Human locomotion: centre of mass and symmetry

In ambito di ricerca (clinica e sportiva), la necessit\ue0 di sviluppare un approccio \u2018multilaterale\u2019 (qualitativo e quantitativo) che caratterizzi matematicamente la traiettoria tri-dimensionale di una variabile fisica assolutamente importante ma spesso dimenticata, quale il centro di massa corporeo (CMC) (ovvero, il punto immaginario assimilabile al corpo umano in cui si suppone che tutte le masse corporee stiano concentrate), diviene oggi sempre pi\uf9 impellente e quanto mai urgente. Pertanto l\u2019obiettivo di questo dottorato, perseguito tramite un differente utilizzo delle classiche metodologie biomeccaniche, \ue8 rappresentare le grandezze cinematiche che descrivono il movimento dei segmenti corporei e del suddetto CMC nel tempo e nello spazio. Per conseguire questo traguardo si sono pensati e realizzati due diversi progetti. Con il primo progetto si sono previsti: a) lo sviluppo di un metodo matematico quantitativo (Serie di Fourier) per descrivere e rappresentare graficamente la traiettoria tri-dimensionale del CMC durante la locomozione su treadmill (la cosiddetta Impronta Digitale Locomotoria, specifica per soggetto/popolazione); b) la caratterizzazione della simmetria nella traiettoria del CMC (il cosiddetto Indice di Simmetria); infine, c) la costituzione di un database di valori normali (coefficienti di equazioni) in un insieme piuttosto esteso di condizioni, al variare di sesso (maschi versus femmine), et\ue0 (dai 6 ai 65 anni), tipologia di locomozione (marcia versus corsa), velocit\ue0 e pendenza (piano, salita e discesa). Questo database iniziale rappresenta il parametro principale di riferimento per la locomozione sana. Attraverso questo studio \ue8 stato ampiamente dimostrato che la locomozione umana risulta genericamente asimmetrica. Nello specifico: 1) tra maschi e femmine non si sono riscontrate differenze significative; 2) indipendentemente da et\ue0 e pendenza, le velocit\ue0 pi\uf9 basse, meno naturali e comuni, sono caratterizzate da pattern di Impronte Digitali Locomotorie pi\uf9 variabili. Viceversa, un aumento di velocit\ue0 \ue8 accoppiato con un progressivo e continuo innalzamento del CMC; 3) l\u2019asimmetria destra e sinistra del passo \ue8 molto probabilmente correlata sia con l\u2019anatomia (lunghezza della gamba) che con la predominanza dell\u2019arto; in linea con l\u2019ipotesi iniziale, 4) mediamente, la corsa \ue8 pi\uf9 asimmetrica della marcia; infine, 5) i bambini e gli anziani presentano maggiori asimmetrie (marcia e corsa): questo \ue8 dovuto alla progressiva maturazione del ciclo del cammino (nei bambini) ed alle caratteristiche muscolari e scheletriche dell\u2019apparato locomotore (negli anziani). Pertanto, attraverso una caratterizzazione matematica della traiettoria tri-dimensionale del CMC, si \ue8 potuto: a) quantificare il suo spostamento nel tempo e nello spazio; b) individuare l\u2019Impronta Digitale Locomotoria specifica di sesso, et\ue0, tipologia di locomozione, velocit\ue0 e pendenza. Questo importante traguardo permetter\ue0, in un immediato futuro, la comparazione con la situazione di normalit\ue0 di condizioni di locomozione compromessa o impedita (ad esempio, bambini con paralisi cerebrale infantile, obesi e amputati). Infine, la stima della principali variabili biomeccaniche \ue8 risultata fondamentale sia nel descrivere la meccanica di marcia e corsa che nel caratterizzarne la corrispondente impronta locomotoria. Le nostre misure di tali variabili (semplici e complesse), ottenute con metodo discreto (ciclo per ciclo), con l\u2019impiego di una funzione matematica continua (Serie di Fourier) e con l\u2019applicazione di un\u2019equazione predittiva (misura indiretta), soddisfano completamente ed addirittura ampliano la letteratura gi\ue0 esistente. Nel secondo progetto, partendo da uno studio sulla performance dei cavalli, si \ue8 cercato di verificare se esiste una correlazione tra simmetrie corporee (statiche e dinamiche) ed economia nella corsa anche in corridori umani variamente allenati (classificati in tre gruppi sulla base del loro miglior tempo nella maratona). Inoltre: a) si sono sviluppati metodi di analisi bi- e tri-dimensionale delle Risonanze Magnetiche per Immagini (regione pelvica ed arti inferiori), impiegate come riferimento per le simmetrie statiche; b) attraverso sia l\u2019Impronta Digitale Locomotoria che l\u2019Indice di Simmetria si sono caratterizzate le simmetrie dinamiche; infine c) l\u2019economia della corsa \ue8 stata espressa attraverso il suo reciproco, ovvero il costo metabolico. L\u2019analisi sia bi- che tri-dimensionale delle immagini ha evidenziato differenze davvero esigue in base al livello di allenamento. Positivamente ed indipendentemente dai corridori, si \ue8 dimostrato che ad una maggiore simmetria nella regione del ginocchio corrisponde una maggiore simmetria nella regione della caviglia. Inoltre l\u2019analisi delle simmetrie dinamiche ha permesso di osservare che: 1) il CMC si solleva leggermente in funzione della velocit\ue0; 2) le asimmetrie destre e sinistre del passo sono principalmente marcate lungo la direzione di movimento e, contemporaneamente, ridotte lungo la direzione verticale. Esse sono strettamente dipendenti dall\u2019anatomia e dall\u2019arto dominante; 3) diversamente da quanto ci si aspettava, sono state comunque evidenziate solamente poche differenze tra i corridori. Negativamente, l\u2019economia della corsa non mostra differenze significative tra i gruppi testati. Perci\uf2, diversamente dall\u2019ipotesi iniziale, non \ue8 stata evidenziata l\u2019esistenza di alcuna relazione tra le simmetrie corporee e l\u2019economia della corsa, quanto piuttosto solo la presenza di una discreta variabilit\ue0 in simmetria statica e dinamica. Infine, l\u2019analisi di bioenergetica (treadmill versus pista) e biomeccanica (variabili semplici/complesse e variabilit\ue0 spazio/temporale del CMC) della corsa ha evidenziato la presenza solamente di poche differenze dovute al livello di allenamento dei soggetti studiati.In both research laboratory and sport/clinical settings, it becomes very important to develop a \u2018multilateral approach\u2019 (qualitative and quantitative) to fully describe the individual behaviour of the centre of mass of the human body (BCOM) (i.e. the imaginary specific point at which the body behaves as if its masses were concentrated) over time and space. Consequently, the aim of this doctorate is to describe kinematic variables of the BCOM in varying locomotion conditions. This purpose, focusing on the BCOM as the investigation object fulfilling such a need, has been achieved through a different use of classic biomechanical procedures. In effect, two different studies were carried out. The first project sought: a) to develop a mathematical method (Fourier Series) which could describe and graphically represent each individual (subject or population) gait signature (i.e. Digital Locomotory Signature, a global index of the BCOM dynamics) during locomotion on a treadmill; b) to assess the symmetry (i.e. Symmetry Index) in each movement direction, along the BCOM trajectory, between the two stride phases; finally, c) to build up an initial comprehensive database of \u2018healthy values\u2019 (equation coefficients) in a set of different conditions considering gender (males versus females), age (from 6 to 65 years), gait (walking versus running), speed and gradient (level, uphill and downhill). Although only slight gender differences were found, human \u2018healthy\u2019 gait is rather asymmetrical. To be precise: 1) the lowest speeds have the most peculiar signature independently of age and gradient: indeed, these speeds are not so completely natural and common. However, if speed increases, the BCOM raises in such a way that its corresponding 3D contour becomes more regular; 2) right and left sides of the stride are quite asymmetrical (i.e. in the forward direction). Globally, this asymmetry is probably related both to anatomy (i.e. leg length) and which hand you use (i.e. right-handedness); 3) on average, the symmetry pattern is slightly lower in running gaits; and as expected, 4) young children and elderly adults are the most asymmetrical subjects, independently of testing conditions: while, during the early stages of life, this global asymmetry could be ascribed to the process of gait development, old age asymmetries are probably due to structural wearing down of the musculoskeletal system. Importantly, the mathematical methodology used here, by analysing even subtle changes in the 3D BCOM trajectory: a) characterizes its displacements over both time and space; b) quantitatively describes the individual gait signature; and c) represents the basis for the evaluation of gait anomaly/pathology (e.g. children with cerebral palsy, obese people and amputees). Finally, knowing the main biomechanical variables becomes fundamental both to fully describe the mechanics of walking and running and to extract and characterize the individual gait signature. In effect, our measurements (discrete method versus continuous mathematical function, and direct versus indirect measurement) of both simple and complex variables wholly confirm, complete and amplify previous literature data. Similarly to what previously demonstrated in horse performances, the second project tried: a) to verify both static anatomical and kinematic functional symmetries as important and relevant indicators of running economy (i.e. the reciprocal of metabolic cost) in humans featuring different running levels (i.e. occasional, skilled and top runners categorized primarily upon their best marathon time); b) to develop imaging based bi- and three-dimensional methods to analyse static symmetries recorded by Magnetic Resonance Imaging (lower limbs and pelvic area); c) to describe the kinematic symmetries defining both the Digital Locomotory Signature and the Symmetry Index; finally, d) to investigate running economy as a performance determinant. In effect, both the 2D/3D analysis of static symmetries highlight very few differences among runners; however, a strong relationship between ankle and knee areas has been underlined in all runners. Furthermore, independently of training ability: as expected, 1) the BCOM raises and lifts slightly as a function of running speed; 2) right and left steps are mostly asymmetrical in the forward direction and symmetrical in the vertical direction (i.e. combined action of gravity and ground reaction force); 3) differently to what was expected, slight differences have been found among runners. On the whole, the asymmetry is probably related both to anatomy and handedness. Other than that, no running economy differences were found. In conclusion, while a relationship between symmetries and running economy has not been found, significant results have however been underlined in each trial (static and dynamic symmetries). Finally, the deep investigation of both bioenergetics (treadmill versus over-ground) and biomechanics (simple/complex variables and spatial/temporal variability of the BCOM) of running has highlights only little (significant) differences among groups

The effect of a secondary task on kinematics during turning in Parkinson's disease with mild to moderate impairment

Patients with Parkinson's disease (PD) show typical gait asymmetries. These peculiar motor impairments are exacerbated by added cognitive and/or mechanical loading. However, there is scarce literature that chains these two stimuli. The aim of this study was to investigate the combined effects of a dual task (cognitive task) and turning (mechanical task) on the spatiotemporal parameters in mild to moderate PD. Participants (nine patients with PD and nine controls (CRs)) were evaluated while walking at their self-selected pace without a secondary task (single task), and while repeating the days of the week backwards (dual task) along a straight direction and a 60 degrees and 120 degrees turn. As speculated, in single tasking, PD patients preferred to walk with a shorter stride length (p< 0.05) but similar timing parameters, compared to the CR group; in dual tasking, both groups walked slower with shorter strides. As the turn angle increased, the speed will be reduced (p< 0.001), whereas the ground-foot contact will become greater (p< 0.001) in all the participants. We showed that the combination of a simple cognitive task and a mechanical task (especially at larger angles) could represent an important training stimulus in PD at the early stages of the pathology

Achilles Tendon mechanical behavior and ankle joint function at the walk-to-run transition

Walking at speeds higher than transition speed is associated with a decrease in the plantar-flexor muscle fibres' ability to produce force and, potentially, to an impaired behaviour of the muscle-tendon unit (MTU) elastic components. This study aimed to investigate the ankle joint functional indexes and the Achilles tendon mechanical behaviour (changes in AT force and power) to better elucidate the mechanical determinants of the walk-to-run transition. Kinematics, kinetic and ultrasound data of the gastrocnemius medialis (GM) were investigated during overground walking and running at speeds ranging from 5-9 km·h-1. AT and GM MTU force and power were calculated during the propulsive phase; the ankle joint function indexes (damper, strut, spring and motor) were obtained using a combination of kinetic and kinematic data. AT force was larger in running at speeds > 6.5 km/h. The contribution of AT to the total power provided by the GM MTU was significantly larger in running at speeds > 7.5 km/h. The spring and strut indexes of the ankle were significantly larger in running at speeds > 7.5 km/h. These data suggest that the walk-to-run transition could (at least partially) be explained by the need to preserve AT mechanical behaviour and the ankle spring function

A novel KCNQ3 mutation in familial epilepsy with focal seizures and intellectual disability

Mutations in the KCNQ2 gene encoding for voltage-gated potassium channel subunits have been found in patients affected with early-onset epilepsies with wide phenotypic expression, ranging from Benign Familial Neonatal Seizures (BFNS) to epileptic encephalopathy with cognitive impairment, drug resistance, and characteristic EEG and neuroradiological features. By contrast, only few KCNQ3 mutations have been rarely described, mostly in patients with typical BFNS. We report clinical, genetic, and functional data from a family in which early-onset epilepsy and neurocognitive deficits segregated with a novel mutations in KCNQ3 (c.989G>T; p.R330L). Electrophysiological studies in mammalian cells revealed that incorporation of KCNQ3 R330L mutant subunits impaired channel function, suggesting a pathogenetic role for such mutation. The degree of functional impairment of channels incorporating KCNQ3 R330L subunits was larger than that of channels carrying another KCNQ3 mutation affecting the same codon but leading to a different amino acid substitution (p.R330C), previously identified in two families with typical BFNS. These data suggest that mutations in KCNQ3, similarly to KCNQ2, can be found in patients with more severe phenotypes including intellectual disability, and that the degree of the functional impairment caused by mutations at position 330 in KCNQ3 may contribute to clinical disease severity

Postharvest Quality during Refrigerated Storage of 'Nadorcott' Mandarin.

Made available in DSpace on 2018-01-09T16:13:40Z (GMT). No. of bitstreams: 1 RobertoPedrosoNadorcottMandarin.pdf: 240377 bytes, checksum: 6f913f64625e95d86347bb0c9092c4a4 (MD5) Previous issue date: 2018-01-09bitstream/item/170609/1/Roberto-Pedroso-Nadorcott-Mandarin.pd

Anatomically asymmetrical runners move more asymmetrically at the same metabolic cost.

We hypothesized that, as occurring in cars, body structural asymmetries could generate asymmetry in the kinematics/dynamics of locomotion, ending up in a higher metabolic cost of transport, i.e. more 'fuel' needed to travel a given distance. Previous studies found the asymmetries in horses' body negatively correlated with galloping performance. In this investigation, we analyzed anatomical differences between the left and right lower limbs as a whole by performing 3D cross-correlation of Magnetic Resonance Images of 19 male runners, clustered as Untrained Runners, Occasional Runners and Skilled Runners. Running kinematics of their body centre of mass were obtained from the body segments coordinates measured by a 3D motion capture system at incremental running velocities on a treadmill. A recent mathematical procedure quantified the asymmetry of the body centre of mass trajectory between the left and right steps. During the same sessions, runners' metabolic consumption was measured and the cost of transport was calculated. No correlations were found between anatomical/kinematic variables and the metabolic cost of transport, regardless of the training experience. However, anatomical symmetry significant correlated to the kinematic symmetry, and the most trained subjects showed the highest level of kinematic symmetry during running. Results suggest that despite the significant effects of anatomical asymmetry on kinematics, either those changes are too small to affect economy or some plastic compensation in the locomotor system mitigates the hypothesized change in energy expenditure of running

Bi-allelic genetic variants in the translational GTPases GTPBP1 and GTPBP2 cause a distinct identical neurodevelopmental syndrome

The homologous genes GTPBP1 and GTPBP2 encode GTP-binding proteins 1 and 2, which are involved in ribosomal homeostasis. Pathogenic variants in GTPBP2 were recently shown to be an ultra-rare cause of neurodegenerative or neurodevelopmental disorders (NDDs). Until now, no human phenotype has been linked to GTPBP1. Here, we describe individuals carrying bi-allelic GTPBP1 variants that display an identical phenotype with GTPBP2 and characterize the overall spectrum of GTP-binding protein (1/2)-related disorders. In this study, 20 individuals from 16 families with distinct NDDs and syndromic facial features were investigated by whole-exome (WES) or whole-genome (WGS) sequencing. To assess the functional impact of the identified genetic variants, semi-quantitative PCR, western blot, and ribosome profiling assays were performed in fibroblasts from affected individuals. We also investigated the effect of reducing expression of CG2017, an ortholog of human GTPBP1/2, in the fruit fly Drosophila melanogaster. Individuals with bi-allelic GTPBP1 or GTPBP2 variants presented with microcephaly, profound neurodevelopmental impairment, pathognomonic craniofacial features, and ectodermal defects. Abnormal vision and/or hearing, progressive spasticity, choreoathetoid movements, refractory epilepsy, and brain atrophy were part of the core phenotype of this syndrome. Cell line studies identified a loss-of-function (LoF) impact of the disease-associated variants but no significant abnormalities on ribosome profiling. Reduced expression of CG2017 isoforms was associated with locomotor impairment in Drosophila. In conclusion, bi-allelic GTPBP1 and GTPBP2 LoF variants cause an identical, distinct neurodevelopmental syndrome. Mutant CG2017 knockout flies display motor impairment, highlighting the conserved role for GTP-binding proteins in CNS development across species