Identifying the brain regions associated with acute spasticity in patients diagnosed with an ischemic stroke

Spasticity is a common impairment found in patients that have been diagnosed with a stroke. Little is known about the pathophysiology of spasticity at the level of the brain. This retrospective study was performed to identify an association between the area of the brain affected by an ischemic stroke and the presence of acute spasticity. Physical and occupational therapy assessments from all patients (n?=?441) that had suffered a stroke and were admitted into a local hospital over a 4-year period were screened for inclusion in this study. Subjects that fit the inclusion criteria were grouped according to the presence (n?=?42) or absence (n?=?129) of acute spasticity by the Modified Ashworth Scale score given during the hospital admission assessment. Magnetic resonance images from 20 subjects in the spasticity group and 52 from the control group were then compared using lesion density plots and voxel-based lesion–symptom mapping. An association of acute spasticity with the gray matter regions of the insula, basal ganglia, and thalamus was found in this study. White matter tracts including the pontine crossing tract, corticospinal tract, internal capsule, corona radiata, external capsule, and the superior fronto-occipital fasciculus were also found to be significantly associated with acute spasticity. This is the first study to describe an association between a region of the brain affected by an infarct and the presence of acute spasticity. Understanding the regions associated with acute spasticity will aid in understanding the pathophysiology of this musculoskeletal impairment at the level of the brain.     

Influence of Action-Effect Associations Acquired by Ideomotor Learning on Imitation

According to the ideomotor theory, actions are represented in terms of their perceptual effects, offering a solution for the correspondence problem of imitation (how to translate the observed action into a corresponding motor output). This effect-based coding of action is assumed to be acquired through action-effect learning. Accordingly, performing an action leads to the integration of the perceptual codes of the action effects with the motor commands that brought them about. While ideomotor theory is invoked to account for imitation, the influence of action-effect learning on imitative behavior remains unexplored. In two experiments, imitative performance was measured in a reaction time task following a phase of action-effect acquisition. During action-effect acquisition, participants freely executed a finger movement (index or little finger lifting), and then observed a similar (compatible learning) or a different (incompatible learning) movement. In Experiment 1, finger movements of left and right hands were presented as action-effects during acquisition. In Experiment 2, only right-hand finger movements were presented during action-effect acquisition and in the imitation task the observed hands were oriented orthogonally to participants’ hands in order to avoid spatial congruency effects. Experiments 1 and 2 showed that imitative performance was improved after compatible learning, compared to incompatible learning. In Experiment 2, although action-effect learning involved perception of finger movements of right hand only, imitative capabilities of right- and left-hand finger movements were equally affected. These results indicate that an observed movement stimulus processed as the effect of an action can later prime execution of that action, confirming the ideomotor approach to imitation. We further discuss these findings in relation to previous studies of action-effect learning and in the framework of current ideomotor approaches to imitation.     

New Type of Papillomavirus and Novel Circular Single Stranded DNA Virus Discovered in Urban Rattus norvegicus Using Circular DNA Enrichment and Metagenomics

Rattus norvegicus (R. norvegicus) are ubiquitous and their presence has several effects on the human populations in our urban areas on a global scale. Both historically and presently, this close interaction has facilitated the dissemination of many pathogens to humans, making screening for potentially zoonotic and emerging viruses in rats highly relevant. We have investigated faecal samples from R. norvegicus collected from urban areas using a protocol based on metagenomic enrichment of circular DNA genomes and subsequent sequencing. We found a new type of papillomavirus, with a L1 region 82% identical to that of the known R. norvegicus Papillomavirus 2. Additionally, we found 20 different circular replication associated protein (Rep)-encoding single stranded DNA (CRESS-DNA) virus-like genomes, one of which has homology to the replication-associated gene of Beak and feather disease virus. Papillomaviruses are a group of viruses known for their carcinogenic potential, and although they are known to infect several different vertebrates, they are mainly studied and characterised in humans. CRESS-DNA viruses are found in many different environments and tissue types. Both papillomaviruses and CRESS-DNA viruses are known to have pathogenic potential and screening for novel and known viruses in R. norvegicus could help identify viruses with pathogenic potential.     

Primary Succession on a Hawaiian Dryland Chronosequence

We used measurements from airborne imaging spectroscopy and LiDAR to quantify the biophysical structure and composition of vegetation on a dryland substrate age gradient in Hawaii. Both vertical stature and species composition changed during primary succession, and reveal a progressive increase in vertical stature on younger substrates followed by a collapse on Pleistocene-aged flows. Tall-stature Metrosideros polymorpha woodlands dominated on the youngest substrates (hundreds of years), and were replaced by the tall-stature endemic tree species Myoporum sandwicense and Sophora chrysophylla on intermediate-aged flows (thousands of years). The oldest substrates (tens of thousands of years) were dominated by the short-stature native shrub Dodonaea viscosa and endemic grass Eragrostis atropioides. We excavated 18 macroscopic charcoal fragments from Pleistocene-aged substrates. Mean radiocarbon age was 2,002 years and ranged from < 200 to 7,730. Genus identities from four fragments indicate that Osteomeles spp. or M. polymorpha once occupied the Pleistocene-aged substrates, but neither of these species is found there today. These findings indicate the existence of fires before humans are known to have occupied the Hawaiian archipelago, and demonstrate that a collapse in vertical stature is prevalent on the oldest substrates. This work contributes to our understanding of prehistoric fires in shaping the trajectory of primary succession in Hawaiian drylands.     

The Link between Knowledge,Attitudes and Practices in Relation to Atmospheric Haze Pollution in Peninsular Malaysia

Transboundary haze episodes caused by seasonal forest fires have become a recurrent phenomenon in Southeast Asia, with serious environmental, economic, and public health implications. Here we present a cross-sectional survey conducted among people in Kuala Lumpur and surrounds to assess the links between knowledge, attitudes, and practices in relation to the transboundary haze episodes. Of 305 respondents, 125 were amateur athletes participating in a duathlon event and the remainder were surveyed in an inner-city shopping mall. Across the whole sample, people who possessed more factual information about the haze phenomenon showed significantly higher levels of concern. Duathletes were more knowledgeable than non-duathletes and also more concerned about the negative effects of haze, especially on health. For all people who regularly practice outdoor sports (including people interviewed at the shopping mall), higher levels of knowledge and concerned attitudes translated into a greater likelihood of engaging in protective practices, such as cancelling their outdoor training sessions, while those with greater knowledge were more likely to check the relevant air pollution index on a daily basis. Our results indicate that the provision of accurate and timely information about air quality to residents will translate into beneficial practices, at least among particularly exposed individuals, such as amateur athletes who regularly practice outdoor sports.     

A speculative model of affective illness cyclicity based on patterns of drug tolerance observed in amygdala-kindled seizures

In this article, we discuss molecular mechanisms involved in the evolution of amygdala kindling and the episodic loss of response to pharmacological treatments during tolerance development. These phenomena allow us to consider how similar principles (in different neurochemical systems) could account for illness progression, cyclicity, and drug tolerance in affective disorders. We describe the phenomenon of amygdala-kindled seizures episodically breaking through effective daily pharmacotherapy with carbamazepine and valproate, suggesting that these observations could reflect the balance of pathological vs compensatory illness-induced changes in gene expression. Under certain circumstances, amygdala-kindled animals that were initially drug responsive can develop highly individualized patterns of seizure breakthroughs progressing toward a complete loss of drug efficacy. This initial drug efficacy may reflect the combination of drug-related exogenous neurochemical mechanisms and illness-induced endogenous compensatory mechanisms. However, we postulate that when seizures are inhibited, the endogenous illness-induced adaptations dissipate (the “time-off seizure” effect), leading to the re-emergence of seizures, a re-induction of a new, but diminished, set of endogenous compensatory mechanisms, and a temporary period of renewed drug efficacy. As this pattern repeats, an intermittent or cyclic response to the anticonvulsant treatment emerges, leading toward complete drug tolerance. We also postulate that the cyclic pattern accelerates over time because of both the failure of robust illness-induced endogenous adaptations to emerge and the progression in pathophysiological mechanisms (mediated by long-lasting changes in gene expression and their downstream consequences) as a result of repeated occurrences of seizures. In this seizure model, this pattern can be inhibited and drug responsivity can be temporarily reinstated by several manipulations, including lowering illness drive (decreasing the stimulation current.), increasing drug dosage, switching to a new drug that does not show crosstolerance to the original medication, or temporarily discontinuing treatment, allowing the illness to re-emerge in an unmedicated animal. Each of these variables is discussed in relation to the potential relevance to the emergence, progression, and suppression of individual patterns of episodic cyclicity in the recurrent affective disorders. A variety of clinical studies are outlined that specifically test the hypotheses derived from this formulation. Data from animal studies suggest that illness cyclicity can develop from the relative ratio between primary pathological processes and secondary endogenous adaptations (assisted by exogenous medications). If this proposition is verified, it further suggests that illness cyclicity is inherent to the neurobiological processes of episode emergence and amelioration, and one does not need to postulate a separate defect in the biological clock. The formulation predicts that early and aggressive long-term interventions may be optimal in order to prevent illness emergence and progression and its associated accumulating neurobiological, vulnerability factors.     

Imaging in five dimensions: time-dependent membrane potentials in individual mitochondria.

Because of its importance in the chemiosmotic theory, mitochondrial membrane potential has been the object of many investigations. Significantly, however, quantitative data on how energy transduction might be regulated or perturbed by the physiological state of the cell has only been gathered via indirect studies on isolated mitochondrial suspensions; quantitative studies on individual mitochondria in situ have not been possible because of their small size, their intrinsic motility, and the absence of appropriate analytical reagents. In this article, we combine techniques for rapid, high resolution, quantitative three-dimensional imaging microscopy and mathematical modeling to determine accurate distributions of a potentiometric fluorescent probe between the cytosol and individual mitochondria inside a living cell. Analysis of this distribution via the Nernst equation permits assignment of potentials to each of the imaged mitochondrial membranes. The mitochondrial membrane potentials are distributed over a narrow range centered at -150 mV within the neurites of differentiated neuroblastoma cells. We find that the membrane potential of a single mitochondrion is generally remarkably stable over times of 40-80 s, but significant fluctuations can occasionally be seen. The motility of individual mitochondria is not directly correlated to membrane potential, but mitochondria do become immobile after prolonged treatment with respiratory inhibitors or uncouplers. Thus, three spatial dimensions, a key physiological parameter, and their changes over time are all quantitated for objects at the resolution limit of light microscopy. The methods described may be readily extended to permit investigations of how mitochondrial function is integrated with other processes in the intact cell.