Focal Stroke in the Developing Rat Motor Cortex Induces Age- and Experience-Dependent Maladaptive Plasticity of Corticospinal System

Motor system development is characterized by an activity-dependent competition between ipsilateral and contralateral corticospinal tracts (CST). Clinical evidence suggests that age is crucial for developmental stroke outcome, with early lesions inducing a "maladaptive" strengthening of ipsilateral projections from the healthy hemisphere and worse motor impairment. Here, we investigated in developing rats the relation between lesion timing, motor outcome and CST remodeling pattern. We induced a focal ischemia into forelimb motor cortex (fM1) at two distinct pre-weaning ages: P14 and P21. We compared long-term motor outcome with changes in axonal sprouting of contralesional CST at red nucleus and spinal cord level using anterograde tracing. We found that P14 stroke caused a more severe long-term motor impairment than at P21, and induced a strong and aberrant contralesional CST sprouting onto denervated spinal cord and red nucleus. The mistargeted sprouting of CST, and the worse motor outcome of the P14 stroke rats were reversed by an early skilled motor training, underscoring the potential of early activity-dependent plasticity in modulating lesion outcome. Thus, changes in the mechanisms controlling CST plasticity occurring during the third postnatal week are associated with age-dependent regulation of the motor outcome after stroke

Focal Stroke in the Developing Rat Motor Cortex Induces Age- and Experience-Dependent Maladaptive Plasticity of Corticospinal System

Motor system development is characterized by an activity-dependent competition between ipsilateral and contralateral corticospinal tracts (CST). Clinical evidence suggests that age is crucial for developmental stroke outcome, with early lesions inducing a “maladaptive” strengthening of ipsilateral projections from the healthy hemisphere and worse motor impairment. Here, we investigated in developing rats the relation between lesion timing, motor outcome and CST remodeling pattern. We induced a focal ischemia into forelimb motor cortex (fM1) at two distinct pre-weaning ages: P14 and P21. We compared long-term motor outcome with changes in axonal sprouting of contralesional CST at red nucleus and spinal cord level using anterograde tracing. We found that P14 stroke caused a more severe long-term motor impairment than at P21, and induced a strong and aberrant contralesional CST sprouting onto denervated spinal cord and red nucleus. The mistargeted sprouting of CST, and the worse motor outcome of the P14 stroke rats were reversed by an early skilled motor training, underscoring the potential of early activity-dependent plasticity in modulating lesion outcome. Thus, changes in the mechanisms controlling CST plasticity occurring during the third postnatal week are associated with age-dependent regulation of the motor outcome after stroke

Modulation of Phenylalanine and Tyrosine Metabolism in HIV-1 Infected Patients with Neurocognitive Impairment: Results from a Clinical Trial

To investigate the effects of oral bacteriotherapy on intestinal phenylalanine and tyrosine metabolism, in this longitudinal, double-arm trial, 15 virally suppressed HIV+ individuals underwent blood and fecal sample collection at baseline and after 6 months of oral bacteriotherapy. A baseline fecal sample was collected from 15 healthy individuals and served as control group for the baseline levels of fecal phenylalanine and tyrosine. CD4 and CD8 immune activation (CD38+) was evaluated by flow cytometry. Amino acid evaluation on fecal samples was conducted by Proton Nuclear Magnetic Resonance. Results showed that HIV+ participants displayed higher baseline phenylalanine/tyrosine ratio values than healthy volunteers. A significand reduction in phenylalanine/tyrosine ratio and peripheral CD4+ CD38+ activation was observed at the end of oral bacteriotherapy. In conclusion, probiotics beneficially affect the immune activation of HIV+ individuals. Therefore, the restoration of intestinal amino acid metabolism could represent the mechanisms through which probiotics exert these desirable effects

Frailty, psychological well-being, and social isolation in older adults with cognitive impairment during the SARS-CoV-2 pandemic: data from the GeroCovid initiative

Background: The containment measures linked to the COVID-19 pandemic negatively affected the phyco-physical well-being of the population, especially older adults with neurocognitive disorders (NCDs). This study aims to evaluate whether the frailty of NCD patients was associated with different changes in multiple health domains, in particular in relation to loneliness and social isolation, pre- and post-lockdown. Materials and methods: Patients were recruited from 10 Italian Centers for Cognitive Disorders and Dementia. Data were collected in the pre-pandemic period (T0), during the pandemic lockdown (T1), and 6-9 months post-lockdown (T2). The UCLA Loneliness Scale-3, Activities of Daily Living (ADL), Instrumental ADL (IADL), Mini-Mental State Examination, and Neuropsychiatric Inventory (NPI) were administered. Caregivers' burden was also tested. Patients were categorized as non-frail, pre-frail, and frail according to the Fatigue, Resistance, Ambulation, Illness, and Loss of Weight scale. Results: The sample included 165 subjects (61.9% women, mean age 79.5 ± 4.9 years). In the whole sample, the ADL, IADL, and NPI scores significantly declined between T0 and T2. There were no significative variations in functional and cognitive domains between the frail groups. During lockdown we recorded higher Depression Anxiety Stress Scales and Perceived Stress Scale scores in frail people. In multivariable logistic regression, frailty was associated with an increase in social isolation, and a loss of IADL. Conclusions: We observed a global deterioration in functional and neuro-psychiatric domains irrespective of the degree of frailty. Frailty was associated with the worsening of social isolation during lockdown. Frail patients and their caregivers seemed to experience more anxiety and stress disorders during SARS-CoV-2 pandemic

Detection of the Diffuse Supernova Neutrino Background with JUNO

As an underground multi-purpose neutrino detector with 20 kton liquid scintillator, Jiangmen Underground Neutrino Observatory (JUNO) is competitive with and complementary to the water-Cherenkov detectors on the search for the diffuse supernova neutrino background (DSNB). Typical supernova models predict 2-4 events per year within the optimal observation window in the JUNO detector. The dominant background is from the neutral-current (NC) interaction of atmospheric neutrinos with 12C nuclei, which surpasses the DSNB by more than one order of magnitude. We evaluated the systematic uncertainty of NC background from the spread of a variety of data-driven models and further developed a method to determine NC background within 15\% with {\it{in}} {\it{situ}} measurements after ten years of running. Besides, the NC-like backgrounds can be effectively suppressed by the intrinsic pulse-shape discrimination (PSD) capabilities of liquid scintillators. In this talk, I will present in detail the improvements on NC background uncertainty evaluation, PSD discriminator development, and finally, the potential of DSNB sensitivity in JUNO

Early mobilisation in critically ill COVID-19 patients: a subanalysis of the ESICM-initiated UNITE-COVID observational study

Background Early mobilisation (EM) is an intervention that may improve the outcome of critically ill patients. There is limited data on EM in COVID-19 patients and its use during the first pandemic wave. Methods This is a pre-planned subanalysis of the ESICM UNITE-COVID, an international multicenter observational study involving critically ill COVID-19 patients in the ICU between February 15th and May 15th, 2020. We analysed variables associated with the initiation of EM (within 72 h of ICU admission) and explored the impact of EM on mortality, ICU and hospital length of stay, as well as discharge location. Statistical analyses were done using (generalised) linear mixed-effect models and ANOVAs. Results Mobilisation data from 4190 patients from 280 ICUs in 45 countries were analysed. 1114 (26.6%) of these patients received mobilisation within 72 h after ICU admission; 3076 (73.4%) did not. In our analysis of factors associated with EM, mechanical ventilation at admission (OR 0.29; 95% CI 0.25, 0.35; p = 0.001), higher age (OR 0.99; 95% CI 0.98, 1.00; p ≤ 0.001), pre-existing asthma (OR 0.84; 95% CI 0.73, 0.98; p = 0.028), and pre-existing kidney disease (OR 0.84; 95% CI 0.71, 0.99; p = 0.036) were negatively associated with the initiation of EM. EM was associated with a higher chance of being discharged home (OR 1.31; 95% CI 1.08, 1.58; p = 0.007) but was not associated with length of stay in ICU (adj. difference 0.91 days; 95% CI − 0.47, 1.37, p = 0.34) and hospital (adj. difference 1.4 days; 95% CI − 0.62, 2.35, p = 0.24) or mortality (OR 0.88; 95% CI 0.7, 1.09, p = 0.24) when adjusted for covariates. Conclusions Our findings demonstrate that a quarter of COVID-19 patients received EM. There was no association found between EM in COVID-19 patients' ICU and hospital length of stay or mortality. However, EM in COVID-19 patients was associated with increased odds of being discharged home rather than to a care facility. Trial registration ClinicalTrials.gov: NCT04836065 (retrospectively registered April 8th 2021)

Is CRX protein a useful marker in differential diagnosis of tumors of the pineal region?

The cone-rod homeobox (CRX) is a gene that belongs to the member of the orthodenticle homeobox (Otx) family, with important function in development and differentiation of retinal and pineal cells. Moreover, CRX appears to be specifically expressed in pineal tumors and retinoblastomas. We performed an immunohistochemical study on 91 pediatric and adult central nervous system tumors, plus 2 normal brain samples. Our results demonstrated that CRX is expressed not only in pineal parenchymal tumors and retinoblastoma, but also in a some medulloblastomas and supratentorial primitive neuroectodermal tumors. None of the glial tumors screened were positive for CRX. In conclusion, CRX could be useful in surgical neuropathology for the differential diagnosis of pineal region tumors, in particular to discriminate pineal tumors from glial tumors

Identification and management of acute alcohol intoxication

: Acute alcohol intoxication (AAI) is a harmful clinical condition, potentially life-threatening, secondary to the intake of large amounts of alcohol. Clinical manifestations of AAI are characterized by behavioural and neurological symptoms, even if its effects involve several organs and apparatus. Moreover, severe alcohol intoxication can produce a global neurological impairment leading to autonomic dysfunction, respiratory depression, coma and cardiac arrest. The evaluation of blood alcohol concentrations (BAC) is useful to confirm the suspicion of intoxication, both for clinical and legal reasons. Most of patients with AAI are referred to Emergency Departments due to behavioural, social, traumatic or clinical complications. Patient's stabilization is the first step in the management of AAI, in order to support vital functions and to prevent complications. Metadoxine represents a useful drug to increase ethanol metabolism and elimination. Given that AAI could represent a sentinel event of chronic alcohol abuse, patients presenting with acute intoxication should be screened for the presence of an underlying alcohol use disorder and referred to and an alcohol addiction unit to start a multidisciplinary treatment to achieve long term alcohol abstinence. The present review will focus on clinical features, diagnostic criteria and treatment strategies of AAI