LFP Analysis of Brain Injured Anesthetized Animals Undergoing Closed-Loop Intracortical Stimulation.

Activity dependent stimulation (ADS) is a closed loop stimulation technique whose neurophysiological effects have not been deeply investigated. Here we explored how Local field Potentials (LFP) are impacted by a focal ischemic lesion and, subsequently, by ADS treatment. Intracortical microelectrode arrays were implanted in the rostral forelimb area (RFA) and in the primary somatosensory area (S1) of anaesthetized rats. An ischemic injury was induced in the caudal forelimb area through microinjections of Endothelin-1. The lesion induced an acute depressive trend in LFP power in RFA (evaluated in 6 bands of interest: Delta (1-4Hz), Theta (4-8Hz), Alpha (8-11Hz), Beta (11-30Hz), LowGamma (30-55Hz) and HighGamma (55-80)) followed by a noticeable significant rebound in both areas. Applying ADS induced an overall decrease of power. The lesion impacted the connectivity in a frequency specific manner, resulting in widespread increase in connectivity in Delta both between and within areas. Two hours after the lesion, without stimulation, correlated activity between areas increased in Beta and Gamma. After stimulation, inter-area connectivity increased in Delta, Theta and Alpha, while considerably dropping within RFA in highGamma. By computing phase-amplitude coupling, we found that the lesion produced an incremental increase in the coupling between (Theta) Alpha phase and (lowGamma) highGamma amplitude within RFA, while S1 had a more generalized increase. Likewise, coupling between Theta phase and lowGamma/highGamma amplitudes increased between areas after lesion. ADS induced a similar increase, but greater in magnitude both within and between RFA and S1. These results have important implications on the emerging field of closed-loop adaptive stimulation promoting ADS as an innovative tool for the treatment of neurological disorders

'Mindful eating' for reducing emotional eating in patients with overweight or obesity in Primary Care settings : A randomized controlled trial

Objective: The primary aim of this study was to analyse the efficacy of a 'mindful eating' program for reducing emotional eating in patients with overweight or obesity. Method: A cluster randomized controlled trial (reg. NCT03927534) was conducted with 76 participants with overweight/obesity who were assigned to 'mindful eating' + treatment as usual (TAU), or to TAU alone. They were assessed at baseline, posttreatment and 12-month follow-up. The main outcome was 'emotional eating' (Dutch Eating Behavior Questionnaire, DEBQ); other eating behaviours were also assessed along with psychological and physiological variables. Results: 'Mindful eating' + TAU reduced emotional eating both at posttreatment (B=-0.27; p=.006; d=0.35) and follow-up (B=-0.53; p< .001; d=0.69). 'External eating' (DEBQ) was also significantly improved by the intervention at both timepoints. Significant effects at follow-up were observed for some secondary outcomes related to bulimic behaviours, mindful eating, mindfulness, and self-compassion. Weight and other physiological parameters were not significantly affected by 'mindful eating' + TAU. Conclusions: These findings support the efficacy of the 'mindful eating' + TAU program for reducing emotional and external eating, along with some other secondary measures, but no significant changes in weight reduction were appreciated

Vaccine effectiveness against symptomatic SARS-CoV-2 infection in adults aged 65 years and older in primary care: I-MOVE-COVID-19 project, Europe, December 2020 to May 2021

I-MOVE-COVID-19 primary care study team (in addition to authors above): Nick Andrews, Jamie Lopez Bernal, Heather Whitaker, Caroline Guerrisi, Titouan Launay, Shirley Masse, Sylvie van der Werf, Vincent Enouf, John Cuddihy, Adele McKenna, Michael Joyce, Cillian de Gascun, Joanne Moran, Ana Miqueleiz, Ana Navascués, Camino Trobajo-Sanmartín, Carmen Ezpeleta, Paula López Moreno, Javier Gorricho, Eva Ardanaz, Fernando Baigorria, Aurelio Barricarte, Enrique de la Cruz, Nerea Egüés, Manuel García Cenoz, Marcela Guevara, Conchi Moreno-Iribas, Carmen Sayón, Verónica Gomez, Baltazar Nunes, Rita Roquete, Adriana Silva, Aryse Melo, Inês Costa, Nuno Verdasca, Patrícia Conde, Diogo FP Marques, Anna Molesworth, Leanne Quinn, Miranda Leyton, Selin Campbell, Janine Thoulass, Jim McMenamin, Ana Martínez Mateo, Luca Basile, Daniel Castrillejo, Carmen Quiñones Rubio, Concepción Delgado-Sanz, Jesús Oliva.The I-MOVE-COVID-19 network collates epidemiological and clinical information on patients with coronavirus disease (COVID-19), including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virological characterisation in 11 European countries [1]. One component of I-MOVE-COVID-19 is the multicentre vaccine effectiveness (VE) study at primary care/outpatient level in nine European study sites in eight countries. We measured overall and product-specific COVID-19 VE against symptomatic SARS-CoV-2 infection among those aged 65 years and older. We also measured VE by time since vaccination.This project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 101003673.info:eu-repo/semantics/publishedVersio

Promoting patient utilization of outpatient cardiac rehabilitation: A joint International Council and Canadian Association of Cardiovascular Prevention and Rehabilitation position statement

Background: Cardiac Rehabilitation (CR) is a recommendation in international clinical practice guidelines given its’ benefits, however use is suboptimal. The purpose of this position statement was to translate evidence on interventions that increase CR enrolment and adherence into implementable recommendations. Methods: The writing panel was constituted by representatives of societies internationally concerned with preventive cardiology, and included disciplines that would be implementing the recommendations. Patient partners served, as well as policy-makers. The statement was developed in accordance with AGREE II, among other guideline checklists. Recommendations were based on our update of the Cochrane review on interventions to promote patient utilization of CR. These were circulated to panel members, who were asked to rate each on a 7-point Likert scale in terms of scientific acceptability, actionability, and feasibility of assessment. A web call was convened to achieve consensus and confirm strength of the recommendations (based on GRADE). The draft underwent external review and public comment. Results: The 3 drafted recommendations were that to increase enrolment, healthcare providers, particularly nurses (strong), should promote CR to patients face-to-face (strong), and that to increase adherence part of CR could be delivered remotely (weak). Ratings for the 3 recommendations were 5.95±0.69 (mean ± standard deviation), 5.33±1.12 and 5.64±1.08, respectively. Conclusions: Interventions can significantly increase utilization of CR, and hence should be widely applied. We call upon cardiac care institutions to implement these strategies to augment CR utilization, and to ensure CR programs are adequately resourced to serve enrolling patients and support them to complete programs

Investigating the impact of novel personalized neurostimulation strategies to promote recovery after brain lesions

Nowadays, non-communicable diseases represents the 80\% of the top ten causes of death worldwide. Among these disorders, stroke is the second leading cause of death and disability. Current assistive technology is limited and only a minority of survivors are able to achieve functional independence in simple activities of daily living. Thus, understanding the impact of a lesion on the brain networks and promoting functional and behavioral recovery has become a global priority in healthcare. The standard-of-care for post-stroke rehabilitation is physical therapy but its effects are often limited or incomplete. To this end, research is exploring innovative approaches, such as the ‘electroceutical’ one. Recent studies have shown how brain stimulation could enhance functions after stroke in both animals and patients. These studies have used electrical stimulation patterns that are ‘adapted’ (i.e., personalized) to the intrinsic dynamics of the networks under examination, primarily through two different modalities, i.e., open loop and closed loop. By using personalized stimulation is possible to: (i) promote both plasticity and motor recovery, as in the case of stroke or traumatic brain injury –TBI; (ii) block the pathological activity and promote the physiological one within the damaged tissue, as in the case of Parkinson's disease or epilepsy; (iii) ‘entrain’ the network under examination and facilitate motor responses. Most of these studies focused mainly on motor recovery but not on the evaluation of functional reorganization and on the possible changes in electrophysiological activity of the involved networks. Recent results demonstrated the capabilities of Activity-Dependent stimulation (i.e., ADS), a closed loop approach, to better entrain network activity with respect to standard open loop random stimulation. Currently, at the clinical level, stimulation-based therapy relies on standardized protocols with not always convincing results. A possible explanation for these inconsistent outcomes is the lack of a stimulation protocol ‘tailored’ on the intrinsic dynamics of the target system. \textit{Objective}. This study aims at going beyond the state of the art and improving current neuromodulation techniques by customizing electrical stimulation on the electrophysiological features of the individual to be treated. Specifically, we aim at investigating possible changes in electrophysiological activity induced by a focal lesion in animal models in-vivo and the subsequent effect of a personalized, open loop stimulation protocol, on both behavior and functions. Thus, this PhD work has the following three main sub-goals: 1) to investigate the effects of an ischemic lesion in anesthetized rats; 2) to design and characterize the short-term effects of novel personalized neurostimulation techniques on neural activity in anesthetized rats; 3) to investigate the effects of a prolonged personalized stimulation protocol on both neural activity and behavior of injured awake animals. \textit{Approach}. We used Long Evans rats implanted in the Rostral Forelimb Area (i.e., RFA, equivalent of the pre-motor cortex in the rat) and in the Somatosensory cortex (i.e., S1). An ischemic lesion was performed in the equivalent of motor cortex (i.e., CFA) by means of a local injection of Endothelin-1. Firstly, we evaluated the effect of the lesion on anesthetized animals in which we tested novel personalised stimulation protocols that we developed by following an open-loop paradigm. The personalization was achieved by designing a stimulation pattern, which reproduced the intrinsic dynamics of a target area. To design the personalized stimulation, we processed the healthy spontaneous activity of a selected channel in the rostral forelimb area (RFA) with one of the following methods: i) Exponential Stimulation: we designed a new spike sequence with some features of the network of reference, according to a pre-defined/mathematical distribution, e.g. exponential distribution. ii) Repeated Stimulation: by following a ‘replay’ and ‘repeat’ strategy, we created a stimulation pattern based on what was recorded during spontaneous activity; iii) Shuffled Stimulation: we generated a new spike sequence according to a data-driven ISI, based on data acquired from the network under experiment. \textit{Main results}. We found that the lesion had a clear-cut effect on decreasing the spontaneous activity at the two monitored locations. In anesthetized animals, the personalized open-loop (i.e., repeated stimulation and shuffled stimulation) protocols showed a tendency to increase the level of spiking activity. These results are in line with the effects induced by a closed loop paradigm named Activity Dependent Stimulation, which demonstrated to be effective in promoting the post-lesion recovery. We can then conclude that non-periodic, tailored stimulation might be the key to restore the firing patterns in the damaged brain. Moreover, we also found that repeated stimulation treatment enhanced motor recovery in behaving animals. \textit{Significance}. These results have the potential to lead novel neurostimulation techniques for treating neurological diseases, thus opening up the possibility of translating the personalized electroceutical therapy to the clinical level