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Ischaemic stroke is characterized by high morbidity, high disability rate, high mortality and high recurrence rate, which can have a grave impact on the quality of life of the patients and consequently becomes an economic burden on their families and society. With the developments in imaging technology in recent years, patients with acute cerebral infarction are predominantly more likely to be diagnosed with leukoaraiosis (LA). LA is a common degenerative disease of the nervous system, which is related to cognitive decline, depression, abnormal gait, ischaemic stroke and atherosclerosis. The aetiology of LA is not clear and there is no gold standard for imaging assessment. Related studies have shown that LA has an adverse effect on the prognosis of cerebral infarction, but some experts have contrary beliefs. Hence, we undertook the present review of the literature on the mechanism and the effect of LA on the prognosis of patients with acute ischaemic stroke.

Sarcopenia is a comprehensive degenerative disease with the progressive loss of skeletal muscle mass with age, accompanied by the loss of muscle strength and muscle dysfunction. As a new type of senile syndrome, sarcopenia seriously threatens the health of the elderly. The first‐line treatment for sarcopenia is exercise and nutritional supplements. However, pharmacotherapy will provide more reliable and sustainable interventions in geriatric medicine. Clinical trials of new drugs targeting multiple molecules are ongoing. This article focuses on the latest progress in pharmacotherapeutic approaches of sarcopenia in recent years by comprehensively reviewing the clinical outcomes of the existing and emerging pharmacotherapies as well as the molecular mechanisms underlying their therapeutic benefits and side effects., Signaling of the pharmacotherapies of sarcopenia.

The importance of autonomic neurology has grown exponentially since the development of neuroscience, genetics, and immunology. Advances in this field have made it possible to elucidate the pathomechanism of dysautonomia and autonomic nervous system interactions in both health and disease. In the special issue ?Recent Advances in Autonomic Neurology,? four articles covering a wide range of topics in clinical neuroscience, including degenerative diseases, genetic disorders, immune-mediated neuropathy, and autoimmune encephalitis, were published. This review focused on presenting the recent progress in the clinical approaches for dysautonomia in autoimmune diseases, Ehlers-Danlos syndrome, myalgic encephalomyelitis/chronic fatigue syndrome, and coronavirus disease 2019 (COVID-19). Of particular current concern, is Long COVID, defined as the persistence of symptoms after 3 weeks from being infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), may involve autonomic dysfunction. The research and clinical practice for autonomic dysfunction in neurology is constantly evolving, which is exemplified by the current clinical research on Long COVID.

Peroxisome biogenesis disorders (PBDs) are a group of autosomal recessive disorders caused due to impaired peroxisome assembly affecting the formation of functional peroxisomes. PBDs are caused by a mutation in PEX gene family resulting in disease manifestation with extreme variability ranging from the onset of profound neurologic symptoms in newborns to progressive degenerative disease in adults. Disease causing variations in PEX7 is known to cause severe rhizomelic chondrodysplasia punctata type 1 and PBD 9B, an allelic disorder resulting in a milder phenotype, often indistinguishable from that of classic Refsum disease. This case report highlights the variability of PEX7 related phenotypes and suggests that other than RCDP1 and late onset phenotype similar to Refsum disease, some cases present with cataract and neurodevelopmetal abnormalities during childhood without chondrodysplasia or rhizomelia. This report also underlines the importance of considering PBD 9B in children presenting with neurodevelopmental abnormalities especially if they have congenital cataract.

Objective To compare the clinical efficacy of percutaneous full‐endoscopic transforaminal lumbar interbody fusion (Endo‐TLIF) with percutaneous pedicle screws (PPSs) performed by using a visualization system with that of minimally invasive transforaminal lumbar interbody fusion (MIS‐TLIF) for the treatment of degenerative lumbar spinal stenosis (LSS). Methods From June 2017 to May 2018, the data of a total of 78 patients who met the selection criteria were retrospectively reviewed and were divided into the Endo‐TLIF group (40 cases) and the MIS‐TLIF group (38 cases) according to the surgical method used. The visual analog scale (VAS) and the Japanese Orthopaedic Association (JOA) scale were administered preoperatively and at the 1‐week, 3‐month, and 1–2‐year follow‐ups. The fusion rate and major complications, including revision, were also recorded. Results All the patients were followed up for 24 to 34 months, with an average follow‐up of 30.7 months. The intraoperative blood loss and length of hospital stay for the Endo‐TLIF group (60.56 ± 0.36 mL, 8.12 ± 0.92 days, respectively) were statistically significantly lower than those for the MIS‐TLIF group (65.47 ± 0.91 mL, 9.66 ± 1.34 days, respectively) (P 0.05). There was no significant difference in the intervertebral altitude between the two groups at the 3‐month (11.36 ± 0.23, 11.21 ± 0.42, respectively) or final follow‐up (10.88 ± 0.64, 10.81 ± 0.39, respectively) (P > 0.05). Dural tears, cerebrospinal fluid leakage, infection, and neurologic injury did not occur. Both groups showed good intervertebral fusion at the last follow‐up. The intervertebral fusion rate was 97.5% (39/40) in the Endo‐TLIF group and 94.7% (36/38) in the MIS‐TLIF group, with no statistically significant difference between the two groups (χ 2 = 0.118, P = 0.731). At the final follow‐up, the modified MacNab's criteria were 92.5% and 89.5% between the two groups. Conclusion Endo‐TLIF with percutaneous pedicle screws (PPS) performed by using a visualization system for lumbar degenerative disease may be regarded as an efficient alternative surgery for degenerative lumbar spinal stenosis. It is a safe and minimally invasive way to perform this surgery and has shown satisfactory clinical outcomes., Endo‐TLIF with percutaneous pedicle screws may be regarded as an efficient alternative surgery for degenerative lumbar spinal stenosis. It is a safe and minimally invasive way to perform this surgery and has shown satisfactory clinical outcomes.

Parkinson's disease is a common degenerative disease of the elderly. Although the majority of studies have focused on the central nervous system (CNS) features of Parkinson's disease, recent findings suggest there is a functional link between the gut microbiome and the hallmarks of the disease. PubMed, Web of Science, EMBASE and other Chinese and English databases were searched for relevant literature. Studies on changes to intestinal microbiota in Parkinson's patients were retrieved and systematically reviewed. Quality filtering, clustering and species annotation were performed on 16s sequencing raw data from retrieved studies to achieve comparability across studies. Alpha-diversity indices and a random effect model were used to analyse significantly altered microbiota. A total of nine studies were included in this retrospective analysis, four of which contained raw data. Alpha diversity was significantly different between control and Parkinson's disease patients in two of the four studies. Using the raw data from four individual studies, we observed differences in the phlya Bacteroidetes and Actinobacteria. Additionally, differences were observed between control and Parkinson's disease patients at the level of family (Prevotellacaea and Lactobacillaceae) and genus (Bifidobacterium and Clostridium). This study confirmed that changes in the microbiome are a consistent feature of Parkinson's disease patients and, therefore, may contribute to the onset of disease.

Osteoarthritis (OA) is a joint degenerative disease that has become one of the leading causes of disability in the world. It is estimated that OA affects 50 million adults in the United States. Currently, there are no FDA-approved treatments that slow OA progression and its treatment is limited to pain management strategies and life style changes. Despite the discovery of several disease-modifying OA drugs (DMOADs) and promising results in preclinical studies, their clinical translation has been significantly limited because of poor intra-articular (IA) bioavailability and challenges in delivering these compounds to tissues of interest within the joint. Here, we review current OA treatments and their effectiveness at reducing joint pain, as well as novel targets for OA treatment and the challenges related to their clinical translation. Moreover, we discuss intra-articular (IA) drug delivery as a promising route of administration, describe its inherent challenges, and review recent advances in biomaterial-based IA drug delivery for OA treatment. Finally, we highlight the potential of tissue targeting in the development of effective IA drug delivery systems.

BACKGROUND Temporomandibular joint osteoarthritis (TMJOA) is a progressive degenerative disease caused by imbalance between anabolic and catabolic stimuli. OBJECTIVE The aim of this study was to evaluate histopathological changes, collagen degeneration and the expression of eleven TMJOA biomarkers in articular discs. METHODS Specimens were obtained from eight female patients submitted to discectomy. Discs were divided into anterior band (AB), intermediate zone (IZ) and posterior band (PB) for computerised histomorphometric analyses. Each was assigned a histopathological degeneration score (HDS). Collagen degeneration was assessed with Picrosirius-polarisation method. Biomarkers were evaluated through immunohistochemistry, including IGF-1, OPG, VEGF, TNF-α, FGF-23, IHH, MMP-3, MMP-9, TGF-β1 , BMP-2 and WNT-3. Image processing software was used to calculate average immature collagen ratios and immunostained areas. Spearman rank tests were applied to verify correlations, with significance level of 0.05. RESULTS The HDS showed negative correlation with expression of VEGF in IZ and PB (P

Contains fulltext : 219118.pdf (Publisher’s version ) (Open Access) PURPOSE: Age-related macular degeneration (AMD) is a degenerative disease of the macula, often leading to progressive vision loss. The rate of disease progression can vary among individuals and has been associated with multiple risk factors. In this review, we provide an overview of the current literature investigating phenotypic, demographic, environmental, genetic, and molecular risk factors, and propose the most consistently identified risk factors for disease progression in AMD based on these studies. Finally, we describe the potential use of these risk factors for personalised healthcare. RECENT FINDINGS: While phenotypic risk factors such as drusen and pigment abnormalities become more important to predict disease progression during the course of the disease, demographic, environmental, genetic and molecular risk factors are more valuable at earlier disease stages. Demographic and environmental risk factors such as age and smoking are consistently reported to be related to disease progression, while other factors such as sex, body mass index (BMI) and education are less often associated. Of all known AMD variants, variants that are most consistently reported with disease progression are rs10922109 and rs570618 in CFH, rs116503776 in C2/CFB/SKIV2L, rs3750846 in ARMS2/HTRA1 and rs2230199 in C3. However, it seems likely that other AMD variants also contribute to disease progression but to a lesser extent. Rare variants have probably a large effect on disease progression in highly affected families. Furthermore, current prediction models do not include molecular risk factors, while these factors can be measured accurately in the blood. Possible promising molecular risk factors are High-Density Lipoprotein Cholesterol (HDL-C), Docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), zeaxanthin and lutein. SUMMARY: Phenotypic, demographic, environmental, genetic and molecular risk factors can be combined in prediction models to predict disease progression, but the selection of the proper risk factors for personalised risk prediction will differ among individuals and is dependent on their current disease stage. Future prediction models should include a wider set of genetic variants to determine the genetic risk more accurately, and rare variants should be taken into account in highly affected families. In addition, adding molecular factors in prediction models may lead to preventive strategies and personalised advice.

Although osteoarthritis (OA) in the hip joint is a common and debilitating degenerative disease, the precise molecular mechanisms underlying its pathological process remains unclear. This study sets out to investigate whether β‐catenin plays a critical role in hip OA pathogenesis. Here, we showed overexpressed β‐catenin protein in human OA cartilage tissues. Then, we analyzed β‐cat(ex3) Col2ER mice, in which β‐catenin gene was conditionally activated in femoral head chondrocytes. At 2 months of age, β‐cat(ex3) Col2ER mice already showed a phenotype of severe cartilage degeneration in the femoral head. More changes observed in β‐cat(ex3) Col2ER mice with age included subchondral sclerosis and osteophyte formation along joint margins, resembling a hip OA phenotype in humans. In addition, cartilage degradation and chondrocyte apoptosis as the results of β‐catenin activation possibly contributed to this hip OA‐like phenotype. Overall our findings provide direct evidence about the importance of β‐catenin in hip OA pathogenesis.

Objectives Oblique lateral interbody fusion is considered a useful surgical option for various lumbar degenerative diseases with favorable clinical results and few complications. However, clinical outcomes following oblique lateral interbody fusion stratified according to the preoperative diagnosis have not been fully evaluated in a large cohort. The purpose of the present study was to evaluate the clinical outcomes following oblique lateral interbody fusion for lumbar degenerative disease and to identify differences in outcomes when stratified according to preoperative diagnosis. Methods All patients receiving oblique lateral interbody fusion for lumbar degenerative diseases were included in the current study and were stratified into four diagnostic groups: (i) degenerative spondylolisthesis; (ii) spondylolytic spondylolisthesis; (iii) spinal stenosis without spondylolisthesis and instability; and (iv) deformity. Clinical outcomes were assessed using multiple patient-reported questionnaires. Radiologic outcomes, including cage subsidence and completion of fusion, were also evaluated. Results Overall, 169 patients with 262 operative levels were included in the study. All clinical scoring items showed significant improvement at 1 year postoperatively for all diagnostic groups. Net and percent improvement, and a proportion of patients reaching a threshold for substantial clinical benefit were not significantly different between the diagnostic groups in all scoring items, except for lower extremity radiating pain of the deformity group. Although the deformity group had the highest overall complication rate, neurologic complications were more frequent in the spondylolytic spondylolisthesis group. The rate of complete fusion and cage subsidence for individual levels at 1 year postoperatively was 62.7% and 32.6% respectively, with no significant difference between the diagnostic groups. Conclusions The large single-institution prospective cohort of the present study showed favorable clinical outcomes following oblique lateral interbody fusion for lumbar degenerative disease, even in spinal stenosis without spondylolisthesis and instability.

There is abundant evidence that the pathophysiology of Parkinson's disease (PD) is not confined to the nigrostriatal dopaminergic pathway but propagates along the cortico-basal ganglia-thalamo-cortical neural network. A critical node in this functional circuit impacted by PD is the primary motor cortex (M1), which plays a key role in generating neural impulses that regulate movements. The past several decades have lay witness to numerous in vivo neuroimaging techniques that provide a window into the function and structure of M1. A consistent observation from numerous studies is that during voluntary movement, but also at rest, the functional activity of M1 is altered in PD relative to healthy individuals, and it relates to many of the motor signs. Although this abnormal functional activity can be partially restored with acute dopaminergic medication, it continues to deteriorate with disease progression and may predate structural degeneration of M1. The current review discusses the evidence that M1 is fundamental to the pathophysiology of PD, as measured by neuroimaging techniques such as positron emission tomography, single-photon emission computed tomography, electroencephalography, magnetoencephalography, and functional and structural MRI. Although novel treatments that target the cortex will not cure PD, they could significantly slow down and alter the progressive course of the disease and thus improve clinical care for this degenerative disease. © 2018 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

Sorsby fundus dystrophy (SFD), an autosomal dominant, fully penetrant, degenerative disease of the macula, is manifested by symptoms of night blindness or sudden loss of visual acuity, usually in the third to fourth decades of life due to choroidal neovascularization (CNV). SFD is caused by specific mutations in the Tissue Inhibitor of Metalloproteinase-3, (TIMP3) gene. The predominant histo-pathological feature in the eyes of patients with SFD are confluent 20–30 m thick, amorphous deposits found between the basement membrane of the retinal pigment epithelium (RPE) and the inner collagenous layer of Bruch’s membrane. SFD is a rare disease but it has generated significant interest because it closely resembles the exudative or “wet” form of the more common age-related macular degeneration (AMD). In addition, in both SFD and AMD donor eyes, sub-retinal deposits have been shown to accumulate TIMP3 protein. Understanding the molecular functions of wild-type and mutant TIMP3 will provide significant insights into the patho-physiology of SFD and perhaps AMD. This review summarizes the current knowledge on TIMP3 and how mutations in TIMP3 cause SFD to provide insights into how we can study this disease going forward. Findings from these studies could have potential therapeutic implications for both SFD and AMD.

Osteoarthritis (OA) is an age-related joint degenerative disease associated with pain, joint deformity, and disability. The disease starts with cartilage damage but then progressively involves subchondral bone, causing an imbalance between osteoclast-driven bone resorption and osteoblast-driven remodeling. Here, we summarize the data for the role of oxidative stress and inflammation in OA pathology and discuss how these two processes are integrated during OA progression, as well as their contribution to abnormalities in cartilage/bone metabolism and integrity. At the cellular level, oxidative stress and inflammation are counteracted by transcription factor nuclear factor erythroid p45-related factor 2 (NRF2), and we describe the regulation of NRF2, highlighting its role in OA pathology. We also discuss the beneficial effect of some phytonutrients, including the therapeutic potential of NRF2 activation, in OA.

Introduction Laparoscopic sacrocolpopexy (LSCP) is a reference operation for apical compartment prolapse repair. Aim of this study is to describe the early and midterm postoperative MRI findings of the lumbosacral region (LSR) in patients undergoing LSCP and to detect any imaging changes that the presence of the mesh may cause on patients with preexisting degenerative disease of the LSR. Methods Patients with POP-Q grade III and IV uterovaginal or vaginal vault prolapse who were considered eligible for LSCP were invited to participate. An MRI of the LSR was performed preoperatively and then 3 and 12 months postoperatively. Patients with vaginal vault prolapse underwent LSCP, while women with uterovaginal prolapse were treated with the vaginally assisted laparoscopic sacrocolpopexy (VALS). Results A total of 30 patients were included in the study; 18 (60%) underwent LSCP and 12 (40%) VALS. On preoperative MRIs, 83.3% (25/30) of patients had degenerative changes and 70% (21/30) reported having low back pain (LBP). Postoperative MRIs did not reveal any imaging changes compared to the preoperative MRI findings both for patients with or without preexisting degenerative abnormalities of the LSR. No significant changes in the LBP score were observed postoperatively. Conclusions Any bone marrow or soft-tissue changes at MRIs of the LSR early after the insertion of a synthetic mesh, does not constitute an expected postoperative finding and should raise the suspicion of an ongoing inflammatory or infectious spinal process (spondylodiscitis). Additionally, LSCP seems to be a safe surgical approach for women with preexisting degenerative disease of the LSR.

Huntington's disease (HD) is an autosomal dominantly inherited, and currently untreatable, neuropsychiatric disorder. This progressive and ultimately fatal disease is named after the American physician George Huntington and according to the underlying molecular biological mechanisms is assigned to the human polyglutamine or CAG-repeat diseases. In the present article we give an overview of the currently known neurodegenerative hallmarks of the brains of HD patients. Subsequent to recent pathoanatomical studies the prevailing reductionistic concept of HD as a human neurodegenerative disease, which is primarily and more or less exclusively confined to the striatum (ie, caudate nucleus and putamen) has been abandoned. Many recent studies have improved our neuropathological knowledge of HD; many of the early groundbreaking findings of neuropathological HD research have been rediscovered and confirmed. The results of this investigation have led to the stepwise revision of the simplified pathoanatomical and pathophysiological HD concept and culminated in the implementation of the current concept of HD as a multisystem degenerative disease of the human brain. The multisystem character of the neuropathology of HD is emphasized by a brain distribution pattern of neurodegeneration (i) which apart from the striatum includes the cerebral neo-and allocortex, thalamus, pallidum, brainstem and cerebellum, and which (ii) therefore, shares more similarities with polyglutamine spinocerebellar ataxias than previously thought.

Neurotrophic keratitis (NK) is a rare degenerative disease of the cornea caused by trigeminal nerve damage, which leads to loss of corneal sensitivity, corneal epithelium breakdown, and poor healing. Though extremely uncommon, NK is increasingly recognized for its characteristics as a distinct and well-defined clinical entity rather than a rare complication of various diseases that can disrupt trigeminal innervation. Indeed, the defining feature of NK is loss of corneal sensitivity, and its clinical findings do not correlate with the wide range of systemic or ocular conditions that underlie trigeminal nerve damage. Despite increasing awareness of NK as a distinct condition, its management continues to be challenged by the lack of treatments that target nerve regeneration. This review focuses on the role of corneal nerves in maintaining ocular surface homeostasis, the consequences (such as alterations in neuromediators and corneal cell morphology/function) of impaired innervation, and advances in NK diagnosis and management. Novel therapeutic strategies should aim to improve corneal innervation in order support corneal renewal and healing. J. Cell. Physiol. 232: 717-724, 2017. © 2016 Wiley Periodicals, Inc.

Multiple sclerosis is a chronic inflammatory, demyelinating degenerative disease of the central nervous system. Current treatments target pathological immune responses to counteract the inflammatory processes. However, these drugs do not restrain the long-term progression of clinical disability. For this reason, new therapeutic approaches and identification of novel target molecules are needed to prevent demyelination or promote repair mechanisms. Transient Receptor Potential Ankyrin 1 (TRPA1) is a nonselective cation channel with relatively high Ca2+ permeability. Its pathophysiological role in central nervous system disorders has not been elucidated yet. In the present study, we aimed to assess the distribution of TRPA1 in the mouse brain and reveal its regulatory role in the cuprizone-induced demyelination. This toxin-induced model, characterized by oligodendrocyte apoptosis and subsequent primary demyelination, allows us to investigate the nonimmune aspects of multiple sclerosis. We found that TRPA1 is expressed on astrocytes in the mouse central nervous system. Interestingly, TRPA1 deficiency significantly attenuated cuprizone-induced demyelination by reducing the apoptosis of mature oligodendrocytes. Our data suggest that TRPA1 regulates mitogen-activated protein kinase pathways, as well as transcription factor c-Jun and a proapoptotic Bcl-2 family member (Bak) expression resulting in enhanced oligodendrocyte apoptosis. In conclusion, we propose that TRPA1 receptors enhancing the intracellular Ca2+ concentration modulate astrocyte functions, and influence the pro or anti-apoptotic pathways in oligodendrocytes. Inhibition of TRPA1 receptors might successfully diminish the degenerative pathology in multiple sclerosis and could be a promising therapeutic target to limit central nervous system damage in demyelinating diseases. GLIA 2016;64:2166-2180.

Sloughing esophagitis, also currently known as esophagitis dissecans superficialis, is a degenerative disease of the squamous epithelium characterized by superficial epithelial necrosis with parakeratosis, but without inflammation, and detachment of the superficial necrotic zone from the deep viable zone. This leads to a spectacular endoscopic appearance of sloughed mucosa in streaks and patches. The cause is unknown, and the clinical characteristics are variable, ranging from incidentally findings to esophageal symptoms. The disease seems to be self-limited, as resolution of the changes was observed in the few cases for which follow-up endoscopic examinations have been reported.

In the modern research era, sequencing and high-throughput analysis have linked genetic factors with a multitude of disease states. Often times, the same cellular machinery is implicated in several different diseases and has made it challenging to drug a particular disease with minimal pleotropic consequences. It is intriguing to see how different fields of disease research can present such differing views when describing the same biological process, pathway, or molecule. As observations in one field converge with research in another, we gain a more complete picture of a biological system and can accurately assess the feasibility for translational science. As an example discussed here, modulating latent stress response pathways within the cell provides exciting therapeutic potential, however, opposing views have emerged in the fields of degenerative disease and cancer. This at first glance seems logical as suppression of degenerative disease entails maintaining cell viability, while cancer aims to enhance selective senescence and cell death. As both of these disciplines seek novel therapeutic interventions, we should not overlook how scientific biases involving one biological process may impact different disease paradigms.

A number of age-dependent degenerative diseases are caused by chronic endoplasmic reticulum (ER) stress in vital cells. In many cases, the afflicted cells suffer from ER stress since birth, but the death of irreplaceable cells occurs only late in life. Although our understanding of ER stress-induced cell death has advanced significantly, most of the known mechanisms involve pathways that signal within hours, and it remains unclear how these pathways regulate cell death that occurs only decades later. Here, I highlight the conceptual issues and suggest ways to make sense of the age-related effect of ER stress-induced cell death in degenerative diseases.

Dynesys (Dynamic Neutralization System) was designed to overcome the shortcomings of fusion. The Dynesys top loading (DTL) system is a new alternative Dynesys system that can be applied via a minimally invasive procedure. This study aimed to ascertain whether DTL is a suitable device for motion preservation and prevention of instability, and to compare the clinical and radiological outcomes between DTL and Dynesys. In this study, 12 patients were treated with Dynesys and 21 patients were treated with DTL. Back and leg pain were evaluated using the visual analog scale. The Oswestry Disability Index was used to evaluate the patients' function. Range of motion (ROM) at the operative level and for the whole lumbar spine was measured pre- and postoperatively. The length of wound, blood loss, length of hospital stay, and operation duration were also compared. All patients were followed up for 12–76 months. Scores on the visual analog scale and Oswestry Disability Index were significantly improved postoperatively. The median ROM of the whole spine and index level ROM in all patients showed 12.5% and 79.6% loss, respectively. The DTL group exhibited significantly better results in terms of blood loss, wound length, and operation duration, in addition to early ambulation. In conclusion, Dynesys and DTL are semirigid fixation systems that can significantly improve clinical symptoms and signs. Our results suggested that DTL was better than Dynesys as a result of it being a minimally invasive procedure. However, further study with large sample sizes and longer follow-up durations is required to validate the effects of these dynamic stabilizers.

In vivo proton (1H) magnetic resonance spectroscopy (MRS) has not yet been systematically used to study joint fluids in human knees. The objective of this study, therefore, was to assess the ability of proton MRS to identify the apparent heterogeneous characteristics of metabolic spectra in the joint fluid regions in human knees using a high-field MRI system. Eighty-four patients with effusion lesions who were referred for routine knee MR imaging underwent proton MRS with point-resolved, single-voxel MR spectroscopy using a clinical 3.0 Tesla MRI system. Thirty-eight patients were confirmed to have the following: degenerative osteoarthritis, 21 patients (Group 1); traumatic diseases, 12 patients (Group 2); infectious diseases, 4 patients and an inflammatory disease, 1 patient (Group 3). Spectroscopy data were analyzed using the public jMRUI freeware software to obtain lipid metabolites. Nonparametric statistical comparisons were performed to investigate any differences in metabolites among the three disease groups. The major metabolites were vinylic CH=CH lipids around 5.1-5.5 ppm, CH2 lipids around 1.1-1.5 ppm, and CH3 lipids around 0.7-1.0 ppm. Each patient had either a CH=CH lipid peak, CH2 and CH3 lipid peaks, or all three peaks. There were no significant differences among the three groups for the CH3 (p = 0.9019), CH2 (p= 0.6406), and CH=CH lipids (p = 0.5467) and water (p = 0.2853); none of the metabolites could differentiate between any of the three types of diseases. The CH2 lipids in the 38 patients who had confirmed fluid characteristics were significantly correlated with CH3 lipids (rho = 0.835, p < 0.0001). The ratio of CH3 to CH2 was highest in the degenerative disease. In both the degenerative and traumatic diseases, metabolite peaks of the vinylic CH=CH lipids around 5.1-5.5 ppm and of the sum of the CH2 and CH3 lipids around 0.7-1.5 ppm were observed, but in the infectious disease, only a metabolite peak of the sum of the CH2 and CH3 lipids was detected. Although none of the metabolites could statistically significantly differentiate between the three types of diseases, the different lipid metabolite peaks and their ratios in the three disease groups may give us a hint at the different mechanisms of joint fluids in the infectious, degenerative, and traumatic diseases.

Charcot-Marie-Tooth disease (CMT) is a slowly progressive hereditary degenerative disease and one of the most common neuromuscular disorders. Exercise may be beneficial to maintain strength and function for people with CMT, however, no comprehensive evaluation of the benefits and risks of exercise have been conducted. A systematic review was completed searching numerous electronic databases from earliest records to February 2015. Studies of any design including participants of any age with confirmed diagnosis of CMT that investigated the effects of exercise were eligible for inclusion. Of 13,301 articles identified following removal of duplicates, 11 articles including 9 unique studies met the criteria. Methodological quality of studies was moderate, sample sizes were small, and interventions and outcome measures used varied widely. Although the majority of the studies identified changes in one or more outcome measurements across exercise modalities, the majority were non-significant, possibly due to Type II errors. Significant effects described included improvements in strength, functional activities, and physiological adaptations following exercise. Despite many studies showing changes in strength and function following exercise, findings of this review should be met with caution due to the few studies available and moderate quality of evidence. Well-powered studies, harmonisation of outcome measures, and clearly described interventions across studies would improve the quality and comparability of the evidence base. The optimal exercise modality and intensity for people with CMT as well as the long-term safety of exercise remain unclear.

Osteoarthritis (OA) is a degenerative disease of the joints and a leading cause of physical disability in adults. Intra-articular (IA) therapy is a popular treatment strategy for localized, single-joint OA; however, small-molecule drugs such as corticosteroids do not provide prolonged relief. One possible reason for their lack of efficacy is high clearance rates from the joint through constant lymphatic drainage of the synovial tissues and synovial fluid and also by their exchange via the synovial vasculature. Advanced drug delivery strategies for extended release of therapeutic agents in the joint space is a promising approach to improve outcomes for OA patients. Broadly, the basic principle behind this strategy is to encapsulate therapeutic agents in a polymeric drug delivery system (DDS) for diffusion- and/or degradation-controlled release, whereby degradation can occur by hydrolysis or tied to relevant microenvironmental cues such as pH, reactive oxygen species (ROS), and protease activity. In this review, we highlight the development of clinically tested IA therapies for OA and highlight recent systems which have been investigated preclinically. DDS strategies including hydrogels, liposomes, polymeric microparticles (MPs) and nanoparticles (NPs), drug conjugates, and combination systems are introduced and evaluated for clinical translational potential.

Numerous therapeutic approaches for Duchenne and Becker Muscular Dystrophy (DMD and BMD), the most common X-linked muscle degenerative disease, have been proposed. So far, the only one showing a clear beneficial effect is the use of corticosteroids. Recent evidence indicates an improvement of dystrophic cardiac and skeletal muscles in the presence of sustained cGMP levels secondary to a blocking of their degradation by phosphodiesterase five (PDE5). Due to these data, we performed a study to investigate the effect of the specific PDE5 inhibitor, tadalafil, on dystrophic skeletal muscle function. Chronic pharmacological treatment with tadalafil has been carried out in mdx mice. Behavioral and physiological tests, as well as histological and biochemical analyses, confirmed the efficacy of the therapy. We then performed a microarray-based genomic analysis to assess the pattern of gene expression in muscle samples obtained from the different cohorts of animals treated with tadalafil. This scrutiny allowed us to identify several classes of modulated genes. Our results show that PDE5 inhibition can ameliorate dystrophy by acting at different levels. Tadalafil can lead to (1) increased lipid metabolism; (2) a switch towards slow oxidative fibers driven by the up-regulation of PGC-1α; (3) an increased protein synthesis efficiency; (4) a better actin network organization at Z-disk. J. Cell. Physiol. 230: 224–232, 2016. © 2015 Wiley Periodicals, Inc.

Huntington's disease is a rare hereditary degenerative disease with a wide variety of symptoms that encompass movement, cognition, and behavior. The genetic mutation that causes the disease has been known for more than 20 y, and animal models have illuminated a host of intracellular derangements that occur downstream of protein translation. A number of clinical trials targeting these metabolic consequences have failed to produce a single effective therapy, although clinical trials continue. New strategies targeting the protein at the level of transcription, translation, and posttranslational modification and aggregation engender new hope that a successful strategy will emerge, but there is much work ahead. Some of the clinical manifestations of the illness, particularly chorea, affective symptoms, and irritability, are amenable to palliative strategies, but physicians have a poor evidence base on which to select the best agents. Clinical trials since 2013 have dashed hopes that coenzyme Q10 or creatine might have disease-modifying properties but suggested other agents were safe or hinted at efficacy (cysteamine, selisistat, hydroxyquinoline) and could proceed into later-stage disease modification trials. The hunt for effective symptom relief suggested that pridopidine might be shown effective given the right outcome measure. This review summarizes recent progress in HD and highlights promising new strategies for slowing disease progression and relieving suffering in HD.

Objectives The purpose of this study was to determine the value of dynamic high-resolution sonography for evaluation of temporomandibular joint (TMJ) disk displacement compared to magnetic resonance imaging (MRI) with the mouth closed and during the maximal mandibular range of motion. Methods Dynamic high-resolution sonography with the mouth closed and during the maximal mandibular range of motion was performed on 39 consecutive patients (78 joints; 13 male and 26 female; age range, 18–77 years; mean age ± SD, 37.23 ± 16.26 years) with TMJ disorders. A TMJ MRI study was performed 1 to 7 days after sonography. We searched for signs of disk displacement and findings compatible with degenerative joint disease. Both studies were performed and interpreted independently by blinded operators. Results Magnetic resonance imaging depicted 22 normal joints (28.2%), 21 (26.9%) with anterior disk displacement with reduction, 15 (19.2%) with anterior disk displacement without reduction, and 20 (25.6%) with degenerative disease. Sonography depicted 30 normal joints (38.5%), 22 (28.2%) with anterior disk displacement with reduction, 12 (15.4%) with anterior disk displacement without reduction, and 14 (17.9%) with degenerative disease. The overall sensitivity, specificity, and accuracy of sonography for diagnosis of disk displacement were 74.3%, 84.2%, and 77.7%, respectively. The sensitivity, specificity, and accuracy for diagnosis of disk displacement with reduction were 78.6%, 66.7%, and 73.0%, and the values for diagnosis of disk displacement without reduction were 66.7%, 78.6%, and 73.0%. Conclusions Dynamic high-resolution sonography is a potential imaging method for diagnosis of TMJ disk displacement and degenerative diseases. Further studies are needed to make dynamic high-resolution sonography the first-line test for diagnosis of TMJ disk displacement.

Objective To evaluate the clinical use of kinetic magnetic resonance imaging (kMRI) in spinal degenerative diseases. Methods A systematic search of PubMed, EMBASE and ISI databases for articles that had been published between January 1978 and February 2013 concerning patients who had undergone kMRI for spinal problems was performed. All selected patients had undergone kMRI in neutral, flexion, and extension weight-bearing positions. Evaluation of cervical and lumbar degeneration by kMRI was analyzed. kMRI showed significant reduction of mobility in cervical segments of patients with severe disc degeneration; in addition, it was more severely reduced in patients with severe cord compression than in those without it. In the cervical spine, it was found that although disc height, translational motion, and angular variation were significantly affected at the level of disc herniation, no significant changes were apparent in adjacent segments. kMRI also showed that lumbar degeneration is closely associated with disc degeneration, facet joint osteoarthritis and the pathological characteristics of the interspinous ligaments, ligamentum flavum and paraspinal muscles. Results Eleven articles (4162 patients) fulfilled the inclusion criteria and were reviewed. It was found that kMRI is more specific and sensitive than conventional MRI regarding relating patients' symptoms to objective findings on imaging that demonstrate pathology and biomechanics. In the kinetic position, kMRI improves detection of disc herniation by 5.78%–19.46% and thus provides a new means of studying the biomechanical mechanism(s) in degenerative spines. Conclusion Kinetic MRI is effective for diagnosing, evaluating, and managing degenerative disease within the spine; however, it still has some limitations.

Brain changes due to development and maturation, normal aging, or degenerative disease are continuous, gradual, and variable across individuals. To quantify the individual progression of brain changes, we propose a spatio-temporal methodology based on Hidden Markov Models (HMM), and apply it on four-dimensional structural brain magnetic resonance imaging series of older individuals. First, regional brain features are extracted in order to reduce image dimensionality. This process is guided by the objective of the study or the specific imaging patterns whose progression is of interest, for example, the evaluation of Alzheimer-like patterns of brain change in normal individuals. These regional features are used in conjunction with HMMs, which aim to measure the dynamic association between brain structure changes and progressive stages of disease over time. A bagging framework is used to obtain models with good generalization capability, since in practice the number of serial scans is limited. An application of the proposed methodology was to detect individuals with the risk of developing MCI, and therefore it was tested on modeling the progression of brain atrophy patterns in older adults. With HMM models, the state-transition paths corresponding to longitudinal brain changes were constructed from two completely independent datasets, the Alzheimer Disease Neuroimaging Initiative and the Baltimore Longitudinal Study of Aging. The statistical analysis of HMM-state paths among the normal, progressive MCI, and MCI groups indicates that, HMM-state index 1 is likely to be a predictor of the conversion from cognitively normal to MCI, potentially many years before clinical symptoms become measurable.

Osteoarthritis has grown to become a widely prevalent disease that has major implications in both individual and public health. Although originally considered to be a degenerative disease driven by "wear and tear" of the articular cartilage, recent evidence has led to a consensus that osteoarthritis pathophysiology should be perceived in the context of the entire joint and multiple tissues. MRI is becoming an increasingly more important modality for imaging osteoarthritis, due to its excellent soft tissue contrast and ability to acquire morphological and biochemical data. This review will describe the pathophysiology of osteoarthritis as it is associated with various tissue types, highlight several promising MR imaging techniques for osteoarthritis and illustrate the expected appearance of osteoarthritis with each technique.

A four-month old female Rottweiler was presented for a ten-week history of progressive dyspnoea, spinocerebellar ataxia and tetraparesis that had been unresponsive to empirical treatment. Neurological examination revealed obtundation, an ambulatory tetraparesis (worse in the hindlimbs) with spinocerebellar ataxia, head titubations, miotic pupils, positional vertical nystagmus, an intermittent ventrolateral strabismus and delayed postural reactions in all four limbs. General physical examination revealed inspiratory stridor. Signs were consistent with multifocal neurological disease with involvement of the brainstem, cerebellum, spinal cord and peripheral nerves. Further diagnostics included an MRI, cerebrospinal fluid analysis, and blood work, which were all unremarkable. The multifocal neurological findings in combination with normal ancillary tests in a young rottweiler were suggestive of a degenerative disease, with the top differential being neuronal vacuolation and spinocerebellar degeneration (NVSCD). Due to the grave prognosis and rapid progression of clinical signs, euthanasia was elected. A complete postmortem examination was performed, which revealed multifocal intracytoplasmic neuronal vacuolisation with axonal degeneration throughout the CNS; severe, generalised bilateral myocyte atrophy and degeneration of the cricoarytenoideus dorsalis (CAD) muscles; and moderate, multifocal, bilateral demyelination of the laryngeal nerves. The histological lesions were pathognomonic for NVSCD, thereby confirming the diagnosis.

BACKGROUND Multiple sclerosis (MS) is an autoimmune, neurodegenerative disease frequently complicated by bowel symptoms. Multiple sclerosis typically first manifests with a demyelination event, also known as a clinically isolated syndrome (CIS). We sought to examine the prevalence of prodromal bowel symptoms predating a CIS in patients with MS as part of a recently characterized prodromal phase of disease. METHODS We constructed a retrospective cohort of MS patients with bowel symptoms and an identifiable CIS at two tertiary care centers over 14 years using administrative and billing data. We determined the date of onset of reported bowel symptoms in comparison with the date of first CIS and determined the overall prevalence of prediagnosis bowel symptoms within 1, 2, 3, and >3 years from a CIS. We used multivariable modeling to determine demographic and clinical risk factors for prediagnosis bowel symptoms. KEY RESULTS Among 385 MS patients with reported bowel symptoms, 122 (31.6%) reported bowel symptoms prior to CIS. The most common first bowel symptom was constipation (50.0%), followed by diarrhea (29.5%). The average lead time between a first bowel symptom and a CIS event was 3.7 ± 3.4 years. Pre-CIS fatigue (OR 4.48, 95% CI: 2.68-7.51, P

Adult acquired flatfoot deformity (AAFD) is a degenerative disease resulting in malalignment of the mid- and hindfoot secondary to posterior tibial tendon dysfunction and increasing implication of ligament pathologies. Despite the complex 3D nature of AAFD, 2D radiographs are still employed to diagnose and stage the disease. Computer modeling techniques allow for accurate 3D recreations of musculoskeletal systems for the investigation of biomechanical factors contributing to disease. Following Institutional Review Board approval, the lower limbs of six diagnosed AAFD sufferers were imaged with MRI, photographs, and X-ray. Next, a radiologist graded the MRI attenuation of eight soft-tissues implicated in AAFD. Six patient-specific rigid-body models were then created and loaded according to patient weight, graded soft-tissues, and extrinsic muscles. Model function was validated using clinically relevant kinematic measures in three planes. Agreement varied depending on the measure, with average absolute deviations of

Color discrimination deficit is a common nonmotor manifestation of Parkinson's disease (PD). However, the pathophysiology of this dysfunction remains poorly understood. Although retinal structure changes found in PD have been suggested to cause color discrimination deficits, the impact of cognitive impairment and cortical alterations remains to be determined. We investigated the contribution of cognitive impairment to color discrimination deficits in PD and correlated them with cortical anomalies. Sixty-six PD patients without dementia and 20 healthy controls performed the Farnsworth-Munsell 100 hue test and underwent a comprehensive neuropsychological assessment for mild cognitive impairment diagnosis. In a subgroup of 26 PD patients, we also used high-definition neuroanatomical magnetic resonance imaging for cortical thickness and diffusion tensor analysis. PD patients with mild cognitive impairment performed poorly on the Farnsworth-Munsell 100 hue test compared with PD patients without mild cognitive impairment and controls. In PD patients, performance on the Farnsworth-Munsell 100 hue test was correlated with measures of visuospatial abilities and executive functions. Neuroimaging analysis revealed higher mean and radial diffusivity values in right posterior white-matter structures that correlated with poor performance on the Farnsworth-Munsell 100 hue test. No cortical thickness correlation reached significance. This study showed that cognitive impairment makes a major contribution to the color discrimination deficits reported in PD. Thus, performance on the Farnsworth-Munsell 100 hue test may reflect cognitive impairment more than color discrimination deficits in PD. Poor performance on the Farnsworth-Munsell 100 hue test was also associated with white-matter alterations in right posterior brain regions.

Loss in insight is a major feature of frontotemporal dementia (FTD) but has been investigated relatively little. More importantly, the neural basis of insight loss is still poorly understood. The current study investigated insight deficit profiles across a large cohort of neurodegenerative patients (n = 81), including FTD and Alzheimer's disease (AD) patients. We employed a novel insight questionnaire, which tapped into changes across different domains: social interaction, emotion, diagnosis/treatment, language, and motivation. FTD subtypes varied considerably for insight loss, with the behavioral variant worst and the progressive non-fluent variant least affected. All other subtypes and AD showed milder but consistent insight loss. Voxel-based morphometry analysis revealed that overall insight loss correlated with ventromedial and frontopolar prefrontal atrophy, with exception of social interaction and emotion insight loss, which additionally correlated with lateral temporal and amygdala atrophy, respectively. Our results show that patients with neurodegenerative conditions show variable loss of insight, with ventromedial and frontopolar cortex regions appearing to be particularly important for insight.

Spinocerebellar ataxia 36 is caused by the expansion of the intronic GGCCTG hexanucleotide repeat in NOP56. The original article describing this condition demonstrated that patients with spinocerebellar ataxia 36 present with tongue atrophy, a finding that had not been seen in previous types of spinocerebellar ataxias. A total of 2121 patients with clinically diagnosed spinocerebellar ataxia participated in the study. We screened our patient samples for spinocerebellar ataxia 36 using the repeat-primed polymerase chain reaction method and also determined the clinical features of spinocerebellar ataxia 36. Of the ataxia cases examined, 12 were identified as spinocerebellar ataxia 36. Of these, 7 cases (6 families) were autosomal dominant, 4 cases (three families) had a positive family history but were not autosomal dominant, and 1 case was sporadic. The average age of onset was 51.7 years, and disease progression was slow. The main symptoms and signs of disease included ataxia, dysarthria, and hyperreflexia. Approximately half the affected patients demonstrated nystagmus, bulging eyes, and a positive pathological reflex, although dysphagia, tongue atrophy, and hearing loss were rare. Moreover, the observed atrophy of the cerebellum and brain stem was not severe. The patients identified in this study were concentrated in western Japan. The frequency of spinocerebellar ataxia 36 was approximately 1.2% in the autosomal dominant group, and the age of onset for this condition was later in comparison with other spinocerebellar ataxia subtypes.

Amyotrophic lateral sclerosis (ALS) remains a rapidly progressive fatal degenerative disease of motor neurons for which there are few interventions to slow disease progression or improve quality of life. A diaphragm pacing system was approved by the U.S. Food and Drug Administration in September 2011 for ALS under a Humanitarian Device Exemption. News of this approval has been met with a combination of excitement and uncertainty by members of the ALS community. We review the currently available data on the diaphragm pacing system and its use in ALS. Diaphragm pacing appears to be reasonably safe in carefully selected patients, but flaws in the reporting on it thus far preclude conclusions regarding efficacy. Further study is needed.

Disruptions of cell death signalling occur in pathological processes, such as cancer and degenerative disease. Increased knowledge of cell death signalling has opened new areas of therapeutic research, and identifying key mediators of cell death has become increasingly important. Early triggering events in cell death may provide potential therapeutic targets, whereas agents affecting later signals may be more palliative in nature. A group of primary mediators are derivatives of the highly unsaturated fatty acids (HUFAs), particularly oxygenated metabolites such as prostaglandins. HUFAs, esterified in cell membranes, act as critical signalling molecules in many pathological processes. Currently, agents affecting HUFA metabolism are widely prescribed in diseases involving disordered cell death signalling. However, partly due to rapid metabolism, their role in cell death signalling pathways is poorly characterized. Recently, HUFA-derived mediators, the resolvins/protectins and endocannabinoids, have added opportunities to target selective signals and pathways. This review will focus on the control of cell death by HUFA, eicosanoid (C20 fatty acid metabolites) and docosanoid (C22 metabolites), HUFA-derived lipid mediators, signalling elements in the micro-environment and their potential therapeutic applications. Further therapeutic approaches will involve cell and molecular biology, the multiple hit theory of disease progression and analysis of system plasticity. Advances in the cell biology of eicosanoid and docosanoid metabolism, together with structure/function analysis of HUFA-derived mediators, will be useful in developing therapeutic agents in pathologies characterized by alterations in cell death signalling.

E. Martinez-Saez, E. Gelpi, M. J. Rey, I. Ferrer, T. Ribalta, T. Botta-Orfila, C. Nos, J. Yague and R. Sanchez-Valle (2012) Neuropathology and Applied Neurobiology38, 153–161 Hirano body-rich subtypes of Creutzfeldt–Jakob disease Background: In definite Creutzfeldt–Jakob disease (CJD), morphological and immunohistochemical patterns are useful to identify molecular subtypes. Severe cerebellar pathology and hippocampal involvement helps to identify VV subtypes. The rare VV1 variant (

Background: Postural deficits in Huntington’s disease are linked to functional impairment. We investigated whether assessment of center-of-mass variability using posturography provides objective and quantitative measures that correlate to the severity of motor phenotype, functional measures, and genotype as assessed by a disease burden score (based on repeat length and age). In addition, we investigated whether withdrawing visual feedback facilitates the detection of postural deficits. Methods: Using a force plate, the ability of symptomatic Huntington’s disease patients (n 5 34) and controls (n 5 20) to stand as stably as possible was assessed in eyes-open and eyes-closed conditions. Results: All posturographic measures (DISTANCE, VELOCITY, and SURFACE of centre-of-mass mobility) were increased in patients and correlated to (1) the UHDRS Total Motor Score, (2) the UHDRS Total Functional Capacity, (3) the UHDRS Functional Assessment Score, and (4) the disease burden score. Correlations to motor and functional measures were stronger when visual feedback was provided. Conclusions: Posturography may provide useful objective and quantitative measures of postural motor dysfunction in Huntington’s disease. V C 2012 Movement

The aim of the present pilot investigation was to compare the effectiveness of six treatment protocols providing temporomandibular joint (TMJ) arthrocentesis with or without additional drugs to manage symptoms in patients with inflammatory-degenerative TMJ disease. A consecutive series of 72 patients with TMJ osteoarthritis (axis group IIIb) with pain lasting from more than 6 months were randomly assigned to one of the groups receiving the following treatment protocols: single-session two-needle arthrocentesis (A), single-session two-needle arthrocentesis plus corticosteroid (B), single-session two-needle arthrocentesis plus low molecular weight hyaluronic acid (HA) (C), single-session two-needle arthrocentesis plus high molecular weight HA (D), 5 weekly two-needle arthrocenteses plus low molecular weight HA (E) and 5 weekly single-needle arthrocenteses plus low molecular weight HA (F). At the 3-month follow-up, improvement with respect to mean baseline values was recorded in all the five treatment groups completing the protocol. No significant differences emerged between groups in any outcome variable. The protocol providing five sessions of two-needle arthrocenteses plus low molecular weight HA allowed achieving the highest improvement in almost all the outcome variables. Findings suggested that no statistically significant differences existed between the treatment groups. The clinical significance of these findings needs to be tested with future studies on larger samples with longer follow-up periods.

Background Folliculitis keloidalis nuchae (FKN), characterized by nucheal pimples and keloids, has a predilection for curly African hair. The disease is 10 times more common in males than females. The aim of this study was to investigate determinants of FKN in males. Methods Factors associated with the presence of FKN were investigated from two cross-sectional studies involving 1042 children and 874 adults, respectively. All participants had given informed consent. A clinical diagnosis of FKN was made only if nucheal keloidal papules (or plaques) were present. Multiple logistic regression was used to assess the relationship between FKN and specific characteristics in male participants. Results The odds ratio (OR) for FKN in males was higher in the adult than the child study [OR = 7.26, 95% confidence interval (CI) 3.13–16.88; P 50 years (OR = 2.44, 95% CI 0.75–7.89; P = 0.14) but significantly higher in those aged >25–50 years (OR = 5.75, 95% CI 2.67–12.64; P

BACKGROUND Dimebolin (latrepirdine), a compound with multiple potential drug targets, is being evaluated in clinical trials for the treatment of Alzheimer's disease (AD) and preliminary results suggest it can slow the disease process. There is also evidence that dimebolin directly improves aspects of cognition. Here we examined the acute effect of dimebolin on components of working memory in non-human primates, young adult (11–17 years old) and aged (20–31 years old) rhesus macaques. EXPERIMENTAL APPROACH The effects of dimebolin (3.9–118 µg kg−1) on working memory, as measured by performance on delayed matching-to-sample (DMTS), were examined in the normal young adult monkeys and aged adult monkeys. All the monkeys studied were proficient in the performance of a computer-assisted DMTS task. In a subsequent experiment in the same subjects, dimebolin was administered 15 min before a cognitively-impairing dose (20 µg kg−1) of scopolamine. KEY RESULTS In both the young adult and aged monkeys, dimebolin significantly increased the DMTS task accuracies. In young adults, the task improvement was associated with long (retention/retrieval) delay trials, and a protracted enhancement was observed for sessions run 24 h post administration of a single dose. Dimebolin did not significantly attenuate the scopolamine-induced impairment. In the aged monkeys, dimebolin significantly improved the reduced task accuracies associated with long delay intervals. CONCLUSIONS AND IMPLICATIONS Here we demonstrated that dimebolin is able to improve components of working memory in monkeys and to induce a protracted response for at least 24 h after administration of a single dose.

Objective: To explore the safety and short-term efficacy of the posterior approach of the Dynesys dynamic neutralization system for degenerative disease of the lumbar vertebrae. Methods: From March 2008 to March 2010, 32 cases of degenerative lumbar vertebral disease, 19 men and 13 women, (mean age 58 ± 5.2, range, 43–78 years), were treated with posterior laminectomy and Dynesys internal fixation. All patients had a history of over 3 months waist or leg pain that had not been relieved by conservative treatment. There were 10 cases of single lumbar intervertebral disc protrusion, 14 of degenerative lumbar spinal stenosis, 5 of degenerative lumbar isthmic spondylolisthesis, and 3 of recurrent lumbar disc protrusion after surgery. A visual analogue score (VAS) was used for pain assessment, and the Oswestry disability index (ODI) for functional evaluation of clinical outcomes. Results: All patients were followed up for 6–23 months (mean, 16.4 ± 5.5 months). Forty-one segments in 32 patients were stabilized; 23 cases (71.9%) underwent single-segmental stabilization, and 9 (28.1%) two-segmental stabilization. VAS of leg pain, root and low back pain was significantly improved postoperatively. The ODI improved from preoperative 69% ± 12.6% to postoperative 28% ± 15.7% (P < 0.001). On the stabilized segment and adjacent segments above and below, the range of movement showed no statistical difference; no loosening of screws, cord and polyester spacer occurred. Conclusion: The Dynesys dynamic neutralization system combined with decompression can achieve satisfactory short-term clinical results in lumbar degenerative disease. This procedure system not only reduces back and leg pain, but also preserves the mobility of fixed segments, minimizes tissue injury and avoids taking bone for spinal fusion.