Imaging Cognitive Impairment and Impulse Control Disorders in Parkinson's Disease

Dementia and mild forms of cognitive impairment as well as neuropsychiatric symptoms (i. e., impulse control disorders) are frequent and disabling non-motor symptoms of Parkinson's disease (PD). The identification of changes in neuroimaging studies for the early diagnosis and monitoring of the cognitive and neuropsychiatric symptoms associated with Parkinson's disease, as well as their pathophysiological understanding, are critical for the development of an optimal therapeutic approach. In the current literature review, we present an update on the latest structural and functional neuroimaging findings, including high magnetic field resonance and radionuclide imaging, assessing cognitive dysfunction and impulse control disorders in PD

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Functional correlates of response inhibition in impulse control disorders in Parkinson’s disease

Available online 11 September 2021.Impulse control disorder is a prevalent side-effect of Parkinson’s disease (PD) medication, with a strong negative impact on the quality of life of those affected. Although impulsivity has classically been associated with response inhibition deficits, previous evidence from PD patients with impulse control disorder (ICD) has not revealed behavioral dysfunction in response inhibition. In this study, 18 PD patients with ICD, 17 PD patients without this complication, and 15 healthy controls performed a version of the conditional Stop Signal Task during functional magnetic resonance imaging. Whole-brain contrasts, regions of interest, and functional connectivity analyses were conducted. Our aim was to investigate the neural underpinnings of two aspects of response inhibition: proactive inhibition, inhibition that has been prepared beforehand, and restrained inhibition, inhibition of an invalid inhibitory tendency. We observed that, in respect to the other two groups, PD patients with ICD exhibited hyperactivation of the stopping network bilaterally while performing proactive inhibition. When engaged in restrained inhibition, they showed hyperactivation of the left inferior frontal gyrus, an area linked to action monitoring. Restrained inhibition also resulted in changes to the functional co-activation between inhibitory regions and left inferior parietal cortex and right supramarginal gyrus. Our findings indicate that PD patients with ICD completed the inhibition task correctly, showing altered engagement of inhibitory and attentional areas. During proactive inhibition they showed bilateral hyperactivation of two inhibitory regions, while during restrained inhibition they showed additional involvement of attentional areas responsible for alerting and orienting.This work was supported by grants from the Carlos III Institute of Health (PI11/02109) and the ERA-Neuron program (PIM2010ERN- 0033). Additionally, the authors received the following grants and honoraria: T.E.-P. received a grant from the Spanish Ministry of Economy and Competitiveness (BES-2016-079489). P.M.P.-A. was supported by grants from the Spanish Ministry of Economy and Competitiveness (RYC-2014-15440), the Spanish Ministry of Science and Innovation (PGC2018-093408-B-I00), and the Fundación Tatiana Pérez de Guzmán el Bueno. I.N.-G. was the recipient of a Rio Hortega grant (CM16/00033) from the Carlos III Institute of Health. I.N.-G. received honoraria from Zambon and TEVA for travel and accommodation to attend scientific meetings. M.C.R.-O. received financial support for her research from national and local government institutions in Spain (Carlos III Institute of Health, Basque Country Government, Diputacion Foral Guipuzcoa, and CIBERNED). M.C.R.-O. received honoraria from Zambon, Bial, and Boston Scientific for lectures, travel, and accommodation to attend scientific meetings. BCBL acknowledges support from the Basque Government through the BERC 2018-2021 program

Functional correlates of response inhibition in impulse control disorders in Parkinson’s disease

Available online 11 September 2021.Impulse control disorder is a prevalent side-effect of Parkinson’s disease (PD) medication, with a strong negative impact on the quality of life of those affected. Although impulsivity has classically been associated with response inhibition deficits, previous evidence from PD patients with impulse control disorder (ICD) has not revealed behavioral dysfunction in response inhibition. In this study, 18 PD patients with ICD, 17 PD patients without this complication, and 15 healthy controls performed a version of the conditional Stop Signal Task during functional magnetic resonance imaging. Whole-brain contrasts, regions of interest, and functional connectivity analyses were conducted. Our aim was to investigate the neural underpinnings of two aspects of response inhibition: proactive inhibition, inhibition that has been prepared beforehand, and restrained inhibition, inhibition of an invalid inhibitory tendency. We observed that, in respect to the other two groups, PD patients with ICD exhibited hyperactivation of the stopping network bilaterally while performing proactive inhibition. When engaged in restrained inhibition, they showed hyperactivation of the left inferior frontal gyrus, an area linked to action monitoring. Restrained inhibition also resulted in changes to the functional co-activation between inhibitory regions and left inferior parietal cortex and right supramarginal gyrus. Our findings indicate that PD patients with ICD completed the inhibition task correctly, showing altered engagement of inhibitory and attentional areas. During proactive inhibition they showed bilateral hyperactivation of two inhibitory regions, while during restrained inhibition they showed additional involvement of attentional areas responsible for alerting and orienting.This work was supported by grants from the Carlos III Institute of Health (PI11/02109) and the ERA-Neuron program (PIM2010ERN- 0033). Additionally, the authors received the following grants and honoraria: T.E.-P. received a grant from the Spanish Ministry of Economy and Competitiveness (BES-2016-079489). P.M.P.-A. was supported by grants from the Spanish Ministry of Economy and Competitiveness (RYC-2014-15440), the Spanish Ministry of Science and Innovation (PGC2018-093408-B-I00), and the Fundación Tatiana Pérez de Guzmán el Bueno. I.N.-G. was the recipient of a Rio Hortega grant (CM16/00033) from the Carlos III Institute of Health. I.N.-G. received honoraria from Zambon and TEVA for travel and accommodation to attend scientific meetings. M.C.R.-O. received financial support for her research from national and local government institutions in Spain (Carlos III Institute of Health, Basque Country Government, Diputacion Foral Guipuzcoa, and CIBERNED). M.C.R.-O. received honoraria from Zambon, Bial, and Boston Scientific for lectures, travel, and accommodation to attend scientific meetings. BCBL acknowledges support from the Basque Government through the BERC 2018-2021 program

Mechanical chest compression devices improve survival of liver grafts from donors after cardiac death.

pre-print107 K

Supuestos de suspensión del plazo para resolver

Resumen del libro: Los autores de esta obra hemos querido tratar uno de los asuntos más complejos del Derecho Administrativo desde un punto de vista sistemático y práctico que ofrezca una utilidad inmediata a los operadores jurídicos. Para este estudio hemos abordado la inactividad y el silencio de la Administración desde sus orígenes hasta la situación normativa actual, considerando la última jurisprudencia y con especial atención a los aspectos procedimentales administrativos y contenciosos. El ordenamiento jurídico otorga a los poderes públicos unas potestades para intervenir en la sociedad en virtud de unos principios constitucionales como los de legalidad y eficacia. La ausencia de actuación positiva puede derivar en una inactividad que puede calificarse de indeseable si supone dejación de competencias, funciones o incumplimiento de obligaciones legales formales o materiales. La inactividad que analizamos en esta obra es aquella que puede desplegar algún efecto jurídico por suponer una ausencia de actividad junto con una obligación de actuar. En este marco el silencio administrativo es su máximo exponente, como un tipo de inactividad consistente en la falta de respuesta por parte de la Administración en plazo. Para el mejor análisis hemos iniciado la obra con una introducción que permite pasar a la definición de diferentes conceptos relevantes para comprender los efectos jurídicos de la inactividad como la obligación de resolver, la caducidad y la prescripción, así como el silencio positivo y negativo. A continuación tratamos el procedimiento administrativo, destacando aspectos como los plazos para resolver y recurrir, la suspensión de los mismos, la posibilidad de ampliación y el cómputo. La revisión de los actos producidos por silencio y la caducidad de los procedimientos y las medidas cautelares en el marco del silencio e inactividad son otros aspectos relevantes del procedimiento administrativo que se analizan en la obra. Hemos querido dar un tratamiento diferenciado a algunos supuestos especiales de silencio o inactividad como: la responsabilidad patrimonial y procedimientos sancionadores como especialidades del procedimiento general, la expropiación forzosa, el acceso a la información pública, el silencio en las reclamaciones previas a la vía judicial social o civil, en materia de gestión de personal, de urbanismo y licencias administrativas, en los procedimientos tributarios o en los aspectos sobre subvenciones. Finalmente, buscando la utilidad práctica de la obra se dedica una parte del libro a las reclamaciones en vía jurisdiccional por el silencio o inactividad, analizando aspectos como el objeto del recurso, la impugnación de la inactividad material, los plazos procesales para recurrir y el siempre interesante tema de la impugnación por falta de reglamentación o la ejecución de sentencias condenatorias por inactividad o silencio. Para remarcar el carácter práctico de la obra se han realizado una serie de modelos administrativos y formularios de utilidad, que se han incluido en cada uno de los apartados en los que podían resultar útiles para los operadores jurídicos ya desde el prisma del interesado ya desde el del gestor de la Administración.2021-2

La revisión en los actos por silencio administrativo positivo

Resumen del libro: Los autores de esta obra hemos querido tratar uno de los asuntos más complejos del Derecho Administrativo desde un punto de vista sistemático y práctico que ofrezca una utilidad inmediata a los operadores jurídicos. Para este estudio hemos abordado la inactividad y el silencio de la Administración desde sus orígenes hasta la situación normativa actual, considerando la última jurisprudencia y con especial atención a los aspectos procedimentales administrativos y contenciosos. El ordenamiento jurídico otorga a los poderes públicos unas potestades para intervenir en la sociedad en virtud de unos principios constitucionales como los de legalidad y eficacia. La ausencia de actuación positiva puede derivar en una inactividad que puede calificarse de indeseable si supone dejación de competencias, funciones o incumplimiento de obligaciones legales formales o materiales. La inactividad que analizamos en esta obra es aquella que puede desplegar algún efecto jurídico por suponer una ausencia de actividad junto con una obligación de actuar. En este marco el silencio administrativo es su máximo exponente, como un tipo de inactividad consistente en la falta de respuesta por parte de la Administración en plazo. Para el mejor análisis hemos iniciado la obra con una introducción que permite pasar a la definición de diferentes conceptos relevantes para comprender los efectos jurídicos de la inactividad como la obligación de resolver, la caducidad y la prescripción, así como el silencio positivo y negativo. A continuación tratamos el procedimiento administrativo, destacando aspectos como los plazos para resolver y recurrir, la suspensión de los mismos, la posibilidad de ampliación y el cómputo. La revisión de los actos producidos por silencio y la caducidad de los procedimientos y las medidas cautelares en el marco del silencio e inactividad son otros aspectos relevantes del procedimiento administrativo que se analizan en la obra. Hemos querido dar un tratamiento diferenciado a algunos supuestos especiales de silencio o inactividad como: la responsabilidad patrimonial y procedimientos sancionadores como especialidades del procedimiento general, la expropiación forzosa, el acceso a la información pública, el silencio en las reclamaciones previas a la vía judicial social o civil, en materia de gestión de personal, de urbanismo y licencias administrativas, en los procedimientos tributarios o en los aspectos sobre subvenciones. Finalmente, buscando la utilidad práctica de la obra se dedica una parte del libro a las reclamaciones en vía jurisdiccional por el silencio o inactividad, analizando aspectos como el objeto del recurso, la impugnación de la inactividad material, los plazos procesales para recurrir y el siempre interesante tema de la impugnación por falta de reglamentación o la ejecución de sentencias condenatorias por inactividad o silencio. Para remarcar el carácter práctico de la obra se han realizado una serie de modelos administrativos y formularios de utilidad, que se han incluido en cada uno de los apartados en los que podían resultar útiles para los operadores jurídicos ya desde el prisma del interesado ya desde el del gestor de la Administración.2021-2

Post ROSC deceased patients are potential donors of organs and tissues.

post-print235 K

Different susceptibility to pramipexole-induced impulsivity in a rat model of parkinson’s disease

Impulse Control Disorders (ICD) in patients with Parkinson’s disease are abnormal behaviors caused by long-term use of dopamine agonists, which pathophysiology is poorly understood. Using parkinsonian rats (adeno-associated viral vectors-mediated overexpression of A53T human α-synuclein in the substantia nigra compacta), we evaluated the impulsive behaviour under acute (0.25 and 3 mg/kg) and chronic (0.25 mg/kg for 4 weeks) administration of pramipexole (PPX) with the Variable Delay-to-Signal (VDS) task (motor and choice impulsivities). Changes in striatal D1 and D2 receptors expression were also analysed. Before treatment, the striatal dopaminergic depletion caused a significant increase of both impulsivity domains with respect to basal condition. In lesioned rats, acutely given PPX 0.25 mg/kg dose increased choice impulsivity only with regard to basal values. Meanwhile, 3 mg/kg PPX increased choice impulsivity compared to their own values at different conditions: basal, before treatment and after acute 0.25 mg/kg PPX administration. After chronic administration, two populations of lesioned animals were distinguished, one showing the same behaviour as control animals and other displaying an increased motor/response (first week of treatment) and cognitive/choice impulsivities (third week of treatment) compared to control animals. This impulsive behaviour disappeared when animals were tested in OFF state. Lower D2 expression in both Caudate-Putamen and Nucleus Accubens and lower D1 levels in Nucleus Accumbens in lesioned rats than in control animals were observed. Therefore, our results indicate that the pro-impulsive effect of PPX in this animal model of PD depends on the dose and administration paradigm employed and the individual predisposition, and it is associated to striatal dopamine receptors expression changes, especially in Nucleus Accumbens. Thus, this model could constitute a valid tool to investigate the pathophysiology of ICD.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech. DFG11/019, PI11/0210

Impact of different waves of COVID-19 on emergency medical services and out-of-hospital cardiopulmonary arrest in Madrid, Spain

Out-of-hospital cardiac arrest (OHCA) is one of the three leading causes of death in industrialized countries.[1,2] Some studies have described the impact of the first COVID-19 pandemic wave in terms of the number of cases and OHCA survival rates in various regions,[3-5] but few have addressed the relationship between the successive phases and how they affected OHCA.[6,7] The 14-d cumulative incidence peaked at more than 990 cases, with these rates remaining above 200 for an eight-month period between 15 March 2020 and 15 March 2021 in Madrid, Spain. The objectives of the current study were twofold. First, we sought to describe how the different waves in the first pandemic year aff ected the healthcare activity of the Spanish emergency medical services (EMS). Second, we compared effects of the pandemic year on OHCA care to those of the preceding non-pandemic year in terms of initiating cardiopulmonary resuscitation and survival in a community with a high incidence of COVID-19.post-print164 K