Severe Palsy Research Articles

Mutagenic impact of the biotoxin of veined rapa whelk <i>Rapana venosa </i> (Valenciennes, 1846) (Gastropoda, Muricidae)

The invasion of the predatory gastropod mollusk Rapana venosa, known as veined rapa whelk, in the Black Sea and its outspread in many regions of the World Ocean have led to complex structural changes in the communities of bivalve mollusks. When capturing a prey, the adult rapa whelk excretes a biotoxin from the hypobranchial gland that causes severe paralysis of the musculature of bivalve mollusks. Under experimental conditions, it was established that the biotoxin, after the short-term exposure of the fertilized eggs of the mussels Mytilus galloprovincialis to it, has a mutagenic effect, causing chromosomal aberrations in the embryos. The acentric groups of chromosomes, single and multiple chromosome bridges, chromosome lags and polyploidy indicate transformation or destruction of threads of the achromatin spindle in the mitosis anaphase. The chromosome fragmentation and emergence of ring chromosomes in the metaphase and anaphase of mitosis of mussel embryos are the consequence of the partial destruction of chromatin. The underdeveloped shell, anomalous development of D-veligers’ velum, and the changed form of the ‘eye spots’ and hepatopancreas of the larvae at the veliconcha stage result from chromosomal mutations during the embryo development. The mechanism of the rapa whelk biotoxin action on the chromosomal apparatus of mussel embryos is discussed.

Brain Functional Networks Study of Subacute Stroke Patients With Upper Limb Dysfunction After Comprehensive Rehabilitation Including BCI Training.

Brain computer interface (BCI)-based training is promising for the treatment of stroke patients with upper limb (UL) paralysis. However, most stroke patients receive comprehensive treatment that not only includes BCI, but also routine training. The purpose of this study was to investigate the topological alterations in brain functional networks following comprehensive treatment, including BCI training, in the subacute stage of stroke. Twenty-five hospitalized subacute stroke patients with moderate to severe UL paralysis were assigned to one of two groups: 4-week comprehensive treatment, including routine and BCI training (BCI group, BG, n = 14) and 4-week routine training without BCI support (control group, CG, n = 11). Functional UL assessments were performed before and after training, including, Fugl-Meyer Assessment-UL (FMA-UL), Action Research Arm Test (ARAT), and Wolf Motor Function Test (WMFT). Neuroimaging assessment of functional connectivity (FC) in the BG was performed by resting state functional magnetic resonance imaging. After training, as compared with baseline, all clinical assessments (FMA-UL, ARAT, and WMFT) improved significantly (p < 0.05) in both groups. Meanwhile, better functional improvements were observed in FMA-UL (p < 0.05), ARAT (p < 0.05), and WMFT (p < 0.05) in the BG. Meanwhile, FC of the BG increased across the whole brain, including the temporal, parietal, and occipital lobes and subcortical regions. More importantly, increased inter-hemispheric FC between the somatosensory association cortex and putamen was strongly positively associated with UL motor function after training. Our findings demonstrate that comprehensive rehabilitation, including BCI training, can enhance UL motor function better than routine training for subacute stroke patients. The reorganization of brain functional networks topology in subacute stroke patients allows for increased coordination between the multi-sensory and motor-related cortex and the extrapyramidal system. Future long-term, longitudinal, controlled neuroimaging studies are needed to assess the effectiveness of BCI training as an approach to promote brain plasticity during the subacute stage of stroke.

Kinesthetic illusion induced by visual stimulation influences sensorimotor event-related desynchronization in stroke patients with severe upper-limb paralysis: A pilot study

Repetition of motor imagery improves the motor function of patients with stroke. However, patients who develop severe upper-limb paralysis after chronic stroke often have an impaired ability to induce motor imagery. We have developed a method to passively induce kinesthetic perception using visual stimulation (kinesthetic illusion induced by visual stimulation [KINVIS]). This pilot study further investigated the effectiveness of KINVIS in improving the induction of kinesthetic motor imagery in patients with severe upper-limb paralysis after stroke. Twenty participants (11 with right hemiplegia and 9 with left hemiplegia; mean time from onset [±standard deviation], 67.0±57.2 months) with severe upper-limb paralysis who could not extend their paretic fingers were included in this study. The ability to induce motor imagery was evaluated using the event-related desynchronization (ERD) recorded during motor imagery before and after the application of KINVIS for 20 min. The alpha- and beta-band ERDs around the premotor, primary sensorimotor, and posterior parietal cortices of the affected and unaffected hemispheres were evaluated during kinesthetic motor imagery of finger extension and before and after the intervention. Beta-band ERD recorded from the affected hemisphere around the sensorimotor area showed a significant increase after the intervention, while the other ERDs remained unchanged. In patients with chronic stroke who were unable to extend their paretic fingers for a prolonged period of time, the application of KINVIS, which evokes kinesthetic perception, improved their ability to induce motor imagery. Our findings suggest that although KINVIS is a passive intervention, its short-term application can induce changes related to the motor output system.

Hypokalemic thyrotoxic periodic paralysis in a young Serbian male

Introduction. Hypokalemic thyrotoxic paralysis is a very rare form of periodic paralysis in Caucasian population. In this population, a more frequent form is familiar hypokalemic periodic paralysis with the same clinical presentation. It is flaccid paralysis of proximal muscles in extremities. Having in mind that clinical presentation of hyperthyroidism in these patients is milder than it could be expected with given values of thyroid hormones, differential diagnosis to other forms of hypokalemic paralysis is essential. Case report. We presented a case of a young male with hyperthyroidism and severe periodic flaccid paralysis particularly of leg muscles. Laboratory findings showed elevated thyroid hormones levels and hypokalemia during the attacks with normalized potassium levels between attacks. The patient had no relatives with the similar condition. Also, he never had anything like these attacks prior to development of hyperthyroidism. After differential diagnosis, other reasons for hypokalemic periodic paralysis were excluded. We intensified the hyperthyroidism treatment and resolved hypokalemic periodic paralysis attacks with potassium chloride (KCl) infusions. The patient was advised to start a definitive treatment of hyperthyroidism after stabilization of hormonal levels. Conclusion. Hypokalemic thyrotoxic paralysis is a rare and potentially dangerous condition which, if recognized, can be prevented by resolving hyperthyroxinemia and the use of nonselective ? blockers.

Upregulating excitability of corticospinal pathways in stroke patients using TMS neurofeedback; A pilot study

Upper limb weakness following a stroke affects 80% of survivors and is a key factor in preventing their return to independence. State-of-the art approaches to rehabilitation often require that the patient can generate some activity in the paretic limb, which is not possible for many patients in the early period following stroke. Approaches that enable more patients to engage with upper limb therapy earlier are urgently needed.Motor imagery has shown promise as a potential means to maintain activity in the brain’s motor network, when the patient is incapable of generating functional movement. However, as imagery is a hidden mental process, it is impossible for individuals to gauge what impact this is having upon their neural activity.Here we used a novel brain-computer interface (BCI) approach allowing patients to gain an insight into the effect of motor imagery on their brain-muscle pathways, in real-time. Seven patients 2–26 weeks post stroke were provided with neurofeedback (NF) of their corticospinal excitability measured by the size of motor evoked potentials (MEP) in response to transcranial magnetic stimulation (TMS). The aim was to train patients to use motor imagery to increase the size of MEPs, using the BCI with a computer game displaying neurofeedback.Patients training finger muscles learned to elevate MEP amplitudes above their resting baseline values for the first dorsal interosseous (FDI) and abductor digiti minimi (ADM) muscles. By day 3 for ADM and day 4 for FDI, MEP amplitudes were sustained above baseline in all three NF blocks.Here we have described the first clinical implementation of TMS NF in a population of sub-acute stroke patients. The results show that in the context of severe upper limb paralysis, patients are capable of using neurofeedback to elevate corticospinal excitability in the affected muscles. This may provide a new training modality for early intervention following stroke.

Characterization, molecular modeling and phylogenetic analysis of a long mammalian neurotoxin from the venom of the Iranian scorpion Androctonus crassicauda

Scorpion venoms are highly complex polypeptides with a wide spectrum of bioactivities. A long chain peptide with eight cysteine residues and four disulfide bonds isolated from the venom of the Iranian scorpion Androctonus crassicauda, a dangerously venomous species belongs to the Buthidae family. Toxin was purified using size exclusion and reverse phase chromatography and was characterized by molecular weight determination and amino acid sequence. The primary structure analysis shows that AnCra1 is a long peptide with 64 amino acid residues and 7255.23 Da. as molecular weight. This toxic peptide, causing severe paralysis and leading to dead. It shows highest homology with voltage-gated sodium channel alpha toxins isolated from Middle-East and North-Africa scorpions. Phylogenetic relationship of AnCra1 and other ion channel toxins from Buthidae family suggested that, separation between these families of scorpions caused by the geographical conditions led to evolutionary alterations in these venoms polypeptide sequences. Homology modeling and three-dimensional structure of AnCra1 indicated that binding residues on exposed part of the peptide have high affinity for receptor residues in Na+V ion channel, site-3. The contact surfaces characteristics and charges may be eventuate to interaction between toxin peptide and targeted channel. Molecular homology between AnCra1 with structure of Na+V neurotoxic peptides illustrated that, AnCra1 can act as novel functional putative Alpha-mammal voltage-gated sodium channel toxin.

A Case Series Clinical Trial of a Novel Approach Using Augmented Reality That Inspires Self-body Cognition in Patients With Stroke: Effects on Motor Function and Resting-State Brain Functional Connectivity.

Barring a few studies, there are not enough established treatments to improve upper limb motor function in patients with severe impairments due to chronic stroke. This study aimed to clarify the effect of the kinesthetic perceptional illusion induced by visual stimulation (KINVIS) on upper limb motor function and the relationship between motor function and resting-state brain networks. Eleven patients with severe paralysis of upper limb motor function in the chronic phase (seven men and four women; age: 54.7 ± 10.8 years; 44.0 ± 29.0 months post-stroke) participated in the study. Patients underwent an intervention consisting of therapy using KINVIS and conventional therapeutic exercise (TherEX) for 10 days. Our originally developed KiNvis™ system was applied to induce KINVIS while watching the movement of the artificial hand. Clinical outcomes were examined to evaluate motor functions and resting-state brain functional connectivity (rsFC) by analyzing blood-oxygen-level-dependent (BOLD) signals measured using functional magnetic resonance imaging (fMRI). The outcomes of motor function (Fugle-Meyer Assessment, FMA) and spasticity (Modified Ashworth Scale, MAS) significantly improved after the intervention. The improvement in MAS scores for the fingers and the wrist flexors reached a minimum of clinically important differences. Before the intervention, strong and significant negative correlations between the motor functions and rsFC of the inferior parietal lobule (IPL) and premotor cortex (PMd) in the unaffected hemisphere was demonstrated. These strong correlations were disappeared after the intervention. A negative and strong correlation between the motor function and rsFC of the bilateral inferior parietal sulcus (IPS) significantly changed to strong and positive correlation after the intervention. These results may suggest that the combination approach of KINVIS therapy and TherEX improved motor functions and decreased spasticity in the paralyzed upper extremity after stroke in the chronic phase, possibly indicating the contribution of embodied-visual stimulation. The rsFC for the interhemispheric IPS and intrahemispheric IPL and PMd may be a possible regulatory factor for improving motor function and spasticity.Clinical Trial Registration: www.ClinicalTrials.gov, identifier NCT01274117.

Brain oscillatory activity as a biomarker of motor recovery in chronic stroke.

In the present work, we investigated the relationship of oscillatory sensorimotor brain activity to motor recovery. The neurophysiological data of 30 chronic stroke patients with severe upper‐limb paralysis are the basis of the observational study presented here. These patients underwent an intervention including movement training based on combined brain–machine interfaces and physiotherapy of several weeks recorded in a double‐blinded randomized clinical trial. We analyzed the alpha oscillations over the motor cortex of 22 of these patients employing multilevel linear predictive modeling. We identified a significant correlation between the evolution of the alpha desynchronization during rehabilitative intervention and clinical improvement. Moreover, we observed that the initial alpha desynchronization conditions its modulation during intervention: Patients showing a strong alpha desynchronization at the beginning of the training improved if they increased their alpha desynchronization. Patients showing a small alpha desynchronization at initial training stages improved if they decreased it further on both hemispheres. In all patients, a progressive shift of desynchronization toward the ipsilesional hemisphere correlates significantly with clinical improvement regardless of lesion location. The results indicate that initial alpha desynchronization might be key for stratification of patients undergoing BMI interventions and that its interhemispheric balance plays an important role in motor recovery.

Detection of a Frameshift Deletion in the SPTBN4 Gene Leads to Prevention of Severe Myopathy and Postnatal Mortality in Pigs.

Piglet mortality is a complex phenotype that depends on the environment, selection on piglet health, but also on the interaction between the piglet and sow. However, also monogenic recessive defects contribute to piglet mortality. Selective breeding has decreased overall piglet mortality by improving both mothering abilities and piglet viability. However, variants underlying recessive monogenic defects are usually not well captured within the breeding values, potentially drifting to higher frequency as a result of intense selection or genetic drift. This study describes the identification by whole-genome sequencing of a recessive 16-bp deletion in the SPTBN4 gene causing postnatal mortality in a pig breeding line. The deletion induces a frameshift and a premature stop codon, producing an impaired and truncated spectrin beta non-erythrocytic 4 protein (SPTBN4). Applying medium density single nucleotide polymorphism (SNP) data available for all breeding animals, a pregnant carrier sow sired by a carrier boar was identified. Of the resulting piglets, two confirmed homozygous piglets suffered from severe myopathy, hind-limb paralysis, and tremors. Histopathological examination showed dispersed degeneration and decrease of cross-striations in the dorsal and hind-limb muscle fibers of the affected piglets. Hence, the affected piglets are unable to walk or drink, usually resulting in death within a few hours after birth. This study demonstrates how growing genomic resources in pig breeding can be applied to identify rare syndromes in breeding populations, that are usually poorly documented and often are not even known to have a genetic basis. The study allows to prevent carrier-by-carrier matings, thereby gradually decreasing the frequency of the detrimental allele and avoiding the birth of affected piglets, improving animal welfare. Finally, these “natural knockouts” increase our understanding of gene function within the mammalian clade, and provide a potential model for human disease.

Severe Acquired Hypokalemic Paralysis in a Bodybuilder After Self-Medication With Triamterene/Hydrochlorothiazide

Severe hypokalemia with severe neurological impairment and electrocardiogram (ECG) abnormalities due to the misuse of triamterene/hydrochlorothiazide (HCTZ) in a bodybuilder has not yet been reported. A 22-year-old bodybuilder developed acute generalized muscle cramps, sensory disturbance of the distal lower and upper limbs, quadriparesis, and urinary retention. These abnormalities were attributed to severe hypokalemia of 1.8 mmol/L (normal range 3.4-4.5 mmol/L) due to misuse of triamterene/HCTZ together with fluid restriction. He was cardiologically asymptomatic, but ECG revealed a corrected QT (QTc) interval of 625 ms. On intravenous application of fluids along with intravenous and oral substitution of potassium, his condition rapidly improved, such that the sensory disturbances, quadriparesis, and bladder dysfunction completely resolved within 2 days after admission. Self-medication with diuretics along with fluid restriction may result in severe hypokalemia, paralysis, and ECG abnormalities. Those responsible for the management of bodybuilding studios and competitions must be aware of the potential severe health threats caused by self-medication with diuretics and anabolic steroids. Although triamterene is potassium-sparing, it may enhance the potassium-lowering effect of HCTZ.

Guillain-Barre syndrome

Guillain-Barre syndrome is the most common and most severe acute flaccid paralysis, usually preceded by an infection or immune stimulation. A literature review of the last five years in Pubmed, Scopus, Embase, and Web of Science databases was done. Data were collected from epidemiological studies using the keywords. Guillain-Barre syndrome (GBS) is an acute, severe, and fulminant polyradiculoneuropathy. It has ascending muscle weakness, rapid evolution, the involvement of respiratory muscles with an evolution period of up to four weeks. It has the Classic and Variant forms of clinical presentation. Guillain-Barre Syndrome is a rapidly progressive disease. The diagnosis is clinical but requires exams such as electroneuromyography and cerebrospinal fluid analysis, so that treatment can be started as soon as possible to improve prognosis and increase survival of affected patients.

Sensorimotor ECoG Signal Features for BCI Control: A Comparison Between People With Locked-In Syndrome and Able-Bodied Controls.

The sensorimotor cortex is a frequently targeted brain area for the development of Brain-Computer Interfaces (BCIs) for communication in people with severe paralysis and communication problems (locked-in syndrome; LIS). It is widely acknowledged that this area displays an increase in high-frequency band (HFB) power and a decrease in the power of the low frequency band (LFB) during movement of, for example, the hand. Upon termination of hand movement, activity in the LFB band typically shows a short increase (rebound). The ability to modulate the neural signal in the sensorimotor cortex by imagining or attempting to move is crucial for the implementation of sensorimotor BCI in people who are unable to execute movements. This may not always be self-evident, since the most common causes of LIS, amyotrophic lateral sclerosis (ALS) and brain stem stroke, are associated with significant damage to the brain, potentially affecting the generation of baseline neural activity in the sensorimotor cortex and the modulation thereof by imagined or attempted hand movement. In the Utrecht NeuroProsthesis (UNP) study, a participant with LIS caused by ALS and a participant with LIS due to brain stem stroke were implanted with a fully implantable BCI, including subdural electrocorticography (ECoG) electrodes over the sensorimotor area, with the purpose of achieving ECoG-BCI-based communication. We noted differences between these participants in the spectral power changes generated by attempted movement of the hand. To better understand the nature and origin of these differences, we compared the baseline spectral features and task-induced modulation of the neural signal of the LIS participants, with those of a group of able-bodied people with epilepsy who received a subchronic implant with ECoG electrodes for diagnostic purposes. Our data show that baseline LFB oscillatory components and changes generated in the LFB power of the sensorimotor cortex by (attempted) hand movement differ between participants, despite consistent HFB responses in this area. We conclude that the etiology of LIS may have significant effects on the LFB spectral components in the sensorimotor cortex, which is relevant for the development of communication-BCIs for this population.

Automated artifact rejection algorithms harm P3 Speller brain-computer interface performance

ABSTRACTBrain-Computer Interfaces (BCIs) have been used to restore communication and control to people with severe paralysis. However, noninvasive BCIs based on electroencephalogram (EEG) are particularly vulnerable to noise artifacts. These artifacts, including electro-oculogram (EOG), can be orders of magnitude larger than the signal to be detected. Many automated methods have been proposed to remove EOG and other artifacts from EEG recordings, most based on blind source separation. This work presents a performance comparison of ten different automated artifact removal methods. Unfortunately, all tested methods substantially and significantly reduced P3 Speller BCI performance, and all methods were more likely to reduce performance than increase it. The least harmful methods were titled SOBI, JADER, and EFICA, but even these methods caused an average of approximately ten percentage points drop in BCI accuracy. Possible mechanistic causes for this empirical performance reduction are proposed.

Classification of Articulator Movements and Movement Direction from Sensorimotor Cortex Activity

For people suffering from severe paralysis, communication can be difficult or nearly impossible. Technology systems called brain-computer interfaces (BCIs) are being developed to assist these people with communication by using their brain activity to control a computer without any muscle activity. To benefit the development of BCIs that employ neural activity related to speech, we investigated if neural activity patterns related to different articulator movements can be distinguished from each other. We recorded with electrocorticography (ECoG), the neural activity related to different articulator movements in 4 epilepsy patients and classified which articulator participants moved based on the sensorimotor cortex activity patterns. The same was done for different movement directions of a single articulator, the tongue. In both experiments highly accurate classification was obtained, on average 92% for different articulators and 85% for different tongue directions. Furthermore, the data show that only a small part of the sensorimotor cortex is needed for classification (ca. 1 cm2). We show that recordings from small parts of the sensorimotor cortex contain information about different articulator movements which might be used for BCI control. Our results are of interest for BCI systems that aim to decode neural activity related to (actual or attempted) movements from a contained cortical area.

Burst fracture Th 9-10 treat with Transthoracal Corpectomy and stabilization: A Cases Report

Abstract. Spinal fracture and dislocation are among the most feared injuries by patients and physicians alike, as the consequences can be devastating, ranging from mild pain and discomfort to severe paralysis and even death. Spinal trauma is commonly found in patients admitted to level-one trauma centers after serious accidents like traffic, falling, and sports accidents.Injuries of the cervical spine account for one third of spinal fractures and half to two thirds of all spinal cord injuries.In the thoracolumbar spine, the most common unstable fracture is the burst fracture. Altogether, burst fractures have been reported to account for about 15% of spinal injuries.Incidence of burst fractures peaked at the thoracolumbar junction and between levels T5 and T8. In 10% of cases,more than one burst fracture was seen, thereof 53% on noncontiguous levels. Main accident mechanisms were falls, traffic, and sports. Neurological deficit was highest in patients with burst fractures of the cervical spine, independent of accident mechanism, and lowest in thoracolumbar junction fractures. Burst fractures occur frequently in high energy traumas and are most commonly associated with falling and traffic accidents.Multiple burst fractures occur in 10% of cases, half thereof on noncontiguous levels.Access to the anterior thoracic spine via the transthoracic approach (via thoracotomy) can be used for decompression and fusion. To perform adequate decompression and stabilization of the thoracic spine, obtaining good exposure is a must. Preservation and protection of the vascular structures in the thoracic cavity is the key to such an exposure. Preoperative workup should include imaging modalities (plain rontgens, MRI/CT scan) to specifically define the area of decompression. If a tumor is being evaluated, CT angiography and embolization are helpful in preoperative planning. Assistance by a thoracic surgeon for exposure is highly recommended.

The time course of dysphagia following traumatic cervical spinal cord injury: a prospective cohort study.

Prospective cohort study. To elucidate serial changes in dysphagia and elucidate the critical period for dysphagia following acute traumatic cervical spinal cord injury (CSCI). Spinal Injuries Center, Fukuoka, Japan. We prospectively examined individuals with acute traumatic CSCI admitted within 2 weeks after injury. Severity of dysphagia was evaluated using both the dysphagia severity scale (DSS) and functional oral intake scale (FOIS) at 2 weeks, 1 month, 2 months, and 3 months after injury. Condition of oral intake before injury was assessed by history taking. American Spinal Injury Association (ASIA) impairment scale grade and motor scores were also assessed at the same timepoints, and the correlation between dysphagia and paresis was analyzed. Sixty-five individuals with CSCI were assessed consecutively for 3 months after injury. Swallowing function, evaluated using both the DSS and FOIS, was significantly decreased at 2 weeks after injury, but significantly improved thereafter. Significant correlations between severity of dysphagia (DSS and FOIS scores) and motor scores were found at 2 weeks after injury (rs = 0.66 and 0.61; p < 0.001 and p < 0.001, respectively), indicating that individuals with lower motor scores had more severe swallowing dysfunction. Dysphagia occurred immediately after injury, but gradually improved over time. Individuals with more severe paralysis had significantly more severe dysphagia. Special attention for dysphagia should be paid to individuals with severe paralysis in acute phase.

Clinical Spectrum of West Nile Virus Neuroinvasive Disease.

West Nile virus (WNV) is the most common arbovirus infection in the United States. The diagnosis requires consideration of not only a broad spectrum of presenting symptoms, ranging from a mild febrile illness to severe encephalitis and acute flaccid paralysis, but also public health risk factors and seasonality. There is no approved targeted therapy for WNV, so treatment relies on supportive care, management of neurologic sequelae and airway, treatment of other systems including the eye, and aggressive rehabilitation. Here, we describe a series of 3 cases of WNV encountered in September 2018 at one institution. First, we describe a case of WNV encephalitis with worsened dyskinesias and a relatively good recovery. Second, we describe a severe WNV encephalitis with overlying motor neuron involvement with a poor outcome. Finally, we describe a case of a WNV meningitis with significant bilateral chorioretinitis, an underappreciated complication of WNV infections. Through these cases, we review the epidemiology of WNV, risk factors for infection, the neurologic sequalae and long-term outcomes, and the importance of recognizing ocular involvement to prevent ophthalmologic complications.

Multifunctional Toxins in Snake Venoms and Therapeutic Implications: From Pain to Hemorrhage and Necrosis

Animal venoms have evolved over millions of years for prey capture and defense from predators and rivals. Snake venoms, in particular, have evolved a wide diversity of peptides and proteins that induce harmful inflammatory and neurotoxic effects including severe pain and paralysis, hemotoxic effects, such as hemorrhage and coagulopathy, and cytotoxic/myotoxic effects, such as inflammation and necrosis. If untreated, many envenomings result in death or severe morbidity in humans and, despite advances in management, snakebite remains a major public health problem, particularly in developing countries. Consequently, the World Health Organization recently recognized snakebite as a neglected tropical disease that affects ~2.7 million p.a. The major protein classes found in snake venoms are phospholipases, metalloproteases, serine proteases, and three-finger peptides. The mechanisms of action and pharmacological properties of many snake venom toxins have been elucidated, revealing a complex multifunctional cocktail that can act synergistically to rapidly immobilize prey and deter predators. However, despite these advances many snake toxins remain to be structurally and pharmacologically characterized. In this review, the multifunctional features of the peptides and proteins found in snake venoms, as well as their evolutionary histories, are discussed with the view to identifying novel modes of action and improving snakebite treatments.

Intact single muscle fibres from SOD1G93A amyotrophic lateral sclerosis mice display preserved specific force, fatigue resistance and training-like adaptations.

How defects in muscle contractile function contribute to weakness in amyotrophic lateral sclerosis (ALS) were systematically investigated. Weakness in whole muscles from late stage SOD1G93A mice was explained by muscle atrophy as seen by reduced mass and maximal force. On the other hand, surviving single muscle fibres in late stage SOD1G93A have preserved intracellular Ca2+ handling, normal force-generating capacity and increased fatigue resistance. These intriguing findings provide a substrate for therapeutic interventions to potentiate muscular capacity and delay the progression of the ALS phenotype. Amyotrophic lateral sclerosis (ALS) is a motor neuron disease characterized by degeneration and loss of motor neurons, leading to severe muscle weakness and paralysis. The SOD1G93A mouse model of ALS displays motor neuron degeneration and a phenotype consistent with human ALS. The purpose of this study was to determine whether muscle weakness in ALS can be attributed to impaired intrinsic force generation in skeletal muscles. In the current study, motor neuron loss and decreased force were evident in whole flexor digitorum brevis (FDB) muscles of mice in the late stage of disease (125-150days of age). However, in intact single muscle fibres, specific force, tetanic myoplasmic free [Ca2+ ] ([Ca2+ ]i ), and resting [Ca2+ ]i remained unchanged with disease. Fibre-type distribution was maintained in late-stage SOD1G93A FDB muscles, but remaining muscle fibres displayed greater fatigue resistance compared to control and showed increased expression of myoglobin and mitochondrial respiratory chain proteins that are important determinants of fatigue resistance. Expression of genes central to both mitochondrial biogenesis and muscle atrophy where increased, suggesting that atrophic and compensatory adaptive signalling occurs simultaneously within the muscle tissue. These results support the hypothesis that muscle weakness in SOD1G93A is primarily attributed to neuromuscular degeneration and not intrinsic muscle fibre defects. In fact, surviving muscle fibres displayed maintained adaptive capacity with an exercise training-like phenotype, which suggests that compensatory mechanisms are activated that can function to delay disease progression.

An Electrooculography based Human Machine Interface for wheelchair control

This paper presents a novel single channel Electrooculography (EOG) based efficient Human–Machine Interface (HMI) for helping the individuals suffering from severe paralysis or motor degenerative diseases to regain mobility. In this study, we propose a robust system that generates control command using only one type of asynchronous eye activity (voluntary eye blink) to navigate the wheelchair without a need of graphical user interface. This work demonstrates a simple but robust and effective multi-level threshold strategy to generate control commands from multiple features associated with the single, double and triple voluntary eye blinks to control predefined actions (forward, right turn, left turn and stop). Experimental trials were carried out on the able-bodied and disabled subjects to validate the universal applicability of the algorithms. It achieved an average command detection and execution accuracy of 93.89% with information transfer rate (ITR) of 62.64 (bits/min) that shows the robust, sensitive and responsive features of the presented interface. In comparison with the established state of art similar HMI systems, our system achieved a better trade-off between higher accuracy and better ITR and while maintaining better performance in all qualitative and quantitative criteria. The results confirm that the proposed system offers a user-friendly, cost-effective and reliable alternative to the existing EOG-based HMI.