Maternal serum adipokines and inflammatory markers at late gestation and newborn weight in mothers with and without gestational diabetes mellitus

Objectives: Maternal obesity increases the risk of gestational diabetes mellitus (GDM) and is positively correlated with neonatal obesity increasing the risk of adiposity in both young and adult offspring. Maternal secreted factors from adipose tissue such as adipokines and inflammatory cytokines may regulate fetal growth. This study investigated associations between maternal adipokines and inflammatory markers at late gestation, and neonatal anthropometric characteristics in mothers with and without GDM. Material and methods: The study included 65 women with GDM and 65 pregnant women with normal glucose tolerance evaluated at the time of term elective Caesarean section. Adiponectin, leptin, resistin, adipsin, neutrophil gelatinase-associated lipocalin (NGAL), nerve growth factor (NGF), monocyte chemotactic protein-1 (MCP-1) and tumor necrosis factor-alpha (TNF-alpha) concentrations were measured in maternal serum by the multiplex immunoassay using Magpix technology. C-reactive protein (CRP) was measured with a particle-enhanced turbidimetric immunoassay and neonatal anthropometric variables were assessed. The association of birthweight with individual biomarkers was analyzed using multivariate logistic regression adjusted for maternal factors. Results: Adiponectin, leptin, resistin, adipsin, NGAL and NGF were not significantly associated with higher birthweight. The maternal factors in association with higher birthweight observed in GDM were CRP, MCP-1 and TNF-alpha levels. Regression analysis showed that TNF-alpha was an independent risk factor for higher birthweight (p = 0.046). Conclusions: These results suggest an involvement of maternal inflammatory markers at late gestation and fetal growth in mothers with GDM, and that TNF-alpha could play a major role

Prostate response to prolactin in sexually active male rats

BACKGROUND: The prostate is a key gland in the sexual physiology of male mammals. Its sensitivity to steroid hormones is widely known, but its response to prolactin is still poorly known. Previous studies have shown a correlation between sexual behaviour, prolactin release and prostate physiology. Thus, here we used the sexual behaviour of male rats as a model for studying this correlation. Hence, we developed experimental paradigms to determine the influence of prolactin on sexual behaviour and prostate organization of male rats. METHODS: In addition to sexual behaviour recordings, we developed the ELISA procedure to quantify the serum level of prolactin, and the hematoxilin-eosin technique for analysis of the histological organization of the prostate. Also, different experimental manipulations were carried out; they included pituitary grafts, and haloperidol and ovine prolactin treatments. Data were analyzed with a One way ANOVA followed by post hoc Dunnet test if required. RESULTS: Data showed that male prolactin has a basal level with two peaks at the light-dark-light transitions. Consecutive ejaculations increased serum prolactin after the first ejaculation, which reached the highest level after the second, and started to decrease after the third ejaculation. These normal levels of prolactin did not induce any change at the prostate tissue. However, treatments for constant elevations of serum prolactin decreased sexual potency and increased the weight of the gland, the alveoli area and the epithelial cell height. Treatments for transient elevation of serum prolactin did not affect the sexual behaviour of males, but triggered these significant effects mainly at the ventral prostate. CONCLUSION: The prostate is a sexual gland that responds to prolactin. Mating-induced prolactin release is required during sexual encounters to activate the epithelial cells in the gland. Here we saw a precise mechanism controlling the release of prolactin during ejaculations that avoid the detrimental effects produced by constant levels. However, we showed that minor elevations of prolactin which do not affect the sexual behaviour of males, produced significant changes at the prostate epithelium that could account for triggering the development of hyperplasia or cancer. Thus, it is suggested that minute elevations of serum prolactin in healthy subjects are at the etiology of prostate abnormal growth

Effectiveness of an intervention for improving drug prescription in primary care patients with multimorbidity and polypharmacy:Study protocol of a cluster randomized clinical trial (Multi-PAP project)

This study was funded by the Fondo de Investigaciones Sanitarias ISCIII (Grant Numbers PI15/00276, PI15/00572, PI15/00996), REDISSEC (Project Numbers RD12/0001/0012, RD16/0001/0005), and the European Regional Development Fund ("A way to build Europe").Background: Multimorbidity is associated with negative effects both on people's health and on healthcare systems. A key problem linked to multimorbidity is polypharmacy, which in turn is associated with increased risk of partly preventable adverse effects, including mortality. The Ariadne principles describe a model of care based on a thorough assessment of diseases, treatments (and potential interactions), clinical status, context and preferences of patients with multimorbidity, with the aim of prioritizing and sharing realistic treatment goals that guide an individualized management. The aim of this study is to evaluate the effectiveness of a complex intervention that implements the Ariadne principles in a population of young-old patients with multimorbidity and polypharmacy. The intervention seeks to improve the appropriateness of prescribing in primary care (PC), as measured by the medication appropriateness index (MAI) score at 6 and 12months, as compared with usual care. Methods/Design: Design:pragmatic cluster randomized clinical trial. Unit of randomization: family physician (FP). Unit of analysis: patient. Scope: PC health centres in three autonomous communities: Aragon, Madrid, and Andalusia (Spain). Population: patients aged 65-74years with multimorbidity (≥3 chronic diseases) and polypharmacy (≥5 drugs prescribed in ≥3months). Sample size: n=400 (200 per study arm). Intervention: complex intervention based on the implementation of the Ariadne principles with two components: (1) FP training and (2) FP-patient interview. Outcomes: MAI score, health services use, quality of life (Euroqol 5D-5L), pharmacotherapy and adherence to treatment (Morisky-Green, Haynes-Sackett), and clinical and socio-demographic variables. Statistical analysis: primary outcome is the difference in MAI score between T0 and T1 and corresponding 95% confidence interval. Adjustment for confounding factors will be performed by multilevel analysis. All analyses will be carried out in accordance with the intention-to-treat principle. Discussion: It is essential to provide evidence concerning interventions on PC patients with polypharmacy and multimorbidity, conducted in the context of routine clinical practice, and involving young-old patients with significant potential for preventing negative health outcomes. Trial registration: Clinicaltrials.gov, NCT02866799Publisher PDFPeer reviewe

Treatment with tocilizumab or corticosteroids for COVID-19 patients with hyperinflammatory state: a multicentre cohort study (SAM-COVID-19)

Objectives: The objective of this study was to estimate the association between tocilizumab or corticosteroids and the risk of intubation or death in patients with coronavirus disease 19 (COVID-19) with a hyperinflammatory state according to clinical and laboratory parameters. Methods: A cohort study was performed in 60 Spanish hospitals including 778 patients with COVID-19 and clinical and laboratory data indicative of a hyperinflammatory state. Treatment was mainly with tocilizumab, an intermediate-high dose of corticosteroids (IHDC), a pulse dose of corticosteroids (PDC), combination therapy, or no treatment. Primary outcome was intubation or death; follow-up was 21 days. Propensity score-adjusted estimations using Cox regression (logistic regression if needed) were calculated. Propensity scores were used as confounders, matching variables and for the inverse probability of treatment weights (IPTWs). Results: In all, 88, 117, 78 and 151 patients treated with tocilizumab, IHDC, PDC, and combination therapy, respectively, were compared with 344 untreated patients. The primary endpoint occurred in 10 (11.4%), 27 (23.1%), 12 (15.4%), 40 (25.6%) and 69 (21.1%), respectively. The IPTW-based hazard ratios (odds ratio for combination therapy) for the primary endpoint were 0.32 (95%CI 0.22-0.47; p < 0.001) for tocilizumab, 0.82 (0.71-1.30; p 0.82) for IHDC, 0.61 (0.43-0.86; p 0.006) for PDC, and 1.17 (0.86-1.58; p 0.30) for combination therapy. Other applications of the propensity score provided similar results, but were not significant for PDC. Tocilizumab was also associated with lower hazard of death alone in IPTW analysis (0.07; 0.02-0.17; p < 0.001). Conclusions: Tocilizumab might be useful in COVID-19 patients with a hyperinflammatory state and should be prioritized for randomized trials in this situatio

Medio ambiente, sociedad, ética, auditoría y educación: reflexiones desde la disciplina contable.

Los servicios y desarrollos tecnológicos en todos los sectores económicos, al igual que la actualidad social, educativa, ambiental y agropecuaria en el mundo, constituyen oportunidades para que los contadores públicos se alejen de los procesos netamente manuales, y se acerquen al desarrollo de actividades que agreguen mayor valor a las unidades económicas en las cuales se desempeñan profesionalmente; en consecuencia, la academia recibe en la misma dimensión retos importantes que conllevan revisar y actualizar constantemente los contenidos, medios y escenarios educativos, a través de los cuales se cumple con la misión de formar contadores públicos idóneos para la sociedad. El programa de Contaduría Pública de la Corporación Universitaria Minuto de Dios – UNIMINUTO, UVD, consiente de la responsabilidad que tiene al ser uno de los programas con mayor número de estudiantes actualmente en Colombia, ha cimentado a lo largo de sus primeros ocho años bases adecuadas y orientadas a constituir una comunidad académica reconocida por sus aportes alternativos a la profesión y a la industria contable en general. El libro Medio ambiente, sociedad, ética, auditoría y educación en su segunda versión es una muestra de cómo el III Encuentro Nacional y II Internacional de Investigación Contable UNIMINUTO UVD, llevado a cabo en Bogotá en Octubre del 2018, se convirtió en un espacio extraordinario en el que se reunieron representantes de los veintiún lugares de oferta del programa de Contaduría Pública UNIMINUTO UVD, para compartir los avances de los proyectos que se tejen diariamente en diferentes lugares del territorio nacional, y que hacen parte integral de las cuatro sublíneas de investigación que se desarrollan al interior del programa y que se visualizan claramente lo largo del presente libro

Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Summary Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung’s disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung’s disease) from 264 hospitals (89 in high-income countries, 166 in middleincome countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in lowincome countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. Interpretation Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between lowincome, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

Temporalidad en el incremento de receptores a prolactina en el hipotálamo de la rata macho durante la conducta sexual

Introduction: Three groups of hypothalamic dopaminergic neurons regulate the adenohypophysis to release systemic prolactin. The inhibition of dopamine stimulates prolactin release that in turn is self-regulated by stimulating the release of dopamine. This is possible because dopaminergic neurons have prolactin receptors which increase their concentration in the presence of prolactin. In a previous study we showed that male sexual behavior increases the systemic level of prolactin, suggesting the hypothesis that also modifies their hypothalamic receptors. Objetive: to analyze the fluctuation of prolactin receptors and its temporality in the hypothalamus of male rats following consecutive ejaculations. Materials and Methods: Hence, two experiments were developed by using sexually experienced male rats. In the first, males copulated from one to three consecutive ejaculations, and the second, the hypothalamus was obtained at different times after the correspondent ejaculation. Then the hypothalamus was obtained to measure the level of mRNA of the prolactin receptor with RT-PCR. Results: First results showed that the level of the receptor increases after the second ejaculation and remains elevated after the third. The second experiment showed increase of the receptors 15 minutes after one ejaculation with a maximal expression between 30 and 40 minutes. Two or three consecutive ejaculations gave a similar curve, but with a higher intensity. Conclusions: This suggests that the level of prolactin during sexual behavior impacts the temporality in the increase of hypothalamic receptors. Thus, we propose that the start of sexual behavior triggers mechanisms for the regulation of prolactin and its hypothalamic receptors, with a conserved fluctuation as a function of time.Introducción: Tres grupos de neuronas dopaminérgicas del hipotálamo regulan a la adenohipófisis para liberar prolactina sistémica. La inhibición de dopamina estimula la liberación de prolactina, que a su vez se autorregula al estimular la liberación de dopamina. Esto es posible dado que las neuronas hipotalámicas tienen receptores a prolactina que además elevan su concentración cuando hay prolactina presente. En estudios previos mostramos que la conducta sexual masculina eleva los niveles sistémicos de prolactina, sugiriendo la hipótesis de que también modifica los receptores hipotalámicos. Objetivo: analizar la fluctuación de los PRLr y su temporalidad en el hipotálamo de la rata macho durante eyaculaciones consecutivas. Material y Método: Con ello, se organizaron dos experimentos utilizando ratas macho sexualmente expertas. En el primero, los machos copularon de una a tres eyaculaciones consecutivas, después se obtuvo el hipotálamo. En el segundo, se obtuvieron los hipotálamos a diferentes tiempos después de la eyaculación correspondiente. En ambos experimentos se cuantificaron los niveles del mRNA del receptor a prolactina mediante RT-PCR. Resultados: Los primeros resultados mostraron que el nivel del receptor incrementa a partir de la segunda eyaculación y se mantiene al mismo nivel después de la tercera. El segundo experimento mostró incrementos del receptor 15 minutos después de una eyaculación con una elevación máxima entre los 30 y 40 minutos. Dos o tres eyaculaciones consecutivas dieron una curva similar, aunque con mayor intensidad. Conclusiones: Esto sugiere que los niveles de prolactina durante la conducta sexual influyen sobre la temporalidad en el incremento de los receptores hipotalámicos. Así, se propone que el inicio de la conducta sexual dispara mecanismos para la regulación de prolactina y sus receptores hipotalámicos, con una fluctuación muy conservada en función del tiempo