Late Protein Synthesis-Dependent Phases in CTA Long-Term Memory: BDNF Requirement

It has been proposed that long-term memory (LTM) persistence requires a late protein synthesis-dependent phase, even many hours after memory acquisition. Brain-derived neurotrophic factor (BDNF) is an essential protein synthesis product that has emerged as one of the most potent molecular mediators for long-term synaptic plasticity. Studies in the rat hippocampus have been shown that BDNF is capable to rescue the late-phase of long-term potentiation as well as the hippocampus-related LTM when protein synthesis was inhibited. Our previous studies on the insular cortex (IC), a region of the temporal cortex implicated in the acquisition and storage of conditioned taste aversion (CTA), have demonstrated that intracortical delivery of BDNF reverses the deficit in CTA memory caused by the inhibition of IC protein synthesis due to anisomycin administration during early acquisition. In this work, we first analyze whether CTA memory storage is protein synthesis-dependent in different time windows. We observed that CTA memory become sensible to protein synthesis inhibition 5 and 7 h after acquisition. Then, we explore the effect of BDNF delivery (2 μg/2 μl per side) in the IC during those late protein synthesis-dependent phases. Our results show that BDNF reverses the CTA memory deficit produced by protein synthesis inhibition in both phases. These findings support the notion that recurrent rounds of consolidation-like events take place in the neocortex for maintenance of CTA memory trace and that BDNF is an essential component of these processes

Razonamiento covariacional de estudiantes universitarios en un acercamiento al concepto de integral definida mediante sumas de Riemann

This study aims to analyze changes in mental actions associated with the covariational reasoning of one pair of students when working on tasks to approach the concept of definite integral through Riemann sums. Mental actions are gathered from student interactions in GeoGebra, from their written reports, and from a semi-structured interview applied to one pair of students from an engineering school in Mexico. Data are analyzed with the theoretical construct of covariational reasoning. The results show an evolution in the way students coordinate simultaneous changes between the variables involved in tasks, from the no coordination level to the chunky continuous covariation level. It is concluded that questions to propose conjectures on the use of rectangles in approximation processes to the area of a region, including their justification, and the process of inferring behaviors from hypothetical situations, reveal behaviors associated with higher levels of covariational reasoning.Revisón por pare

Epidemiology and risk factors for invasive pneumococcal disease in pediatrics: Descriptive, postvaccinal study

En 2011 se incorporó la vacuna 13-valente al Calendario Nacional de Inmunización, con aplicación efectiva desde 2012. El objetivo fue describir la epidemiología de la enfermedad y los factores de riesgo observados en pacientes con diagnóstico de enfermedad invasiva neumocócica en la población pediátrica que se atiende en el Hospital “Dr. F. Barreyro” y en el Hospital SAMIC-Oberá entre mayo de 2013 y abril de 2014. Se obtuvieron datos clínicos y epidemiológicos de los pacientes con diagnóstico confirmado y se realizaron técnicas de iología molecular para descartar y/o confirmar casos sospechosos. Se diagnosticaron 23 casos, con picos en invierno y primavera. Predominaron los pacientes mayores de 2 años (82%), los varones (65%) y las neumonías (69,6%). Los neumococos sensibles a penicilina preponderaron en todo el estudio. Se distinguieron dos serotipos (1 y 12F). No observamos prevalencia de factores de riesgo considerados. Es necesario continuar con la vigilancia activa.The 13-valent pneumococcal conjugate vaccine was added to the National Immunization Program in 2011, and effectively administered since 2012. The aim of this study was to describe the post–vaccine epidemiology of pneumococcal invasive disease, in the pediatric population who come for consultation at the "Dr. F. Barreyro" and "SAMIC-Oberá" Hospitals, between May-2013 and April-2014. Clinical and epidemiological data were obtained and the suspected cases were confirmed by polymerase chain reaction. Twenty three cases were diagnosed, a seasonal pattern was observed with peaks in winter and spring. Patients older than 2 years old (82%), the masculine gender (65%), and who were diagnosed with pneumonia(69,6%) prevailed. Penicillin-sensitive pneumococci predominated throughout the study. Two serotypes (1 and 12F) were mainly distinguished. We did not observe any prevalence in the factors considered.It is necessary to continue active surveillance.Fil: Benitez, Jesica Deolina. Universidad Nacional de Misiones. Facultad de Ciencias Exactas, Químicas y Naturales; ArgentinaFil: Martínez, Mónica Elisabeth. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Misiones. Facultad de Ciencias Exactas, Químicas y Naturales; Argentina. Provincia de Misiones. Ministerio de Salud de la Provincia de Misiones. Hospital Publico Provincial de Pediatria de Autogestion Dr. Fernando Barreyro; ArgentinaFil: Von Specht, Martha Helena. Universidad Nacional de Misiones. Facultad de Ciencias Exactas, Químicas y Naturales; ArgentinaFil: Gerlach, Erica. Gobierno de la Provincia de Misiones. Hospital Samic Eldorado; ArgentinaFil: Gonzalez, Cristina A.. Gobierno de la Provincia de Misiones. Hospital Samic Eldorado; ArgentinaFil: Grenón, Sandra L.. Universidad Nacional de Misiones. Facultad de Ciencias Exactas, Químicas y Naturales; Argentin

Uso de la analgesia acupuntural quirúrgica en la herniorrafía inguinal. The use of surgical acupunctural analysis in inguinal herniarhaphy

Por la importancia que ha alcanzado en nuestro país la aplicación de la medicina natural y tradicional y dentro de ésta la acupuntura, no sólo en el orden clínico sino con fines quirúrgicos, se realizó un estudio descriptivo y retrospectivo de 40 pacientes operados por hernia inguinal en el Hospital General Docente "Abel Santamaría Cuadrado" de Pinar del Río durante el período comprendido de enero a julio del año 2003, con el objetivo de evaluar la efectividad de la analgesia quirúrgica acupuntural en este tipo de cirugía. Se conformaron dos grupos (control y estudio). Al control se le aplicó anestesia espinal y al de estudio, analgesia quirúrgica acupuntural. Se comparó grado de analgesia transoperatoria y postoperatoria, así como las complicaciones. Se determinó el grado de satisfacción de los pacientes, para lo cual fue aplicada una escala analógica visual, siendo buena en un 90% de los pacientes, a los cuales se les aplicó la analgesia acupuntural. Este proceder es inocuo, de fácil aplicación, bien aceptado por el paciente, y representa un ahorro económico considerable, ya que disminuye los costos hospitalarios, por lo que recomendamos su empleo de forma sistemática. En todos los pacientes se aplicó la cirugía mayor ambulatoria. Palabras clave: ACUPUNTURA, ANALGESIA, HERNIA INGUINAL, MEDICINA TRADICIONAL. ABSTRACT By the importance the application of the traditional and natural medicine has gotten in our country, specially acupuncture, not only clinically but also with surgical purposes, a descriptive and retrospective study was performed with 40 patients operated on for inguinal hernia at "Abel Santamaría Cuadrado" Teaching University Hospital in Pinar del Río, from January to July 2003, with the purpose of assessing the effectiveness of the surgical acupunctural analgesia in this type of surgery. Two groups were formed (control and study). The control group was applied spinal anesthesia, and the study group was applied surgical acupunctural analgesia. The degree of transoperative and post-operative analgesia was compared, as well as the complications. The degree of the patient's satisfaction was registered, for which a visual analogical scale was applied, being good in 90% patients who underwent acupunctural analgesia. This procedure is harmless, easily applicable, well accepted by the patient, and represents a significant economical saving since it diminishes hospital costs. This is why its systematic use is recommended. All patients underwent major ambulatory surgery. Key words: ACUPUNCTURE, ANALGESIA, INGUINAL HERNIA, TRADITIONAL MEDICINE

The effect of occupational exposure to welding fumes on trachea, bronchus and lung cancer: A systematic review and meta-analysis from the WHO/ILO Joint Estimates of the Work-related Burden of Disease and Injury

Background: The World Health Organization (WHO) and the International Labour Organization (ILO) are the producers of the WHO/ILO Joint Estimates of the Work-related Burden of Disease and Injury (WHO/ILO Joint Estimates). Welding fumes have been classified as carcinogenic to humans (Group 1) by the WHO International Agency for Research on Cancer (IARC) in IARC Monograph 118; this assessment found sufficient evidence from studies in humans that welding fumes are a cause of lung cancer. In this article, we present a systematic review and meta-analysis of parameters for estimating the number of deaths and disability-adjusted life years from trachea, bronchus, and lung cancer attributable to occupational exposure to welding fumes, to inform the development of WHO/ILO Joint Estimates on this burden of disease (if considered feasible). Objectives: We aimed to systematically review and meta-analyse estimates of the effect of any (or high) occupational exposure to welding fumes, compared with no (or low) occupational exposure to welding fumes, on trachea, bronchus, and lung cancer (three outcomes: prevalence, incidence, and mortality). Data sources: We developed and published a protocol, applying the Navigation Guide as an organizing systematic review framework where feasible. We searched electronic databases for potentially relevant records from published and unpublished studies, including Medline, EMBASE, Web of Science, CENTRAL and CISDOC. We also searched grey literature databases, Internet search engines, and organizational websites; hand-searched reference lists of previous systematic reviews; and consulted additional experts. Study eligibility and criteria: We included working-age (≥15 years) workers in the formal and informal economy in any Member State of WHO and/or ILO but excluded children (<15 years) and unpaid domestic workers. We included randomized controlled trials, cohort studies, case-control studies, and other non-randomized intervention studies with an estimate of the effect of any (or high) occupational exposure to welding fumes, compared with occupational exposure to no (or low) welding fumes, on trachea, bronchus, and lung cancer (prevalence, incidence, and mortality). Study appraisal and synthesis methods: At least two review authors independently screened titles and abstracts against the eligibility criteria at a first review stage and full texts of potentially eligible records at a second stage, followed by extraction of data from qualifying studies. If studies reported odds ratios, these were converted to risk ratios (RRs). We combined all RRs using random-effects meta-analysis. Two or more review authors assessed the risk of bias, quality of evidence, and strength of evidence, using the Navigation Guide tools and approaches adapted to this project. Subgroup (e.g., by WHO region and sex) and sensitivity analyses (e.g., studies judged to be of “high”/“probably high” risk of bias compared with “low”/“probably low” risk of bias) were conducted. Results: Forty-one records from 40 studies (29 case control studies and 11 cohort studies) met the inclusion criteria, comprising over 1,265,512 participants (≥22,761 females) in 21 countries in three WHO regions (Region of the Americas, European Region, and Western Pacific Region). The exposure and outcome were generally assessed by job title or self-report, and medical or administrative records, respectively. Across included studies, risk of bias was overall generally probably low/low, with risk judged high or probably high for several studies in the domains for misclassification bias and confounding.Our search identified no evidence on the outcome of having trachea, bronchus, and lung cancer (prevalence). Compared with no (or low) occupational exposure to welding fumes, any (or high) occupational exposure to welding fumes increased the risk of acquiring trachea, bronchus, and lung cancer (incidence) by an estimated 48 % (RR 1.48, 95 % confidence interval [CI] 1.29–1.70, 23 studies, 57,931 participants, I2 24 %; moderate quality of evidence). Compared with no (or low) occupational exposure to welding fumes, any (or high) occupational exposure to welding fumes increased the risk dying from trachea, bronchus, and lung cancer (mortality) by an estimated 27 % (RR 1.27, 95 % CI 1.04–1.56, 3 studies, 8,686 participants, I2 0 %; low quality of evidence). Our subgroup analyses found no evidence for difference by WHO region and sex. Sensitivity analyses supported the main analyses. Conclusions: Overall, for incidence and mortality of trachea, bronchus, and lung cancer, we judged the existing body of evidence for human data as “sufficient evidence of harmfulness” and “limited evidence of harmfulness”, respectively. Occupational exposure to welding fumes increased the risk of acquiring and dying from trachea, bronchus, and lung cancer. Producing estimates for the burden of trachea, bronchus, and lung cancer attributable to any (or high) occupational exposure to welding fumes appears evidence-based, and the pooled effect estimates presented in this systematic review could be used as input data for the WHO/ILO Joint Estimates. Protocol identifier: https://doi.org/10.1016/j.envint.2020.106089

Rare Germline DICER1 Variants in Pediatric Patients With Cushing's Disease: What Is Their Role?

Context: The DICER1 syndrome is a multiple neoplasia disorder caused by germline mutations in the DICER1 gene. In DICER1 patients, aggressive congenital pituitary tumors lead to neonatal Cushing's disease (CD). The role of DICER1 in other corticotropinomas, however, remains unknown. Objective: To perform a comprehensive screening for DICER1 variants in a large cohort of CD patients, and to analyze their possible contribution to the phenotype. Design, setting, patients, and interventions: We included 192CD cases: ten young-onset (age <30 years at diagnosis) patients were studied using a next generation sequencing panel, and 182 patients (170 pediatric and 12 adults) were screened via whole-exome sequencing. In seven cases, tumor samples were analyzed by Sanger sequencing. Results: Rare germline DICER1 variants were found in seven pediatric patients with no other known disease-associated germline defects or somatic DICER1 second hits. By immunohistochemistry, DICER1 showed nuclear localization in 5/6 patients. Variant transmission from one of the parents was confirmed in 5/7 cases. One patient had a multinodular goiter; another had a family history of melanoma; no other patients had a history of neoplasms. Conclusions: Our findings suggest that DICER1 gene variants may contribute to the pathogenesis of non-syndromic corticotropinomas. Clarifying whether DICER1 loss-of-function is disease-causative or a mere disease-modifier in this setting, requires further studies.This work was supported by the Intramural Research Programs of Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) and National Institute for Neurological Diseases and Stroke, National Institutes of Health, a grant from the Basque Department of Education (IT795-13), a grant from the Basque Department of Health (GV2018111082), the Merck Serono Research award from Fundacion Salud 2000 (15-EP-004) and the Jose Igea 2018 grant, sponsored by Pfizer, from Fundacion Sociedad Espanola de Endocrinologia Pediatrica (SEEP)

Rationing tests for drug-resistant tuberculosis - who are we prepared to miss?

BACKGROUND: Early identification of patients with drug-resistant tuberculosis (DR-TB) increases the likelihood of treatment success and interrupts transmission. Resource-constrained settings use risk profiling to ration the use of drug susceptibility testing (DST). Nevertheless, no studies have yet quantified how many patients with DR-TB this strategy will miss. METHODS: A total of 1,545 subjects, who presented to Lima health centres with possible TB symptoms, completed a clinic-epidemiological questionnaire and provided sputum samples for TB culture and DST. The proportion of drug resistance in this population was calculated and the data was analysed to demonstrate the effect of rationing tests to patients with multidrug-resistant TB (MDR-TB) risk factors on the number of tests needed and corresponding proportion of missed patients with DR-TB. RESULTS: Overall, 147/1,545 (9.5%) subjects had culture-positive TB, of which 32 (21.8%) had DR-TB (MDR, 13.6%; isoniazid mono-resistant, 7.5%; rifampicin mono-resistant, 0.7%). A total of 553 subjects (35.8%) reported one or more MDR-TB risk factors; of these, 506 (91.5%; 95% CI, 88.9-93.7%) did not have TB, 32/553 (5.8%; 95% CI, 3.4-8.1%) had drug-susceptible TB, and only 15/553 (2.7%; 95% CI, 1.5-4.4%) had DR-TB. Rationing DST to those with an MDR-TB risk factor would have missed more than half of the DR-TB population (17/32, 53.2%; 95% CI, 34.7-70.9). CONCLUSIONS: Rationing DST based on known MDR-TB risk factors misses an unacceptable proportion of patients with drug-resistance in settings with ongoing DR-TB transmission. Investment in diagnostic services to allow universal DST for people with presumptive TB should be a high priority

Galaxy Zoo and ALFALFA: Atomic Gas and the Regulation of Star Formation in Barred Disc Galaxies

We study the observed correlation between atomic gas content and the likelihood of hosting a large scale bar in a sample of 2090 disc galaxies. Such a test has never been done before on this scale. We use data on morphologies from the Galaxy Zoo project and information on the galaxies' HI content from the ALFALFA blind HI survey. Our main result is that the bar fraction is significantly lower among gas rich disc galaxies than gas poor ones. This is not explained by known trends for more massive (stellar) and redder disc galaxies to host more bars and have lower gas fractions: we still see at fixed stellar mass a residual correlation between gas content and bar fraction. We discuss three possible causal explanations: (1) bars in disc galaxies cause atomic gas to be used up more quickly, (2) increasing the atomic gas content in a disc galaxy inhibits bar formation, and (3) bar fraction and gas content are both driven by correlation with environmental effects (e.g. tidal triggering of bars, combined with strangulation removing gas). All three explanations are consistent with the observed correlations. In addition our observations suggest bars may reduce or halt star formation in the outer parts of discs by holding back the infall of external gas beyond bar co-rotation, reddening the global colours of barred disc galaxies. This suggests that secular evolution driven by the exchange of angular momentum between stars in the bar, and gas in the disc, acts as a feedback mechanism to regulate star formation in intermediate mass disc galaxies.Comment: 16 pages, 10 figures. In press at MNRAS. v2 contains corrections found in proof