Activation of cerebellum and basal ganglia during the observation and execution of manipulative actions

Studies on action observation mostly described the activation of a network of cortical areas, while less investigation focused specifically on the activation and role of subcortical nodes. In the present fMRI study, we investigated the recruitment of cerebellum and basal ganglia during the execution and observation of object manipulation performed with the right hand. The observation conditions consisted in: (a) observation of manipulative actions; (b) observation of sequences of random finger movements. In the execution conditions, participants had to perform the same actions or movements as in (a) and (b), respectively. The results of conjunction analysis showed significant shared activations during both observation and execution of manipulation in several subcortical structures, including: (1) cerebellar lobules V, VI, crus I, VIIIa and VIIIb (bilaterally); (2) globus pallidus, bilaterally, and left subthalamic nucleus; (3) red nucleus (bilaterally) and left thalamus. These findings support the hypothesis that the action observation/execution network also involves subcortical structures, such as cerebellum and basal ganglia, forming an integrated network. This suggests possible mechanisms, involving these subcortical structures, underlying learning of new motor skills, through action observation and imitation

Simulation of secondary flows in turbomachinery by the discontinuous Galerkin method

Secondary flows have a huge impact on the losses in low pressure gas turbines and the inlet boundary layer state is one of the factors which most affects the endwall flow field. The present work aims at investigating secondary flows in a low-pressure gas turbine cascade by means of RANS simulations for two different inlet conditions. The equations are discretised in space by the Discontinuous Galerkin method and implicit time integration is adopted. Changes in the peculiarities of the flow field within the cascade passage are discussed. The results are compared with experimental and numerical data available in the literature

RANS simulation of secondary flows in a low pressure turbine cascade: Influence of inlet boundary layer profile

Secondary flows have a huge impact on losses generation in modern low pressure gas turbines (LPTs). At design point, the interaction of the blade profile with the end-wall boundary layer is responsible for up to 40% of total losses. Therefore, predicting accurately the end-wall flow field in a LPT is extremely important in the industrial design phase. Since the inlet boundary layer profile is one of the factors which most affects the evolution of secondary flows, the first main objective of the present work is to investigate the impact of two different inlet conditions on the end-wall flow field of the T106A, a well known LPT cascade. The first condition, labeled in the paper as C1, is represented by uniform conditions at the inlet plane and the second, C2, by a flow characterized by a defined inlet boundary layer profile. The code used for the simulations is based on the Discontinuous Galerkin (DG) formulation and solves the Reynolds-averaged Navier-Stokes (RANS) equations coupled with the Spalart Allmaras turbulence model. Secondly, this work aims at estimating the influence of viscosity and turbulence on the T106A end-wall flow field. In order to do so, RANS results are compared with those obtained from an inviscid simulation with a prescribed inlet total pressure profile, which mimics a boundary layer. A comparison between C1 and C2 results highlights an influence of secondary flows on the flow field up to a significant distance from the end-wall. In particular, the C2 end-wall flow field appears to be characterized by greater over turning and under turning angles and higher total pressure losses. Furthermore, the C2 simulated flow field shows good agreement with experimental and numerical data available in literature. The C2 and inviscid Euler computed flow fields, although globally comparable, present evident differences. The cascade passage simulated with inviscid flow is mainly dominated by a single large and homogeneous vortex structure, less stretched in the spanwise direction and closer to the end-wall than vortical structures computed by compressible flow simulation. It is reasonable, then, asserting that for the chosen test case a great part of the secondary flows details is strongly dependent on viscous phenomena and turbulence

Lesion mapping and functional characterization of hemiplegic children with different patterns of hand manipulation

Brain damage in children with unilateral cerebral palsy (UCP) affects motor function, with varying severity, making it difficult the performance of daily actions. Recently, qualitative and semi-quantitative methods have been developed for lesion classification, but studies on mild to moderate hand impairment are lacking. The present study aimed to characterize lesion topography and preserved brain areas in UCP children with specific patterns of hand manipulation. A homogeneous sample of 16 UCP children, aged 9 to 14 years, was enrolled in the study. Motor assessment included the characterization of the specific pattern of hand manipulation, by means of unimanual and bimanual measures (Kinematic Hand Classification, KHC; Manual Ability Classification System, MACS; House Functional Classification System, HFCS; Melbourne Unilateral Upper Limb Assessment, MUUL; Assisting Hand Assessment, AHA). The MRI morphological study included multiple methods: (a) qualitative lesion classification, (b) semi-quantitative classification (sq-MRI), (c) voxel-based morphometry comparing UCP and typically developed children (VBM-DARTEL), and (d) quantitative brain tissue segmentation (q-BTS). In addition, functional MRI was used to assess spared functional activations and cluster lateralization in the ipsilesional and contralesional hemispheres of UCP children during the execution of simple movements and grasping actions with the more affected hand. Lesions most frequently involved the periventricular white matter, corpus callosum, posterior limb of the internal capsule, thalamus, basal ganglia and brainstem. VMB-DARTEL analysis allowed to detect mainly white matter lesions. Both sq-MRI classification and q-BTS identified lesions of thalamus, brainstem, and basal ganglia. In particular, UCP patients with synergic hand pattern showed larger involvement of subcortical structures, as compared to those with semi-functional hand. Furthermore, sparing of gray matter in basal ganglia and thalamus was positively correlated with MUUL and AHA scores. Concerning white matter, q-BTS revealed a larger damage of fronto-striatal connections in patients with synergic hand, as compared to those with semi-functional hand. The volume of these connections was correlated to unimanual function (MUUL score). The fMRI results showed that all patients, but one, including those with cortical lesions, had activation in ipsilesional areas, regardless of lesion timing. Children with synergic hand showed more lateralized activation in the ipsilesional hemisphere both during grasping and simple movements, while children with semi-functional hand exhibited more bilateral activation during grasping. The study demonstrates that lesion localization, rather than lesion type based on the timing of their occurrence, is more associated with the functional level of hand manipulation. Overall, the preservation of subcortical structures and white matter can predict a better functional outcome. Future studies integrating different techniques (structural and functional imaging, TMS) could provide further evidence on the relation between brain reorganization and specific pattern of manipulation in UCP children

Can a pathological model improve the abilities of the paretic hand in hemiplegic children? the PAM-AOT study protocol of a randomised controlled trial

Introduction Action Observation Treatment (AOT) is an innovative therapeutic approach consisting in the observation of actions followed by subsequent repetition. In children with unilateral cerebral palsy (UCP), it improves upper limb function in daily activities. The standard paradigm of AOT requires the observation of healthy models; however, it has been demonstrated that the mirror neuron system of children with UCP is more activated by observation of pathological models, showing a similar motor repertoire, than by the healthy model, suggesting that AOT based on pathological models is superior to the standard paradigm of AOT in the functional rehabilitation of the affected upper limb of children with UCP. Methods and analysis This protocol describes an active two-arm randomised controlled evaluator-blinded trial. Twenty-six children with UCP will participate in 3 weeks of intensive AOT: the experimental group will observe a pathological model, while the control group will observe a typically developed model. The primary outcome is the spontaneous use of the paretic hand, measured with the Assisting Hand Assessment. Secondary outcome measures are the Melbourne Assessment of Unilateral Upper Limb Function, the ABILHAND-Kids and the Activities Scale for Kids-performance. Assessments will be performed at baseline (T0), at the end of intensive AOT (T1), at 8-12 weeks (T2) and at 24-28 weeks (T3) after the end of intensive AOT. Ethics and dissemination The trial was approved by the Area Vasta Emilia Nord Ethics Committee (AVEN prot. n. 133117, 29 November 2018), and it was prospectively registered on ClinicalTrials.gov. The results will be submitted for publication to a peer-reviewed journal, discussed with parents of children participating in the trial and disseminated at suitable conferences. Trial registration number NCT04088994; Pre-results

Can a pathological model improve the abilities of the paretic hand in hemiplegic children? the PAM-AOT study protocol of a randomised controlled trial

Introduction Action Observation Treatment (AOT) is an innovative therapeutic approach consisting in the observation of actions followed by subsequent repetition. In children with unilateral cerebral palsy (UCP), it improves upper limb function in daily activities. The standard paradigm of AOT requires the observation of healthy models; however, it has been demonstrated that the mirror neuron system of children with UCP is more activated by observation of pathological models, showing a similar motor repertoire, than by the healthy model, suggesting that AOT based on pathological models is superior to the standard paradigm of AOT in the functional rehabilitation of the affected upper limb of children with UCP. Methods and analysis This protocol describes an active two-arm randomised controlled evaluator-blinded trial. Twenty-six children with UCP will participate in 3 weeks of intensive AOT: the experimental group will observe a pathological model, while the control group will observe a typically developed model. The primary outcome is the spontaneous use of the paretic hand, measured with the Assisting Hand Assessment. Secondary outcome measures are the Melbourne Assessment of Unilateral Upper Limb Function, the ABILHAND-Kids and the Activities Scale for Kids-performance. Assessments will be performed at baseline (T0), at the end of intensive AOT (T1), at 8-12 weeks (T2) and at 24-28 weeks (T3) after the end of intensive AOT. Ethics and dissemination The trial was approved by the Area Vasta Emilia Nord Ethics Committee (AVEN prot. n. 133117, 29 November 2018), and it was prospectively registered on ClinicalTrials.gov. The results will be submitted for publication to a peer-reviewed journal, discussed with parents of children participating in the trial and disseminated at suitable conferences. Trial registration number NCT04088994; Pre-results

HLA-G 3'UTR Polymorphisms Impact the Prognosis of Stage II-III CRC Patients in Fluoropyrimidine-Based Treatment

An important hallmark of CRC is the evasion of immune surveillance. HLA-G is a negative regulator of host's immune response. Overexpression of HLA-G protein in primary tumour CRC tissues has already been associated to worse prognosis; however a definition of the role of immunogenetic host background is still lacking. Germline polymorphisms in the 3'UTR region of HLA-G influence the magnitude of the protein by modulating HLA-G mRNA stability. Soluble HLA-G has been associated to 3'UTR +2960 Ins/Ins and +3035 C/T (lower levels) and +3187 G/G (high levels) genotypes. HLA-G 3'UTR SNPs have never been explored in CRC outcome. The purpose of this study was to investigate if common HLA-G 3'UTR polymorphisms have an impact on DFS and OS of 253 stage II-III CRC patients, after primary surgery and ADJ-CT based on FL. The 3'UTR was sequenced and SNPs were analyzed for their association with survival by Kaplan-Meier and multivariate Cox models; results underwent internal validation using a resampling method (bootstrap analysis). In a multivariate analysis, we estimated an association with improved DFS in Ins allele (Ins/Del +Ins/Ins) carriers (HR 0.60, 95% CI 0.38-0.93, P = 0.023) and in patients with +3035 C/T genotype (HR 0.51, 95% CI 0.26-0.99, P = 0.045). The +3187 G/G mutated carriers (G/G vs A/A+A/G) were associated to a worst prognosis in both DFS (HR 2.46, 95% CI 1.19-5.05, P = 0.015) and OS (HR 2.71, 95% CI 1.16-6.63, P = 0.022). Our study shows a prognostic and independent role of 3 HLA-G 3'UTR SNPs, +2960 14-bp INDEL, +3035 C>T, and +3187 A>G

Effectiveness of infection control measures in controlling a nosocomial outbreak of multidrug-resistant tuberculosis among HIV patients in Italy

SETTING: Between October 1992 and February 1994, 33 cases of multidrug-resistant tuberculosis (MDR-TB) were diagnosed among patients infected by the human immunodeficiency virus (HIV) and hospitalised in an HIV ward in Milan, Italy. This outbreak was part of a much larger outbreak, begun in another hospital and probably transferred through a patient. OBJECTIVE: TO evaluate risk factors for transmission and the effectiveness of infection control measures. DESIGN: 1) Active follow-up of exposed patients, 2) cohort study among HIV-infected patients exposed to MDR-TB cases before and after the implementation of control measures, 3) screening of close contacts of MDR-TB cases, and 1) molecular typing by restriction fragment length polymorphism (RFLP) analysis. RESULTS: The risk of MDR-TB was higher in patients with lower CD4+ lymphocyte percentages and longer duration of exposure. No difference in the daily risk was observed for in-patients vs day-hospital patients or by room distance from an infectious case. Of the 90 patients exposed before the implementation of infection control measures (i,e,, October 1992-June 1993) 26 (28.9%) developed MDR-TB, whereas none of the 44 patients exclusively exposed after implementation developed MDR-TB, despite the continuing presence of infectious MDR-TB cases in the ward. CONCLUSION: Simple control measures were effective in significantly reducing nosocomial transmission among patients

Systematic review of the therapeutic use of Schwann cells in the repair of peripheral nerve injuries: Advancements from animal studies to clinical trials

ObjectiveTo systematically evaluate the literature on the therapeutic use of Schwann cells (SC) in the repair of peripheral nerve injuries.MethodsThe Cochrane Library and PubMed databases were searched using terms [(“peripheral nerve injury” AND “Schwann cell” AND “regeneration”) OR (“peripheral nerve injuries”)]. Studies published from 2008 to 2022 were eligible for inclusion in the present study. Only studies presenting data from in-vivo investigations utilizing SCs in the repair of peripheral nerve injuries qualified for review. Studies attempting repair of a gap of ≥10 mm were included. Lastly, studies needed to have some measure of quantifiable regenerative outcome data such as histomorphometry, immunohistochemical, electrophysiology, or other functional outcomes.ResultsA search of the PubMed and Cochrane databases revealed 328 studies. After screening using the abstracts and methods, 17 studies were found to meet our inclusion criteria. Good SC adherence and survival in conduit tubes across various studies was observed. Improvement in morphological and functional outcomes with the use of SCs in long gap peripheral nerve injuries was observed in nearly all studies.ConclusionBased on contemporary literature, SCs have demonstrated clear potential in the repair of peripheral nerve injury in animal studies. It has yet to be determined which nerve conduit or graft will prove superior for delivery and retention of SCs for nerve regeneration. Recent developments in isolation and culturing techniques will enable further translational utilization of SCs in future clinical trials