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Lo A.C.,Brown University | Lo A.C.,Center for Restorative and Regenerative Medicine | Lo A.C.,Neuroscience Research
American Journal of Physical Medicine and Rehabilitation | Year: 2012

Rehabilitation robots are increasingly being tested and promoted for clinical neurorehabilitation. Compared with conventional and manual methods, robots allow for a variety of advantages, particularly in the areas of interventional control and the ability to provide a high volume of facilitated movement. Since 1997, there have been more than 60 clinical trials reporting the use of two dozen different robots for neurorehabilitation. Although there are a number of smaller pilot studies, there are only few larger clinical trials. There may be a number of reasons why pilot robot studies do not materialize into larger studies. Beyond devices that failed to perform as intended, what are the clinical design issues that have limited these studies? Some basic considerations include randomization, inclusion of a control group, power calculation based on a clinically meaningful outcome, and finally, reproducible descriptions of the intervention being tested. Although many of these issues are general challenges presented for all rehabilitation studies, there are clinical design features that would likely greatly improve interpretation of results and better position robot devices toward the next clinical trial step. On the other hand, the absence of these elements, even in the setting of a pilot study, may significantly hamper the interpretation of results and not yield sufficient information on treatment effects, adverse event rates, dropout rate, and so on, to allow further testing to proceed to follow-up Food and Drug Administration phase II and III studies. Development of rehabilitation robots for clinical use needs to occur hand in hand with well-conducted clinical trials to provide evidence of efficacy while also taking into account costs. Copyright © 2012 by Lippincott Williams & Wilkins. Source

Chauhan N.B.,Neuroscience Research | Chauhan N.B.,University of Illinois at Chicago
Restorative Neurology and Neuroscience | Year: 2014

Traumatic brain injury (TBI) is a serious public health concern and a major cause of death and disability worldwide. Each year, an estimated 1.7 million Americans sustain TBI of which ∼52,000 people die, ∼275,000 people are hospitalized and 1,365,000 people are treated as emergency outpatients. Currently there are ∼5.3 million Americans living with TBI. TBI is more of a disease process than of an event that is associated with immediate and long-term sensomotor, psychological and cognitive impairments. TBI is the best known established epigenetic risk factor for later development of neurodegenerative diseases and dementia. People sustaining TBI are ∼4 times more likely to develop dementia at a later stage than people without TBI. Single brain injury is linked to later development of symptoms resembling Alzheimer's disease while repetitive brain injuries are linked to later development of chronic traumatic encephalopathy (CTE) and/or Dementia Pugilistica (DP). Furthermore, genetic background of ß-amyloid precursor protein (APP), Apolipoprotein E (ApoE), presenilin (PS) and neprilysin (NEP) genes is associated with exacerbation of neurodegenerative process after TBI. This review encompasses acute effects and chronic neurodegenerative consequences after TBI. © 2014 - IOS Press. Source

Knight J.,National Health Research Institute | Knight J.,Neuroscience Research | Spain S.L.,Kings College London | Capon F.,Kings College London | And 7 more authors.
Human Molecular Genetics | Year: 2012

Psoriasis is a common, chronic, inflammatory skin disorder. A number of genetic loci have been shown to confer risk for psoriasis. Collectively, these offer an integrated model for the inherited basis for susceptibility to psoriasis that combines altered skin barrier function together with the dysregulation of innate immune pathogen sensing and adaptive immunity. The major histocompatibility complex (MHC) harbours the psoriasis susceptibility region which exhibits the largest effect size, driven in part by variation contained on the HLA-Cw*0602 allele. However, the resolution of the number and genomic location of potential independent risk loci are hampered by extensive linkage disequilibrium across the region. We leveraged the power of large psoriasis case and control data sets and the statistical approach of conditional analysis to identify potential further association signals distributed across the MHC. In addition to the major loci at HLA-C (P = 2.20 × 10-236), we observed and replicated four additional independent signals for disease association, three of which are novel. We detected evidence for association at SNPs rs2507971 (P = 6.73 × 10-14), rs9260313 (P = 7.93 × 10-09), rs66609536 (P = 3.54 × 10-07) and rs380924 (P = 6.24 × 10-06), located within the class I region of the MHC, with each observation replicated in an independent sample (P ≤ 0.01). The previously identified locus is close to MICA, the other three lie near MICB, HLA-A and HCG9 (a non-coding RNA gene). The identification of disease associations with both MICA and MICB is particularly intriguing, since each encodes an MHC class I-related protein with potent immunological function. © The Author 2012. Published by Oxford University Press. All rights reserved. Source

Until now, however, exactly how that happens has been somewhat of a scientific mystery. New research conducted by UC Santa Barbara neuroscientists has deciphered some of the earliest changes that occur before stems cells transform into neurons and other cell types. Working with human embryonic stems cells in petri dishes, postdoctoral fellow Jiwon Jang discovered a new pathway that plays a key role in cell differentiation. The findings appear in the journal Cell. "Jiwon's discovery is very important because it gives us a fundamental understanding of the way stem cells work and the way they begin to undergo differentiation," said senior author Kenneth S. Kosik, the Harriman Professor of Neuroscience Research in UCSB's Department of Molecular, Cellular, and Developmental Biology. "It's a very fundamental piece of knowledge that had been missing in the field." When stem cells begin to differentiate, they form precursors: neuroectoderms that have the potential to become brain cells, such as neurons; or mesendoderms, which ultimately become cells that comprise organs, muscles, blood and bone. Jang discovered a number of steps along what he and Kosik labeled the PAN (Primary cilium, Autophagy Nrf2) axis. This newly identified pathway appears to determine a stem cell's final form. "The PAN axis is a very important player in cell fate decisions," explained Jang. "G1 lengthening induces cilia protrusion and the longer those cellular antennae are exposed, the more signals they can pick up." For some time, scientists have known about Gap 1 (G1), the first of four phases in the cell cycle, but they weren't clear about its role in stem cell differentiation. Jang's research demonstrates that in stem cells destined to become neurons, the lengthening phase of G1 triggers other actions that cause stem cells to morph into neuroectoderms. During this elongated G1 interval, cells develop primary cilia, antennalike protrusions capable of sensing their environment. The cilia activate the cells' trash disposal system in a process known as autophagy. Another important factor is Nrf2, which monitors cells for dangerous molecules such as free radicals—a particularly important job for healthy cell formation. "Nrf2 is like a guardian to the cell and makes sure the cell is functioning properly," said Kosik, co-director of the campus's Neuroscience Research Institute. "Nrf2 levels are very high in stem cells because stem cells are the future. Without Nrf2 watching out for the integrity of the genome, future progeny are in trouble." Jang's work showed that levels of Nrf2 begin to decline during the elongated G1 interval. This is significant, Kosik noted, because Nrf2 doesn't usually diminish until the cell has already started to differentiate. "We thought that, under the same conditions if the cells are identical, that both would differentiate the same way, but that is not what we found," Jang said. "Cell fate is controlled by G1 lengthening, which extends cilia's exposure to signals from their environment. That is one cool concept." Explore further: Scientists find a groovy way to influence specialization of stem cells

Kalkman H.O.,Neuroscience Research | Feuerbach D.,Neuroscience Research
Cellular and Molecular Life Sciences | Year: 2016

The clinical development of selective alpha-7 nicotinic acetylcholine receptor (α7 nAChR) agonists has hitherto been focused on disorders characterized by cognitive deficits (e.g., Alzheimer’s disease, schizophrenia). However, α7 nAChRs are also widely expressed by cells of the immune system and by cells with a secondary role in pathogen defense. Activation of α7 nAChRs leads to an anti-inflammatory effect. Since sterile inflammation is a frequently observed phenomenon in both psychiatric disorders (e.g., schizophrenia, melancholic and bipolar depression) and neurological disorders (e.g., Alzheimer’s disease, Parkinson’s disease, and multiple sclerosis), α7 nAChR agonists might show beneficial effects in these central nervous system disorders. In the current review, we summarize information on receptor expression, the intracellular signaling pathways they modulate and reasons for receptor dysfunction. Information from tobacco smoking, vagus nerve stimulation, and cholinesterase inhibition is used to evaluate the therapeutic potential of selective α7 nAChR agonists in these inflammation-related disorders. © 2016, The Author(s). Source

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