The presence of cytotoxic CD4 and exhausted-like CD8+ T-cells is a signature of active tuberculosis.

Chronic infections induce CD4+ T-cells with cytotoxic functions (CD4 CTLs); at present, it is still unknown whether latent tuberculosis (LTB) and active tuberculosis (ATB) induce CD4 CTLs. Plasma and cells from four patient groups-uninfected contact (UC), LTB, and ATB (divided as sensitive [DS-TB]- or resistant [DR-TB]-drug)-were evaluated by flow cytometry, q-PCR, and proteomics. The data showed that ATB patients had an increased frequency of CD4+ T-cells and a decreased frequency of CD8+ T-cells. The latter displays an exhausted-like profile characterized by CD39, CD279, and TIM-3 expression. ATB had a high frequency of CD4 + perforin+ cells, suggesting a CD4 CTL profile. The expression (at the transcriptional level) of granzyme A, granzyme B, granulysin, and perforin, as well as the genes T-bet (Tbx21) and NKG2D (Klrk1), in enriched CD4+ T-cells, confirmed the cytotoxic signature of CD4+ T-cells during ATB (which was stronger in DS-TB than in DR-TB). Moreover, proteomic analysis revealed the presence of HSP70 (in DS-TB) and annexin A5 (in DR-TB), which are molecules that have been associated with favoring the CD4 CTL profile. Finally, we found that lipids from Mycobacterium tuberculosis increased the presence of CD4 CTLs in DR-TB patients. Our data suggest that ATB is characterized by exhausted-like CD8+ T-cells, which, together with a specific microenvironment, favor the presence of CD4 CTLs.

A comprehensive and critical review of the unstandardized Folin-Ciocalteu assay to determine the total content of polyphenols: The conundrum of the experimental factors and method validation.

The Folin-Ciocalteu method can be considered to be the most widely used in laboratories around the world, to quantify the total polyphenols content. Many different variations found in this assay have been reported in the scientific literature. In this review, the full experimental conditions influencing the Folin-Ciocalteu assay have been comparatively assessed and discussed. Furthermore, few studies relating to the method validation have been evaluated according to the results of selectivity, linearity, precision, trueness, limit of determination, limit of quantification and robustness. In general, the results derived from the reviewed literature are widely variable according to both, the experimental factors selected and the performance parameters reported, making difficult the comparison of the overall results published.

Valganciclovir modulates the tumor necrosis factor axis molecules expression and CD4+ T-cell subsets in disseminated Kaposi Sarcoma patients.

Valganciclovir (VGC) was used in a randomized clinical trial in patients with disseminated Kaposi Sarcoma/human immunodeficiency virus (DKS/HIV) as add-on therapy to evaluate the proinflammatory axis tumor necrosis factor (TNF) and its receptors (TNFRs) in T cells. Two treatment schedules were used: an experimental regime (ER) and a conventional treatment (CT). Mononuclear cells from patients with DKS/HIV were obtained at baseline (W0), 4 (W4), and 12 weeks (W12). Ten DKS/HIV patients received CT (antiretroviral therapy [cART]) and 10 ER (valganciclovir [VGC] initially, plus cART at the fourth week). HIV+ without KS and HIV- patient groups were included as controls. Correlation between T-cell subsets and HHV-8 viral load (VL) and a multivariate linear regression was performed. Data showed that DKS/HIV patients have an increased frequency of CD8+ T cells, which display a high density of CD8 expression. The ER scheme increases naïve and central memory CD4+ T cells at W4 and W12 of follow-up and induces a balanced distribution of activated CD4+ T-cell subsets. Moreover, ER decreases solTNFR2 since W4 and CT decreased the transmembrane forms of TNF axis molecules. Although CT induces a positive correlation between HHV-8 VL and TNFRs, the use of ER positively correlates with TNF and TNFRs levels through follow-up and a moderate correlation with HHV-8 VL and TNF soluble levels. In conclusion, VGC, as an add-on therapy in DKS/HIV patients, gradually modulates the activation of CD4+ T-cell subsets and the TNF/TNFRs axis, suggesting a better regulation of the inflammatory status.

Variant rs4986790 of toll-like receptor 4 affects the signaling and induces cell dysfunction in patients with severe COVID-19.

OBJECTIVES: We investigated the expression of toll-like receptor (TLR)-4 on the cell surface of innate and adaptive cells from patients with COVID-19 carrying the rs4986790 GG genotype in the TLR4 gene and the functional profile of these cells. METHODS: We included 1169 hospitalized patients with COVID-19. The rs4986790 in TLR4 was identified by real-time polymerase chain reaction. Peripheral blood mononuclear cells were isolated and cultured to evaluate TLR-4 expression on immune cells. Supernatants recovered culture assays were stored, and we measured cytokines and cytotoxic molecules. RESULTS: We showed that the rs4986790 (GG) was significantly associated (P = 0.0310) with severe COVID-19. Cells of patients with COVID-19 carrying the GG genotype have increased the frequency of monocytes and activated naïve and non-switched B cells positive to TLR-4 when cells are stimulated with lipopolysaccharide and with spike protein of SARS-CoV-2. Also, cells from patients with GG COVID-19 cannot produce pro-inflammatory cytokines after lipopolysaccharide stimulus, but they are high producers of cytotoxic molecules at baseline. CONCLUSIONS: The rs4986790 GG genotype of the TLR4 is associated with the risk of COVID-19 and acute respiratory distress syndrome. Peripheral blood mononuclear cells of patients carrying the rs4986790 (TLR4) GG genotype had a limited delivery of pro-inflammatory cytokines compared to the AA and AG genotypes in which TLR-4 stimulation induces IL-10, IL-6, tumor necrosis factor-α, and Fas ligand production.

Physiologic Repair of Congenitally Corrected Transposition of the Great Arteries in a Criss-Cross Heart.

Congenitally corrected transposition of great arteries is an uncommon congenital heart disease characterized by discordance at both the atrioventricular and ventriculoarterial connections. A rare subgroup of patients with congenitally corrected transposition of the great arteries also has a criss-cross heart. The morphology of these patients represents a diagnostic challenge that requires critical analysis to perform a satisfactory surgical procedure. We present a case of a 12-year-old patient with the above mentioned anatomy who underwent physiologic repair.

High levels of PF4, VEGF-A, and classical monocytes correlate with the platelets count and inflammation during active tuberculosis.

Platelets play a major role in coagulation and hemostasis; evidence supports the hypothesis that they also contribute to immunological processes. Increased platelet counts have been associated with poor prognosis in tuberculosis (TB). Platelet-monocyte aggregates have been reported in patients with TB, but it is still unclear if only one monocyte subpopulation is correlated to the platelet count; moreover, the platelet-monocyte axis has not been studied during latent tuberculosis (LTB). In this study, mononuclear cells and plasma were obtained from patients diagnosed with active drug-sensitive TB (DS-TB, n = 10) and LTB (n = 10); cytokines and growth factors levels associated to platelets were evaluated, and correlations with monocyte subpopulations were performed to identify a relationship between them, as well as an association with the degree of lung damage. Our data showed that, compared to LTB, DS-TB patients had an increased frequency of platelets, monocytes, and neutrophils. Although DS-TB patients showed no significant difference in the frequency of classical and non-classical monocytes, the classical monocytes had increased CD14 intensity of expression and frequency of TLR-2+. Furthermore, the plasma levels of angiogenic factors such as vascular endothelial growth factor (VEGF-A), platelet-derived growth factor (PDGF-BB), and platelet factor-4 (PF4), and pro-inflammatory cytokines like interleukin 6 (IL-6), interleukin 1 beta (IL-1ß), and interferon-γ-inducible protein 10 (IP-10) were increased in DS-TB patients. In addition, PF-4 and VEGF-A correlated positively with the frequency of classical monocytes and the platelet count. Using a principal component analysis, we identified four groups of DS-TB patients according to their levels of pro-inflammatory cytokines, angiogenic factors, and degree of lung damage. This study establishes that there is a correlation between VEGF-A and PF4 with platelets and classical monocytes during active TB, suggesting that those cell subpopulations are the major contributors of these molecules, and together, they control the severity of lung damage by amplification of the inflammatory environment.

Application of machine learning to predict aneuploidy and mosaicism in embryos from in vitro fertilization cycles.

BACKGROUND: The factors associated with embryo aneuploidy have been extensively studied. Mostly maternal age and to a lesser extent male factor and ovarian stimulation have been related to the occurrence of chromosomal alterations in the embryo. On the other hand, the main factors that may increase the incidence of embryo mosaicism have not yet been established. OBJECTIVE: This study aimed to establish a machine learning model that would allow prediction of aneuploidies and mosaicism in embryos conceived via in vitro fertilization, and thus help to determine which variables are associated with these chromosomal alterations. STUDY DESIGN: The study design was observational and retrospective. A total of 6989 embryos from 2476 cycles of preimplantation genetic testing for aneuploidies were included (January 2013 to December 2020). The trophoectoderm biopsies on day-5, -6, or -7 blastocysts were analyzed by preimplantation genetic testing for aneuploidies (PGT-A). The different maternal, paternal, couple, embryo, and in vitro fertilization cycle characteristics were recorded in a database (22 predictor variables) from which predictive models of embryo aneuploidy and mosaicism were developed; 16 different unsupervised classification machine learning algorithms were used to establish the predictive models. RESULTS: Two different predictive models were performed: one for aneuploidy and the other for mosaicism. The predictor variable was of multiclass type because it included the segmental- and whole-chromosome alteration categories. The best predicting models for both aneuploidies and mosaicism were those obtained from the Random Forest algorithm. The area under ROC curve (AUC) value was 0.792 for the aneuploidy explanatory model and 0.776 for mosaicism. The most important variable in the final aneuploidy model was maternal age, followed by paternal and maternal karyotype and embryo quality. In the predictive model of mosaicism, the most important variable was the technique used in preimplantation genetic testing for aneuploidies and embryo quality, followed by maternal age and day of biopsy. CONCLUSION: It is possible to predict embryo aneuploidy and mosaicism from certain characteristics of the patients and their embryos.

Involvement of Helicobacter pylori in Preoperative Gastric Findings on a Bariatric Population.

The prevalence of Helicobacter pylori (Hp) in bariatric patients is common and related to gastric pathology. With preoperative upper gastrointestinal endoscopy (UGE), these pathologies and the presence of Hp are diagnosed. The histopathological study of the UGE biopsies is classified based on the Sydney System, a scoring system that stages chronic gastritis (CG) and precancerous gastric lesions. The objective is to assess the histological findings of gastric biopsies during routine UGE and to determine the involvement of Hp in gastric disorders in patients undergoing bariatric surgery. A multicenter retrospective review of prospectively collected databases was performed. The presence of CG, gastric atrophy (GA), and gastric intestinal metaplasia (GIM) in the study of the biopsies was assessed and correlated with Hp infection. The incidence of Hp among our bariatric population was 36.1%, and it increases with age. The percentage of patients with severe Hp infection is higher in patients with GA or GIM. The Hp eradication rate is also reduced when GA and GIM are present. A histological examination of all the biopsies did not show features of malignancy in any of the cases. Hp is not the only factor involved in the development of gastric pathology in bariatric patients.

Where did the finch go? Insights from radio telemetry of the medium ground finch (Geospiza fortis).

Movement patterns and habitat selection of animals have important implications for ecology and evolution. Darwin's finches are a classic model system for ecological and evolutionary studies, yet their spatial ecology remains poorly studied. We tagged and radio-tracked five (three females, two males) medium ground finches (Geospiza fortis) to examine the feasibility of telemetry for understanding their movement and habitat use. Based on 143 locations collected during a 3-week period, we analyzed for the first time home-range size and habitat selection patterns of finches at El Garrapatero, an arid coastal ecosystem on Santa Cruz Island (Galápagos). The average 95% home range and 50% core area for G. fortis in the breeding season was 20.54 ha ± 4.04 ha SE and 4.03 ha ± 1.11 ha SE, respectively. For most of the finches, their home range covered a diverse set of habitats. Three finches positively selected the dry-forest habitat, while the other habitats seemed to be either negatively selected or simply neglected by the finches. In addition, we noted a communal roosting behavior in an area close to the ocean, where the vegetation is greener and denser than the more inland dry-forest vegetation. We show that telemetry on Darwin's finches provides valuable data to understand the movement ecology of the species. Based on our results, we propose a series of questions about the ecology and evolution of Darwin's finches that can be addressed using telemetry.

Aplicación de la técnica WALANT en las cirugías de mano / Use of WALANT Technique in Hand Surgeries

Introducción: En los últimos años la anestesia local sin torniquete y con el paciente despierto, técnica conocida por WALANT (por sus siglas en inglés), ha ganado mucha popularidad en las cirugías de la mano y la muñeca. Objetivo: Reportar nuestra experiencia con el uso de la técnica WALANT, a fin de prescindir del uso del torniquete en las cirugías de la mano. Métodos: En noviembre del 2020 fueron intervenidos 30 pacientes por diversas enfermedades ortopédicas, entre las que figuraron: dedos en resorte, síndrome del túnel carpiano, tenovaginitis estenosante del pulgar, gangliones del carpo y amputación del tercer radio por rigidez en extensión postraumática, entre otras. Para la evaluación de la técnica tuvimos en cuenta: tiempo quirúrgico, magnitud del sangrado, dolor durante la infiltración anestésica, la intervención, y en las primeras 24 horas del postoperatorio, la necesidad de refuerzo anestésico, uso de isquemia, complicaciones y nivel de satisfacción del paciente. Resultados: Los resultados obtenidos con esta técnica anestésica son semejantes a otras, con las ventajas que el sangrado es leve, no hay que utilizar isquemia, el tiempo quirúrgico es menor y el efecto anestésico duró entre 10 y 12 horas en todos los pacientes. En ninguno de los pacientes hubo necesidad de refuerzo anestésico. Conclusiones: Se demuestra la efectividad de la técnica WALANT en las cirugías de mano. Con ella se disminuye el gasto de materiales para el acto quirúrgico, así como de personal, es de fácil aplicación y disminuyen las sensaciones desagradables y los peligros del uso de isquemia en los pacientes(AU)

Introduction: Currently, the use of local anaesthetic with no tourniquet and wide awake patient (Wide Awake Local Anaesthetic No Tourniquet - WALANT) has gained popularity in surgeries of the hand and wrist. Objective: To report our experience in the use of WALANT technique in order to discard the use of tourniquet in hand surgeries. Method: In November 2020, thirty patients underwent surgery due to different orthopaedic conditions, among them trigger fingers, carpal tunnel syndrome, stenosing tenovaginitis of the thumb, carpal ganglion and amputation of the third radius due to post trauma stiffness, among others. In order to assess this technique, we considered surgical time, volume of bleeding, pain during anesthetic infiltration, intervention and the need for additional anesthetic during the first 24 hours after surgery; we considered also ischemia, complications and level patient´s satisfaction. Results: This technique had similar results to others; however, the bleeding is mild, there is no need for ischemia, the surgical time is lesser and the anesthetic effect lasted 10 to 12 hours in all patients. None of them required additional anesthetic. All subjects felt the initial infiltration but none complained of pain during the rest of the anesthetic injection or during the surgical act. There were no complications. Conclusions: The effectiveness of WALANT technique in hand surgeries is shown. The cost of materials for the surgical act is reduced with it, as well as the surgical staff, it is easy to use and unpleasant sensations and dangers of the use of ischemia in patients are reduced(AU)

Enfermedades que limitan el ingreso al trabajo en población económicamente activa

Introducción: Actualmente la relación hombre-trabajo se encuentra limitada por condiciones de salud, que pueden agravarse frente a la exposición a factores de riesgo. Materiales y métodos: Estudio descriptivo, transversal, diseño no experimental, enfoque cuantitativo, realizado en 1570 consultantes a ingreso laboral, durante el período de octubre de 2019 a marzo de 2020 a nivel local; con una muestra probabilística de 1073, nivel de confianza de 98,00 % y margen de error del 2,00 %. Criterios de inclusión: solicitantes de consulta pre-empleo, mayores de edad, de ambos sexos que aceptaron participar en el estudio; excluidos menores de edad, autorizados por el Ministerio de Trabajo. La recolección de la información se realizó mediante evaluación médico-ocupacional y exámenes complementarios, utilizando equipos biomédicos calibrados y formatos validados por la Institución. El análisis de la información se realizó mediante estadística descriptiva, aplicando media, moda, desviación estándar, tablas y figuras. Se respetaron los principios éticos para la investigación en humanos. Resultados: Edad promedio 32 años, edad mínima de 18 y máxima de 66 años, desviación estándar de 9,2. De los participantes, 51,57 % presentó antecedentes personales patológicos; 47,15 % índice de masa corporal normal, seguido de sobrepeso 11.00 % e hipertensión arterial 1,95 %. La prevalencia de restricciones y aplazamientos laborales fue de 12,86 %, generadas principalmente por enfermedades cardiovasculares, visuales, osteomusculares y digestivas. Conclusiones: Las restricciones y aplazamientos para el ingreso al trabajo guardan correspondencia con las enfermedades que se describen en las estadísticas vitales presentadas en el país y en el departamento de Sucre.

Introduction: Currently the man-work relationship is limited by health conditions, which can be aggravated by exposure to risk factors. Materials and methods: Descriptive, cross-sectional study, non-experimental design with a quantitative approach, carried out in 1570 consultants at work admission, carried out between October 2019 to March 2020; Probabilistic sample of 1073 people, confidence level of 98.00% and margin of error of 2.00 %. Inclusion criteria: applicants for pre-employment consultation, of legal age, both sexes and who consented to participate in the research; minors are excluded, authorized by the Ministry of Labor. The information was collected through occupational medical evaluations and complementary examinations with formats validated by the Institution and calibrated biomedical equipment. The information analysis was carried out with descriptive statistics, using mean, mode, standard deviation, tables, and figures. The ethical principles for research in humans were respected. Results: Average age 32 years, minimum age of 18 and maximum of 66 years, standard deviation of 9.2. 51.57 % of the participants had a personal pathological history, 47.15 % had a normal body mass index, followed by overweight; 11.00% presented arterial hypertension. The prevalence of work restrictions and postponements was 12.86 %, mainly caused by cardiovascular, visual, musculoskeletal, and digestive diseases. Conclusions: The restrictions and postponements for entering work correspond to the diseases described in the vital statistics presented in the country and in the Department of Sucre.

Valganciclovir as Add-On Therapy Modifies the Frequency of NK and NKT Cell Subpopulations in Disseminated Kaposi Sarcoma Patients.

Human herpesvirus-8 infection (HHV-8) is the causative agent of Kaposi sarcoma (KS) and is highly prevalent among people living with HIV (KS/HIV). It has been reported that valganciclovir (VGC) reduces HHV-8 replication in KS/HIV patients. However, currently it is unclear if VGC modifies the frequency and induces changes in markers of immune regulation of immune cells necessary to eliminate HHV8-infected cells, such as Natural Killer (NK) and NK T cells (NKT). This study evaluated the effect of VGC used as antiviral HHV8 therapy in KS patients on the frequency of NK and NKT subpopulations based on the CD27 and CD57 expression, and the immunosenescence markers, PD-1 and KLRG1. Twenty KS/HIV patients were followed-up at baseline (W0), 4 (W4), and 12 weeks (W12) of the study protocol. Among them, 10 patients received a conventional treatment scheme (CT), solely antiretroviral therapy (ART), and 10 patients received a modified treatment regime (MT), including VGC plus ART. In both groups, bleomycin/vincristine was administrated according to the treating physician's decision. The soluble levels of IL-15, PD-L1, PD-L2, and E-cadherin were quantified across the follow-up. Our results showed that the higher IL-15 levels and lower NK frequencies cells in KS/HIV patients reach almost normal values with both treatments regimes at W12. CD27+ NK and NKT cell frequencies increased since W4 on KS/HIV patients with MT. Furthermore, PD-1 expression decreased while KLRG1 increased on NK and NKT subpopulations at W12, and it is accompanied by increased PD-L1 plasma level since W4. Our study highlights the disruption of NK and NKT subpopulations in patients with KS/HIV and explores VGC treatment's contribution to immune reconstitution during the first weeks of treatment.

Antiproliferative, Antiangiogenic, and Antimetastatic Therapy Response by Mangiferin in a Syngeneic Immunocompetent Colorectal Cancer Mouse Model Involves Changes in Mitochondrial Energy Metabolism.

In spite of the current advances and achievements in cancer treatments, colorectal cancer (CRC) persists as one of the most prevalent and deadly tumor types in both men and women worldwide. Drug resistance, adverse side effects and high rate of angiogenesis, metastasis and tumor relapse remain one of the greatest challenges in long-term management of CRC and urges need for new leads of anticancer drugs. We demonstrate that CRC treatment with the phytopharmaceutical mangiferin (MGF), a glucosylxanthone present in Mango tree stem bark and leaves (Mangifera Indica L.), induces dose-dependent tumor regression and decreases lung metastasis in a syngeneic immunocompetent allograft mouse model of murine CT26 colon carcinoma, which increases overall survival of mice. Antimetastatic and antiangiogenic MGF effects could be further validated in a wound healing in vitro model in human HT29 cells and in a matrigel plug implant mouse model. Interestingly, transcriptome pathway enrichment analysis demonstrates that MGF inhibits tumor growth, metastasis and angiogenesis by multi-targeting of mitochondrial oxidoreductase and fatty acid ß-oxidation metabolism, PPAR, SIRT, NFκB, Stat3, HIF, Wnt and GP6 signaling pathways. MGF effects on fatty acid ß-oxidation metabolism and carnitine palmitoyltransferase 1 (CPT1) protein expression could be further confirmed in vitro in human HT29 colon cells. In conclusion, antitumor, antiangiogenic and antimetastatic effects of MGF treatment hold promise to reduce adverse toxicity and to mitigate therapeutic outcome of colorectal cancer treatment by targeting mitochondrial energy metabolism in the tumor microenvironment.

Bidirectional association between tobacco use and depression risk in the SUN cohort study. / Asociación bidireccional entre uso de tabaco y riesgo de depresión en el estudio de cohorte SUN.

We assessed the association of tobacco use or smoking cessation with depression risk and determined if the presence of a depressive disorder was associated with smoking onset. We conducted a prospective cohort study (SUN Project) based on 16,519 Spanish university graduates without depression at baseline. Tobacco use was determined at baseline and after four years of follow-up. Incident cases of depression were ascertained according to a previously validated report of a clinical diagnosis of depression during follow-up. Multivariable Cox regression models were used to estimate hazard ratios (HR) of depression according to previous smoking status. We used logistic regression models as a secondary analysis to estimate Odds Ratios (OR) of smoking onset during the first four years of follow-up according to lifetime depression prevalence at baseline. The multivariable HR (95% CI) for current smokers was 1.24 (1.05-1.46) as compared to participants who had never smoked. Participants with the highest exposure to tobacco (≥ 20 packs-years) had a significant 38% relative increment in depression risk. Smoking cessation during the first four years of follow-up was inversely associated with depression (HR = 0.63; 95% CI = 0.40-0.99). Finally, a significant increment in the risk of smoking onset for participants with lifetime depression prevalence was observed (multivariable OR = 1.44; 95% CI = 1.13-1.83). A bidirectional association between tobacco use and depression in the SUN cohort was found. Therefore, tobacco control and health promotion campaigns for smoking cessation could be considered as effective strategies of public health for the prevention and management of depressive disorders.

Evaluamos la asociación del consumo de tabaco o su abandono con el riesgo de depresión y determinamos si presentar depresión se asoció al inicio de fumar. Diseño: estudio de cohortes prospectivo de 16.519 graduados universitarios españoles sin depresión al inicio del estudio. El consumo de tabaco se determinó al inicio y tras cuatro años de seguimiento. Los casos incidentes de depresión fueron autoinformados en los cuestionarios de seguimiento. Usamos modelos de regresión de Cox para estimar los Hazard Ratios (HR) de depresión según el nivel de tabaquismo inicial y sus cambios. Se estimaron los Odds Ratios (OR) para la asociación entre prevalencia de tabaquismo a lo largo de la vida y comienzo del hábito con modelos de regresión logística. Se observó un HR (IC 95%) para fumadores de 1,24 (1,05-1,46) en comparación con los que nunca habían fumado. Los participantes con la exposición más alta al tabaco (≥ 20 paquetes-año) tuvieron un incremento relativo del riesgo de depresión de 38%. Dejar de fumar durante los primeros cuatro años de seguimiento se asoció inversamente con la depresión (HR = 0,63; IC 95% = 0,40-0,99). Observamos un incremento significativo del riesgo de aparición de tabaquismo en los participantes con prevalencia de depresión a lo largo de la vida (OR multivariable = 1,44; IC 95% = 1,13-1,83). Encontramos una asociación bidireccional entre el consumo de tabaco y la depresión en la cohorte SUN. El control del tabaco y las campañas sanitarias de abstinencia deberían considerarse estrategias efectivas de salud pública para prevenir y manejar los trastornos depresivos.

Impaired T helper cell responses in human immunodeficiency virus-exposed uninfected newborns.

INTRODUCTION: HIV-exposed uninfected (HEU) newborns suffer from higher risks of opportunistic infections during the first months of life compared to HIV-unexposed uninfected (HUU) newborns. Alterations in thymic mass, amounts of T helper (Th) cells, T-cell receptor diversity, and activation markers have been found in HEU newborns, suggesting alterations in T cell ontogeny and differentiation. However, little is known about the ability of these cells to produce specialized Th responses from CD4+ T cells. METHOD: To characterize the Th cell profile, we evaluated the frequency of Th1 (CD183+ CD194- CD196- /CXCR3+ CCR4- CCR6- ), Th2 (CD183- CD194+ CD196- /CXCR3- CCR4+ CCR6- ), Th17 (CD183- CD194+ CD196+ /CXCR3- CCR4+ CCR6+ ), and CD4+ CD25++ blood T-cell phenotypes in 50 HEU and 25 HUU newborns. Early activation markers on CD4+ T cells and the Th cytokine profile produced from mononuclear cells under polyclonal T cell stimulation were also studied. Additionally, we probed the ability of CD4+ T cells to differentiate into interferon (IFN)-γ-producing Th1 CD4+ T cells in vitro. RESULTS: Lower percentages of differentiated Th1 , Th2 , Th17, and CD4+ CD25++ T cells were found in blood from HEU newborns than in blood from HUU newborns. However, polyclonally stimulated Th cells showed a similar ability to express CD69 and CD279 but produced less secreted interleukin (IL)-2 and IL-4. Interestingly, under Th1 differentiation conditions, the percentages of CD4+ IFN-γ+ T cells and soluble IFN-γ were higher in HEU newborns than in HUU newborns. CONCLUSION: HEU neonates are born with reduced proportions of differentiated Th1 /Th2 /Th17 and CD4+ CD25++ T cells, but the intrinsic abilities of CD4+ T cells to acquire a Th1 profile are not affected by the adverse maternal milieu during development.

Telomere Shortening and Its Association with Cell Dysfunction in Lung Diseases.

Telomeres are localized at the end of chromosomes to provide genome stability; however, the telomere length tends to be shortened with each cell division inducing a progressive telomere shortening (TS). In addition to age, other factors, such as exposure to pollutants, diet, stress, and disruptions in the shelterin protein complex or genes associated with telomerase induce TS. This phenomenon favors cellular senescence and genotoxic stress, which increases the risk of the development and progression of lung diseases such as idiopathic pulmonary fibrosis, chronic obstructive pulmonary disease, SARS-CoV-2 infection, and lung cancer. In an infectious environment, immune cells that exhibit TS are associated with severe lymphopenia and death, whereas in a noninfectious context, naïve T cells that exhibit TS are related to cancer progression and enhanced inflammatory processes. In this review, we discuss how TS modifies the function of the immune system cells, making them inefficient in maintaining homeostasis in the lung. Finally, we discuss the advances in drug and gene therapy for lung diseases where TS could be used as a target for future treatments.

Sociodemographic and Maternal Risk Factors Associated with Psychomotor Retardation in Infants under Two Years Old in Tabasco / Factores de riesgo sociodemográficos y maternos asociados al retraso psicomotor en infantes menores de dos años en Tabasco / Fatores de risco sociodemográficos e maternos associados ao atraso psicomotor em crianças menores de dois anos em Tabasco

Abstract Introduction: Adequate psychomotor development during the first years of life significantly impacts the growth of each infant, so the timely detection of risk factors that affect this development is of vital importance. The objective was to determine sociodemographic and maternal factors associated with the presentation of psychomotor retardation in infants under two years old who attended the Centro de Rehabilitación y Educación Especial in Villahermosa (Tabasco, Mexico) in 2017. Materials and methods: An observational, retrospective study of cases and controls in infants under two years old. Data collection was performed using a questionnaire consisting of 45 questions, which included variables such as psychomotor retardation, prenatal, perinatal, and postnatal risk factors, that used Pearson's chi-square test and Fisher's exact test, with a significant correlation of p <.05 being accepted . Results: A low social class showed a significant relationship with psychomotor retardation (p =.000), while the presence of infections at a very young age in the newborn, a family history of psychomotor retardation, and a history of disease during pregnancy showed a value of p <.05. Conclusión: A low socioeconomic status, pregnancy-associated diseases such as malnutrition, high blood pressure, and traumatic accidents, as well as infectious diseases at birth were the main factors that conditioned psychomotor retardation.

Resumen Introducción: el adecuado desarrollo psicomotor en los primeros años de vida influye significativamente en el crecimiento de cada sujeto, por lo que la detección oportuna de factores de riesgo que lo afecten es de vital importancia. El objetivo fue determinar factores sociodemográficos y maternos asociados a la presentación del retraso psicomotor en infantes menores de dos años que acudieron al Centro de Rehabilitación y Educación Especial en Villahermosa (Tabasco, México) en el 2017. Materiales y métodos: estudio observacional, retrospectivo de casos y controles en infantes menores de dos años. Los datos se recolectaron mediante un cuestionario de 45 ítems, que incluyó variables como retraso psicomotor, factores de riesgo prenatales, perinatales y posnatales. Se emplearon las pruebas chi cuadrado de Pearson y la prueba exacta de Fisher. Se aceptó una correlación significativa de p<0.05. Resultados: el estrato social bajo mostró una relación significativa con el retraso psicomotor (p = 0.000), así como la presencia de infecciones a una edad muy temprana en el recién nacido, el historial de antecedente familiar y el antecedente de enfermedad en el embarazo (p<0.05). Conclusión: un estatus socioeconómico bajo, enfermedades asociadas al embarazo como malnutrición, hipertensión arterial y accidentes traumáticos, además de las enfermedades infecciosas al nacer, fueron los principales factores que condicionaron el retraso psicomotor.

Resumo Introdução: o adequado desenvolvimento psicomotor nos primeiros anos de vida impacta significativamente no crescimento de cada sujeito, pelo que a detecção oportuna de fatores de risco que o afetem é de vital importância. O objetivo foi determinar fatores sociodemográficos e maternos associados à apresentação do atraso psicomotor em crianças menores de dois anos que acorrem ao Centro de Reabilitação e Educação Especial em Villahermosa (Tabasco, México) em 2017. Materiais e métodos: estudo observa-cional, retrospectivo de casos e controles em crianças menores de dois anos. A recolecção de dados se realizou mediante um questionário de 45 itens o qual incluiu variáveis como atraso psicomotor, fatores de risco pré-natais, perinatais, e pós-natais, empregando as provas qui-quadrado de Pearson, prova exata de Fisher. Se aceitou uma correlação significativa de p<.05. Resultados: o estrato social baixo mostrou relação significativa com o atraso psicomotor (p=.000); também a presença de infeções a uma idade muito precoce no recém-nascido, o historial de antecedente familiar e antecedente de doença na gravidez (p<.05). Conclusão: o status socioeconómico baixo, doenças associadas à gravidez como subnutrição, hipertensão arterial e acidentes traumáticos, para além das doenças infeciosas ao nascer, foram os principais fatores que condicionaram o atraso psicomotor.

Rinoplastia estética y funcional, experiencia en la Cátedra y Servicio de Otorrinolaringología y Cirugía de Cabeza y Cuello / Funcional and aesthetic rhinoplasty, our experience in the Otorhinolaryngology and Head and Neck Surgery Service

Introducción: En la región son varios los centros de ambiente académico que realizan rinoplastia, y la experiencia del otorrinolaringólogo es cada vez más basta en cuanto a estética nasal se refiere. Debido a la alta prevalencia de trastornos estéticos y funcionales asociados, es necesario que el profesional esté capacitado para resolver ambas problemáticas, incluso en el mismo acto quirúrgico. Objetivos: Describir los abordajes y técnicas utilizados en cirugía de rinoplastia en nuestro servicio. Materiales y métodos: Estudio observacional, descriptivo con componentes analíticos, transversal, retrospectivo, de muestreo no probabilístico de casos consecutivos, de pacientes con alteración de la estética y de la funcionalidad nasal que acudieron al servicio de Otorrinolaringología del Hospital de Clínicas, San Lorenzo desde enero del 2016 a junio del 2019. Resultados: Se realizaron 76 Rinoplastias en el servicio, 76,3% de ellos también requirió septoplastia y el 61,8% requirió turbinectomía. El 68% fue de sexo femenino. La media de edades fue de 25,21±8,79 años. El 47,36% de los motivos de consulta fue por obstrucción nasal, seguido de síntomas tanto obstructivos como estéticos en el 42,1%; y el 10,52% puramente estéticos. El 40,78% de los pacientes del estudio refería antecedente de traumatismo nasal. Se realizó la cirugía por abordaje abierto en el 71,05% de los casos y en el 28,95% por abordaje cerrado. Los procedimientos más frecuentes fueron la colocación de Strut Columellar (89,47%), la Resección de Dorso (78,94%) y la Osteotomía (72,36%). La complicación más frecuente fue la epistaxis en el 5,26%, todos ellos con antecedente de osteotomía. El 100% de los pacientes con obstrucción refirió mejoría, y en 3 se vio persistencia de ligera laterorrinia. Conclusión: Se realizaron 76 Rinoplastias desde enero del 2016 a junio del 2019, la mayoría también requirió septoplastia y turbinectomía. La edad promedio fue 25,21 años, y la mayoría del sexo femenino. La cirugía estética en la población masculina fue más frecuente en pacientes con antecedente traumático (p<0,05 en la prueba de xi cuadrado). La mayor parte de los pacientes tenía como principal inconveniente la funcionalidad más que la estética. El abordaje más frecuente fue por vía abierta, y los procedimientos más frecuentemente fueron el Strut Columellar, la Resección de Dorso y la Osteotomía. La complicación más frecuente fue la epistaxis, la cual en la mayoría de los casos se resolvió con métodos tópicos. Todos los pacientes con síntomas obstructivos refirieron mejoría funcional, la laterorrinia fue la alteración más difícil de corregir.