Background and Purpose
N‐Acylethanolamine acid amidase (NAAA) is a lysosomal enzyme accountable for the breakdown of N‐acylethanolamines (NAEs) and its pharmacological inhibition has beneficial ...effects in inflammatory conditions. The knowledge of NAAA in cancer is fragmentary with an unclarified mechanism, whereas its contribution to colorectal cancer (CRC) is unknown to date.
Experimental Approach
CRC xenograft and azoxymethane models were used to assess the in vivo effect of NAAA inhibition. Further, the tumour secretome was evaluated by an oncogenic array, CRC cell lines were used for in vitro studies, cell cycle was analysed by cytofluorimetry, NAAA was knocked down with siRNA, human biopsies were obtained from surgically resected CRC patients, gene expression was measured by RT‐PCR and NAEs were measured by LC–MS.
Key Results
The NAAA inhibitor AM9053 reduced CRC xenograft tumour growth and counteracted tumour development in the azoxymethane model. NAAA inhibition affected the composition of the tumour secretome inhibiting the expression of EGF family members. In CRC cells, AM9053 reduced proliferation with a mechanism mediated by PPAR‐α and TRPV1. AM9053 induced cell cycle arrest in the S phase associated with cyclin A2/CDK2 down‐regulation. NAAA knock‐down mirrored the effects of NAAA inhibition with AM9053. NAAA expression was down‐regulated in human CRC tissues, with a consequential augmentation of NAE levels and dysregulation of some of their targets.
Conclusion and Implications
Our results show novel data on the functional importance of NAAA in CRC progression and the mechanism involved. We propose that this enzyme is a valid drug target for the treatment of CRC growth and development.
In recent years, the potential usefulness of cognitive training procedures in normal aging and mild cognitive impairment (MCI) have received increased attention.
The main aim of this study was to ...evaluate the efficacy of the face-to-face cognitive virtual reality rehabilitation system (VRRS) and to compare it to that of face-to-face cognitive treatment as usual for individuals with MCI. Moreover, we assessed the possibility of prolonging the effects of treatment with a telerehabilitation system.
A total of 49 subjects with MCI were assigned to 1 of 3 study groups in a randomized controlled trial design: (a) those who received face-to-face cognitive VRRS (12 sessions of individualized cognitive rehabilitation over 4 weeks) followed by telerehabilitation (36 sessions of home-based cognitive VRRS training, three sessions for week); (b) those who received face-to-face cognitive VRRS followed by at-home unstructured cognitive stimulation (36 sessions of home-based unstructured cognitive stimulation, three sessions for week); and (c) those who received face-to-face cognitive treatment as usual (12 sessions of face-to-face cognitive treatment as usual).
An improvement in memory, language and visuo-constructional abilities was observed after the end of face-to-face VRRS treatment compared to face-to-face treatment as usual. The application of home-based cognitive VRRS telerehabilitation seems to induce more maintenance of the obtained gains than home-based unstructured stimulation.
The present study provides preliminary evidence in support of individualized VRRS treatment and telerehabilitation delivery for cognitive rehabilitation and should pave the way for future studies aiming at identifying optimal cognitive treatment protocols in subjects with MCI.
www.ClinicalTrials.gov, identifier NCT03486704.
The identification and staging of Alzheimer's Disease (AD) represent a challenge, especially in the prodromal stage of Mild Cognitive Impairment (MCI), when cognitive changes can be subtle. Worldwide ...efforts were dedicated to select and harmonize available neuropsychological instruments. In Italy, the Italian Network of Neuroscience and Neuro-Rehabilitation has promoted the adaptation of the Uniform Data Set Neuropsychological Test Battery (I-UDSNB), collecting normative data from 433 healthy controls (HC). Here, we aimed to explore the ability of I-UDSNB to differentiate between a) MCI and HC, b) AD and HC, c) MCI and AD.
One hundred thirty-seven patients (65 MCI, 72 AD) diagnosed after clinical-neuropsychological assessment, and 137 HC were included. We compared the I-UDSNB scores between a) MCI and HC, b) AD and HC, c) MCI and AD, with t-tests. To identify the test(s) most capable of differentiating between groups, significant scores were entered in binary logistic and in stepwise regressions, and then in Receiver Operating Characteristic curve analyses.
Two episodic memory tests (Craft Story and Five Words test) differentiated MCI from HC subjects; Five Words test, Semantic Fluency (vegetables), and TMT-part B differentiated AD from, respectively, HC and MCI.
Our findings indicate that the I-UDSNB is a suitable tool for the harmonized and concise assessment of patients with cognitive decline, showing high sensitivity and specificity for the diagnosis of MCI and AD.
Objective: Parkinson's disease (PD) is associated with impairment in producing emotions conveyed by voice which could depend on motor limitations of the vocal apparatus and/or alterations in ...emotional processing. This study explores the relationship between the standard deviation of fundamental frequency (F0SD) of emotional speech and the volume of specific gray matter regions. Method: Fifteen PD patients and 15 healthy controls (HC) were asked to produce different emotions vocally elicited by reading short stories. For each vocal track, the F0SD was calculated as index of variability. All subjects underwent a structural magnetic resonance imaging and a voxel-based morphometry analysis. An ad hoc mask of brain regions implicated in emotional prosody was constructed to test the relationship between F0SD and the level of brain atrophy. Results: PD patients showed lower F0SD values than HC in the expression of anger. Neuroimaging results showed brain atrophy in PD patients in a widespread bilateral network, including frontal areas, left cingulate cortex, parietal areas as well as occipital cortices. In the PD group, a positive correlation was observed between F0SD values of anger and volumes of the bilateral supramarginal gyrus, left thalamus, right inferior frontal gyrus, and amygdala. Conclusions: The lower F0SD values observed in PD patients in anger production are consistent with their lower ability to express anger effectively through voice compared to HC. Our data demonstrated the involvement of right-lateralized areas, such as the inferior frontal gyrus and amygdala, which are typically involved in emotional prosody. Disturbances in emotion processing might contribute to speech production deficits in PD, probably in addition to the motor impairment of the articulatory system.
Key Points
Question: Among acoustic parameters, does fundamental frequency variability correlate with the volume of brain regions involved in emotional prosody? Findings: Patients with Parkinson's disease showed a reduction of fundamental frequency variability in the expression of anger. This parameter is associated with the volume of predominantly right-lateralized areas such as the amygdala and the inferior frontal gyrus, which are typically implicated in the production of emotions by voice. Importance: Deficit in emotional prosody might reduce the ability to express emotions vocally in addition to the motor impairment affecting the vocal apparatus. Next Steps: Future studies should consider more acoustic parameters and explore their association with indices of gray and white matter structural integrity.
Introduction
Parkinson’s disease (PD) is a motor disorder that initially presents with unilateral symptoms. Widespread white matter (WM) alterations have been reported since the early stages of the ...disease. The aim of this study was to investigate WM alterations in right-dominant and left-dominant symptom PD patients (RPD and LPD, respectively) with respect to healthy controls (HC) by diffusion-weighted magnetic resonance imaging (MRI).
Methods
Thirty-eight subjects participated in this study: 12 RPD (median H&Y IQR = 1.5 1.1–2, median UPDRS III IQR = 23 7.8–25), 9 LPD (median H&Y IQR = 1.5 1–2.5, median UPDRS III IQR = 17 12–22), and 17 HC. All the participants were scanned on a 1.5-T MRI scanner. Maps of fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) were computed for all the subjects. Tract-based spatial statistics (TBSS) was performed for each diffusion parameter, to test WM differences between RPD, LPD, and HC (ANCOVA design). Family-wise error (FWE) correction was performed and
p
values lower than 0.05 were considered significant.
Results
No significant FA and RD differences were observed between RPD, LPD, and HC. Significantly increased MD and AD were observed in RPD with respect to HC within widespread WM regions, bilaterally. Conversely, no significant WM alterations were detected in LPD.
Conclusion
WM integrity was found to be significantly altered in RPD but not in LPD, suggesting that LPD profile may be associated to more favorable prognosis. Since clinical laterality onset may affect the extent of WM integrity changes, it should be taken into account in neuroimaging studies investigating PD.
The occurrence of clinically significant changes in empathy is a matter of debate in Alzheimer’s disease (AD). Altered empathic mechanisms observed in AD may be a consequence of cognitive impairment, ...more specifically of reduced mental flexibility and self-regulation. The present study explored possible changes in empathy for subjects in the prodromal phase of AD, namely mild cognitive impairment (MCI) due to AD, and of their neural substrates. Eighteen MCI patients and 20 healthy controls (HC) were included in the study. The Interpersonal Reactivity Index (IRI) questionnaire was administered to each participant. The IRI encompasses four factors: Perspective Taking; Fantasy; Empathic Concern; Personal Distress. MCI patients underwent a magnetic resonance imaging structural examination and were compared to 30 healthy controls (HC-MRI). A limited number of cortical and subcortical regions involved in social cognition was selected as regions of interest (ROIs). MCI individuals obtained lower scores than HC in the Perspective Taking and Fantasy subscales of the IRI, whereas they obtained higher scores on Empathic Concern. Regarding neuroimaging data, a significant correlation emerged between IRI scores and the neural measurements of different regions involved in empathy, especially covering the temporoparietal junction, which is a critical region engaged in both affective and cognitive dimensions of empathy. The results of the present study suggest that a subtle impairment in regulatory mechanisms of empathy may occur very early during the course of AD, possibly as a consequence of neuropathological changes occurring in brain regions involved in social cognition.
Background and purpose
Non-motor impairment such as emotion recognition deficit in both facial and vocal expressions has been previously reported in Parkinson’s disease (PD). We investigated whether ...the decoding of emotional prosody is impaired in PD and whether this deficit is related to striatal damage.
Methods
Fifteen PD patients and 15 healthy controls (HCs) were requested to listen to six audio tracks and to recognize the emotions expressed by a professional actor while reading a meaning-neutral sentence. All subjects also received a structural MRI examination. Volumetric measurements were extracted for the striatum, a key region involved in emotional processing and typically impaired in PD.
Results
Decoding sadness conveyed by voice was impaired in PD compared with HC and was related to the volume of the dorsal striatum bilaterally.
Conclusions
The dorsal striatum is involved in the decoding of vocal negative emotions in PD.
Neuropsychological testing plays a cardinal role in the diagnosis and monitoring of Alzheimer's disease. A major concern is represented by the heterogeneity of the neuropsychological batteries ...currently adopted in memory clinics and healthcare centers. The current study aimed to solve this issue.
Following the initiative of the University of Washington's National Alzheimer's Coordinating Center (NACC), we presented the Italian adaptation of the Neuropsychological Test Battery of the Uniform Data Set (I-UDSNB). We collected data from 433 healthy Italian individuals and employed regression models to evaluate the impact of demographic variables on the performance, deriving the reference norms.
Higher education and lower age were associated with a better performance in the majority of tests, while sex affected only fluency tests and Digit Span Forward.
The I-UDSNB offers a valuable and harmonized tool for neuropsychological testing in Italy, to be used in clinical and research settings.
The presence of Serious Games (SGs) in the medical educational field is spreading due to their beneficial results in terms of learning outcomes and user' engagement. The effectiveness of these tools ...for physical therapy students is, however, still to be proven and prototypes for this user target are lacking. We adopted a user-centered design (UCD) approach to develop and validate a SG on dual task motor and cognitive rehabilitation for junior physical therapists training. The SG development and validation consisted in two phases: a design-evaluation-redesign phase with two groups of junior and senior physiotherapists (group 1, N = 10; group 2, N = 28), and the SG prototype testing phase comparing outcomes of junior physiotherapists in lab (N = 20) and physical therapy students in real context (N = 23). Usability, motivation, flow state, affective engagement and learning were tested. Results showed a high usability of the tool together with good levels of engagement in all groups. Interestingly, we observed a decrease in physiotherapists' negative affect and an increment of students' positive affect after experiencing the prototype. The adoption of the UCD for the validation of a SG on neurorehabilitation allowed the development of a usable and engaging prototype. Future research on SG topics should include a rehabilitation paradigm in their content.
•We validated a serious game on neuromotor rehabilitation for physiotherapists, following a user centered design approach.•Senior and junior physiotherapists and physical therapy students found the serious game engaging and motivating.•The integration of SG to lectures for physiotherapists could increase engagement and participation in training.
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