Predictive equations not always overestimate the resting energy expenditure in amyotrophic lateral sclerosis patients

Fil: Libere, Guillermo P.. Centro del Parque; ArgentinaFil: Guastavino, Sabrina. Centro del Parque; ArgentinaFil: Escobar, Miguel A.. Centro del Parque; ArgentinaFil: de Vito, Eduardo. Centro del Parque; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentin

Comparison of Gadoterate Meglumine and Gadobutrol in the MRI Diagnosis of Primary Brain Tumors: A Double-Blind Randomized Controlled Intraindividual Crossover Study (the REMIND Study)

ABSTRACT BACKGROUNDANDPURPOSE: Effective management of patients with brain tumors depends on accurate detection and characterization of lesions. This study aimed to demonstrate the noninferiority of gadoterate meglumine versus gadobutrol for overall visualization and characterization of primary brain tumors. MATERIALS AND METHODS: This multicenter, double-blind, randomized, controlled intraindividual, crossover, noninferiority study included279patients.Bothcontrastagents(dose=0.1mmol/kgofbodyweight)wereassessedwith2identicalMRIsatatimeintervalof 2–14 days. The primary end point was overall lesion visualization and characterization, scored independently by 3 off-site readers on a 4-point scale, ranging from “poor” to “excellent.” Secondary end points were qualitative assessments (lesion border delineation, internal morphology, degree of contrast enhancement, diagnostic confidence), quantitative measurements (signal intensity), and safety (adverse events). All qualitative assessments were also performed on-site. RESULTS: Forall3readers,imagesofmostpatients(>90%)werescoredgoodorexcellentforoveralllesionvisualizationandcharacterizationwitheithercontrastagent;andthenoninferiorityofgadoteratemeglumineversusgadobutrolwasstatisticallydemonstrated.No significant differences were observed between the 2 contrast agents regarding qualitative end points despite quantitative mean lesion percentageenhancementbeinghigherwithgadobutrol(P81%ofthe patientswithbothcontrastagents.Similarpercentagesofpatientswithadverseeventsrelatedtothecontrastagentswereobservedwith gadoterate meglumine (7.8%) and gadobutrol (7.3%), mainly injection site pain. CONCLUSIONS: Thenoninferiorityofgadoteratemeglumineversusgadobutrolforoverallvisualizationandcharacterizationofprimary brain tumors was demonstrated

Assessment of oxidative damage to proteins and DNA in urine of newborn infants by a validated UPLC-MS/MS approach

The assessment of oxidative stress is highly relevant in clinical Perinatology as it is associated to adverse outcomes in newborn infants. This study summarizes results from the validation of an Ultra Performance Liquid Chromatography-tandem Mass Spectrometry (UPLC-MS/MS) method for the simultaneous quantification of the urinary concentrations of a set of endogenous biomarkers, capable to provide a valid snapshot of the oxidative stress status applicable in human clinical trials, especially in the field of Perinatology. The set of analytes included are phenylalanine (Phe), para-tyrosine (p-Tyr), ortho-tyrosine (o-Tyr), meta-tyrosine (m-Tyr), 3-NO2-tyrosine (3NO 2-Tyr), 3-Cl-tyrosine (3Cl-Tyr), 2′-deoxyguanosine (2dG) and 8-hydroxy-2′-deoxyguanosine (8OHdG). Following the FDA-based guidelines, appropriate levels of accuracy and precision, as well as adequate levels of sensitivity with limits of detection (LODs) in the low nanomolar (nmol/L) range were confirmed after method validation. The validity of the proposed UPLC-MS/MS method was assessed by analysing urine samples from a clinical trial in extremely low birth weight (ELBW) infants randomized to be resuscitated with two different initial inspiratory fractions of oxygen

Eradication of invasive species: science, attitude and understanding. The beaver in Tierra del Fuego

El manejo de especies invasoras presenta desafíos, que incluyen la necesidad de generar conocimiento aplicado y capacidades de gestión, así como modificar actitudes y comportamientos de la sociedad. El caso de la especie invasora castor canadiense, Castor canadensis, ejemplifica enfoques que pueden aplicarse para tratar otras especies invasoras. Repasamos la historia de manejo del castor y el cambio de enfoque que derivó en un acuerdo binacional inédito para restaurar los ecosistemas afectados por la especie mediante su erradicación, acuerdo que avanza mediante un proceso de generación de capacidades y escalamiento en la complejidad del trabajo, desde áreas piloto hacia todo el rango de distribución actual de la especie. Destacamos cómo la investigación aporta al manejo del castor, presentando detalles de la investigación en marcha en algunos ejes principales: 1) la factibilidad de erradicar en áreas piloto; 2) la estimación de tasas vitales y de dispersión y la construcción de modelos predictivos de expansión de la invasión, y 3) la determinación de criterios objetivos para declarar la erradicación del castor en sectores bajo manejo. La generación de capacidades es crucial para este complejo proceso. La construcción del capital social necesario para manejar el problema requiere de un diálogo continuo entre los diversos sectores involucrados y la construcción de agendas consensuadas. El sector científico puede asistir este proceso, pero sin imponer agendas unilaterales, sino identificando y contribuyendo a resolver las preguntas correctas y entendiendo las particularidades de los demás sectores, la cultura de las organizaciones y los tiempos para dar respuestas prácticas para lograr conservación basada en ciencia.The management of invasive species involves several challenges, ranging from the need to generate applied knowledge and capacity building abilities to a change in perceptions and behaviors in society. The case of the invasive Canadian beaver, Castor canadensis, illustrates possible approaches to address other invasive species. We reviewed the management history of the beaver and the change of approach that led to an unprecedented bi-national agreement to restore the affected ecosystems by means of the eradication of the species. This agreement advances by means of a training process of capacity building and a gradual scaling in the complexity of the work, from pilot areas to the whole current distribution of the species. We highlight how scientific research contributes to the management of the species, presenting details of the ongoing research in three major areas: 1) feasibility of eradication in pilot areas; 2) assessment of vital and dispersion rates and building predictive models of the spread of the invasion, and 3) determination of objective criteria to declare beaver eradication in areas under management. Capacity building is critical for this complex process. Assembling the social capital needed to manage the problem requires a continuous dialogue and agreed agendas among various stakeholders. The scientific sector can assist in this process without imposing unilateral agendas, but identifying the right questions and understanding the particularities of other sectors, the culture of organizations and the time frames needed for practical responses to achieve science-based conservation.Fil: Schiavini, Adrian Carlos Miguel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Austral de Investigaciones Científicas; ArgentinaFil: Carranza, M. L.. Secretaria de Desarrollo Sustentable y Ambiente; ArgentinaFil: Deferrari, Guillermo Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Austral de Investigaciones Científicas; ArgentinaFil: Escobar, Julio Martin. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Austral de Investigaciones Científicas; ArgentinaFil: Malmierca, Laura Margarita Elvira. Administración de Parques Nacionales. Delegación Regional Patagonia; ArgentinaFil: Pietrek, A.. University of Duke; Estados Unido

Case report: De novo SAMD9L truncation causes neonatal-onset autoinflammatory syndrome which was successfully treated with hematopoietic stem cell transplantation

During recent years, the identification of monogenic mutations that cause sterile inflammation has expanded the spectrum of autoinflammatory diseases, clinical disorders characterized by uncontrolled systemic and organ-specific inflammation that, in some cases, can mirror infectious conditions. Early studies support the concept of innate immune dysregulation with a predominance of myeloid effector cell dysregulation, particularly neutrophils and macrophages, in causing tissue inflammation. However, recent discoveries have shown a complex overlap of features of autoinflammation and/or immunodeficiency contributing to severe disease phenotypes. Here, we describe the first Argentine patient with a newly described frameshift mutation in SAMD9L c.2666delT/p.F889Sfs*2 presenting with a complex phenotypic overlap of CANDLE-like features and severe infection-induced cytopenia and immunodeficiency. The patient underwent a fully matched unrelated HSCT and has since been in inflammatory remission 5 years post-HSCT.Instituto de Estudios Inmunológicos y Fisiopatológico

Plk1 regulates contraction of postmitotic smooth muscle cells and is required for vascular homeostasis

Polo-like kinase 1 (PLK1), an essential regulator of cell division, is currently undergoing clinical evaluation as a target for cancer therapy. We report an unexpected function of Plk1 in sustaining cardiovascular homeostasis. Plk1 haploinsufficiency in mice did not induce obvious cell proliferation defects but did result in arterial structural alterations, which frequently led to aortic rupture and death. Specific ablation of Plk1 in vascular smooth muscle cells (VSMCs) led to reduced arterial elasticity, hypotension, and an impaired arterial response to angiotensin II in vivo. Mechanistically, we found that Plk1 regulated angiotensin II-dependent activation of RhoA and actomyosin dynamics in VSMCs in a mitosis-independent manner. This regulation depended on Plk1 kinase activity, and the administration of small-molecule Plk1 inhibitors to angiotensin II-treated mice led to reduced arterial fitness and an elevated risk of aneurysm and aortic rupture. We thus conclude that a partial reduction of Plk1 activity that does not block cell division can nevertheless impair aortic homeostasis. Our findings have potentially important implications for current approaches aimed at PLK1 inhibition for cancer therapy.This work-was supported by the Marie Curie activities of the European Commission (Oncotrain program; fellowship to P.W), the Spanish Ministry of Economy and Competitiveness (MINECO; fellowship to A.G.-L.), the CENIT AMIT Project "Advanced Molecular Imaging Technologies" (TEC2008-06715-C02-1, RD07/0014/2009 to F.M.), the Red de investigacion Cardiovascular (RIC), cofunded by FEDER (grant RD12/004240022 to J.M.R.; grant RD12/0042/0056 to L.J.J.-B), Fundacio La Marato TV3 (grant 20151331 to J.M.R.), the Castilla-Leon Autonomous Government (BIO/SA01/15, CS049U16 to X.R.B.), the Solorzano and Ramon Areces Foundations (to X.R.B.), MINECO (grants RD12/0036/0002 and SAF2015-64556-R to X.R.B.; SAF2015-63633-R to J.M.R.; and SAF2015-69920-R to M.M.), Consolider-Ingenio 2010 Programme (grant SAF2014-57791-REDC to M.M.), Red Tematica CellSYS (grant BFU2014-52125-REDT to M.M.), Comunidad de Madrid (OncoCycle Programme; grant S2010/BMD-2470 to M.M.), Worldwide Cancer Research (grants 14-1248 to X.R.B., and 15-0278 to M.M.) and the MitoSys project (European Union Seventh Framework Programme; grant HEALTH-F5-2010-241548 to M.M.). CNIC is supported by MINECO and the Pro-CNIC Foundation. CNIO and CNIC are Severo Ochoa Centers of Excellence (MINECO awards SEV-2015-0510 and SEV-2015-0505, respectively).S

Generación de Mallas y Simulación Numérica en Medioambiente

[ES]En esta conferencia se introducen ideas básicas sobre la simulación numérica, mediante el método de los elementos finitos (MEF), de problemas medioambientales que han sido abordados por nuestro grupo en diversos proyectos de investigación sobre simulación de campos de viento, radiación solar, contaminación atmosférica y la modelización de yacimientos de petróleo

Severe paraneoplastic hypoglycemia in a patient with a gastrointestinal stromal tumor with an exon 9 mutation: a case report

BACKGROUND: Non-islet cell tumor induced hypoglycemia (NICTH) is a very rare phenomenon, but even more so in gastrointestinal stromal tumors. It tends to present in large or metastatic tumors, and can appear at any time in the progression of the disease. We present herein a case of NICTH in a GIST tumor and report an exon 9 mutation associated to it. CASE PRESENTATION: A thirty nine year-old man with a recurrent, metastatic gastrointestinal stromal tumor presented to the hospital with nausea, dizziness, loss of consciousness, and profound hypoglycemia (20 mg/dL). There was no evidence of factitious hypoglycemia. He was stabilized with a continuous glucose infusion and following selective vascular embolization, the patient underwent debulking of a multicentric 40 cm × 25 cm × 10 cm gastrointestinal stromal tumor. After resection, the patient became euglycemic and returned to his normal activities. Tumor analysis confirmed excessive production of insulin-like growth factor II m-RNA and the precursor protein, "big" insulin-like growth factor II. Mutational analysis also identified a rare, 6 bp tandem repeat insert (gcctat) at position 1530 in exon 9 of KIT. CONCLUSION: Optimal management of gastrointestinal stromal tumor-induced hypoglycemia requires a multidisciplinary approach, and surgical debulking is the treatment of choice to obtain immediate symptom relief. Imatinib or combinations of glucocorticoids and growth hormone are alternative palliative strategies for symptomatic hypoglycemia. In addition, mutations in exon 9 of the tyrosine kinase receptor KIT occur in 11–20% of GIST and are often associated with poor patient outcomes. The association of this KIT mutation with non-islet cell tumor induced hypoglycemia has yet to be established