Polycystic ovary syndrome and fetal programming

Cecilia Alonso: Estudiante de Medicina, Ciclo de Metodología Científica II, Facultad de Medicina, Universidad de la República, Uruguay. La contribución en la realización del trabajo fue equivalente a la de los demás estudiantes.-- Carolina Aristarán: Estudiante de Medicina, Ciclo de Metodología Científica II, Facultad de Medicina, Universidad de la República, Uruguay. La contribución en la realización del trabajo fue equivalente a la de los demás estudiantes.-- Esthefani Ávila: Estudiante de Medicina, Ciclo de Metodología Científica II, Facultad de Medicina, Universidad de la República, Uruguay. La contribución en la realización del trabajo fue equivalente a la de los demás estudiantes.-- Virginia Bermolen: Estudiante de Medicina, Ciclo de Metodología Científica II, Facultad de Medicina, Universidad de la República, Uruguay. La contribución en la realización del trabajo fue equivalente a la de los demás estudiantes.-- Ana Tihista: Estudiante de Medicina, Ciclo de Metodología Científica II, Facultad de Medicina, Universidad de la República, Uruguay. La contribución en la realización del trabajo fue equivalente a la de los demás estudiantes.-- Gabriel Anesetti: Docente supervisor. Departamento de Histología y Embriología, Facultad de Medicina, Universidad de la República, Montevideo, Uruguay. Contacto: Gabriel Anesetti. Departamento de Histología y Embriología, Facultad de Medicina, Gral. Flores 2125, CP 11800, Montevideo, Uruguay. Tel: (598) 29243414 ext. 3481. E-mail: [email protected] síndrome de ovario poliquístico es un trastorno frecuente en las mujeres en edad reproductiva. En su patogenia influyen factores genéticos y ambientales. El hiperandrogenismo durante la vida fetal es el que se ha visto más vinculado a su desarrollo. En animales de experimentación se induce un síndrome similar, desarrollando un ambiente hiperandrogénico durante la gestación que conduce a una programación fetal. En estos modelos se vio que la exposición a un exceso de andrógenos durante la gestación determina en la descendencia femenina características similares a las encontradas en mujeres con síndrome de ovario poliquístico; como subfertilidad, alteraciones en el ciclo reproductivo, ovarios poliquísticos, alteraciones en el perfil lipídico y en la homeostasis insulina-glucosa, que difieren según el tiempo de exposición a andrógenos y la etapa de la gestación en la que ésta ocurre. Los factores genéticos juegan un rol importante en el desarrollo del síndrome de ovario poliquístico. Los que se han vinculado con más fuerza son aquellos que influyen en el sistema endócrino, como los relacionados con la secreción y acción de la insulina, de gonadotrofinas y andrógenos. Los factores inmunológicos también juegan un papel importante, entre éstos se pueden destacar los mediadores inflamatorios. Es necesario realizar más investigaciones para determinar si existen factores sobre los cuales se pueda actuar, además de tratamientos exitosos, para disminuir el hiperandrogenismo durante la gestación y de esta forma disminuir la incidencia del síndrome y sus repercusiones.Polycystic ovary syndrome is a common disorder in women of reproductive age. Its pathogenesis is influenced by genetic and environmental factors. Hyperandrogenism during fetal life has been closely linked to its development. A similar syndrome has been induced in research animals, developing an hyperandrogenic envi ronment during pregnancy leading to a fetal programming. Results show that exposure to androgen excess during pregnancy determined in female offspring characteristics such as subfertility, alterations in the reproductive cycle, polycystic ovaries, abnormal lipid profile and insulin-glucose homeostasis, similar to those found in women with polycystic ovary syndrome. These differ depending on the time of exposure and the stage of gestation when it occurs. Genetics plays an important role in the development of polycystic ovary syndrome. Genetic factors which have been linked more strongly are the ones that affect the endocrine system, such as those related to the secretion and action of insulin, gonadotrophins and androgens. Immunological factors also play an important role; among them, inflammatory mediators can be highlighted. Further research is necessary to determine whether there are factors over which it can be acted to re duce hyperandrogenism during pregnancy in order to decrease the incidence and impact of polycystic ovary syndrome, as well as successful treatments

Elaboración de pan multigrano con harinas precocidas por extrusión = Multigrain bread processing with extruded flours

Se estudió el efecto en la calidad del pan según el proceso de elaboración y del nivel de sustitución (20%, 36%) de una harina precocida por extrusión preparada en base a combinación de avena, soja y salvado de trigo en la calidad del pan. Se caracterizó la harina compuesta según sus propiedades funcionales (Índice de Absorción de Agua), granulometría y propiedades nutricionales (proteína, fibra total, fibra soluble, cenizas, materia grasa). Se realizó seguimiento del volumen, índice de blancura, medidas reológicas (dureza, cohesividad, elasticidad y masticabilidad) de los panes. Las condiciones del proceso de elaboración fue lo que generó mayor impacto en la calidad del pan. Los cambios operativos realizados provocaron un incremento del 37% en el volumen, 6% de elasticidad y 15% de cohesividad, y una disminución del 44% de dureza y 34% de masticabilidad. Esta tendencia se mantuvo en los cuatro días siguientes al día de elaboración. El nivel de sustitución de harina compuesta no provocó cambios significativos en la dureza, elasticidad y masticabilidad del pan, pero se observaron cambios en la cohesividad y volumen. El pan con 36% de sustitución resultó un 7% menos cohesivo y con un 27% menos de volumen que el de 20% de sustitución

A highly potent anti-VISTA antibody KVA12123 - a new immune checkpoint inhibitor and a promising therapy against poorly immunogenic tumors

BackgroundImmune checkpoint therapies have led to significant breakthroughs in cancer patient treatment in recent years. However, their efficiency is variable, and resistance to immunotherapies is common. VISTA is an immune-suppressive checkpoint inhibitor of T cell response belonging to the B7 family and a promising novel therapeutic target. VISTA is expressed in the immuno-suppressive tumor microenvironment, primarily by myeloid lineage cells, and its genetic knockout or antibody blockade restores an efficient antitumor immune response.MethodsFully human monoclonal antibodies directed against VISTA were produced after immunizing humanized Trianni mice and sorting and sequencing natively-linked B cell scFv repertoires. Anti-VISTA antibodies were evaluated for specificity, cross-reactivity, monocyte and T cell activation, Fc-effector functions, and antitumor efficacy using in vitro and in vivo models to select the KVA12123 antibody lead candidate. The pharmacokinetics and safety profiles of KVA12123 were evaluated in cynomolgus monkeys.ResultsHere, we report the development of a clinical candidate anti-VISTA monoclonal antibody, KVA12123. KVA12123 showed high affinity binding to VISTA through a unique epitope distinct from other clinical-stage anti-VISTA monoclonal antibodies. This clinical candidate demonstrated high specificity against VISTA with no cross-reactivity detected against other members of the B7 family. KVA12123 blocked VISTA binding to its binding partners. KVA12123 induced T cell activation and demonstrated NK-mediated monocyte activation. KVA12123 treatment mediated strong single-agent antitumor activity in several syngeneic tumor models and showed enhanced efficacy in combination with anti-PD-1 treatment. This clinical candidate was engineered to improve its pharmacokinetic characteristics and reduce Fc-effector functions. It was well-tolerated in preclinical toxicology studies in cynomolgus monkeys, where hematology, clinical chemistry evaluations, and clinical observations revealed no indicators of toxicity. No cytokines associated with cytokine release syndrome were elevated.ConclusionThese results establish that KVA12123 is a promising drug candidate with a distinct but complementary mechanism of action of the first generation of immune checkpoint inhibitors. This antibody is currently evaluated alone and in combination with pembrolizumab in a Phase 1/2 open-label clinical trial in patients with advanced solid tumors

Análisis de la situación actual de los biocarburantes de primera generación en la Unión Europea

Ingeniería Técnica AgrícolaNekazaritza Ingeniaritza Tekniko

The Effect of PGY Status on Rates of Postoperative Complications in All Orthopedic Surgeries – A study on the National Surgical Quality Improvement Project Database

Background: The influence of residents’ participation on patient morbidity has been thoroughly studied across all specialties in the field of medicine. The focus of these studies was on residents as a whole relative to a control (i.e. attending only). The present study assessed the influence of resident involvement on patient morbidity, but stratified the data among residents based on level of experience. Methods: The present study utilized the 2005-2014 NSQIP dataset to assess rate of complications in 36,020 patients after all orthopedic surgeries between two tiers of residents by PGY status. Only residents with PGY value of 1-6 were included in the study. Orthopedic training was separated into two groups: PGY 1-3 and PGY 4-6, signifying first and second half of orthopedic surgery training. Results: Univariate analysis for operative complications showed higher rate of organ space infection in PGY 4-6 group (0.4% vs. 0.3%, p-value: 0.042). Once controlling for comorbidities on multivariate analysis, these differences disappeared (p-value: 0.111). On univariate analysis for non-operative complications, PGY 4-6 group had higher rates of pulmonary embolism (0.5% vs. 0.3%, p-value: 0.006), requiring transfusion (9.0% vs. 7.7%, pvalue: \u3c0.001), and myocardial infarction (0.4% vs. 0.2%, p-value: 0.009). On multivariate analysis, pulmonary embolism (Odds ratio: 1.74, p-value: 0.004), post-operative transfusions (Odds ratio: 1.12, p-value: 0.007), and myocardial infarction (Odds ratio: 2.35, pvalue: 0.001) were shown to be higher in the more experienced residents, even after controlling for pre-operative comorbidities. Conclusion: We found no significant difference between inexperienced residents (PGY 1-3) and more experienced residents (PGY 4-6) in rates of operative complications. However, it was found that there is a greater risk of non-operative complications in the group of more experienced residents, signifying a discrepancy exists in medical management post-operatively as orthopedic residents advance through training. Level of Evidence: Level II Retrospective Cohort Stud

The impact of long-term corticosteroid use on acute postoperative complications following lumbar decompression surgery

© 2020 Delhi Orthopedic Association Background: Corticosteroids have a negative impact on the human immune system\u27s ability to function at an optimal level. Studies have shown that patients on long-term corticosteroids have higher infection rates. However, the rates of infection and other complications following lumbar decompression surgery remains under-investigated. The aim of our study was to determine the impact of preoperative long-term corticosteroid usage on acute, 30-day postoperative complications in a subset of patients undergoing lumbar spine decompression surgery, without fusion or instrumentation. We hypothesize that patients on long-term corticosteroids will have higher rates of infection and other postoperative complications after undergoing lumbar decompression surgery of the spine. Methods: A retrospective cohort study was conducted using data collected from the National Surgical Quality Improvement Program database data from 2005 to 2016. Lumbar decompression surgeries, including discectomies, laminectomies, and others were identified using CPT codes. Chi-square analysis was used to evaluate differences among the corticosteroid and non-corticosteroid groups for demographics, preoperative comorbidities, and postoperative complications. Logistic regression analysis was done to determine if long-term corticosteroid use predicts incidence of postoperative infections following adjustment. Results: 26,734 subjects met inclusion criteria. A total of 1044 patients (3.9%) were on long-term corticosteroids prior to surgical intervention, and 25,690 patients (96.1%) were not on long-term corticosteroids. Patients on long-term corticosteroids were more likely to be older (p \u3c 0.001), female (p \u3c 0.001), nonsmokers (p \u3c 0.001), and have a higher American Society of Anesthesiologist class (p \u3c 0.001). Multivariate analysis demonstrated that long-term corticosteroid usage was associated with increased overall complications (odds ratio [OR]: 1.543; p \u3c 0.001), and an independent risk factor for the development of minor complications (OR: 1.808; p \u3c 0.001), urinary tract infection (OR: 2.033; p = 0.002), extended length of stay (OR: 1.244; p = 0.039), thromboembolic complications (OR: 1.919; p = 0.023), and sepsis complications (OR: 2.032; p = 0.024). Conclusion: Long-term corticosteroid usage is associated with a significant increased risk of acute postoperative complication development, including urinary tract infection, sepsis and septic shock, thromboembolic complications, and extended length of hospital stay, but not with superficial or deep infection in patients undergoing lumbar decompression procedures. Spine surgeons should remain vigilant regarding postoperative complications in patients on long-term corticosteroids, especially as it relates to UTI and propensity to decompensate into sepsis or septic shock. Thromboembolic risk attenuation is also imperative in this patient group during the postoperative period and the surgeon should weigh the risks and benefits of more intensive anticoagulation measures