Neuroimaging of human motor control in real world scenarios: from lab to urban environment

The main goal of this research programme was to explore the neurophysiological correlates of human motor control in real-world scenarios and define mechanism-specific markers that could eventually be employed as targets of novel neurorehabilitation practice. As a result of recent developments in mobile technologies it is now possible to observe subjects' behaviour and monitor neurophysiological activity whilst they perform natural activities freely. Investigations in real-world scenarios would shed new light on mechanisms of human motor control previously not observed in laboratory settings and how they could be exploited to improve rehabilitative interventions for the neurologically impaired. This research programme was focussed on identifying cortical mechanisms involved in both upper- (i.e. reaching) and lower-limb (i.e. locomotion) motor control. Complementary results were obtained by the simultaneous recordings of kinematic, electromyographic and electrocorticographic signals. To study motor control of the upper-limb, a lab­based setup was developed, and the reaching movement of healthy young individuals was observed in both stable and unstable (i.e. external perturbation) situations. Robot-mediated force-field adaptation has the potential to be employed in rehabilitation practice to promote new skills learning and motor recovery. The muscular (i.e. intermuscular couplings) and neural (i.e. spontaneous oscillations and cortico­muscular couplings) indicators of the undergoing adaptation process were all symbolic of adaptive strategies employed during early stages of adaptation. The medial frontal, premotor and supplementary motor regions appeared to be the principal cortical regions promoting adaptive control and force modulation. To study locomotion control, a mobile setup was developed and daily life human activities (i.e. walking while conversing, walking while texting with a smartphone) were investigated outside the lab. Walking in hazardous environments or when simultaneously performing a secondary task has been demonstrated to be challenging for the neurologically impaired. Healthy young adults showed a reduced motor performance when walking in multitasking conditions, during which whole-brain and task-specific neural correlates were observed. Interestingly, the activity of the left posterior parietal cortex was predictive of the level of gait stability across individuals, suggesting a crucial role of this area in gait control and determination of subject specific motor capabilities. In summary, this research programme provided evidence on different cortical mechanisms operative during two specific scenarios for "real­world" motor behaviour in and outside the laboratory-setting in healthy subjects. The results suggested that identification of neuro-muscular indicators of specific motor control mechanisms could be exploited in future "real-world" rehabilitative practice

Resting-state functional connectivity predicts the ability to adapt to robot-mediated force fields

Motor deficits are common outcomes of neurological conditions such as stroke. In order to design personalised motor rehabilitation programmes such as robot-assisted therapy, it would be advantageous to predict how a patient might respond to such treatment. Spontaneous neural activity has been observed to predict differences in the ability to learn a new motor behaviour in both healthy and stroke populations. This study investigated whether spontaneous resting-state functional connectivity could predict the degree of motor adaptation of right (dominant) upper limb reaching in response to a robot-mediated force field. Spontaneous neural activity was measured using resting-state electroencephalography (EEG) in healthy adults before a single session of motor adaptation. The degree of beta frequency (β; 15–25 Hz) resting-state functional connectivity between contralateral electrodes overlying the left primary motor cortex (M1) and the anterior prefrontal cortex (aPFC) could predict the subsequent degree of motor adaptation. This result provides novel evidence for the functional significance of resting-state synchronization dynamics in predicting the degree of motor adaptation in a healthy sample. This study constitutes a promising first step towards the identification of patients who will likely gain most from using robot-mediated upper limb rehabilitation training based on simple measures of spontaneous neural activity

An integrated peptidomics and in silico approach to identify novel anti-diabetic peptides in parmigiano-reggiano cheese

Inhibition of key metabolic enzymes linked to type-2-diabetes (T2D) by food-derived compounds is a preventive emerging strategy in the management of T2D. Here, the impact of Parmigiano- Reggiano (PR) cheese peptide fractions, at four different ripening times (12, 18, 24, and 30 months), on the enzymatic activity of α-glucosidase, α-amylase, and dipeptidyl peptidase-IV (DPPIV) as well as on the formation of fluorescent advanced glycation end-products (fAGEs) was assessed. The PR peptide fractions were able to inhibit the selected enzymes and fAGEs formation. The 12-month-ripening PR sample was the most active against the three enzymes and fAGEs. Mass spectrometry analysis enabled the identification of 415 unique peptides, 54.9% of them common to the four PR samples. Forty-nine previously identified bioactive peptides were found, mostly characterized as angiotensin-converting enzyme-inhibitors. The application of an integrated approach that combined peptidomics, in silico analysis, and a structure–activity relationship led to an efficient selection of 6 peptides with potential DPP-IV and α-glucosidase inhibitory activities. Peptide APFPE was identified as a potent novel DPP-IV inhibitor (IC50 = 49.5 ± 0.5 μmol/L). In addition, the well-known anti-hypertensive tripeptide, IPP, was the only one able to inhibit the three digestive enzymes, highlighting its possible new and pivotal role in diabetes management

Exploring the potential of NIR hyperspectral imaging for automated quantification of rind amount in grated Parmigiano Reggiano cheese

Parmigiano Reggiano (P-R) is one of the most important Italian food products labelled with Protected Designation of Origin (PDO). The PDO denomination is applied also to grated P-R cheese products meeting the requirements regulated by the Specifications of Parmigiano Reggiano Cheese. Different quality parameters are monitored, including the percentage of rind, which is edible and should not exceed the limit of 18% (w/w). The present study aims at evaluating the possibility of using near infrared hyperspectral imaging (NIR-HSI) to quantify the rind percentage in grated Parmigiano Reggiano cheese samples in a fast and non-destructive manner. Indeed, NIR-HSI allows the simultaneous acquisition of both spatial and spectral information from a sample, which is more suitable than classical single-point spectroscopy for the analysis of heterogeneous samples like grated cheese. Hyperspectral images of grated P-R cheese samples containing increasing levels of rind were acquired in the 900–1700 nm spectral range. Each hyperspectral image was firstly converted into a one-dimensional signal, named hyperspectrogram, which codifies the relevant information contained in the image. Then, the matrix of hyperspectrograms was used to calculate a calibration model for the prediction of the rind percentage using Partial Least Squares (PLS) regression. The calibration model was validated considering two external test sets of samples, confirming the effectiveness of the proposed approach

Evaluation of the effect of factors related to preparation and composition of grated Parmigiano Reggiano cheese using NIR hyperspectral imaging

The present study is focused on the evaluation of the effect of grater type and fat content of the pulp on the spectral response obtained by near infrared hyperspectral imaging (NIR-HSI), when this technique is used to determine the rind percentage in Parmigiano Reggiano (P-R) cheese. To this aim, grated P-R cheese samples were prepared considering all the possible combinations between three levels of rind amount (8%, 18% and 28%), two levels of fat content of the pulp and two different grater types, and the corresponding hyperspectral images were acquired in the 900–1700 nm spectral range. In a first step, the average spectrum (AS) was calculated from each hyperspectral image, and the corresponding dataset was analysed by means of Analysis of Variance Simultaneous Component Analysis (ASCA) to assess the effect of the three considered factors and their two-way interactions on the spectral response. Then, the hyperspectral images were converted into Common Space Hyperspectrograms (CSH), which are signals obtained by merging in sequence the frequency distribution curves of quantities calculated from a Principal Component Analysis (PCA) model common to the whole hyperspectral image dataset. ASCA was also applied to the CSH dataset, in order to evaluate the effect of the considered factors on this kind of signals. Generally, all the three factors resulted to have a significant effect, but with a different extent according to the method used to analyse the hyperspectral images. Indeed, while fat content of the pulp and rind percentage showed a comparable effect on the spectral response of AS dataset, in the case of CSH signals rind percentage had a greater effect compared to the other main factors. However, CSH were also more sensitive to differences ascribable to the natural variability between diverse Parmigiano Reggiano cheese samples

Characterization of yeasts isolated from parmigiano reggiano cheese natural whey starter: From spoilage agents to potential cell factories for whey valorization

Whey is the main byproduct of the dairy industry and contains sugars (lactose) and proteins (especially serum proteins and, at lesser extent, residual caseins), which can be valorized by the fermentative action of yeasts. In the present study, we characterized the spoilage yeast population inhabiting natural whey starter (NWS), the undefined starter culture of thermophilic lactic acid bacteria used in Parmigiano Reggiano (PR) cheesemaking, and evaluated thermotolerance, mating type, and the aptitude to produce ethanol and bioactive peptides from whey lactose and proteins, respectively, in a selected pool of strains. PCR-RFLP assay of ribosomal ITS regions and phylogenetic analysis of 26S rDNA D1/D2 domains showed that PR NWS yeast population consists of the well-documented Kluyveromyces marxianus, as well as of other species (Saccharomyces cerevisiae, Wickerhamiella pararugosa, and Torulaspora delbrueckii), with multiple biotypes scored within each species as demonstrated by (GTG)5-based MSP-PCR. Haploid and diploid K. marxianus strains were identified through MAT genotyping, while thermotolerance assay allowed the selection of strains suitable to grow up to 48◦C. In whey fermentation trials, one thermotolerant strain was suitable to release ethanol with a fermentation efficiency of 86.5%, while another candidate was able to produce the highest amounts of both ethanol and bioactive peptides with potentially anti-hypertensive function. The present work demonstrated that PR NWS is a reservoir of ethanol and bioactive peptides producer yeasts, which can be exploited to valorize whey, in agreement with the principles of circularity and sustainability

Peptide profiling and biological activities of 12- month ripened parmigiano reggiano cheese

Proteolysis degree, biological activities, and water-soluble peptide patterns were evaluated in 12 month-ripened Parmigiano Reggiano (PR) cheeses collected in different dairy farms and showing different salt and fat content. Samples classified in high-salt and high-fat group (HH) generally showed lower proteolysis degree than samples having low-salt and low-fat content (LL). This positive correlation between salt/fat reduction and proteolysis was also confirmed by the analysis of biological activities, as the LL group showed higher average values of angiotensin-converting enzyme (ACE)-inhibitory and antioxidant activities. UHPLC/HR-MS allowed the identification of 805 unique peptides: LL and HH groups shared 59.3% of these peptides, while 20.9% and 19.9% were LL and HH specific, respectively. Frequency analysis of peptides identified a core of 183 peptides typical of 12-month ripened PR cheeses (corresponding to the 22.7% of total peptides), but no significant differences were detected in peptide patterns between LL and HH groups. Forty bioactive peptides, including 18 ACE-inhibitors and 12 anti-microbial peptides, were identified, of which 25 firstly found in PR cheese. Globally, this work contributed to unraveling the potentially healthy benefits of peptides fraction in PR cheese and provided prior evidence that PR with reduced at/salt content showed the highest antihypertensive and antioxidant activities

Data and performances evaluation of the SPIDIA-DNA Pan-European External Quality Assessment: 2nd SPIDIA-DNA laboratory report.

AbstractWithin the EU-SPIDIA project (www.spidia.eu), the quality parameters of blood genomic DNA were defined [SPIDIA-DNA: an External Quality Assessment for the pre-analytical phase of blood samples used for DNA-based analyses – [1]; Influence of pre-analytical procedures on genomic DNA integrity in blood samples: the SPIDIA experience – [2]; Combining qualitative and quantitative imaging evaluation for the assessment of genomic DNA integrity: the SPIDIA experience – [3]. DNA quality parameters were used to evaluate the laboratory performance within an External Quality Assessment (EQA) [Second SPIDIA-DNA External Quality Assessment (EQA): Influence of pre-analytical phase of blood samples on genomic DNA quality – [4]. These parameters included DNA purity and yield by UV spectrophotometric measurements, the presence of PCR interferences by Kineret software and genomic DNA integrity analysis by Pulsed Field Gel Electrophoresis.Here we present the specific laboratory report of the 2nd SPIDIA-DNA EQA as an example of data and performances evaluation

Tracing the identity of Parmigiano Reggiano “Prodotto di Montagna - Progetto Territorio” cheese using NMR spectroscopy and multivariate data analysis

Background Nuclear magnetic resonance (NMR) spectroscopy is one of the well-established tools for food metabolomic analysis, as it proved to be very effective in authenticity and quality control of dairy products, as well as to follow product evolution during processing and storage. The analytical assessment of the EU mountain denomination label, specifically for Parmigiano Reggiano "Prodotto di Montagna - Progetto Territorio" (Mountain-CQ) cheese, has received limited attention. Although it was established in 2012 the EU mountain denomination label has not been much studied from an analytical point of view. Nonetheless, tracing a specific profile for the mountain products is essential to support the value chain of this specialty. Results The aim of the study was to produce an identity profile for Parmigiano Reggiano “Prodotto di Montagna - Progetto Territorio” (Mountain-CQ) cheese, and to differentiate it from Parmigiano Reggiano PDO samples (conventional-PDO) using 1H NMR spectroscopy coupled with multivariate data analysis. Three different approaches were applied and compared. First, the spectra-as-such were analysed after proper preprocessing. For the other two approaches, Multivariate Curve Resolution-Alternating Least Squares (MCR-ALS) was used for signals resolution and features extraction, either individually on manually-defined spectral intervals or by reapplying MCR-ALS on the whole spectra with selectivity constraints using the reconstructed “pure profiles” as initial estimates and targets. All approaches provided comparable information regarding the samples’ distribution, as in all three cases the separation between the two product categories conventional-PDO and Mountain-CQ could be highlighted. Moreover, a novel MATLAB toolbox for features extraction via MCR-ALS was developed and used in synergy with the Chenomx library, allowing for a putative identification of the selected features. Significance A first identity profile for Parmigiano Reggiano “Prodotto di Montagna - Progetto Territorio” obtained by interpreting the metabolites signals in NMR spectroscopy was obtained. Our workflow and toolbox for generating the features dataset allows a more straightforward interpretation of the results, to overcome the limitations due to dimensionality and to peaks overlapping, but also to include the signals assignment and matching since the early stages of the data processing and analysis

First presentation of LPIN1 acute rhabdomyolysis in adolescence and adulthood

LPIN1 mutations are a known common cause of autosomal recessive, recurrent and life-threatening acute rhabdomyolysis of childhood-onset. The first episode of rhabdomyolysis usually happens in nearly all cases before the age of 5 and death is observed in 1/3 of patients. Here we present two cases of acute rhabdomyolysis with a milder phenotype caused by LPIN1 mutation presenting in adolescence (11 years old) and adulthood (40 years old) after Parvovirus infection and metabolic stress, respectively. In our opinion, the mutation types, epigenetic factors, the environment exposition to triggers or the existence of proteins with a similar structure of LPIN1, may have a role in modulating the onset of rhabdomyolysis. LPIN1 should be included on a panel of genes analysed in the investigation of adult individuals with rhabdomyolysis. Metabolic and viral stressors should be included in the list of possible rhabdomyolysis precipitant