Proteomics is advancing the understanding of stallion sperm biology.

The mammalian ejaculate is very well suited to proteomics studies. As such, research concerning sperm proteomics is offering a huge amount of new information on the biology of spermatozoa. Among domestic animals, horses represent a species of special interest, in which reproductive technologies and a sizeable market of genetic material have grown exponentially in the last decade. Studies using proteomic approaches have been conducted in recent years, showing that proteomics is a potent tool to dig into the biology of the stallion spermatozoa. The aim of this review is to present an overview of the research conducted, and how these studies have improved our knowledge of stallion sperm biology. The main outcomes of the research conducted so far have been an improved knowledge of metabolism, and its importance in sperm functions, the impact of different technologies on the sperm proteome, and the identification of potential biomarkers. Moreover, proteomics of seminal plasma and phosphoproteomics are identified as areas of major interest.

The future of equine semen analysis.

We are currently experiencing a period of rapid advancement in various areas of science and technology. The integration of high throughput 'omics' techniques with advanced biostatistics, and the help of artificial intelligence, is significantly impacting our understanding of sperm biology. These advances will have an appreciable impact on the practice of reproductive medicine in horses. This article provides a brief overview of recent advances in the field of spermatology and how they are changing assessment of sperm quality. This article is written from the authors' perspective, using the stallion as a model. We aim to portray a brief overview of the changes occurring in the assessment of sperm motility and kinematics, advances in flow cytometry, implementation of 'omics' technologies, and the use of artificial intelligence/self-learning in data analysis. We also briefly discuss how some of the advances can be readily available to the practitioner, through the implementation of 'on-farm' devices and telemedicine.

Interplay of Andreev Reflection and Coulomb Blockade in Hybrid Superconducting Single-Electron Transistors.

We study the interplay between Coulomb blockade and superconductivity in a tunable superconductor-superconductor-normal-metal single-electron transistor. The device is realized by connecting the superconducting island via an oxide barrier to the normal-metal lead and with a break junction to the superconducting lead. The latter enables Cooper pair transport and (multiple) Andreev reflection. We show that these processes are relevant also far above the superconducting gap and that signatures of Coulomb blockade may reoccur at high bias while they are absent for small bias in the strong-coupling regime. Our experimental findings agree with simulations using a rate equation approach in combination with the full counting statistics of multiple Andreev reflection.

Pyruvate enhances stallion sperm function in high glucose media improving overall metabolic efficiency.

If a mechanism of more efficient glycolysis depending on pyruvate is present in stallion spermatozoa, detrimental effects of higher glucose concentrations that are common in current commercial extenders could be counteracted. To test this hypothesis, spermatozoa were incubated in a 67 mM Glucose modified Tyrode's media in the presence of 1- or 10-mM pyruvate and in the Tyrode's basal media which contains 5 mM glucose. Spermatozoa incubated for 3 h at 37 °C in 67 mM Tyrode's media with 10 mM pyruvate showed increased motility in comparison with aliquots incubated in Tyrode's 5 mM glucose and Tyrode's 67 mM glucose (57.1 ± 3.5 and 58.1 ± 1.9 to 73.0 ± 1.1 %; P < 0.01). Spermatozoa incubated in Tyrode's with 67 mM glucose 10 mM pyruvate maintained the viability along the incubation (64.03 ± 15.4 vs 61.3 ± 10.2), while spermatozoa incubated in 67 mM Glucose-Tyrode's showed a decrease in viability (38.01 ± 11.2, P < 0.01). 40 mM oxamate, an inhibitor of the lactate dehydrogenase LDH, reduced sperm viability (P < 0.05, from 76 ± 5 in 67 mM Glucose/10 mM pyruvate to 68.0 ± 4.3 %, P < 0.05). Apoptotic markers increased in the presence of oxamate. (P < 0.01). UHPLC/MS/MS showed that 10 mM pyruvate increased pyruvate, lactate, ATP and NAD+ while phosphoenolpyruvate decreased. The mechanisms that explain the improvement of in presence of 10 mM pyruvate involve the conversion of lactate to pyruvate and increased NAD+ enhancing the efficiency of the glycolysis.

Aging of stallion spermatozoa stored in vitro is delayed at 22°C using a 67 mm glucose-10 mm pyruvate-based media.

BACKGROUND: Most commerce of equine seminal doses is carried out using commercial extenders under refrigeration at 5°C. OBJECTIVES: To determine if 10 mm pyruvate in a 67 mm glucose extender and storage at 22°C could be the basis of an alternative storage method to cooling to 5°C. MATERIAL AND METHODS: Stallion ejaculates were extendedin: INRA96 (67 mm glucose, non-pyruvate control), modified Tyrode's (67 mm glucose-10 mm pyruvate), supplemented with 0, 10, 50, and 100 µM itaconate. As itaconate was vehiculated in DMSO, a control vehicle was also included. Sperm motility, viability, mitochondrial membrane potential, and production of reactive oxygen species were measured after collection and again after 48 and 96 h of storage at 22°C. To disclose molecular metabolic changes, spermatozoa were incubated up to 3 h in modified Tyrode's 67 mm glucose-10 mm pyruvate and modified Tyrode's 67 mm glucose, and metabolic analysis conducted. RESULTS: After 96 h of storage aliquots stored in the control, INRA96 had a very poor total motility of 5.6% ± 2.3%, while in the 67 mm glucose-10 mm pyruvate/10 µm itaconate extender, total motility was 34.7% ± 3.8% (p = 0.0066). After 96 h, viability was better in most pyruvate-based media, and the mitochondrial membrane potential in spermatozoa extended in INRA96 was relatively lower (p < 0.0001). Metabolomics revealed that in the spermatozoa incubated in the high pyruvate media, there was an increase in the relative amounts of NAD+ , pyruvate, lactate, and ATP. DISCUSSION AND CONCLUSIONS: Aliquots stored in a 67 mm glucose-10 mm pyruvate-based medium supplemented with 10 µM itaconate, maintained a 35% total motility after 96 h of storage at 22°C, which is considered the minimum acceptable motility for commercialization. Improvements may be related to the conversion of pyruvate to lactate and regeneration of NAD+ .

Adicción al tabaco y adolescencia: riesgos psicobiológicos / Psychobiological risks of tobacco during adolescence. A narrative review

Resumen La investigación moderna, tanto en humanos como preclínica, que utiliza modelos animales indica que fumar durante la edad adolescente resulta en cambios cerebrales y psicológicos a corto y largo plazo en el fumador, así como en un aumento significativo en los riesgos de desarrollar adicción al tabaco durante la vida. Por lo tanto, en la presente revisión narrativa se describirán y profundizarán los hallazgos investigativos modernos de la psicobiología de la adolescencia y los efectos del tabaco en el desarrollo, con un énfasis particular en la comprensión de los efectos psicológicos y cerebrales del consumo de tabaco durante la adolescencia, tanto a corto como a largo plazo. Se considerarán de manera detallada los avances investigativos sobre la psicobiología de la adolescencia y sus riesgos en las adicciones desde los aspectos: conductual, cognitivo, reactividad al estrés y psicobiología. Sobre esta base, se revisará la investigación sobre la psicobiología de la adolescencia y la evidencia de vulnerabilidad a la adicción durante esta etapa. Al final, se abordarán los efectos del tabaco en el cerebro y conducta durante el desarrollo adolescente y vida posterior, ya que se ha encontrado evidencia relacionada con alteraciones cerebrales crónicas en los sistemas colinérgicos y regiones cerebrales asociadas con la dependencia de la nicotina. Se espera que la revisión y divulgación de esta información en el idioma español sea de valor para la comprensión de los problemas de vulnerabilidad y predisposiciones a la adicción al tabaco en el contexto de Latinoamérica.

Abstract Tobacco use and its harmful health-related problems have become one of the largest modern preventable public health issues. Current research strongly suggests that smoking during adolescence enhances addictive smoking behaviors during life, which can be related to adolescence as a critical ontogenetic period characterized by behaviors that can increase the probability of risk-related behaviors such as sensation and novelty seeking. Adolescent development is also a period of maturation of frontal and subcortical neural systems, brain changes that underlie higher impulsivity tendencies to promote adequate learning and adaptations necessary to succeed the novel challenges of the adult life, but those changes also enhance vulnerabilities to the addictive effects of drugs. Consistent with this, tobacco use affects brain development processes which underlie long-term psychobiological alterations and the enhanced risks for tobacco addiction during adult life. Thus, the present review describes current psychobiological approaches to understand general addiction processes and tobacco addiction, highlighting the behavioral and neural short-term effects of tobacco use during adolescence and its long-term effects during adulthood. Current research has advanced on four aspects for the understanding of both the psychobiology of adolescent development and the effects of drugs of abuse during this time. The first aspect is behavioral, as adolescence is related to important changes on motivational and emotional behaviors such as sensation seeking. Other important behavioral changes are social approach, a higher variety of opportunity for personal choices, and development of personal independence. Research on a second aspect has focused on cognition. A review of research is presented showing enhanced abilities during adolescence development for reading, abstract and logical thinking, and novel problem solving. Stress reactivity is the third aspect of reviewed psychobiological mechanisms. The stress biological system undergoes important changes during adolescence, including changes on stress-related hormones and neural architecture. An important issue is that exposure to early and/or chronic stressful circumstances during adolescence could be related to higher risk to the start and maintenance of addiction states, as suggested by research assessing the disruptive effects of stress on psychobiological homeostatic processes needed to maintain stable biological and emotional regulation. The fourth aspect is psychobiology. In this section research is reviewed related to the development of monoaminergic brain circuits underlying motivation, novelty-seeking, impulsivity, and addiction processes. Using as model the previous review integration, the effects of nicotine are discussed, the essential addictive component of tobacco, on the neurochemical systems underlying tobacco addiction. Following this, important research is introduced that describes psychobiological changes during adolescence and evidence of vulnerability to addiction during this life stage. Then, current research on both short-term and long-term effects of tobacco or nicotine administration during adolescence on the brain, behavior, and cognition is introduced. The current research advances and discussions on the psychobiology of addictions in general, and tobacco addiction in particular, have been possible to a large extent from the use of animal models and preclinical research, since animal models have become crucial to identify learning, motivational, emotional, and cognitive mechanisms that underlie addictive processes, and making possible to perform experimental procedures to discover the functioning and participation of biological components. One example of such components is the cholinergic system, which is activated by nicotine and is part of the neurochemical machinery on different brain areas important for both tobacco addiction and adolescence development such as the dorsal striatum, amygdala, ventral tegmental area, nucleus accumbens, prefrontal cortex, and hippocampus. The present review and research divulgation written in Spanish are expected to clarify modern research on addiction and encourage current scientific education on the vulnerabilities and predispositions for tobacco abuse in Latin-American countries.

Hypovitaminosis D and its relationship with nutritional status and quality of life in patients undergoing haemodialysis / Hipovitaminosis D y su relación con el estado nutricional y la calidad de vida en pacientes incluidos en un programa de hemodiálisis

Objective: to assess the prevalence of hypovitaminosis D in patients undergoing haemodialysis (HD) and to determine its relationship with nutritional status and quality of life (QoL). Material and methods: 120 patients were included in the study. The Malnutrition-Inflammation Score (MIS) was used to detect nutritional risk. QoL was evaluated by Kidney Disease Quality of Life version 1.2 (KDQOL-SF). Patients were stratified into three groups according to their vitamin D status: sufficiency (≥ 30 ng/dl), insufficiency (29-10 ng/dl) and deficiency (< 10 ng/dl). Results: hypovitaminosis D was detected in 71 % of the patients studied. Multiple linear regression analysis showed that vitamin-D deficiency was the most significant predictor of low KDQOL-SF scores. It explained 21 % of the variance in the Kidney Disease Component Summary, 27 % of that in the Physical Component Summary, and 22 % of that in the Mental Component Summary. Multiple logistic regression analysis showed that only vitamin-D deficiency was significantly associated with malnutrition (OR, 14.6, p < 0.001). Conclusion: HD patients frequently present with hypovitaminosis D. There is a significant correlation between vitamin-D deficiency, poorer nutritional status, and worse QoL in dialysed patients. (AU)

Objetivo: evaluar la prevalencia de la hipovitaminosis D en pacientes en hemodiálisis (HD) y su relación con el estado nutricional y la calidad de vida (CV). Material y métodos: un total de 120 pacientes fueron incluidos. La escala de Malnutrición-Inflamación (MIS) se utilizó para la detección del riesgo nutricional. La CV fue evaluada por el cuestionario Kidney Disease Quality of Life versión 1.2 (KDQOL-SF). Los pacientes fueron estratificados en tres grupos de acuerdo con el estado de la vitamina D: suficiencia (≥ 30 ng/dl), insuficiencia (29-10 ng/dl) y deficiencia (< 10 ng/dl). Resultados: se observó hipovitaminosis D en el 71 % de los pacientes. El análisis de regresión lineal múltiple mostró que la deficiencia devitamina D fue el predictor más significativo de peores resultados en el cuestionario KDQOL-SF. La deficiencia de 25(OH)D explicó el 21 % de la varianza en el componente sumatorio de la enfermedad renal, el 27 % en el componente sumatorio físico y el 22 % en el componente sumatorio mental. Cuando evaluamos el estado nutricional, el análisis de regresión logística multivariante mostró que solo la deficiencia de vitamina D presenta un efecto significativo en la desnutrición (OR: 14.6, p < 0,001). Conclusión: de nuestros hallazgos concluimos que la hipovitaminosis D es muy frecuente entre los pacientes en HD y que su deficiencia está asociada un deterioro del estado nutricional y peor percepción de la calidad de vida. (AU)

Hypovitaminosis D and its relationship with nutritional status and quality of life in patients undergoing haemodialysis.

Introduction: Objective: to assess the prevalence of hypovitaminosis D in patients undergoing haemodialysis (HD) and to determine its relationship with nutritional status and quality of life (QoL). Material and methods: 120 patients were included in the study. The Malnutrition-Inflammation Score (MIS) was used to detect nutritional risk. QoL was evaluated by Kidney Disease Quality of Life version 1.2 (KDQOL-SF). Patients were stratified into three groups according to their vitamin D status: sufficiency (≥ 30 ng/dl), insufficiency (29-10 ng/dl) and deficiency (< 10 ng/dl). Results: hypovitaminosis D was detected in 71 % of the patients studied. Multiple linear regression analysis showed that vitamin-D deficiency was the most significant predictor of low KDQOL-SF scores. It explained 21 % of the variance in the Kidney Disease Component Summary, 27 % of that in the Physical Component Summary, and 22 % of that in the Mental Component Summary. Multiple logistic regression analysis showed that only vitamin-D deficiency was significantly associated with malnutrition (OR, 14.6, p < 0.001). Conclusion: HD patients frequently present with hypovitaminosis D. There is a significant correlation between vitamin-D deficiency, poorer nutritional status, and worse QoL in dialysed patients.

Introducción: Objetivo: evaluar la prevalencia de la hipovitaminosis D en pacientes en hemodiálisis (HD) y su relación con el estado nutricional y la calidad de vida (CV). Material y métodos: un total de 120 pacientes fueron incluidos. La escala de Malnutrición-Inflamación (MIS) se utilizó para la detección del riesgo nutricional. La CV fue evaluada por el cuestionario Kidney Disease Quality of Life versión 1.2 (KDQOL-SF). Los pacientes fueron estratificados en tres grupos de acuerdo con el estado de la vitamina D: suficiencia (≥ 30 ng/dl), insuficiencia (29-10 ng/dl) y deficiencia (< 10 ng/dl) Resultados: se observó hipovitaminosis D en el 71 % de los pacientes. El análisis de regresión lineal múltiple mostró que la deficiencia de vitamina D fue el predictor más significativo de peores resultados en el cuestionario KDQOL-SF. La deficiencia de 25(OH)D explicó el 21 % de la varianza en el componente sumatorio de la enfermedad renal, el 27 % en el componente sumatorio físico y el 22 % en el componente sumatorio mental. Cuando evaluamos el estado nutricional, el análisis de regresión logística multivariante mostró que solo la deficiencia de vitamina D presenta un efecto significativo en la desnutrición (OR: 14.6, p < 0,001). Conclusión: De nuestros hallazgos concluimos que la hipovitaminosis D es muy frecuente entre los pacientes en HD y que su deficiencia está asociada un deterioro del estado nutricional y peor percepción de la calidad de vida.

The impact of nutritional status on health-related quality of life in hemodialysis patients.

Malnutrition is frequent in hemodialysis (HD) patients. Nutritional deficiencies may negatively impact quality of life (QOL). This study examines the utility of the Malnutrition-Inflammation Score (MIS) in detecting nutritional risk (NR) and assesses the correlation between nutritional status and QOL in dialysis patients upon starting a nutritional intervention program (NIP). One hundred and twenty patients were included in this cross-sectional study. The MIS was used to detect NR and the Kidney Disease Quality of Life (KDQOL-SF) instrument version 1.2 was used to assess QOL. 62% of patients were found to be at NR (MIS > 5). Nutritional status was significantly correlated with all generic QOL sub-scales. On a multiple linear regression analysis, malnutrition showed the highest level of explanation in the Kidney Disease Summary Component which explained 28.9% of the variance; the Physical Component Summary which explained 33% of the variance; and the Mental Component Summary which explained 21.5% of the variance. Malnutrition was found to be the most significant predictor of impaired scores on the KDQOL-SF. The use of MIS to identify patients at NR and a nutritional assessment to detect malnutrition in its early stages are important given the effects a NIP can have on improving QOL in HD patients.

Candida spp. co-infection in COVID-19 patients with severe pneumonia: Prevalence study and associated risk factors.

BACKGROUND: Invasive fungal infections (IFI) are increasing in prevalence in recent years. In the last few months, the rise of COVID-19 patients has generated a new escalation in patients presenting opportunistic mycoses, mainly by Aspergillus. Candida infections are not being reported yet. OBJECTIVES: We aimed to determine the prevalence of systemic candidiasis in patients admitted to ICUs due to severe pneumonia secondary to SARS-CoV-2 infection and the existence of possible associated risk factors that led these patients to develop candidiasis. PATIENTS/METHODS: We designed a study including patients with a confirmed diagnosis of COVID-19. RESULTS: The prevalence of systemic candidiasis was 14.4%, and the main isolated species were C. albicans and C. parapsilosis. All patients that were tested positive for Candida spp. stayed longer in the ICU in comparison to patients who tested negative. Patients with candidiasis had higher MuLBSTA score and mortality rates and a worse radiological involvement. In our study, Candida spp. isolates were found in patients that were submitted to: tocilizumab, tocilizumab plus systemic steroids, interferon type 1ß and Lopinavir-Ritonavir. CONCLUSIONS: Results suggested a high prevalence of systemic candidiasis in severe COVID-19-associated pneumonia patients. Patients with Candidiasis had the worst clinical outcomes. Treatment with tocilizumab could potentialize the risk to develop systemic candidiasis.

A case-control study of factors associated with SARS-CoV-2 infection among healthcare workers in Colombia.

BACKGROUND: Healthcare Workers (HCW) are repeatedly exposed to SARS-CoV-2 infection. The aim of this study was to identify factors associated with SARS-CoV-2 infection among HCW in one of the largest cities in Colombia. METHODS: We conducted a case-control study, where cases had a positive reverse transcription-polymerase chain reaction and controls had a negative result. Participants were randomly selected and interviewed by phone. Analyses were performed using logistic regression models. RESULTS: A total of 110 cases and 113 controls were included. Men (AdjOR 4.13 95% CI 1.70-10.05), Nurses (AdjOR 11.24 95% CI 1.05-119.63), not using a high-performance filtering mask (AdjOR 2.27 95% CI 1.02-5.05) and inadequate use of personal protective equipment (AdjOR 4.82 95% CI 1.18-19.65) were identified as risk factors. Conversely, graduate (AdjOR 0.06 95% CI 0.01-0.53) and postgraduate (AdjOR 0.05 95% CI 0.005-0.7) education, feeling scared or nervous (AdjOR 0.45 95% CI 0.22-0.91), not always wearing any gloves, caps and goggles/face shields (AdjOR 0.10 95% CI 0.02-0.41), and the use of high-performance filtering or a combination of fabric plus surgical mask (AdjOR 0.27 95% CI 0.09-0.80) outside the workplace were protective factors. CONCLUSION: This study highlights the protection provided by high-performance filtering masks or double masking among HCW. Modifiable and non-modifiable factors and the difficulty of wearing other protective equipment needs to be considered in designing, implementing and monitoring COVID-19 biosafety protocols for HCW.

In vitro antimicrobial effect of chloroaluminum phthalocyanine nanoemulsion on periodontal bacteria.

CONTEXT: Nowadays, complementary therapies are necessary for a major removal of microbial subgingival biofilm in the conventional treatment of periodontitis. Research has suggested the use of photodynamic therapy (PDT) as a promising therapy to manage oral cavity infections. This project proposes a new combination of photosensitizer chloroaluminum phthalocyanine and nanoemulsion as a strategy for improving bioactivity. The main purpose of this in vitro study was to evaluate the antimicrobial activity of nanoemulsion ClAlPc (ClAlPc-NE) on relevant periodontal bacteria before and after PDT. MATERIALS AND METHODS: The phototoxic and antibacterial effect of ClAlPc-NE was evaluated against epithelial cells derived from an African green monkey kidney using the colorimetric method with salt tetrazolium 3-(4.5-dimethylthiazolyl-2)-2.5-Diphenyltetrazolium bromide (Merck) and periodontopathogen bacteria (Porphyromonas gingivalis (ATCC 33277), Aggregatibacter actinomycetemcomitans (ATCC 33384), and Prevotella intermedia (ATCC 25611) using the plate microdilution method according to Tavares et al., 2018, respectively. The light source used for the PDT was a LED laser (400-700 nm); the cells were irradiated for 2 min using 4.83 joules/cm2. RESULTS: Antibacterial effect of NE-PcAlCl against P. intermedia with minimum inhibitory concentration (MIC) 0.63 µM after TFD was determined. In the case of P. gingivalis and A. actinomycetemcomitans, no biological activity was found after PDT (MIC > 20 µM) under-evaluated experimental conditions. On the other hand, the ClAlPc-free and ClAlPc-NE cells were phototoxic on epithelial cells. CONCLUSION: The results helped to identify the potential use of ClAlPc-NE to inhibit the periodontal bacterial and additional studies are being developed.

Prevalence of opportunistic invasive aspergillosis in COVID-19 patients with severe pneumonia.

BACKGROUND: As the global coronavirus pandemic (COVID-19) spreads across the world, new clinical challenges emerge in the hospital landscape. Among these challenges, the increased risk of coinfections is a major threat to the patients. Although still in a low number, due to the short time of the pandemic, studies that identified a significant number of hospitalised patients with COVID-19 who developed secondary fungal infections that led to serious complications and even death have been published. OBJECTIVES: In this scenario, we aim to determine the prevalence of invasive fungal infections (IFIs) and describe possible associated risk factors in patients admitted due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. PATIENTS/METHODS: We designed an open prospective observational study at the Rey Juan Carlos University Hospital (Mostoles, Spain), during the period from February 1 to April 30, 2020. RESULTS: In this article, we reported seven patients with COVID-19-associated pulmonary aspergillosis (CAPA) who had a poor prognosis. Severely ill patients represent a high-risk group; therefore, we must actively investigate the possibility of aspergillosis in all of these patients. Larger cohort studies are needed to unravel the role of COVID-19 immunosuppressive therapy as a risk factor for aspergillosis. CONCLUSIONS: As the pandemic continues to spread across the world, further reports are needed to assess the frequency of emergent and highly resistant reemergent fungal infections during severe COVID-19. These coinfections are leading a significant number of patients with COVID-19 to death due to complications following the primary viral disease.

Coronavirus Disease 2019 (COVID-19) in a Patient with Disseminated Histoplasmosis and HIV-A Case Report from Argentina and Literature Review.

The disease caused by the new SARS-CoV-2, known as Coronavirus disease 2019 (COVID-19), was first identified in China in December 2019 and rapidly spread around the world. Coinfections with fungal pathogens in patients with COVID-19 add challenges to patient care. We conducted a literature review on fungal coinfections in patients with COVID-19. We describe a report of a patient with disseminated histoplasmosis who was likely infected with SARS-CoV-2 and experienced COVID-19 during hospital care in Buenos Aires, Argentina. This patient presented with advanced HIV disease, a well-known factor for disseminated histoplasmosis; on the other hand, we suspected that COVID-19 was acquired during hospitalization but there is not enough evidence to support this hypothesis. Clinical correlation and the use of specific Histoplasma and COVID-19 rapid diagnostics assays were key to the timely diagnosis of both infections, permitting appropriate treatment and patient care.

LAP+ Cells Modulate Protection Induced by Oral Vaccination with Rhesus Rotavirus in a Neonatal Mouse Model.

Transforming growth factor ß (TGF-ß) has been shown to play a role in immunity against different pathogens in vitro and against parasites in vivo However, its role in viral infections in vivo is incompletely understood. Using a neonatal mouse model of heterologous rhesus rotavirus (RV) vaccination, we show that the vaccine induced rotavirus-specific CD4 T cells, the majority of which lacked expression of KLRG1 or CD127, and a few regulatory rotavirus-specific CD4 T cells that expressed surface latency-associated peptide (LAP)-TGF-ß. In these mice, inhibiting TGF-ß, with both a neutralizing antibody and an inhibitor of TGF-ß receptor signaling (activin receptor-like kinase 5 inhibitor [ALK5i]), did not change the development or intensity of the mild diarrhea induced by the vaccine, the rotavirus-specific T cell response, or protection against a subsequent challenge with a murine EC-rotavirus. However, mice treated with anti-LAP antibodies had improved protection after a homologous EC-rotavirus challenge, compared with control rhesus rotavirus-immunized mice. Thus, oral vaccination with a heterologous rotavirus stimulates regulatory RV-specific CD4 LAP-positive (LAP+) T cells, and depletion of LAP+ cells increases vaccine-induced protection.IMPORTANCE Despite the introduction of several live attenuated animal and human rotaviruses as efficient oral vaccines, rotaviruses continue to be the leading etiological agent for diarrhea mortality among children under 5 years of age worldwide. Improvement of these vaccines has been partially delayed because immunity to rotaviruses is incompletely understood. In the intestine (where rotavirus replicates), regulatory T cells that express latency-associated peptide (LAP) play a prominent role, which has been explored for many diseases but not specifically for infectious agents. In this paper, we show that neonatal mice given a live oral rotavirus vaccine develop rotavirus-specific LAP+ T cells and that depletion of these cells improves the efficiency of the vaccine. These findings may prove useful for the design of strategies to improve rotavirus vaccines.

Scleroderma Renal Crisis Debute with Thrombotic Microangiopathy: A Successful Case Treated with Eculizumab.

We had the challenged to treat a 40-year-old female with Systemic Scleroderma who was showing unspecific symptoms. During her time at the hospital she rapidly develops renal dysfunction, associated with hypertension. She required renal replacement therapy initiation and we observed a decline in hemoglobin and platelets numbers. We confirm a microangiopathic hemolytic anemia and rule out other immune diseases or thrombotic thrombocytopenic purpura. Systemic Sclerosis is a chronic immune disorder of unknown origin that it is not completely understood. It is believed that environmental factors may contribute and also altered genes may be implicated in the immune system's function. Microangiopathic hemolytic anemia occurs in 43% of patients who develop scleroderma renal crisis and an activation of the complement system through the classical pathway may be involved. Given that context we decided to treat the patients with C5 blocker Eculizumab and obtain an extraordinary positive response.

Transición epitelio mesénquima: de lo molecular a lo fisiológico / Epitelial Mesenchymal Transition: From the Molecular to Physiologic

La transición epitelio mesénquima (EMT) es un proceso compuesto de diferentes fases, donde una célula epitelial adquiere un fenotipo mesenquimal. Dentro de los cambios involucrados se encuentran: pérdida de la polaridad celular, adquisición de una capacidad migratoria, capacidad invasora, resistencia a la apoptosis y aumento en la producción de componentes de la matriz extracelular. Todos estos cambios ocurren como una consecuencia de la activación y represión de genes involucrados con rutas de señalización específicas relacionadas con este evento. La EMT está relacionada con procesos fisiológicos y patológicos como el cáncer. Consta de tres fases: una de células no migratorias, células premigratorias y células migratorias; cada una de ellas producto de diferentes señales intra o extracelulares, factores de transcripción (TGF-B, Snail, TWIST, Sox, Slug, ZEB1, entre otras) y proteínas involucradas (E-cadherina, integrina, vimentina, ocludinas y claudinas).

Transition mesenchymal epithelium (EMT) is a process composed of different phases where an epithelial cell acquires a mesenchymal phenotype. Among the changes involved are: loss of cellular polarity, acquisition of a migratory capacity, invasive capacity, resistance to apoptosis, and increase in the production of components of the extracellular matrix. All these changes occur as a consequence of the activation and repression of genes involved with specific signaling pathways related to this event. EMT is related to physiological and pathological processes such as cancer. It consists of three phases: A phase of non-migratory cells, pre-migratory cells and migratory cells; (TGF-B, Snail, TWIST, Sox, Slug, ZEB1 among others), and proteins involved (E-cadherin, integrin, vimentin, occludins and claudins).

Neumonía bilateral por Ralstonia pickettii en una paciente inmunocompetente / Bilateral pneumonia due to Ralstonia picketti in immunocompetent patient

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