Propagation of extended fractures by local nucleation and rapid transverse expansion of crack-front distortion.

Fractures are ubiquitous and can lead to the catastrophic material failure of materials. Although fracturing in a two-dimensional plane is well understood, all fractures are extended in and propagate through three-dimensional space. Moreover, their behaviour is complex. Here we show that the forward propagation of a fracture front occurs through an initial rupture, nucleated at some localized position, followed by a very rapid transverse expansion at velocities as high as the Rayleigh-wave speed. We study fracturing in a circular geometry that achieves an uninterrupted extended fracture front and use a fluid to control the loading conditions that determine the amplitude of the forward jump. We find that this amplitude correlates with the transverse velocity. Dynamic rupture simulations capture the observations for only a high transverse velocity. These results highlight the importance of transverse dynamics in the forward propagation of an extended fracture.

Doublecortin mutation leads to persistent defects in the Golgi apparatus and mitochondria in adult hippocampal pyramidal cells.

Human doublecortin (DCX) mutations are associated with severe brain malformations leading to aberrant neuron positioning (heterotopia), intellectual disability and epilepsy. DCX is a microtubule-associated protein which plays a key role during neurodevelopment in neuronal migration and differentiation. Dcx knockout (KO) mice show disorganized hippocampal pyramidal neurons. The CA2/CA3 pyramidal cell layer is present as two abnormal layers and disorganized CA3 KO pyramidal neurons are also more excitable than wild-type (WT) cells. To further identify abnormalities, we characterized Dcx KO hippocampal neurons at subcellular, molecular and ultrastructural levels. Severe defects were observed in mitochondria, affecting number and distribution. Also, the Golgi apparatus was visibly abnormal, increased in volume and abnormally organized. Transcriptome analyses from laser microdissected hippocampal tissue at postnatal day 60 (P60) highlighted organelle abnormalities. Ultrastructural studies of CA3 cells performed in P60 (young adult) and > 9 months (mature) tissue showed that organelle defects are persistent throughout life. Locomotor activity and fear memory of young and mature adults were also abnormal: Dcx KO mice consistently performed less well than WT littermates, with defects becoming more severe with age. Thus, we show that disruption of a neurodevelopmentally-regulated gene can lead to permanent organelle anomalies contributing to abnormal adult behavior.

Regulation of microglia by neuromodulators: Modulations in major and minor modes.

Microglial cells, the brain resident macrophages, participate to brain development and function and help maintaining its homeostasis. To play these roles, they need to detect and adapt to modifications of their environment, including changes in the activity of neurons. The neuromodulators serotonin, dopamine, norepinephrine, acetylcholine and histamine are synthesized and released by specialized neurons to coordinate the activity of other neurons in different regions. In this review, we summarize the current evidence obtained in vitro or in vivo that neuromodulators act on microglia. On the short term, they can modify their motility, morphology and phagocytic activity; on the mid-long term they can modulate their transition between different immune activation states. Lastly, we review some recent data suggesting that these regulations of microglia by neuromodulators are involved in vivo in some aspects of central nervous system development, function and homeostasis.

The coefficient of friction in Parkinson's disease gait.

This study aimed to characterize the coefficient of friction (COF) curves of patients with Parkinson's disease (PD) during barefoot gait and to evaluate the relationships between this variable and functional scales. Twenty-two subjects with PD (ON phase of levodopa) and 22 healthy subjects participated in this study. The participants walked barefoot along a pathway that went over two force plates embedded in the floor of the data collection room. The instantaneous COF was calculated as the ratio between the horizontal and vertical components of the ground reaction forces. Two-sample t-tests applied to every 1% of the support phase of the COF curve were used to compare the groups and to identify the phases in which the two groups were different. Specifically, three COF areas were computed: Area 1 (for the loading response phase), Area 2 (for the midstance phase) and Area 3 (for the terminal stance phase). Pearson's tests were applied to assess the associations between the COF curve areas and the clinical scales. The subjects with PD exhibited lower COF values during the loading response and terminal stance phases and higher COF values during the mid-stance phase compared with the control group. A strong positive correlation was observed between Area 1 and the Timed Up and Go Test (90.3%). In conclusion, the patients' COFs exhibited patterns that were different from those of the control group. Moreover, during the loading response phase, these differences were well-correlated with the Timed Up and Go Test scale data; Timed Up and Go Test data can be used to identify the risk of falls among PD patients.

Robot-assisted gait training versus treadmill training in patients with Parkinson's disease: a kinematic evaluation with gait profile score.

The purpose of this study was to quantitatively compare the effects, on walking performance, of end-effector robotic rehabilitation locomotor training versus intensive training with a treadmill in Parkinson's disease (PD). Fifty patients with PD were randomly divided into two groups: 25 were assigned to the robot-assisted therapy group (RG) and 25 to the intensive treadmill therapy group (IG). They were evaluated with clinical examination and 3D quantitative gait analysis [gait profile score (GPS) and its constituent gait variable scores (GVSs) were calculated from gait analysis data] at the beginning (T0) and at the end (T1) of the treatment. In the RG no differences were found in the GPS, but there were significant improvements in some GVSs (Pelvic Obl and Hip Ab-Add). The IG showed no statistically significant changes in either GPS or GVSs. The end-effector robotic rehabilitation locomotor training improved gait kinematics and seems to be effective for rehabilitation in patients with mild PD.

Does neuromuscular taping influence hand kinesiology? A pilot study on Down's Syndrome.

PURPOSE: This paper is a first attempt analysis of hand and upper limb proprioception coordination induced by NeuroMuscular Taping (NMT): application in a group of 5 participants with Down syndrome. MATERIALS AND METHODS: The participants underwent a drawing test with motion capture system acquisition before and after NMT application. Specific and descriptive parameters were computed and analysed in order to quantify the differences. RESULTS: Results showed statistical differences between pre and post treatment sessions: the 5 participants with Down syndrome evidenced more reliance on proprioceptive signals in the post treatment session during the execution of the specific writing tasks. CONCLUSIONS: Based on the hypothesis that modifications in proprioception should alter motor pathway mapping of the motor cortex, Neuromuscular taping may play a role in the treatment of dysgraphia and improving hand coordination following CNS impairment, even though a small treatment group was chosen for this pilot study the results lead to further discussions concerning the role of different afferent signals in a pathological context.

Clumsiness in fine motor tasks: evidence from the quantitative drawing evaluation of children with Down Syndrome.

INTRODUCTION: Drawing tests are commonly used for the clinical evaluation of cognitive capabilities in children with learning disabilities. We analysed quantitatively the drawings of children with Down Syndrome (DS) and of healthy, mental age-matched controls to characterise the features of fine motor skills in DS during a drawing task, with particular attention to clumsiness, a well-known feature of DS gross movements. METHODS: Twenty-three children with DS and 13 controls hand-copied the figures of a circle, a cross and a square on a sheet. An optoelectronic system allowed the acquisition of the three-dimensional track of the drawing. The participants' posture and upper limb movements were analysed as well. RESULTS: Results showed that the participants with DS tended to draw faster but with less accuracy than controls. DISCUSSION: While clumsiness in gross movements manifests mainly as slow, less efficient movements, it manifests as high velocity and inaccurate movements in fine motor tasks such as drawing.

The effects of low arched feet on foot rotation during gait in children with Down syndrome.

BACKGROUND: In children with Down syndrome (DS) hypotonia and ligament laxity are characteristic features which cause a number of orthopaedic issues, such as flat foot. The aim of this study was to determine if children with flat foot are characterised by an accentuated external foot rotation during walking. METHOD: Fifty-five children with DS and 15 typically developing children recruited as control group were assessed using three-dimensional gait analysis, using an optoelectronic system, force platforms and video recording. Parameters related to foot rotation were identified and calculated and the participants' foot morphology was assessed using the arch index. RESULTS: Data obtained in this study showed that while DS children without flat foot displayed the foot position on the transverse plane globally close to controls during the whole gait cycle, the DS children with flat foot were characterised by higher extra-rotation of the foot in comparison with those without flat foot and controls. CONCLUSIONS: Our results suggest that the presence of flatfoot lead the children with DS to extra-rotate their feet more than the children without flat foot. From a clinical point of view, these results could enhance the rehabilitative programmes in DS.

Relationship between flat foot condition and gait pattern alterations in children with Down syndrome.

BACKGROUND: In patients with Down syndrome (DS) one of the most common abnormalities is flat foot which can interfere significantly with normal daily activities, such as gait. The aim of this study was to quantitatively assess the relationship between the flat foot and the gait alterations in DS children. METHOD: Twenty-nine patients with DS and 15 non-affected subjects were assessed using 3D Gait Analysis, using an optoelectronic system, force platforms and video recording. The degree of flat foot was assessed using the arch index and kinematic and kinetic parameters were identified and calculated from 3D Gait Analysis for each study participant. RESULTS: Data showed that ankle plantarflexion moment and ankle power during terminal stance were significant to differentiate the patients with and without flat feet: their peak values were significantly lower for the patients with flat foot. In addition, the research for correlation demonstrated that the higher the arch index value, the lower the peak of ankle moment and of the generated ankle power during terminal stance and the minimum of absorbed ankle power. CONCLUSIONS: Children with flat foot displayed a less functional gait pattern in terms of ankle kinetics than children without flat foot, suggesting that the presence of flat foot may lead to a weaker efficient walking. Then, the increasing flat foot tended to result in lower push-off ability, leading to a less functional walking.

Evaluation of posture signal using entropy analysis and fractal dimension in adults with Down syndrome.

The aim of this study was to explore new techniques in analysing postural control using nonlinear time-series analysis and to relate these results with the clinical knowledge on the postural system in Down syndrome (DS) subjects. In order to achieve the goal, we analysed the time domain and the frequency domain behaviour, the fractal dimension and the entropy of the centre of pressure signal in both directions during quiet standing in 35 participants with DS, comparing the results with a control population. DS patients evidenced a lack in postural control in anterior-posterior direction due to the impairment both in the high organisation and synergies and in the impairments due to ligament laxity and hypotonia. Maintaining posture is a task achieved by the integration of visual, vestibular and somatosensory receptors and the dynamical nature of this signal gives fundamental data about the lack of postural control in specific pathological condition.

Multiple primary melanomas: do they look the same?

BACKGROUND: A series of studies has investigated epidemiological, clinical and genetic characteristics of patients with multiple primary melanoma (MPM). However, comparison of the clinical and dermoscopic features of MPM within a given individual has been described only in case reports. OBJECTIVES: To describe the dermoscopic features of MPM for each given patient, and to evaluate the characteristics eventually associated with similar or dissimilar appearance. METHODS: From the databases of three skin-lesion clinics in the U.S.A., Italy and Spain we collected the dermoscopic images of melanomas in patients diagnosed with MPM. RESULTS: Among 58 patients with MPM, we found that 53% of patients had dermoscopically similar melanomas and 47% of patients had dermoscopically different melanomas. In older patients 59% of melanomas were dermoscopically similar vs. 47% in younger patients (P=0·377). Similar thickness was associated with the occurrence of dermoscopically similar melanomas (19/30 cases, 63%; P=0·039). Most (65%) of the synchronous lesions were similar, compared with 36% of nonsynchronous lesions (P=0·029), and most (69%) of the melanomas on sun-damaged skin were similar, vs. 37% of melanomas on nonsun-damaged skin (P=0·015; odds ratio 3·88, 95% confidence interval 1·11-13·98). The percentage of dermoscopically different melanomas was higher in patients with a family history of melanoma (67% vs. 48%). CONCLUSIONS: MPMs in a given patient have almost the same chance of looking dermoscopically similar or different. However, a subset of elderly patients with sun-damaged skin may present multiple, similar, thin melanomas characterized by pigment-network and regression structures.

Quantitative 3D evaluation of step ascent and descent in individuals with Down syndrome--analysis of a daily challenging task.

BACKGROUND: Step ascent and descent can perturb stability increasing the incidence of falls, especially in older individuals with functional limitations and intellectual disabilities, such as those with Down syndrome (DS). The aim of this study was to investigate the biomechanics and motor coordination of step ascent and descent in adults with DS and compare them with a group of healthy individuals, considering movement kinematics and kinetics. METHOD: Fourteen adults with DS and 12 similarly aged adults without DS who were free of known motor problems were quantitatively assessed during ascending and descending a step using an optoelectronic system (BTS SMART-D), force platforms and video recording. Kinematic and kinetic parameters were identified and calculated for each study participant and comparisons were made between the DS and a control group (CG). RESULTS: Despite similar age ranges, subjects in the DS group performed the step ascent and descent movements slower, with longer duration and with a more accentuated range of motion of the trunk and of the ankle joint than those in the CG. Additionally, the double stance phase on the step was substantially longer in the DS group when represented as a percentage of the entire stepping sequence (ascent, double stance on the step and descent). In terms of kinetics, ground force platform data revealed that the DS subjects showed higher instability in the medio-lateral direction during double support phase than similarly aged CG subjects and cannot be attributed to age-associated changes in stability. CONCLUSIONS: These findings help to elucidate the complex biomechanical strategy of people with DS during a step ascent and descent movement task and may have a major role in the multidimensional evaluation and tailored management for them.

The relation between Parkinson's disease and ageing. Comparison of the gait patterns of young Parkinson's disease subjects with healthy elderly subjects.

BACKGROUND: The gait of healthy elderly and of subjects with Parkinson's disease (PD) displays some common features, suggesting that PD may be a model of ageing. AIM: The aim of the study was to quantify highlight the differences and similarities between the gait patterns of young PD and healthy elderly, to uncover if PD could be assumed as a model of ageing. DESIGN: An optoelectronic system was used for 3D gait analysis evaluation. POPULATION AND METHODS: We compared the gait parameters of 15 young PD (YPD) with the gait of 32 healthy elderly subjects (ES) and 21 healthy subjects age-matched with the PD subjects. RESULTS. Common features between YPD and ES were majorly found in the parameters that reflect the presence of an unstable, uncertain gait, and of corrective strategies employed to reduce instability. On the other side, typical features were present in the gait patterns of PD subjects. CONCLUSION. Our study helped identifying some typical characteristics of the onset disease, and to unravel the symptoms of ageing from those of PD by comparing young PD subjects to elderly healthy subjects. CLINICAL REHABILITATION IMPACT: This allows a deeper understanding of the mechanisms underlying the gait in ageing and PD.

Clinical, dermoscopic and reflectance confocal microscopy features of sebaceous neoplasms in Muir-Torre syndrome.

BACKGROUND: Muir-Torre syndrome (MTS) is an autosomal-dominant disorder characterized by the association of sebaceous tumors or keratoacanthomas with an early onset visceral cancer in the spectrum of Lynch syndrome. OBSERVATIONS: A total of 20 sebaceous tumors including 18 sebaceous adenoma and two sebaceomas of six patients with MTS were analysed. Two main clinico-dermoscopic features were observed: (1) clinically pink to white papules/nodules with a central crater, dermoscopically characterized by radially arranged, elongated crown vessels surrounding opaque structureless yellow areas at times covered by blood crusts (n = 13) and (2), clinically pink to yellow papules/nodules without a central crater, dermoscopically exhibiting a few, loosely arranged yellow comedo-like globules and branching arborizing vessels (n = 7). Confocal microscopy was available in three sebaceous adenomas and revealed a good histopathologic correlation; sebaceous lobules were composed by clusters of ovoid cells with dark nuclei and bright, highly refractile glistening cytoplasm. They were delimited by a rim of epithelial cells, corresponding to basaloid cells. CONCLUSIONS: A better characterization of clinical, dermoscopic and confocal microscopy features of sebaceous tumors may improve their recognition and consequently, aid to rise the suspect for MTS.

Plasma renin concentration as a predictor of outcome in a medical intensive care setting: a retrospective pilot study.

BACKGROUND: Renin and aldosterone are involved in an organ perfusion pathway that may be an estimate of disease severity. The primary objective was to explore the relationship between outcome and aldosterone and renin levels at medical intensive care unit (MICU) admissions in comparison to SAPS II scores. METHODS: This retrospective study was conducted on patients admitted to the adult MICU during 12 months. Exclusion: subjects with creatinine >176 mmol/l, chronic arrhythmia and ACE-inhibitor therapy. Admission aldosterone and renin plasma levels were measured and SAPS II scores were calculated. RESULTS: Eighty-two patients were included. Only the plasma renin median concentration difference between survivors and non-survivors was significant (P=0.0168). The area under the ROC curve for mortality and plasma renin concentration was similar to that of SAPS II. The correlation between mortality and renin >84 pg/mL showed an odds ratio of 5.78±3.45, P=0.003. CONCLUSION: Renin was correlated to outcome in critically ill medical patients.

Form of dual-specificity tyrosine-(Y)-phosphorylation-regulated kinase 1A nonphosphorylated at tyrosine 145 and 147 is enriched in the nuclei of astroglial cells, adult hippocampal progenitors, and some cholinergic axon terminals.

Compelling lines of evidence indicate that overexpression of dual-specificity tyrosine-(Y)-phosphorylation regulated kinase 1A (DYRK1A) in subjects with trisomy 21 (Down syndrome[DS]) contributes to the abnormal structure and function of the DS brain. In the present study, we used a novel, phospho-dependent antibody recognizing DYRK1A only with nonphosphorylated tyrosine 145 and 147 (DYRK1A Tyr-145/147P(-)), to investigate the expression pattern of this DYRK1A species in trisomic and disomic human and mouse brains. Immunoblotting and dephosphorylation experiments demonstrated higher levels of DYRK1A Tyr-145/147P(-) in postnatal trisomic brains in comparison with controls (by ∼40%) than those of the DYRK1A visualized by three other N- and C-terminally directed antibodies to DYRK1A. By immunofluorescence, the immunoreactivity to DYRK1A Tyr-145/147P(-) was the strongest in the nuclei of astroglial cells, which contrasted with the predominantly neuronal localization of DYRK1A visualized by the three other antibodies to DYRK1A we used. In addition, DYRK1A Tyr-145/147P(-) was enriched in the nuclei of neuronal progenitors and newly born neurons in the adult hippocampal proliferative zone and also occurred in some cholinergic axonal terminals. Our data show a distinctive expression pattern of DYRK1A forms nonphosphorylated at Tyr-145 and Tyr-147 in the brain tissue and suggest that DS subjects may exhibit not only upregulation of total DYRK1A, but also more subtle differences in phosphorylation levels of this kinase in comparison with control individuals.

Spectral analysis of the voice in Down Syndrome.

The voice quality of individuals with Down Syndrome (DS) is generally described as husky, monotonous and raucous. On the other hand, the voice of DS children is characterized by breathiness, roughness, and nasality and is typically low pitched. However, research on phonation and intonation in these participants is limited. The present study was designed to provide data from the spectral analysis of the human voice in DS people. A cross-sectional, observational design was applied. Thirty DS adults and 48 DS children were enrolled after clinical evaluation. Thirty men, 30 women and 46 children constituted the control group. The participants had to repeat a set of Italian words twice. The Real Time Pitch software manufactured by KayPENTAX recorded the voice. The following spectral descriptors were obtained for each word: Mean Frequency and standard deviation, Energy, Duration, Jitter and Shimmer. Test-retest performance was also checked. The voice of DS adults was characterized by a significantly higher Mean Frequency, particularly in males (p<0.0001), by a smaller variation (p=0.0044 in males and p=0.0046 in females) and by a significantly lower level of Energy (p=0.0037 in males and p=0.0025 females). Furthermore, limited to male adults, a shorter Duration (p=0.0156) and a smaller value of Shimmer (p=0.0014) was observed. The difference between DS children and age-matched controls was limited, reaching significance only for the Coefficient of Variation (CV) (p=0.031). The difference in Mean Frequency between adults and children was more evident in the control males than in all other groups. The lack of marked difference between voice characteristics of children with and without DS is outlined by findings. Pearson's correlation coefficients on repeated productions ranged from 0.23 (Jitter) to 0.86 (Mean Frequency) in children, and from 0.07 (Shimmer) to 0.86 (Mean Frequency) in adults. In the control group, all the coefficients ranged between 0.85 and 0.98. As expected, women had a higher Mean Frequency than men, but the CV was around 0.1 for both. By contrast, children had a significantly higher Mean Frequency and a lower CV. In conclusion, spectral analysis of the human voice is recommended in each laboratory of speech and language rehabilitation to exploit the accuracy of voice descriptors.