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Abstract The paper-and-pencil Rey–Osterrieth Complex Figure (ROCF) copy task has been extensively used to assess visuo-constructional skills in children and adults. The scoring systems utilized in clinical practice provide an integrated evaluation of the drawing process, without differentiating between its visuo-constructional, organizational, and motor components. Here, a tablet-based ROCF copy task capable of providing a quantitative assessment of the drawing process, differentiating between visuo-constructional, organizational, and motor skills, is trialed in 94 healthy children, between 7 and 11 years of age. Through previously validated algorithms, 12 indices of performance in the ROCF copy task were obtained for each child. Principal component analysis of the 12 indices identified spatial, procedural, and kinematic components as distinct dimensions of the drawing process. A composite score for each dimension was determined, and correlation analysis between composite scores and conventional paper-and-pencil measures of visuo-constructional, procedural, and motor skills performed. The results obtained confirmed that the constructional, organizational, and motor dimensions underlie complex figure drawing in children; and that each dimension can be measured by a unique composite score. In addition, the composite scores here obtained from children were compared with previsions results from adults, offering a novel insight into how the interplay between the three dimensions of drawing evolves with age.

5′-Phosphorylation of nucleosides is a reaction as important in nature and in industry as it is cumbersome to be performed. Whilst chemical phosphorylation relies on the use of harsh reagents, solvents, and conditions, as well as on the need for protection–deprotection steps, biocatalysis can be a tool to achieve one-step phosphorylation reactions, which are selective, protecting group-free, and occurring under mild and sustainable conditions. In this work, the wild-type non-specific acid phosphatase from Morganella morganii (PhoC-Mm) was expressed, purified, and used for the synthesis of inosine 5′-monophosphate (IMP), an important food additive, by using pyrophosphate (PPi) as an inexpensive phosphate donor in a fully aqueous medium at 30 °C. Via the fine-tuning of the reaction set-up taking into account the type of buffer, amount of PPi, mode/time of PPi addition, and enzyme and substrate concentration, PhoC-Mm could be used for catalyzing the phosphorylation of inosine (I) to IMP in a good yield and high purity (62% yield). The catalysis of the hydrolytic reaction direction, which is the primary function of phosphatases in nature, was here reversed to a certain extent by a reaction engineering approach, without the need for protein engineering strategies.

The β-d-mannopyranoside linkage is found in a number of biological structures, in particular, in the core trisaccharide of N-linked glycoproteins, as well as within the antigenic polysaccharides of Salmonella, yeasts, and glycolipids. The construction of this glycosydic bond by chemical approach is very challenging and requires cumbersome protection and activation steps prior to glycosylation. In this context, β-mannosidase from Cellulomonas fimi (Cf-β-Man) was immobilized for the first time, and it was employed in the synthesis of β-mannosides. Cf-β-Man immobilized on IDA-Co2+-agarose allows the synthesis of the disaccharide, cyanomethyl β-d-mannopyranosyl-(1→6)-2-acetamido-2-deoxy-1-thio-β-d-glucopyranoside, with a higher conversion compared to the soluble enzyme (20% vs. 5%) after 6 h under best conditions. This explorative work opens new scenarios concerning the design of engineered Cf-β-Man mutants and their immobilization in order to obtain a robust and recyclable biocatalyst for applications in chemoenzymatic glycan synthesis.

Keypoints Different monoterpenes can be regioselectively hydroxylated by CYP153A6 monooxygenase The biotransformation with whole cells is complementary to chemical oxyfunctionalization Fed-batch biotransformations have been applied for preparative purposes

Abstract Smoothness (i.e. non-intermittency) of movement is a clinically important property of the voluntary movement with accuracy and proper speed. Resting head position and head voluntary movements are impaired in cervical dystonia. The current work aims to evaluate if the smoothness of voluntary head rotations is reduced in this disease. Twenty-six cervical dystonia patients and 26 controls completed rightward and leftward head rotations. Patients’ movements were differentiated into “towards-dystonia” (rotation accentuated the torticollis) and “away-dystonia”. Smoothness was quantified by the angular jerk and arc length of the spectrum of angular speed (i.e. SPARC, arbitrary units). Movement amplitude (mean, 95% CI) on the horizontal plane was larger in controls (63.8°, 58.3°–69.2°) than patients when moving towards-dystonia (52.8°, 46.3°–59.4°; P = 0.006). Controls’ movements (49.4°/s, 41.9–56.9°/s) were faster than movements towards-dystonia (31.6°/s, 25.2–37.9°/s; P

Abstract Background Instrumental gait analysis in nephrology is widely neglected, although patients with chronic kidney disease (CKD) show brain changes due to cerebrovascular disease and metabolic disorders that can potentially influence gait quality. Our study assesses the association between CKD stages and gait parameters, to understand the prevalent status of brain related gait parameters (i.e. variability) and of performance related parameters (i.e. gait speed, stride length). We hypothesize that gait changes are detectable already in early stages of CKD. Methods Forty-five participants distributed in 5 CKD severity groups underwent an instrumental gait analysis via a triaxial accelerometer affixed to the lower trunk under single- and dual-task conditions. In addition to spatio-temporal parameters, variability and dual-task cost of gait were extracted. A battery of clinical assessments was conducted with the aim of helping to better explain the findings of the gait analysis. A correlation analysis was made to investigate a linear relation between gait parameters and CKD severity. Results Statistically significant correlations (Pearson correlation coefficient) with CKD severity were found for gait speed (p

Abstract Accuracy in copying a figure is one of the most sensitive measures of visuo-constructional ability. However, drawing tasks also involve other cognitive and motor abilities, which may influence the final graphic produced. Nevertheless, these aspects are not taken into account in conventional scoring methodologies. In this study, we have implemented a novel Tablet-based assessment, acquiring data and information for the entire execution of the Rey Complex Figure copy task (T-RCF). This system extracts 12 indices capturing various dimensions of drawing abilities. We have also analysed the structure of relationships between these indices and provided insights into the constructs that they capture. 102 healthy adults completed the T-RCF. A subgroup of 35 participants also completed a paper-and-pencil drawing battery from which constructional, procedural, and motor measures were obtained. Principal component analysis of the T-RCF indices was performed, identifying spatial, procedural and kinematic components as distinct dimensions of drawing execution. Accordingly, a composite score for each dimension was determined. Correlational analyses provided indications of their validity by showing that spatial, procedural, and kinematic scores were associated with constructional, organisational and motor measures of drawing, respectively. Importantly, final copy accuracy was found to be associated with all of these aspects of drawing. In conclusion, copying complex figures entails an interplay of multiple functions. T-RCF provides a unique opportunity to analyse the entire drawing process and to extract scores for three critical dimensions of drawing execution.

Actigraphy is a tool used to describe limb motor activity. Some actigraphic parameters, namely Motor Activity (MA) and Asymmetry Index (AR), correlate with stroke severity. However, a long-lasting actigraphic monitoring was never performed previously. We hypothesized that MA and AR can describe different clinical conditions during the evolution of the acute phase of stroke. We conducted a multicenter study and enrolled 69 stroke patients. NIHSS was assessed every hour and upper limbs’ motor activity was continuously recorded. We calculated MA and AR in the first hour after admission, after a significant clinical change (NIHSS ± 4) or at discharge. In a control group of 17 subjects, we calculated MA and AR normative values. We defined the best model to predict clinical status with multiple linear regression and identified actigraphic cut-off values to discriminate minor from major stroke (NIHSS ≥ 5) and NIHSS 5–9 from NIHSS ≥ 10. The AR cut-off value to discriminate between minor and major stroke (namely NIHSS ≥ 5) is 27% (sensitivity = 83%, specificity = 76% (AUC 0.86 p < 0.001), PPV = 89%, NPV = 42%). However, the combination of AR and MA of the non-paretic arm is the best model to predict NIHSS score (R2: 0.482, F: 54.13), discriminating minor from major stroke (sensitivity = 89%, specificity = 82%, PPV = 92%, NPV = 75%). The AR cut-off value of 53% identifies very severe stroke patients (NIHSS ≥ 10) (sensitivity = 82%, specificity = 74% (AUC 0.86 p < 0.001), PPV = 73%, NPV = 82%). Actigraphic parameters can reliably describe the overall severity of stroke patients with motor symptoms, supporting the addition of a wearable actigraphic system to the multi-parametric monitoring in stroke units.

(1) Background: A noticeable association between the motor activity (MA) profiles of persons living together has been found in previous studies. Social actigraphy methods have shown that this association, in marital dyads composed of healthy individuals, is greater than that of a single person compared to itself. This study aims at verifying the association of MA profiles in dyads where one component is affected by Parkinson’s disease (PD). (2) Methods: Using a wearable sensor-based social actigraphy approach, we continuously monitored, for 7 days, the activities of 27 marital dyads including one component with PD. (3) Results: The association of motor activity profiles within a marital dyad (cross-correlation coefficient 0.344) is comparable to the association of any participant with themselves (0.325). However, when considering the disease severity quantified by the UPDRS III score, it turns out that the less severe the symptoms, the more associated are the MA profiles. (4) Conclusions: Our findings suggest that PD treatment could be improved by leveraging the MA of the healthy spouse, thus promoting lifestyles also beneficial for the component affected by PD. The actigraphy approach provided valuable information on habitual functions and motor fluctuations, and could be useful in investigating the response to treatment.

There is a strong need to develop eco-sustainable agricultural techniques to improve crop yields while preserving biomolecule contents and reducing the adverse environmental impact of agro-chemicals. The use of microorganisms in agriculture represents an attractive and innovative solution. Herein, a chemical study on the nutritional and sensory qualities of San Marzano Cirio 3 (SMC3), Corbarino (CO) and Brandywine (BW) tomato varieties cultivated with and without effective microorganisms (EM) is reported. LC–MS analysis of the methanolic extracts allowed for the identification of 21 polyphenol derivatives. In different proportions among the studied varieties, the two main polyphenols were rutin and naringenin chalcone; the latter was isolated and chemically identified by complementary HR-ESIMS/MS and NMR methods. SMC3 and CO were richer in naringenin chalcone. Conversely, BW showed higher proportions of rutin; however, in all cases, the relative amounts of the two polyphenols considered together increased over the other minor components after the EM treatment. The qualitative and quantitative HPLC analyses of taste-active compounds (aspartic acid, glutamic acid, AMP and GMP) revealed a significant difference in aspartic and glutamic acids and ribonucleotide contents according to the cultivation condition (±EM), particularly in BW. This study provides chemical data in support of the use of EM green technology for the cultivation of edible agricultural products, such as tomato preserves, and may even improve nutritional and sensory qualities while safeguarding the environment.

In primates, the parietal cortex plays a crucial role in hand-object manipulation. However, its involvement in object manipulation and related hand-muscle control has never been investigated in humans with a direct and focal electrophysiological approach. To this aim, during awake surgery for brain tumors, we studied the impact of direct electrical stimulation (DES) of parietal lobe on hand-muscles during a hand-manipulation task (HMt). Results showed that DES applied to fingers-representation of postcentral gyrus (PCG) and anterior intraparietal cortex (aIPC) impaired HMt execution. Different types of EMG-interference patterns were observed ranging from a partial (task-clumsy) or complete (task-arrest) impairment of muscles activity. Within PCG both patterns coexisted along a medio (arrest)–lateral (clumsy) distribution, while aIPC hosted preferentially the task-arrest. The interference patterns were mainly associated to muscles suppression, more pronounced in aIPC with respect to PCG. Moreover, within PCG were observed patterns with different level of muscle recruitment, not reported in the aIPC. Overall, EMG-interference patterns and their probabilistic distribution suggested the presence of different functional parietal sectors, possibly playing different roles in hand-muscle control during manipulation. We hypothesized that task-arrest, compared to clumsy patterns, might suggest the existence of parietal sectors more closely implicated in shaping the motor output.

Abstract Background Stroke units provide patients with a multiparametric monitoring of vital functions, while no instruments are actually available for a continuous monitoring of patients motor performance. Our aim was to develop an actigraphic index able both to identify the paretic limb and continuously monitor the motor performance of stroke patients in the stroke unit environment. Methods Twenty consecutive acute stroke patients (mean age 69.2 years SD 10.1, 8 males and 12 females) and 17 bed-restrained patients (mean age 70.5 years SD 7.3, 7 males and 10 females) hospitalized for orthopedic diseases of the lower limbs, but not experiencing neurological symptoms, were enrolled. This last group represented our control group. The motor activity of arms was recorded for 24 h using two programmable actigraphic systems showing off as wrist-worn watches. The firmware segmented the acquisition in epochs of 1 minute and for each epoch calculates two motor activity indices: MAe1 (Epoch-related Motor Activity index) and MAe2 (Epoch-related Motor Activity index 2). MAe1 is defined as the standard deviation of the acceleration module and MAe2 as the module of the standard deviation of acceleration components. To describe the 24 h motor performance of each limb, we calculated the mean value of MAe1 and MAe2 (respectively MA1_24h and MA2_24h). Then we obtained two Asymmetry Rate Indices: AR1_24h and AR2_24h to show the motor activity prevalence. AR1_24h refers to the asymmetry index between the values of MAe1 of both arms and AR2_24h to MAe2 values. The stroke patients were clinically evaluated by NIHSS at the beginning (NIHSST0) and at the end (NIHSST1) of the 24 h actigraphic recordings. Results Both MA1_24h and MA2_24h indices were smaller in the paretic than in the unaffected arm (respectively p = 0.004 and p = 0.004). AR2_24h showed a better capability (95% of paretic arms correctly identified, Phi Coefficient: 0.903) to discriminate the laterality of the clinical deficit than AR1_24h (85% of paretic arms correctly identified, Phi Coefficient: 0,698). We also found that AR1_24h did not differ between the two groups of patients while AR2_24h was greater in stroke patients than in controls and positively correlated with NIHSS total scores (r: 0.714, p

Soft tissue artefacts (STAs) undermine the validity of skin-mounted approaches to measure skeletal kinematics. Magneto-inertial measurement units (MIMU) gained popularity due to their low cost and ease of use. Although the reliability of different protocols for marker-based joint kinematics estimation has been widely reported, there are still no indications on where to place MIMU to minimize STA. This study aims to find the most stable positions for MIMU placement, among four positions on the thigh, four on the shank, and three on the foot. Stability was investigated by measuring MIMU movements against an anatomical reference frame, defined according to a standard marker-based approach. To this aim, markers were attached both on the case of each MIMU (technical frame) and on bony landmarks (anatomical frame). For each MIMU, the nine angles between each versor of the technical frame with each versor of the corresponding anatomical frame were computed. The maximum standard deviation of these angles was assumed as the instability index of MIMU-body coupling. Six healthy subjects were asked to perform barefoot gait, step negotiation, and sit-to-stand. Results showed that (1) in the thigh, the frontal position was the most stable in all tasks, especially in gait; (2) in the shank, the proximal position is the least stable, (3) lateral or medial calcaneus and foot dorsum positions showed equivalent stability performances. Further studies should be done before generalizing these conclusions to different motor tasks and MIMU-body fixation methods. The above results are of interest for both MIMU-based gait analysis and rehabilitation approaches using wearable sensors-based biofeedback.

Fatigue is a key factor that affects human motion and modulates physiology, biochemistry, and performance. Prolonged cyclic human movements (locomotion primarily) are characterized by a regular pattern, and this extended activity can induce fatigue. However, the relationship between fatigue and regularity has not yet been extensively studied. Wearable sensor methodologies can be used to monitor regularity during standardized treadmill tests (e.g., the widely used Bruce test) and to verify the effects of fatigue on locomotion regularity. Our study on 50 healthy adults [27 males and 23 females;

Background: The frailty status of hemodialysis patients is well-known, but the role of the therapy in the frailty process is not yet clear. Nowadays gait analysis in nephrology is neglected, although gait performance is known to be related to frailty and kidney function. We hypothesized that gait quality and physical activity level is already affected before, and does not change because of the start of hemodialysis.Methods: Fourteen patients (72.3 ± 5.7 years old) in a pre-dialysis program underwent an instrumental gait analysis and their physical activity was monitored for a week. This protocol was repeated 3, 6, 12, and 24 months after the first hemodialysis session.Results: At baseline, our sample showed a conservative gait with pathologic gait variability, high dual-task cost, and a sedentary lifestyle. No statistically significant change was found in any parameter in the analyzed period, but there was a tendency toward an improvement of gait quality and physical activity in the first year of treatment, and a decline in the second year.Conclusion: Elderly patients in the pre-dialysis stage show a conservative gait, however variability was in a pathological range and did not change post-hemodialysis. This hints toward changes in the central nervous system due to the kidney disease. This finding suggests the importance of gait analysis in the early stages of renal disease in the diagnosis of changes in the nervous system due to kidney failure that affect gait. Early detection of these changes would potentially allow a prevention program tailored to this population to be developed.

A soy protein isolate was hydrolyzed with Alcalase®, Flavourzyme® and their combination, and the resulting hydrolysates (A, F and A + F) were ultrafiltered and analyzed through SDS-PAGE. Fractions with MW < 1 kDa were investigated for their ACE-inhibitory activity, and the most active one (A < 1 kDa) was purified by semi-preparative RP-HPLC, affording three further subfractions. NMR analysis and Edman degradation of the most active subfraction (A1) enabled the identification of four putative sequences (ALKPDNR, VVPD, NDRP and NDTP), which were prepared by solid-phase synthesis. The comparison of their ACE-inhibitory activities suggested that the novel peptide NDRP might be the main agent responsible for A1 fraction ACE inhibition (ACE inhibition = 87.75 ± 0.61%; IC50 = 148.28 ± 9.83 μg mL−1). NDRP acts as a non-competitive inhibitor and is stable towards gastrointestinal simulated digestion. The Multiple Reaction Monitoring (MRM) analysis confirmed the presence of NDRP in A < 1 kDa.

(1) Background: Actigraphic methods allow prolonged monitoring of human physical activity (PA) by wearable sensors in a real-life unsupervised context. They generally do not characterize the social context, and nearby persons can have a modulating effect on the performed PA. The present study aims to apply an existing method for bimanual actigraphy to both components of a marital dyad to verify the level of association between the two PA profiles. Other dyad comparisons complete the overall figure. (2) Methods: Seven-day actigraphic recordings collected from both components of 20 married couples of retired, cohabiting, healthy subjects (age ranging from 58 to 87 years) were considered. (3) Results: PA profiles of a marital dyad are significantly more correlated (coefficient: 0.444) than unrelated couples (0.278). Interestingly, participants’ profiles compared with their own recording shifted by 24 h, evidencing an intermediate level of association (0.335). Data from the literature, the high association (0.875) of individual right and left wrist profiles, enforce the analysis. (4) Conclusions: The proposed method, called “social actigraphy”, confirmed that the partner has a relevant effect on one’s PA profile, thus suggesting involving the partner in programs concerning lifestyle changes and patient rehabilitation.

γ-Glutamyl derivatives of sulfur amino acids have been prepared in multigram scale starting from readily available starting materials. The synthesis comprises two one-pot operations, both consisting of two reactions. In the first operation, N-phtaloyl-l-glutamic acid anhydride is obtained from l-glutamic acid and phtalic anhydride. In the second one, N-phtaloyl-l-glutamic acid anhydride is used to acylate amino acids and the N-phtaloyl protecting group is removed. The described approach offers a viable entry to γ-glutamyl derivatives of sulfur-containing amino acids with flavor-enhancer and nutraceutical properties.

Increasing evidence suggests that non-pharmacological therapies impact on neuropsychiatric symptoms and quality of life in people with Alzheimer’s disease. Among these, art-based interventions seem particularly suitable for elders’ rehabilitation as they act both on cognitive functions and quality of life. However, their benefits are not yet appropriately explored. The main aim of this quasi-experimental study was to test the feasibility and the likely efficacy of a novel multi-dimensional visual art intervention for people with Alzheimer’s disease (PWAD), named Art, Colors, and Emotions treatment (ACE-t). A group of PWAD (N = 10) was recruited from the Memory Clinic of Don Gnocchi Foundation to take part in the ACE-t. A historical control group that followed a usual care program (N = 10) was used for comparison. We considered both feasibility output (adherence and acceptability) and efficacy outcome measures (neuropsychological and neurobehavioral scales). We observed a good adherence to and acceptability of the ACE-t. The following significant intervention-related changes were also observed in ACE-t with respect to usual care: improvement in general cognition, as assessed with the Alzheimer’s Disease Assessment Scale–Cognitive, amelioration in language, and in executive functions, and reduction in Neuropsychiatric Inventory Scale score. In conclusion, ACE-t could be considered as a suitable intervention for the rehabilitation of PWAD, with positive effects on the cognitive and the behavioral status. ACE is a promising new art-based intervention that merits further research, including confirmatory trials of our preliminary results.

The aim of this study was to investigate the potential of surface plasmon resonance (SPR) spectroscopy for the measurement of real-time ligand-binding affinities and kinetic parameters for GPR17, a G protein-coupled receptor (GPCR) of major interest in medicinal chemistry as potential target in demyelinating diseases. The receptor was directly captured, in a single-step, from solubilized membrane extracts on the sensor chip through a covalently bound anti-6x-His-antibody and retained its ligand binding activity for over 24 h. Furthermore, our experimental setup made possible, after a mild regeneration step, to remove the bound receptor without damaging the antibody, and thus to reuse many times the same chip. Two engineered variants of GPR17, designed for crystallographic studies, were expressed in insect cells, extracted from crude membranes and analyzed for their binding with two high affinity ligands: the antagonist Cangrelor and the agonist Asinex 1. The calculated kinetic parameters and binding constants of ligands were in good agreement with those reported from activity assays and highlighted a possible functional role of the N-terminal residues of the receptor in ligand recognition and binding. Validation of SPR results was obtained by docking and molecular dynamics of GPR17-ligands interactions and by functional in vitro studies. The latter allowed us to confirm that Asinex 1 behaves as GPR17 receptor agonist, inhibits forskolin-stimulated adenylyl cyclase pathway and promotes oligodendrocyte precursor cell maturation and myelinating ability.

Background: It is often challenging to formulate a reliable prognosis for patients with acute ischemic stroke. The most accepted prognostic factors may not be sufficient to predict the recovery process. In this view, describing the evolution of motor deficits over time via sensors might be useful for strengthening the prognostic model. Our aim was to assess whether an actigraphic-based parameter (Asymmetry Rate Index for the 24 h period (AR2_24 h)) obtained in the acute stroke phase could be a predictor of a 90 d prognosis. Methods: In this observational study, we recorded and analyzed the 24 h upper limb movement asymmetry of 20 consecutive patients with acute ischemic stroke during their stay in a stroke unit. We recorded the motor activity of both arms using two programmable actigraphic systems positioned on patients’ wrists. We clinically evaluated the stroke patients by NIHSS in the acute phase and then assessed them across 90 days using the modified Rankin Scale (mRS). Results: We found that the AR2_24 h parameter positively correlates with the 90 d mRS (r = 0.69, p < 0.001). Moreover, we found that an AR2_24 h > 32% predicts a poorer outcome (90 d mRS > 2), with sensitivity = 100% and specificity = 89%. Conclusions: Sensor-based parameters might provide useful information for predicting ischemic stroke prognosis in the acute phase.

Abstract Background In human-centered robotics, exoskeletons are becoming relevant for addressing needs in the healthcare and industrial domains. Owing to their close interaction with the user, the safety and ergonomics of these systems are critical design features that require systematic evaluation methodologies. Proper transfer of mechanical power requires optimal tuning of the kinematic coupling between the robotic and anatomical joint rotation axes. We present the methods and results of an experimental evaluation of the physical interaction with an active pelvis orthosis (APO). This device was designed to effectively assist in hip flexion-extension during locomotion with a minimum impact on the physiological human kinematics, owing to a set of passive degrees of freedom for self-alignment of the human and robotic hip flexion-extension axes. Methods Five healthy volunteers walked on a treadmill at different speeds without and with the APO under different levels of assistance. The user-APO physical interaction was evaluated in terms of: (i) the deviation of human lower-limb joint kinematics when wearing the APO with respect to the physiological behavior (i.e., without the APO); (ii) relative displacements between the APO orthotic shells and the corresponding body segments; and (iii) the discrepancy between the kinematics of the APO and the wearer’s hip joints. Results The results show: (i) negligible interference of the APO in human kinematics under all the experimented conditions; (ii) small (i.e., < 1 cm) relative displacements between the APO cuffs and the corresponding body segments (called stability); and (iii) significant increment in the human-robot kinematics discrepancy at the hip flexion-extension joint associated with speed and assistance level increase. Conclusions APO mechanics and actuation have negligible interference in human locomotion. Human kinematics was not affected by the APO under all tested conditions. In addition, under all tested conditions, there was no relevant relative displacement between the orthotic cuffs and the corresponding anatomical segments. Hence, the physical human-robot coupling is reliable. These facts prove that the adopted mechanical design of passive degrees of freedom allows an effective human-robot kinematic coupling. We believe that this analysis may be useful for the definition of evaluation metrics for the ergonomics assessment of wearable robots.

Previous evidence has shown that tool-use can reshape one’s own body schema, extending peripersonal space and modulating the representation of related body parts. Here, we investigated the role of tool action in shaping the body metric representation, by contrasting two different views. According to a first view, the shaping would rely on the mere execution of tool action, while the second view suggests that the shaping induced by tool action on body representation would primarily depend on the representation of the action goals to be accomplished. To this aim, we contrasted a condition in which participants voluntarily accomplish the movement by representing the program and goal of a tool action (i.e., active tool-use training) with a condition in which the tool-use training was produced without any prior goal representation (i.e., passive tool-use training by means of robotic assistance). If the body metric representation primarily depends on the coexistence between goal representation and bodily movements, we would expect an increase of the perceived forearm length in the post- with respect to the pre-training phase after the active training phase only. Healthy participants were asked to estimate the midpoint of their right forearm before and after 20 min of tool-use training. In the active condition, subjects performed “enfold-and-push” movements using a rake to prolong their arm. In the passive condition, subjects were asked to be completely relaxed while the movements were performed with robotic assistance. Results showed a significant increase in the perceived arm length in the post- with respect to the pre-training phase only in the active task. Interestingly, only in the post-training phase, a significant difference was found between active and passive conditions, with a higher perceived arm length in the former than in the latter. From a theoretical perspective, these findings suggest that tool-use may shape body metric representation only when action programs are motorically represented and not merely produced. From a clinical perspective, these results support the use of robots for the rehabilitation of brain-damaged hemiplegic patients, provided that robot assistance during the exercises is present only “as-needed” and that patients’ motor representation is actively involved.

When we successfully achieve willed actions, the feeling that our moving body parts belong to the self (i.e., body ownership) is barely required. However, how and to what extent the awareness of our own body contributes to the neurocognitive processes subserving actions is still debated. Here we capitalized on immersive virtual reality in order to examine whether and how body ownership influences motor performance (and, secondly, if it modulates the feeling of voluntariness). Healthy participants saw a virtual body either from a first or a third person perspective. In both conditions, they had to draw continuously straight vertical lines while seeing the virtual arm doing the same action (i.e., drawing lines) or deviating from them (i.e., drawing ellipses). Results showed that when there was a mismatch between the intended and the seen movements (i.e., participants had to draw lines but the avatar drew ellipses), motor performance was strongly "attracted" towards the seen (rather than the performed) movement when the avatar's body part was perceived as own (i.e., first person perspective). In support of previous studies, here we provide direct behavioral evidence that the feeling of body ownership modulates the interference of seen movements to the performed movements.

Despite the impressive progress in nucleoside chemistry to date, the synthesis of nucleoside analogues is still a challenge. Chemoenzymatic synthesis has been proven to overcome most of the constraints of conventional nucleoside chemistry. A purine nucleoside phosphorylase from Aeromonas hydrophila (AhPNP) has been used herein to catalyze the synthesis of Ribavirin, Tecadenoson, and Cladribine, by a “one-pot, one-enzyme„ transglycosylation, which is the transfer of the carbohydrate moiety from a nucleoside donor to a heterocyclic base. As the sugar donor, 7-methylguanosine iodide and its 2′-deoxy counterpart were synthesized and incubated either with the “purine-like„ base or the modified purine of the three selected APIs. Good conversions (49–67%) were achieved in all cases under screening conditions. Following this synthetic scheme, 7-methylguanine arabinoside iodide was also prepared with the purpose to synthesize the antiviral Vidarabine by a novel approach. However, in this case, neither the phosphorolysis of the sugar donor, nor the transglycosylation reaction were observed. This study was enlarged to two other ribonucleosides structurally related to Ribavirin and Tecadenoson, namely, Acadesine, or AICAR, and 2-chloro-N6-cyclopentyladenosine, or CCPA. Only the formation of CCPA was observed (52%). This study paves the way for the development of a new synthesis of the target APIs at a preparative scale. Furthermore, the screening herein reported contributes to the collection of new data about the specific substrate requirements of AhPNP.

The regularity of pseudo-periodic human movements, including locomotion, can be assessed by autocorrelation analysis of measurements using inertial sensors. Though sensors are generally placed on the trunk or pelvis, movement regularity can be assessed at any body location. Pathological factors are expected to reduce regularity either globally or on specific anatomical subparts. However, other non-pathological factors, including gait strategy (walking and running) and speed, modulate locomotion regularity, thus potentially confounding the identification of the pathological factor. The present study’s objectives were (1) to define a multi-sensor method based on the autocorrelation analysis of the acceleration module (norm of the acceleration vector) to quantify regularity; (2) to conduct an experimental study on healthy adult subjects to quantify the effect on movement regularity of gait strategy (walking and running at the same velocity), gait speed (four speeds, lower three for walking, upper two for running), and sensor location (on four different body parts). Twenty-five healthy adults participated and four triaxial accelerometers were located on the seventh cervical vertebra (C7), pelvis, wrist, and ankle. The results showed that increasing velocity was associated with increasing regularity only for walking, while no difference in regularity was observed between walking and running. Regularity was generally highest at C7 and ankle, and lowest at the wrist. These data confirm and complement previous literature on regularity assessed on the trunk, and will support future analyses on individuals or groups with specific pathologies affecting locomotor functions.

Cognitive assessment in a clinical setting is generally made by pencil-and-paper tests, while computer-based tests enable the measurement and the extraction of additional performance indexes. Previous studies have demonstrated that in a research context exploration deficits occur also in patients without evidence of unilateral neglect at pencil-and-paper tests. The objective of this study is to apply a touchscreen-based cancellation test, feasible also in a clinical context, to large groups of control subjects and unilaterally brain-damaged patients, with and without unilateral spatial neglect (USN), in order to assess disturbances of the exploratory skills. A computerized cancellation test on a touchscreen interface was used for assessing the performance of 119 neurologically unimpaired control subjects and 193 patients with unilateral right or left hemispheric brain damage, either with or without USN. A set of performance indexes were defined including Latency, Proximity, Crossings and their spatial lateral gradients, and Preferred Search Direction. Classic outcome scores were computed as well. Results show statistically significant differences among groups (assumed p