A poor and delayed anti-SARS-CoV2 IgG response is associated to severe COVID-19 in children.

BACKGROUND: Most children and youth develop mild or asymptomatic disease during severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. However, a very small number of patients suffer severe Coronavirus induced disease 2019 (COVID-19). The reasons underlying these different outcomes remain unknown. METHODS: We analyzed three different cohorts: children with acute infection (n=550), convalescent children (n=138), and MIS-C (multisystem inflammatory syndrome in children, n=42). IgG and IgM antibodies to the spike protein of SARS-CoV-2, serum-neutralizing activity, plasma cytokine levels, and the frequency of circulating Follicular T helper cells (cTfh) and plasmablasts were analyzed by conventional methods. FINDINGS: Fifty-eight percent of the children in the acute phase of infection had no detectable antibodies at the time of sampling while a seronegative status was found in 25% and 12% of convalescent and MIS-C children, respectively. When children in the acute phase of the infection were stratified according disease severity, we found that contrasting with the response of children with asymptomatic, mild and moderate disease, children with severe COVID-19 did not develop any detectable response. A defective antibody response was also observed in the convalescent cohort for children with severe disease at the time of admission. This poor antibody response was associated to both, a low frequency of cTfh and a high plasma concentration of inflammatory cytokines. INTERPRETATION: A weak and delayed kinetic of antibody response to SARS-CoV-2 together with a systemic pro-inflammatory profile characterize pediatric severe COVID-19. Because comorbidities are highly prevalent in children with severe COVID-19, further studies are needed to clarify their contribution in the weak antibody response observed in severe disease. FUNDING: National Agency for Scientific and Technological Promotion from Argentina (IP-COVID-19-0277 and PMO-BID-PICT2018-2548).

Reversal of SARS-CoV2-Induced Hypoxia by Nebulized Sodium Ibuprofenate in a Compassionate Use Program.

INTRODUCTION: Sodium ibuprofenate in hypertonic saline (NaIHS) administered directly to the lungs by nebulization and inhalation has antibacterial and anti-inflammatory effects, with the potential to deliver these benefits to hypoxic patients. We describe a compassionate use program that offered this therapy to hospitalized COVID-19 patients. METHODS: NaIHS (50 mg ibuprofen, tid) was provided in addition to standard of care (SOC) to hospitalized COVID-19 patients until oxygen saturation levels of > 94% were achieved on ambient air. Patients wore a containment hood to diminish aerosolization. Outcome data from participating patients treated at multiple hospitals in Argentina between April 4 and October 31, 2020, are summarized. Results were compared with a retrospective contemporaneous control (CC) group of hospitalized COVID-19 patients with SOC alone during the same time frame from a subset of participating hospitals from Córdoba and Buenos Aires. RESULTS: The evolution of 383 patients treated with SOC + NaIHS [56 on mechanical ventilation (MV) at baseline] and 195 CC (21 on MV at baseline) are summarized. At baseline, NaIHS-treated patients had basal oxygen saturation of 90.7 ± 0.2% (74.3% were on supplemental oxygen at baseline) and a basal respiratory rate of 22.7 ± 0.3 breath/min. In the CC group, basal oxygen saturation was 92.6 ± 0.4% (52.1% were on oxygen supplementation at baseline) and respiratory rate was 19.3 ± 0.3 breath/min. Despite greater pulmonary compromise at baseline in the NaIHS-treated group, the length of treatment (LOT) was 9.1 ± 0.2 gs with an average length of stay (ALOS) of 11.5 ± 0.3 days, in comparison with an ALOS of 13.3 ± 0.9 days in the CC group. In patients on MV who received NaIHS, the ALOS was lower than in the CC group. In both NaIHS-treated groups, a rapid reversal of deterioration in oxygenation and NEWS2 scores was observed acutely after initiation of NaIHS therapy. No serious adverse events were considered related to ibuprofen therapy. Mortality was lower in both NaIHS groups compared with CC groups. CONCLUSIONS: Treatment of COVID-19 pneumonitis with inhalational nebulized NaIHS was associated with rapid improvement in hypoxia and vital signs, with no serious adverse events attributed to therapy. Nebulized NaIHS s worthy of further study in randomized, placebo-controlled trials (ClinicalTrials.gov: NCT04382768).

An intensive follow-up in subjects with cardiometabolic high-risk.

BACKGROUND AND AIM: Addressing chronic problems requires a model of care that promotes self-management of the disease and facilitates adherence to treatment. This project was designed to enhance patient's clinical and functional outcomes through a Comprehensive Model to be implemented in our health system and to evaluate the results. METHODS AND RESULTS: Different population stratification tools were tested and designed to classify subjects according to different variables. We have developed a program to detect and screen cardiometabolic risk by integrating most of the Chronic Care Model recommendations through in-house developed management software (MoviHealth®). From the results, 1317 subjects were evaluated (27% of the whole population) during the first year of follow-up which significantly improved for all variables along the follow-up period. The blood pressure of the hypertensive population in 2010 and 2015 showed the importance of enrollment of subjects and the optimization of the blood pressure control. The result of HbA1c observed in 2010 decreased progressively to 7.1 ± 1.4% in 2015, and dyslipidemia levels improved gradually. The number of cardiovascular events requiring hospitalization decreased significantly (48%), from 1.9 events per 100 subjects in 2011 to 0.98 in 2015. CONCLUSION: Our program has combined strategies for the prevention and control of non-communicable diseases, incorporating interventions to control risk factors and to reduce morbidity and mortality. It also had improvements in life quality, accessibility to health-care services, and the promotion of self-care.

Blood neutrophils from children with COVID-19 exhibit both inflammatory and anti-inflammatory markers.

BACKGROUND: Perhaps reflecting that children with COVID-19 rarely exhibit severe respiratory symptoms and often remain asymptomatic, little attention has been paid to explore the immune response in pediatric COVID-19. Here, we analyzed the phenotype and function of circulating neutrophils from children with COVID-19. METHODS: An observational study including 182 children with COVID-19, 21 children with multisystem inflammatory syndrome (MIS-C), and 40 healthy children was performed in Buenos Aires, Argentina. Neutrophil phenotype was analyzed by flow cytometry in blood samples. Cytokine production, plasma levels of IgG antibodies directed to the spike protein of SARS-CoV-2 and citrullinated histone H3 were measured by ELISA. Cell-free DNA was quantified by fluorometry. FINDINGS: Compared with healthy controls, neutrophils from children with COVID-19 showed a lower expression of CD11b, CD66b, and L-selectin but a higher expression of the activation markers HLA-DR, CD64 and PECAM-1 and the inhibitory receptors LAIR-1 and PD-L1. No differences in the production of cytokines and NETs were observed. Interestingly, the expression of CD64 in neutrophils and the serum concentration of IgG antibodies directed to the spike protein of SARS-CoV-2 distinguished asymptomatic from mild and moderate COVID-19. INTERPRETATION: Acute lung injury is a prominent feature of severe COVID-19 in adults. A low expression of adhesion molecules together with a high expression of inhibitory receptors in neutrophils from children with COVID-19 might prevent tissue infiltration by neutrophils preserving lung function. FUNDING: This study was supported by the Ministry of Science and Technology (National Agency for Scientific and Technological Promotion, IP-COVID-19-0277 and PMO BID PICT 2018-2548), and University of Buenos Aires from Argentina (20020170100573BA).

Obesidad central, sarcopenia y conductas sedentarias en el riesgo cardiovascular por score Framingham y área total de placa carotídea / Central Obesity, Sarcopenia, and Sedentary Behaviors Related to Cardiovascular Risk by Framingham Score and Total Carotid Plaque Area

Resumen Antecedentes: las enfermedades cardiovasculares son la principal causa de morbimortalidad mundial. La obesidad, sarcopenia, actividad física insuficiente y las conductas sedentarias impactan de manera sinérgica en el riesgo cardiovascular. Objetivo: evaluar el riesgo cardiovascular en relación con la actividad física, las conductas sedentarias y la composición corporal. Materiales y métodos: estudio observacional transversal de 95 personas adultas de ambos sexos. Se determinó el riesgo cardiovascular mediante el score de Framingham y el score de Framingham corregido por área total de placa aterosclerótica; la composición corporal, por antropometría, bioimpedancia y dinamometría como indicador indirecto; y la actividad física y las conductas sedentarias, por cuestionario validado. Se condujeron análisis descriptivos, de correlación y asociación con un 95 % de confianza. Resultados: el 95 % de las mujeres y el 98 % de los varones presentaron riesgo cardiovascular elevado; el 51,5 %, obesidad; el 95,5%, obesidad central; y el 47,3 %, fuerza muscular disminuida. Se observaron asociaciones positivas significativas entre riesgo cardiovascular y circunferencia de cintura (rho=0,26; p=0,024). No hubo asociación significativa entre la fuerza muscular y el riesgo cardiovascular (rho=-0,21; p=0,065). La conducta sedentaria tuvo un efecto promotor del riesgo cardiovascular (OR=3,9; p=0,033). Conclusiones: la obesidad central y permanecer más de 6/h día en posición sedente son factores asociados al riesgo cardiovascular.

Abstract Background: Cardiovascular diseases are the principal cause of morbidity and mortality worldwide. Obesity, sarco-penia, insufficient physical activity, and sedentary behaviors synergistically impact cardiovascular risk. Objective: Evaluate cardiovascular risk in relation to physical activity, sedentary behaviors, and body composition. Materials and Methods: Cross-sectional observational study in 95 total males and females. Cardiovascular risk was determined using the Framingham score, which corrects for total area of atherosclerotic plaque. Risk was also determined using body composition, anthropometry, bioimpedance and dynamometry as indirect indicators, physical activity, sedentary behaviors, and a validated questionnaire. Descriptive, correlation and association analyses were conducted with 95% confidence. Results: 95% of women and 98% of men presented with an elevated cardiovascular risk; 51.5% with obesity, 95.5% central obesity, and 47.3% with diminished muscular strength. Significant positive associations were observed between cardiovascular risk and waist circumference (rho=0.26; p=0.024). There was no significant association between muscle strength and cardiovascular risk (rho=-0.21, p=0.065). Sedentary behavior increased cardiovascular risk (OR=3.9; p=0.033). Conclusions: Central obesity and staying more than six hours per day in a sitting position are factors associated with cardiovascular risk.

p66Shc Inactivation Modifies RNS Production, Regulates Sirt3 Activity, and Improves Mitochondrial Homeostasis, Delaying the Aging Process in Mouse Brain.

Programmed and damage aging theories have traditionally been conceived as stand-alone schools of thought. However, the p66Shc adaptor protein has demonstrated that aging-regulating genes and reactive oxygen species (ROS) are closely interconnected, since its absence modifies metabolic homeostasis by providing oxidative stress resistance and promoting longevity. p66Shc(-/-) mice are a unique opportunity to further comprehend the bidirectional relationship between redox homeostasis and the imbalance of mitochondrial biogenesis and dynamics during aging. This study shows that brain mitochondria of p66Shc(-/-) aged mice exhibit a reduced alteration of redox balance with a decrease in both ROS generation and its detoxification activity. We also demonstrate a strong link between reactive nitrogen species (RNS) and mitochondrial function, morphology, and biogenesis, where low levels of ONOO- formation present in aged p66Shc(-/-) mouse brain prevent protein nitration, delaying the loss of biological functions characteristic of the aging process. Sirt3 modulates age-associated mitochondrial biology and function via lysine deacetylation of target proteins, and we show that its regulation depends on its nitration status and is benefited by the improved NAD+/NADH ratio in aged p66Shc(-/-) brain mitochondria. Low levels of protein nitration and acetylation could cause the metabolic homeostasis maintenance observed during aging in this group, thus increasing its lifespan.

Adding carotid total plaque area to the Framingham risk score improves cardiovascular risk classification.

INTRODUCTION: Cardiovascular events (CE) due to atherosclerosis are preventable. Identification of high-risk patients helps to focus resources on those most likely to benefit from expensive therapy. Atherosclerosis is not considered for patient risk categorization, even though a fraction of CE are predicted by Framingham risk factors. Our objective was to assess the incremental value of combining total plaque area (TPA) with the Framingham risk score (FramSc) using post-test probability (Ptp) in order to categorize risk in patients without CE and identify those at high risk and requiring intensive treatment. MATERIAL AND METHODS: A descriptive cross-sectional study was performed in the primary care setting in an Argentine population aged 22-90 years without CE. Both FramSc based on body mass index and Ptp-TPA were employed in 2035 patients for risk stratification and the resulting reclassification was compared. Total plaque area was measured with a high-resolution duplex ultrasound scanner. RESULTS: 57% male, 35% hypertensive, 27% hypercholesterolemia, 14% diabetes. 20.1% were low, 28.5% moderate, and 51.5% high risk. When patients were reclassified, 36% of them changed status; 24.1% migrated to a higher and 13.6% to a lower risk level (κ index = 0.360, SE κ = 0.16, p < 0.05, FramSc vs. Ptp-TPA). With this reclassification, 19.3% were low, 18.9% moderate and 61.8% high risk. CONCLUSIONS: Quantification of Ptp-TPA leads to higher risk estimation than FramSc, suggesting that Ptp-TPA may be more sensitive than FramSc as a screening tool. If our observation is confirmed with a prospective study, this reclassification would improve the long-term benefits related to CE prevention.

The Imaging Appearance of Sinus Mycetoma: A Case Series / El Aspecto Imagenológico del Micetoma Sinusal: Serie de Casos

Sinus mycetoma is a dense accumulation of hyphae that form a rounded mass within the mucosal confines of a paranasal sinus. The aim of this study was to present a case series of three patients with maxillary sinus mycetoma and to describe their radiographic presentations. Three cases are presented. The first two, a 44-year-old woman and an 88 year-old man, both diabetics, were referred to maxillofacial treatment by other specialties. They both had a bad odor of unknown origin on the facial level and their respective computerized tomographies revealed a unilateral opacification of the maxillary sinus with a region of greater radio-opacity. The third case is a 31-year-old woman with a history of a severe facial trauma who had undergone surgery and for whom orthognathic surgery had been planned to correct side effects. In addition to the orthognathic surgery, the removal of the lesion that appeared opacified in the pre-surgery scan was planned. She showed opacification of the maxillary sinus and during the intraoperative stage, tissue of a whitish-gray appearance was detected on the maxillary sinus. The lesion was completely removed and the result of the histopathological study was sinus mycetoma. The patients evolved favorably and the symptomatology disappeared completely. The growing occurrence of mycetoma and the lack of information on it make publicizing this pathology fundamental so it can be considered as a differential imaging, clinical, and pathological diagnosis and in that way receive adequate and opportune treatment.

El micetoma sinusal es una patología de origen fúngico, que afecta a pacientes inmunocomprometidos, capaz de desorientar en su diagnóstico por su clínica y expresión imagenológica particular. El objetivo de este estudio es presentar una serie de tres casos con micetoma en el seno maxilar y describir su presentación imagenológica. Se presentan tres casos. Los dos primeros, una mujer de 44 años y un hombre de 88 años, ambos diabéticos y derivados a atención maxilofacial por otras especialidades. Coincidía un mal olor expelido de origen desconocido a nivel facial y en sus respectivas tomografías computarizadas se observó velamiento unilateral del seno maxilar con una zona de mayor hiperdensidad. El tercer caso corresponde a una mujer de 31 años con antecedente de trauma facial severo operado, a la cual se le planificó cirugía ortognática para corregir secuelas. En conjunto con la cirugía ortognática, se planificó la biopsia excisional de una lesión hiperdensa que se presentó en el escáner pre-quirúrgico; en el intraoperatorio se pesquisó tejido de aspecto blanquecino grisáceo en el seno maxilar. A todos los pacientes se les realizó la exéresis total de la lesión y el estudio histopatológico dio como resultado micetoma sinusal. Los pacientes evolucionaron favorablemente, desapareciendo por completo la sintomatología. La creciente incidencia del micetoma y el desconocimiento sobre el mismo hacen que sea fundamental la difusión de esta patología para ser considerada como diagnóstico diferencial clínico y patológico, y realizar así un tratamiento adecuado y oportuno.

C-arm as intraoperative control in reduction of isolated zygomatic arch fractures: a randomized clinical trial.

PURPOSE: Isolated zygomatic arch fractures (IZAFs) are habitually reduced at a distance, via a temporal approach. Open reductions are not recommended due to the associated morbidity and complications. However, performing closed reductions makes it difficult to determine whether it was done satisfactorily. This study aims to determine whether the acquisition of intraoperative images with a C-arm to evaluate IZAF reductions is a useful technique in treating such fractures. METHODS: Our hypothesis is that acquiring intraoperative images with a C-arm reduces the need for a second surgery. Between 2009 and 2012, 50 patients who were diagnosed with IZAF requiring surgery were randomly distributed into two groups: 25 patients were in the experimental group, where fracture reduction was performed and immediately corroborated intraoperatively for an adequate result using a C-arm, and 25 patients were assigned to a control group where the fracture reduction was controlled with post-surgery imaging. RESULTS: The results did not reveal significant differences between both groups (p = 0.5). Nevertheless, the experimental group had the advantage of being able to immediately reduce the fracture again if the result was unsatisfactory. CONCLUSIONS: Despite the fact that the results are not statistically significant (p = 0.5), the authors recommend undertaking an intraoperative imaging analysis in areas where we are not certain of the reduction.

ß2-adrenoceptor stimulation restores frontal cortex plasticity and improves visuospatial performance in hidden-prenatally-malnourished young-adult rats.

Moderate reduction in dietary protein composition of pregnant rats from 25% to 8% casein, calorically compensated by carbohydrates, has been described as a "hidden malnutrition" because it does not alter body and brain weights of pups at birth. However, this dietary treatment leads to altered central noradrenergic systems, impaired cortical long-term potentiation (LTP) and worsened visuo-spatial memory performance. Given the increasing interest on the role played by ß2-adrenoceptors (ß2-ARs) on brain plasticity, the present study aimed to address the following in hidden-malnourished and eutrophic control rats: (i) the expression levels of ß2-ARs in the frontal cortex determined by immunohistochemistry, and (ii) the effect of the ß2 selective agonist clenbuterol on both LTP elicited in vivo in the prefrontal cortex and visuospatial performance measured in an eight-arm radial maze. Our results showed that, prenatally malnourished rats exhibited a significant reduction of neocortical ß2-AR expression in adulthood. Concomitantly, they were unable to elicit and maintain prefrontal cortex LTP and exhibited lower visuospatial learning performance. Administration of clenbuterol (0.019, 0.038 and 0.075 mg/kg i.p.) enhanced LTP in malnourished and control animals and restored visuospatial learning performance in malnourished but not in normal rats, in a dose-dependent manner. The results suggest that decreased density of neocortical ß2-ARs during postnatal life, subsequent to hidden prenatal malnutrition might affect some synaptic networks required to elicit neocortical LTP and form visuospatial memory, since those neuroplastic deficits were counteracted by ß2-AR stimulation.

Knockdown of α2C-adrenoceptors in the occipital cortex rescued long-term potentiation in hidden prenatally malnourished rats.

Moderate reduction in the protein content of the mother's diet calorically compensated by carbohydrates (the so-called "hidden" prenatal malnutrition) leads to increased neocortical expression of the α(2C)-adrenoceptor subtype, together with decreased cortical release of noradrenaline and impaired long-term potentiation (LTP) and visuospatial memory performance during the rat postnatal life. In order to study whether overexpression of the α(2C)-adrenoceptor subtype is causally related to the decreased indices of neocortical plasticity found in prenatally malnourished rats, we evaluated the effect of intracortical (occipital cortex) administration of an antisense oligodeoxynucleotide (ODN) raised against the α(2C)-adrenoceptor mRNA on the LTP elicited in vivo in the occipital cortex of hidden prenatally malnourished rats. In addition, we compare the effect of the antisense ODN to that produced by systemical administration of the subtype-nonselective α(2)-adrenoceptor antagonist atipamezole. Prenatal protein malnutrition led to impaired occipital cortex LTP together with increased expression of α(2C)-adrenoceptors (about twice Bmax) in the same cortical region. [(3)H]-rauwolscine binding assay showed that a 7-day intracortical antisense ODN treatment in the malnourished rats resulted in 50% knockdown of α(2C)-adrenoceptor expression and, in addition, completely rescued the ability of the occipital cortex to develop and maintain long-term potentiation. Atipamezole (0.3 mg/kg i.p.) also led to full recovery of neocortical LTP in malnourished rats. The present results argue in favor of our original hypothesis that the deleterious effect of prenatal malnutrition on neocortical plasticity in the adult progeny is in part consequence of increased neocortical α(2C)-adrenoceptor expression. This receptor subtype is known to be involved in the presynaptic control of noradrenaline release from central neurons, a neurotransmitter that critically influences LTP and memory formation.

Anatomy of corpus callosum in prenatally malnourished rats.

The effect of prenatal malnutrition on the anatomy of the corpus callosum was assessed in adult rats (45-52 days old). In the prenatally malnourished animals we observed a significant reduction of the corpus callosum total area, partial areas, and perimeter, as compared with normal animals. In addition, the splenium of corpus callosum (posterior fifth) showed a significant decrease of fiber diameters in the myelinated fibers without changing density. There was also a significant decrease in diameter and a significant increase in density of unmyelinated fibers. Measurements of perimeter's fractal dimensions from sagittal sections of the brain and corpus callosum did not show significant differences between malnourished and control animals. These findings indicate that cortico-cortical connections are vulnerable to the prenatal malnutrition, and suggest this may affect interhemispheric conduction velocity, particularly in visual connections (splenium).

Anatomy of corpus callosum in prenatally malnourished rats

The effect of prenatal malnutrition on the anatomy of the corpus callosum was assessed in adult rats (45-52 days old). In the prenatally malnourished animals we observed a significant reduction of the corpus callosum total area, partial areas, and perimeter, as compared with normal animals. In addition, the splenium of corpus callosum (posterior fifth) showed a significant decrease of fiber diameters in the myelinated fibers without changing density. There was also a significant decrease in diameter and a significant increase in density of unmyelinated fibers. Measurements of perimeter's fractal dimensions from sagittal sections of the brain and corpus callosum did not show significant differences between malnourished and control animals. These findings indicate that cortico-cortical connections are vulnerable to the prenatal malnutrition, and suggest this may affect interhemispheric conduction velocity, particulary in visual connections (splenium).

Hidden prenatal malnutrition in the rat: role of ß1-adrenoceptors on synaptic plasticity in the frontal cortex.

Moderate reduction in the protein content of the mother's diet (hidden malnutrition) does not alter body and brain weights of rat pups at birth, but leads to dysfunction of neocortical noradrenaline systems together with impaired long-term potentiation and visuo-spatial memory performance. As ß1-adrenoceptors and downstream protein kinase signaling are critically involved in synaptic long-term potentiation and memory formation, we evaluated the ß1-adrenoceptor density and the expression of cyclic-AMP dependent protein kinase, calcium/calmodulin-dependent protein kinase and protein kinase Fyn, in the frontal cortex of prenatally malnourished adult rats. In addition, we also studied if ß1-adrenoceptor activation with the selective ß1 agonist dobutamine could improve deficits of prefrontal cortex long-term potentiation presenting these animals. Prenatally malnourished rats exhibited half of ß1-adrenoceptor binding, together with a 51% and 65% reduction of cyclic AMP-dependent protein kinase α and calcium/calmodulin-dependent protein kinase α expression, respectively, as compared with eutrophic animals. Administration of the selective ß1 agonist dobutamine prior to tetanization completely rescued the ability of the prefrontal cortex to develop and maintain long-term potentiation in the malnourished rats. Results suggest that under-expression of neocortical ß1-adrenoceptors and protein kinase signaling in hidden malnourished rats functionally affects the synaptic networks subserving prefrontal cortex long-term potentiation. ß1-adrenoceptor activation was sufficient to fully recover neocortical plasticity in the PKA- and calcium/calmodulin-dependent protein kinase II-deficient undernourished rats, possibly by producing extra amounts of cAMP and/or by recruiting alternative signaling cascades.

A putative role for hypothalamic glucocorticoid receptors in hypertension induced by prenatal undernutrition in the rat.

Prenatal undernutrition induces hypertension later in life, possibly by disturbing the hypothalamo-pituitary-adrenal axis through programming decreased expression of hypothalamic glucocorticoid receptors. We examined the systolic blood pressure, heart rate and plasma corticosterone response to intra-paraventricular dexamethasone, mifepristone and corticosterone in eutrophic and prenatally undernourished young rats. Undernutrition was induced during fetal life by restricting the diet of pregnant mothers to 10 g daily (40% of diet consumed by well-nourished controls). At day 40 of postnatal life (i) intra-paraventricular administration of dexamethasone significantly reduced at least for 24h both the systolic pressure (-11.6%), the heart rate (-20.8%) and the plasma corticosterone (-40.0%) in normal animals, while producing lower effects (-5.5, -8.7, and -22.3%, respectively) on undernourished rats; (ii) intra-paraventricular administration of the antiglucocorticoid receptor ligand mifepristone to normal rats produced opposite effects (8.2, 20.3, and 48.0% increase, respectively) to those induced by dexamethasone, being these not significant in undernourished animals; (iii) intra-paraventricular corticosterone did not exert any significant effect. Results suggest that the low sensitivity of paraventricular neurons to glucocorticoid receptor ligands observed in prenatally undernourished rats could be due to the already reported glucocorticoid receptor expression, found in the hypothalamus of undernourished animals.

beta-Adrenoceptor blockade depresses molecular and functional plasticities in the rat neocortex.

beta-Adrenergic receptor stimulation can significantly facilitate synaptic potentiation in the hippocampus and enhance memory processes, but its effect on neocortical plastic mechanisms is less conclusive. In the present study we determined the effect of propranolol, a beta-adrenoceptor antagonist, on long-term potentiation (LTP) induced in vivo in rat occipital cortex by tetanizing stimulation of corpus callosum and observed a dose-dependent inhibition of LTP. We further administered propranolol through mini-osmotic pumps during 3 days, and observed the performance of rats in a complex operant conditioning learning paradigm and assessed the expression of brain-derived neurotrophic factor (BDNF) in the occipital cortex. Propranolol exposure depressed both the number of reinforced responses in the operant conditioning task and BDNF expression in occipital cortex. Taken together, our results suggest that propranolol impairs memory formation by inhibiting cortical LTP induction and associated BDNF expression.

Impact of nutritional status at the onset of elementary school on academic aptitude test achievement at the end of high school in a multicausal approach.

Like in many other countries, few investigations have been carried out in Chile to measure the long-term effects of nutritional status at an early age on scholastic achievement in a multicausal approach. The objectives of the present study were to describe the impact of nutritional, intellectual, family, educational and socio-economic variables at the onset of elementary school in 1987 that may affect achievement on the academic aptitude test (AAT) taken in 1998 at the end of high school, and to quantify the impact of these independent variables on the AAT. The present study comprises two cross-sectional stages: in 1987, a representative sample of 813 elementary school first-grader Chilean children from the Metropolitan Region was randomly chosen; in 1998, 12 years later, 632 school-age children were located and only 351 of them graduated from high school and, from these, 260 students took the AAT. In 1987 nutritional status was assessed through anthropometric parameters, intellectual ability by the Raven's Progressive Matrices Test, scholastic achievement through Spanish language and mathematics tests, and socio-economic status using Graffar's modified scale; family variables were also recorded. Maternal schooling, scholastic achievement, intellectual ability and head circumference-for-age z-score (anthropometric indicator of both nutritional background and brain development) all in 1987 were the independent variables with the greatest explanatory power for AAT variance in 1998 (r2 0.402). These results provide a foundation to identify the risk factors at an early age that affect AAT scores and should be useful to improve nutritional and educational policies.

Eventos centinela y la notificación por el personal de enfermería / Sentinel events and notification by nursing staff

Introducción: Reportes internacionales indican que sólo 5 % de los eventos adversos son notificados, esto se debe a factores inherentes al personal de salud, como miedo al castigo, evidencia al ejercicio de la práctica, desconocimiento del programa de notificación y falta de reinformación posterior a la notificación, entre otros. Objetivo: Identificar en el personal de enfermería el conocimiento que tienen del programa VENCER, "Sistema de Vigilancia de Eventos Centinela y Riesgos" y determinar los factores relacionados en la notificación de los eventos. Metodología: Estudio transversal, en 226 enfermeras seleccionadas con muestreo probabilístico, por conglomerado. Se elaboró instrumento con 62 reactivos, validado mediante alpha de Cronbach, obteniéndose una confiabilidad de 0.73, para el análisis se utilizó el programa SPSS V 14, y se aplicó estadística descriptiva. Resultados: Edad promedio del personal de enfermería 38 años, con predominio del sexo femenino 96 %, enfermeras generales 51 %, enfermeras especialistas 21 %, y 22 % enfermeras con estudios de licenciatura. El factor que limitó el registro de eventos fue el desconocimiento del programa de notificación 92 % y falta de reinformación 84 %. La categoría institucional p = 0.02, es factor asociado significativamente al conocimiento del evento centinela, no se encontraron diferencias en relación al conocimiento del personal del evento centinela p = 0.03 y el conocimiento del Programa VENCER p- 0.04, respecto a cada unidad de adscripción. La falta de reinformación por el personal directivo posterior a la notificación del evento es uno de los factores asociados a la notificación. Conclusiones: Es imperativo la difusión del Programa VENCER a todo el personal para garantizar la seguridad del paciente en las unidades hospitalarias.

Abstract Introduction: International reports show that only 5 % of adversity effects are notified; which is due to inherent factors related to health staff, such as being afraid to be punished, being exposed to the professional praxis, unknowing the notification program and the lack of reinformation after the first notification, among others. Objective: To identify among nursing staff their knowledge of the program: VENCER, or "system of surveillance for sentinel events and risks" and determine factors related in the notification of events. Methodology: Transversal study done in 226 nurses selected through probabilistic sampling, by conglomerates. An instrument was elaborated with 62 items, and validated with Cronbach's alfa, obtaining a level of confidence of 0.73. For the analysis, the software SPSS V14 was utilized, applying descriptive statistics. Results: Average age of nursing staff was 38 years old, 96 % of them female, 51 % professional nurses, 21 % specialized nurses, and 22 % with level of baccalaureate degree. Conclusions: It is imperative the difussions of the program VENCER to all the operative personnel according to guarantee the security to the patient in all hospital units.

Fetal undernutrition induces overexpression of CRH mRNA and CRH protein in hypothalamus and increases CRH and corticosterone in plasma during postnatal life in the rat.

Prenatal undernutrition induces a variety of cardiovascular alterations in mammals when adults, including hypertension and hypercortisolism, which are thought to be caused by decreased glucocorticoid feedback control of the hypothalamus-pituitary-adrenal (HPA) axis programmed during fetal life. Hypothalamic CRH seems to be involved in blood pressure elevation of spontaneously hypertensive rats and in primary hypertension of humans, but the influence of prenatal undernutrition on CRH expression has deserved little attention. Here, we studied the expression of both CRH mRNA and CRH protein in the hypothalamus of neonatal and juvenile offspring of rats undernourished during fetal life, as well as the plasma levels of CRH and corticosterone. Prenatal undernutrition of pups was induced by submitting pregnant rats to diet restriction (10g daily of 21% protein standard laboratory diet). Pups born from dams with free access to the standard laboratory diet served as controls. At day 2 of postnatal age, undernourished pups showed lower body and brain weights, but higher plasma CRH and corticosterone than normal pups. At day 40 of age, brain weight was significantly decreased in the undernourished rats, while plasma corticosterone, plasma CRH and systolic pressure were significantly increased in these animals. At days 2 and 40 of postnatal age, increased CRH mRNA expression and CRH concentration were found in the hypothalamus of undernourished rats. Results indicate that, in the rat, prenatal undernutrition led to fetal programming of CRH overexpression, a neuropeptide serving as activating signal to the HPA axis and/or to extrahypothalamic brain regions concerned with cardiovascular regulation.

Effect of prenatal protein malnutrition on long-term potentiation and BDNF protein expression in the rat entorhinal cortex after neocortical and hippocampal tetanization.

Reduction of the protein content from 25 to 8% casein in the diet of pregnant rats results in impaired neocortical long-term potentiation (LTP) of the offspring together with lower visuospatial memory performance. The present study was aimed to investigate whether this type of maternal malnutrition could result in modification of plastic capabilities of the entorhinal cortex (EC) in the adult progeny. Unlike normal eutrophic controls, 55-60-day-old prenatally malnourished rats were unable to develop LTP in the medial EC to tetanizing stimulation delivered to either the ipsilateral occipital cortex or the CA1 hippocampal region. Tetanizing stimulation of CA1 also failed to increase the concentration of brain-derived neurotrophic factor (BDNF) in the EC of malnourished rats. Impaired capacity of the EC of prenatally malnourished rats to develop LTP and to increase BDNF levels during adulthood may be an important factor contributing to deficits in learning performance having adult prenatally malnourished animals.