Project description:Studies on adult stroke patients have demonstrated functional changes in cortical excitability, metabolic rate, or blood flow after motor therapy, measures that can fluctuate rapidly over time. This study evaluated whether evidence could also be found for structural brain changes during an efficacious rehabilitation program.Chronic stroke patients were randomly assigned to receive either constraint-induced movement therapy (n=16) or a comparison therapy (n=20). Longitudinal voxel-based morphometry was performed on structural MRI scans obtained immediately before and after patients received therapy.The group receiving constraint-induced movement therapy exhibited far greater improvement in use of the more affected arm in the life situation than the comparison therapy group. Structural brain changes paralleled these improvements in spontaneous use of the more impaired arm for activities of daily living. There were profuse increases in gray matter in sensory and motor areas both contralateral and ipsilateral to the affected arm that were bilaterally symmetrical, as well as bilaterally in the hippocampus. In contrast, the comparison therapy group failed to show gray matter increases. Importantly, the magnitude of the observed gray matter increases was significantly correlated with amount of improvement in real-world arm use.These findings suggest that a previously overlooked type of brain plasticity, structural remodeling of the human brain, is harnessed by constraint-induced movement therapy for a condition once thought to be refractory to treatment: motor deficit in chronic stroke patients.
Project description:Parkinson's disease (PD) alters cortico-basal ganglia-thalamic circuitry and susceptibility to an illusion of bodily awareness, the Rubber Hand Illusion (RHI). Bodily awareness is thought to result from multisensory integration in a predominantly cortical network; the role of subcortical connections is unknown. We studied the effect of modulating cortico-subcortical circuitry on multisensory integration for bodily awareness in 24 PD patients treated with subthalamic nucleus (STN) deep brain stimulation (DBS), in comparison to 21 healthy volunteers, using the RHI experiment. Typically, synchronous visuo-tactile cues induce a false perception of touch on the rubber hand as if it were the subject's hand, whereas asynchronous visuo-tactile cues do not. However, we found that in the asynchronous condition, patients in the off-stimulation state did not reject the RHI as strongly as healthy controls; patients' rejection of the RHI strengthened when STN-DBS was switched on, although it remained weaker than that of controls. Patients in the off-stimulation state also misjudged the position of their hand, indicating it to be closer to the rubber hand than controls. However, STN-DBS did not affect proprioceptive judgements or subsequent arm movements altered by the perceptual effects of the illusion. Our findings support the idea that the STN and subcortical connections have a key role in multisensory integration for bodily awareness. Decision-making in multisensory bodily illusions is discussed.
Project description:Dispersal is the movement of organisms from one habitat to another that potentially results in gene flow. It is often plastic, allowing organisms to adjust dispersal movements depending on environmental conditions. A fundamental aim in ecology is to understand the determinants underlying dispersal and its plasticity. We utilized 22 strains of the ciliate Tetrahymena thermophila to determine if different phenotypic dispersal strategies co-exist within a species and which mechanisms underlie this variability. We quantified the cell morphologies impacting cell motility and dispersal. Distinct differences in innate cellular morphology and dispersal rates were detected, but no universally utilized combinations of morphological parameters correlate with dispersal. Rather, multiple distinct and plastic morphological changes impact cilia-dependent motility during dispersal, especially in proficient dispersing strains facing challenging environmental conditions. Combining ecology and cell biology experiments, we show that dispersal can be promoted through plastic motility-associated changes to cell morphology and motile cilia.
Project description:IntroductionMost solid organ transplantation is viewed as lifesaving, whereas vascularized composite allotransplantation (VCA) has been viewed as life enhancing. This article challenges the latter and argues that "social death" evident in severe face, hand, and larynx disfigurement can be potentially treated via VCA. Social death (from a social science perspective) consists of a combination of 7 components: social isolation, loneliness, ostracism, loss of personhood, change of role and identity, harm, and disfigurement.MethodsIn February 2016, PubMed and Google were searched for case reports of human face, hand, and larynx transplantation. Patient and team narratives were then coded for components of social death using social science and medical model criteria.ResultsEleven narratives were identified among 9 articles. The social science model (but not the medical model) described pretransplant social death and the resolution of social death by receiving VCA. Notably, the medical model of social death was deemed unsuitable for application to VCA. This is because case narratives consistently contradict elements of the medical model.ConclusionsBy including social death as a patient inclusion criterion for face, hand, and larynx VCA, these transplants can be considered lifesaving. Additionally, because VCA requires lifelong immunosuppressant medication, considering VCA as a lifesaving intervention improves the technology's risk-benefit analysis. Guidance for assessing social death is provided.
Project description:Despite their common use as eating utensils in East Asia, chopsticks require complex fine motor-skills for adequate operation and are thus most frequently used with the dominant hand; however, the effect of training time on the proficiency of using chopsticks with the non-dominant hand, as well as the brain activity underlying changes in skill, remain unclear. This study characterised the effect of time spent training in chopstick operation with the non-dominant hand on chopstick-use proficiency and the related brain activity to obtain data that may help individuals who are obliged to change handedness due to neurological disease to learn to use their non-dominant hand in performing daily activities. Thirty-two healthy right-handed students were randomly allocated to training (n?=?16) or control (n?=?16) groups; the former received 6 weeks of training in chopstick use with their non-dominant (left) hand, and the latter received none. After training, significant improvements in the execution speed and smoothness of upper extremity joints were observed in the training group. Moreover, left dorsolateral prefrontal cortex activity significantly decreased, and bilateral premotor cortex activity significantly increased across training. These results indicated that 6 weeks of chopstick training with the non-dominant hand effectively improved chopstick operation.
Project description:Vascularized composite allotransplantation of the eye is an appealing, novel method for reconstruction of the nonfunctioning eye. The authors' group has established the first orthotopic model for eye transplantation in the rat. With advancements in immunomodulation strategies together with new therapies in neuroregeneration, parallel development of human surgical protocols is vital for ensuring momentum toward eye transplantation in actual patients.Cadaveric donor tissue harvest (n = 8) was performed with orbital exenteration, combined open craniotomy, and endonasal approach to ligate the ophthalmic artery with a cuff of paraclival internal carotid artery, for transection of the optic nerve at the optic chiasm and transection of cranial nerves III to VI and the superior ophthalmic vein at the cavernous sinus. Candidate recipient vessels (superficial temporal/internal maxillary/facial artery and superficial temporal/facial vein) were exposed. Vein grafts were required for all anastomoses. Donor tissue was secured in recipient orbits followed by sequential venous and arterial anastomoses and nerve coaptation. Pedicle lengths and calibers were measured. All steps were timed, photographed, video recorded, and critically analyzed after each operative session.The technical feasibility of cadaveric donor procurement and transplantation to cadaveric recipient was established. Mean measurements included optic nerve length (39 mm) and caliber (5 mm), donor artery length (33 mm) and caliber (3 mm), and superior ophthalmic vein length (15 mm) and caliber (0.5 mm). Recipient superficial temporal, internal maxillary artery, and facial artery calibers were 0.8, 2, and 2 mm, respectively; and superior temporal and facial vein calibers were 0.8 and 2.5 mm, respectively.This surgical protocol serves as a benchmark for optimization of technique, large-animal model development, and ultimately potentiating the possibility of vision restoration transplantation surgery.Therapeutic, V.
Project description:Fabrication of inexpensive and flexible electronic and electrochemical sensors is in high demand for a wide range of biochemical and biomedical applications. We explore hand fabrication of CNT modified AgNPs electrodes using wax-on-plastic platforms and their application in electrochemical immunosensing. Wax patterns were printed on polyethylene terephthalate-based substrates to laydown templates for the electrodes. Hand painting was employed to fabricate a silver conductive layer using AgNPs ink applied in the hydrophilic regions of the substrate surrounded by wax. CNT was drop cast on top of the working electrodes to improve their electrochemical signal. The device layers were characterized by scanning electron microscopy. The electrochemical performance of the hand fabricated AgNPs and CNT/AgNPs electrodes was tested using cyclic voltammetry, differential pulse voltammetry, and amperometry. The electrochemical response of CNT/AgNPs electrodes was relatively faster, higher, and more selective than unmodified AgNPs sensing electrodes. Finally, the hand-painted CNT/AgNPs electrodes were applied to detect carcinoembryonic antigen (CEA) by measuring the end-product of immunoassay performed on magnetic particles. The detection limit for CEA was found to be 0.46 ng/mL.
Project description:Cellular plasticity is a hallmark of rare Claudin-low (CL) and metaplastic (MBC) breast cancer subtypes, with a documented overlap whose exact extent is yet unknown, and which are associated to resistance and poor survival. We used spatial transcriptomics to further characterise these plastic subtypes, respectively defined molecularly and histopathologically. We identified 3 putative CL tumours (CL-like) and 4 genomically unstable TNBC samples via molecular analyses, combined with 4 MBCs identified by a breast pathologist.
Project description:Given the global abundance and environmental persistence, exposure of humans and (aquatic) animals to micro- and nanoplastics is unavoidable. Current evidence indicates that micro- and nanoplastics can be taken up by aquatic organism as well as by mammals. Upon uptake, micro- and nanoplastics can reach the brain, although there is limited information regarding the number of particles that reaches the brain and the potential neurotoxicity of these small plastic particles.Earlier studies indicated that metal and metal-oxide nanoparticles, such as gold (Au) and titanium dioxide (TiO2) nanoparticles, can also reach the brain to exert a range of neurotoxic effects. Given the similarities between these chemically inert metal(oxide) nanoparticles and plastic particles, this review aims to provide an overview of the reported neurotoxic effects of micro- and nanoplastics in different species and in vitro. The combined data, although fragmentary, indicate that exposure to micro- and nanoplastics can induce oxidative stress, potentially resulting in cellular damage and an increased vulnerability to develop neuronal disorders. Additionally, exposure to micro- and nanoplastics can result in inhibition of acetylcholinesterase activity and altered neurotransmitter levels, which both may contribute to the reported behavioral changes.Currently, a systematic comparison of the neurotoxic effects of different particle types, shapes, sizes at different exposure concentrations and durations is lacking, but urgently needed to further elucidate the neurotoxic hazard and risk of exposure to micro- and nanoplastics.
Project description:Short-term motor practice leads to plasticity in the primary motor cortex (M1). The purpose of this study is to investigate the factors that determine the increase in corticospinal tract (CST) excitability after motor practice, with special focus on two factors; "the level of muscle activity" and "the presence/absence of a goal of keeping the activity level constant." Fifteen healthy subjects performed four types of rapid thumb adduction in separate sessions. In the "comfortable task" (C) and "forceful task" (F), the subjects adducted their thumb using comfortable and strong forces. In the "comfortable with a goal task" (CG) and "forceful with a goal task" (FG), subjects controlled the muscle activity at the same level as in the C and F, respectively, by adjusting the peak electromyographic amplitude within the target ranges. Paired associative stimulation (PAS), which combines peripheral nerve (median nerve) stimulation and transcranial magnetic stimulation (TMS), with an inter-stimulus interval of 25 ms (PAS25) was also done. Before and after the motor tasks and PAS25, TMS was applied to the M1. None of the four tasks showed any temporary changes in behavior, meaning no learning occurred. Motor-evoked potential (MEP) amplitude increased only after the FG and it exhibited a positive correlation with the MEP increase after PAS25, suggesting that FG and PAS25 share at least similar plasticity mechanisms in the M1. Resting motor threshold (RMT) decreased only after FG, suggesting that FG would also be associated with the membrane depolarization of M1 neurons. These results suggest task-dependent plasticity from the synergistic effect of forceful muscle activity and of setting a goal of keeping the activity level constant.