Time-dependent recovery of brain hypometabolism in neuro-COVID-19 patients

Purpose We evaluated brain metabolic dysfunctions and associations with neurological and biological parameters in acute, subacute and chronic COVID-19 phases to provide deeper insights into the pathophysiology of the disease.Methods Twenty-six patients with neurological symptoms (neuro-COVID-19) and [F-18]FDG-PET were included. Seven patients were acute (< 1 month (m) after onset), 12 subacute (4 >= 1-m, 4 >= 2-m and 4 >= 3-m) and 7 with neuro-post-COVID-19 (3 >= 5-m and 4 >= 7-9-m). One patient was evaluated longitudinally (acute and 5-m). Brain hypo- and hypermetabolism were analysed at single-subject and group levels. Correlations between severity/extent of brain hypo- and hypermetabolism and biological (oxygen saturation and C-reactive protein) and clinical variables (global cognition and Body Mass Index) were assessed.Results The "fronto-insular cortex" emerged as the hypometabolic hallmark of neuro-COVID-19. Acute patients showed the most severe hypometabolism affecting several cortical regions. Three-m and 5-m patients showed a progressive reduction of hypometabolism, with limited frontal clusters. After 7-9 months, no brain hypometabolism was detected. The patient evaluated longitudinally showed a diffuse brain hypometabolism in the acute phase, almost recovered after 5 months. Brain hypometabolism correlated with cognitive dysfunction, low blood saturation and high inflammatory status. Hypermetabolism in the brainstem, cerebellum, hippocampus and amygdala persisted over time and correlated with inflammation status.Conclusion Synergistic effects of systemic virus-mediated inflammation and transient hypoxia yield a dysfunction of the fronto-insular cortex, a signature of CNS involvement in neuro-COVID-19. This brain dysfunction is likely to be transient and almost reversible. The long-lasting brain hypermetabolism seems to reflect persistent inflammation processes

Sustained seizure freedom with adjunctive brivaracetam in patients with focal onset seizures

The maintenance of seizure control over time is a clinical priority in patients with epilepsy. The aim of this study was to assess the sustained seizure frequency reduction with adjunctive brivaracetam (BRV) in real-world practice. Patients with focal epilepsy prescribed add-on BRV were identified. Study outcomes included sustained seizure freedom and sustained seizure response, defined as a 100% and a ≥50% reduction in baseline seizure frequency that continued without interruption and without BRV withdrawal through the 12-month follow-up. Nine hundred ninety-four patients with a median age of 45 (interquartile range = 32–56) years were included. During the 1-year study period, sustained seizure freedom was achieved by 142 (14.3%) patients, of whom 72 (50.7%) were seizure-free from Day 1 of BRV treatment. Sustained seizure freedom was maintained for ≥6, ≥9, and 12 months by 14.3%, 11.9%, and 7.2% of patients from the study cohort. Sustained seizure response was reached by 383 (38.5%) patients; 236 of 383 (61.6%) achieved sustained ≥50% reduction in seizure frequency by Day 1, 94 of 383 (24.5%) by Month 4, and 53 of 383 (13.8%) by Month 7 up to Month 12. Adjunctive BRV was associated with sustained seizure frequency reduction from the first day of treatment in a subset of patients with uncontrolled focal epilepsy

Growing medicinal plants in hydroponic culture

Medicinal plants are increasingly cultivated on a commercial scale to satisfy the large demand for natural remedies. These species are generally grown in open field, which results in large year-to-year variability in both biomass production and content of active principles. Hydroponic technology may be applied to produce highstandard plant material all year-round in consideration of the possibility to control growing conditions and to stimulate secondary metabolism by appropriate manipulation of mineral nutrition. A series of experiments were conducted between 2005 and 2010 at the University of Pisa to investigate the application of the floating raft growing system for the greenhouse cultivation of echinacea (Echinacea angustifolia DC) and basil (Ocimum basilicum L), which are typically cultivated for their roots and leaves, respectively. Growth and content of distinctive caffeic acid derivatives (CADs), specifically echinacoside in echinacea and rosmarinic acid in basil, were determined. Both species grew rapidly and healthy and in two to four months they accumulated large biomass with minimal contamination. Nevertheless, in echinacea the high biomass production was not associated with high levels of CADs and the concentration of echinacoside (the marker compound used for quality standardization) never reached the minimum standard (1% on a dry weight basis) for the industrial production of dry extract. In contrast, basil accumulated an adequate content of rosmarinic acid. One additional advantage was the possibility to harvest also the root system of basil, which contained higher levels of rosmarinic acid compared to the leaves

In vivo evaluation of cannabis sativa full extract on zebrafish larvae development, locomotion behavior and gene expression

Historically, humans have been using Cannabis sativa for both recreational and medical purposes. Nowadays, cannabis-based products have gained scientific interest due to their beneficial effects on several syndromes and illnesses. The biological activity of cannabinoids is essentially due to the interaction with the endocannabinoid system, and zebrafish (Danio rerio) is a very well-known and powerful in vivo model for studying such specific interactions. The aim of the study was to investigate the effects of different doses of a Cannabis sativa whole extract [dissolved in dimethyl sulfoxide (DMSO)] on zebrafish eggs’ hatchability, embryo post-hatching survival, larvae locomotion behavior and mRNA gene expression. The results showed the absence of toxicity, and no significant differences were observed between treatments for both embryo hatching and survival rate. In addition, larvae exposed to the cannabis extract at the highest dose [containing 1.73 nM and 22.3 nM of ∆9-tetrahydrocannabinol (THC) and cannabidiol (CBD), respectively] showed an increased locomotion compared to the control and DMSO treated groups. Moreover, qRT-PCR analysis showed that the highest dosage of cannabis induced an over-expression of cnr1 and cnr2 cannabinoid receptors. In conclusion, the exposition of zebrafish larvae to the whole extract of Cannabis sativa showed no negative effects on embryo development and survival and enhanced the larvae’s locomotor performances. These findings may open up possible Cannabis sativa applications in human pharmacology as well as in other animal sectors

Visual hallucinations in Parkinson's disease are not influenced by polymorphisms of serotonin 5-HT2A receptor and transporter genes

Psychiatric disorders are common in Parkinson's disease (PD) and hallucinations are observed in nearly 40% of PD patients. The involvement of dopaminergic system in the pathogenesis of psychosis has been sustained by most of the authors even if several evidences indicate that multiple neurochemical substrates might underlie psychosis in PD. In PD there is an extensive loss of serotoninergic raphe neurons and serotonin dysfunction had been implicated in the pathogenesis of many psychiatric disorders such as depression, schizophrenia, and in psychosis of patients with Alzheimer disease. The association of a serotonin transporter gene-linked polymorphic region (5-HTTLPR) and the 5-HT2A receptor T102C polymorphism with psychosis in a group of patients with PD was investigated. No significant differences in the distribution of allele and genotype frequencies of the 5-HTTLPR (p > 0.01) and 5-HT2A T102C (p > 0.05) were found between patients and controls as well as between the patients' subgroups without and with psychosis. These data might suggest that 5-HTTLPR and 5-HT2A polymorphisms are not major susceptibility factors of psychotic symptoms in PD patients

Metabolic changes induced by theta burst stimulation of the cerebellum in dyskinetic Parkinson's disease patients

Cerebellar repetitive transcranial magnetic stimulation may be effective in reducing peak-dose levodopa induced dyskinesia in Parkinson's disease patients. It was proposed that the antidyskinetic effect could be due to modulation of cerebello-thalamo-cortical pathways. However the neural basis for these clinical effects have not yet been demonstrated