Involving the cerebellum in cocaine-induced memory: pattern of CFOS expression in mice trained to acquire conditioned preference for cocaine

Because of its primary role in drug-seeking, consumption and addictive behaviour, there is a growing interest in identifying the neural circuits and molecular mechanisms underlying the formation, maintenance and retrieval of drug-related memories. Human studies, which focused on neuronal systems that store and control drug-conditioned memories, have found cerebellar activations during the retrieval of drug-associated cue memory. However, at the pre-clinical level, almost no attention has been paid to a possible role of the cerebellum in drug-related memories. In the present study, we ought to fill this gap by aiming to investigate the pattern of neuronal activation (as revealed by cFos expression) in different regions of the prefrontal cortex and cerebellum of mice trained to develop conditioned preference for an olfactory stimulus (CS+) paired with cocaine. Our results indicate that CS+ preference was directly associated with cFos expression in cells at the apical region of the granule cell layer of the cerebellar vermis; this relationship being more prominent in some specific lobules. Conversely, cFos+ immunostaining in other cerebellar regions seems to be unrelated to CS+ preference but to other aspects of the conditioning procedure. At the prefrontal cortex, cFos expression seemed to be related to cocaine administration rather than to its ability to establish conditioned preference. The present results suggest that as it has been observed in some clinical studies, the cerebellum might be an important and largely overlooked part of the neural circuits involved in generating, maintaining and/or retrieving drug memories

Transitando la transformación digital: análisis comparativo de las industrias automotriz y naval en Argentina

El objetivo general es comprender el alcance y las características del proceso de transformación digital (TD) en la industria automotriz y la industria naval en Argentina en términos comparativos. Utilizamos un abordaje metodológico cualitativo. Los principales resultados indican que: (i) la industria automotriz presenta un grado de avance en el proceso de TD mucho mayor al de la industria naval en Argentina; y (ii) los principales factores que explican el atraso relativo de la industria naval en este proceso son las características del proceso productivo, la cultura organizacional, y el rol de las empresas líderes de la cadena de valor.Fil: Manzo, Franco. Universidad Nacional de Mar del Plata. Facultad de Ciencias Económicas y Sociales; Argentina.Fil: Mauro, Lucía Mercedes. Universidad Nacional de Mar del Plata. Facultad de Ciencias Económicas y Sociales; Argentina.Fil: Calá, Carla Daniela. Universidad Nacional de Mar del Plata. Facultad de Ciencias Económicas y Sociales; Argentina

Have we been ignoring the elephant in the room? Seven arguments for considering the cerebellum as part of addiction circuitry

Addiction involves alterations in multiple brain regions that are associated with functions such as memory, motivation and executive control. Indeed, it is now well accepted that addictive drugs produce long-lasting molecular and structural plasticity changes in corticostriatal-limbic loops. However, there are brain regions that might be relevant to addiction other than the prefrontal cortex, amygdala, hippocampus and basal ganglia. In addition to these circuits, a growing amount of data suggests the involvement of the cerebellum in many of the brain functions affected in addicts, though this region has been overlooked, traditionally, in the addiction field. Therefore, in the present review we provide seven arguments as to why we should consider the cerebellum in drug addiction. We present and discuss compelling evidence about the effects of drugs of abuse on cerebellar plasticity, the involvement of the cerebellum in drug-induced cue-related memories, and several findings showing that the instrumental memory and executive functions also recruit the cerebellar circuitry. In addition, a hypothetical model of the cerebellum's role relative to other areas within corticostriatal-limbic networks is also provided. Our goal is not to review animal and human studies exhaustively but to support the inclusion of cerebellar alterations as a part of the physiopathology of addiction disorder.This work was supported by grants and fellowships: FPU12/04059, PPF 2015 (15I082.01/1) and UJI (14I307.01/1). We also thank Timothy Attwood Gibbons for the English revision of the manuscript

Cerebellar hallmarks of conditioned preference for cocaine

Pavlovian conditioning tunes the motivational drive of drug-associated stimuli, fostering the probability of those environmental stimuli to promote and trigger drug seeking and taking. Interestingly, different areas in the cerebellum are involved in the formation and long-lasting storage of Pavlovian emotional memory. Very recently, we have shown that conditioned preference for an odour associated with cocaine was directly correlated with cFOS expression in cells at the dorsal region of the granule cell layer of the cerebellar vermis. The main goal of the current investigation was to further extend the description of cFOS-IR patterns in cerebellar circuitry after training mice in a cocaine-odour Pavlovian conditioning procedure, including now the major inputs (the inferior olive and pontine nuclei) and one of the output nuclei (the medial deep nucleus) of the cerebellum. The results showed that the cerebellar hallmark of preference towards an odour cue associated to cocaine is an increase in cFOS expression in the dorsal part of the granule cell layer. cFOS-IR levels expressed in the granule cell layer of mice that did not show cocaine conditioned preference did not differ from the basal levels. Remarkably, mice subjected to a random cocaine-odour pairing procedure (the unpaired group) exhibited higher cFOS-IR in the inferior olive, the pontine nuclei and in the deep medial nucleus. Therefore, our findings suggest that inputs and the output of cerebellar circuitry are enhanced when contingency between the CS+ and cocaine is lacking

UTILIZAÇÃO DE BARREIRAS DE SEGURANÇA NO PREPARO DE DROGAS VASOATIVAS E SEDATIVOS/ANALGÉSICOS EM TERAPIA INTENSIVA PEDIÁTRICA

Objective: to analyze the use of safety barriers in the preparation of vasoactive drugs and sedatives/analgesics. Method:quantitative study, with 204 observations during the preparation of medications in a Pediatric Intensive Care Unit in the Pediatric Hospital of the State of Santa Catarina, between March 2016 and May 2017. The barriers analyzed were: type of prescription; transcription of the medication, identification of the patient and data on the label; label attachment; double checking; preparation of continuous infusions; and interruptions. The data were analyzed using descriptive statistics. Results:the safety barriers were related to written prescription (93.6%); transcription of the medication on the label (87.7%); patient identification on the label only by the first name (96%); data relating to the medication on the label failing to include the transcription of the route of administration (99.4%); double checking (34.6%); and interruptions during the preparation (52.9%). Conclusion: this study alerts the area to the need to implement barriers so as to promote safe clinical practice.Objetivo: analisar a utilização de barreiras de segurança no preparo de drogas vasoativas e sedativos/analgésicos. Método: estudo quantitativo, com 204 observações durante o preparo de medicamentos em uma Unidade de Terapia Intensiva Pediátrica no Hospital Pediátrico do Estado de Santa Catarina, de março de 2016 a maio de 2017. As barreiras analisadas foram: tipo de prescrição; transcrição da medicação, identificação do paciente e dados no rótulo; local de fixação; dupla checagem; preparo de infusões contínuas; interrupções. Os dados foram analisados por estatística descritiva. Resultados: as barreiras de segurança foram relacionadas à prescrição escrita (93,6%); transcrição da medicação em rótulo (87,7%); identificação do primeiro nome do paciente no rótulo (96%); dados da medicação no rótulo sem a transcrição da via de administração (99,4%); dupla checagem (34,6%); interrupções durante o preparo (52,9%). Conclusão: este estudo alerta a área sobre a necessidade da implementação de barreiras no intuito de uma prática clínica segura.Objetivo: analizar el uso de barreras de seguridaden la preparación de drogas vasoactivas y sedantes/analgésicos. Método: estudio cuantitativo, con 204 observaciones durante la preparación de medicamentos en una Unidad de Terapia Intensiva Pediátrica en el Hospital Pediátrico del Estado de Santa Catarina, de marzo de 2016 a mayo de 2017. Las barreras analizadas fueron: tipo de prescripción; transcripción de la medicación, identificación del paciente y datos en el rótulo; local de fijación; doble verificación; preparación de infusiones continuas; interrupciones. Se hizo el análisis dedatos por medio de estadística descriptiva. Resultados: se asociaronlas barreras de seguridad a la prescripción escrita (93,6%); transcripción de la medicación en rótulo (87,7%); identificación del primer nombre del paciente en el rótulo (96%); datos de la medicaciónen el rótulo sinla transcripción de la vía de administración (99,4%); doble verificación (34,6%); interrupciones durante lapreparación(52,9%). Conclusión: este estudio hace un alerta sobre la necesidad de la implementación de barreras con el objetivo de llegar a una práctica clínica segura

COVID-19 Severity in Multiple Sclerosis: Putting Data Into Context

Background and objectives: It is unclear how multiple sclerosis (MS) affects the severity of COVID-19. The aim of this study is to compare COVID-19-related outcomes collected in an Italian cohort of patients with MS with the outcomes expected in the age- and sex-matched Italian population. Methods: Hospitalization, intensive care unit (ICU) admission, and death after COVID-19 diagnosis of 1,362 patients with MS were compared with the age- and sex-matched Italian population in a retrospective observational case-cohort study with population-based control. The observed vs the expected events were compared in the whole MS cohort and in different subgroups (higher risk: Expanded Disability Status Scale [EDSS] score > 3 or at least 1 comorbidity, lower risk: EDSS score ≤ 3 and no comorbidities) by the χ2 test, and the risk excess was quantified by risk ratios (RRs). Results: The risk of severe events was about twice the risk in the age- and sex-matched Italian population: RR = 2.12 for hospitalization (p < 0.001), RR = 2.19 for ICU admission (p < 0.001), and RR = 2.43 for death (p < 0.001). The excess of risk was confined to the higher-risk group (n = 553). In lower-risk patients (n = 809), the rate of events was close to that of the Italian age- and sex-matched population (RR = 1.12 for hospitalization, RR = 1.52 for ICU admission, and RR = 1.19 for death). In the lower-risk group, an increased hospitalization risk was detected in patients on anti-CD20 (RR = 3.03, p = 0.005), whereas a decrease was detected in patients on interferon (0 observed vs 4 expected events, p = 0.04). Discussion: Overall, the MS cohort had a risk of severe events that is twice the risk than the age- and sex-matched Italian population. This excess of risk is mainly explained by the EDSS score and comorbidities, whereas a residual increase of hospitalization risk was observed in patients on anti-CD20 therapies and a decrease in people on interferon

DMTs and Covid-19 severity in MS: a pooled analysis from Italy and France

We evaluated the effect of DMTs on Covid-19 severity in patients with MS, with a pooled-analysis of two large cohorts from Italy and France. The association of baseline characteristics and DMTs with Covid-19 severity was assessed by multivariate ordinal-logistic models and pooled by a fixed-effect meta-analysis. 1066 patients with MS from Italy and 721 from France were included. In the multivariate model, anti-CD20 therapies were significantly associated (OR = 2.05, 95%CI = 1.39–3.02, p < 0.001) with Covid-19 severity, whereas interferon indicated a decreased risk (OR = 0.42, 95%CI = 0.18–0.99, p = 0.047). This pooled-analysis confirms an increased risk of severe Covid-19 in patients on anti-CD20 therapies and supports the protective role of interferon

Colorectal Cancer Stage at Diagnosis Before vs During the COVID-19 Pandemic in Italy

IMPORTANCE Delays in screening programs and the reluctance of patients to seek medical attention because of the outbreak of SARS-CoV-2 could be associated with the risk of more advanced colorectal cancers at diagnosis. OBJECTIVE To evaluate whether the SARS-CoV-2 pandemic was associated with more advanced oncologic stage and change in clinical presentation for patients with colorectal cancer. DESIGN, SETTING, AND PARTICIPANTS This retrospective, multicenter cohort study included all 17 938 adult patients who underwent surgery for colorectal cancer from March 1, 2020, to December 31, 2021 (pandemic period), and from January 1, 2018, to February 29, 2020 (prepandemic period), in 81 participating centers in Italy, including tertiary centers and community hospitals. Follow-up was 30 days from surgery. EXPOSURES Any type of surgical procedure for colorectal cancer, including explorative surgery, palliative procedures, and atypical or segmental resections. MAIN OUTCOMES AND MEASURES The primary outcome was advanced stage of colorectal cancer at diagnosis. Secondary outcomes were distant metastasis, T4 stage, aggressive biology (defined as cancer with at least 1 of the following characteristics: signet ring cells, mucinous tumor, budding, lymphovascular invasion, perineural invasion, and lymphangitis), stenotic lesion, emergency surgery, and palliative surgery. The independent association between the pandemic period and the outcomes was assessed using multivariate random-effects logistic regression, with hospital as the cluster variable. RESULTS A total of 17 938 patients (10 007 men [55.8%]; mean [SD] age, 70.6 [12.2] years) underwent surgery for colorectal cancer: 7796 (43.5%) during the pandemic period and 10 142 (56.5%) during the prepandemic period. Logistic regression indicated that the pandemic period was significantly associated with an increased rate of advanced-stage colorectal cancer (odds ratio [OR], 1.07; 95%CI, 1.01-1.13; P = .03), aggressive biology (OR, 1.32; 95%CI, 1.15-1.53; P < .001), and stenotic lesions (OR, 1.15; 95%CI, 1.01-1.31; P = .03). CONCLUSIONS AND RELEVANCE This cohort study suggests a significant association between the SARS-CoV-2 pandemic and the risk of a more advanced oncologic stage at diagnosis among patients undergoing surgery for colorectal cancer and might indicate a potential reduction of survival for these patients