Behavioral domains in compulsive rats: implications for understanding compulsive spectrum disorders

IntroductionCompulsive behavior has been proposed as a transdiagnostic trait observed in different neuropsychiatric disorders, such as obsessive-compulsive disorder, autism, and schizophrenia. Research Domain Criteria (RDoC) strategy could help to disentangle the neuropsychological basis of compulsivity for developing new therapeutic and preventive approaches. In preclinical research, the selection of high-drinker (HD) vs. low-drinker (LD) animals by schedule-induced polydipsia (SIP) is considered a putative model of compulsivity, which includes a well-differentiated behavioral pattern.MethodsThe purpose of this research was to assess the cognitive control and the negative valence system domains in a phenotype of compulsive HD rats. After the selection of animals as HD or LD, we assessed behavioral inflexibility by probabilistic spatial reversal learning (PSRL), motor and cognitive impulsivity by variable delay-to-signal (VDS), and risky decision-making by rodent gambling task (rGT).ResultsHD rats performed fewer reversals and showed less probability of pressing the same lever that was previously reinforced on PSRL, more premature responses after the exposure to longer delays on VDS, and more disadvantageous risky choices on rGT. Moreover, HD animals performed more perseverative responses under the punishment period on rGT.DiscussionThese results highlight that HD compulsive phenotype exhibits behavioral inflexibility, insensitivity to positive feedback, waiting impulsivity, risky decision-making, and frustrative non-reward responsiveness. Moreover, these findings demonstrate the importance of mapping different behavioral domains to prevent, treat, and diagnose compulsive spectrum disorders correctly

XV International Congress of Control Electronics and Telecommunications: "The role of technology in times of pandemic and post-pandemic: innovation and development for strategic social and productive sectors"

La anterior selección, motivados por la aseveración de Manuel Castells -hace casi 20 años ya- que la innovación y la difusión de la tecnología parecía ser la herramienta apropiada para el desarrollo en la era de la información. Este 2020, sin embargo, ante la situación disruptiva que aquejó y aqueja a la sociedad red como una estructura social emergente de la Era de la Información basada en redes de producción, energizadas por el poder y la experiencia; falló y debe reencontrar su rumbo. Es así que los problemas acuciantes, ahora, fueron: la atención sanitaria y la superación de la epidemia de Sars Cov 2; tomó forma la, hasta entonces, visión irrealista de Castells que … no podemos avanzar con nuestros modelos de desarrollo actual, destruyendo nuestro entorno y excluyendo a la mayor parte de la humanidad de los beneficios de la revolución tecnológica más extraordinaria de la historia, sin sufrir una devastadora reacción por parte de la sociedad y la naturaleza. Fue así que el Cuarto Mundo, específicamente, donde la suficiencia de recurso humano, de capital, trabajo, información y mercado -vinculados todos a través de la tecnología- supuso que atendería eficazmente a través de la población que podía por su capacidad hacer uso racional y profesional del conocimiento, las necesidades de la mayoritaria población vulnerable y vulnerada. Por lo anterior, poner en el centro a las personas, en entornos de tarea y trabajo globales hiperconectados combinando espacios físicos, corrientes de información con canales de conexión expeditos, y formando profesionales del conocimiento que asuman y afronten los retos derivados de la transformación digital de empresas, universidades, y organizaciones, pero en condiciones de equidad y sujetos de prosperidad, será el desafío en los escenarios presentes y futuros inmediatos.The previous selection, motivated by the assertion of Manuel Castells -almost 20 years ago- that innovation and diffusion of technology seemed to be the appropriate tool for development in the information age. This 2020, however, in the face of the disruptive situation that afflicted and continues to afflict the network society as an emerging social structure of the Information Age based on production networks, energized by power and experience; He failed and must find his way again. Thus, the pressing problems now were: health care and overcoming the Sars Cov 2 epidemic; Castells' until then unrealistic vision took shape that... we cannot advance with our current development models, destroying our environment and excluding the majority of humanity from the benefits of the most extraordinary technological revolution in history, without suffering a devastating reaction from society and nature. It was thus that the Fourth World, specifically, where the sufficiency of human resources, capital, work, information and market - all linked through technology - meant that it would serve effectively through the population that could, due to its capacity, make rational use. and knowledge professional, the needs of the majority vulnerable and vulnerable population. Therefore, putting people at the center, in hyperconnected global task and work environments, combining physical spaces, information flows with expedited connection channels, and training knowledge professionals who assume and face the challenges derived from the digital transformation of companies, universities, and organizations, but in conditions of equality and subject to prosperity, will be the challenge in the present and immediate future scenarios.Bogot

Compilación de Proyectos de Investigacion de 1984-2002

Instituto Politecnico Nacional. UPIICS

A 12-gene pharmacogenetic panel to prevent adverse drug reactions: an open-label, multicentre, controlled, cluster-randomised crossover implementation study

© 2023Background: The benefit of pharmacogenetic testing before starting drug therapy has been well documented for several single gene–drug combinations. However, the clinical utility of a pre-emptive genotyping strategy using a pharmacogenetic panel has not been rigorously assessed. Methods: We conducted an open-label, multicentre, controlled, cluster-randomised, crossover implementation study of a 12-gene pharmacogenetic panel in 18 hospitals, nine community health centres, and 28 community pharmacies in seven European countries (Austria, Greece, Italy, the Netherlands, Slovenia, Spain, and the UK). Patients aged 18 years or older receiving a first prescription for a drug clinically recommended in the guidelines of the Dutch Pharmacogenetics Working Group (ie, the index drug) as part of routine care were eligible for inclusion. Exclusion criteria included previous genetic testing for a gene relevant to the index drug, a planned duration of treatment of less than 7 consecutive days, and severe renal or liver insufficiency. All patients gave written informed consent before taking part in the study. Participants were genotyped for 50 germline variants in 12 genes, and those with an actionable variant (ie, a drug–gene interaction test result for which the Dutch Pharmacogenetics Working Group [DPWG] recommended a change to standard-of-care drug treatment) were treated according to DPWG recommendations. Patients in the control group received standard treatment. To prepare clinicians for pre-emptive pharmacogenetic testing, local teams were educated during a site-initiation visit and online educational material was made available. The primary outcome was the occurrence of clinically relevant adverse drug reactions within the 12-week follow-up period. Analyses were irrespective of patient adherence to the DPWG guidelines. The primary analysis was done using a gatekeeping analysis, in which outcomes in people with an actionable drug–gene interaction in the study group versus the control group were compared, and only if the difference was statistically significant was an analysis done that included all of the patients in the study. Outcomes were compared between the study and control groups, both for patients with an actionable drug–gene interaction test result (ie, a result for which the DPWG recommended a change to standard-of-care drug treatment) and for all patients who received at least one dose of index drug. The safety analysis included all participants who received at least one dose of a study drug. This study is registered with ClinicalTrials.gov, NCT03093818 and is closed to new participants. Findings: Between March 7, 2017, and June 30, 2020, 41 696 patients were assessed for eligibility and 6944 (51·4 % female, 48·6% male; 97·7% self-reported European, Mediterranean, or Middle Eastern ethnicity) were enrolled and assigned to receive genotype-guided drug treatment (n=3342) or standard care (n=3602). 99 patients (52 [1·6%] of the study group and 47 [1·3%] of the control group) withdrew consent after group assignment. 652 participants (367 [11·0%] in the study group and 285 [7·9%] in the control group) were lost to follow-up. In patients with an actionable test result for the index drug (n=1558), a clinically relevant adverse drug reaction occurred in 152 (21·0%) of 725 patients in the study group and 231 (27·7%) of 833 patients in the control group (odds ratio [OR] 0·70 [95% CI 0·54–0·91]; p=0·0075), whereas for all patients, the incidence was 628 (21·5%) of 2923 patients in the study group and 934 (28·6%) of 3270 patients in the control group (OR 0·70 [95% CI 0·61–0·79]; p <0·0001). Interpretation: Genotype-guided treatment using a 12-gene pharmacogenetic panel significantly reduced the incidence of clinically relevant adverse drug reactions and was feasible across diverse European health-care system organisations and settings. Large-scale implementation could help to make drug therapy increasingly safe. Funding: European Union Horizon 2020