New-onset tachycardia-bradycardia syndrome following acute non-medullary brainstem infarction.

Tachycardia-bradycardia syndrome (TBS) is a variant of sick sinus syndrome (SSS) characterized by alternating tachycardia and bradycardia. A few cases of SSS secondary to structural lesions in the medulla have been reported, but there has never been a reported case of the rare sign akin to TBS following acute non-medullary brainstem infarction. Furthermore, new-onset cardiac arrhythmias in stroke often presented in one continuous pattern - either as bradycardia or tachycardia, but instances of an alternating fashion have been rarely reported. We present the case of a 46-year-old female who developed severe dizziness with vomiting, diplopia, and slurred speech, which gradually worsened to quadriplegia, severe hypophonia, and dysphagia. Brain magnetic resonance imaging (MRI) demonstrated acute midbrain and pontine infarction. Except for neurological symptoms, the patient experienced unexpected TBS with the symptoms of excessive sweating, palpitations, and irritability without any other predisposing factors. The frequency of the episodes gradually declined until it spontaneously disappeared the 5th day after admission. Given the unpredictable nature of the tachycardia and bradycardia, it was challenging to manage the arrythmias with medications. A pacemaker was recommended, but financial reasons led the patient to reject this option. Two weeks after antithrombotic therapy and rehabilitation, she was discharged with residual symptoms of diplopia, moderate dysarthria, mild quadriplegia, and no cardiac symptoms. Our case highlighted the occurrence of TBS as a new-onset arrhythmia that can manifest during the acute phase of non-medullary brainstem infarcts. Further research into brainstem lesions contributing to TBS is warranted us to elucidate the underlying mechanisms.

Hemichorea secondary to isolated temporal infarction with severe middle cerebral artery stenosis: a case report and review of literature.

BACKGROUND: Hemichorea typically results from a contralateral subthalamic nuclei (STN) lesion, although it has been reported in the cortex in a minority of cases. However, to our best knowledge, there are no documented cases in literature of hemichorea occurring as a secondary condition to an isolated temporal stroke. CASE PRESENTATION: We present a case of an elderly female who sustained a sudden onset of hemichorea in her right extremities, predominantly in the distal region, lasting over a period of two days. Brain diffuse weighted image (DWI) demonstrated a high signal in the temporal region, while magnetic resonance angiography (MRA) revealed severe stenosis of the middle cerebral artery. During the symptomatic phase, computed tomography perfusion (CTP) revealed delayed perfusion in the left middle cerebral artery territory, characterized by the time-to-peak (TTP) measure. Based on the results of her medical history and laboratory tests, we were able to rule out the possibility of infectious, toxic, or metabolic encephalopathy. Her symptoms gradually improved with antithrombotic and symptomatic treatment. CONCLUSIONS: It is important to recognize and consider acute onset hemichorea as an initial symptom of stroke to avoid misdiagnosis and delays in appropriate treatment. Further research on temporal lesion that lead to hemichorea is warranted to gain a better understanding of the underlying mechanisms.

Introduction of Nanobiotechnology.

Nano is a fine metric unit which means "one billionth." Nanotechnology is attracting attention as a technological basis to lead the fourth industry. By utilizing synergistic properties obtained from controlling the structure or arrangement of materials at the nanoscale, nanotechnology has evolved rapidly over the past half century and is active in a variety of fields such as materials, pharmaceuticals, and biology. This chapter briefly describes the concept and features of nanotechnology, as well as the preparation, analysis, characterization, and application of nanomaterials. Also, the prospects for nanotechnology along with the nanotoxicity are described.

Bioapplications of Nanomaterials.

Nanobiotechnology is known as the application of nanoscaled techniques in biology which bridges natural science to living organism for improving the quality of life of humans. Nanotechnology was first issued in 1959 and has been rapidly developed, supplying numerous benefits to basic scientific academy and to clinical application including human healthcare, specifically in cancer therapy. This chapter discusses recent advances and potentials of nanotechnology in pharmaceutics, therapeutics, biosensing, bioimaging, and gene delivery that demonstrate the multifunctionality of nanotechnology.

Whole-body kinematics and coordination in a complex dance sequence: Differences across skill levels.

This study examined differences across skill levels in the kinematics of a complex, whole-body, asymmetrical, cyclical dance sequence, the 'Alternate Basic' in Cha-Cha-Cha, to determine whether observed differences were consistent with Bernstein's (1967) model of development of coordination. Bernstein proposed that with novel motor skills, beginners move their bodies rigidly and spastically, freezing kinematic degrees of freedom (DOF) to constrain the motor system. As the skill becomes practised, the DOF unfreeze and movements become more dynamic, allowing the integration of reactional elements (passive forces, moments, etc.) and organisation of more complex coordinative structures. Twenty-nine dancers - beginners (n = 10), intermediates (n = 10), experts (n = 9) - performed 12 cycles of the dance sequence (total duration ~60 s). Three-dimensional kinematic data from 36 joint angles were collected using a 14-camera infrared motion capture system. Most joints displayed increased amplitude and speed of movement, especially early in skill progression (beginner-intermediate stage), with no evidence of any decreases, showing that unfreezing occurred around the general movement pattern early. Speed of movement continued to increase later (intermediate-expert stage), as well as further unfreezing of the upper limbs. Changes to intra-limb couplings were limited, comprising some early reductions in coupling strength. Principal component analyses (PCA) showed that the structure of movement became more organised with increased skill. There was an early reduction in the number of coordinative structures, while later, movement was integrated more into the first coordinative structure. As predicted by Bernstein's coordination development model, therefore, the kinematic DOF unfroze as skill level progressed, leading to increased organisation of coordinative structures. The results of this study support the importance of a whole-body perspective in studies of coordination, with incorporation of kinetic variables in future research in order to examine the role that reactional elements play in motor skill development.

Whole-body angular momentum in a complex dance sequence: Differences across skill levels.

Due to the redundant degrees of freedom (DOF) and nonlinearity of reactional kinetic elements within the human motor apparatus, controlling the complex dynamics of the human musculoskeletal system presents considerable difficulties. Based on this challenge, Bernstein (1967) viewed skill development as the process whereby the central nervous system (CNS) gains mastery of kinematic DOF and kinetic reactional elements (passive forces, moments etc.), with the highest level of skill characterised by optimal exploitation of reactional elements in the achievement of movement goals. A previous kinematic investigation into coordination differences in a complex multidirectional dance sequence demonstrated that general unfreezing of kinematic DOF occurred as dance skill progressed (Chang et al., submitted for publication). To gain insight into the role of angular reactional elements in skill, the present kinetic study investigated angular momentum and associated variables across three skill levels (beginners, intermediates, experts) within this same complex dance sequence. The results showed that the angular momenta of segments and accompanying angular reactional elements generally increased with skill level. More specifically, the findings suggested that while improvements in movement economy from cancellation of angular momentum between body segments occur early in skill progression, later in skill progression, experts utilise increased whole-body angular momentum. Although this is energetically expensive, it may enhance the aesthetic value of dance movements, and/or have mechanical advantages. Overall, the findings here provide support for Bernstein's (1967) model of skill development. Future research should quantify the relations between energy expenditure, key biomechanical variables that reflect skill and dance aesthetics as perceived by audiences.

Integrated genome sizing (IGS) approach for the parallelization of whole genome analysis.

BACKGROUND: The use of whole genome sequence has increased recently with rapid progression of next-generation sequencing (NGS) technologies. However, storing raw sequence reads to perform large-scale genome analysis pose hardware challenges. Despite advancement in genome analytic platforms, efficient approaches remain relevant especially as applied to the human genome. In this study, an Integrated Genome Sizing (IGS) approach is adopted to speed up multiple whole genome analysis in high-performance computing (HPC) environment. The approach splits a genome (GRCh37) into 630 chunks (fragments) wherein multiple chunks can simultaneously be parallelized for sequence analyses across cohorts. RESULTS: IGS was integrated on Maha-Fs (HPC) system, to provide the parallelization required to analyze 2504 whole genomes. Using a single reference pilot genome, NA12878, we compared the NGS process time between Maha-Fs (NFS SATA hard disk drive) and SGI-UV300 (solid state drive memory). It was observed that SGI-UV300 was faster, having 32.5 mins of process time, while that of the Maha-Fs was 55.2 mins. CONCLUSIONS: The implementation of IGS can leverage the ability of HPC systems to analyze multiple genomes simultaneously. We believe this approach will accelerate research advancement in personalized genomic medicine. Our method is comparable to the fastest methods for sequence alignment.

Cancer Drug Response Profile scan (CDRscan): A Deep Learning Model That Predicts Drug Effectiveness from Cancer Genomic Signature.

In the era of precision medicine, cancer therapy can be tailored to an individual patient based on the genomic profile of a tumour. Despite the ever-increasing abundance of cancer genomic data, linking mutation profiles to drug efficacy remains a challenge. Herein, we report Cancer Drug Response profile scan (CDRscan) a novel deep learning model that predicts anticancer drug responsiveness based on a large-scale drug screening assay data encompassing genomic profiles of 787 human cancer cell lines and structural profiles of 244 drugs. CDRscan employs a two-step convolution architecture, where the genomic mutational fingerprints of cell lines and the molecular fingerprints of drugs are processed individually, then merged by 'virtual docking', an in silico modelling of drug treatment. Analysis of the goodness-of-fit between observed and predicted drug response revealed a high prediction accuracy of CDRscan (R2 > 0.84; AUROC > 0.98). We applied CDRscan to 1,487 approved drugs and identified 14 oncology and 23 non-oncology drugs having new potential cancer indications. This, to our knowledge, is the first-time application of a deep learning model in predicting the feasibility of drug repurposing. By further clinical validation, CDRscan is expected to allow selection of the most effective anticancer drugs for the genomic profile of the individual patient.

Primary medullary hemorrhage in a patient with coagulopathy due to alcoholic cirrhosis: A case report.

RATIONALE: Mild-to-moderate alcoholic cirrhosis of the liver is related to spontaneous intracerebral hemorrhage (ICH). In terms of spontaneous brainstem hemorrhage, pontine is considered as the most common site in contrast to medulla oblongata where the hemorrhage is rarely seen. This rare primary medullary hemorrhage has been attributed so far to vascular malformation (VM), anticoagulants, hypertension, hemorrhagic transformation, and other undetermined factors. PATIENT CONCERNS: Herein, we describe a 53-year-old patient with 35-year history of alcohol abuse was admitted for acute-onset isolated hemianesthesia on the right side. He was normotensive on admission. A neurological examination revealed isolated hemihypoaesthesia on the right side. He had no history of hypertension, and viral hepatitis, and nil use of anticoagulants. DIAGNOSES: Brain computed tomography (CT) image demonstrated hemorrhagic lesion in dorsal and medial medulla oblongata which was ruptured into the fourth ventricle. Brain magnetic resonance imaging (MRI), and magnetic resonance angiography (MRA) demonstrated no evidence of VM. The laboratory tests implied liver dysfunction, thrombocytopenia, and coagulation disorders. Abdominal ultrasound, and CT image showed a small, and nodular liver with splenomegaly, suggestive of moderate alcoholic cirrhosis. INTERVENTIONS: Liver protection therapy and the management of coagulation disorders. OUTCOMES: After 14 days, he was discharged with mild hemianesthesia but with more improved parameters in laboratory tests. At the 6-month follow-up, brain MRI, MRA, and non-contrast MRI showed no significant findings except for a malacic lesion. LESSONS: We conclude that the patient had alcoholic cirrhosis with coagulopathy, and this may have resulted in primary medullary hemorrhage. This is a first case to report alcoholic cirrhosis as etiology of primary medullary hemorrhage.

Combined focal myoclonus and dystonia secondary to a cerebellar hemorrhage: a case report.

BACKGROUND: Myoclonus is a clinical sign characterized by sudden, brief jerky, shock-like involuntary movements of a muscle or group of muscles. Dystonia is defined as a syndrome of sustained muscle contractions, frequently causing twisting and repetitive movements or abnormal postures. Cases of myoclonus or dystonia secondary to a structural lesion in the cerebellum have been reported. However, there has never been a reported case of combined myoclonus and dystonia secondary to a cerebellar lesion. CASE PRESENTATION: Herein, we report a 22-year-old female patient with sudden-onset myoclonic jerks, dystonic posture and mild ataxia in the right upper extremity. At age 19, she experienced sudden headache with vomiting. The neurological examination showed ataxia, myoclonus and dystonia in the right upper extremity. Brain images demonstrated a hemorrhage in the right cerebellar hemisphere secondary to a cavernous malformation. After resection of the hemorrhagic mass, headache with vomiting disappeared and ataxia improved, but myoclonus and dystonia persisted. CONCLUSIONS: It is the first report of combined focal myoclonus and dystonia secondary to a cerebellar lesion.

An Exploration of the Perception of Dance and Its Relation to Biomechanical Motion: A Systematic Review and Narrative Synthesis.

In dance, the goals of actions are not always clearly defined. Investigations into the perceived quality of dance actions and their relation to biomechanical motion should give insight into the performance of dance actions and their goals. The purpose of this review was to explore and document current literature concerning dance perception and its relation to the biomechanics of motion. Seven studies were included in the review. The study results showed systematic differences between expert, non-expert, and novice dancers in biomechanical and perceptual measures, both of which also varied according to the actions expressed in dance. Biomechanical and perceptual variables were found to be correlated in all the studies in the review. Significant relations were observed between kinematic variables such as amplitude, speed, and variability of movement, and perceptual measures of beauty and performance quality. However, in general, there were no clear trends in these relations. Instead, the evidence suggests that perceptual ratings of dance may be specific to both the task (the skill of the particular action) and the context (the music and staging). The results also suggest that the human perceptual system is sensitive to skillful movements and neuromuscular coordination. Since the value perceived by audiences appears to be related to dance action goals and the coordination of dance elements, practitioners could place a priority on development and execution of those factors.

A Surrogate Technique for Investigating Deterministic Dynamics in Discrete Human Movement.

Entropy is an effective tool for investigation of human movement variability. However, before applying entropy, it can be beneficial to employ analyses to confirm that observed data are not solely the result of stochastic processes. This can be achieved by contrasting observed data with that produced using surrogate methods. Unlike continuous movement, no appropriate method has been applied to discrete human movement. This article proposes a novel surrogate method for discrete movement data, outlining the processes for determining its critical values. The proposed technique reliably generated surrogates for discrete joint angle time series, destroying fine-scale dynamics of the observed signal, while maintaining macro structural characteristics. Comparison of entropy estimates indicated observed signals had greater regularity than surrogates and were not only the result of stochastic but also deterministic processes. The proposed surrogate method is both a valid and reliable technique to investigate determinism in other discrete human movement time series.

Determining optimal trial size using sequential analysis.

When characterising typical human movement profiles, the optimal number of trials analysed for each participant should ensure a stable mean. Sequential analysis is one method able to establish the number of trials to stability by assessing a moving point mean against a set bandwidth. As the total trial number determining this bandwidth is selected arbitrarily, the effect of applying different total trial numbers on the results of sequential analysis was investigated. Twenty participants performed 30 trials of overarm throwing, and sequential analyses were applied to three dimensional (3-D) kinematic data over 10, 20 and 30 trial numbers. We found a total of 20 to be the preferred trial number for sequential analyses. Erroneous results were produced consistently by 10 trial number groups, while moving point means were statistically unchanged after the 10th trial. Subsequently, sequential analyses were applied to 20 trials to establish trials to stability in discrete and time series elements of the 3-D kinematic data. The results suggest that a trial size between 13 and 17 provides stable means for overarm throwing kinematics.

Perceptual and motor learning underlies human stick-balancing skill.

We investigated the acquisition of skill in balancing a stick (52 cm, 34 g) on the fingertip in nine participants using three-dimensional motion analysis. After 3.5 h of practice over 6 wk, the participants could more consistently balance the stick for longer durations with greatly reduced magnitude and speed of stick and finger movements. Irrespective of level of skill, the balanced stick behaved like a normal noninverted pendulum oscillating under greater-than-gravity torque with simple harmonic motion about a virtual pivot located at the radius of gyration above the center of mass. The control input parameter was the magnitude ratio between the torque applied on the stick by the participant and the torque due to gravity. The participants utilized only a narrow range of this parameter, which did not change with practice, to rotate the stick like a linear mass-spring system. With increased skill, the stick therefore maintained the same period of oscillation but showed marked reductions in magnitude of both oscillation and horizontal translation. Better balancing was associated with 1) more accurate visual localization of the stick and proprioceptive localization of the finger and 2) reduced cross-coupling errors between finger and stick movements in orthogonal directions; i.e., finger movements in the anteroposterior plane became less coupled with stick tip movements in the mediolateral plane, and vice versa. Development of this fine motor skill therefore depended on perceptual and motor learning to provide improved estimation of sensorimotor state and precision of motor commands to an unchanging internal model of the rotational dynamics.

Human stick balancing: an intermittent control explanation.

There are two issues in balancing a stick pivoting on a finger tip (or mechanically on a moving cart): maintaining the stick angle near to vertical and maintaining the horizontal position within the bounds of reach or cart track. The (linearised) dynamics of the angle are second order (although driven by pivot acceleration), and so, as in human standing, control of the angle is not, by itself very difficult. However, once the angle is under control, the position dynamics are, in general, fourth order. This makes control quite difficult for humans (and even an engineering control system requires careful design). Recently, three of the authors have experimentally demonstrated that humans control the stick angle in a special way: the closed-loop inverted pendulum behaves as a non-inverted pendulum with a virtual pivot somewhere between the stick centre and tip and with increased gravity. Moreover, they suggest that the virtual pivot lies at the radius of gyration (about the mass centre) above the mass centre. This paper gives a continuous-time control-theoretical interpretation of the virtual-pendulum approach. In particular, by using a novel cascade control structure, it is shown that the horizontal control of the virtual pivot becomes a second-order problem which is much easier to solve than the generic fourth-order problem. Hence, the use of the virtual pivot approach allows the control problem to be perceived by the subject as two separate second-order problems rather than a single fourth-order problem, and the control problem is therefore simplified. The theoretical predictions are verified using the data previously presented by three of the authors and analysed using a standard parameter estimation method. The experimental data indicate that although all subjects adopt the virtual pivot approach, the less expert subjects exhibit larger amplitude angular motion and poorly controlled translational motion. It is known that human control systems are delayed and intermittent, and therefore, the continuous-time strategy cannot be correct. However, the model of intermittent control used in this paper is based on the virtual pivot continuous-time control scheme, handles time delays and moreover masquerades as the underlying continuous-time controller. In addition, the event-driven properties of intermittent control can explain experimentally observed variability.

A new paradigm for human stick balancing: a suspended not an inverted pendulum.

We studied 14 skilled subjects balancing a stick (a television antenna, 52 cm, 34 g) on their middle fingertip. Comprehensive three-dimensional analyses revealed that the movement of the finger was 1.75 times that of the stick tip, such that the balanced stick behaved more like a normal noninverted pendulum than the inverted pendulum common to engineering models for stick balancing using motors. The average relation between the torque applied to the stick and its angle of deviation from the vertical was highly linear, consistent with simple harmonic motion. We observed clearly greater rotational movement of the stick in the anteroposterior plane than the mediolateral plane. Despite this magnitude difference, the duration of stick oscillatory cycles was very similar in both planes, again consistent with simple harmonic motion. The control parameter in balancing was the ratio of active torque applied to the stick relative to gravitational torque. It determined both the pivot point and oscillatory cycle period of the pendulum. The pivot point was located at the radius of gyration (about the centre of mass) of the stick from its centre of mass, showing that the subjects attuned to the gravitational dynamics and mass distribution of the stick. Hence, the key to controlling instability here was mastery of the physics of the unstable object. The radius of gyration may--similar to centre of mass--contribute to the kinesthesis of rotating limb segments and control of their gravitational dynamics.