Measurement of 10B concentration through autoradiography images in polycarbonate nuclear track detectors

The determination of the local concentration of boron in the different regions of tissue samples treated by Boron Neutron Capture Therapy (BNCT) could be made through the evaluation of the number of tracks forming autoradiography images. It is necessary to get a "standard" material containing a known amount of 10B, to correlate the number of tracks and boron concentration, i.e. to be used as a reference. Different systems were tested in order to find a suitable standard. Films made of 2% agarose in boron solutions showed a homogeneous distribution of the 10B atoms in the material structure. This system is easy handled and its physical properties are satisfactory. On the other hand, a small volume polycarbonate box was designed to contain 10B solutions of known concentration. This system showed a reduced number of background tracks and a promising behavior in many aspects. There is proportionality between track numbers per surface unit and 10B concentration, and between track numbers per surface unit and neutron fluence. Experimental results were compared to calculated values through formulas developed for thick samples autoradiography.Fil: Portu, Agustina Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Comisión Nacional de Energía Atómica; ArgentinaFil: Bernaola, Omar Alberto. Comisión Nacional de Energía Atómica. Gerencia de Area de Aplicaciones de la Tecnología Nuclear. Gerencia de Radiobiología (Centro Atómico Constituyentes); ArgentinaFil: Nievas, Susana Isabel. Comisión Nacional de Energía Atómica; ArgentinaFil: Liberman, Sara. Comisión Nacional de Energía Atómica; ArgentinaFil: Saint Martin, María Laura Gisela. Comisión Nacional de Energía Atómica. Gerencia de Area de Aplicaciones de la Tecnología Nuclear. Gerencia de Radiobiología (Centro Atómico Constituyentes); Argentin

Reference systems for the determination of 10B through autoradiography images: Application to a melanoma experimental model

The amount of 10B in tissue samples may be determined by measuring the track density in the autoradiography image produced on a nuclear track detector. Different systems were evaluated as reference standards to be used for a quantitative evaluation of boron concentration. The obtained calibration curves were applied to evaluate the concentration of 10B in melanoma tumour of NIH nude mice after a biodistribution study. The histological features observed in the tissue sections were accurately reproduced by the autoradiography images.Fil: Portu, Agustina Mariana. Comisión Nacional de Energía Atómica. Centro Atómico Constituyentes; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Carpano, M.. Comisión Nacional de Energía Atómica. Centro Atómico Constituyentes; ArgentinaFil: Dagrosa, María Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Comisión Nacional de Energía Atómica. Centro Atómico Constituyentes; ArgentinaFil: Nievas, S.. Comisión Nacional de Energía Atómica. Centro Atómico Constituyentes; ArgentinaFil: Pozzi, E.. Comisión Nacional de Energía Atómica. Centro Atómico Constituyentes; ArgentinaFil: Thorp, S.. Comisión Nacional de Energía Atómica. Centro Atómico Constituyentes; ArgentinaFil: Cabrini, R.. Comisión Nacional de Energía Atómica. Centro Atómico Constituyentes; Argentina. Universidad de Buenos Aires. Facultad de Odontología; ArgentinaFil: Liberman, S.. Comisión Nacional de Energía Atómica. Centro Atómico Constituyentes; ArgentinaFil: Saint Martin, María Laura Gisela. Comisión Nacional de Energía Atómica. Centro Atómico Constituyentes; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Articulating theory and practice and producing innovation in the professional master's degree program in Health Sciences Teaching

This paper aims to analyze the experience of the discipline "Grupo de Estudos e Pesquisas sobre as Práticas" (GEPPRA - Study and Research Group on Practices) of the Professional Master's Degree Program in Health Sciences Teaching of the Federal University of São Paulo (UNIFESP), Baixada Santista Campus. The focus was on the scribe method and its strong points as a teaching-learning method and as a source of reflection. The analyzed corpus was composed of fourteen texts written by students and professors. The analysis stages were: automatic pragmatic analysis of the texts with the aid of the Alceste software; content analysis of passages that contained the following keywords: Geppra (Geppra I, Geppra II), Scribe (written, write) and Work (action, practice and reflection), in order to identify some of the meanings attributed to GEPPRA; the scribe method; and effects of this discipline in the professional practice. Results show that it was possible to build a new network textuality collectively, based on a reflective experience, with exchanges, discussions and questionings concerning ways to deal with challenging work scenarios. This study shows that the scribe methodology is a powerful tool that can be used in other professional education contexts or group processes, both academic and/or clinical.Este artigo tem como objetivo analisar a experiência da disciplina de pós-graduação Grupo de Estudos e Pesquisas sobre as Práticas (GEPPRA) do Programa de Mestrado Profissional em Ensino em Ciências da Saúde, da Universidade Federal de São Paulo UNIFESP, campus Baixada Santista, com foco na metodologia dos escribas, sua potência como método de ensino-aprendizagem e como fonte de reflexão. O corpus analisado foi de 14 registros elaborados por estudantes e docentes, e as etapas de análise foram: análise pragmática automática dos textos com auxílio do programa Alceste; análise de conteúdo dos trechos que continham as palavras-chave: Geppra (Geppra I, Geppra II), Escriba (escrito, escrever) e Trabalho (fazer, prática e reflexão) para identificar alguns sentidos atribuídos ao GEPPRA; a metodologia dos escribas; e efeitos da disciplina na prática profissional. Os resultados apontam que foi possível construir coletivamente uma nova textualidade em rede, a partir de uma experiência reflexiva, com troca, discussão e questionamento sobre as maneiras de lidar com situações desafiadoras no trabalho. Afirma-se a potência da ferramenta dos escribas e o seu uso em outros contextos de formação ou nos processos grupais, sejam acadêmicos e/ou clínicos

Curcumin ameliorates autoimmune diabetes. Evidences in accelerated murine models of type 1 diabetes

Type 1 diabetes (T1DM) is a T cell-mediated autoimmune disease that selectively destroys pancreatic β cells. The only possible cure for T1DM is to control autoimmunity against β cell-specific antigens. We explored whether the natural compound curcumin, with anti-oxidant and anti-inflammatory activities, might down-regulate the T cell response that destroys pancreatic β cells to improve disease outcome in autoimmune diabetes. We employed two accelerated autoimmune diabetes models: (i) cyclophosphamide (CYP) administration to non-obese diabetic (NOD) mice and (ii) adoptive transfer of diabetogenic splenocytes into NODscid mice. Curcumin treatment led to significant delay of disease onset, and in some instances prevented autoimmune diabetes by inhibiting pancreatic leucocyte infiltration and preserving insulin-expressing cells. To investigate the mechanisms of protection we studied the effect of curcumin on key immune cell populations involved in the pathogenesis of the disease. Curcumin modulates the T lymphocyte response impairing proliferation and interferon (IFN)-γ production through modulation of T-box expressed in T cells (T-bet), a key transcription factor for proinflammatory T helper type 1 (Th1) lymphocyte differentiation, both at the transcriptional and translational levels. Also, curcumin reduces nuclear factor (NF)-κB activation in T cell receptor (TCR)-stimulated NOD lymphocytes. In addition, curcumin impairs the T cell stimulatory function of dendritic cells with reduced secretion of proinflammatory cytokines and nitric oxide (NO) and low surface expression of co-stimulatory molecules, leading to an overall diminished antigen-presenting cell activity. These in-vitro effects correlated with ex-vivo analysis of cells obtained from curcumin-treated mice during the course of autoimmune diabetes. These findings reveal an effective therapeutic effect of curcumin in autoimmune diabetes by its actions on key immune cells responsible for β cell death.Fil: Castro, Carla Noemí. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigación En Biomedicina de Buenos Aires; ArgentinaFil: Barcala Tabarrozzi, Andrés Ezequiel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigación En Biomedicina de Buenos Aires; ArgentinaFil: Winnewisser, Julia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigación En Biomedicina de Buenos Aires; ArgentinaFil: Gimeno, Maria Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigación En Biomedicina de Buenos Aires; ArgentinaFil: Antunica Noguerol, María de Las Nieves. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigación En Biomedicina de Buenos Aires; ArgentinaFil: Liberman, Ana Clara. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigación En Biomedicina de Buenos Aires; ArgentinaFil: Paz, Dante Agustin. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias; ArgentinaFil: Dewey, Ricardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico La Plata. Instituto de Investigaciones Biotecnológicas - Instituto Tecnológico Chascomús. Instituto de Investigaciones Biotecnológicas (sede Chascomús); ArgentinaFil: Perone, Marcelo Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigación En Biomedicina de Buenos Aires; Argentin

GR-independent down-modulation on GM-CSF bone marrow-derived dendritic cells by the selective glucocorticoid receptor modulator Compound A

Dendritic cells (DC) initiate the adaptive immune response. Glucocorticoids (GCs) down-modulate the function of DC. Compound A (CpdA, (2-(4-acetoxyphenyl)-2-chloro-N-methyl-ethylammonium chloride) is a plant-derived GR-ligand with marked dissociative properties. We investigated the effects of CpdA on in vitro generated GM-CSF-conditioned bone marrow-derived DC (BMDC). CpdA-exposed BMDC exhibited low expression of cell-surface molecules and diminution of the release of proinflammatory cytokines upon LPS stimulation; processes associated with BMDC maturation and activation. CpdA-treated BMDC were inefficient at Ag capture via mannose receptor-mediated endocytosis and displayed reduced T-cell priming. CpdA prevented the LPS-induced rise in pErk1/2 and pP38, kinases involved in TLR4 signaling. CpdA fully inhibited LPS-induced pAktSer473, a marker associated with the generation of tolerogenic DC. We used pharmacological blockade and selective genetic loss-of-function tools and demonstrated GR-independent inhibitory effects of CpdA in BMDC. Mechanistically, CpdA-mediated inactivation of the NF-κB intracellular signaling pathway was associated with a short-circuiting of pErk1/2 and pP38 upstream signaling. Assessment of the in vivo function of CpdA-treated BMDC pulsed with the hapten trinitrobenzenesulfonic acid showed impaired cell-mediated contact hypersensitivity. Collectively, we provide evidence that CpdA is an effective BMDC modulator that might have a benefit for immune disorders, even when GR is not directly targeted.Fil: Barcala Tabarrozzi, Andrés Ezequiel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Pque. Centenario. Instituto de Investigación En Biomedicina de Buenos Aires - Instituto Partner de la Sociedad Max Planck; ArgentinaFil: Andreone, Luz. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Pque. Centenario. Instituto de Investigación En Biomedicina de Buenos Aires - Instituto Partner de la Sociedad Max Planck; ArgentinaFil: Deckers, Julie. University of Ghent; BélgicaFil: Castro, Carla Noemí. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Pque. Centenario. Instituto de Investigación En Biomedicina de Buenos Aires - Instituto Partner de la Sociedad Max Planck; ArgentinaFil: Gimeno, Maria Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Pque. Centenario. Instituto de Investigación En Biomedicina de Buenos Aires - Instituto Partner de la Sociedad Max Planck; ArgentinaFil: Ariolfo, Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Pque. Centenario. Instituto de Investigación En Biomedicina de Buenos Aires - Instituto Partner de la Sociedad Max Planck; ArgentinaFil: Berguer, Paula Mercedes. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Antunica Noguerol, María de Las Nieves. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Pque. Centenario. Instituto de Investigación En Biomedicina de Buenos Aires - Instituto Partner de la Sociedad Max Planck; ArgentinaFil: Liberman, Ana Clara. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Pque. Centenario. Instituto de Investigación En Biomedicina de Buenos Aires - Instituto Partner de la Sociedad Max Planck; ArgentinaFil: Vettorazzi, Sabine. Universitat Ulm; AlemaniaFil: Tuckermann, Jan P.. Universitat Ulm; AlemaniaFil: De Bosscher, Karolien. University of Ghent; BélgicaFil: Perone, Marcelo Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Pque. Centenario. Instituto de Investigación En Biomedicina de Buenos Aires - Instituto Partner de la Sociedad Max Planck; Argentin

Trauma dentario en un paciente con trastorno del espectro autista. Reporte de caso clínico

A 12-year-old girl diagnosed with autism spectrum disorder (ASD), epilepsy, and intellectual deficit, was seen at the dental clinic for patients with special needs at the Dental School of the Federal University of Rio Grande do Sul, due to a gingival hemorrhage on tooth 21, after a fall due to a seizure. The clinical examination of the patient identified active caries and the presence of visible biofilm on almost all dental surfaces. A radiographic exam of tooth 21 showed a fracture in the middle-third root of the tooth. All the necessary dental procedures were carried out during the endodontic treatment on tooth 21, filling the canal with calcium hydroxide paste. During the beginning of the care, the patient presented an agitated behavior requiring specialized management, always keeping the caregiver in the same clinical setting so that the patient felt welcomed. It concluded the knowledge of the particularities of the patient-reported with ASD was of utmost importance for the conduct of her dental treatment, enabling appropriate behaviors in her rehabilitation.Se presenta una niña de 12 años con diagnóstico de trastorno del espectro autista (TEA), epilepsia y déficit intelectual, quien fue llevada a la clínica odontológica para pacientes con necesidades especiales de la Facultad de Odontología de la Universidade Federal Rio Grande do Sul, por sangrado gingival a la altura del diente 21, luego de caer por una convulsión. El examen clínico identificó una paciente con lesiones de caries activas y se observó la presencia de biofilm visible en casi todas las superficies dentales. El examen radiográfico del diente 21 mostró una fractura en el tercio medio radicular del mismo. Se realizaron todos los procedimientos dentales necesarios para realizar el tratamiento de endodoncia del 21, rellenando el conducto con pasta de hidróxido de calcio. Al inicio de la atención odontológica, la paciente presentó un comportamiento agitado que requirió un manejo especializado, manteniendo siempre al cuidador en el ambiente clínico, para que el paciente se sintiera bienvenido. Se concluyó que el conocimiento de las particularidades de la paciente reportada con TEA fue de suma importancia para la realización de su tratamiento odontológico, permitiendo tener comportamientos adecuados en su rehabilitación

SCN5A mutations in 442 neonates and children: genotype-phenotype correlation and identification of higher-risk subgroups.

Aims To clarify the clinical characteristics and outcomes of children with SCN5A-mediated disease and to improve their risk stratification. Methods and results A multicentre, international, retrospective cohort study was conducted in 25 tertiary hospitals in 13 countries between 1990 and 2015. All patients ≤16 years of age diagnosed with a genetically confirmed SCN5A mutation were included in the analysis. There was no restriction made based on their clinical diagnosis. A total of 442 children {55.7% boys, 40.3% probands, median age: 8.0 [interquartile range (IQR) 9.5] years} from 350 families were included; 67.9% were asymptomatic at diagnosis. Four main phenotypes were identified: isolated progressive cardiac conduction disorders (25.6%), overlap phenotype (15.6%), isolated long QT syndrome type 3 (10.6%), and isolated Brugada syndrome type 1 (1.8%); 44.3% had a negative electrocardiogram phenotype. During a median follow-up of 5.9 (IQR 5.9) years, 272 cardiac events (CEs) occurred in 139 (31.5%) patients. Patients whose mutation localized in the C-terminus had a lower risk. Compound genotype, both gain- and loss-of-function SCN5A mutation, age ≤1 year at diagnosis in probands and age ≤1 year at diagnosis in non-probands were independent predictors of CE. Conclusion In this large paediatric cohort of SCN5A mutation-positive subjects, cardiac conduction disorders were the most prevalent phenotype; CEs occurred in about one-third of genotype-positive children, and several independent risk factors were identified, including age ≤1 year at diagnosis, compound mutation, and mutation with both gain- and loss-of-function

Design and baseline characteristics of the finerenone in reducing cardiovascular mortality and morbidity in diabetic kidney disease trial

Background: Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. Patients and Methods: The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate >= 25 mL/min/1.73 m(2) and albuminuria (urinary albumin-to-creatinine ratio >= 30 to <= 5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level alpha = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. Conclusions: FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049

Effects of hospital facilities on patient outcomes after cancer surgery: an international, prospective, observational study

Background Early death after cancer surgery is higher in low-income and middle-income countries (LMICs) compared with in high-income countries, yet the impact of facility characteristics on early postoperative outcomes is unknown. The aim of this study was to examine the association between hospital infrastructure, resource availability, and processes on early outcomes after cancer surgery worldwide.Methods A multimethods analysis was performed as part of the GlobalSurg 3 study-a multicentre, international, prospective cohort study of patients who had surgery for breast, colorectal, or gastric cancer. The primary outcomes were 30-day mortality and 30-day major complication rates. Potentially beneficial hospital facilities were identified by variable selection to select those associated with 30-day mortality. Adjusted outcomes were determined using generalised estimating equations to account for patient characteristics and country-income group, with population stratification by hospital.Findings Between April 1, 2018, and April 23, 2019, facility-level data were collected for 9685 patients across 238 hospitals in 66 countries (91 hospitals in 20 high-income countries; 57 hospitals in 19 upper-middle-income countries; and 90 hospitals in 27 low-income to lower-middle-income countries). The availability of five hospital facilities was inversely associated with mortality: ultrasound, CT scanner, critical care unit, opioid analgesia, and oncologist. After adjustment for case-mix and country income group, hospitals with three or fewer of these facilities (62 hospitals, 1294 patients) had higher mortality compared with those with four or five (adjusted odds ratio [OR] 3.85 [95% CI 2.58-5.75]; p&lt;0.0001), with excess mortality predominantly explained by a limited capacity to rescue following the development of major complications (63.0% vs 82.7%; OR 0.35 [0.23-0.53]; p&lt;0.0001). Across LMICs, improvements in hospital facilities would prevent one to three deaths for every 100 patients undergoing surgery for cancer.Interpretation Hospitals with higher levels of infrastructure and resources have better outcomes after cancer surgery, independent of country income. Without urgent strengthening of hospital infrastructure and resources, the reductions in cancer-associated mortality associated with improved access will not be realised