Rationale and design of the NODE-303 study: evaluating the safety of symptom-prompted, self-administered etripamil for paroxysmal supraventricular tachycardia episodes in real-world settings.

BACKGROUND: Paroxysmal supraventricular tachycardia (PSVT) is a common episodic arrhythmia characterized by unpredictable onset and burdensome symptoms including palpitations, dizziness, chest pain, distress, and shortness of breath. Treatment of acute episodes of PSVT in the clinical setting consists of intravenous adenosine, beta-blockers, and calcium channel blockers (CCBs). Etripamil is an intranasally self-administered L-type CCB in development for acute treatment of AV-nodal dependent PSVT in a nonmedical supervised setting. METHODS: This paper summarizes the rationale and study design of NODE-303 that will assess the efficacy and safety of etripamil. In the randomized, double-blinded, placebo-controlled, Phase 3 RAPID trial, etripamil was superior to placebo in the conversion of single PSVT episodes by 30 minutes post initial dose when administered in the nonhealthcare setting; this study required a mandatory and observed test dosing prior to randomization. The primary objective of NODE-303 is to evaluate the safety of symptom-prompted, self-administered etripamil for multiple PSVT episodes in real-world settings, without the need for test dosing prior to first use during PSVT. Secondary endpoints include efficacy and disease burden. Upon perceiving a PSVT episode, the patient applies an electrocardiographic monitor, performs a vagal maneuver, and, if the vagal maneuver is unsuccessful, self-administers etripamil 70 mg, with an optional repeat dose if symptoms do not resolve within 10 minutes after the first dose. A patient may treat up to four PSVT episodes during the study. Adverse events are recorded as treatment-emergent if they occur within 24 hours after the administration of etripamil. RESULTS: Efficacy endpoints include time to conversion to sinus rhythm within 30 and 60 minutes after etripamil administration, and the proportion of patients who convert at 3, 5, 10, 20, 30, and 60 minutes. Patient-reported outcomes are captured by the Brief Illness Perception Questionnaire, the Cardiac Anxiety Questionnaire, the Short Form Health Survey 36, the Treatment Satisfaction Questionnaire for Medication and a PSVT survey. CONCLUSIONS: Overall, these data will support the development of a potentially paradigm-changing long-term management strategy for recurrent PSVT

Global urban environmental change drives adaptation in white clover.

Urbanization transforms environments in ways that alter biological evolution. We examined whether urban environmental change drives parallel evolution by sampling 110,019 white clover plants from 6169 populations in 160 cities globally. Plants were assayed for a Mendelian antiherbivore defense that also affects tolerance to abiotic stressors. Urban-rural gradients were associated with the evolution of clines in defense in 47% of cities throughout the world. Variation in the strength of clines was explained by environmental changes in drought stress and vegetation cover that varied among cities. Sequencing 2074 genomes from 26 cities revealed that the evolution of urban-rural clines was best explained by adaptive evolution, but the degree of parallel adaptation varied among cities. Our results demonstrate that urbanization leads to adaptation at a global scale

La respuesta molecular mayor en el estudio IRIS: Una reflexión a partir de un grupo de pacientes respondedores subóptimos con leucemia mieloide crónica (LMC) de más de 5 años de seguimiento.

YesLos análisis efectuados a partir del estudio IRIS, ensayo aleatorizado fase III a nivel europeo sobre pacientes con LMC que permitió la aprobación de imatinib en esta enfermedad, establecían que el mayor riesgo de progresión de la enfermedad se acumulaba en los 4 primeros años desde el inicio del fármaco en pacientes no respondedores o respondedores subóptimos, entre los que se incluía aquéllos que no alcanzaban una respuesta molecular mayor (tránscritos bcr-abl inferiores al 0,1%) en los primeros 18 meses de tratamiento

Mucormicosis en pacientes oncohematológicos y receptores de transplantes de progenitores hematopoyéticos. Experiencia de los últomos 10 años de un solo centro.

YesLas mucormicosis son un tipo de infección fúngica invasora(IFI) emergente en pacientes con hemopatías malignas y receptores de trasplantes de progenitores hematopoyéticos (TPH). Su pronóstico es infausto con alta mortalidad y graves secuelas pero un mejor conocimiento de estas IFI podría ayudar a mejorar su pronóstico

Attenuation of liver cancer development by oral glycerol supplementation in the rat

PURPOSE: Glycerol usage is increasing in food industry for human and animal nutrition. This study analyzed the impact of glycerol metabolism when orally supplemented during the early stage of rat liver carcinogenesis. METHODS: Wistar rats were subjected to a 2-phase model of hepatocarcinogenesis (initiated-promoted, IP group). IP animals also received glycerol by gavage (200 mg/kg body weight, IPGly group). RESULTS: Glycerol treatment reduced the volume of preneoplastic lesions by decreasing the proliferative status of liver foci, increasing the expression of p53 and p21 proteins and reducing the expression of cyclin D1 and cyclin-dependent kinase 1. Besides, apoptosis was enhanced in IPGly animals, given by an increment of Bax/Bcl-2 ratio, Bad and PUMA mitochondrial expression, a concomitant increase in cytochrome c release and caspase-3 activation. Furthermore, hepatic levels of glycerol phosphate and markers of oxidative stress were increased in IPGly rats. Oxidative stress intermediates act as intracellular messengers, inducing p53 activation and changes in JNK and Erk signaling pathways, with JNK activation and Erk inhibition. CONCLUSION: The present work provides novel data concerning the preventive actions of glycerol during the development of liver cancer and represents an economically feasible intervention to treat high-risk individuals.Fil: Capiglioni, Alejo Matías. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Fisiología Experimental. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Fisiología Experimental; ArgentinaFil: Lorenzetti, Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Fisiología Experimental. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Fisiología Experimental; ArgentinaFil: Quiroga, Ariel Dario. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Fisiología Experimental. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Fisiología Experimental; Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Departamento de Ciencias Fisiológicas. Área Morfología; ArgentinaFil: Parody, Juan Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Fisiología Experimental. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Fisiología Experimental; ArgentinaFil: Ronco, Maria Teresa. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Fisiología Experimental. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Fisiología Experimental; ArgentinaFil: Pisani, Gerardo B.. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Departamento de Ciencias Fisiológicas. Área Morfología; ArgentinaFil: Carrillo, Maria Cristina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Fisiología Experimental. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Fisiología Experimental; Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Departamento de Ciencias Fisiológicas. Área Morfología; ArgentinaFil: Ceballos Mancini, María Paula. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Fisiología Experimental. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Fisiología Experimental; ArgentinaFil: Alvarez, María de Luján. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Fisiología Experimental. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Fisiología Experimental; Argentin