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Abstract Treatment based on immune checkpoint blockade has revolutionized cancer therapy. Despite the remarkable success achieved and the preclinical development of multiple checkpoint inhibitors targeting other checkpoints, only antibodies targeting the PD-1/PD-L1 axis and CTLA-4 have been approved for patient treatment, especially in solid tumors. Currently, with the approval of relatlimab, a LAG-3 blocking antibody, a third player, has been used in the fight against cancer. The endorsement of relatlimab marks a significant milestone in cancer immunotherapy, opening new avenues for combination therapies and enhancing treatment outcomes. However, the complex biology of LAG-3 may hinder its full development as a therapeutic alternative. In this review, we provide in-depth insight into the biology of LAG-3 and its current and future development in cancer treatment.

Background: The Phosphatase and Tensin Homolog gene (PTEN) is pivotal in regulating diverse cellular processes, including growth, differentiation, proliferation, and cell survival, mainly by modulating the PI3K/AKT/mTOR pathway. Alterations in the expression of the PTEN gene have been associated with epigenetic mechanisms, particularly the regulation by small non-coding RNAs, such as miRNAs. Modifications in the expression levels of miRNAs that control PTEN have been shown to lead to its underexpression. This underexpression, in turn, impacts the PI3K/AKT/mTOR pathway, thereby influencing crucial mechanisms like proliferation and apoptosis, playing an important role in the initiation and progression of prostate cancer (PCa). Thus, we aimed to systematically reviewed available information concerning the regulation of PTEN mediated by miRNA in PCa. Methods: Electronic databases were searched to identify studies assessing PTEN regulation via PCa miRNAs, the search included combination of the words microRNAs, PTEN and prostatic neoplasms. The quality assessment of the articles included was carried out using an adapted version of SYRCLE and CASP tool. Results: We included 39 articles that measured the relative gene expression of miRNAs in PCa and their relationship with PTEN regulation. A total of 42 miRNAs were reported involved in the development and progression of PCa via PTEN dysregulation (34 miRNAs up-regulated and eight miRNAs down-regulated). Sixteen miRNAs were shown as the principal regulators for genetic interactions leading to carcinogenesis, being the miR-21 the most reported in PCa associated with PTEN down-regulation. We showed the silencing of PTEN could be promoted by a loop between miR-200b and DNMT1 or by direct targeting of PTEN by microRNAs, leading to the constitutive activation of PI3K/AKT/mTOR and interactions with intermediary genes support apoptosis inhibition, proliferation, invasion, and metastasis in PCa. Conclusion: According to our review, dysregulation of PTEN mediated mainly by miR-21, -20a, −20b, −93, −106a, and −106b up-regulation has a central role in PCa development and could be potential biomarkers for diagnosis, prognostic, and therapeutic targets.

Applications of learning analytics (LA) can raise concerns from students about their privacy in higher education contexts. Developing effective privacy-enhancing practices requires a systematic understanding of students’ privacy concerns and how they vary across national and cultural dimensions. We conducted a survey study with established instruments to measure privacy concerns and cultural values for university students in five countries (Germany, South Korea, Spain, Sweden, and the United States; N = 762). The results show that students generally trusted institutions with their data and disclosed information as they perceived the risks to be manageable even though they felt somewhat limited in their ability to control their privacy. Across the five countries, German and Swedish students stood out as the most trusting and least concerned, especially compared to US students who reported greater perceived risk and less control. Students in South Korea and Spain responded similarly on all five privacy dimensions (perceived privacy risk, perceived privacy control, privacy concerns, trusting beliefs, and non-self-disclosure behavior), despite their significant cultural differences. Culture measured at the individual level affected the antecedents and outcomes of privacy concerns. Perceived privacy risk and privacy control increase with power distance. Trusting beliefs increase with a desire for uncertainty avoidance and lower masculinity. Non-self-disclosure behaviors rise with power distance and masculinity and decrease with more uncertainty avoidance. Thus, cultural values related to trust in institutions, social equality and risk-taking should be considered when developing privacy-enhancing practices and policies in higher education.

Livestock production is one of the most important agricultural sources of greenhouses gasses (GHG). Transforming the livestock sector is a critical task to mitigate the effects of climate change, and the implementation of silvopastoral systems (SPS) may be a way to do so. Carbon footprint (CF) estimation was carried out for 131 conventional livestock farms (CONF) and SPS farms (SPSF) selected in the states of Jalisco, Chiapas and Campeche (Mexico). GHG emissions were estimated based on interviews with the farmers and farm monitoring to collect information about management, milk production and the live weight gain (LWG) of calves (for meat production) using national emission factors. Emissions from animals, fossil fuels, electricity and nitrogen fertilizers were estimated using Tier I and II criteria. Land use distribution was recorded for each farm, and their carbon fixation in total biomass and soils was estimated using studies from tropical Latin America. CF was estimated for area and for production of milk and the LWG of calves. SPSF had lower GHG emissions, higher carbon fixation rates and a better CF than CONF (5.7 vs. 8.0 t CO2e/ha/year; 6.9 vs. 5.5 t C/ha/year and − 5.0 vs. −2.9 t CO2e/ha/year, respectively). The CF of milk production and calf LWG were − 68.6 to −4.6 kg CO2e/kg and − 3.2 to −0.1 t CO2e/kg, respectively. Our results highlight the importance of implementing SPS to mitigate climate change in livestock production, given its contribution to GHG emissions and the importance of capturing atmospheric carbon in biomass and soils. National and regional policies should focus on promoting implementing SPS as an active and effective strategy for improving CF in livestock farms.

Abstract Background and aims There is a link between genetics with metabolic balance and adiposity homeostasis on metabolic syndrome (MetS). Polymorphism in adipokine genes such as leptin and adiponectin may play an important role in its development. This study aimed to determine the association of the individual and general components of MetS with genetic alterations in LEP (rs7799039 and rs2167270) and ADIPOQ (rs1501299 and rs2241766) genes in the Mexican population. Methods and results The polymorphisms of the LEP gene rs7799039 and rs2167270, together with rs1501299 and rs2241766 polymorphisms of the ADIPOQ gene were genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) on 328 individuals (n = 131 MetS). The rs7799039 under the recessive inheritance model was found to be associated with increased risk of MetS (OR = 2.16, 95% CI = 1.06–4.37), dyslipidemia (OR = 7.97, 95% CI = 2.17–29.36), low HDL (OR = 7.01, 95% CI = 1.65–29.71) and hypertension (OR = 13.02, 95% CI = 1.76–96.44); the heterozygote demonstrate a protective effect on MetS (OR = 0.48, 95% CI = 0.28–0.88) and diabetes (OR = 0.09, 95% CI = 0.02–0.53) under the over the dominant model. Haplotype analysis showed linkage disequilibrium between the SNPs of ADIPOQ rs1501299/rs2241766, and their association as risk factors for low HDL and hypertension. Conclusion The association of rs7799039 with the presence of MetS, suggests a risk factor for the development of dyslipidemia, as well as its heterozygous as a protective factor for DM. There is a linkage disequilibrium between the SNPs of ADIPOQ.

Abstract Background In 2010, a political and social crisis pushed thousands of Venezuelans out of their country; today, seven million Venezuelans live abroad. In addition, during the COVID-19 pandemic, border closure increased and affected specific vulnerable migration flows, such as Venezuelans trying to migrate to Chile through the Northern borders. In this context, there is little evidence of migrants’ health status and needs, their access to health services, and other basic needs (e.g., housing) from a human rights perspective. Therefore, we qualitatively explored the effects of border closure due to the COVID-19 pandemic on Venezuelan migrants’ health and human rights, focusing on access to healthcare in the Northern Chilean border that adjoins Peru and Bolivia. Methods Following a case-study qualitative design, we conducted an ethnography that included participatory observation of relevant sites (e.g., hospitals, main squares, migrant shelters) in Antofagasta, Iquique, and Arica and 30 in-depth interviews with actors in the health sector (n = 7), experts from the non-governmental sector (n = 16), and governmental actors (n = 7) in three large cities close to the Northern border. Results We found four main dimensions: (i) border and migration processes, (ii) specific groups and intersectionality, (iii) barriers to healthcare services, and (iv) regional and local responses to the crisis during the COVID-19 pandemic. Programs characterized by the presence of healthcare providers in the field were essential to attend to migrants’ health needs at borders. Conclusions Coordination between actors is crucial to implement regional protocols that respond to current migration phenomena and migrants’ health needs. Health policies using a human rights approach are urgently required to respond to migrants’ healthcare needs at borders in South America.

Viral hepatitis is the main cause of infectious liver disease. During pregnancy, a risk of vertical transmission exists both during gestation and at birth. HAV, HBV, and HCV might progress similarly in pregnant and non-pregnant women. In this study, we found a prevalence of 0.22% of viral hepatitis in pregnant women, with a light preponderance of HCV over HAV and HBV. Here, it was observed that acute HAV infection is more symptomatic and has higher risks for the mother and fetus, in a similar manner to what has been reported for HEV. Histopathological alterations were observed in all except one placenta, indicating that it is an important tissue barrier. Regarding the Mexican strategies for viral hepatitis eradication, success may be related to vaccination at birth, whereas for HCV, the national program for eradication is aimed at treating the infection via direct-acting antiviral agents. The HBV strategy has positively impacted pregnant women and their children, diminishing the risk of vertical transmission. The HCV strategy is still in its early years, and it is expected to be just as successful. For acute hepatitis, HAV and HEV, programs promoting hand washing and those aimed at providing clean food and water are applicable as preventive strategies, alongside other programs such as vaccination.

Soils are a valuable renewable resource on human timescales, and they interact with distinctive grassland ecosystems characterized by unique biodiversity and essential provision of ecosystem services, such as water supply and carbon sequestration. However, knowledge of the effects of wildfires on soil properties and nutrient availability in the Andes remains limited. Andean grasslands are currently one of the ecosystems of the Peruvian Andes most affected by wildfires. Our objective is to analyze the effect of fire activity on the physicochemical properties of soil and analyze its social context in Cusco, in the southern Andes of Peru. Soil samples were collected during five periods, spanning both the dry and rainy seasons, to characterize changes in soil properties and monitor vegetation recovery post-fire in two local communities dedicated to livestock activities. The vegetation restored after the wildfire was measured by the “step transect” method. Post-fire changes in soil properties indicate slight increases in pH, electrical conductivity, organic matter, nitrogen, phosphorus, and potassium during the onset of the rainy season; thereafter, a gradual reduction in these values was observed. This reduction can be attributed to leaching associated with the seasonal rainfall and runoff regime. Our findings indicate that one-year post-fire, the biomass in burned areas is reduced to 30–46% of the biomass in unburned areas. A complete regeneration is likely to occur in up to 4 years; this assertion is supported by the perceptions of the affected population, as expressed in interviews conducted in the two farming communities. These results are significant for decision-makers formulation of policies and regulations regarding grasslands and their seasonal restoration.

Abstract Recent introduction of monoclonal antibodies targeting immune checkpoints to harness antitumor immunity has revolutionized the cancer treatment landscape. The therapeutic success of immune checkpoint blockade (ICB)-based therapies mainly relies on PD-1/PD-L1 and CTLA-4 blockade. However, the limited overall responses and lack of reliable predictive biomarkers of patient´s response are major pitfalls limiting immunotherapy success. Hence, this reflects the compelling need of unveiling novel targets for immunotherapy that allow to expand the spectrum of ICB-based strategies to achieve optimal therapeutic efficacy and benefit for cancer patients. This review thoroughly dissects current molecular and functional knowledge of BTLA/HVEM axis and the future perspectives to become a target for cancer immunotherapy. BTLA/HVEM dysregulation is commonly found and linked to poor prognosis in solid and hematological malignancies. Moreover, circulating BTLA has been revealed as a blood-based predictive biomarker of immunotherapy response in various cancers. On this basis, BTLA/HVEM axis emerges as a novel promising target for cancer immunotherapy. This prompted rapid development and clinical testing of the anti-BTLA blocking antibody Tifcemalimab/icatolimab as the first BTLA-targeted therapy in various ongoing phase I clinical trials with encouraging results on preliminary efficacy and safety profile as monotherapy and combined with other anti-PD-1/PD-L1 therapies. Nevertheless, it is anticipated that the intricate signaling network constituted by BTLA/HVEM/CD160/LIGHT involved in immune response regulation, tumor development and tumor microenvironment could limit therapeutic success. Therefore, in-depth functional characterization in different cancer settings is highly recommended for adequate design and implementation of BTLA-targeted therapies to guarantee the best clinical outcomes to benefit cancer patients.

The mammalian carboxylesterase 1 (Ces1/CES1) family comprises several enzymes that hydrolyze many xenobiotic chemicals and endogenous lipids. To investigate the pharmacological and physiological roles of Ces1/CES1, we generated Ces1 cluster knockout (Ces1–/–) mice, and a hepatic human CES1 transgenic model in the Ces1–/– background (TgCES1). Ces1–/– mice displayed profoundly decreased conversion of the anticancer prodrug irinotecan to SN-38 in plasma and tissues. TgCES1 mice exhibited enhanced metabolism of irinotecan to SN-38 in liver and kidney. Ces1 and hCES1 activity increased irinotecan toxicity, likely by enhancing the formation of pharmacodynamically active SN-38. Ces1–/– mice also showed markedly increased capecitabine plasma exposure, which was moderately decreased in TgCES1 mice. Ces1–/– mice were overweight with increased adipose tissue, white adipose tissue inflammation (in males), a higher lipid load in brown adipose tissue, and impaired blood glucose tolerance (in males). These phenotypes were mostly reversed in TgCES1 mice. TgCES1 mice displayed increased triglyceride secretion from liver to plasma, together with higher triglyceride levels in the male liver. These results indicate that the carboxylesterase 1 family plays essential roles in drug and lipid metabolism and detoxification. Ces1–/– and TgCES1 mice will provide excellent tools for further study of the in vivo functions of Ces1/CES1 enzymes.

Dexamethasone implementation for COVID-19 management represented a milestone but data regarding its impact and safety have not been consistently reproduced. We aimed to evaluate in-hospital mortality before and after the implementation of corticosteroid treatment (CS-T) for severe and critical COVID-19. We conducted a cohort study that included patients admitted with severe and critical COVID-19. The primary outcome was death during hospitalization. Secondary outcomes included the length of stay (LOS), need for invasive mechanical ventilation (IMV), time to IMV initiation, IMV duration, and development of hospital-acquired infections (HAIs). Bivariate, multivariate, and propensity-score matching analysis were performed. Among 1540 patients, 688 (45%) received CS-T. Death was less frequent in the CS-T group (18 vs 31%, p

Abstract A large area of the terrestrial land surface is used for livestock grazing. Trees on grazing lands provide and can enhance multiple ecosystem services such as provisioning, cultural and regulating, that include carbon sequestration. In this study, we assessed the above- and belowground carbon stocks across six different land-uses in livestock-dominated landscapes of Mexico. We measured tree biomass and soil organic carbon (SOC) stocks in fodder banks, live fences, pasturelands with dispersed trees, secondary forests, and primary forests from three different geographical regions and compared them with conventional open pasturelands respectively. We also calculated tree diversity indices for each land-use and their similarity with native primary forests. The aboveground woody biomass stocks differed significantly between land-uses and followed the gradient from less diverse conventional open pasturelands to silvopastoral systems and ecologically complex primary forests. The SOC stocks showed a differential response to the land-use gradient dependent on the study region. Multivariate analyses showed that woody biomass, fine root biomass, and SOC concentrations were positively related, while land-use history and soil bulk density showed an inverse relationship to these variables. Silvopastoral systems and forest remnants stored 27–163% more carbon compared to open pasturelands. Our results demonstrate the importance of promoting appropriate silvopastoral systems and conserving forest remnants within livestock-dominated landscapes as a land-based carbon mitigation strategy. Furthermore, our findings also have important implications to help better manage livestock-dominated landscapes and minimize pressures on natural protected areas and biodiversity in the hotspots of deforestation for grassland expansion.

Context: Studies carried out in low voltage networks have explored the modeling of linear single-phase loads (such as motors) and non-linear ones (such as those based on power electronics). However, induction motors exhibit non-linear characteristics between voltage and current due to the saturation of their magnetic parts. Therefore, it is necessary to study induction motors in the frequency domain with a model that allows reviewing the characteristic nonlinearity of their voltage-current interaction. Methodology: This article presents the frequency domain modeling of a single-phase induction motor used as a silent air extractor (127 V, 60 Hz, 66 W), which presents a capacitive behavior (fp = 0,93 in leading) and harmonic distortion due to a third-order component (7,0%) when fed with a pure sinusoidal voltage of 127 V. Results: This work establishes the parameters of two approaches to the Norton equivalent model (coupled and decoupled admittance matrix) which are used to estimate the distorted current signal and the values ​​of consumed active and non-active power. The results show comparisons errors of P, Q, THDi, and NRMSE indices of less than 7, 4, 14, and 3%, respectively. Conclusions: The parameters of the Norton equivalent model estimated for the single-phase induction motor allow calculating the current signal with a high degree of precision. This signal exhibits nonlinear characteristics and a capacitive behavior due to the permanent presence of a capacitor aiding the start and operation of the engine.

Mammalian carboxylesterase 1 enzymes can hydrolyze many xenobiotic chemicals and endogenous lipids. We here identified and characterized a mouse strain (FVB/NKI) in which three of the eight Ces1 genes were spontaneously deleted, removing Ces1c and Ces1e partly, and Ces1d entirely. We studied the impact of this Ces1c/d/e deficiency on drug and lipid metabolism and homeostasis. Ces1c/d/e-/- mice showed strongly impaired conversion of the anticancer prodrug irinotecan to its active metabolite SN-38 in plasma, spleen and lung. Plasma hydrolysis of the oral anticancer prodrug capecitabine to 5-DFCR was also profoundly reduced in Ces1c/d/e-/- mice. Our findings resolved previously unexplained FVB/NKI pharmacokinetic anomalies. On a medium-fat diet, Ces1c/d/e-/- female mice exhibited moderately higher body weight, mild inflammation in gonadal white adipose tissue (gWAT), and increased lipid load in brown adipose tissue (BAT). Ces1c/d/e-/- males showed more pronounced inflammation in gWAT and an increased lipid load in BAT. On a 5-week high-fat diet exposure, Ces1c/d/e deficiency predisposed to developing obesity, enlarged and fatty liver, glucose intolerance and insulin resistance, with severe inflammation in gWAT and increased lipid load in BAT. Hepatic proteomics analysis revealed that the acute phase response, involved in the dynamic cycle of immunometabolism, was activated in these Ces1c/d/e-/- mice. This may contribute to the obesity-related chronic inflammation and adverse metabolic disease in this strain. While Ces1c/d/e deficiency clearly exacerbated metabolic syndrome development, long-term (18-week) high-fat diet exposure overwhelmed many, albeit not all, observed phenotypic differences.

Introduction and objectives: Intrahepatic cholestasis is a frequent disease during pregnancy. It is unknown if liver function alterations produce specific placental lesions. The aim of this study was to evaluate placental histopathological changes in patients with intrahepatic cholestasis of pregnancy (ICP), and to explore correlations between the placental histopathology and hepatic function alteration or patient comorbidities, and body mass index. Patients and methods: A retrospective cohort study included women with ICP, most of them showing comorbidities such as overweight/obesity, preeclampsia and gestational diabetes. They were attended at the National Institute of Perinatology in Mexico City for three years. Placental histopathological alterations were evaluated according to the Amsterdam Placental Workshop Group Consensus Statement. Data was analyzed using Graph-Pad Prism 5. Results: The results indicated that the placenta of ICP patients showed many histopathological alterations; however, no correlations were observed between the increase in bile acids or liver functional parameters and specific placental lesions. The most frequent comorbidities found in ICP patients were obesity, overweight and preeclampsia. Surprisingly, high percentage of ICP patients did not respond to UDCA treatment independently of the BMI group to which they belonged. Conclusion: The data suggest that ICP contribute to placental lesions. In addition, in patients with normal weight, an increase of chorangiosis and a reduced accelerated villous maturation without syncytial knots were observed in comparison with overweight and obese patients. It is necessary to improve the medical strategies in the treatment and liver disfunction surveillance of ICP patients.

Objectives: The purpose of this study was (i) to investigate whether nanocomposite poly(methyl-methacrylate)-zinc oxide nanowires (PMMA-ZnO-NWs) have C. albicans antibiofilm activity; (ii) to evaluate the interaction between components of the nanocomposites based on PMMA-ZnO-NWs by Raman spectroscopy; and (iii) to assess ultrastructural alterations. Design: Sixty-eight rectangles (17 PMMA (control) and 51 PMMA–ZnO-NWs (250, 500, 1000 ppm ZnO nanowires) were fabricated. C. albicans ATCC 10231 and a C. albicans clinical strain were tested. Adherence, biofilm formation and ultrastructural alterations were assessed by transmission electron microscopy. Raman mapping images and spectra were analyzed using main component analysis. Results: Nanocomposite PMMA-ZnO-NWs inhibited the formation of C. albicans biofilms 94% at 1000 ppm and 80% at 500 ppm against both C. albicans strains. PMMA-ZnO-NWs induced ultrastructural alterations, including cell wall damage and disorganization of the cytoplasmic membrane, resulting in cell lysis. Raman spectroscopy showed new vibrational modes (300–365–485–600 cm−1) for PMMA and ZnO-NW interactions. Conclusions: PMMA-ZnO-NWs inhibited C. albicans dose-dependent biofilm formation and led to changes in the structures and cell membrane. Raman spectroscopy showed chemical interactions between ZnO-NWs and PMMA, as suggested by the appearance of new bands at 301 and 485 cm−1.

RESUMEN Objetivo: Estudiar en pacientes mayores de 65 años las prescripciones potencialmente inapropiadas y omisiones de prescripción en patología cardiovascular en atención primaria. Metodología: Estudio descriptivo transversal en un centro de salud urbano utilizando la versión 2 de los criterios STOPP-START. Resultados: En los 170 pacientes incluidos (62,4% mujeres; mediana de edad, 79 años) hubo un 15,3% de prescripciones potencialmente inapropiadas y un 8,8% de omisiones de prescripción. El 72,9% tenía más de 4 enfermedades y el 57,1% tomaba más de 4 fármacos. A mayor pluripatología, mayor consumo de fármacos, sin relación entre las prescripciones potencialmente inapropiadas y las características epidemiológicas y clínicas de los pacientes. Conclusiones: Los criterios STOPP-START son útiles para revisar la prescripción en personas mayores de 65 años con enfermedades cardiovasculares entre su pluripatología.

El agua es un elemento fundamental para la generación de servicios ecosistémicos de aprovisionamiento. La comprensión de los servicios ecosistémicos hídricos requiere entender las interrelaciones entre hidrología, paisajes y ecología (Martin-Ortega et al., 2015).

Los ranchos ganaderos albergan gran variedad de árboles que pueden ser manejados para generar beneficios (Marinidou y Ferrer, 2010).

Prostate cancer (PCa) is the second most frequent cancer diagnosed in men worldwide. The detection methods for PCa are either unreliable, like prostate-specific antigen (PSA), or extremely invasive, such as in the case of biopsies. Therefore, there is an urgent necessity for reliable and less invasive detection procedures that can differentiate between patients with benign diseases and those with cancer. In this matter, microRNAs (miRNAs) are suggested as potential biomarkers for cancer. MiRNAs have been found to be dysregulated in several different cancers, and these genetic alterations may present specific signatures for a given malignancy. Here, we examined the expression of miR141-3p, miR145-5p, miR146a-5p, and miR148b-3p in human tissue samples of PCa ( n = 41) and benign prostatic diseases (BPD) ( n = 30) using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). We combined the expression results with patient clinicopathological characteristics in logistic regression models to create accurate PCa predictive models. A model including information of miR148b-3p and patient age showed relevant prediction results (area under the curve [AUC] = 0.818, precision = 0.763, specificity = 0.762, and accuracy = 0.762). A model including all four miRNAs and patient age presented outstanding prediction results (AUC = 0.918, precision = 0.861, specificity = 0.861, and accuracy = 0.857). Our results represent a potential novel procedure based on logistic regression models that utilize miRNA expressions and patient age to assist with PCa diagnosis.

Objective: To describe the perception of vulnerability to HIV and its associated factors among transgender women (TW) in Bogotá, Medellín and Santiago de Cali, Colombia. Materials and methods: We conducted a cross-sectional study, using respondent-driven sampling (RDS) in which 620 TW participated. Sociodemographic aspects, sexual behavior, consumption of psychoactive substances and the perception of vulnerability to HIV were studied. We carried out a descriptive analysis, in which bivariate associations were evaluated using chi-square. We also conducted a multivariate analysis and built a model using Poisson regression. Results: Of the participants, 63% were 35 years old or younger, had low income, started sexual relations at an early age and worked mainly as sex workers, webcam models and hairdressers; 84.7% of the participants had received money in exchange for sex at some point. The perception of vulnerability to HIV increased among those who were single, worked in prostitution, had sexually transmitted infections in the last year, avoided preventive health services and consumed cocaine during the six months before this survey. Conclusion: The perception of vulnerability to HIV among the TW participants in this study is high; therefore, effective interventions are required to improve the living conditions and sexual behavior of this population.

Abstract Analysing pig class II mayor histocompatibility complex (MHC) molecules is mainly related to antigen presentation. Identifying frequently-occurring alleles in pig populations is an important aspect to be considered when developing peptide-based vaccines. Colombian creole pig populations have had to adapt to local conditions since entering Colombia; a recent census has shown low amounts of pigs which is why they are considered protected by the Colombian government. Commercial hybrids are more attractive regarding production. This research has been aimed at describing the allele distribution of Colombian pigs from diverse genetic backgrounds and comparing Colombian SLA-DRB1 locus diversity to that of internationally reported populations. Twenty SLA-DRB1 alleles were identified in the six populations analysed here using sequence-based typing. The amount of alleles ranged from six (Manta and Casco Mula) to nine (San Pedreño). Only one allele (01:02) having > 5% frequency was shared by all three commercial line populations. Allele 02:01:01 was shared by five populations (around > 5% frequency). Global FST indicated that pig populations were clearly structured, as 20.6% of total allele frequency variation was explained by differences between populations (F ST = 0.206). This study’s results confirmed that the greatest diversity occurred in wild boars, thereby contrasting with low diversity in domestic pig populations.

Existe evidencia de que el uso de juegos digitales basados en herramientas multisensoriales proporciona beneficios en diferentes dimensiones del aprendizaje del alumnado con necesidades educativas especiales. Sin embargo, el uso de estas herramientas en aulas de infantil y primaria para favorecer la inclusión de dicho alumnado no ha sido tratado en profundidad. El trabajo tiene como objetivo analizar de qué modo la participación de un grupo de docentes en un programa de desarrollo profesional centrado en la integración en el aula de juegos basados en tecnologías multisensoriales, contribuyó a hacer evolucionar sus actitudes sobre la adopción de estas tecnologías en contextos escolares desde una perspectiva inclusiva. En esta investigación se ha empleado un método mixto con estrategia secuencial explicativa. Las técnicas e instrumentos empleados, entrevistas y cuestionarios, nos han permitido recabar datos sobre la evolución de las preocupaciones docentes tras la formación recibida en el marco del Proyecto Europeo INTELed. Los resultados muestran que los docentes otorgaron gran valor a las colaboraciones surgidas en el proyecto, y experimentaron una evolución hacia mayores grados de preocupación en relación con la sostenibilidad y la transferencia de este tipo de innovaciones en el aula. /// There is evidence that the use of digital games based on multisensory tools provides benefits in different dimensions of learning for students with special educational needs. However, the use of these tools in early childhood and primary education classrooms to promote the inclusion of such students has not been treated in depth. The aim of this paper is to analyze how the participation of a group of teachers in a professional development program focused on the integration in the classroom of games based on multisensory technologies contributed to the evolution of their attitudes about the adoption of these technologies in school contexts from an inclusive perspective. In this research, a mixed method with a sequential explanatory strategy has been used. The techniques and instruments used, interviews and questionnaires, have allowed us to collect data on the evolution of the concerns that arose after the training received in the framework of the European project INTELed. The results show that the teachers highly valued the collaborations that emerged during the project, and that they experienced an evolution towards higher levels of concern regarding sustainability and transfer in this type of innovations in the classroom.

Objetivo: Reportar un caso de migraña oftalmopléjica interna en una paciente que presenta midriasis bilateral persistente y visión borrosa. Caso clínico: Mujer de 18 años con fotofobia, fonofobia e intensa cefalea pulsante en toda la cabeza. Sus pupilas no reaccionan a la luz y presentan pérdida de acomodación. Después de visualizar el fondo de ojo, se reportó edema papilar del ojo derecho. Fue referida a neurología para evaluarla adicionalmente. Resultados: La resonancia magnética cerebral, la angiorresonancia arterial y los estudios de laboratorio se reportan normales. Se diagnosticó migraña oftalmopléjica interna por exclusión de todos los diagnósticos diferenciales. Conclusiones: La migraña oftalmopléjica se considera una cefalea rara caracterizada por parálisis del tercero, cuarto o sexto nervio craneal. Los episodios de migraña asociados con midriasis, conocidos como migraña oftalmopléjica interna, son notablemente raros y el diagnóstico es de exclusión. La migraña se resolvió con dexametasona y parecoxib, pero la midriasis no se resolvió.

The psychedelic alkaloid ibogaine is increasingly used as an oral treatment for substance use disorders, despite being unlicensed in most countries and having reported adverse events. Using wild-type and genetically modified mice, we investigated the impact of mouse (m)Abcb1a/1b and Abcg2 drug efflux transporters, human and mouse OATP drug uptake transporters, and the CYP3A drug-metabolizing complex on the pharmacokinetics of ibogaine and its main metabolites. Following oral ibogaine administration (10 mg/kg) to mice, we observed a rapid and extensive conversion of ibogaine to noribogaine (active metabolite) and noribogaine glucuronide. Mouse Abcb1a/1b, in combination with mAbcg2, modestly restricted the systemic exposure (plasma AUC) and peak plasma concentration (Cmax) of ibogaine. Accordingly, we found a ∼2-fold decrease in the relative recovery of ibogaine in the small intestine with fecal content in the absence of both transporters compared to the wild-type situation. Ibogaine presented good intrinsic brain penetration even in wild-type mice (brain-to-plasma ratio of 3.4). However, this was further increased by 1.5-fold in Abcb1a/1b;Abcg2−/− mice, but not in Abcg2−/− mice, revealing a stronger effect of mAbcb1a/1b in restricting ibogaine brain penetration. The studied human OATP transporters showed no major impact on ibogaine plasma and tissue disposition, but the mOatp1a/1b proteins modestly affected the plasma exposure of ibogaine metabolites and the tissue disposition of noribogaine glucuronide. No considerable role of mouse Cyp3a knockout or transgenic human CYP3A4 overexpression was observed in the pharmacokinetics of ibogaine and its metabolites. In summary, ABCB1, in combination with ABCG2, limits the oral availability of ibogaine, possibly by mediating its hepatobiliary and/or direct intestinal excretion. Moreover, ABCB1 restricts ibogaine brain penetration. Variation in ABCB1/ABCG2 activity due to genetic variation and/or pharmacologic inhibition might therefore affect ibogaine exposure in patients, but only to a limited extent. The insignificant impact of human CYP3A4 and OATP1B1/1B3 transporters may be clinically advantageous for ibogaine and noribogaine use, as it decreases the risks of undesirable drug interactions or interindividual variation related to CYP3A4 and/or OATP activity.

Objective. To estimate the usual intake and the prevalence of inadequacy of selected nutrients in the Mexican population and the potential effect that the nutrient retention factors (NRF) could have on these estimates. Likewise, document the methodology used in the analysis of the 24 hours of the mid-way National Health and Nutrition Survey 2016 (Ensanut MC 2016). Materials and methods. Dietary information from the Ensanut MC 2016 was analyzed with and without the use of NRFs. Results. Most nutrients evaluated showed a relevant inadequacy prevalence above 10% in all age groups. Likewise, we documented that, when NRFs were not applied, estimated intakes and prevalence were significantly under­estimated in a range of 2% to 55.5%. Conclusions. We documented the relevance of the application of NRFs for adequate estimation of the prevalence of inadequate intake of selected nutrients in population studies.

Abstract Background Modern imaging plays a central role in the care of obese patients, and there is an integral focus on its use and accessibility in individuals who have alterations of various in various organs. The objective in this study was to perform an echographic analysis of musculoskeletal system disorders, endothelial dysfunction and the left ventricle (LV) in obese rats. Methods Sprague Dawley rats (250 ± 5 g) were obtained and divided into two groups: the control (C) group was fed with a standard diet, and the obese (Ob) group was fed hyper caloric diet with a high fructose-fat content for 4 months. Body weight, cholesterol, triglycerides, glucose, inflammatory cytokines and adhesion molecules (ICAM-1, VCAM-1) were measured. Additionally, two-dimensional echocardiography, abdominal ultrasound and musculoskeletal system studies were performed in the lower extremities. Results The body weight in the Ob group was increased compared to that in the control group, (p

As in other research fields, the development of learning analytics is influenced by the networks of researchers that contribute to it. This paper describes one of such networks: the Spanish Network of Learning Analytics (SNOLA). The paper presents the research lines of the members of SNOLA, as well as the main challenges that learning analytics has to address in the next few years as perceived by these researchers. This analysis is based on SNOLA’s archival data and on a survey carried out to the current members of the network. Although this approach does not cover all the activity related to learning analytics in Spain, the results provide a representative overview of the current state of research related to learning analytics in this context. The paper describes these trends and the main challenges, among which we can point out the need to adopt an ethical commitment with data, to develop systems that respond to the requirements of the end users, and to reach a wider institutional impact.

[This corrects the article DOI: 10.1371/journal.pone.0245772.].

Existen diferentes enfoques que permiten transferir conocimientos, en particular tecnologías agropecuarias. Sin embargo, la eficiencia de muchos de ellos es cuestionada al no considerar la participación de productores, por ello, el proyecto BioPaSOS (Biodiversidad y Paisajes Ganaderos Agrosilvopastoriles Sostenibles) optó por utilizar las Escuelas de Campo (ECA) como principal mecanismo para la transferencia de conocimientos.

En México se practica ampliamente la ganadería extensiva, la cual contribuye a la degradación de las pasturas y suelos, a la pérdida de la biodiversidad y a exacerbar los efectos negativos del cambio climático (Zepeda-Cancino et al., 2016). La reconversión productiva, el paso de una ganadería extensiva a una ganadería sustentable es una alternativa para minimizar los impactos negativos de la producción ganadera sobre el ambiente y de contribuir a mejorar la calidad de vida de los productores.

Los sistemas silvopastoriles tienen gran potencial para simultáneamente aumentar la productividad de las fincas ganaderas y conservar la biodiversidad. Sin embargo, las investigaciones de quirópteros en paisajes ganaderos son escasas en México.

Los sistemas silvopastoriles (SSP) se implementan con éxito en América Latina y el Caribe. Los SSP combinan pastos, arbustivas, árboles y animales en un mismo espacio.

El cambio climático (CC) es uno de los principales problemas ambientales que afectan a la humanidad. La ganadería extensiva y sus malas prácticas contribuyen a exacerbar los efectos negativos del CC. Los sistemas silvopastoriles (SSP) promueven la inclusión de árboles en los ranchos, proporcionando así múltiples beneficios (Pérez, 2008, Navas, 2010).

Silymarin is obtained from the Milk thistle plant Silybum marianum and has been used over the centuries to treat principally liver disease, although it has also been studied for its beneficial effects in cardioprotection, neuroprotection, immune modulation, and cancer among others. Importantly, silymarin’s active component silybin is a flavonolignan that exhibits different activities such as; scavenger, anti-oxidant, anti-inflammatory, and recently revealed, insulin-sensitizing properties which have been explored in clinical trials in patients with insulin resistance. In this review, we summarize the most relevant research of silymarin’s effect on lipid and carbohydrate metabolism, focusing the attention on insulin resistance, which is well known to play a crucial role in metabolic disease progression.

Fishes are a paraphyletic group composed by craniates except for the four-limbed clade Tetrapoda. This group was the only vertebrate representative until the Devonian but now comprises almost half of the vertebrate species, dominating nearly all aquatic environments. The fossil record is the key to understand the ancient paleobiodiversity and the patterns that lead the modern fish fauna, and paleontological collections play a fundamental role in providing accommodation, maintenance, and access to the specimens and their respective metadata. Here we present a systematic checklist of fossil fishes housed in the type collection of the Colección Nacional de Paleontología which is located at the Instituto de Geología of Universidad Nacional Autónoma de México. Currently housed in the type collection are 14 chondrichthyan specimens, belonging to two superorders, five orders, seven families, 10 genera, and five nominal species, and 361 osteichthyan specimens, belonging to eight orders, nine families, nine genera, and 26 nominal species. These fossils come from 32 localities and 15 geological units, which range temporally from the Jurassic to the Pleistocene. The paleoichthyofauna housed in the type collection of the Colección Nacional de Paleontología is remarkable for its singularity and reveals new insights about the origin and diversification of many groups of fishes. The recovery and curation of this fossil material indicates that knowledge of Mexican fossil fish diversity and its role in understanding lower vertebrate evolution are just emerging and reaffirms the importance of the biological and paleontological collections to the future biodiversity research.

Este artículo aborda la temática de la masculinidad en un contexto de carencia (la pérdida de la salud y el empleo del varón a cargo de una familia), y es producto de un trabajo de investigación más amplio, que reflexiona sobre la problemática de las “nuevas” masculinidades en el contexto latinoamericano. Específicamente en la ciudad de Córdoba, Argentina. En este escrito utilizo la autoetnografía, situada en el marco de la etnografía performativa, y describo mi propia experiencia como hija de un hombre que, dada una enfermedad crónica, debió alejarse de su actividad laboral siendo muy joven. Finalizo proponiendo una reflexión en torno a la masculinidad hegemónica así como respecto de la autoetnografía, como método analítico e interpretativo.

The extrapolation of drug exposure between species remains a challenging step in drug development, contributing to the low success rate of drug approval. As a consequence, extrapolation of toxicology from animal models to humans to evaluate safe, first-in-human (FIH) doses requires high safety margins. We hypothesized that a human-CYP3A4-expressing transgenic (Cyp3aXAV) mouse is a more predictive model for human drug exposure of CYP3A4-metabolized small-molecule drugs. Population pharmacokinetic models based on wild-type (WT) and Cyp3aXAV mouse pharmacokinetic data of oral lorlatinib, brigatinib, ribociclib and fisogatinib were allometrically scaled and compared to human exposure. Extrapolation of the Cyp3aXAV mouse model closely predicted the observed human exposure for lorlatinib and brigatinib with a 1.1-fold and 1.0-fold difference, respectively, compared to a 2.1-fold and 1.9-fold deviation for WT-based extrapolations of lorlatinib and brigatinib, respectively. For ribociclib, the extrapolated WT mouse model gave better predictions with a 1.0-fold deviation compared to a 0.3-fold deviation for the extrapolated Cyp3aXAV mouse model. Due to the lack of a human population pharmacokinetic model for fisogatinib, only median maximum concentration ratios were calculated, resulting in ratios of 1.0 and 0.6 for WT and Cyp3aXAV mice extrapolations, respectively. The more accurate predictions of human exposure in preclinical research based on the Cyp3aXAV mouse model can ultimately result in FIH doses associated with improved safety and efficacy and in higher success rates in drug development.

Di(2-ethylhexyl) phthalate (DEHP) is a chemical widely distributed in the environment as is extensively used in the plastic industry. DEHP is considered an endocrine disruptor chemical (EDC) and humans are inevitably and unintentionally exposed to this EDC through several sources including food, beverages, cosmetics, medical devices, among others. DEHP exposure has been associated and may be involved in the development of various pathologies; importantly, pregnant women are a particular risk group considering that endocrine alterations during gestation may impact fetal programming leading to the development of several chronic diseases in adulthood. Recent studies have indicated that exposure to DEHP and its metabolite Mono(2-ethylhexyl) phthalate (MEHP) may impair placental development and function, which in turn would have a negative impact on fetal growth.Studies performed in several trophoblastic and placental models have shown the negative impact of DEHP and MEHP in key processes related to placental development such as implantation, differentiation, invasion and angiogenesis. In addition, many alterations in placental functions like hormone signaling, metabolism, transfer of nutrients, immunomodulation and oxidative stress response have been reported. Moreover, clinical-epidemiological evidence supports the association between DEHP exposure and adverse pregnancy outcomes and pathologies. In this review, we aim to summarize for the first time current knowledge about the impact of DEHP and MEHP exposure on placental development and pathophysiology, as well as the mechanisms involved. We also remark the importance of exploring DEHP and MEHP effects in different trophoblast cell populations and discuss new perspectives regarding this topic.

BackgroundAs the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has remained in Latin America, Mexico has become the third country with the highest death rate worldwide. Data regarding in-hospital mortality and its risk factors, as well as the impact of hospital overcrowding in Latin America has not been thoroughly explored.Methods and findingsIn this prospective cohort study, we enrolled consecutive adult patients hospitalized with severe confirmed COVID-19 pneumonia at a SARS-CoV-2 referral center in Mexico City from February 26th, 2020, to June 5th, 2020. A total of 800 patients were admitted with confirmed diagnosis, mean age was 51.9 ± 13.9 years, 61% were males, 85% were either obese or overweight, 30% had hypertension and 26% type 2 diabetes. From those 800, 559 recovered (69.9%) and 241 died (30.1%). Among survivors, 101 (18%) received invasive mechanical ventilation (IMV) and 458 (82%) were managed outside the intensive care unit (ICU); mortality in the ICU was 49%. From the non-survivors, 45.6% (n = 110) did not receive full support due to lack of ICU bed availability. Within this subgroup the main cause of death was acute respiratory distress syndrome (ARDS) in 95% of the cases, whereas among the non-survivors who received full (n = 105) support the main cause of death was septic shock (45%) followed by ARDS (29%). The main risk factors associated with in-hospital death were male sex (RR 2.05, 95% CI 1.34-3.12), obesity (RR 1.62, 95% CI 1.14-2.32)-in particular morbid obesity (RR 3.38, 95%CI 1.63-7.00)-and oxygen saturation < 80% on admission (RR 4.8, 95%CI 3.26-7.31).ConclusionsIn this study we found similar in-hospital and ICU mortality, as well as risk factors for mortality, compared to previous reports. However, 45% of the patients who did not survive justified admission to ICU but did not receive IMV / ICU care due to the unavailability of ICU beds. Furthermore, mortality rate over time was mainly due to the availability of ICU beds, indirectly suggesting that overcrowding was one of the main factors that contributed to hospital mortality.

The high utilization of nonlinear devices in buildings increases harmonic distortion in the electrical voltage and current signals, which has led to the requirement of characterizing and predicting the impact of such devices on low-voltage networks using load models. One of the charges that still performs an important role in the energy consumption of commercial, industrial, and educational buildings is the recessed fluorescent light with electronic ballast, which is commonly used in Colombia. However, information regarding the modeling of their behavior in the case of distorted power supply voltages is scarce. Therefore, this work presents the parameter configuration and performance analysis of two load models in the time domain, i.e., ZIP and exponential, and one model in the frequency domain, i.e., Norton equivalent model to the coupled admittance matrix method, for two commonly used recessed fluorescent lights.

Primary lymphoma of the uterine cervix is a very infrequent disease, usually affecting perimenopausal women. Symptoms are very similar to other gynecological malignancies, but treatment and prognosis completely differ, as most of these patients have a better survival. This condition has to be suspected in women with recent normal Pap smear test, rapidly growing tumor and initially non-contributory biopsies.We report a case of primary diffuse large-B-cell lymphoma of the uterine cervix mimicking a locally advanced cervical cancer with right ureter hydronephrosis at diagnosis. She was medically managed with a combination of rituximab and chemotherapy with cyclophosphamide, hydroxydaunorubicin, oncovin, and prednisone, associated to methotrexate for central nervous system prophylaxis. We will discuss about the role of combined treatments with surgery and radiotherapy, and the fertility sparing management in young women.

Pregnancy presents some interesting challenges for the philosophy of embodied cognition. Mother and fetus are generally considered to be passive during pregnancy, both individually and in their relation. In this paper, we use the enactive operational concepts of autonomy, agency, individuation, and participation to examine the relation between mother and fetus in utero. Based on biological, physiological, and phenomenological research, we explore the emergence of agentive capacities in embryo and fetus, as well as how maternal agency changes as pregnancy advances. We show that qualitatively different kinds of agency have their beginnings already in utero, and to what extent fetal and maternal movement modulate affectivity and individuation in pregnancy. We thus propose that mother and fetus are both agents who participate in pregnancy. Pregnancy then emerges as a relational developmental organization that anchors and holds its developing participants. We end the paper with reflections on ethical implications of this proposal, and suggestions for future research.

In this work, unsupported Pd aerogel catalysts were synthesized for the very first time by using microwaves as a heating source followed by a lyophilization drying process and used towards formic acid electro-oxidation in a microfluidic fuel cell. Aerogels were also made by heating in a conventional oven to evaluate the microwave effect during the synthesis process of the unsupported Pd aerogels. The performance of the catalysts obtained by means of microwave heating favored the formic acid electro-oxidation with H2SO4 as the electrolyte. The aerogels’ performance as anodic catalysts was carried out in a microfluidic fuel cell, giving power densities of up to 14 mW cm−2 when using mass loads of only 0.1 mg on a 0.019 cm2 electrode surface. The power densities of the aerogels obtained by microwave heating gave a performance superior to the resultant aerogel prepared using conventional heating and even better than a commercial Pd/C catalyst.

Impulsar una educación de calidad y la igualdad de género son temas prioritarios que están en la agenda regional y global, junto con los otros 15 objetivos de desarrollo sostenible que integran la Agenda 2030 definida por las Naciones Unidas (UNESCO). Este artículo presenta los primeros avances de un proyecto de cooperación entre Uruguay y México que tiene por objetivo trabajar por una educación de calidad con perspectiva de género a partir de una experiencia innovadora de formación orientada por el pensamiento de Diseño. A través de procesos de innovación conducidos por diseño se busca aportar soluciones originales que contribuyan a alcanzar el objetivo antes planteado. Al mismo tiempo que se pretende subrayar la importancia que tiene aprovechar el potencial de la disciplina de Diseño para atender los problemas que aquejan a la región.

The objectives of this work were to identify the relationship between self-concept and social support in high school students, compare both variables according to sex and, finally, recognize the strength of the dimensions of social support (family and friends) in the prediction of self-concept. The sample consisted of 567 students. The instruments were the Self-concept Scale (AF-5) and the Family and Friends Social Support Scale (AFA-R). The results indicated a correlation between the study variables. Significant differences were found by sex in the total score of the Self-concept and in the dimensions "Emotional self-concept", "Physical self-concept" and "Friends support". Through a multiple linear regression analysis, a model was generated that considers the dimensions of social support and sex in the prediction of self-concept, being the family's support the predictor of greater weight. The study confirms the importance of family support in the constitution of the self-concept of young students and suggests developing preventive and remedial actions in those cases in which it is necessary.

The mouth can be affected by important inflammatory processes resulting from localized or systemic diseases such as diabetes, AIDS and leukemia, among others, and are manifested in various types of buccal sores typically presenting pain. This work focuses on the design, formulation, and characterization of four semisolid formulations for oral mucosa in order to symptomatically treat these painful processes. The formulations have two active pharmaceutical ingredients, triamcinolone acetonide (TA) and lidocaine hydrochloride (LIDO). The formula also contains, as an excipient, Orabase®, which is a protective, hydrophobic, and anhydrous adhesive vehicle, used to retain or facilitate the application of active pharmaceutical ingredients to the oral mucosa. After designing the formulations, an analytical method for TA was validated using HPLC so as to achieve reliable analytical results. Franz-type diffusion cells were used to perform drug release studies using synthetic membrane, and permeation studies using buccal mucosa, estimating the amount and rate of TA permeated across the tissue. Additionally, sublingual permeation studies were carried out to evaluate a scenario of a continuous contact of the tongue with the applied formulation. Permeation fluxes and the amount of TA retained within sublingual mucosa were similar to those in buccal mucosa, also implying anti-inflammatory activity in the part of the tongue that is in direct contact with the formulation. In addition, the dynamic conditions of the mouth were recreated in terms of the presence of phosphate buffered saline, constant movement of the tongue, pH, and temperature, using dissolution equipment. The amount of TA released into the phosphate buffered saline in dynamic conditions (subject to being ingested) is well below the normal oral doses of TA, for which the formulation can be considered safe. The formulations applied to buccal or sublingual mucosas under dynamic conditions permit the successful retention of TA within either tissue, where it exerts anti-inflammatory activity. The four formulations studied show a pseudoplastic and thixotropic behavior, ideal for topical application. These results evidence the potential of these topical formulations in the treatment of inflammatory processes in the buccal mucosa.