NOACs added to WHO’s essential medicines list: recommendations for future policy actions

The introduction of non-vitamin K antagonists oral anticoagulants, a class of medicines which includes dabigatran, apixaban, edoxaban and rivaroxaban, has resulted in improvements in the safety and efficacy of non valvular atrial fibrillation treatment for stroke prevention, with significant reductions in stroke, intracranial haemorrhage, and mortality. For these reasons, a team of World Heart Federation Emerging Leaders led efforts to add non-vitamin K antagonists oral anticoagulants to the World Health Organization’s Model List of Essential Medicines in 2019. Following the inclusion of this class of medicines in the Essential Medicines List, this editorial proposes several recommendations to improve the accessibility, affordability and acceptability of non-vitamin K oral anticoagulants, especially in low- and middle-income settings, in order to successfully manage non-valvular atrial fibrillation and to lower the risk of stroke

Psychometric properties of the Internalized Stigma of Mental Illness scale adapted for people who use psychoactive substances.

Background: People who consume psychoactive substances may experience situations of social stigma on the part of the society in general, and also situations of internalized-stigma derived from their own consumption of substances. The Internalized Stigma of Mental Illness (ISMI) scale has been shown to be valid and reliable to evaluate the internalized-stigma in people with severe mental disorders, but in Argentina there is no a Spanish version of this scale for use with people who use psychoactive substances. The objective of this work was to evaluate the psychometric properties of the Spanish version of the Internalized Stigma of Mental Illness instrument adapted for people who use psychoactive substances.Method: The work was carried out on a sample of 200 patients older than 18 years under treatment of rehabilitation by consumption of psychoactive substances in a public institution of the city of Córdoba (Argentina) between the years 2014 and 2016. The instrument used was the Internalized Stigma of Mental Illness (ISMI) previously adapted for use in these groups of patients. It was determined the reliability of the scale through Cronbach’s coefficients ? and factorial structure was analyzed through an exploratory factor analysis.Results: The obtained coefficients showed a high reliability, while in the factorial structure emerged the 4 theoretical dimensions described by Ritsher, namely: social isolation, perceived discrimination, alienation and stereotyping. Conclusion: It is concluded that the scale adapted for people who use psychoactive substances is reliable and with an adequate factorial structure.</p

A simplified biventricular defibrillator with fixed long detection intervals reduces implantable cardioverter defibrillator (ICD) interventions and heart failure hospitalizations in patients with non-ischaemic cardiomyopathy implanted for primary prevention: the RELEVANT [Role of long dEtection window programming in patients with LEft VentriculAr dysfunction, Non-ischemic eTiology in primary prevention treated with a biventricular ICD] study

To investigate the efficacy and safety of a cardiac resynchronization therapy with cardioverter-defibrillator (CRT-D) device with simplified ventricular tachycardia management in patients with non-ischaemic heart failure (HF) and primary prevention implantable cardioverter defibrillator (ICD) indication

Hospitalización por trastornos mentales y consumo de sustancias en adolescentes argentinos. 2005-2006

Objetivo: Determinar la prevalencia de trastornos mentales y del comportamiento como causa de hospitalización en la población adolescente de 10 a 19 años en Argentina en el período 2005 -2006. Metodología: estudio observacional, analítico y transversal, se utilizaron las Bases de Datos de los Informes Estadísticos de Egresos Hospitalarios (IEH) de la Dirección de Estadística e Información de Salud del Ministerio de Salud de la Nación, años 2005-2006. Los datos fueron analizados según sexo, edad y causa de egreso hospitalario. El procesamiento estadístico de los datos consistió en test de chi–cuadrado, Mantel Haenzel o test de Fisher, p<0,05. Resultados: el 2% de los egresos hospitalarios fueron por Trastornos Mentales y del Comportamiento (TMyC). Los TMyC de mayor frecuencia para el grupo de 10-14 años fueron: trastornos neuróticos (29,89%), consumo de sustancias (23,49%) (p<0,001) y trastornos del comportamiento de inicio en la infancia (15,40%) y para el grupo de 15-19 años fueron: consumo de sustancias (30,94%) (p<0,001), alcohol la más frecuente, trastornos neuróticos (21,04%) y esquizofrenia (17,34%) (p<0,001). La distribución por sexos y edad mostró al consumo de sustancias (p< 0,0001) como la patología más frecuente en varones y trastornos neuróticos (p< 0,0001) en mujeres de ambos grupos de edad. Conclusión: los TMyC son un motivo de hospitalización que aumenta con la edad de los adolescentes y mostró un comportamiento diferenciado por sexo. El consumo de sustancias psicoactivas y los trastornos del comportamiento fueron más frecuentes en los varones y los trastornos neuróticos en las mujeres

A Synaptic Mechanism for Temporal Filtering of Visual Signals

The visual system transmits information about fast and slow changes in light intensity through separate neural pathways. We used in vivo imaging to investigate how bipolar cells transmit these signals to the inner retina. We found that the volume of the synaptic terminal is an intrinsic property that contributes to different temporal filters. Individual cells transmit through multiple terminals varying in size, but smaller terminals generate faster and larger calcium transients to trigger vesicle release with higher initial gain, followed by more profound adaptation. Smaller terminals transmitted higher stimulus frequencies more effectively. Modeling global calcium dynamics triggering vesicle release indicated that variations in the volume of presynaptic compartments contribute directly to all these differences in response dynamics. These results indicate how one neuron can transmit different temporal components in the visual signal through synaptic terminals of varying geometries with different adaptational properties

Homeostatic Plasticity Studied Using In Vivo Hippocampal Activity-Blockade: Synaptic Scaling, Intrinsic Plasticity and Age-Dependence

Homeostatic plasticity is thought to be important in preventing neuronal circuits from becoming hyper- or hypoactive. However, there is little information concerning homeostatic mechanisms following in vivo manipulations of activity levels. We investigated synaptic scaling and intrinsic plasticity in CA1 pyramidal cells following 2 days of activity-blockade in vivo in adult (postnatal day 30; P30) and juvenile (P15) rats. Chronic activity-blockade in vivo was achieved using the sustained release of the sodium channel blocker tetrodotoxin (TTX) from the plastic polymer Elvax 40W implanted directly above the hippocampus, followed by electrophysiological assessment in slices in vitro. Three sets of results were in general agreement with previous studies on homeostatic responses to in vitro manipulations of activity. First, Schaffer collateral stimulation-evoked field responses were enhanced after 2 days of in vivo TTX application. Second, miniature excitatory postsynaptic current (mEPSC) amplitudes were potentiated. However, the increase in mEPSC amplitudes occurred only in juveniles, and not in adults, indicating age-dependent effects. Third, intrinsic neuronal excitability increased. In contrast, three sets of results sharply differed from previous reports on homeostatic responses to in vitro manipulations of activity. First, miniature inhibitory postsynaptic current (mIPSC) amplitudes were invariably enhanced. Second, multiplicative scaling of mEPSC and mIPSC amplitudes was absent. Third, the frequencies of adult and juvenile mEPSCs and adult mIPSCs were increased, indicating presynaptic alterations. These results provide new insights into in vivo homeostatic plasticity mechanisms with relevance to memory storage, activity-dependent development and neurological diseases

An Improved Test for Detecting Multiplicative Homeostatic Synaptic Scaling

Homeostatic scaling of synaptic strengths is essential for maintenance of network “gain”, but also poses a risk of losing the distinctions among relative synaptic weights, which are possibly cellular correlates of memory storage. Multiplicative scaling of all synapses has been proposed as a mechanism that would preserve the relative weights among them, because they would all be proportionately adjusted. It is crucial for this hypothesis that all synapses be affected identically, but whether or not this actually occurs is difficult to determine directly. Mathematical tests for multiplicative synaptic scaling are presently carried out on distributions of miniature synaptic current amplitudes, but the accuracy of the test procedure has not been fully validated. We now show that the existence of an amplitude threshold for empirical detection of miniature synaptic currents limits the use of the most common method for detecting multiplicative changes. Our new method circumvents the problem by discarding the potentially distorting subthreshold values after computational scaling. This new method should be useful in assessing the underlying neurophysiological nature of a homeostatic synaptic scaling transformation, and therefore in evaluating its functional significance

Phosphorylation of Syntaxin‐1a by casein kinase 2α (CK2α) regulates presynaptic vesicle exocytosis from the reserve pool

The t-soluble NSF-attachment protein receptor protein Syntaxin-1a (Stx-1a) is abundantly expressed at pre-synaptic terminals where it plays a critical role in the exocytosis of neurotransmitter-containing synaptic vesicles. Stx-1a is phosphorylated by Casein kinase 2α (CK2α) at Ser14, which has been proposed to regulate the interaction of Stx-1a and Munc-18 to control of synaptic vesicle priming. However, the role of CK2α in synaptic vesicle dynamics remains unclear. Here, we show that CK2α over-expression reduces evoked synaptic vesicle release. Furthermore, shRNA-mediated knockdown of CK2α in primary hippocampal neurons strongly enhanced vesicle exocytosis from the reserve pool, with no effect on the readily releasable pool of primed vesicles. In neurons in which endogenous Stx-1a was knocked down and replaced with a CK2α phosphorylation-deficient mutant, Stx-1a(D17A), vesicle exocytosis was also increased. These results reveal a previously unsuspected role of CK2α phosphorylation in specifically regulating the reserve synaptic vesicle pool, without changing the kinetics of release from the readily releasable pool

Inhibition decorrelates visual feature representations in the inner retina

The retina extracts visual features for transmission to the brain. Different types of bipolar cell split the photoreceptor input into parallel channels and provide the excitatory drive for downstream visual circuits. Mouse bipolar cell types have been described at great anatomical and genetic detail, but a similarly deep understanding of their functional diversity is lacking. Here, by imaging light-driven glutamate release from more than 13,000 bipolar cell axon terminals in the intact retina, we show that bipolar cell functional diversity is generated by the interplay of dendritic excitatory inputs and axonal inhibitory inputs. The resulting centre and surround components of bipolar cell receptive fields interact to decorrelate bipolar cell output in the spatial and temporal domains. Our findings highlight the importance of inhibitory circuits in generating functionally diverse excitatory pathways and suggest that decorrelation of parallel visual pathways begins as early as the second synapse of the mouse visual system