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Changes in synaptic excitability and reduced brain metabolism are among the earliest detectable alterations associated with the development of Alzheimer's disease (AD). Stimulation of synaptic activity has been shown to be protective in models of AD beta-amyloidosis. Remarkably, deep brain stimulation (DBS) provides beneficial effects in AD patients, and represents an important therapeutic approach against AD and other forms of dementia. While several studies have explored the effect of synaptic activation on beta-amyloid, little is known about Tau protein. In this study, we investigated the effect of synaptic stimulation on Tau pathology and synapses in in vivo and in vitro models of AD and frontotemporal dementia (FTD). We found that chronic DBS or chemically induced synaptic stimulation reduced accumulation of pathological forms of Tau and protected synapses, while chronic inhibition of synaptic activity worsened Tau pathology and caused detrimental effects on pre- and post-synaptic markers, suggesting that synapses are affected. Interestingly, degradation via the proteasomal system was not involved in the reduction of pathological Tau during stimulation. In contrast, chronic synaptic activation promoted clearance of Tau oligomers by autophagosomes and lysosomes. Chronic inhibition of synaptic activity resulted in opposite outcomes, with build-up of Tau oligomers in enlarged auto-lysosomes. Our data indicate that synaptic activity counteracts the negative effects of Tau in AD and FTD by acting on autophagy, providing a rationale for therapeutic use of DBS and synaptic stimulation in tauopathies.

An analysis and modeling of the linear viscoelastic behavior of maltenes (M) blended with styrene–butadiene–styrene block copolymer (SBS) are presented in this study. M were mixed with different amounts of SBS (Elastomer, E ) (0.25–80 wt%) to investigate the effect of polymer concentration on linear viscoelastic response of the blends; storage and loss moduli were obtained from small amplitude oscillatory shear tests (SAOS). Time–temperature superposition master curves were analyzed by a Maxwell multi-modal model with up to nine relaxation times. Han, Cole–Cole and Van Gurp-Palmen diagrams were prepared from the rheological data. Two different responses were observed: At low E contents, a dispersed system rheological response was observed and verified by microscopy with elastomer as the dispersed phase and maltenes as the matrix, while at high E content the response was that of a co-continuous system. Mixtures with E  > 2 wt% exhibited change in their thermomechanical properties with a phase inversion at E  > 50 wt%. Furthermore, at low E concentration resins stabilize the dispersed phase by diminishing the magnitude of the viscoelastic moduli, conversely, at high E concentration a swelled polymer-rich phase creates a network that significantly influences of the viscoelastic properties.

Background/Objectives: The pathogenesis of enteritis after abdominal radiotherapy (RT) is unknown, although changes in fecal microbiota may be involved. Prebiotics stimulate the proliferation of Lactobacillus spp and Bifidobacterium spp, and this may have positive effects on the intestinal mucosa during abdominal RT. Subjects/Methods: We performed a randomized, double-blind, placebo-controlled trial involving patients with gynecological cancer who received abdominal RT after surgery. Patients were randomized to receive prebiotics or placebo. The prebiotic group received a mixture of fiber (50 inulin and 50% fructo-oligosaccharide), and the placebo group received 6 g of maltodextrin twice daily from 1 week before to 3 weeks after RT. The number of bowel movements and stool consistency was recorded daily. Diarrhea was evaluated according to the Common Toxicity Criteria of the National Cancer Institute. Stool consistency was assessed using the 7-point Bristol scale. Patients’ quality-of-life was evaluated at baseline and at completion of RT using the EORTC-QLQ-C30 (European Organization for Research and Treatment of Cancer quality-of-life Questionnaire C30) test. Results: Thirty-eight women with a mean age of 60.3±11.8 years participated in the study. Both groups (prebiotic ( n =20) and placebo (n =18)) were comparable in their baseline characteristics. The number of bowel movements per month increased in both groups during RT. The number of bowel movements per day increased in both groups. The number of days with watery stool (Bristol score 7) was lower in the prebiotic group (3.3±4.4 to 2.2±1.6) than in the placebo group ( P =0.08). With respect to quality-of-life, the symptoms with the highest score in the placebo group were insomnia at baseline and diarrhea toward the end of the treatment. In the prebiotic group, insomnia was the symptom with the highest score at both assessments, although the differences were not statistically significant. Conclusions: Prebiotics can improve the consistency of stools in gynecologic cancer patients on RT. This finding could have important implications in the quality-of-life of these patients during treatment.

More than 180 years ago, James Parkinson first described the disorder that bears his name, and 30 years ago levodopa, still the most effective therapy, was introduced. Parkinson's disease is a neurodegenerative disorder of unknown cause that affects over 1 million people in North America. Age is the single most consistent risk factor, and with the increasing age of the general population, the prevalence of Parkinson's disease will rise steadily in the future. The impact of the disease is indicated by the fact that mortality is two to five times as high among affected persons as among age matched controls, resulting in a marked reduction in life expectancy. In fact, neurodegenerative diseases (Parkinson's disease, motor neuron disease, and dementia) are projected to surpass cancer as the second most common cause of death among the elderly by the year 2040. Thus, Parkinson's disease greatly shortens life as well as causing debility during life.

Although it is widely accepted that the cortex participates in pain perception, there is no direct evidence for the existence of cortical neurons that respond to noxious or painful stimuli in humans. Anatomical and neurophysiological studies in animals as well as brain imaging and evoked potential studies in humans suggest that the anterior cingulate cortex (ACC) is an important area for processing sensory information related to pain 1 , 2 , 3 , 4 , 5 , 6 , 7 . We have now identified single neurons in ACC that respond selectively to painful thermal and mechanical stimuli, supporting a role for the ACC in pain perception.

At no time in the past have the basic and clinical sciences applied to Parkinson's disease been so active. Experimental therapies under study at present promise to improve on the limitations of existing treatments. Future progress in understanding the causation and pathogenesis of the disorder will permit the development of new treatments that will slow, halt, or even reverse the currently inexorable progressive course of Parkinson's disease.

Summary The major motor disturbances in Parkinson's disease are thought to be caused by overactivity of the internal segment of the globus pallidus (GPi), in large part due to excessive drive from the subthalamic nucleus. The excessive inhibitory activity of GPi is thought to \"brake' the motor thalamus and the cortical motor system to produce the slowness, rigidity, and poverty of movement characteristic of parkinsonian states. To test the hypothesis that direct reduction of Gpi activity can improve motor function, we studied the effect of GPi pallidotomy in 14 patients. The location of the GPi nucleus was confirmed by microelectrode recording before lesion creation. Standardised videotape recordings before and after operation were randomised and scored by a \"blinded' evaluator. 6 months after surgery, total motor score in the \"off\" state had improved by 30% and the total akinesia score by 33%. The gait score in the \"off\" state improved by 15% and a composite postural instability and gait score by 23%. After surgery there was almost total elimination of drug-induced involuntary movements (dyskinesias), with a 92% reduction on the side contralateral to the pallidotomy. No patient had visual or corticospinal complications. In these patients GPi pallidotomy enhanced motor performance, reduced akinesia, improved gait, and eliminated the neural elements responsible for levodopa-induced dyskinesias.

Background For patients with psychiatric illnesses remaining refractory to ‘standard’ therapies, neurosurgical procedures may be considered. Guidelines for safe and ethical conduct of such procedures have previously and independently been proposed by various local and regional expert groups. Methods To expand on these earlier documents, representative members of continental and international psychiatric and neurosurgical societies, joined efforts to further elaborate and adopt a pragmatic worldwide set of guidelines. These are intended to address a broad range of neuropsychiatric disorders, brain targets and neurosurgical techniques, taking into account cultural and social heterogeneities of healthcare environments. Findings The proposed consensus document highlights that, while stereotactic ablative procedures such as cingulotomy and capsulotomy for depression and obsessive-compulsive disorder are considered ‘established’ in some countries, they still lack level I evidence. Further, it is noted that deep brain stimulation in any brain target hitherto tried, and for any psychiatric or behavioural disorder, still remains at an investigational stage. Researchers are encouraged to design randomised controlled trials, based on scientific and data-driven rationales for disease and brain target selection. Experienced multidisciplinary teams are a mandatory requirement for the safe and ethical conduct of any psychiatric neurosurgery, ensuring documented refractoriness of patients, proper consent procedures that respect patient's capacity and autonomy, multifaceted preoperative as well as postoperative long-term follow-up evaluation, and reporting of effects and side effects for all patients. Interpretation This consensus document on ethical and scientific conduct of psychiatric surgery worldwide is designed to enhance patient safety.

Despite the introduction of several new medical therapies, patients with advanced Parkinson's disease continue to have fluctuations between pronounced increases in parkinsonism (“off” periods) and episodes of improved mobility (“on” periods), which are often complicated by choreoathetotic movements (dyskinesias). For this reason, there has been a resurgence of interest in neurosurgical interventions, particularly posteroventral medial pallidotomy. Defining the role of such an invasive therapy requires a long-term prospective study of a large number of patients using methods of evaluation with established sensitivity during off and on periods. To date, none of the few reports describing the effects of posteroventral medial . . .

Study design: Proof of concept study to control a neuroprosthesis for grasping using identification of arm movements from ECoG signals. Objective: To test the feasibility of using electrocorticographic (ECoG) signals as a control method for a neuroprosthesis for grasping. Setting: Acute care hospital, Toronto Western Hospital and spinal cord injury (SCI) rehabilitation centre, Toronto Rehabilitation Institute, Lyndhurst Centre. Both hospitals are located in Toronto, Canada. Methods: Two subjects participated in this study. The first subject had subdural electrodes implanted on the motor cortex for the treatment of essential tremor (ET). ECoG signals were recorded while the subject performed specific arm movements. The second subject had a complete SCI at C6 level (ASIA B score) and was fitted with a neuroprosthesis, capable of identifying arm movements from ECoG signals off-line, for grasping. To operate the neuroprosthesis, subject 2 issued a command that would trigger the release of a randomly selected ECoG signal recorded from subject 1, associated with a particular arm movement. The neuroprosthesis identified which arm movement was performed at the time of recording and used that information to trigger the stimulation sequence. A correct ECoG classification resulted in the neuroprosthesis producing the correct hand function (that is grasp and release). Results: The neuroprosthesis classified ECoG signals correctly delivering the correct stimulation strategy with 94.5% accuracy. Conclusions: The feasibility of using ECoG signals as a control strategy for a neuroprosthesis for grasping was shown.