A novel GLM-based method for the Automatic IDentification of functional Events (AIDE) in fNIRS data recorded in naturalistic environments.

Recent technological advances have allowed the development of portable functional Near-Infrared Spectroscopy (fNIRS) devices that can be used to perform neuroimaging in the real-world. However, as real-world experiments are designed to mimic everyday life situations, the identification of event onsets can be extremely challenging and time-consuming. Here, we present a novel analysis method based on the general linear model (GLM) least square fit analysis for the Automatic IDentification of functional Events (or AIDE) directly from real-world fNIRS neuroimaging data. In order to investigate the accuracy and feasibility of this method, as a proof-of-principle we applied the algorithm to (i) synthetic fNIRS data simulating both block-, event-related and mixed-design experiments and (ii) experimental fNIRS data recorded during a conventional lab-based task (involving maths). AIDE was able to recover functional events from simulated fNIRS data with an accuracy of 89%, 97% and 91% for the simulated block-, event-related and mixed-design experiments respectively. For the lab-based experiment, AIDE recovered more than the 66.7% of the functional events from the fNIRS experimental measured data. To illustrate the strength of this method, we then applied AIDE to fNIRS data recorded by a wearable system on one participant during a complex real-world prospective memory experiment conducted outside the lab. As part of the experiment, there were four and six events (actions where participants had to interact with a target) for the two different conditions respectively (condition 1: social-interact with a person; condition 2: non-social-interact with an object). AIDE managed to recover 3/4 events and 3/6 events for conditions 1 and 2 respectively. The identified functional events were then corresponded to behavioural data from the video recordings of the movements and actions of the participant. Our results suggest that "brain-first" rather than "behaviour-first" analysis is possible and that the present method can provide a novel solution to analyse real-world fNIRS data, filling the gap between real-life testing and functional neuroimaging

Using fiberless, wearable fNIRS to monitor brain activity in real-world cognitive tasks

Functional Near Infrared Spectroscopy (fNIRS) is a neuroimaging technique that uses near-infrared light to monitor brain activity. Based on neurovascular coupling, fNIRS is able to measure the haemoglobin concentration changes secondary to neuronal activity. Compared to other neuroimaging techniques, fNIRS represents a good compromise in terms of spatial and temporal resolution. Moreover, it is portable, lightweight, less sensitive to motion artifacts and does not impose significant physical restraints. It is therefore appropriate to monitor a wide range of cognitive tasks (e.g., auditory, gait analysis, social interaction) and different age populations (e.g., new-borns, adults, elderly people). The recent development of fiberless fNIRS devices has opened the way to new applications in neuroscience research. This represents a unique opportunity to study functional activity during real-world tests, which can be more sensitive and accurate in assessing cognitive function and dysfunction than lab-based tests. This study explored the use of fiberless fNIRS to monitor brain activity during a real-world prospective memory task. This protocol is performed outside the lab and brain haemoglobin concentration changes are continuously measured over the prefrontal cortex while the subject walks around in order to accomplish several different tasks

HDAC6 mediates the acetylation of TRIM50

The E3 Ubiquitin ligase TRIM50 promotes the formation and clearance of aggresome-associated polyubiquitinated proteins through HDAC6 interaction, a tubulin specific deacetylase that regulates microtubule-dependent aggresome formation. In this report we showed that TRIM50 is a target of HDAC6 with Lys-372 as a critical residue for acetylation. We identified p300 and PCAF as two TRIM50 acetyltransferases and we further showed that a balance between ubiquitination and acetylation regulates TRIM50 degradatio

Thermographic imaging in sports and exercise medicine: A Delphi study and consensus statement on the measurement of human skin temperature

This is an accepted manuscript of an article published by Elsevier in Journal of Thermal Biology on 18/07/2017, available online: https://doi.org/10.1016/j.jtherbio.2017.07.006 The accepted version of the publication may differ from the final published version.© 2017 Elsevier Ltd The importance of using infrared thermography (IRT) to assess skin temperature (tsk) is increasing in clinical settings. Recently, its use has been increasing in sports and exercise medicine; however, no consensus guideline exists to address the methods for collecting data in such situations. The aim of this study was to develop a checklist for the collection of tsk using IRT in sports and exercise medicine. We carried out a Delphi study to set a checklist based on consensus agreement from leading experts in the field. Panelists (n  =  24) representing the areas of sport science (n = 8; 33%), physiology (n = 7; 29%), physiotherapy (n = 3; 13%) and medicine (n = 6; 25%), from 13 different countries completed the Delphi process. An initial list of 16 points was proposed which was rated and commented on by panelists in three rounds of anonymous surveys following a standard Delphi procedure. The panel reached consensus on 15 items which encompassed the participants’ demographic information, camera/room or environment setup and recording/analysis of tsk using IRT. The results of the Delphi produced the checklist entitled “Thermographic Imaging in Sports and Exercise Medicine (TISEM)” which is a proposal to standardize the collection and analysis of tsk data using IRT. It is intended that the TISEM can also be applied to evaluate bias in thermographic studies and to guide practitioners in the use of this technique.Published versio

Comparison of Transcranial Magnetic Stimulation Dosimetry between Structured and Unstructured Grids Using Different Solvers

In recent years, the interest in transcranial magnetic stimulation (TMS) has surged, necessitating deeper understanding, development, and use of low-frequency (LF) numerical dosimetry for TMS studies. While various ad hoc dosimetric models exist, commercial software tools like SimNIBS v4.0 and Sim4Life v7.2.4 are preferred for their user-friendliness and versatility. SimNIBS utilizes unstructured tetrahedral mesh models, while Sim4Life employs voxel-based models on a structured grid, both evaluating induced electric fields using the finite element method (FEM) with different numerical solvers. Past studies primarily focused on uniform exposures and voxelized models, lacking realism. Our study compares these LF solvers across simplified and realistic anatomical models to assess their accuracy in evaluating induced electric fields. We examined three scenarios: a single-shell sphere, a sphere with an orthogonal slab, and a MRI-derived head model. The comparison revealed small discrepancies in induced electric fields, mainly in regions of low field intensity. Overall, the differences were contained (below 2% for spherical models and below 12% for the head model), showcasing the potential of computational tools in advancing exposure assessment required for TMS protocols in different bio-medical applications

The coordination of cell growth during fission yeast mating requires Ras1-GTP hydrolysis

The spatial and temporal control of polarity is fundamental to the survival of all organisms. Cells define their polarity using highly conserved mechanisms that frequently rely upon the action of small GTPases, such as Ras and Cdc42. Schizosaccharomyces pombe is an ideal system with which to study the control of cell polarity since it grows from defined tips using Cdc42-mediated actin remodeling. Here we have investigated the importance of Ras1-GTPase activity for the coordination of polarized cell growth during fission yeast mating. Following pheromone stimulation, Ras1 regulates both a MAPK cascade and the activity of Cdc42 to enable uni-directional cell growth towards a potential mating partner. Like all GTPases, when bound to GTP, Ras1 adopts an active conformation returning to an inactive state upon GTP-hydrolysis, a process accelerated through interaction with negative regulators such as GAPs. Here we show that, at low levels of pheromone stimulation, loss of negative regulation of Ras1 increases signal transduction via the MAPK cascade. However, at the higher concentrations observed during mating, hyperactive Ras1 mutations promote cell death. We demonstrate that these cells die due to their failure to coordinate active Cdc42 into a single growth zone resulting in disorganized actin deposition and unsustainable elongation from multiple tips. These results provide a striking demonstration that the deactivation stage of Ras signaling is fundamentally important in modulating cell polarity

Design and operation of a femtosecond micro-CARS experimental apparatus

La spettroscopia Raman consente di misurare mappe vibrazionali di campioni con alta risoluzione spaziale, utili per l’identificazione di composti chimici senza l’utilizzo di marcatori. In generale però, le tecniche di Raman spontaneo soffrono di alcuni svantaggi, principalmente dovuti ai bassi livelli di segnale e alla eventuale presenza di segnali di fluorescenza, che possono limitarne l’applicabilità. Per contro, le tecniche di Raman coerente, come ad esempio la diffusione Raman Anti-Stokes coerente (CARS), sfruttando la nonlinearità dell’interazione tra luce di sonda e campione, permettono di superare i limiti sopra descritti, e per questa ragione sono ampiamente utilizzate nonostante la maggior complessità e il costo dell’apparato sperimentale. D’altronde, negli ultimi venti anni, la grande diffusione di oscillatori laser a impulsi ultracorti e la disponibilità di fibre a cristalli fotonici per la generazione di luce bianca coerente hanno facilitato lo sviluppo di microscopi CARS a bassa energia di eccitazione e tempi di acquisizione brevi, che sono di particolare utilità in campo biologico e biomedico. In questo rapporto tecnico, dopo un breve richiamo alle caratteristiche della spettroscopia CARS al femtosecondo, viene descritto il microspettrometro CARS realizzato nel C. R. Casaccia nell’ambito di un progetto ENEA inter-dipartimentale. Inoltre, vengono riportati e discussi i risultati sperimentali ottenuti durante i primi due anni di operatività del sistema.Raman spectroscopy allows the measurement of vibrational maps of samples with high spatial resolution, useful for the identification of chemical compounds without the use of labels. In general, however, spontaneous Raman techniques suffer from some disadvantages, mainly due to low signal levels and the possible presence of fluorescence signals, which can limit their applicability. On the other hand, coherent Raman techniques, such as Coherent Anti-Stokes Raman Scattering (CARS), exploiting the nonlinearity of the interaction between probe and sample light, permit to overcome the limits described above, and for this reason they are widely used despite the greater complexity and cost of the experimental apparatus. On the other hand, in the last twenty years, the great diffusion of ultrashort pulse laser oscillators and the availability of photonic crystal fibers for the generation of coherent white light have facilitated the development of CARS microscopes with low excitation energy and short acquisition times, which are particularly useful in the biological and biomedical fields. In this technical report, after a brief reference to the characteristics of the femtosecond CARS spectroscopy, the CARS microspectrometer made in C. R. Casaccia in the framework of an inter-departmental ENEA project is described. Furthermore, the experimental results obtained during the first two years of operation of the system are reported and discussed

COVID-19 Accelerated Cognitive Decline in Elderly Patients with Pre-Existing Dementia Followed up in an Outpatient Memory Care Facility

Introduction: Coronavirus disease 2019 (COVID-19) may affect the cognitive function and activities of daily living (ADL) of elderly patients. This study aimed to establish the COVID-19 effect on cognitive decline and the velocity of cognitive function and ADL changes in elderly patients with dementia followed up in an outpatient memory care facility. Methods: In total, 111 consecutive patients (age 82 ± 5 years, 32% males) with a baseline visit before infection were divided into those who had or did not have COVID-19. Cognitive decline was defined as a five-point loss of Mini-Mental State Examination (MMSE) score and ADL comprising basic and instrumental ADL indexes (BADL and IADL, respectively). COVID-19 effect on cognitive decline was weighted for confounding variables by the propensity score, whereas the effect on change in the MMSE score and ADL indexes was analyzed using multivariate mixed-effect linear regression. Results: COVID-19 occurred in 31 patients and a cognitive decline in 44. Cognitive decline was about three and a half times more frequent in patients who had COVID-19 (weighted hazard ratio 3.56, 95% confidence interval 1.50–8.59, p = 0.004). The MMSE score lowered on average by 1.7 points/year, independently of COVID-19, but it lowered twice faster in those who had COVID-19 (3.3 vs. 1.7 points/year, respectively, p < 0.050). BADL and IADL indexes lowered on average less than 1 point/year, independently of COVID-19 occurrence. Patients who had COVID-19 had a higher incidence of new institutionalization than those who did not have the disease (45% versus 20%, p = 0.016, respectively). Conclusions: COVID-19 had a significant impact on cognitive decline and accelerated MMSE reduction in elderly patients with dementia

Exposure of the SH-SY5Y Human Neuroblastoma Cells to 50-Hz Magnetic Field: Comparison Between Two-Dimensional (2D) and Three-Dimensional (3D) In Vitro Cultures

We here characterize the response to the extremely low-frequency (ELF) magnetic field (MF, 50 Hz, 1 mT) of SH-SY5Y human neuroblastoma cells, cultured in a three-dimensional (3D) Alvetex® scaffold compared to conventional two-dimensional (2D) monolayers. We proved that the growing phenotype of proliferating SH-SY5Y cells is not affected by the culturing conditions, as morphology, cell cycle distribution, proliferation/differentiation gene expression of 3D-cultures overlap what reported in 2D plates. In response to 72-h exposure to 50-Hz MF, we demonstrated that no proliferation change and apoptosis activation occur in both 2D and 3D cultures. Consistently, no modulation of Ki67, MYCN, CCDN1, and Nestin, of invasiveness and neo-angiogenesis-controlling genes (HIF-1α, VEGF, and PDGF) and of microRNA epigenetic signature (miR-21-5p, miR-222-3p and miR-133b) is driven by ELF exposure. Conversely, intracellular glutathione content and SOD1 expression are exclusively impaired in 3D-culture cells in response to the MF, whereas no change of such redox modulators is observed in SH-SY5Y cells if grown on 2D monolayers. Moreover, ELF-MF synergizes with the differentiating agents to stimulate neuroblastoma differentiation into a dopaminergic (DA) phenotype in the 3D-scaffold culture only, as growth arrest and induction of p21, TH, DAT, and GAP43 are reported in ELF-exposed SH-SY5Y cells exclusively if grown on 3D scaffolds. As overall, our findings prove that 3D culture is a more reliable experimental model for studying SH-SY5Y response to ELF-MF if compared to 2D conventional monolayer, and put the bases for promoting 3D systems in future studies addressing the interaction between electromagnetic fields and biological systems

ERYTHROPOIETIN FOR THE TREATMENT OF SUBARACHNOID HEMORRAGE: A FEASIBLE INGREDIENT FOR A SUCCESS MEDICAL RECIPE

Subaracnhoid hemorrage (SAH) following aneurysm bleeding accounts for 6% to 8% of all cerebrovascular accidents. Althoug an aneurysm can be effectively managed by surgery or endovascular therapy, delayed cerebral ischemia is diagnosed in a high percentage of patients resulting in significant morbility and mortality. Cerebral vasospasm occurs in more than half of all patients after aneurysm rupture and is recognized as the leading cause of delayed cerebral ischemia after SAH. Hemodynamic strategies and endovascular procedures may be considered fo the treatment of cerebral vasospasm. In recent years, the mechanism contributing to the development of vasospasm, abnormal reactivity of cerebral arteries and cerebral ischemia following SAH, have been intensively investigated. A number of pathological processes have been identified in the pathogenesis of vasospasm including endothelial injury, smooth muscle cell contraction from spasmogenic substances produced by the subarachnoid blood clots, changes in vascular responsiveness and inflammatory response of the vascular endothelium. to date, the current therapeutic interventions remain ineffective being limited to the manipulation os systemic blood pressure, variation of blood volume and viscosity, and control of arterial carbon dioxide tension. In this scenario, the hormone erythropoietin (EPO), has been found to exert neuroprotective action during experimental SAH when its recombinant form (rHuEPO) is systematically administered. However, recent translation of experimental data into clinical trials has suggested an unclear role of recombinant human EPO in the setting of SAH. In this context, the aim of the recurrent review is to present current evidence on the potential role of EPO in cerebrovascular dysfunction following aneurysmal subarachnoid hemorrage