Biology subjects

Romeo, A.

Publications and source records attributed to Romeo, A..

4 recordsLinked to original sources

bioRxiv2020

Pleiotropic effect of Lactoferrin in the prevention and treatment of COVID-19 infection: in vivo, in silico and in vitro preliminary evidences

Lactoferrin, a multifunctional cationic glycoprotein, secreted by exocrine glands and neutrophils, possesses an antiviral activity extendable to SARS-CoV-2. We performed in vitro assays proving lactoferrin antiviral activity through direct attachment to both virus and cell surface components. This activity varied according to concentration (100/500g/ml), multiplicity of infection (0.1/0.01) and cell type (Vero E6/Caco-2 cells). Interestingly, the in silico results strongly supported the hypothesis of a direct recognition between the lactoferrin and the Spike S glycoprotein, thus hindering the viral entry into the cells. Hence, we conducted a clinical trial to investigate effect and tolerability of a liposomal lactoferrin formulation as a supplementary nutraceutical agent in mild-to-moderate and asymptomatic COVID-19 patients. A total of 92 mild-to-moderate (67/92) and asymptomatic (25/92) COVID-19 patients were recruited and divided in 3 groups according to the administered regimen. Thirty-two patients, 14 hospitalised and 18 in home-based insolation received oral and intranasal liposomal bovine lactoferrin (bLf), 32 hospitalised patients were treated with standard of care treatment (hydroxychloroquine, azitromicin and lopinavir/darunavir), and 28, in home-based isolation, did not take any medication. Furthermore, 32 COVID-19 negative, not-treated, healthy subjects were added as a control group for ancillary analysis. bLf-supplemented COVID-19 patients obtained an earlier and significant (p < 0,0001.) median rRT-PCR SARS-COV-2 RNA negative conversion than standard of care-treated and non-treated COVID-19 patients (14.25 vs 27.13 vs 32.61 days, respectively). In addition, bLf-supplemented COVID-19 patients showed significant fast clinical symptoms recovery than standard of care-treated and non-treated COVID-19 patients. Moreover, in bLf-supplemented patients, a significant decrease of either serum ferritin or IL-6 levels or host iron overload, all parameters characterizing inflammatory processes, were observed. Serum D-dimers was also found significantly decreased following bLf supplement. No adverse events were reported. These in vitro and in vivo observations led us to speculate a potential and safe supplementary role of Blf in the management of mild-to-moderate and asymptomatic COVID-19 patients.

microbiology↗

bioRxiv2020

Implantation technique, safety and complications of robot-assisted stereoelectroencephalography exploration of the limbic thalamus in human focal epilepsy

IntroductionDespite numerous imaging studies highlighting the importance of thalamus in surgical prognosis, human electrophysiological studies involving the limbic thalamic nuclei are limited. The objective of this study was to evaluate the safety and accuracy of robot-assisted stereotactic electrode placement in the limbic thalamic nuclei in patients with suspected temporal lobe epilepsy (TLE). MethodsAfter obtaining informed consent, 24 adults with drug-resistant suspected TLE undergoing Stereo-EEG evaluation were enrolled in this prospective study. The trajectory of one electrode planned for clinical sampling the operculo-insular cortex was modified to extend to the thalamus, thereby preventing the need for additional electrode placement for research. The anterior thalamus (ANT) (N=13) and the medial group of thalamic nuclei (MED) (N=11), including mediodorsal (MD) and centromedian (CeM) were targeted. The post-implantation CT was co-registered to the pre-operative MRI, and Morels thalamic atlas was used to confirm the accuracy of implantation. ResultsTen out of 13 (77%) in the ANT group and 10 out of 11 patients (90%) in the medial group had electrodes accurately placed in the thalamic nuclei. None of the patients had a thalamic hemorrhage. However, trace asymptomatic hemorrhages at the cortical level entry site were noted in 20.8% of patients and they did not require additional surgical intervention. SEEG data from all the patients were interpretable and analyzable. The trajectories for the ANT implant differed slightly from the medial group at the entry point i.e., precentral gyrus in the former and postcentral gyrus in the latter. ConclusionsUsing judiciously planned robot-assisted SEEG, we demonstrate the safety of electrophysiological sampling from various thalamic nuclei for research recordings, presenting a technique that avoids implanting additional depth electrodes, or comprising clinical care. With these results, we propose that if patients are fully informed of the risks involved, there are potential benefits of gaining mechanistic insights to seizure genesis, which may help to develop neuromodulation therapies.

neuroscience↗

bioRxiv2019

Ictal recruitment of anterior nucleus of thalamus in human focal epilepsy

The thalamic nuclei play diverse roles in the initiation, propagation, and termination of temporal lobe seizures. The role of the anterior nucleus of the thalamus (ANT) - a node that is integral to the limbic network is unclear. The objective of this study was to characterize temporal and - spectral patterns of ANT ictal recruitment in drug-resistant temporal lobe epilepsy (TLE). We hypothesized that seizures localized to the temporolimbic network are likely to recruit ANT, and the odds of recruitment were higher in seizures that had altered consciousness. Ten patients undergoing stereo-electroencephalography (SEEG) were recruited prospectively to record field potentials from the ANT. Using epileptogenicity index and line length, we computed the number of seizures that recruited the ANT (recruitment ratio), the recruitment latencies between the ANT and the epileptogenic zone (EZ), and latency of ANT recruitment to clinical manifestation for seventy-nine seizures. We observed that seizures localized to mesial temporal subregions (hippocampus, amygdala, anterior cingulate) have a higher predilection for ANT recruitment, and the recruitment was faster (ranged 5-12 secs) and preceded clinical onset for seizures that impaired consciousness. Seizures that recruited ANT lasted significantly longer (t=1.795, p=0.005). Recruitment latency was inversely correlated to seizure duration (r=-0.78, p=0.004). Electrical stimulation of the EZ induced seizures, in which early recruitment of ANT was confirmed. Stimulation of ANT did not induce a seizure. Finally, we tested the hypothesis that spectral and entropy-based features extracted from thalamic field potentials can distinguish its state of ictal recruitment from other interictal states (including awake, sleep). For this, we employed classification machine learning that discriminated thalamic ictal state from other interictal states with high accuracy (92.8%) and precision (93.1%). Among the features, the emergence of the theta rhythm (4-8 Hz) maximally discriminated the endogenous ictal state from other interictal states of vigilance. These results prompt a mechanistic role for the ANT in the early organization and sustaining of seizures, and the possibility to serve as a target for therapeutic closed-loop stimulation in TLE.

neuroscience↗

bioRxiv2019

Early Ictal Recruitment of Midline Thalamus in Mesial Temporal Lobe Epilepsy

The causal role of midline thalamus in the initiation and early organization of mesial temporal lobe seizures is studied. Three patients undergoing stereoelectroencephalography were enrolled for the placement of an additional depth electrode targeting the midline thalamus. The midline thalamus was recruited in all three patients at varying points of seizure initiation (0-13 seconds) and early propagation (9-60 seconds). Stimulation of either thalamus or hippocampus induced similar habitual seizures. Seizure-induced in the hippocampus rapidly recruited the thalamus. Evoked potentials demonstrated stronger connectivity from the hippocampus to the thalamus than in the opposite direction. The midline thalamus can be within the seizure initiation and symptomatogenic circuits.

neuroscience↗