for inhibiting virus replication, here demonstrated in a SARSCoV-2 infection model.

Abstract Exacerbated pro‐inflammatory immune response contributes to COVID‐19 pathology. However, despite the mounting evidence about SARS‐CoV‐2 infecting the human gut, little is known about the antiviral programs triggered in this organ. To address this gap, we performed single‐cell transcriptomics of SARS‐CoV‐2‐infected intestinal organoids. We identified a subpopulation of enterocytes as the prime target of SARS‐CoV‐2 and, interestingly, found the lack of positive correlation between susceptibility to infection and the expression of ACE2. Infected cells activated strong pro‐inflammatory programs and produced interferon, while expression of interferon‐stimulated genes was limited to bystander cells due to SARS‐CoV‐2 suppressing the autocrine action of interferon. These findings reveal that SARS‐CoV‐2 curtails the immune response and highlights the gut as a pro‐inflammatory reservoir that should be considered to fully understand SARS‐CoV‐2 pathogenesis.

Dementia is becoming increasingly prevalent in Latin America, contrasting with stable or declining rates in North America and Europe. This scenario places unprecedented clinical, social, and economic burden upon patients, families, and health systems. The challenges prove particularly pressing for conditions with highly specific diagnostic and management demands, such as frontotemporal dementia. Here we introduce a research and networking initiative designed to tackle these ensuing hurdles, the Multi-partner consortium to expand dementia research in Latin America (ReDLat). First, we present ReDLat's regional research framework, aimed at identifying the unique genetic, social, and economic factors driving the presentation of frontotemporal dementia and Alzheimer's disease in Latin America relative to the US. We describe ongoing ReDLat studies in various fields and ongoing research extensions. Then, we introduce actions coordinated by ReDLat and the Latin America and Caribbean Consortium on Dementia (LAC-CD) to develop culturally appropriate diagnostic tools, regional visibility and capacity building, diplomatic coordination in local priority areas, and a knowledge-to-action framework toward a regional action plan. Together, these research and networking initiatives will help to establish strong cross-national bonds, support the implementation of regional dementia plans, enhance health systems' infrastructure, and increase translational research collaborations across the continent.

Interferons (IFNs) constitute the first line of defense against microbial infections particularly against viruses. They provide antiviral properties to cells by inducing the expression of hundreds of genes known as interferon-stimulated genes (ISGs). The two most important IFNs that can be produced by virtually all cells in the body during intrinsic innate immune response belong to two distinct families: the type I and type III IFNs. The type I IFN receptor is ubiquitously expressed whereas the type III IFN receptor’s expression is limited to epithelial cells and a subset of immune cells. While originally considered to be redundant, type III IFNs have now been shown to play a unique role in protecting mucosal surfaces against pathogen challenges. The mucosal specific functions of type III IFN do not solely rely on the restricted epithelial expression of its receptor but also on the distinct means by which type III IFN mediates its anti-pathogen functions compared to the type I IFN. In this review we first provide a general overview on IFNs and present the similarities and differences in the signal transduction pathways leading to the expression of either type I or type III IFNs. By highlighting the current state-of-knowledge of the two archetypical mucosal surfaces (e.g. the respiratory and intestinal epitheliums), we present the differences in the signaling cascades used by type I and type III IFNs to uniquely induce the expression of ISGs. We then discuss in detail the role of each IFN in controlling pathogen infections in intestinal and respiratory epithelial cells. Finally, we provide our perspective on novel concepts in the field of IFN (stochasticity, response heterogeneity, cellular polarization/differentiation and tissue microenvironment) that we believe have implications in driving the differences between type I and III IFNs and could explain the preferences for type III IFNs at mucosal surfaces.

Global brain states are frequently placed within a unidimensional continuum by correlational studies, ranging from states of deep unconsciousness to ordinary wakefulness. An alternative is their multidimensional and mechanistic characterization in terms of different cognitive capacities, using computational models to reproduce the underlying neural dynamics. We explore this alternative by introducing a semi-empirical model linking regional activation and long-range functional connectivity in the different brain states visited during the natural wake-sleep cycle. Our model combines functional magnetic resonance imaging (fMRI) data, in vivo estimates of structural connectivity, and anatomically-informed priors to constrain the independent variation of regional activation. The best fit to empirical data was achieved using priors based on functionally coherent networks, with the resulting model parameters dividing the cortex into regions presenting opposite dynamical behavior. Frontoparietal regions approached a bifurcation from dynamics at a fixed point governed by noise, while sensorimotor regions approached a bifurcation from oscillatory dynamics. In agreement with human electrophysiological experiments, sleep onset induced subcortical deactivation with low correlation, which was subsequently reversed for deeper stages. Finally, we introduced periodic forcing of variable intensity to simulate external perturbations, and identified the key regions relevant for the recovery of wakefulness from deep sleep. Our model represents sleep as a state with diminished perceptual gating and the latent capacity for global accessibility that is required for rapid arousals. To the extent that the qualitative characterization of local dynamics is exhausted by the dichotomy between unstable and stable behavior, our work highlights how expanding the model parameter space can describe states of consciousness in terms of multiple dimensions with interpretations given by the choice of anatomically-informed priors.

El Padre Hurtado (1901-1952) fue un adelantado. Se lo debe leer como alguien que abrió una senda para la Iglesia chilena y latinoamericana. En sus escritos ya se ve una profunda preocupación por “saber escrutar los signos de los tiempos”, la que dio forma a la gran revolución teoló- gica y eclesial del Concilio Vaticano II. Su lectura también se constituye como la antesala precisa a la necesidad de configurar una reflexión teológica en América Latina que desarrollará la opción preferencial por los pobres. Su intuición fue demasiado profunda. Pienso que aún no alcanzamos a hacer una buena lectura de sus textos y su vida.

Los asentamientos informales corresponden a una de las expresiones más relevantes de la pobreza urbana. A pesar de que no existen modelos teóricos o empíricos que den cuenta de su real complejidad, existe cierta evidencia reciente que puede servir de base para una futura investigación. En este trabajo se analizan tres problemas que, integradamente, exigen comprender este fenómeno más allá de la realidad de quienes ahí viven, intentando mostrar que la demanda específica de los pobladores no sólo busca mejorar su precariedad habitacional, sino además tener un acceso adecuado a la ciudad y a las oportunidades que ésta ofrece. En primer lugar, se revisan algunos datos recientes de Chile que indican que, pese a la enorme vulnerabilidad de estos hogares, sus ingresos pueden superar en muchos casos al del grupo pobre. Vivir en un asentamiento informal aparece -en estos casos- como una estrategia que los hogares movilizan para reducir su vulnerabilidad o riesgo de caer/permanecer en pobreza, cediendo calidad de vivienda a cambio de mejor localización. Por último, se presentan algunos antecedentes que introducen la mirada del capital social y algunas recientes pautas de participación para la superación de la pobreza, como una buena guía para acoger en forma eficaz la demanda estos hogares

Este artículo reconstruye panorámicamente la posición de Agustín de Hipona con respecto a la filosofía en la obra De civitate Dei. Sostiene que la valoración y el reproche que le hace Agustín a los platonici descansan en último término en un concepto de filosofía tomado del mismo platonismo y reinterpretado según textos bíblicos que enfatizan la centralidad de la mediación y el culto para alcanzar la beata vita.

Ambient Intelligence promises to transform current spaces into electronic environments that are responsive, assistive and sensitive to human presence. Those electronic environments will be fully populated with dozens, hundreds or even thousands of connected devices that share information and thus become intelligent. That massive wave of electronic devices will also invade everyday objects, turning them into smart entities, keeping their native features and characteristics while seamlessly promoting them to a new class of thinking and reasoning everyday objects. Although there are strong expectations that most of the users’ needs can be fulfilled without their intervention, there are still situations where interaction is required. This paper presents work being done in the field of human-computer interaction, focusing on smart home environments, while being a part of a larger project called Aging Inside a Smart Home. This initiative arose as a way to deal with a large scourge of our country, where lots of elderly persons live alone in their homes, often with limited or no physical mobility. The project relies on the mobile agent computing paradigm in order to create a Virtual Butler that provides the interface between the elderly and the smart home infrastructure. The Virtual Butler is receptive to user questions, answering them according to the context and knowledge of the AISH. It is also capable of interacting with the user whenever it senses that something has gone wrong, notifying next of kin and/or medical services, etc. The Virtual Butler is aware of the user location and moves to the computing device which is closest to the user, in order to be always present. Its avatar can also run in handheld devices keeping its main functionality in order to track user when s/he goes out. According to the evaluation carried out, the Virtual Butler is assessed as a very interesting and loved digital friend, filling the gap between the user and the smart home. The evaluation also showed that the Virtual Butler concept can be easily ported to other types of possible smart and assistive environments like airports, hospitals, shopping malls, offices, etc.

La estimación de ancestría individual posee gran relevancia en el estudio de la composición poblacional en regiones como Sudamérica, que han atravesado intensos procesos de mestizaje, lo que también tiene implicancia en ciencias de la salud. Debido a esto, es importante conocer los factores que influyen en la confiabilidad de los resultados obtenidos. En este trabajo se evalúa el número mínimo de marcadores informativos de ancestría (AIMs) a partir del cual las estimaciones resultarían aceptables. Se toma como ejemplo el cálculo en individuos provenientes de una muestra poblacional de diferentes regiones de Argentina. Considerando un modelo de tres componentes (nativo americano, euroasiático y subsahariano), se calculó la ancestría de 441 individuos utilizando 10, 20, 30 y 50 AIMs. Los resultados indican que el número de marcadores influye sobre la estimación de ancestría y su precisión aumenta al incrementarse la cantidad de AIMs. Al comparar con las estimaciones obtenidas en un trabajo previo a partir de 99 AIMs, se observó que para el componente minoritario (en este caso subsahariano) se obtiene una buena correlación utilizando al menos 30 marcadores. Se concluye que es necesario considerar en los estudios de ancestría individual el número de marcadores, su capacidad informativa y las características de la población bajo estudio.

A novel ecosystem to promote the physical, emotional and psychic health and well-being of the elderly is presented. Our proposal was designed to add several services developed to meet the needs of the senior population, namely services to improve social inclusion and increase contribution to society. Moreover, the solution monitors the vital signs of elderly individuals, as well as environmental parameters and behavior patterns, in order to seek eminent danger situations and predict potential hazardous issues, acting in accordance with the various alert levels specified for each individual. The platform was tested by seniors in a real scenario. The experimental results demonstrated that the proposed ecosystem was well accepted and is easy to use by seniors.

Presentamos una serie de 6 pacientes con eyaculación retrógrada tratados en la Unidad de Medicina Reproductiva de Clínica Alemana discutiendo su etiología, criterios diagnósticos y alternativas terapéuticasWe present 6 patients with retrograde ejaculation who were treated at the Reproductive Medicine Unit of Clinica Alemana discussing it's etiology, diagnostic criteria and therapeutic alternatives

Se presenta un análisis retrospectivo de ciclos de inseminación intrauterina efectuados por factor masculino entre Enero de 1998 y Marzo de 2002. El objetivo fue evaluar el valor predictivo de los parámetros seminales en el resultado de la inseminación intrauterina tanto en la muestra nativa como en la separación espermática. Se analizaron 423 ciclos de inseminación intrauterina por factor masculino en 193 pacientes, con una tasa de embarazo por ciclo de un 14,2%. Sólo el tiempo de infertilidad y la morfología espermática resultaron ser variables con diferencias significativas entre el grupo con y sin embarazo. Concluimos que los parámetros espermáticos no constituyen por sí solos elementos predictores del resultado de la inseminación intrauterinaThe aim of this study is to establish the predictive value of the seminal parameters in the result of intrauterine insemination in couples with male factor infertility. A retrospective study of cycles in couples with male factor between January 1998 and March 2002 is analyzed. A total of four hundred twenty three intrauterine insemination cycles for male factor on 193 patients were studied. The overall pregnancy per cycle was 14,2%. Time of infertility and sperm morphology showed a good predictive value for a successful pregnancy. In conclusion seminal parameters by themselves have no predictive value on the result of intrauterine insemination

The aim of this work was to study the population structure of Ocotea puberula (Nees et Mart.) Nees (Lauraceae), in a secondary and a primary forests Northeast of Misiones in Argentina, at 26º 15 ¢ S and 54º 15¢ W. Two permanent sampling plots of 3 hectares each were installed in the secondary and primary forest, respectively. Each sampling plot was divided into 75 subplots of 20 x 20 m. In each subplot all individuals of Ocotea puberula equal or greater than 20 cm of height were measured. The structure of size and spatial distribution was surveyed. Ocotea puberula was a secondary species, with a high number of individuals of natural regeneration in the secondary forest, and only adult trees in the primary forest. The species presented a clustered pattern of spatial distribution in both forests.

Se realiza un análisis retrospectivo de los casos de pacientes azoospérmicos obstructivos y no obstructivos en los cuales se recuperó espermatozoides mediante TESE con el objetivo de comparar los resultados de fecundación asistida utilizando espermatozoides testiculares frescos y criopreservados-descongelados. De un total de 18 ciclos realizados en 13 pacientes, 7 correspondieron a microinyección con transferencia inmediata a la trompa (SOFT) y 11 a ICSI con cultivo y transferencia uterina. En 4 pacientes que fueron sometidas a SOFT se empleó espermatozoides frescos resultando en 2 embarazos y en 3 pacientes espermios congelados-descongelados obteniéndose un embarazo. Con respecto a los ciclos de ICSI con transferencia uterina, 9 se practicaron con espermios frescos obteniendo 3 embarazos y 2 con espermatozoides congelados lográndose una gestión. La tasa de fertilización se calculó considerando sólo aquellos ciclos con transferencia uterina siendo de un 78% para los espermios frescos y de un 57,14% para los congelados. Las tasas de embarazo por ciclo fueron de 38,46% y 40% para los espermios frescos y congelados respectivamente. Se concluye que la utilización de espermios testiculares criopreservados-descongelados para ICSI en pacientes azoospérmicos demuestra resultados comparables a los obtenidos con espermios testiculares frescos constituyendo una herramienta invaluable en el manejo de esta patologíaWe performed a retrospective study in obstructive and non-obstructive azoospermic patients in which spermatozooa had been recovered through testicular biopsy (TESE). The main objective was to compare the results of assisted reproductive technique using fresh testicular spermatozoa and frozen-thawed testicular spermatozoa. From a total of 18 cycles in 13 patients, 7 were done with sperm-injected oocyte fallopian transfer (SOFT) and 11 with ICSI and uterine embryo transfer. Fresh spermatozoa were used in 4 patients in the SOFT group and frozen-thawed spermatozoa in 3 patients resulting in 3 and 1 clinical pregnancy respectively. In the ICSI group, 9 cycles used fresh spermatozoa obtaining three prergnancies and two frozen-thawed achieving 1 pregnancy. The fertilization rate was calculed considering only the cycles with uterine embryo transfer resulting in 78% for fresh sperm and 57.14% for frozen-thawed. The pregnancy rate per cycle was 38.46% and 40% for fresh and frozen-thawed sperm respectively. We conclude that the use of frozen thawed testicular sperm for ICSI in azoospermic patients shows comparable results to fresh testicular sperm being an iinvaluable tool for the management of this pathology

El objetivo de este trabajo fue evaluar la relación entre el porcentaje de cuello comprometido por neoplasia intraepitelial de alto grado en pacientes conizadas por asa leep y la persistencia de lesión residual en la pieza de histerectomía. Se presentan 78 casos de pacientes conizadas por asa leep y que posteriormente fueron sometidas a histerectomía entre junio de 1994 y diciembre del 2000 por enfermedad residual u otra patología ginecológica concomitante. Una vez obtenida la pieza de conización esta fue analizada en anatomía patológica evaluando el porcentaje de muestras comprometidas por nie de alto grado y se comparo con la persistencia de enfermedad en la pieza de histerectomía. Encontramos un valor significativamente estadístico entre el porcentaje de muestras comprometidas y la persistencia de enfermedad.The objetive of this research was to compare the percentage of persistence of residual lesion on hysterectomy specimen after a cone biopsy done with leep (loop electroexcision procedure) in patients with "high grade SIL" (squamous intraepithelial lesion). We present 78 patients that a cone biopsy with leep was done and subsequently had a histerectomy, between June 1994 and December 2000, for residual disease or other gynecological conditions. The pathology reports were statistically significant in between the percentage of compromised cervical biopsies and the persistence of disease in the uterus

The influence of acidic and alkaline conditions on the solubilisation process of waste activated sludge (WAS) was investigated using HCl and NaOH at pH 2, 10, 11 and 12. The rise in concentration of solubilised compounds, the influence of reaction time, and the influence of the concentration of total solids (TS) during the solubilisation process were determined. Physical and chemical tests demonstrated that pre-treatment provided a release of compounds from the sludge floc matrix into the soluble fraction, characterising the solubilisation process. The highest degree of WAS solubilisation was observed when a pH of 12 was applied. Although largest effects were already attained after 0.25 h, WAS solubilisation continued reaching an increase in total dissolved solids by a factor 10.4 after 720 hrs. Under these conditions, the dissolved organic carbon (DOC), proteins, and carbohydrates resulted in releases up to 15, 40 and 41 times, respectively; phosphorus increased 5.7 times. Results indicate that by applying alkaline pre-treatment, higher TS concentrations can be treated per reactor volume compared to non-pre-treated WAS. Aerobic and anaerobic biodegradability tests showed increased bioconversion potentials in full-scale treatment plants. The respirometry tests ratify the improvement in solubilisation, with O2 consumption rates increasing 1.4 times, concomitant with an additional 261 mg·L−1 of the COD used, which represents 90% bioconversion of waste activated sludge. Biomethanisation test indicated an increase of 3.6 times relative to the blank. HIGHLIGHTS Increased biodegradability of sludge identified by respirometric test.; Increased applicable sludge loading rates per reactor volume.; Increased degree of depolymerisation, characterised by the release of COD, TKN, phosphorus, protein, and carbohydrate in soluble fraction.; The alkaline process significantly favours the solubilisation of microbial aggregates over the acid process.;

The establishment of a virus infection is the result of the pathogen's ability to replicate in a hostile environment generated by the host's immune system. Here, we found that ISG15 restricts Dengue and Zika viruses' replication through the stabilization of its binding partner USP18. ISG15 expression was necessary to control DV replication driven by both autocrine and paracrine type one interferon (IFN-I) signaling. Moreover, USP18 competes with NS5-mediated STAT2 degradation, a major mechanism for establishment of flavivirus infection. Strikingly, reconstitution of USP18 in ISG15-deficient cells was sufficient to restore the STAT2's stability and restrict virus growth, suggesting that the IFNAR-mediated ISG15 activity is also antiviral. Our results add a novel layer of complexity in the virus/host interaction interface and suggest that NS5 has a narrow window of opportunity to degrade STAT2, therefore suppressing host's IFN-I mediated response and promoting virus replication., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Espada, da Rocha, Ricciardi-Jorge, dos Santos, Soares, Malaquias, Patrício, Gonzalez Kozlova, dos Santos, Bordignon, Sanford, Fajardo, Sweeney, Báfica and Mansur.)

Monocyte counts are increased during human tuberculosis (TB) but it has not been determined whether Mycobacterium tuberculosis ( Mtb ) directly regulates myeloid commitment. We demonstrated that exposure to Mtb directs primary human CD34 + cells to differentiate into monocytes/macrophages. In vitro myeloid conversion did not require type I or type II IFN signaling. In contrast, Mtb enhanced IL-6 responses by CD34 + cell cultures and IL-6R neutralization inhibited myeloid differentiation and decreased mycobacterial growth in vitro. Integrated systems biology analysis of transcriptomic, proteomic and genomic data of large data sets of healthy controls and TB patients established the existence of a myeloid IL-6/IL6R/CEBP gene module associated with disease severity. Furthermore, genetic and functional analysis revealed the IL6/IL6R/CEBP gene module has undergone recent evolutionary selection, including Neanderthal introgression and human pathogen adaptation, connected to systemic monocyte counts. These results suggest Mtb co-opts an evolutionary recent IFN-IL6-CEBP feed-forward loop, increasing myeloid differentiation linked to severe TB in humans., Competing Interests: MD, DM, EK, ER, GR, LM, GD, DP, TD, MB, GB, YT, MS, DR, JD, DM, JV, AB No competing interests declared, (© 2019, Delgobo et al.)