Mitochondrial DNA sequence variation in human evolution and disease.

PubMed

Wallace, D C

1994-09-13

Germ-line and somatic mtDNA mutations are hypothesized to act together to shape our history and our health. Germ-line mtDNA mutations, both ancient and recent, have been associated with a variety of degenerative diseases. Mildly to moderately deleterious germ-line mutations, like neutral polymorphisms, have become established in the distant past through genetic drift but now may predispose certain individuals to late-onset degenerative diseases. As an example, a homoplasmic, Caucasian, tRNA(Gln) mutation at nucleotide pair (np) 4336 has been observed in 5% of Alzheimer disease and Parkinson disease patients and may contribute to the multifactorial etiology of these diseases. Moderately to severely deleterious germ-line mutations, on the other hand, appear repeatedly but are eliminated by selection. Hence, all extant mutations of this class are recent and associated with more devastating diseases of young adults and children. Representative of these mutations is a heteroplasmic mutation in MTND6 at np 14459 whose clinical presentations range from adult-onset blindness to pediatric dystonia and basal ganglial degeneration. To the inherited mutations are added somatic mtDNA mutations which accumulate in random arrays within stable tissues. These mutations provide a molecular clock that measures our age and may cause a progressive decline in tissue energy output that could precipitate the onset of degenerative diseases in individuals harboring inherited deleterious mutations.

Association between disk position and degenerative bone changes of the temporomandibular joints: an imaging study in subjects with TMD.

PubMed

Cortés, Daniel; Sylvester, Daniel Cortés; Exss, Eduardo; Marholz, Carlos; Millas, Rodrigo; Moncada, Gustavo

2011-04-01

The aim of this study was to determine the frequency and relationship between disk position and degenerative bone changes in the temporomandibular joints (TMJ), in subjects with internal derangement (ID). MRI and CT scans of 180 subjects with temporomandibular disorders (TMD) were studied. Different image parameters or characteristics were observed, such as disk position, joint effusion, condyle movement, degenerative bone changes (flattened, cortical erosions and irregularities), osteophytes, subchondral cysts and idiopathic condyle resorption. The present study concluded that there is a significant association between disk displacement without reduction and degenerative bone changes in patients with TMD. The study also found a high probability of degenerative bone changes when disk displacement without reduction is present. No association was found between TMD and condyle range of motion, joint effusion and/or degenerative bone changes. The following were the most frequent morphological changes observed: flattening of the anterior surface of the condyle; followed by erosions and irregularities of the joint surfaces; flattening of the articular surface of the temporal eminence, subchondral cysts, osteophytes; and idiopathic condyle resorption, in decreasing order.

Monoamine neurons in the human brain stem: anatomy, magnetic resonance imaging findings, and clinical implications.

PubMed

Sasaki, Makoto; Shibata, Eri; Tohyama, Koujiro; Kudo, Kohsuke; Endoh, Jin; Otsuka, Kotaro; Sakai, Akio

2008-11-19

By using high-resolution, conventional, and neuromelanin-sensitive magnetic resonance imaging techniques, we reviewed the normal anatomy of the nuclei consisting of monoamine neurons such as dopaminergic, noradrenergic, and serotoninergic neurons and noted the changes in these nuclei that occur in some degenerative and psychiatric disorders. Multimodal MR images can directly or indirectly help in identifying the substantia nigra, locus ceruleus, and raphe nuclei that contain monoamine neurons. Neuromelanin-sensitive magnetic resonance imaging can detect signal alterations in the substantia nigra pars compacta and/or locus ceruleus that occur in Parkinson's disease and psychiatric disorders such as depression and schizophrenia. This technique seems to be promising for the noninvasive evaluation of the pathological or functional changes in the monoamine system that occur in degenerative and psychiatric disorders.

Using Ferumoxytol-Enhanced MRI to Measure Inflammation in Patients With Brain Tumors or Other Conditions of the CNS

ClinicalTrials.gov

2017-08-30

Brain Injury; Central Nervous System Degenerative Disorder; Central Nervous System Infectious Disorder; Central Nervous System Vascular Malformation; Hemorrhagic Cerebrovascular Accident; Ischemic Cerebrovascular Accident; Primary Brain Neoplasm; Brain Cancer; Brain Tumors

Does balneotherapy with low radon concentration in water influence the endocrine system? A controlled non-randomized pilot study.

PubMed

Nagy, Katalin; Berhés, István; Kovács, Tibor; Kávási, Norbert; Somlai, János; Bender, Tamás

2009-08-01

Radon bath is a well-established modality of balneotherapy for the management of degenerative musculoskeletal disorders. The present study was conducted to ascertain whether baths of relatively low (80 Bq/l) radon concentration have any influence on the functioning of the endocrine system. In the study, a non-randomized pilot study, 27 patients with degenerative musculoskeletal disorders received 30-min radon baths (of 31-32 degrees C temperature and 80 Bq/l average radon concentration) daily, for 15 days. Twenty-five patients with matching pathologies were subjected to balneotherapy according to the same protocol, using thermal water with negligible radon content (6 Bq/l). Serum thyroid stimulating hormone, prolactin, cortisol, adrenocorticotropic hormone, and dehydroepiandrosterone levels were measured before and after a balneotherapy course of 15 sessions. Comparison of the accumulated data using the Wilcoxon test did not reveal any significant difference between pre- and post-treatment values or between the two patient groups. It is noted that while the beneficial effects of balneotherapy with radon-containing water on degenerative disorders is widely known, only few data have been published in the literature on its effect on endocrine functions. The present study failed to demonstrate any substantial effect of thermal water with relatively low radon content on the functioning of the endocrine system.

What's on Your Mind? Conversation Topics Chosen by People With Degenerative Cognitive-Linguistic Disorders for Communication Boards

PubMed Central

Daniels, Darlene; Ettinger, Olivia; Mooney, Aimee; Noethe, Glory; Rowland, Charity

2015-01-01

Purpose Conversational topics chosen by a group of adults with degenerative cognitive-linguistic disorders for personalized communication board development were examined. The patient-generated themes commonly selected are presented to guide treatment planning and communication board development. Method Communication boards were created for 109 adults as part of a larger research project. One autobiographical topic that each participant would enjoy discussing multiple times was represented on each communication board with 16 pictures and word labels. For this review, topics were collapsed into general themes through a consensus process and examined by gender and age. Results Sixty unique conversational topics were identified from 109 participants and collapsed into 9 general themes: Hobbies, Family, Travel, Work, Home/Places I've Lived, Sports/Fitness, Religion, Animals, and World War II. Age and gender produced variations in themes chosen, though no significance in rank orders was found across groups. Conclusions Topics selected by adults with degenerative cognitive-linguistic disorders for communication boards resemble common conversational adult themes and do not center around basic needs or medical issues. Differences in gender and age for topic selection tend to be based on traditional roles. These general themes should be used when creating personalized communication boards for those who benefit from conversational aids. PMID:25835511

A Review of Neuropsychological and Neuroimaging Research in Autistic Spectrum Disorders: Attention, Inhibition and Cognitive Flexibility

ERIC Educational Resources Information Center

Sanders, Jane; Johnson, Katherine A.; Garavan, Hugh; Gill, Michael; Gallagher, Louise

2008-01-01

Autistic spectrum disorders (ASD) are devastating neurodevelopmental disorders of unknown aetiology with characteristic deficits in social interaction, communication and behaviour. Individuals with ASD show deficits in executive function (EF), which are hypothesised to underlie core repetitive, stereotyped behaviours of autism. Neuroimaging…

Induced pluripotent stem cells (iPSC)-derived retinal cells in disease modeling and regenerative medicine.

PubMed

Rathod, Reena; Surendran, Harshini; Battu, Rajani; Desai, Jogin; Pal, Rajarshi

2018-02-12

Retinal degenerative disorders are a leading cause of the inherited, irreversible and incurable vision loss. While various rodent model systems have provided crucial information in this direction, lack of disease-relevant tissue availability and species-specific differences have proven to be a major roadblock. Human induced pluripotent stem cells (iPSC) have opened up a whole new avenue of possibilities not just in understanding the disease mechanism but also potential therapeutic approaches towards a cure. In this review, we have summarized recent advances in the methods of deriving retinal cell types from iPSCs which can serve as a renewable source of disease-relevant cell population for basic as well as translational studies. We also provide an overview of the ongoing efforts towards developing a suitable in vitro model for modeling retinal degenerative diseases. This basic understanding in turn has contributed to advances in translational goals such as drug screening and cell-replacement therapies. Furthermore we discuss gene editing approaches for autologous repair of genetic disorders and allogeneic transplantation of stem cell-based retinal derivatives for degenerative disorders with an ultimate goal to restore vision. It is pertinent to note however, that these exciting new developments throw up several challenges that need to be overcome before their full clinical potential can be realized. Copyright © 2018 Elsevier B.V. All rights reserved.

[Amusia].

PubMed

Midorikawa, Akira

2007-08-01

This report reviewed recent cases of amusia and drew the following conclusions. First, amusia is an ill-defined condition. The classical definition restricted amusia to musical disorders caused by brain lesions. By the end of the last century, however, some researchers included developmental or innate musical disorders in amusia. Second, although recent case reports were based on the classical schema of amusia, there have been an increasing number of case studies that have described more restricted and specific symptoms, such as receptive amusia for harmony or musical alexia for rhythm notation. Third, although we can now obtain more accurate information about the brain lesions, we have not taken advantage of this information. Traditionally, it has been thought that the pitch element of vocal performance is referred to the right frontal or temporal lobe. Lastly, the relationship between musical function and degenerative disease deserves attention. Degenerative diseases can cause either a musical deficit or, paradoxically, improve musical function. For example, the musical competence of some patients improved after selective atrophy of the left hemisphere. In conclusion, recent ideas concerning the relationship between music and the brain have been derived from patients with brain damage, developmental disorders, and degenerative diseases. However, there is a missing link with respect to amusia. We know a lot about the cognitive aspect of music, but the 'true' function of music from an evolutionary perspective, something that is lacking in amusia, is not known.

Increased polyamines as protective disease modifiers in congenital muscular dystrophy.

PubMed

Kemaladewi, D U; Benjamin, J S; Hyatt, E; Ivakine, E A; Cohn, R D

2018-06-01

Most Mendelian disorders, including neuromuscular disorders, display extensive clinical heterogeneity that cannot be solely explained by primary genetic mutations. This phenotypic variability is largely attributed to the presence of disease modifiers, which can exacerbate or lessen the severity and progression of the disease. LAMA2-deficient congenital muscular dystrophy (LAMA2-CMD) is a fatal degenerative muscle disease resulting from mutations in the LAMA2 gene encoding Laminin-α2. Progressive muscle weakness is predominantly observed in the lower limbs in LAMA2-CMD patients, whereas upper limbs muscles are significantly less affected. However, very little is known about the molecular mechanism underlying differential pathophysiology between specific muscle groups. Here, we demonstrate that the triceps muscles of the dy2j/dy2j mouse model of LAMA2-CMD demonstrate very mild myopathic findings compared with the tibialis anterior (TA) muscles that undergo severe atrophy and fibrosis, suggesting a protective mechanism in the upper limbs of these mice. Comparative gene expression analysis reveals that S-Adenosylmethionine decarboxylase (Amd1) and Spermine oxidase (Smox), two components of polyamine pathway metabolism, are downregulated in the TA but not in the triceps of dy2j/dy2j mice. As a consequence, the level of polyamine metabolites is significantly lower in the TA than triceps. Normalization of either Amd1 or Smox expression in dy2j/dy2j TA ameliorates muscle fibrosis, reduces overactive profibrotic TGF-β pathway and leads to improved locomotion. In summary, we demonstrate that a deregulated polyamine metabolism is a characteristic feature of severely affected lower limb muscles in LAMA2-CMD. Targeted modulation of this pathway represents a novel therapeutic avenue for this devastating disease.

Short-term results of physiotherapy in patients with newly diagnosed degenerative cervical spine disease.

PubMed

Hey, H W; Lau, P H; Hee, H T

2012-03-01

Degenerative cervical spine diseases are common, and physiotherapy is widely used as an initial form of treatment. We aimed to analyse the effects of the initial sessions of physiotherapy for patients who were newly diagnosed with degenerative cervical spine disorders. A prospective series of 30 patients with newly diagnosed degenerative cervical spine disease were referred to our department and followed up for the initial two sessions of physiotherapy. The patients were assessed after each session. Outcome parameters studied included pain using a visual analogue scale (VAS), neck range of movements and activities of daily living (ADL). Our study subjects comprised mainly females (60%) in their fifties (46.7%) who worked as clerks or secretaries (53.3%). There was an improvement in the patients' pain score (VAS) from a median of 8 to 4 after two visits to the physiotherapists. Slight improvement in the neck range of movements was also observed. Marked improvement was seen in ADL, especially in the ability to carry heavy objects. Physiotherapy is an effective initial option for patients with newly presented degenerative cervical spine disease. The results of this study can be used to advise patients on the short-term benefits of physiotherapy.

Biological Markers of Cognition in Prodromal Huntington's Disease: A Review

ERIC Educational Resources Information Center

Papp, Kathryn V.; Kaplan, Richard F.; Snyder, Peter J.

2011-01-01

Huntington's disease (HD), an autosomal-dominant genetic disorder, has historically been viewed as a degenerative movement disorder but it also includes psychiatric symptoms and progressive cognitive decline. There has been a lack of consensus in the literature about whether or not cognitive signs can be detected in carriers before clinical…

[Nineteen cases of school-aged children with degenerative or metabolic neurological disorders initially presenting with learning difficulty and/or behavior disturbance].

PubMed

Honzawa, Shiho; Sugai, Kenji; Akaike, Hiroto; Nakayama, Tojo; Fujikawa, Yoshinao; Komaki, Hirofumi; Nakagawa, Eiji; Sasaki, Masayuki

2012-07-01

We reported 19 cases of school-aged children. They were initially judged to have learning difficulty or school maladaptation because of attention deficits, hyperactive behaviors or poor school performance, followed by the diagnosis such as degenerative or metabolic neurological diseases. The patients consisted of 4 cases of adrenoleukodystrophy, 5 cases of dentatorubral-pallidoluysian atrophy, 3 cases of Sanfilippo syndrome, 3 cases of subacute sclerosing panencephalitis, and each one case of juvenile Gaucher disease, juvenile Huntington disease, juvenile metachromatic leukodystrophy and Leigh disease. They had markedly poor school performance, and/or abnormal behaviors, followed by seizures, character disorders or psychomotor regression. The diagnostic clues included brain CT scan and/or MRI, peculiar facial appearance and notable family histories. When the children were indicated to have learning difficulty or maladjustment to school life, we should make deliberate differential diagnoses before concluding that they have a learning disorder and/or attention-deficit/hyperactivity disorder. Instead they should be recommended to visit child neurologists, when they present with any problems as aforesaid.

Nonsurgically managed patients with degenerative spondylolisthesis: a 10- to 18-year follow-up study.

PubMed

Matsunaga, S; Ijiri, K; Hayashi, K

2000-10-01

Controversy exists concerning the indications for surgery and choice of surgical procedure for patients with degenerative spondylolisthesis. The goals of this study were to determine the clinical course of nonsurgically managed patients with degenerative spondylolisthesis as well as the indications for surgery. A total of 145 nonsurgically managed patients with degenerative spondylolisthesis were examined annually for a minimum of 10 years follow-up evaluation. Radiographic changes, changes in clinical symptoms, and functional prognosis were surveyed. Progressive spondylolisthesis was observed in 49 patients (34%). There was no correlation between changes in clinical symptoms and progression of spondylolisthesis. The intervertebral spaces of the slipped segments were decreased significantly in size during follow-up examination in patients in whom no progression was found. Low-back pain improved following a decrease in the total intervertebral space size. A total of 84 (76%) of 110 patients who had no neurological deficits at initial examination remained without neurological deficit after 10 years of follow up. Twenty-nine (83%) of the 35 patients who had neurological symptoms, such as intermittent claudication or vesicorectal disorder, at initial examination and refused surgery experienced neurological deterioration. The final prognosis for these patients was very poor. Low-back pain was improved by restabilization. Conservative treatment is useful for patients who have low-back pain with or without pain in the lower extremities. Surgical intervention is indicated for patients with neurological symptoms including intermittent claudication or vesicorectal disorder, provided that a good functional outcome can be achieved.

Surgical results of dynamic nonfusion stabilization with the Segmental Spinal Correction System for degenerative lumbar spinal diseases with instability: Minimum 2-year follow-up

PubMed Central

Ohta, Hideki; Matsumoto, Yoshiyuki; Morishita, Yuichirou; Sakai, Tsubasa; Huang, George; Kida, Hirotaka; Takemitsu, Yoshiharu

2011-01-01

Background When spinal fusion is applied to degenerative lumbar spinal disease with instability, adjacent segment disorder will be an issue in the future. However, decompression alone could cause recurrence of spinal canal stenosis because of increased instability on operated segments and lead to revision surgery. Covering the disadvantages of both procedures, we applied nonfusion stabilization with the Segmental Spinal Correction System (Ulrich Medical, Ulm, Germany) and decompression. Methods The surgical results of 52 patients (35 men and 17 women) with a minimum 2-year follow-up were analyzed: 10 patients with lumbar spinal canal stenosis, 15 with lumbar canal stenosis with disc herniation, 20 with degenerative spondylolisthesis, 6 with disc herniation, and 1 with lumbar discopathy. Results The Japanese Orthopaedic Association score was improved, from 14.4 ± 5.3 to 25.5 ± 2.8. The improvement rate was 76%. Range of motion of the operated segments was significantly decreased, from 9.6° ± 4.2° to 2.0° ± 1.8°. Only 1 patient had adjacent segment disease that required revision surgery. There was only 1 screw breakage, but the patient was asymptomatic. Conclusions Over a minimum 2-year follow-up, the results of nonfusion stabilization with the Segmental Spinal Correction System for unstable degenerative lumbar disease were good. It is necessary to follow up the cases with a focus on adjacent segment disorders in the future. PMID:25802671

Increased risk of tinnitus in patients with temporomandibular disorder: a retrospective population-based cohort study.

PubMed

Lee, Chun-Feng; Lin, Ming-Chia; Lin, Hui-Tzu; Lin, Cheng-Li; Wang, Tang-Chuan; Kao, Chia-Hung

2016-01-01

This study determined whether there is an increased risk of tinnitus in patients with temporomandibular joint (TMJ). We used information from health insurance claims obtained from Taiwan National Health Insurance (TNHI). Patients aged 20 years and older who were newly diagnosed with TMJ disorder served as the study cohort. The demographic factors and comorbidities that may be associated with tinnitus were also identified, including age, sex, and comorbidities of hearing loss, noise effects on the inner ear, and degenerative and vascular ear disorders. A higher proportion of TMJ disorder patients suffered from hearing loss (5.30 vs. 2.11 %), and degenerative and vascular ear disorders (0.20 vs. 0.08 %) compared with the control patients. The crude hazard ratio (HR) of tinnitus in the TMJ disorder cohort was 2.73-fold higher than that in the control patients, with an adjusted HR of 2.62 (95 % CI = 2.29-3.00). The comorbidity-specific TMJ disorder cohort to the control patients' adjusted HR of tinnitus was higher for patients without comorbidity (adjusted HR = 2.75, 95 % CI = 2.39-3.17). We also observed a 3.22-fold significantly higher relative risk of developing tinnitus within the 3-year follow-up period (95 % CI = 2.67-3.89). Patients with TMJ disorder might be at increased risk of tinnitus.

Devastating metabolic brain disorders of newborns and young infants.

PubMed

Yoon, Hyun Jung; Kim, Ji Hye; Jeon, Tae Yeon; Yoo, So-Young; Eo, Hong

2014-01-01

Metabolic disorders of the brain that manifest in the neonatal or early infantile period are usually associated with acute and severe illness and are thus referred to as devastating metabolic disorders. Most of these disorders may be classified as organic acid disorders, amino acid metabolism disorders, primary lactic acidosis, or fatty acid oxidation disorders. Each disorder has distinctive clinical, biochemical, and radiologic features. Early diagnosis is important both for prompt treatment to prevent death or serious sequelae and for genetic counseling. However, diagnosis is often challenging because many findings overlap and may mimic those of more common neonatal conditions, such as hypoxic-ischemic encephalopathy and infection. Ultrasonography (US) may be an initial screening method for the neonatal brain, and magnetic resonance (MR) imaging is the modality of choice for evaluating metabolic brain disorders. Although nonspecific imaging findings are common in early-onset metabolic disorders, characteristic patterns of brain involvement have been described for several disorders. In addition, diffusion-weighted images may be used to characterize edema during an acute episode of encephalopathy, and MR spectroscopy depicts changes in metabolites that may help diagnose metabolic disorders and assess response to treatment. Imaging findings, including those of advanced MR imaging techniques, must be closely reviewed. If one of these rare disorders is suspected, the appropriate biochemical test or analysis of the specific gene should be performed to confirm the diagnosis. ©RSNA, 2014.

[Disturbed sleep, anxiety and stress are possible risk indicators for temporomandibular disorders with myofascialpain].

PubMed

Lei, J; Liu, M Q; Fu, K Y

2016-02-18

To explore the relationship betweensleep/psychological distress and temporomandibular disorders (TMD) and to discuss the possibility of disturbed sleep and psychological distress as risk indicators in relation to TMD in a Chinese population. The standardized and validated self-reported Chinese version questionnaires including Pittsburgh sleep quality index (PSQI) and depression, anxietyandstress scales-21 (DASS-21) were used to measure sleep quality and psychological distress. A total of 755 TMD patients (172 males and 583 females)with a mean age (29.99 ± 13.60) years were included in the study. The patients were divided into 7 diagnostic groups based on the Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD), including Group I(exclusively myofascial pain), Group II(exclusively disc displacement), Group III (exclusively arthralgia or degenerative joint disease), Group IV (myofascial pain plus disc displacement), Group V (myofascial pain plus arthralgia or degenerative joint disease), Group VI (disc displacement plus arthralgia or degenerative joint disease) and Group VII (myofascial pain plus disc displacement plus arthralgia or degenerative joint disease). For statistical analysis, the patients were subsequently grouped into those with (181 patients) and without (574 patients) myofascial pain. Chi-square tests, independent-samples t test, partial correlation as well as stepwise Logistic regression analysis were used to analyze the data, using software SPSS 20.0 and P<0.05 was of significance. The prevalence of moderate to (extremely) severe disturbed sleep and psychological distress was significantly higher in the myofascial pain group (27.1%, 28.7%, 60.8% and 32.0%) than in the non-myofascial pain group (disc displacement and arthralgia or degenerative joint disease, 11.1%, 10.1%, 27.4% and 11.0%, P<0.05).The comorbidity of self-reported disturbed sleep and psychological distress was significantly higher in the myofascial pain patients than those without myofascial pain (P<0.05). Stepwise logistic regression analysis demonstrated that disturbed sleep (OR=1.74), more specifically, subjective sleep quality (OR=1.69) and sleep disturbance (OR=1.63) respectively, anxiety (OR=3.14) and stress (OR=2.15) were possible risk indicators for myofascial pain, and the results were still significant even after controlling for age, sex, educational level, disease duration, sleep quality, depression, anxiety and stress respectively (P<0.05). Disturbed sleep and psychological distress symptoms are common in TMD patients. Disturbed sleep, anxiety and stress are possible risk indicators for myofascial pain, compared with disc displacement and arthralgia or degenerative joint diseases.

[Disturbed sleep, anxiety and stress are possible risk indicators for temporomandibular disorders with myofascialpain].

PubMed

Lei, J; Liu, M Q; Fu, K Y

2016-08-18

To explore the relationship betweensleep/psychological distress and temporomandibular disorders (TMD) and to discuss the possibility of disturbed sleep and psychological distress as risk indicators in relation to TMD in a Chinese population. The standardized and validated self-reported Chinese version questionnaires including Pittsburgh sleep quality index (PSQI) and depression, anxietyandstress scales-21 (DASS-21) were used to measure sleep quality and psychological distress. A total of 755 TMD patients (172 males and 583 females)with a mean age (29.99 ± 13.60) years were included in the study. The patients were divided into 7 diagnostic groups based on the Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD), including Group I(exclusively myofascial pain), Group II(exclusively disc displacement), Group III (exclusively arthralgia or degenerative joint disease), Group IV (myofascial pain plus disc displacement), Group V (myofascial pain plus arthralgia or degenerative joint disease), Group VI (disc displacement plus arthralgia or degenerative joint disease) and Group VII (myofascial pain plus disc displacement plus arthralgia or degenerative joint disease). For statistical analysis, the patients were subsequently grouped into those with (181 patients) and without (574 patients) myofascial pain. Chi-square tests, independent-samples t test, partial correlation as well as stepwise Logistic regression analysis were used to analyze the data, using software SPSS 20.0 and P<0.05 was of significance. The prevalence of moderate to (extremely) severe disturbed sleep and psychological distress was significantly higher in the myofascial pain group (27.1%, 28.7%, 60.8% and 32.0%) than in the non-myofascial pain group (disc displacement and arthralgia or degenerative joint disease, 11.1%, 10.1%, 27.4% and 11.0%, P<0.05).The comorbidity of self-reported disturbed sleep and psychological distress was significantly higher in the myofascial pain patients than those without myofascial pain (P<0.05). Stepwise logistic regression analysis demonstrated that disturbed sleep (OR=1.74), more specifically, subjective sleep quality (OR=1.69) and sleep disturbance (OR=1.63) respectively, anxiety (OR=3.14) and stress (OR=2.15) were possible risk indicators for myofascial pain, and the results were still significant even after controlling for age, sex, educational level, disease duration, sleep quality, depression, anxiety and stress respectively (P<0.05). Disturbed sleep and psychological distress symptoms are common in TMD patients. Disturbed sleep, anxiety and stress are possible risk indicators for myofascial pain, compared with disc displacement and arthralgia or degenerative joint diseases.

Clinical Evaluation of the TITAN™ Total Shoulder System

ClinicalTrials.gov

2018-02-14

Arthritis; Arthritis, Degenerative; Rheumatoid Arthritis; Post-traumatic Arthrosis of Other Joints, Shoulder Region; Rotator Cuff Syndrome of Shoulder and Allied Disorders; Fracture; Avascular Necrosis; Joint Instability; Joint Trauma; Dislocation, Shoulder; Pain, Shoulder

Proximal Junctional Failure After Long-Segment Instrumentation for Degenerative Lumbar Kyphosis With Ankylosing Spinal Disorder.

PubMed

Ikegami, Daisuke; Matsuoka, Takashi; Miyoshi, Yuji; Murata, Yoichi; Aoki, Yasuaki

2015-06-15

Case report. We report a case of proximal junctional failure at the ankylosed, but not the mobile, junction after segmental instrumented fusion for degenerative lumbar kyphosis with ankylosing spinal disorder. Proximal junctional failure (PJF) and proximal junctional kyphosis (PJK) are important complications that occur subsequent to long-segment instrumentation for correction of adult spinal deformity. Thus far, most studies have focused on the mobile junction as a site at which PJK/PJF can occur, and little is known about the relationship between PJK/PJF and ankylosing spinal disorders such as diffuse idiopathic skeletal hyperostosis. The patient was an 82-year-old female with degenerative lumbar kyphosis. She had abnormal confluent hyperostosis in the anterior longitudinal ligaments from Th5 to Th10. The patient was treated operatively with spinal instrumented fusion from Th10 to the sacrum. Four weeks subsequent to initial surgery, the patient developed progressive lower extremity paresis caused by the uppermost instrumented vertebrae fracture (Th10) and adjacent subluxation (Th9). Extension of fusion to Th5 with decompression at Th9-Th10 was performed. However, the patient showed no improvement in neurological function. PJF can occur at the ankylosing site above the uppermost instrumented vertebrae after long-segment instrumentation for adult spinal deformity. PJF in the ankylosed spine may cause severe fracture instability and cord deficit. The ankylosed spine should be integrated into the objective determination of materials contributing to the appropriate selection of fusion levels. 3.

Swespine: the Swedish spine register : the 2012 report.

PubMed

Strömqvist, Björn; Fritzell, Peter; Hägg, Olle; Jönsson, Bo; Sandén, Bengt

2013-04-01

Swespine, the Swedish National Spine Register, has existed for 20 years and is in general use within the country since over 10 years regarding degenerative lumbar spine disorders. Today there are protocols for registering all disorders of the entire spinal column. Patient-based pre- and postoperative questionnaires, completed before surgery and at 1, 2, 5 and 10 years postoperatively. Among patient-based data are VAS pain, ODI, SF-36 and EQ-5D. Postoperatively evaluation of leg and back pain as compared to preoperatively ("global assessment"), overall satisfaction with outcome and working conditions are registered in addition to the same parameters as preoperatively evaluation. A yearly report is produced including an analytic part of a certain topic, in this issue disc prosthesis surgery. More than 75,000 surgically treated patients are registered to date with an increasing number yearly. The present report includes 7,285 patients; 1-, 2- and 5-year follow-up data of previously operated patients are also included for lumbar disorders as well as for disc prosthesis surgery. For the degenerative lumbar spine disorders (disc herniation, spinal stenosis, spondylolisthesis and DDD) significant improvements are seen in all aspects as exemplified by pronounced improvement regarding EQ-5D and ODI. Results seem to be stable over time. Spinal stenosis is the most common indication for spine surgery. Disc prosthesis surgery yields results on a par with fusion surgery in disc degenerative pain. The utility of spine surgery is well documented by the results. Results of spine surgery as documented on a national basis can be utilized for quality assurance and quality improvement as well as for research purposes, documenting changes over time and bench marking when introducing new surgical techniques. A basis for international comparisons is also laid.

Stroke from systemic vascular disorders in Saudi children. The devastating role of hypernatremic dehydration.

PubMed

Salih, Mustafa A; Zahraa, Jihad N; Al-Jarallah, Ahmed A; Alorainy, Ibrahim A; Hassan, Hamdy H

2006-03-01

Systemic vascular disorders, leading to childhood stroke, include volume depletion or systemic hypotension and hypernatremic dehydration. We describe 3 cases of stroke following systemic vascular disorders. These were diagnosed during a prospective and retrospective study on childhood stroke, which included 104 patients. Post-gastroenteritis hypernatremic dehydration is an important, potentially preventable, cause of stroke in Saudi children.

Spine Degenerative Conditions and Their Treatments: National Trends in the United States of America.

PubMed

Buser, Zorica; Ortega, Brandon; D'Oro, Anthony; Pannell, William; Cohen, Jeremiah R; Wang, Justin; Golish, Ray; Reed, Michael; Wang, Jeffrey C

2018-02-01

Retrospective database study. Low back and neck pain are among the top leading causes of disability worldwide. The aim of our study was to report the current trends on spine degenerative disorders and their treatments. Patients diagnosed with lumbar or cervical spine conditions within the orthopedic subset of Medicare and Humana databases (PearlDiver). From the initial cohorts we identified subgroups based on the treatment: fusion or nonoperative within 1 year from diagnosis. Poisson regression was used to determine demographic differences in diagnosis and treatment approaches. Within the Medicare database there were 6 206 578 patients diagnosed with lumbar and 3 156 215 patients diagnosed with cervical degenerative conditions between 2006 and 2012, representing a 16.5% (lumbar) decrease and 11% (cervical) increase in the number of diagnosed patients. There was an increase of 18.5% in the incidence of fusion among lumbar patients. For the Humana data sets there were 1 160 495 patients diagnosed with lumbar and 660 721 patients diagnosed with cervical degenerative disorders from 2008 to 2014. There was a 33% (lumbar) and 42% (cervical) increases in the number of diagnosed patients. However, in both lumbar and cervical groups there was a decrease in the number of surgical and nonoperative treatments. There was an overall increase in both lumbar and cervical conditions, followed by an increase in lumbar fusion procedures within the Medicare database. There is still a burning need to optimize the spine care for the elderly and people in their prime work age to lessen the current national economic burden.

Recessive resistance to Cucurbit yellow stunting disorder virus in melon

USDA-ARS?s Scientific Manuscript database

Cucurbit yellow stunting disorder virus (CYSDV) reduces melon (Cucumis melo L.) fruit quality and yield in many parts of the world. CYSDV and its vector, sweetpotato whitefly (MEAM1 cryptic species of Bemisia tabaci; SPWF) are a devastating combination in the Sonoran Desert areas of California and A...

Measuring outcomes for neurological disorders: a review of disease-specific health status instruments for three degenerative neurological conditions.

PubMed

Heffernan, Catherine; Jenkinson, Crispin

2005-06-01

Health-related quality-of-life measures have been increasingly used in research into neurological disorders in recent years. The aim of this paper is to provide an objective appraisal of the evidence in regard to disease-specific quality-of-life measures used in research on health interventions for three degenerative neurological disorders: multiple sclerosis, motor neurone disease/amyotrophic lateral sclerosis and Parkinson's disease. A comprehensive search strategy was developed to include nine relevant electronic databases. Only studies pertaining to patient-based outcome measurements in multiple sclerosis, motor neurone disease and Parkinson's disease were included. We identified 76 eligible studies. As studies consisted of descriptive and cross-sectional survey study designs, results were reported qualitatively rather than in the form of a meta-analysis. Four disease-specific measures were found for Parkinson's disease, 11 for multiple sclerosis and one for motor neurone disease. We conclude that health-related quality-of-life measures are useful in assessing the impact of treatments and interventions for neurological disorders. However, further research is needed on the development of instruments using psychometric methods and on the validation, utilization and responsiveness of instruments to change.

Vitreous floaters.

PubMed

Roufail, E D; Polkinghorne, Philip

2006-01-01

Floaters are a common presenting ophthalmic symptom that may accompany sight-threatening disorders. In most cases, they are often secondary to benign, degenerative changes in the vitreous. In this review, we briefly examine the anatomy of the vitreous and describe how degenerative vitreous change contributes to the development of floaters. The causality of floaters in the presence and absence of a posterior vitreous detachment is reviewed, as is the clinical significance of these symptoms and signs in relation to their predictive value for determining the presence of sight-threatening retinal tears and/or detachment. Finally, a brief review of management options for debilitating floaters is presented.

Neck Pain

MedlinePlus

... Vomiting Nausea and Vomiting in Infants and Children Neck Pain Neck Swelling Shortness of Breath Shortness of Breath ... worse or doesn’t get better. Start OverDiagnosisYour pain may be from DEGENERATIVE CERVICAL ARTHRITIS, a disorder that affects the bones and ...

Focal neurological deficits

MedlinePlus

... include: Abnormal blood vessels (vascular malformation) Brain tumor Cerebral palsy Degenerative nerve illness (such as multiple sclerosis) Disorders of a single nerve or nerve group (for example, carpal tunnel syndrome ) Infection of the brain (such as meningitis or encephalitis) Injury Stroke Home ...

Cellular Reparative Mechanisms of Mesenchymal Stem Cells for Retinal Diseases.

PubMed

Ding, Suet Lee Shirley; Kumar, Suresh; Mok, Pooi Ling

2017-07-28

The use of multipotent mesenchymal stem cells (MSCs) has been reported as promising for the treatment of numerous degenerative disorders including the eye. In retinal degenerative diseases, MSCs exhibit the potential to regenerate into retinal neurons and retinal pigmented epithelial cells in both in vitro and in vivo studies. Delivery of MSCs was found to improve retinal morphology and function and delay retinal degeneration. In this review, we revisit the therapeutic role of MSCs in the diseased eye. Furthermore, we reveal the possible cellular mechanisms and identify the associated signaling pathways of MSCs in reversing the pathological conditions of various ocular disorders such as age-related macular degeneration (AMD), retinitis pigmentosa, diabetic retinopathy, and glaucoma. Current stem cell treatment can be dispensed as an independent cell treatment format or with the combination of other approaches. Hence, the improvement of the treatment strategy is largely subjected by our understanding of MSCs mechanism of action.

Cellular Reparative Mechanisms of Mesenchymal Stem Cells for Retinal Diseases

PubMed Central

Ding, Suet Lee Shirley; Kumar, Suresh; Mok, Pooi Ling

2017-01-01

The use of multipotent mesenchymal stem cells (MSCs) has been reported as promising for the treatment of numerous degenerative disorders including the eye. In retinal degenerative diseases, MSCs exhibit the potential to regenerate into retinal neurons and retinal pigmented epithelial cells in both in vitro and in vivo studies. Delivery of MSCs was found to improve retinal morphology and function and delay retinal degeneration. In this review, we revisit the therapeutic role of MSCs in the diseased eye. Furthermore, we reveal the possible cellular mechanisms and identify the associated signaling pathways of MSCs in reversing the pathological conditions of various ocular disorders such as age-related macular degeneration (AMD), retinitis pigmentosa, diabetic retinopathy, and glaucoma. Current stem cell treatment can be dispensed as an independent cell treatment format or with the combination of other approaches. Hence, the improvement of the treatment strategy is largely subjected by our understanding of MSCs mechanism of action. PMID:28788088

Degenerative lumbosacral stenosis in dogs.

PubMed

Meij, Björn P; Bergknut, Niklas

2010-09-01

Degenerative lumbosacral stenosis (DLSS) is the most common disorder of the caudal lumbar spine in dogs. This article reviews the management of this disorder and highlights the most important new findings of the last decade. Dogs with DLSS are typically neuro-orthopedic patients and can be presented with varying clinical signs, of which the most consistent is lumbosacral pain. Due to the availability of advanced imaging techniques such as computed tomography and magnetic resonance imaging that allow visualization of intervertebral disc degeneration, cauda equina compression, and nerve root entrapment, tailor-made treatments can be adopted for the individual patient. Current therapies include conservative treatment, decompressive surgery, and fixation-fusion of the L7-S1 junction. New insight into the biomechanics and pathobiology of DLSS and developments in minimally invasive surgical techniques will influence treatment options in the near future. Copyright 2010 Elsevier Inc. All rights reserved.

A fully organic retinal prosthesis restores vision in a rat model of degenerative blindness

NASA Astrophysics Data System (ADS)

Maya-Vetencourt, José Fernando; Ghezzi, Diego; Antognazza, Maria Rosa; Colombo, Elisabetta; Mete, Maurizio; Feyen, Paul; Desii, Andrea; Buschiazzo, Ambra; di Paolo, Mattia; di Marco, Stefano; Ticconi, Flavia; Emionite, Laura; Shmal, Dmytro; Marini, Cecilia; Donelli, Ilaria; Freddi, Giuliano; Maccarone, Rita; Bisti, Silvia; Sambuceti, Gianmario; Pertile, Grazia; Lanzani, Guglielmo; Benfenati, Fabio

2017-06-01

The degeneration of photoreceptors in the retina is one of the major causes of adult blindness in humans. Unfortunately, no effective clinical treatments exist for the majority of retinal degenerative disorders. Here we report on the fabrication and functional validation of a fully organic prosthesis for long-term in vivo subretinal implantation in the eye of Royal College of Surgeons rats, a widely recognized model of retinitis pigmentosa. Electrophysiological and behavioural analyses reveal a prosthesis-dependent recovery of light sensitivity and visual acuity that persists up to 6-10 months after surgery. The rescue of the visual function is accompanied by an increase in the basal metabolic activity of the primary visual cortex, as demonstrated by positron emission tomography imaging. Our results highlight the possibility of developing a new generation of fully organic, highly biocompatible and functionally autonomous photovoltaic prostheses for subretinal implants to treat degenerative blindness.

The role of arthroscopy in ankle and subtalar degenerative joint disease.

PubMed

Cheng, J C; Ferkel, R D

1998-04-01

Treatment options for degenerative joint disease of the ankle and subtalar joints are limited. When conservative management fails, the only effective procedure is arthrodesis. With the advent of the small arthroscope and the development of better instrumentation and distraction techniques, small joint arthroscopy has gained popularity as an important diagnostic and therapeutic tool in the treatment of ankle and subtalar disorders. Although the benefits of arthroscopic ankle arthrodesis are well established, and arthroscopic subtalar arthrodesis has been described recently, the role of arthroscopic debridement for degenerative joint disease of the ankle and subtalar joints remains controversial. Traditionally, operative arthroscopy for ankle arthritis has not met with great success; however, recent studies have shown that it can provide an interim alternative to arthrodesis in early arthritis with preserved range of motion. Lesions associated with arthritis, such as impinging osteophytes and loose bodies, can be treated effectively with arthroscopy.

A fully organic retinal prosthesis restores vision in a rat model of degenerative blindness

PubMed Central

Antognazza, Maria Rosa; Colombo, Elisabetta; Mete, Maurizio; Feyen, Paul; Desii, Andrea; Buschiazzo, Ambra; Di Paolo, Mattia; Di Marco, Stefano; Ticconi, Flavia; Emionite, Laura; Shmal, Dmytro; Marini, Cecilia; Donelli, Ilaria; Freddi, Giuliano; Maccarone, Rita; Bisti, Silvia; Sambuceti, Gianmario; Pertile, Grazia; Lanzani, Guglielmo; Benfenati, Fabio

2017-01-01

The degeneration of photoreceptors in the retina is one of the major causes of adult blindness in humans. Unfortunately, no effective clinical treatments exist for the majority of retinal degenerative disorders. Here we report on the fabrication and functional validation of a fully organic prosthesis for long-term in vivo subretinal implantation in the eye of Royal College of Surgeons rats, a widely recognized model of Retinitis pigmentosa. Electrophysiological and behavioral analyses reveal a prosthesis-dependent recovery of light-sensitivity and visual acuity that persists up to 6-10 months after surgery. The rescue of the visual function is accompanied by an increase in the basal metabolic activity of the primary visual cortex, as demonstrated by positron emission tomography imaging. Our results highlight the possibility of developing a new generation of fully organic, highly biocompatible and functionally autonomous photovoltaic prostheses for subretinal implants to treat degenerative blindness. PMID:28250420

An Unusual Splice Defect in the Mitofusin 2 Gene (MFN2) Is Associated with Degenerative Axonopathy in Tyrolean Grey Cattle

PubMed Central

Drögemüller, Cord; Reichart, Ursula; Seuberlich, Torsten; Oevermann, Anna; Baumgartner, Martin; Kühni Boghenbor, Kathrin; Stoffel, Michael H.; Syring, Claudia; Meylan, Mireille; Müller, Simone; Müller, Mathias; Gredler, Birgit

2011-01-01

Tyrolean Grey cattle represent a local breed with a population size of ∼5000 registered cows. In 2003, a previously unknown neurological disorder was recognized in Tyrolean Grey cattle. The clinical signs of the disorder are similar to those of bovine progressive degenerative myeloencephalopathy (weaver syndrome) in Brown Swiss cattle but occur much earlier in life. The neuropathological investigation of an affected calf showed axonal degeneration in the central nervous system (CNS) and femoral nerve. The pedigrees of the affected calves suggested a monogenic autosomal recessive inheritance. We localized the responsible mutation to a 1.9 Mb interval on chromosome 16 by genome-wide association and haplotype mapping. The MFN2 gene located in this interval encodes mitofusin 2, a mitochondrial membrane protein. A heritable human axonal neuropathy, Charcot-Marie-Tooth disease-2A2 (CMT2A2), is caused by MFN2 mutations. Therefore, we considered MFN2 a positional and functional candidate gene and performed mutation analysis in affected and control Tyrolean Grey cattle. We did not find any non-synonymous variants. However, we identified a perfectly associated silent SNP in the coding region of exon 20 of the MFN2 gene. This SNP is located within a putative exonic splice enhancer (ESE) and the variant allele leads to partial retention of the entire intron 19 and a premature stop codon in the aberrant MFN2 transcript. Thus we have identified a highly unusual splicing defect, where an exonic single base exchange leads to the retention of the preceding intron. This splicing defect represents a potential explanation for the observed degenerative axonopathy. Marker assisted selection can now be used to eliminate degenerative axonopathy from Tyrolean Grey cattle. PMID:21526202

An unusual splice defect in the mitofusin 2 gene (MFN2) is associated with degenerative axonopathy in Tyrolean Grey cattle.

PubMed

Drögemüller, Cord; Reichart, Ursula; Seuberlich, Torsten; Oevermann, Anna; Baumgartner, Martin; Kühni Boghenbor, Kathrin; Stoffel, Michael H; Syring, Claudia; Meylan, Mireille; Müller, Simone; Müller, Mathias; Gredler, Birgit; Sölkner, Johann; Leeb, Tosso

2011-04-15

Tyrolean Grey cattle represent a local breed with a population size of ∼5000 registered cows. In 2003, a previously unknown neurological disorder was recognized in Tyrolean Grey cattle. The clinical signs of the disorder are similar to those of bovine progressive degenerative myeloencephalopathy (weaver syndrome) in Brown Swiss cattle but occur much earlier in life. The neuropathological investigation of an affected calf showed axonal degeneration in the central nervous system (CNS) and femoral nerve. The pedigrees of the affected calves suggested a monogenic autosomal recessive inheritance. We localized the responsible mutation to a 1.9 Mb interval on chromosome 16 by genome-wide association and haplotype mapping. The MFN2 gene located in this interval encodes mitofusin 2, a mitochondrial membrane protein. A heritable human axonal neuropathy, Charcot-Marie-Tooth disease-2A2 (CMT2A2), is caused by MFN2 mutations. Therefore, we considered MFN2 a positional and functional candidate gene and performed mutation analysis in affected and control Tyrolean Grey cattle. We did not find any non-synonymous variants. However, we identified a perfectly associated silent SNP in the coding region of exon 20 of the MFN2 gene. This SNP is located within a putative exonic splice enhancer (ESE) and the variant allele leads to partial retention of the entire intron 19 and a premature stop codon in the aberrant MFN2 transcript. Thus we have identified a highly unusual splicing defect, where an exonic single base exchange leads to the retention of the preceding intron. This splicing defect represents a potential explanation for the observed degenerative axonopathy. Marker assisted selection can now be used to eliminate degenerative axonopathy from Tyrolean Grey cattle.

Canine Degenerative Myelopathy: Biochemical characterization of superoxide dismutase 1 in the first naturally occurring non-human amyotrophic lateral sclerosis model1

PubMed Central

Crisp, Matthew J.; Beckett, Jeffrey; Coates, Joan R.; Miller, Timothy M.

2013-01-01

Mutations in canine superoxide dismutase 1 (SOD1) have recently been shown to cause canine degenerative myelopathy, a disabling neurodegenerative disorder affecting specific breeds of dogs characterized by progressive motor neuron loss and paralysis until death, or more common, euthanasia. This discovery makes canine degenerative myelopathy the first and only naturally occurring non-human model of amyotrophic lateral sclerosis (ALS), closely paralleling the clinical, pathological, and genetic presentation of its human counterpart, SOD1-mediated familial ALS. To further understand the biochemical role that canine SOD1 plays in this disease and how it may be similar to human SOD1, we characterized the only two SOD1 mutations described in affected dogs to date, E40K and T18S. We show that a detergent-insoluble species of mutant SOD1 is present in spinal cords of affected dogs that increases with disease progression. Our in vitro results indicate that both canine SOD1 mutants form enzymatically active dimers, arguing against a loss of function in affected homozygous animals. Further studies show that these mutants, like most human SOD1 mutants, have an increased propensity to form aggregates in cell culture, with 10-20% of cells possessing visible aggregates. Creation of the E40K mutation in human SOD1 recapitulates the normal enzymatic activity but not the aggregation propensity seen with the canine mutant. Our findings lend strong biochemical support to the toxic role of SOD1 in canine degenerative myelopathy and establish close parallels for the role mutant SOD1 plays in both canine and human disorders. PMID:23707216

Canine degenerative myelopathy: biochemical characterization of superoxide dismutase 1 in the first naturally occurring non-human amyotrophic lateral sclerosis model.

PubMed

Crisp, Matthew J; Beckett, Jeffrey; Coates, Joan R; Miller, Timothy M

2013-10-01

Mutations in canine superoxide dismutase 1 (SOD1) have recently been shown to cause canine degenerative myelopathy, a disabling neurodegenerative disorder affecting specific breeds of dogs characterized by progressive motor neuron loss and paralysis until death, or more common, euthanasia. This discovery makes canine degenerative myelopathy the first and only naturally occurring non-human model of amyotrophic lateral sclerosis (ALS), closely paralleling the clinical, pathological, and genetic presentation of its human counterpart, SOD1-mediated familial ALS. To further understand the biochemical role that canine SOD1 plays in this disease and how it may be similar to human SOD1, we characterized the only two SOD1 mutations described in affected dogs to date, E40K and T18S. We show that a detergent-insoluble species of mutant SOD1 is present in spinal cords of affected dogs that increases with disease progression. Our in vitro results indicate that both canine SOD1 mutants form enzymatically active dimers, arguing against a loss of function in affected homozygous animals. Further studies show that these mutants, like most human SOD1 mutants, have an increased propensity to form aggregates in cell culture, with 10-20% of cells possessing visible aggregates. Creation of the E40K mutation in human SOD1 recapitulates the normal enzymatic activity but not the aggregation propensity seen with the canine mutant. Our findings lend strong biochemical support to the toxic role of SOD1 in canine degenerative myelopathy and establish close parallels for the role mutant SOD1 plays in both canine and human disorders. Copyright © 2013 Elsevier Inc. All rights reserved.

Batten's Disease: Determining Educational Interventions.

ERIC Educational Resources Information Center

Johnson, Barbara; Jochum, Julie

1996-01-01

This article presents basic information on the causes, physical and emotional characteristics, diagnosis and treatment, and educational implications of Batten's Disease, a degenerative neurological disorder which strikes children and adults, causes progressive loss of neurological function, and leads to eventual premature death. Discussion also…

A Morpholino Strategy to Assess TSC Gene Function in Zebrafish

DTIC Science & Technology

2006-11-01

ABSTRACT Tuberous sclerosis complex (TSC) is a genetic disorder associated with severe neurological symptoms including mental retardation, autism ...ABSTRACT Tuberous sclerosis complex (TSC) is a genetic disorder associated with severe neurological symptoms including mental retardation, autism ...devastating autosomal dominant disease that results in severe neurological symptoms including mental retardation, autism , and seizures (DiMario, 2004

Personality in Parkinson's disease: Clinical, behavioural and cognitive correlates.

PubMed

Santangelo, Gabriella; Piscopo, Fausta; Barone, Paolo; Vitale, Carmine

2017-03-15

Affective disorders and personality changes have long been considered pre-motor aspects of Parkinson's disease (PD). Many authors have used the term "premorbid personality" to define distinctive features of PD patients' personality characterized by reduced exploration of new environmental stimuli or potential reward sources ("novelty seeking") and avoidance behaviour ("harm avoidance") present before motor features. The functional correlates underlying the personality changes described in PD, implicate dysfunction of meso-cortico-limbic and striatal circuits. As disease progresses, the imbalance of neurotransmitter systems secondary to degenerative processes, along with dopamine replacement therapy, can produce a reversal of behaviours and an increase in reward seeking, laying the foundations for the emergence of the impulse control disorders. Personality disorders can be interpreted, therefore, as the result of individual susceptibility arising from intrinsic degenerative processes and individual personality features, in combination with extrinsic factors such as lifestyle, PD motor dysfunction and drug treatment. For a better understanding of personality disorders observed in PD and their relationship with the prodromal stage of the disease, prospective clinical studies are needed that correlate different personality profiles with other disease progression markers. Here, we review previous studies investigating the clinical, cognitive and behavioural correlates of personality traits in PD patients. Copyright © 2017 Elsevier B.V. All rights reserved.

Excitatory amino acid neurotoxicity and neurodegenerative disease.

PubMed

Meldrum, B; Garthwaite, J

1990-09-01

The progress over the last 30 years in defining the role of excitatory amino acids in normal physiological function and in the abnormal neuronal activity of epilepsy has been reviewed in earlier articles in this series. In the last five years it has become clear that excitatory amino acids also play a role in a wide range of neurodegenerative processes. The evidence is clearest where the degenerative process is acute, but is more controversial for slow degenerative processes. In this article Brian Meldrum and John Garthwaite review in vivo and in vitro studies of the cytotoxicity of amino acids and summarize the contribution of such toxicity to acute and chronic neurodegenerative disorders.

[Locomotive syndrome and frailty. Locomotive syndrome due to the underlying disease of degenerative arthritis].

PubMed

Chosa, Etsuo

2012-04-01

Japan became a superaging society. We have been putting a new focus on locomotive syndrome and frailty. The prevention and treatment of locomotive syndromes, such as osteoarthritis, degenerative spondylosis, lumbar canal stenosis, osteoporosis, upper extremity diseases, rheumatoid arthritis, and many other disorders of the locomotive organs are important. Because, the locomotive syndrome results in deterioration of the exercise function and loss of mental and physical health. The aim of locomotive syndrome exercises are: to reduce pain, to restore and improve joint function. We need to take a comprehensive approach to locomotive syndrome, including lifestyle modification, muscle exercise, stretching and therapeutic exercise.

CNS changes in Usher's syndrome with mental disorder: CT, MRI and PET findings.

PubMed Central

Koizumi, J; Ofuku, K; Sakuma, K; Shiraishi, H; Iio, M; Nawano, S

1988-01-01

CNS changes in a case of Usher's syndrome associated with schizophrenia-like mental disorder were observed by CT, MRI and PET. The neuro-radiological findings of the case demonstrate the degenerative and metabolic alterations in various regions of cortex, white matter and subcortical areas in the brain. Mental disorder of the case is almost indistinguishable from that of schizophrenia, but the psychotic feature is regarded as an atypical or mixed organic brain syndrome according to the classification in the third edition of the American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders (DSM-III). Images PMID:3264568

Does hybrid fixation prevent junctional disease after posterior fusion for degenerative lumbar disorders? A minimum 5-year follow-up study.

PubMed

Baioni, Andrea; Di Silvestre, Mario; Greggi, Tiziana; Vommaro, Francesco; Lolli, Francesco; Scarale, Antonio

2015-11-01

Medium- to long-term retrospective evaluation of clinical and radiographic outcome in the treatment of degenerative lumbar diseases with hybrid posterior fixation. Thirty patients were included with the mean age of 47.8 years (range 35 to 60 years). All patients underwent posterior lumbar instrumentation using hybrid fixation for lumbar stenosis with instability (13 cases), degenerative spondylolisthesis Meyerding grade I (6 cases), degenerative disc disease of one or more adjacent levels in six cases and mild lumbar degenerative scoliosis in five patients. Clinical outcomes were evaluated using Oswestry disability index (ODI), Roland and Morris disability questionnaire (RMDQ), and the visual analog scale (VAS) pain scores. All patients were assessed by preoperative, postoperative and follow-up standing plain radiographs and lateral X-rays with flexion and extension. Adjacent disc degeneration was also evaluated by magnetic resonance imaging (MRI) at follow-up. At a mean follow-up of 6.1 years, we observed on X-rays and/or MRI 3 cases of adjacent segment disease (10.0 %): two of them (6.6 %) presented symptoms and recurred a new surgery. The last patient (3.3 %) developed asymptomatic retrolisthesis of L3 not requiring revision surgery. The mean preoperative ODI score was 67.6, RMDQ score was 15.1, VAS back pain score was 9.5, and VAS leg pain score was 8.6. Postoperatively, these values improved to 28.1, 5.4, 3.1, and 2.9, respectively, and remained substantially unchanged at the final follow-up: (27.7, 5.2, 2.9, and 2.7, respectively). After 5-year follow-up, hybrid posterior lumbar fixation presented satisfying clinical outcomes in the treatment of degenerative disease.

Drug delivery, cell-based therapies, and tissue engineering approaches for spinal cord injury.

PubMed

Kabu, Shushi; Gao, Yue; Kwon, Brian K; Labhasetwar, Vinod

2015-12-10

Spinal cord injury (SCI) results in devastating neurological and pathological consequences, causing major dysfunction to the motor, sensory, and autonomic systems. The primary traumatic injury to the spinal cord triggers a cascade of acute and chronic degenerative events, leading to further secondary injury. Many therapeutic strategies have been developed to potentially intervene in these progressive neurodegenerative events and minimize secondary damage to the spinal cord. Additionally, significant efforts have been directed toward regenerative therapies that may facilitate neuronal repair and establish connectivity across the injury site. Despite the promise that these approaches have shown in preclinical animal models of SCI, challenges with respect to successful clinical translation still remain. The factors that could have contributed to failure include important biologic and physiologic differences between the preclinical models and the human condition, study designs that do not mirror clinical reality, discrepancies in dosing and the timing of therapeutic interventions, and dose-limiting toxicity. With a better understanding of the pathobiology of events following acute SCI, developing integrated approaches aimed at preventing secondary damage and also facilitating neuroregenerative recovery is possible and hopefully will lead to effective treatments for this devastating injury. The focus of this review is to highlight the progress that has been made in drug therapies and delivery systems, and also cell-based and tissue engineering approaches for SCI. Copyright © 2015 Elsevier B.V. All rights reserved.

Advances in the Studies of Ginkgo Biloba Leaves Extract on Aging-Related Diseases

PubMed Central

Zuo, Wei; Yan, Feng; Zhang, Bo; Li, Jiantao; Mei, Dan

2017-01-01

The prevalence of degenerative disorders in public health has promoted in-depth investigations of the underlying pathogenesis and the development of new treatment drugs. Ginkgo biloba leaves extract (EGb) is obtained from Ginkgo biloba leaves and has been used for thousands of years. In recent decades, both basic and clinical studies have established the effects of EGb. It is widely used in various degenerative diseases such as cerebrovascular disease, Alzheimer’s disease, macroangiopathy and more. Here, we reviewed several pharmacological mechanisms of EGb, including its antioxidant properties, prevention of mitochondrial dysfunctions, and effect on apoptosis. We also described some clinical applications of EGb, such as its effect on neuro and cardiovascular protection, and anticancer properties. The above biological functions of EGb are mainly focused on aging-related disorders, but its effect on other diseases remains unclear. Thus, through this review, we aim to encourage further studies on EGb and discover more potential applications PMID:29344418

Minimally Invasive Unilateral vs. Bilateral Pedicle Screw Fixation and Lumbar Interbody Fusion in Treatment of Multi-Segment Lumbar Degenerative Disorders.

PubMed

Liu, Xiaoyang; Li, Guangrun; Wang, Jiefeng; Zhang, Heqing

2015-11-25

BACKGROUND The choice for instrumentation with minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) in treatment of degenerative lumbar disorders (DLD) remains controversial. The goal of this study was to investigate clinical outcomes in consecutive patients with multi-segment DLD treated with unilateral pedicle screw (UPS) vs. bilateral pedicle screw (BPS) instrumented TLIF. MATERIAL AND METHODS Eighty-four consecutive patients who had multi-level MIS-TLIF were retrospectively reviewed. All data were collected to compare the clinical outcomes between the 2 groups. RESULTS Both groups showed similar clinical function scores in VAS and ODI. The two groups differed significantly in operative time (P<0.001), blood loss (P<0.001), and fusion rate (P=0.043), respectively. CONCLUSIONS This study demonstrated similar clinical outcomes between UPS fixation and BPS procedure after MIS-TLIF for multi-level DLD. Moreover, UPS technique was superior in operative time and blood loss, but represented lower fusion rate than the BPS construct did.

Risk factors for respiratory failure of motor neuron disease in a multiracial Asian population.

PubMed

Deng, Xiao; Hao, Ying; Xiao, Bin; Tan, Eng-King; Lo, Yew-Long

2017-05-01

Motor neuron disease (MND) is a devastating degenerative disorder. Amyotrophic Lateral Sclerosis (ALS) is the most common and severe form of MND. Respiratory failure arising from ventilator musculature atrophy is the most common cause of death for ALS patients. Exploring the factors correlated with respiratory failure can contribute to disease management. To characterize the clinical features of MND and determine the factors that may affect respiratory failure of MND patients. The case records of all MND patients seen in Singapore General Hospital (SGH) between January 2004 and December 2014 were examined. Demographic, clinical information were collected by reviewing case records. Mortality data, if not available from records, were obtained via phone call interview of family members. Demographic data and clinical treatments were compared between Respiratory support group and Non-respiratory support group. There were 73 patients included in our study. 49 (67.1%) patients died during follow-up. The mean age of onset was 58±11.1years. With regard to treatment, 63% needed feeding support, and 42.5% required ventilation aid. The median overall survival was 36months from symptom onset. Chi-square tests showed there was significantly higher percentage of respiratory support needed in Chinese than in other races (P=0.016). Compared with non-feeding support patients, patients with feeding support were more likely to require assisted ventilation (P=0.001). We report for the first time that the need of feeding support is significantly associated with assisted ventilation. Chinese MND patients may be more inclined to require respiratory support. Copyright © 2017 Elsevier Ltd. All rights reserved.

Drosophila models of amyotrophic lateral sclerosis with defects in RNA metabolism.

PubMed

Zhang, Ke; Coyne, Alyssa N; Lloyd, Thomas E

2018-05-09

The fruit fly Drosophila Melanogaster has been widely used to study neurodegenerative diseases. The conservation of nervous system biology coupled with the rapid life cycle and powerful genetic tools in the fly have enabled the identification of novel therapeutic targets that have been validated in vertebrate model systems and human patients. A recent example is in the study of the devastating motor neuron degenerative disease amyotrophic lateral sclerosis (ALS). Mutations in genes that regulate RNA metabolism are a major cause of inherited ALS, and functional analysis of these genes in the fly nervous system has shed light on how mutations cause disease. Importantly, unbiased genetic screens have identified key pathways that contribute to ALS pathogenesis such as nucleocytoplasmic transport and stress granule assembly. In this review, we will discuss the utilization of Drosophila models of ALS with defects in RNA metabolism. Copyright © 2018 Elsevier B.V. All rights reserved.

Bilateral self-enucleation in acute transient psychotic disorder: the influence of sociocultural factors on psychopathology.

PubMed

Harish, Thippeswamy; Chawan, Namdev; Rajkumar, Ravi Philip; Chaturvedi, Santosh Kumar

2012-07-01

Self-inflicted eye injuries are rare but a devastating consequence of a serious mental disorder. Bilateral self-enucleation also known as oedipism has been documented in ancient texts and myths. Various biologic, psychologic, and social theories have been put forward to explain this rare phenomenon. In this report, we describe a case of oedipism, which highlights the influence of sociocultural factors on the psychopathology in acute transient psychotic disorder. Copyright © 2012 Elsevier Inc. All rights reserved.

A scoping review of biopsychosocial risk factors and co-morbidities for common spinal disorders.

PubMed

Green, Bart N; Johnson, Claire D; Haldeman, Scott; Griffith, Erin; Clay, Michael B; Kane, Edward J; Castellote, Juan M; Rajasekaran, Shanmuganathan; Smuck, Matthew; Hurwitz, Eric L; Randhawa, Kristi; Yu, Hainan; Nordin, Margareta

2018-01-01

The purpose of this review was to identify risk factors, prognostic factors, and comorbidities associated with common spinal disorders. A scoping review of the literature of common spinal disorders was performed through September 2016. To identify search terms, we developed 3 terminology groups for case definitions: 1) spinal pain of unknown origin, 2) spinal syndromes, and 3) spinal pathology. We used a comprehensive strategy to search PubMed for meta-analyses and systematic reviews of case-control studies, cohort studies, and randomized controlled trials for risk and prognostic factors and cross-sectional studies describing associations and comorbidities. Of 3,453 candidate papers, 145 met study criteria and were included in this review. Risk factors were reported for group 1: non-specific low back pain (smoking, overweight/obesity, negative recovery expectations), non-specific neck pain (high job demands, monotonous work); group 2: degenerative spinal disease (workers' compensation claim, degenerative scoliosis), and group 3: spinal tuberculosis (age, imprisonment, previous history of tuberculosis), spinal cord injury (age, accidental injury), vertebral fracture from osteoporosis (type 1 diabetes, certain medications, smoking), and neural tube defects (folic acid deficit, anti-convulsant medications, chlorine, influenza, maternal obesity). A range of comorbidities was identified for spinal disorders. Many associated factors for common spinal disorders identified in this study are modifiable. The most common spinal disorders are co-morbid with general health conditions, but there is a lack of clarity in the literature differentiating which conditions are merely comorbid versus ones that are risk factors. Modifiable risk factors present opportunities for policy, research, and public health prevention efforts on both the individual patient and community levels. Further research into prevention interventions for spinal disorders is needed to address this gap in the literature.

A scoping review of biopsychosocial risk factors and co-morbidities for common spinal disorders

PubMed Central

Smuck, Matthew; Hurwitz, Eric L.; Randhawa, Kristi; Yu, Hainan; Nordin, Margareta

2018-01-01

Objective The purpose of this review was to identify risk factors, prognostic factors, and comorbidities associated with common spinal disorders. Methods A scoping review of the literature of common spinal disorders was performed through September 2016. To identify search terms, we developed 3 terminology groups for case definitions: 1) spinal pain of unknown origin, 2) spinal syndromes, and 3) spinal pathology. We used a comprehensive strategy to search PubMed for meta-analyses and systematic reviews of case-control studies, cohort studies, and randomized controlled trials for risk and prognostic factors and cross-sectional studies describing associations and comorbidities. Results Of 3,453 candidate papers, 145 met study criteria and were included in this review. Risk factors were reported for group 1: non-specific low back pain (smoking, overweight/obesity, negative recovery expectations), non-specific neck pain (high job demands, monotonous work); group 2: degenerative spinal disease (workers’ compensation claim, degenerative scoliosis), and group 3: spinal tuberculosis (age, imprisonment, previous history of tuberculosis), spinal cord injury (age, accidental injury), vertebral fracture from osteoporosis (type 1 diabetes, certain medications, smoking), and neural tube defects (folic acid deficit, anti-convulsant medications, chlorine, influenza, maternal obesity). A range of comorbidities was identified for spinal disorders. Conclusion Many associated factors for common spinal disorders identified in this study are modifiable. The most common spinal disorders are co-morbid with general health conditions, but there is a lack of clarity in the literature differentiating which conditions are merely comorbid versus ones that are risk factors. Modifiable risk factors present opportunities for policy, research, and public health prevention efforts on both the individual patient and community levels. Further research into prevention interventions for spinal disorders is needed to address this gap in the literature. PMID:29856783

3 CFR 8406 - Proclamation 8406 of August 31, 2009. National Alcohol and Drug Addiction Recovery Month, 2009

Code of Federal Regulations, 2010 CFR

2010-01-01

... promote healthy living. Without effective treatment, abuse of alcohol, illicit drugs, or prescription medications can devastate the mind and body. With treatment, substance use disorders can be managed, giving...

Getting an Insight into the Complexity of Major Chronic Inflammatory and Degenerative Diseases: A Potential New Systemic Approach to Their Treatment.

PubMed

Biava, Pier M; Norbiato, Guido

2015-01-01

As the modern society is troubled by multi-factorial diseases, research has been conducted on complex realities including chronic inflammation, cancer, obesity, HIV infection, metabolic syndrome and its detrimental cardiovascular complications as well as depression and other brain disorders. Deterioration of crucial homeostatic mechanisms in such diseases invariably results in activation of inflammatory mediators, chronic inflammation, loss in immunological function, increased susceptibility to diseases, alteration of metabolism, decrease of energy production and neuro-cognitive decline. Regulation of genes expression by epigenetic code is the dominant mechanism for the transduction of environmental inputs, such as stress and inflammation to lasting physiological changes. Acute and chronic stress determines DNA methylation and histone modifications in brain regions which may contribute to neuro-degenerative disorders. Nuclear glucocorticoids receptor interacts with the epigenoma resulting in a cortisol resistance status associated with a deterioration of the metabolic and immune functions. Gonadal steroids receptors have a similar capacity to produce epigenomic reorganization of chromatine structure. Epigenomic-induced reduction in immune cells telomeres length has been observed in many degenerative diseases, including all types of cancer. The final result of these epigenetic alterations is a serious damage to the neuro-endocrine-immune-metabolic adaptive systems. In this study, we propose a treatment with stem cells differentiation stage factors taken from zebrafish embryos which are able to regulate the genes expression of normal and pathological stem cells in a different specific way.

Assessment of berry fruit's effects on mobility and cognition in aging

USDA-ARS?s Scientific Manuscript database

Changes in aging, in both animals and humans, include parallel decrements in mobility and cognition, even in the absence of degenerative disorders such as Parkinson’s or Alzheimer’s diseases. Diet has long been known to influence aging; however, specific whole foods are now being investigated for t...

Sensory neuropathy in two Border collie puppies.

PubMed

Vermeersch, K; Van Ham, L; Braund, K G; Bhatti, S; Tshamala, M; Chiers, K; Schrauwen, E

2005-06-01

A peripheral sensory neuropathy was diagnosed in two Border collie puppies. Neurological, electrophysiological and histopathological examinations suggested a purely sensory neuropathy with mainly distal involvement. Urinary incontinence was observed in one of the puppies and histological examination of the vagus nerve revealed degenerative changes. An inherited disorder was suspected.

Epilepsy; A Review of Basic and Clinical Research. NINDB Monograph Number 1.

ERIC Educational Resources Information Center

Robb, Preston

A discussion of the incidence of epilepsy is followed by a discussion of etiology including the following causes: genetic and birth factors, infectious diseases, toxic factors, trauma or physical agents, heredofamilial and degenerative disorders, circulatory disturbances, metabolic and nutritional disturbances, and neoplasms. Epileptic seizures…

PREPARE: Pre-surgery physiotherapy for patients with degenerative lumbar spine disorder: a randomized controlled trial protocol.

PubMed

Lindbäck, Yvonne; Tropp, Hans; Enthoven, Paul; Abbott, Allan; Öberg, Birgitta

2016-07-11

Current guidelines for the management of patients with specific low back pain pathology suggest non-surgical intervention as first-line treatment, but there is insufficient evidence to make recommendations of the content in the non-surgical intervention. Opinions regarding the dose of non-surgical intervention that should be trialled prior to decision making about surgery intervention vary. The aim of the present study is to investigate if physiotherapy administrated before surgery improves function, pain and health in patients with degenerative lumbar spine disorder scheduled for surgery. The patients are followed over two years. A secondary aim is to study what factors predict short and long term outcomes. This study is a single blinded, 2-arm, randomized controlled trial with follow-up after the completion of pre-surgery intervention as well as 3, 12 and 24 months post-surgery. The study will recruit men and women, 25 to 80 years of age, scheduled for surgery due to; disc herniation, spinal stenosis, spondylolisthesis or degenerative disc disease. A total of 202 patients will be randomly allocated to a pre-surgery physiotherapy intervention or a waiting list group for 9 weeks. The waiting-list group will receive standardized information about surgery, post-surgical rehabilitation and advice to stay active. The pre-surgery physiotherapy group will receive physiotherapy 2 times per week, consisting of a stratified classification treatment, based on assessment findings. One of the following treatments will be selected; a) Specific exercises and mobilization, b) Motor control exercises or c) Traction. The pre-surgery physiotherapy group will also be prescribed a tailor-made general supervised exercise program. The physiotherapist will use a behavioral approach aimed at reducing patient fear avoidance and increasing activity levels. They will also receive standardized information about surgery, post-surgical rehabilitation and advice to stay active. Primary outcome measure is Oswestry Disability Index. Secondary outcome measures are the visual analogue scale for back and leg pain, pain drawing, health related quality of life, Hospital anxiety and depression scale, Fear avoidance beliefs questionnaire, Self-efficacy scale and Work Ability Index. The study findings will help improve the treatment of patients with degenerative lumbar spine disorder scheduled for surgery. ClinicalTrials.gov reference: NCT02454400 (Trial registration date: August 31st 2015) and has been registered on ClinicalTrials.gov, identifier: NCT02454400 .

[Intra-articular injections of hyaluronic acid for anterior disc displacement of temporomandibular joint].

PubMed

Long, X

2017-03-09

Anterior disc displacement (ADD) of temporomandibular joint (TMJ) is regarded as one of the major findings in temporomandibular disorders (TMD). It is related to joint noise, pain, mandibular dysfunction, degenerative change and osteoarthritis. In the mean time, the pathological changes were found in synovial membrane and synovial fluid. Hyaluronic acid is a principal component of the synovial fluid which plays an important role in nutrition, lubrication, anti-inflammation and cartilage repair. The synthesis, molecule weight, and concentration of hyaluronic acid are decreased during TMD and cause TMJ degenerative changes. The clinical conditions, pathological changes, the mechanism of action for hyaluronic acid and the treatment of anterior disc displacement of TMJ are discussed in this article.

Lipid deregulation in UV irradiated skin cells: Role of 25-hydroxycholesterol in keratinocyte differentiation during photoaging.

PubMed

Olivier, Elodie; Dutot, Mélody; Regazzetti, Anne; Dargère, Delphine; Auzeil, Nicolas; Laprévote, Olivier; Rat, Patrice

2017-05-01

Skin photoaging due to UV irradiation is a degenerative process that appears more and more as a growing concern. Lipids, including oxysterols, are involved in degenerative processes; as skin cells contain various lipids, the aim of our study was to evaluate first, changes in keratinocyte lipid levels induced by UV exposure and second, cellular effects of oxysterols in cell morphology and several hallmarks of keratinocyte differentiation. Our mass spectrometry results demonstrated that UV irradiation induces changes in lipid profile of cultured keratinocytes; in particular, ceramides and oxysterols, specifically 25-hydroxycholesterol (25-OH), were increased. Using holography and confocal microscopy analyses, we highlighted cell thickening and cytoskeletal disruption after incubation of keratinocytes with 25-OH. These alterations were associated with keratinocyte differentiation patterns: autophagy stimulation and intracellular calcium increase as measured by cytofluorometry, and increased involucrin level detected by immunocytochemistry. To conclude, oxysterol deregulation could be considered as a common marker of degenerative disorders. During photoaging, 25-OH seems to play a key role inducing morphological changes and keratinocyte differentiation. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Zebrafish models for the functional genomics of neurogenetic disorders.

PubMed

Kabashi, Edor; Brustein, Edna; Champagne, Nathalie; Drapeau, Pierre

2011-03-01

In this review, we consider recent work using zebrafish to validate and study the functional consequences of mutations of human genes implicated in a broad range of degenerative and developmental disorders of the brain and spinal cord. Also we present technical considerations for those wishing to study their own genes of interest by taking advantage of this easily manipulated and clinically relevant model organism. Zebrafish permit mutational analyses of genetic function (gain or loss of function) and the rapid validation of human variants as pathological mutations. In particular, neural degeneration can be characterized at genetic, cellular, functional, and behavioral levels. Zebrafish have been used to knock down or express mutations in zebrafish homologs of human genes and to directly express human genes bearing mutations related to neurodegenerative disorders such as spinal muscular atrophy, ataxia, hereditary spastic paraplegia, amyotrophic lateral sclerosis (ALS), epilepsy, Huntington's disease, Parkinson's disease, fronto-temporal dementia, and Alzheimer's disease. More recently, we have been using zebrafish to validate mutations of synaptic genes discovered by large-scale genomic approaches in developmental disorders such as autism, schizophrenia, and non-syndromic mental retardation. Advances in zebrafish genetics such as multigenic analyses and chemical genetics now offer a unique potential for disease research. Thus, zebrafish hold much promise for advancing the functional genomics of human diseases, the understanding of the genetics and cell biology of degenerative and developmental disorders, and the discovery of therapeutics. This article is part of a Special Issue entitled Zebrafish Models of Neurological Diseases. Copyright © 2010 Elsevier B.V. All rights reserved.

Applying Skinner's Analysis of Verbal Behavior to Persons with Dementia

ERIC Educational Resources Information Center

Dixon, Mark; Baker, Jonathan C.; Sadowski, Katherine Ann

2011-01-01

Skinner's 1957 analysis of verbal behavior has demonstrated a fair amount of utility to teach language to children with autism and other various disorders. However, the learning of language can be forgotten, as is the case for many elderly suffering from dementia or other degenerative diseases. It appears possible that Skinner's operants may…

Effects of Focal Basal Ganglia Lesions on Timing and Force Control

ERIC Educational Resources Information Center

Aparicio, P.; Diedrichsen, J.; Ivry, R.B.

2005-01-01

Studies of basal ganglia dysfunction in humans have generally involved patients with degenerative disorders, notably Parkinson's disease. In many instances, the performance of these patients is compared to that of patients with focal lesions of other brain structures such as the cerebellum. In the present report, we studied the performance of…

Teaching Children with Niemann-Pick Disease

ERIC Educational Resources Information Center

Gartin, Barbara C.; Murdick, Nikki L.; Cooley, Jennifer; Barnett, Sara

2013-01-01

Niemann-Pick Disease (NPD) is a group of rare inherited disorders that are both systemic and degenerative. Knowledge of the disease, its characteristics, and its progression are essential for the teacher and related service personnel to provide an appropriate educational experience for the student. For the teacher who has a student with NPC in…

Wilms Tumor 1b defines a wound-specific sheath cell subpopulation associated with notochord repair

PubMed Central

Lopez-Baez, Juan Carlos; Zeng, Zhiqiang; Brunsdon, Hannah; Salzano, Angela; Brombin, Alessandro; Wyatt, Cameron; Rybski, Witold; Huitema, Leonie F A; Dale, Rodney M; Kawakami, Koichi; Englert, Christoph; Chandra, Tamir; Schulte-Merker, Stefan

2018-01-01

Regenerative therapy for degenerative spine disorders requires the identification of cells that can slow down and possibly reverse degenerative processes. Here, we identify an unanticipated wound-specific notochord sheath cell subpopulation that expresses Wilms Tumor (WT) 1b following injury in zebrafish. We show that localized damage leads to Wt1b expression in sheath cells, and that wt1b+cells migrate into the wound to form a stopper-like structure, likely to maintain structural integrity. Wt1b+sheath cells are distinct in expressing cartilage and vacuolar genes, and in repressing a Wt1b-p53 transcriptional programme. At the wound, wt1b+and entpd5+ cells constitute separate, tightly-associated subpopulations. Surprisingly, wt1b expression at the site of injury is maintained even into adult stages in developing vertebrae, which form in an untypical manner via a cartilage intermediate. Given that notochord cells are retained in adult intervertebral discs, the identification of novel subpopulations may have important implications for regenerative spine disorder treatments. PMID:29405914

[Correlation analysis on the disorders of patella-femoral joint and torsional deformity of tibia].

PubMed

Sun, Zhen-Jie; Yuan, Yi; Liu, Rui-Bo

2015-03-01

To reveal the possible mechanism involved in patella-femoral degenerative arthritis (PFDA) in- duced by torsion-deformity of tibia via analyzing the relationship between torsion-deformity of the tibia in patients with PFDA and the disorder of patella-femoral joint under the static and dynamic conditions. From October 2009 to October 2010, 50 patients (86 knees, 24 knees of male patients and 62 knees of female patients) with PFDA were classified as disease group and 16 people (23 knees, 7 knees of males and 16 knees of females) in the control group. The follow indexes were measured: the torsion-angle of tibia on CT scanning imagings, the patella-femoral congruence angle and lateral patella-femoral angle under static and dynamic conditions when the knee bent at 30 degrees of flexion. Based on the measurement results, the relationship between the torsion-deformity of tibias and the disorders of patella-femoral joints in patients with PFDA were analyzed. Finally,the patients were divided into three groups including large torsion-angle group, small torsion-angle group and normal group according to the size of torsion-angle, in order to analyze the relationship between torsion-deformity and disorders of patella-femoral joint, especially under the dynamic conditions. Compared with patients without PFDA, the ones with PFDA had bigger torsion-angle (30.30 ± 7.11)° of tibia, larger patella-femoral congruence angle (13.20 ± 3.94)° and smaller lateral patella-femoral angle (12.30 ± 3.04)°. The congruence angle and lateral patella-femoral angle under static and dynamic conditions had statistical differences respectively in both too-big torsion-angle group and too-small torsion-angle group. The congruence angle and lateral patella-femoral angle under static and dynamic conditions had no statistical differences in normal torsion-angle group. Torsion-deformity of tibia is the main reason for disorder of patella-femoral joint in the patients with PFDA. Torsion-deformity of tibia is always accompanied by instability of patella-femoral joint,especially under the dynamic condition, thus causing PFDA. It can not only provide arrangement information and degenerative condition of patella-femoral joint,but also provide guidance through the analysis on the relationship for better clinical prevention and early treatment of degenerative bone and joint disease.

Prevalence of temporomandibular disorders: samples taken from attendees of medical health-care centers in the Islamic Republic of Iran.

PubMed

Balke, Zibandeh; Rammelsberg, Peter; Leckel, Michael; Schmitter, Marc

2010-01-01

To determine the prevalence of facial pain and temporomandibular disorders (TMD) in people located in urban and rural areas in a newly industrialized country (Iran). Two-hundred twenty-three subjects between 18 and 65 years of age (mean: 32.07; SD: 10.83) were randomly selected from an urban area and a rural area. One-hundred nineteen subjects from Mashhad (major city) and 104 subjects from Zoshk (village) were voluntarily recruited from medical health-care centers. Subjects who consulted the health-care center for dental, ear, nose, or throat issues were excluded. The monitoring of public health attendance of all citizens at designated health-care centers is compulsory by local law. All subjects were examined in accordance with the Research Diagnostic Criteria for TMD (RDC/TMD). Facial pain was assessed by using a questionnaire; the prevalence of myofascial pain, disc displacement, and degenerative disorders was determined by clinical examination. Nonparametric tests were used to assess group differences (ie, between village and city). Subjects in urban areas suffered less from facial pain (20.2% versus 46.2%; P < .01 [Mann-Whitney U test]) than subjects in rural areas. The frequency of TMD, disc displacement, and degenerative disorders was greater in the rural area. The symptoms under investigation were significantly more widespread in rural than in urban areas. With regard to TMD per se, the place of residence appears to be unimportant. However, the rural population was significantly affected by facial pain.

Abnormal Repetitive Behaviours: Shared Phenomenology and Pathophysiology

ERIC Educational Resources Information Center

Muehlmann, A. M.; Lewis, M. H.

2012-01-01

Background: Self-injurious behaviour (SIB) is a devastating problem observed in individuals with various neurodevelopmental disorders, including specific genetic syndromes as well as idiopathic intellectual and developmental disability. Although an increased prevalence of SIB has been documented in specific genetic mutations, little is known about…

Neuropathology in movement disorders.

PubMed Central

Gibb, W R

1989-01-01

This review concentrates on the definition and classification of degenerative movement disorders in which Parkinsonian symptoms are often prominent. The pathological spectrum and clinical manifestations of Lewy body disease are described, and associations with Alzheimer's disease and motor neuron disease are explored. A classification of pallidonigral degenerations is based on clinical features, distribution of pathology, and morphological abnormalities; some of these patients have mild nigral degeneration and no Parkinsonian features. Many other juvenile and familial Parkinsonian cases are not included among the pallidonigral degenerations. Most of these latter syndromes have been organised into preliminary groups, in particular, autosomal dominant dystonia-Parkinson syndrome, juvenile Parkinsonian disorder and autosomal dominant Lewy body disease. Images PMID:2547027

Global warming and neurodegenerative disorders: speculations on their linkage.

PubMed

Habibi, Laleh; Perry, George; Mahmoudi, Morteza

2014-01-01

Climate change is having considerable impact on biological systems. Eras of ice ages and warming shaped the contemporary earth and origin of creatures including humans. Warming forces stress conditions on cells. Therefore, cells evolved elaborate defense mechanisms, such as creation of heat shock proteins, to combat heat stress. Global warming is becoming a crisis and this process would yield an undefined increasing rate of neurodegenerative disorders in future decades. Since heat stress is known to have a degenerative effects on neurons and, conversely, cold conditions have protective effect on these cells, we hypothesize that persistent heat stress forced by global warming might play a crucial role in increasing neurodegenerative disorders.

The "tract" of history in the treatment of lumbar degenerative disc disease.

PubMed

Chedid, Khalil J; Chedid, Mokbel K

2004-01-15

In this paper past, present, and future treatments of degenerative disc disease (DDD) of the lumbar spine are outlined in a straight forward manner. This is done to review previous knowledge of the disease, define current treatment procedures, and discuss future perspectives. An analysis of a subject of this magnitude dictates that one describes as accurate a history as possible: an anatomical/historical "tract" with emphasis on all possible deviations. Although spinal disorders have been recognized for a long time, the view of DDD as a particular disease entity is a more recent development. In this paper, the authors attempt to outline the history of DDD of the lumbar spine in an unbiased and scientific fashion. Physiological, diagnostic, and therapeutic implications will all be addressed in this study.

Nutritionally enhanced rice to combat malnutrition disorders of the poor.

PubMed

Potrykus, Ingo

2003-06-01

Major deficiency disorders, including vitamin A deficiency, are especially common in countries in which rice is the staple food. In response to the devastating effects of vitamin A deficiency, which may include blindness and, even death, "Golden Rice" has been developed to deliver this nutrient to those populations who need it most. The case of Golden Rice is used to demonstrate the challenges of radical GMO opposition, consumer acceptance, and regulation of biotechnology-derived foods.

Next-generation sequencing in schizophrenia and other neuropsychiatric disorders.

PubMed

Schreiber, Matthew; Dorschner, Michael; Tsuang, Debby

2013-10-01

Schizophrenia is a debilitating lifelong illness that lacks a cure and poses a worldwide public health burden. The disease is characterized by a heterogeneous clinical and genetic presentation that complicates research efforts to identify causative genetic variations. This review examines the potential of current findings in schizophrenia and in other related neuropsychiatric disorders for application in next-generation technologies, particularly whole-exome sequencing (WES) and whole-genome sequencing (WGS). These approaches may lead to the discovery of underlying genetic factors for schizophrenia and may thereby identify and target novel therapeutic targets for this devastating disorder. © 2013 Wiley Periodicals, Inc.

Nosology and Diagnosis of Rett Syndrome

ERIC Educational Resources Information Center

Matson, Johnny L.; Fodstad, Jill C.; Boisjoli, Jessica A.

2008-01-01

Rett Syndrome is one of the least commonly occurring autism spectrum disorders (ASD), but certainly one of the most devastating. A genetic profile has been identified, but checklists still have an important role for prescreening, especially before expensive genetic testing, and to provide precise strengths and weaknesses with respect to the core…

Teaching dementia care to physical therapy doctoral students: A multimodal experiential learning approach.

PubMed

Lorio, Anne K; Gore, Jane B; Warthen, Lindsey; Housley, Stephen N; Burgess, Elisabeth O

2017-01-01

As the population aged 65 and older grows, it becomes imperative for health care providers to expand their knowledge regarding geriatric conditions and concerns. Dementia is a devastating degenerative disease process that is affecting millions of individuals in the United States, with significant economic and emotional burden on family and caregivers. The need for further dementia education in physical therapy school is essential to improve attitudes and treatment that affect patient outcomes and quality of care. This physical therapy program implemented a 12-hour multimodal experiential learning module designed to educate their students on the challenges associated with dementia to increase knowledge and confidence when treating these patients. The results of this study showed statistically significant improvements in overall confidence and knowledge of treating patients with dementia. The study finds the addition of experiential learning to traditional didactic coursework improves students' reported confidence in working with patients with dementia and understanding the challenges associated with treating patients with dementia.

Hip replacement in femoral head osteonecrosis: current concepts

PubMed Central

Scaglione, Michelangelo; Fabbri, Luca; Celli, Fabio; Casella, Francesco; Guido, Giulio

2015-01-01

Summary Osteonecrosis of the femoral head is a destructive disease that usually affects young adults with high functional demands and can have devastating effects on hip joint. The treatment depends on extent and location of the necrosis lesion and on patient’s factors, that suggest disease progression, collapse probability and also implants survival. Non-idiopathic osteonecrosis patients had the worst outcome. There is not a gold standard treatment and frequently it is necessary a multidisciplinary approach. Preservation procedures of the femoral head are the first choice and can be attempted in younger patients without head collapse. Replacement procedure remains the main treatment after failure of preserving procedures and in the late-stage ONFH, involving collapse of the femoral head and degenerative changes to the acetabulum. Resurfacing procedure still has good results but the patient selection is a critical factor. Total hip arthroplasties had historically poor results in patients with osteonecrosis. More recently, reports have shown excellent results, but implant longevity and following revisions are still outstanding problems. PMID:27134633

Pathogenesis of autism: a patchwork of genetic causes

PubMed Central

Grigorenko, Elena L

2009-01-01

Autism spectrum disorders (ASDs) are relatively infrequent but are devastating developmental conditions characterized by marked deficiencies in social, communicative and other behavioral domains. It has been known for a substantial period of time that these disorders are genetic in nature. However, elucidating the specific mechanisms of these disorders has been difficult. A major reason for such difficulty is the recognized genetic heterogeneity of ASDs. Specifically, many genetic mechanisms related to structural variations in the genome have been reported as possible genetic causes of these disorders. This review briefly exemplifies these genetic mechanisms, presents a concise overview of the evidence for the genetic basis of ASDs and provides an appraisal of the specific structural genetic variants thought to contribute to the pathogenesis of these complex disorders. PMID:19953194

Obstetric nephrology: preeclampsia--the nephrologist's perspective.

PubMed

Umans, Jason G

2012-12-01

Preeclampsia, a common and potentially devastating multisystem disorder unique to human pregnancy, represents a novel form of secondary hypertension with complex renal and systemic effects. Recent translational and clinical research reveals key pathophysiologic contributions due to dysregulation of angiogenic factors and of angiotensin signaling. Despite these insights, there are still difficulties in the clinical definition of preeclampsia and in the diagnosis of women with this disorder. Although recent research suggests the potential for new preventive and treatment strategies, most have not yet been shown ready for clinical use.

Recognition and treatment of neuropsychiatric disturbances in Parkinson's disease.

PubMed

Akbar, Umer; Friedman, Joseph H

2015-01-01

The non-motor symptoms of Parkinson's disease (PD) have been attracting increasing attention due to their ubiquitous nature and their often devastating effects on the quality of life. Behavioral problems in PD include dementia, depression, apathy, fatigue, anxiety, psychosis, akathisia, personality change, sleep disorders and impulse control disorders. Some of these are intrinsic to the neuropathology while others occur as an interplay between pathology, psychology and pharmacology. While few data exist for guiding therapy, enough is known to guide therapy in a rational manner.

[Biochemical evaluation of metabolic disorders in the tissues of the locomotor system in patients with occupational diseases caused by physical stress].

PubMed

Shatskaia, N N; Tarasova, A A; Fedorova, V I; Shardakova, E F; Selezneva, A I; Fedosova, N F

1991-01-01

A group of patients with occupational disease and female sewing-machine operators were medically examined with a broad set of biochemical techniques aimed at the detection of metabolic disorders in the locomotor system tissues. Noninflammatory dystrophic changes were found. The muscular component was dominating in comparison with the osseous one in the genesis of the degenerative dystrophic processes, which manifested in the clinical course. Laboratory manifestations were revealed related to the lowered energy supply and oxygenation of the skeleton muscles in patients with neuromuscular and osteo-muscular++ syndromes. The metabolic disorders were diagnosed at the early stages of myalgia.

In the swim of things: recent insights to neurogenetic disorders from zebrafish.

PubMed

Kabashi, Edor; Champagne, Nathalie; Brustein, Edna; Drapeau, Pierre

2010-08-01

The advantage of zebrafish as a model to study human pathologies lies in the ease of manipulating gene expression in vivo. Here we focus on recent progress in our understanding of motor neuron diseases and neurodevelopmental disorders and discuss how novel technologies will permit further disease models to be developed. Together these advances set the stage for this simple functional model, with particular advantages for transgenesis, multigenic analyses and chemical biology, to become uniquely suited for advancing the functional genomics of neurological and possibly psychiatric diseases - from understanding the genetics and cell biology of degenerative and developmental disorders to the discovery of therapeutics. Copyright 2010 Elsevier Ltd. All rights reserved.

A probable case of gigantism/acromegaly in skeletal remains from the Jewish necropolis of "Ronda Sur" (Lucena, Córdoba, Spain; VIII-XII centuries CE).

PubMed

Viciano, Joan; De Luca, Stefano; López-Lázaro, Sandra; Botella, Daniel; Diéguez-Ramírez, Juan Pablo

2015-01-01

Pituitary gigantism is a rare endocrine disorder caused by hypersecretion of growth hormone during growing period. Individuals with this disorder have an enormous growth in height and associated degenerative changes. The continued hypersecretion of growth hormone during adulthood leads to acromegaly, a condition related to the disproportionate bone growth of the skull, hands and feet. The skeletal remains studied belong to a young adult male from the Jewish necropolis of "Ronda Sur" in Lucena (Córdoba, Spain, VIII-XII centuries CE). The individual shows a very large and thick neurocranium, pronounced supraorbital ridges, an extremely prominent occipital protuberance, and an extremely large and massive mandible. Additional pathologies include enlargement of the vertebral bodies with degenerative changes, thickened ribs, and a slight increased length of the diaphysis with an increased cortical bone thickness of lower limbs. Comparative metric analysis of the mandible with other individuals from the same population and a contemporary Mediterranean population shows a trend toward acromegalic morphology. This case is an important contribution in paleopathological literature because it is a rare condition that has not been widely documented in ancient skeletal remains.

Association of decision-making in spinal surgery with specialty and emotional involvement-the Indications in Spinal Surgery (INDIANA) survey.

PubMed

Sollmann, Nico; Morandell, Carmen; Albers, Lucia; Behr, Michael; Preuss, Alexander; Dinkel, Andreas; Meyer, Bernhard; Krieg, Sandro M

2018-03-01

Although recent trials provided level I evidence for the most common degenerative lumbar spinal disorders, treatment still varies widely. Thus, the Indications in Spinal Surgery (INDIANA) survey explores whether decision-making is influenced by specialty or personal emotional involvement of the treating specialist. Nationwide, neurosurgeons and orthopedic surgeons specialized in spine surgery were asked to answer an Internet-based questionnaire with typical clinical patient cases of lumbar disc herniation (DH), lumbar spinal stenosis (SS), and lumbar degenerative spondylolisthesis (SL). The surgeons were assigned to counsel a patient or a close relative, thus creating emotional involvement. This was achieved by randomly allocating the surgeons to a patient group (PG) and relative group (RG). We then compared neurosurgeons to orthopedic surgeons and the PG to the RG regarding treatment decision-making. One hundred twenty-two spine surgeons completed the questionnaire (response rate 78.7%). Regarding DH and SS, more conservative treatment among orthopedic surgeons was shown (DH: odds ratio [OR] 4.1, 95% confidence interval [CI] 1.7-9.7, p = 0.001; SS: OR 3.9, CI 1.8-8.2, p < 0.001). However, emotional involvement (PG vs. RG) did not affect these results for any of the three cases (DH: p = 0.213; SS: p = 0.097; SL: p = 0.924). The high response rate indicates how important the issues raised by this study actually are for dedicated spine surgeons. Moreover, there are considerable variations in decision-making for the most common degenerative lumbar spinal disorders, although there is high-quality data from large multicenter trials available. Emotional involvement, though, did not influence treatment recommendations.

Complement, a target for therapy in inflammatory and degenerative diseases.

PubMed

Morgan, B Paul; Harris, Claire L

2015-12-01

The complement system is a key innate immune defence against infection and an important driver of inflammation; however, these very properties can also cause harm. Inappropriate or uncontrolled activation of complement can cause local and/or systemic inflammation, tissue damage and disease. Complement provides numerous options for drug development as it is a proteolytic cascade that involves nine specific proteases, unique multimolecular activation and lytic complexes, an arsenal of natural inhibitors, and numerous receptors that bind to activation fragments. Drug design is facilitated by the increasingly detailed structural understanding of the molecules involved in the complement system. Only two anti-complement drugs are currently on the market, but many more are being developed for diseases that include infectious, inflammatory, degenerative, traumatic and neoplastic disorders. In this Review, we describe the history, current landscape and future directions for anti-complement therapies.

What the Stopwatch Doesn't Tell

ERIC Educational Resources Information Center

Strout, Erin

2007-01-01

Lurking behind the championships, trophies, and academic achievements of many top female athletes is a devastating battle with eating disorders--not a new problem, but one that has changed the way coaches talk to their teams about weight and nutrition. The illnesses, which are often difficult to detect, can throw an entire team into a tailspin.…

Autism Disorder (AD): An Updated Review for Paediatric Dentists.

PubMed

J, Udhya; M M, Varadharaja; J, Parthiban; Srinivasan, Ila

2014-02-01

Over the past two decades, there has been an explosion of interest in Autism Disorder (AD). Knowledge and awareness on the condition has grown exponentially at all levels among the general public, parents, health professionals, the research community and more recently, at parliamentary level. The world has begun to recognize the scope of this problem and act internationally and locally to improve the lives of the growing number of individuals and families affected by this devastating disorder. This article reviews the dental literature since 1969 and it summarizes characteristics of patients with AD, oral health status and dental management of patients with AD.

Autism Disorder (AD): An Updated Review for Paediatric Dentists

PubMed Central

J., Udhya; M.M, Varadharaja; J., Parthiban; Srinivasan, Ila

2014-01-01

Over the past two decades, there has been an explosion of interest in Autism Disorder (AD). Knowledge and awareness on the condition has grown exponentially at all levels among the general public, parents, health professionals, the research community and more recently, at parliamentary level. The world has begun to recognize the scope of this problem and act internationally and locally to improve the lives of the growing number of individuals and families affected by this devastating disorder. This article reviews the dental literature since 1969 and it summarizes characteristics of patients with AD, oral health status and dental management of patients with AD. PMID:24701555

MicroRNAs in neuronal function and dysfunction

PubMed Central

Im, Heh-In; Kenny, Paul J.

2012-01-01

MicroRNAs (miRNAs) are small noncoding RNA transcripts expressed throughout the brain that can regulate neuronal gene expression at the post-transcriptional level. Here, we provide an overview of the role for miRNAs in brain development and function, and review evidence suggesting that dysfunction in miRNA signaling contributes to neurodevelopment disorders such as Rett and fragile X syndromes, as well as complex behavioral disorders including schizophrenia, depression and drug addiction. A better understanding of how miRNAs influence the development of neuropsychiatric disorders may reveal fundamental insights into the causes of these devastating illnesses and offer novel targets for therapeutic development. PMID:22436491

Degenerative spinal disease in large felids.

PubMed

Kolmstetter, C; Munson, L; Ramsay, E C

2000-03-01

Degenerative spinal disorders, including intervertebral disc disease and spondylosis, seldom occur in domestic cats. In contrast, a retrospective study of 13 lions (Panthera leo), 16 tigers (Panthera tigris), 4 leopards (Panthera pardis), 1 snow leopard (Panthera uncia), and 3 jaguars (Panthera onca) from the Knoxville Zoo that died or were euthanatized from 1976 to 1996 indicated that degenerative spinal disease is an important problem in large nondomestic felids. The medical record, radiographic data, and the necropsy report of each animal were examined for evidence of intervertebral disc disease or spondylosis. Eight (three lions, four tigers, and one leopard) animals were diagnosed with degenerative spinal disease. Clinical signs included progressively decreased activity, moderate to severe rear limb muscle atrophy, chronic intermittent rear limb paresis, and ataxia. The age at onset of clinical signs was 10-19 yr (median = 18 yr). Radiographic evaluation of the spinal column was useful in assessing the severity of spinal lesions, and results were correlated with necropsy findings. Lesions were frequently multifocal, included intervertebral disc mineralization or herniation with collapsed intervertebral disc spaces, and were most common in the lumbar area but also involved cervical and thoracic vertebrae. Marked spondylosis was present in the cats with intervertebral disc disease, presumably subsequent to vertebral instability. Six of the animals' spinal cords were examined histologically, and five had acute or chronic damage to the spinal cord secondary to disc protrusion. Spinal disease should be suspected in geriatric large felids with decreased appetite or activity. Radiographic evaluation of the spinal column is the most useful method to assess the type and severity of spinal lesions.

Design and Analysis of Blast Induced Traumatic Brain Injury Mechanism Using a Surrogate Headform: Instrumentation and Outcomes

DTIC Science & Technology

2011-05-01

51 4.5.1: FABRY -PÉROT FIBER OPTIC GAUGES...aggressive social behavior, impaired thinking, language, learning, emotions, behavior, sensation, and neuro-degenerative diseases such as epilepsy...Alzheimer’s disease , Parkinson’s disease , and other brain disorders that become more prevalent with age [9, Figure 2.1: Causes of TBI- A diagram of

Pulsed magnetotherapy in Czechoslovakia--a review.

PubMed

Jerabek, J

1994-01-01

Pulsed magnetotherapy has been used in Czechoslovakia for more than one decade. It has been proved that this type of physical therapy is very efficient mainly in rheumatic diseases, in paediatrics (sinusitis, enuresis), and in balneological care of patients suffering from ischaemic disorders of lower extremities. Promising results have also been obtained in neurological diseases (multiple sclerosis, spastic conditions) and in ophthalmology, in degenerative diseases of the retina.

Semantic memory assessment in 15 patients with amyotrophic lateral sclerosis.

PubMed

Hervieu-Bègue, M; Rouaud, O; Graule Petot, A; Catteau, A; Giroud, M

2016-01-01

A total of 30 to 50% of amyotrophic lateral sclerosis patients suffer from cognitive disorders. The aim of the study is to characterize these disorders and to assess semantic memory in non-demented ALS patients. The secondary aim is to look for a link between disease type and neuropsychological characteristics. Patients were followed in an ALS center in Dijon. The following neuropsychological tests were used in this study: Folstein test, BREF test, verbal fluency, Isaac test, GRESEM test and TOP 30 test. Fifteen ALS patients were included. Nine of them (60%) were suffering from a semantic memory disorder. There was no correlation between ALS characteristics and the semantic memory disorder. This is the first study to reveal a semantic memory disorder in ALS. This result accentuates the hypothesis that ALS and semantic dementia are two phenotypes of the same degenerative process linked to TDP 43 proteinopathy. Copyright © 2016. Published by Elsevier Masson SAS.

Numeracy Skills in Patients With Degenerative Disorders and Focal Brain Lesions

PubMed Central

Cappelletti, Marinella; Butterworth, Brian; Kopelman, Michael

2012-01-01

Objective: To characterize the numerical profile of patients with acquired brain disorders. Method: We investigated numeracy skills in 76 participants—40 healthy controls and 36 patients with neurodegenerative disorders (Alzheimer dementia, frontotemporal dementia, semantic dementia, progressive aphasia) and with focal brain lesions affecting parietal, frontal, and temporal areas as in herpes simplex encephalitis (HSE). All patients were tested with the same comprehensive battery of paper-and-pencil and computerized tasks assessing numerical abilities and calculation. Degenerative and HSE patients also performed nonnumerical semantic tasks. Results: Our results, based on nonparametric group statistics as well as on the analysis of individual patients, and all highly significant, show that: (a) all patients, including those with parietal lesions—a key brain area for numeracy processing—had intact processing of number quantity; (b) patients with impaired semantic knowledge had much better preserved numerical knowledge; and (c) most patients showed impaired calculation skills, with the exception of most semantic dementia and HSE patients. Conclusion: Our results allow us, for the first time, to characterize the numeracy skills in patients with a variety of neurological conditions and to suggest that the pattern of numerical performance can vary considerably across different neurological populations. Moreover, the selective sparing of calculation skills in most semantic dementia and HSE suggest that numerical abilities are an independent component of the semantic system. Finally, our data suggest that, besides the parietal areas, other brain regions might be critical to the understanding and processing of numerical concepts. PMID:22122516

[The incidence of craniomandibular disorders in patients with cervical dysfunctions. A clinico-statistical assessment].

PubMed

Carossa, S; Catapano, S; Previgliano, V; Preti, G

1993-05-01

The aim of this research was to measure the incidence of craniomandibular disorders in a group of patients with functional-type cervical alterations. The group consisted of 50 patients undergoing treatment for disorders of the cervical sectors of the spine. Each patient was subjected to a medical examination to investigate the presence of CMD signs or symptoms. From the data statistical analysis a higher percentage of cases with muscular and joint pain, limited mouth opening, deviation and deflection, were found in comparison with the percentage found among the general population. This demonstrates an overloading of the entire masticatory apparatus. Joint noise was less frequent, probably due to its exclusion from our sample of patients with arthrosis-type degenerative pathology.

Serum creatine kinase isoenzymes and macroenzymes in dogs with different neurologic diseases.

PubMed

Paltrinieri, Saverio; Pintore, Laura; Balducci, Federica; Giordano, Alessia; Costabile, Annaluce; Bernardini, Marco

2017-03-01

Increased serum activity of CK isoenzymes and macroenzymes, and in particular of the brain isoenzyme (CK-BB) has been reported in dogs with central nervous system (CNS) disorders. However, no studies on the possible differences in serum activities of CK iso- or macroenzymes (Macro-CK1 and Macro-CK2) in different neurologic diseases are available. The aim of this study was to describe the electrophoretic distribution of CK iso- and macroenzymes in dogs with CNS disorders in order to assess whether this distribution depends on a specific neurologic disease. This study was done on sera from 45 dogs with neurologic diseases (degenerative, n = 7; idiopathic epilepsy [IE], n = 14; inflammatory, n = 16; space occupying lesions [SOL], n = 8) and from 10 clinically healthy dogs. The separation of serum CK isoenzymes and macroenzymes was performed using an automated electrophoretic method already validated in dogs. Compared with healthy dogs, dogs with CNS disorders had significantly higher total CK and CK-BB activities, and a significantly lower Macro-CK2 activity (P < .001). Comparison of pathologic subgroups and healthy dogs revealed significant differences (P < .01) in dogs with IE and inflammatory disorders for total CK activity, in all the subgroups for CK-BB (P < .01), and in dogs with IE and SOL for Macro-CK2 (P < .01). The results of this study suggest that CK-BB is released by neurons damaged by inflammatory or degenerative conditions or due to compressive effects of SOL. However, the neurologic diseases cannot be differentiated based on CK-BB or Macro-CK2 activities, unless further studies allow the definition of diagnostic thresholds. © 2017 American Society for Veterinary Clinical Pathology.

Cardiotrophin-like cytokine factor 1 (CLCF1) and neuropoietin (NP) signalling and their roles in development, adulthood, cancer and degenerative disorders.

PubMed

Sims, Natalie A

2015-10-01

Mutations in cardiotrophin-like cytokine factor (CLCF1) and the related cytokine to which it binds, cytokine receptor-like factor 1 (CRLF1), are associated with Crisponi/cold induced sweating syndromes, and lead to early neonatal death in mice due to a suckling defect. These cytokines are members of the IL-6 superfamily, and form a range of composite cytokines that signal through gp130 bound either to the ciliary neurotrophic factor receptor (CNTFR) or a complex that involves the IL-27 p28 subunit. This review describes current knowledge of the signalling complexes formed by these cytokines, and explores their described and suggested roles in the neural, haematopoietic, skeletal, renal, immune and respiratory systems during development and adulthood, and in degenerative diseases and cancer. Copyright © 2015 Elsevier Ltd. All rights reserved.

Identification of Neurodegenerative Factors Using Translatome-Regulatory Network Analysis

PubMed Central

Brichta, Lars; Shin, William; Jackson-Lewis, Vernice; Blesa, Javier; Yap, Ee-Lynn; Walker, Zachary; Zhang, Jack; Roussarie, Jean-Pierre; Alvarez, Mariano J.; Califano, Andrea; Przedborski, Serge; Greengard, Paul

2016-01-01

For degenerative disorders of the central nervous system, the major obstacle to therapeutic advancement has been the challenge of identifying the key molecular mechanisms underlying neuronal loss. We developed a combinatorial approach including translational profiling and brain regulatory network analysis to search for key determinants of neuronal survival or death. Following the generation of transgenic mice for cell type-specific profiling of midbrain dopaminergic neurons, we established and compared translatome libraries reflecting the molecular signature of these cells at baseline or under degenerative stress. Analysis of these libraries by interrogating a context-specific brain regulatory network led to the identification of a repertoire of intrinsic upstream regulators that drive the dopaminergic stress response. The altered activity of these regulators was not associated with changes in their expression levels. This strategy can be generalized for the elucidation of novel molecular determinants involved in the degeneration of other classes of neurons. PMID:26214373

Predictive Medicine: Recombinant DNA Technology and Adult-Onset Genetic Disorders

PubMed Central

Hayden, Michael

1988-01-01

Genetic factors are of great importance in common adult-onset disorders such as atherosclerosis, cancer, and neuro-degenerative diseases. Advances in DNA technology now allow identification of persons at high-risk of developing some of these diseases. This advance is leading to predictive medicine. In some genetic disorders, such as those leading to atherosclerosis and cancer, identification of high-risk individuals allows intervention which alters the natural history of the disorder. In other diseases, for which there is no treatment, such as Huntington's disease, the application of this technology provides information that relieves uncertainty and may affect quality of life, but does not alter the course of the illness. General implementation of predictive testing programs awaits the results of pilot projects, which will demonstrate the needs, appropriate levels of support, and guidelines for delivery of such testing. PMID:21253100

Late-onset obsessive compulsive disorder associated with possible gliomatosis cerebri.

PubMed

Kumar, Vineet; Chakrabarti, Subho; Modi, Manish; Sahoo, Manoj

2009-01-01

Onset of obsessive-compulsive disorder (OCD) after the age of 50 years is rare, and should alert the physician to possible "organic" causes of OCD. These include infections, degenerative disorders, brain injury and cerebrovascular lesions, principally involving the frontal lobes and basal ganglia. The current patient had obsessive images, anxiety, auditory hallucinations and seizures following (possible) gliomatosis cerebri, with onset around 69 years of age. The atypical presentation, lesions involving the cortical-basal ganglia-thalamic-cortical circuit and the association with neurological signs/symptoms, was characteristic. However, late-onset OCD has not been commonly reported with diffuse lesions, and the association with gliomatosis cerebri is not known. This patient's case illustrates the need for careful screening of older patients with recently acquired OCD, and for further systematic study of OCD in the broad range of neuropsychiatric disorders affecting the elderly.

Psychological consequences of sexual assault.

PubMed

Mason, Fiona; Lodrick, Zoe

2013-02-01

Sexual violence is an important issue worldwide and can have long-lasting and devastating consequences. In this chapter, we outline the psychological reactions to serious sexual assault and rape, including development of post-traumatic stress disorder. Myths and stereotypes surrounding this subject, and their potential effect on the emotional response and legal situation, are discussed. Copyright © 2012. Published by Elsevier Ltd.

Cultural Considerations in the Treatment of Mental Illness among Sexually Abused Children and Adolescents: The Case of Bali, Indonesia

ERIC Educational Resources Information Center

Lesmana, Cokorda Bagus J.; Suryani, Luh Ketut; Tiliopoulos, Niko

2015-01-01

Childhood and adolescence sexual abuse can have long-lasting and devastating effects on personal and interpersonal growth and development. Sexually abused children tend to exhibit higher rates of poor school performance, aggressive behavior, PTSD (posttraumatic stress disorder), or depressive symptomatology, as well as social and relational…

Adult onset urea cycle disorder in a patient with presumed hepatic encephalopathy.

PubMed

Atiq, Muslim; Holt, Andrew F; Safdar, Kamran; Weber, Frederick; Ravinuthala, Ravi; Jonas, Mark E; Neff, Guy W

2008-02-01

Deficiency of any of the 5 enzymes in the urea cycle results in the accumulation of ammonia, leading to encephalopathy; which if untreated, can be lethal and produce devastating neurologic sequelae in long-term survivors. We hereby present an interesting case that presented with hyperammonemia and encephalopathy; later found to have an urea cycle defect.

Activity-Dependent Changes in MAPK Activation in the Angelman Syndrome Mouse Model

ERIC Educational Resources Information Center

Filonova, Irina; Trotter, Justin H.; Banko, Jessica L.; Weeber, Edwin J.

2014-01-01

Angelman Syndrome (AS) is a devastating neurological disorder caused by disruption of the maternal "UBE3A" gene. Ube3a protein is identified as an E3 ubiquitin ligase that shows neuron-specific imprinting. Despite extensive research evaluating the localization and basal expression profiles of Ube3a in mouse models, the molecular…

Fulminant hemolysis in glucose-6-phosphate dehydrogenase deficiency.

PubMed

Moiz, Bushra; Ali, Sidra Asad

2018-01-01

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an X-linked disorder affecting some 400 million people worldwide. Though clinically silent, it may result in hemolysis on oxidative stress induced by drugs or infections. Viral hepatitis A with coexisting G6PD deficiency can be devastating associated with severe hemolysis, anemia, renal failure, and hepatic encephalopathy.

Genes implicated in the pathogenesis of spinocerebellar ataxias.

PubMed

Wüllner, Ullrich

2003-12-01

The degenerative ataxias comprise a number of heterogeneous diseases, many of which are genetically determined. Loss of cerebellar Purkinje and brainstem neurons as well as degeneration of spinal pathways are the major morphological findings of most ataxias, but neuronal loss may also affect the basal ganglia and the retina. While the degenerative ataxias initially were classified on a neuropathological basis, more recent classifications focused on clinical hallmarks and the mode of inheritance, separating inherited, sporadic and symptomatic ataxias. Genetic linkage analysis and molecular genetic studies identified various genotypes and revealed genetic heterogeneity of the autosomal dominant ataxias (ADCA), which on the basis of the genotypes are now classified as spinocerebellar ataxias (SCA1-22). Based on pathogenesis these disorders fall into three discrete groups: the polyglutamine disorders, SCA1-3, 7 and 17; the channelopathies, SCA6 and episodic ataxia types 1 and 2 (EA1-2); and SCA8, 10 and 12, which result from repeat expansions outside the coding regions and reduce gene expression. The etiologies of SCAs 4, 5, 9, 11, 13-16, 19, 21 and 22 remain unknown as of today. The recent advances in the identification of the underlying gene defects of most of the inherited ataxias have opened new avenues to a better understanding of the molecular mechanisms leading to cellular dysfunction and cell death.

The ubiquitin-proteasome system in spongiform degenerative disorders

PubMed Central

Whatley, Brandi R.; Li, Lian; Chin, Lih-Shen

2008-01-01

Summary Spongiform degeneration is characterized by vacuolation in nervous tissue accompanied by neuronal death and gliosis. Although spongiform degeneration is a hallmark of prion diseases, this pathology is also present in the brains of patients suffering from Alzheimer's disease, diffuse Lewy body disease, human immunodeficiency virus (HIV) infection, and Canavan's spongiform leukodystrophy. The shared outcome of spongiform degeneration in these diverse diseases suggests that common cellular mechanisms must underlie the processes of spongiform change and neurodegeneration in the central nervous system. Immunohistochemical analysis of brain tissues reveals increased ubiquitin immunoreactivity in and around areas of spongiform change, suggesting the involvement of ubiquitin-proteasome system dysfunction in the pathogenesis of spongiform neurodegeneration. The link between aberrant ubiquitination and spongiform neurodegeneration has been strengthened by the discovery that a null mutation in the E3 ubiquitin-protein ligase mahogunin ring finger-1 (Mgrn1) causes an autosomal recessively inherited form of spongiform neurodegeneration in animals. Recent studies have begun to suggest that abnormal ubiquitination may alter intracellular signaling and cell functions via proteasome-dependent and proteasome-independent mechanisms, leading to spongiform degeneration and neuronal cell death. Further elucidation of the pathogenic pathways involved in spongiform neurodegeneration should facilitate the development of novel rational therapies for treating prion diseases, HIV infection, and other spongiform degenerative disorders. PMID:18790052

[News on hyponatremia].

PubMed

Fenske, Wiebke; Christ-Crain, Mirjam

2016-04-01

Hyponatremia is the most common electrolyte disorder in clinical practice with often severe and devastating complications. Hyponatremia itself as well as its inappropriate management is associated with pronounced morbidity and increased mortality risk. This manuscript presents some relevant novel findings in this field and discusses them in the context of the recently elaborated first European Guideline of hyponatremia. © Georg Thieme Verlag KG Stuttgart · New York.

Unraveling the Mysteries of Progeria | Center for Cancer Research

Cancer.gov

Hutchinson-Gilford progeria syndrome is a rare and devastating genetic disorder in which patients appear normal at birth, but by 12 to 18 months display signs of premature aging such as hair loss, slowed growth, weakening of bone and joint integrity, and cardiovascular disease. Because no treatments currently exist, most patients with progeria die in their mid-teens from heart

OrthoIllustrated Web Based Orthopaedic Sports Medicine Registry

ClinicalTrials.gov

2018-04-06

Degenerative and Traumatic Pathology of the Knee; Degenerative and Traumatic Pathology of the Shoulder and Elbow; Degenerative and Traumatic Pathology of the Foot and Ankle; Degenerative and Traumatic Pathology of the Hand and Wrist; Degenerative and Traumatic Pathology of the Hip

Aphasia and the Diagram Makers Revisited: an Update of Information Processing Models

PubMed Central

2006-01-01

Aphasic syndromes from diseases such as stroke and degenerative disorders are still common and disabling neurobehavioral disorders. Diagnosis, management and treatment of these communication disorders are often dependent upon understanding the neuropsychological mechanisms that underlie these disorders. Since the work of Broca it has been recognized that the human brain is organized in a modular fashion. Wernicke realized that the types of signs and symptoms displayed by aphasic patients reflect the degradation or disconnection of the modules that comprise this speech-language network. Thus, he was the first to propose a diagrammatic or information processing model of this modular language-speech network. Since he first published this model many new aphasic syndromes have been discovered and this has led to modifications of this model. This paper reviews some of the early (nineteenth century) models and then attempts to develop a more up-to-date and complete model. PMID:20396501

Teleost fish as a model system to study successful regeneration of the central nervous system.

PubMed

Zupanc, Günther K H; Sîrbulescu, Ruxandra F

2013-01-01

Traumatic brain injury and spinal cord injury are devastating conditions that may result in death or long-term disability. A promising strategy for the development of effective cell replacement therapies involves the study of regeneration-competent organisms. Among this group, teleost fish are distinguished by their excellent potential to regenerate nervous tissue and to regain function after injury to the central nervous system. In this chapter, we summarize our current understanding of the cellular processes that mediate this regenerative potential, and we show that several of these processes are shared with the normal development of the intact central nervous system; we describe how the spontaneous self-repair of the teleostean central nervous system leads to functional recovery, at physiological and behavioral levels; we discuss the possible function of molecular factors associated with the degenerative and regenerative processes after injury; and, finally, we speculate on evolutionary aspects of adult neurogenesis and neuronal regeneration, and on how a better understanding of these aspects could catalyze the development of therapeutic strategies to overcome the regenerative limits of the mammalian CNS.

Role of indigenous herbs in the management of Alzheimer's disease

PubMed Central

Nishteswar, K.; Joshi, Hemang; Karra, Rahul Dutt

2014-01-01

Ageing is a natural phenomenon and decline of physiological and structural changes are incurable in advancing years of human life. When such degenerative changes occur in the brain they may lead to dementia and other memory related conditions. The Ayurvedic classics identified the importance of higher faculties dealing with memory and introduced a separate group of drugs namely Medhya Rasayanas. Regular intake of such drugs will help to prevent the onset of degenerative changes in the brain prematurely. Ayurveda can play a useful role in the management of such geriatric conditions. The current review has been done with a view to update documented Ayurvedic therapeutic modalities for certain geriatric conditions suggested by Ayurvedic classics in the management of diseases called Vātavyādhi (nervous system disorders), which also include conditions related to memory functions. Recent studies have started validating the claims recorded in Ayurvedic texts. The pathogenesis and remedies for Vātavyādhi documented in Ayurvedic classics have been reviewed with special emphasis on disorders related to dementia. A review of recent researches on the herbs mentioned in management of vāta disorders including dementia have been done to understand their role in management of Alzheimer's disease (AD). There are many herbs of ethno-medicinal source studied experimentally for their potential in treatment of AD. A judicious combination of modern research methodology and Ayurvedic principles could go a long way in the management and care of AD which is going to be a heavy burden on the society in the future. PMID:25737604

Evidence and practice in spine registries

PubMed Central

van Hooff, Miranda L; Jacobs, Wilco C H; Willems, Paul C; Wouters, Michel W J M; de Kleuver, Marinus; Peul, Wilco C; Ostelo, Raymond W J G; Fritzell, Peter

2015-01-01

Background and purpose We performed a systematic review and a survey in order to (1) evaluate the evidence for the impact of spine registries on the quality of spine care, and with that, on patient-related outcomes, and (2) evaluate the methodology used to organize, analyze, and report the “quality of spine care” from spine registries. Methods To study the impact, the literature on all spinal disorders was searched. To study methodology, the search was restricted to degenerative spinal disorders. The risk of bias in the studies included was assessed with the Newcastle-Ottawa scale. Additionally, a survey among registry representatives was performed to acquire information about the methodology and practice of existing registries. Results 4,273 unique references up to May 2014 were identified, and 1,210 were eligible for screening and assessment. No studies on impact were identified, but 34 studies were identified to study the methodology. Half of these studies (17 of the 34) were judged to have a high risk of bias. The survey identified 25 spine registries, representing 14 countries. The organization of these registries, methods used, analytical approaches, and dissemination of results are presented. Interpretation We found a lack of evidence that registries have had an impact on the quality of spine care, regardless of whether intervention was non-surgical and/or surgical. To improve the quality of evidence published with registry data, we present several recommendations. Application of these recommendations could lead to registries showing trends, monitoring the quality of spine care given, and ultimately improving the value of the care given to patients with degenerative spinal disorders. PMID:25909475

Problems of the glenohumeral joint in overhead sports - literature review. Part II - pathology and pathophysiology.

PubMed

Lubiatowski, Przemysław; Kaczmarek, Piotr K; Ślęzak, Marta; Długosz, Jan; Bręborowicz, Maciej; Dudziński, Witold; Romanowski, Leszek

2014-05-23

In throwing sports shoulder is exposed to enormous and often repetitive overloads. Some sports (contact sports) are also connected with direct trauma. We are thus dealing with traumatic injuries, overload and degenerative damage. The article discusses the most frequent injuries of the shoulder characteristic for throwing sports. These are mainly disorders of arm rotation, internal impingement, lesion of the labrum (SLAP) and rotator cuff tears (PASTA).

Physiological Response in Ovis Aries Resulting from Electrical Stimuli Delivered by an Implantable Vision Prosthesis

DTIC Science & Technology

2001-10-25

inner retina. The device is intended as a treatment to blindness. Specifically, degenerative disorders of the retina such as retinitis pigmentosa ...Trullemans C., Chronic electrical stimulation of the optic nerve in a retinitis pigmentosa blind volunteer. Inv. Ophth. Vis. Sci., 1999, 40: S783...stimulation delivered to the retinal tissue is derived from two stimulation channels of the 100 channel neurostimulation electronics [9]. Power and

Implant rehabilitation for a patient with Hallerman-Streiff syndrome: a case report.

PubMed

Abadi, Behruz J; Van Sickels, Joseph E; McConnell, Thomas A; Kluemper, G Thomas

2009-01-01

Hallermann-Streiff syndrome is a rare genetic disorder characterized by craniofacial malformations, sparse hair, eye abnormalities, dental defects, degenerative skin changes, and short stature. The syndrome has many implications for dental treatment. Patients typically present with multiple missing and poorly formed teeth. The purpose of this case report is to discuss the overall management of a patient with Hallermann-Streiff syndrome by oral maxillofacial surgery, orthodontic treatment, and prosthodontic reconstruction.

[Neuroprogression and cognition in Bipolar Disorders: A systematic review of cognitive performance in euthymic patients].

PubMed

Lolich, María; Holtzman, Jessica N; Rago, Carlo M; Vázquez, Gustavo H

2015-01-01

In recent years, investigators have begun to consider the possibility of explaining the physiopathology of bipolar disorder from a neuroprogressive perspective. The evidence that supports the feasibility of such an approach is varied, and arises from neuroimaging studies, batteries of neurocognitive evaluations, and tests to identify the specific biomarkers of the disorder. The present article seeks to perform a review of the research that investigates the cognitive deficits in bipolar disorder. A bibliographic revision was performed of articles published between 1990 and 2015. Levels of cognitive performance were explored in both cross-sectional and longitudinal studies. The compiled studies signal the presence of altered cognitive function, even during periods of euthymia. However, there are contradictory results as to whether bipolar disorder presents a degenerative course. New lines of investigation suggest that only a percentage of individuals with bipolar disorder are affected in a progressive manner. It is of paramount importance to perform new longitudinal studies in high-risk populations, so as to validate or refute a neuroprogressive model of cognitive deficits in patients with bipolar disorder.

Stress-related regulation of the kynurenine pathway: Relevance to neuropsychiatric and degenerative disorders.

PubMed

O'Farrell, Katherine; Harkin, Andrew

2017-01-01

The kynurenine pathway (KP), which is activated in times of stress and infection has been implicated in the pathophysiology of neurodegenerative and psychiatric disorders. Activation of this tryptophan metabolising pathway results in the production of neuroactive metabolites which have the potential to interfere with normal neuronal functioning which may contribute to altered neuronal transmission and the emergence of symptoms of these brain disorders. This review investigates the involvement of the KP in a range of neurological disorders, examining recent in vitro, in vivo and clinical discoveries highlights evidence to indicate that the KP is a potential therapeutic target in both neurodegenerative and stress-related neuropsychiatric disorders. Furthermore, this review identifies gaps in our knowledge with regard to this field which are yet to be examined to lead to a more comprehensive understanding of the role of KP activation in brain health and disease. This article is part of the Special Issue entitled 'The Kynurenine Pathway in Health and Disease'. Copyright © 2015 Elsevier Ltd. All rights reserved.

Clinical and radiological outcome of conservative vs. surgical treatment of atraumatic degenerative rotator cuff rupture: design of a randomized controlled trial.

PubMed

Lambers Heerspink, Frederik O; Hoogeslag, Roy Ag; Diercks, Ron L; van Eerden, Pepijn Jm; van den Akker-Scheek, Inge; van Raay, Jos Jam

2011-01-26

Subacromial impingement syndrome is a frequently observed disorder in orthopedic practice. Lasting symptoms and impairment may occur when a subsequent atraumatic rotator cuff rupture is also present. However, degenerative ruptures of the rotator cuff can also be observed in asymptomatic elderly individuals. Treatment of these symptomatic degenerative ruptures may be conservative or surgical. Acceptable results are reported for both treatment modalities. No evidence-based level-1 studies have been conducted so far to compare these treatment modalities. The objective of this study is to determine whether there is a difference in outcome between surgical reconstruction and conservative treatment of a degenerative atraumatic rotator cuff tendon rupture. A randomized controlled trial will be conducted. Patients aged between 45 and 75 with a symptomatic atraumatic rotator cuff rupture as diagnosed by MRI will be included. Exclusion criteria are traumatic rotator cuff rupture, frozen shoulder and diabetes mellitus. Patients will be randomized into two groups. Conservative treatment includes physical therapy according to a standardized protocol, NSAIDs and, if indicated, subacromial infiltration with a local anesthetic and corticosteroids. Surgical reconstruction is performed under general anesthesia in combination with an interscalenus plexus block. An acromioplasty with reconstruction of the rotator cuff tendon is performed, as described by Rockwood et al. Measurements take place preoperatively and 6 weeks, 3 months, 6 months and 1 year postoperatively. The primary outcome measure is the Constant score. Secondary measures include both disease-specific and generic outcome measures, and an economic evaluation. Additionally, one year after inclusion a second MRI will be taken of all patients in order to determine whether extent and localization of the rupture as well as the amount of fatty degeneration are prognostic factors. Both surgical as conservative treatment of a symptomatic atraumatic rotator cuff tendon rupture is used in current practice. There is a lack of level-1 studies comparing surgical vs. conservative treatment. This randomized controlled trial has been designed to determine whether the surgical treatment of a degenerative atraumatic rotator cuff tendon rupture may lead to a better functional and radiological outcome than conservative treatment after one year of follow-up. Netherlands Trial Register (NTR): NTRTC2343.

Occupational Neurological Disorders in Korea

PubMed Central

Kang, Seong-Kyu

2010-01-01

The purpose of this article was to provide a literature review of occupational neurological disorders and related research in Korea, focusing on chemical hazards. We reviewed occupational neurological disorders investigated by the Occupational Safety and Health Research Institute of Korean Occupational Safety and Health Agency between 1992 and 2009, categorizing them as neurological disorders of the central nervous system (CNS), of the peripheral nervous system (PNS) or as neurodegenerative disorders. We also examined peer-reviewed journal articles related to neurotoxicology, published from 1984 to 2009. Outbreaks of occupational neurological disorder of the CNS due to inorganic mercury and carbon disulfide poisoning had helped prompt the development of the occupational safety and health system of Korea. Other major neurological disorders of the CNS included methyl bromide intoxication and chronic toxic encephalopathy. Most of the PNS disorders were n-hexane-induced peripheral neuritis, reported from the electronics industry. Reports of manganese-induced Parkinsonism resulted in the introduction of neuroimaging techniques to occupational medicine. Since the late 1990s, the direction of research has been moving toward degenerative disorder and early effect of neurotoxicity. To understand the early effects of neurotoxic chemicals in the preclinical stage, more follow-up studies of a longer duration are necessary. PMID:21258587

Cerebellar degeneration following neuroleptic malignant syndrome.

PubMed Central

Lal, V.; Sardana, V.; Thussu, A.; Sawhney, I. M.; Prabhakar, S.

1997-01-01

A 55-year-old woman with a history of bipolar affective disorder developed hyperpyrexia, rigidity and depressed consciousness (neuroleptic malignant syndrome) after commencing neuroleptic therapy. On regaining consciousness, she was mute and had signs suggesting pancerebellar involvement. Hyperpyrexia, which is a cardinal feature of neuroleptic malignant syndrome, may have caused cerebellar damage. Neuroleptic malignant syndrome needs both early recognition and prompt treatment to obviate devastating complications. PMID:9519191

Unraveling the Mysteries of Progeria | Center for Cancer Research

Cancer.gov

Hutchinson-Gilford progeria syndrome is a rare and devastating genetic disorder in which patients appear normal at birth, but by 12 to 18 months display signs of premature aging such as hair loss, slowed growth, weakening of bone and joint integrity, and cardiovascular disease. Because no treatments currently exist, most patients with progeria die in their mid-teens from heart disease or stroke.

Pleiotropic effects of statins: new therapeutic targets in drug design.

PubMed

Bedi, Onkar; Dhawan, Veena; Sharma, P L; Kumar, Puneet

2016-07-01

The HMG Co-enzyme inhibitors and new lipid-modifying agents expand their new therapeutic target options in the field of medical profession. Statins have been described as the most effective class of drugs to reduce serum cholesterol levels. Since the discovery of the first statin nearly 30 years ago, these drugs have become the main therapeutic approach to lower cholesterol levels. The present scientific research demonstrates numerous non-lipid modifiable effects of statins termed as pleiotropic effects of statins, which could be beneficial for the treatment of various devastating disorders. The most important positive effects of statins are anti-inflammatory, anti-proliferative, antioxidant, immunomodulatory, neuroprotective, anti-diabetes, and antithrombotic, improving endothelial dysfunction and attenuating vascular remodeling besides many others which are discussed under the scope of this review. In particular, inhibition of Rho and its downstream target, Rho-associated coiled-coil-containing protein kinase (ROCK), and their agonistic action on peroxisome proliferator-activated receptors (PPARs) can be viewed as the principle mechanisms underlying the pleiotropic effects of statins. With gradually increasing knowledge of new therapeutic targets of statins, their use has also been advocated in chronic inflammatory disorders for example rheumatoid arthritis (RA) and in systemic lupus erythematosus (SLE). In the scope of review, we highlight statins and their pleiotropic effects with reference to their harmful and beneficial effects as a novel approach for their use in the treatment of devastating disorders. Graphical abstract Pleiotropic effect of statins.

L-dihydroxyphenylserine (Droxidopa): a new therapy for neurogenic orthostatic hypotension: the US experience.

PubMed

Kaufmann, Horacio

2008-03-01

Neurogenic orthostatic hypotension results from failure to release norepinephrine, the neurotransmitter of sympathetic postganglionic neurons, appropriately upon standing. In double blind, cross over, placebo controlled trials, administration of droxidopa, a synthetic amino acid that is decarboxylated to norepinephrine by the enzyme L: -aromatic amino acid decarboxylase increases standing blood pressure, ameliorates symptoms of orthostatic hypotension and improves standing ability in patients with neurogenic orthostatic hypotension due to degenerative autonomic disorders. The pressor effect results from conversion of droxidopa to norepinephrine outside the central nervous system both in neural and non-neural tissue. This mechanism of action makes droxidopa effective in patients with central and peripheral autonomic disorders.

Orally ingestion of krokodil in Spain: report of a case.

PubMed

Baquero Escribano, Abel; Beltrán Negre, María Teresa; Calvo Orenga, Gema; Carratalá Monfort, Sonia; Arnau Peiró, Francisco; Meca Zapatero, Sara; Haro Cortés, Gonzalo

2016-06-14

The krokodil use disorder is an addictive pathology with quite severe organic effects, especially at the skin level, that causes severe and degenerative necrosis of blood and muscle tissue. Though this disorder has a low prevalence in Spain, compared to the large number of consumers in other countries such as Ukraine or Russia, its consumption is slowly but gradually expanding in countries of the European Union and America. The simplicity of the process of obtaining the substance from desomorphine, together with its high availability and low cost, contribute toward consumers' self-sufficiency. This article presents the case of a user of krokodil and reviews the clinical symptoms of oral ingestion.

Endoplasmic Reticulum Stress and Unfolded Protein Response Pathways: Potential for Treating Age-related Retinal Degeneration

PubMed Central

Haeri, Mohammad; Knox, Barry E

2012-01-01

Accumulation of misfolded proteins in the endoplasmic reticulum (ER) and their aggregation impair normal cellular function and can be toxic, leading to cell death. Prolonged expression of misfolded proteins triggers ER stress, which initiates a cascade of reactions called the unfolded protein response (UPR). Protein misfolding is the basis for a variety of disorders known as ER storage or conformational diseases. There are an increasing number of eye disorders associated with misfolded proteins and pathologic ER responses, including retinitis pigmentosa (RP). Herein we review the basic cellular and molecular biology of UPR with focus on pathways that could be potential targets for treating retinal degenerative diseases. PMID:22737387

Health benefits of the Mediterranean Diet: an update of research over the last 5 years.

PubMed

Gotsis, Efthymios; Anagnostis, Panagiotis; Mariolis, Anargyros; Vlachou, Athanasia; Katsiki, Niki; Karagiannis, Asterios

2015-04-01

The Mediterranean Diet (MedDiet) has been reported to be protective against the occurrence of several diseases. Increasing evidence suggests that the MedDiet could counter diseases associated with chronic inflammation, including metabolic syndrome, atherosclerosis, cancer, diabetes, obesity, pulmonary diseases, and cognition disorders. Adoption of a MedDiet was associated with beneficial effects on the secretion of anti-inflammatory cytokines, antioxidant cellular and circulating biomarkers as well as with regulation of gene polymorphisms involved in the atherosclerotic process. The MedDiet has been considered for the prevention of cardiovascular and other chronic degenerative diseases focusing on the impact of a holistic dietary approach rather than on single nutrients. Epidemiological dietary scores measuring adherence to a MedDiet have been developed. This narrative review considers the results of up-to-date clinical studies (with a focus on the last 5 years) that evaluated the effectiveness of the MedDiet in reducing the prevalence of chronic and degenerative diseases. © The Author(s) 2014.

Canonical Nlrp3 inflammasome links systemic low grade inflammation to functional decline in aging

PubMed Central

Youm, Yun-Hee; Grant, Ryan W.; McCabe, Laura R.; Albarado, Diana C.; Nguyen, Kim Yen; Ravussin, Anthony; Pistell, Paul; Newman, Susan; Carter, Renee; Laque, Amanda; Münzberg, Heike; Rosen, Clifford J.; Ingram, Donald K.; Salbaum, J. Michael; Dixit, Vishwa Deep

2014-01-01

SUMMARY Despite a wealth of clinical data showing an association between inflammation and degenerative disorders in elderly, the immune sensors that causally link systemic inflammation to aging remain unclear. Here we detail a mechanism that the Nlrp3 inflammasome controls systemic low grade age-related ‘sterile’ inflammation in both periphery and brain independently of the non-canonical caspase-11 inflammasome. Ablation of Nlrp3 inflammasome protected mice from age-related increases in the innate immune activation, alterations in CNS transcriptome and astrogliosis. Consistent with the hypothesis that systemic low grade inflammation promotes age-related degenerative changes, the deficient Nlrp3 inflammasome mediated caspase-1 activity improved glycemic control and attenuated bone loss and thymic demise. Notably, IL-1 mediated only Nlrp3 inflammasome dependent improvement in cognitive function and motor performance in aged mice. These studies reveal Nlrp3 inflammasome as an upstream target that controls age-related inflammation and offer innovative therapeutic strategy to lower Nlrp3 activity to delay multiple age-related chronic diseases. PMID:24093676

Low dopamine activity in Lesch Nyhan Disease. An 18-fluorodopa PET study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ernst, M.; Zametkin, A.; Matochik, J.

1996-05-01

Lesch-Nyhan Disease (LND) is a rare devastating X-linked recessive disorder characterized by the virtual absence of hypoxanthine guanine phosphoribosyl transferase (HPRT), a major enzyme of the salvage pathway of purine metabolism. The clinical presentation includes hyperuricemia choreoathetosis, dystonia, aggression and self-injurious behavior. The genetic and biochemical abnormalities are fully identified. However, the neuropathophysiological process by which the lack of HPRT produces the neuropsychiatric syndrome of LND in unclear. Presynaptic uptake of 18-Fluorodopa (FD) in basal ganglia, substantia nigra, and frontal and occipital cortices was measured by PET in 12 patients with LND, 10 to 20 years old, and 15 healthmore » controls, 12 to 23 years old. Radioactive counts (mCi/cc), recorded between 90 and 130 minutes after tracer injection, were measured in regions of interest by a rater blind to subjects` identities. Results were expressed as ratios of FD uptake in specific to non-specific (occipital cortex) brain areas. Presynaptic dopamine activity was significantly lower by 69% in putamen (p<0.0001), 61% in caudate (p<0.0001), 56% in frontal cortex (p=0.003) and 43% in substantiat nigra (p<0.016) in LND patients than in control subjects. Absolute FD measures in occipital regions did not differ between the two groups. Activity of FD in the basal ganglia was stable over time in the LND group and tended to increase in the control group (r=0.50, n=15, p=0.060). In the LND group, aggressive behavior was worse as FD activity was higher (r=0.60, n=12, p=0.40). LND is associated with a striking reduction of presynaptic dopamine activity that is not region-specific. The temporal stability of FD measures and of the severity of LND symptomatology is consistent with a developmental rather than degenerative process.« less

Genetic forms of pituitary dwarfism.

PubMed

Rimoin, D L

1971-05-01

Pituitary dwarfism represents a genetically heterogeneous group of disorders which may be classified on the basis of: associated developmental anomalies or degenerative disease; deficiency of, or peripheral insensitivity to HGH; the number of deficient hormones; the associated metabolic disturbances; and the mode of inheritance. Hereditary forms of pituitary dwarfism include: congenital absence of the pituitary, panhypopituitary dwarfism (autosomal and X-linked recessive forms), isolated HGH deficiency (Types I and II), Laron type of dwarfism, and peripheral unresponsiveness to HGH (the African Pygmies).

Cystic chondromalacia of the auricle treated with dual-plane excision with intracartilaginous dissection.

PubMed

Zoccali, Giovanni; Pajand, Reza; Vrentzos, Nikolaos; Giuliani, Maurizio

2014-09-01

Cystic chondromalacia of the auricle is an uncommon condition in which a degenerative process occurs within the cartilage. The disorder affects young and middle-aged people. Clinically, it manifests as a painless, fluctuant swelling that frequently relapses despite various therapeutic approaches. In this article we report a typical case of cystic chondromalacia of the auricle that was successfully treated by surgery-specifically, dual-plane dissection-and we briefly review the literature.

Pathogenic mechanisms and therapeutic strategies in spinobulbar muscular atrophy

PubMed Central

Chua, Jason P.; Lieberman, Andrew P.

2014-01-01

We review the genetic and clinical features of spinobulbar muscular atrophy (SBMA), a progressive neuromuscular disorder caused by a CAG/glutamine tract expansion in the androgen receptor. SBMA was the first polyglutamine disease to be discovered, and we compare and contrast it with related degenerative disorders of the nervous system caused by expanded glutamine tracts. We review the cellular and animals models that have been most widely used to study this disorder, and highlight insights into disease pathogenesis derived from this work. These model systems have revealed critical aspects of the disease, including its hormone dependence, a feature that underlies disease occurrence only in men with the mutant allele. We discuss how this and other findings have been translated to clinical trials for SBMA patients, and examine emerging therapeutic targets that have been identified by recent work. PMID:24040817

High-resolution nuclear magnetic resonance spectroscopic study of metabolites in the cerebrospinal fluid of patients with cervical myelopathy and lumbar radiculopathy

PubMed Central

Morio, Yasuo; Meshitsuka, Shunsuke; Yamane, Koji; Nanjo, Yoshiro; Teshima, Ryota

2010-01-01

There have been few reports describing substances related to oxidative and intermediary metabolism in the cerebrospinal fluid (CSF) in patients with spinal degenerative disorders. This study investigated whether the concentrations of metabolites in the CSF differed between patients with spinal degenerative disorders and controls, and whether the concentrations of these metabolites correlated with the severity of symptoms. CSF samples were obtained from 30 patients with cervical myelopathy (Group M), 30 patients with lumbar radiculopathy (Group R), and 10 volunteers (control). Metabolites in these CSF samples were measured by nuclear magnetic resonance spectroscopy. There were no differences in the concentrations of lactate, alanine, acetate, glutamate, pyruvate, or citrate between Groups M and R, between Group M and the control, or between Group R and the control. In Group M, neither symptom duration nor the Japanese Orthopaedic Association score correlated with the concentration of any metabolite. In Group R, the symptom duration positively correlated with the concentration of lactate, glutamate, and citrate in CSF. The duration of nerve root block showed a negative correlation with the concentrations of acetate in CSF of the patients in Group R. In patients with lumbar radiculopathy, there is a possibility of increased aerobic metabolic activity or decreased gluconeogenic activity in patients with shorter symptom duration, and increased aerobic metabolic activity in patients with severe inflammation around a nerve root. PMID:20490871

Neurocardiology: Therapeutic Implications for Cardiovascular Disease

PubMed Central

Goldstein, David S.

2016-01-01

SUMMARY The term “neurocardiology” refers to physiologic and pathophysiological interplays of the nervous and cardiovascular systems. This selective review provides an update about cardiovascular therapeutic implications of neurocardiology, with emphasis on disorders involving primary or secondary abnormalities of catecholamine systems. Concepts of scientific integrative medicine help understand these disorders. Scientific integrative medicine is not a treatment method or discipline but a way of thinking that applies systems concepts to acute and chronic disorders of regulation. Some of these concepts include stability by negative feedback regulation, multiple effectors, effector sharing, instability by positive feedback loops, allostasis, and allostatic load. Scientific integrative medicine builds on systems biology but is also distinct in several ways. A large variety of drugs and non-drug treatments are now available or under study for neurocardiologic disorders in which catecholamine systems are hyperfunctional or hypofunctional. The future of therapeutics in neurocardiology is not so much in new curative drugs as in applying scientific integrative medical ideas that take into account concurrent chronic degenerative disorders and interactions of multiple drug and non-drug treatments with each other and with those disorders. PMID:21108771

A large, nationwide, longitudinal study of central nervous system diseases among Korean workers exposed to manganese.

PubMed

Yoon, Jin-Ha; Ahn, Yeon-Soon

2015-03-01

In occupational epidemiologic studies, the low incidence and chronic process of central nervous system (CNS) diseases has complicated the determination of the relationship between increased morbidity and manganese (Mn) exposure. Therefore, through this large cohort study, we evaluated CNS disease morbidity among Korean workers exposed to Mn Data were collected from Mn-associated specialized medical check-up 2000 and 2004 in Korea. The number of workers admitted to hospital because of clinically diagnosed CNS disease was analyzed in male workers exposed to Mn (n = 104,544). As a control reference population, 2% of Korean men were randomly selected and their hospital admission data were analyzed. For Mn-exposed workers, Standardized admission ratios (SARs) for CNS disease, as determined by ICD-10 classifications, were estimated in reference to the control population During follow up, 64 workers admitted because of CNS diseases. Chronic exposure to Mn (≥ 10 years) was significantly associated with the SAR (95% CI) of extrapyramidal and movement disorders (SAR: 2.03, 95% CI: 1.05-3.55), in particular, other extrapyramidal and movement disorders (SAR: 4.81, 95% CI: 1.29-12.32). Also borderline association (SAR = 4.88, 90% CI: 1.05-7.04) was noted for secondary Parkinsonism among workers with chronic Mn exposure. SARs (95% CI) for other degenerative nervous system diseases were significantly higher in Mn-exposed workers compared with the control population (SAR: 3.60, 95% CI: 1.16-8.40) CONCLUSION: In conclusion, Mn-exposed workers exhibited significantly elevated SARs for degenerative nervous system diseases and extrapyramidal and movement disorders, compared to the age-matched reference population, suggesting a relatedness with Mn exposure. Copyright © 2014 Elsevier Ltd. All rights reserved.

Intracranial Hemorrhage: A Devastating Outcome of Congenital Bleeding Disorders-Prevalence, Diagnosis, and Management, with a Special Focus on Congenital Factor XIII Deficiency.

PubMed

Alavi, Seyed Ezatolla Rafiee; Jalalvand, Masumeh; Assadollahi, Vahideh; Tabibian, Shadi; Dorgalaleh, Akbar

2018-04-01

Intracranial hemorrhage (ICH) is a medical emergency. In congenital bleeding disorders, ICH is a devastating presentation accompanied with a high rate of morbidity and mortality. The prevalence of ICH is highly variable among congenital bleeding disorders, with the highest incidence observed in factor (F) XIII deficiency (FXIIID) (∼30%). This life-threatening presentation is less common in afibrinogenemia, FVIII, FIX, FVII, and FX deficiencies, and is rare in severe FV and FII deficiencies, type 3 von Willebrand disease and inherited platelet function disorders (IPFDs). In FXIIID, this diathesis most often occurs after trauma in children, whereas spontaneous ICH is more frequent in adults. About 15% of patients with FXIIID and ICH die; the bleeding causes 80% of deaths in this coagulopathy. Although in FXIIID, the bleed most commonly is intraparenchymal (> 90%), epidural, subdural, and subarachnoid hemorrhages also have been reported, albeit rarely. As this life-threatening bleeding causes neurological complications, early diagnosis can prevent further expansion of the hematoma and secondary damage. Neuroimaging plays a crucial role in the diagnosis of ICH, but signs and symptoms in patients with severe FXIIID should trigger replacement therapy even before establishment of the diagnosis. Although a high dose of FXIII concentrate can reduce the rate of morbidity and mortality of ICH in FXIIID, it may occasionally trigger inhibitor development, thus complicating ICH management and future prophylaxis. Nevertheless, replacement therapy is the mainstay of treatment for ICH in FXIIID. Neurosurgery is performed in patients with FXIIID and epidural hematoma and a hemorrhage diameter exceeding 2 cm or a volume of ICH is more than 30 cm 3 . Contact sports are not recommended in people with FXIIID as they can elicit ICH. However, a considerable number of safe sports and activities have been suggested to have more benefits than dangers for patients with congenital bleeding disorders, and are hence suitable for these patients. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Therapy for Duchenne muscular dystrophy: renewed optimism from genetic approaches.

PubMed

Fairclough, Rebecca J; Wood, Matthew J; Davies, Kay E

2013-06-01

Duchenne muscular dystrophy (DMD) is a devastating progressive disease for which there is currently no effective treatment except palliative therapy. There are several promising genetic approaches, including viral delivery of the missing dystrophin gene, read-through of translation stop codons, exon skipping to restore the reading frame and increased expression of the compensatory utrophin gene. The lessons learned from these approaches will be applicable to many other disorders.

Anorexia Nervosa and Bulimia: Problems of “The Pleasing Child”

PubMed Central

McSherry, J. A.

1984-01-01

Widespread media publicity has resulted in increased case findings of eating disorders such as anorexia nervosa and bulimia. The etiology of these conditions is complex and multifactorial, and they may have devastating effects on physical and psychological health. Family physicians have an important role to play in recognizing, evaluating and managing eating disorders. Severe anorexics—those who have lost 25% or more of the average weight for their age and height—require specialist management, but milder forms respond to treatment which can be undertaken by an interested family physician. Most cases of uncomplicated bulimia can be treated successfully in a family practice setting. PMID:21278973

The impact of prolonged disorders of consciousness on the occupational life of family members.

PubMed

Elliott, Karen; McVicar, Andrew

2016-10-27

The impact of vegetative state (VS) and minimally conscious states (MCSs) on an individual is devastating. VS and MCSs may be transitional towards recovery, but may become permanent. Although devastating for the individual the nature of these conditions also has a profound effect on the family. This study examined the impact on the family member and the changes in the individuals' occupation. Six participants (spouses, partners or parents) were recruited to the study. Mixed methods were adopted to meet the requirements of the research and participants. Data were collected at 6 and 12 months post-injury, using time diaries, a questionnaire and semi-structured interviews. At 6 months post-injury the greatest amount of carers' time was allocated to occupations involving the person in a Disorder of Consciousness and less time to social and leisure activities. Participants had difficulty viewing the future, lacked the desire or capacity to engage in previously enjoyed activities. At 12 months those impacts were still evident although changing. The transition to balanced occupational activity is slow, requiring a number of catalysts to change. A conceptual framework for a return to balance is provided, and guidance on advice from family members to families in a similar situation is given.

Molecular bases of anorexia nervosa, bulimia nervosa and binge eating disorder: shedding light on the darkness.

PubMed

Cuesto, Germán; Everaerts, Claude; León, Leticia G; Acebes, Angel

2017-12-01

Eating-disorders (EDs) consequences to human health are devastating, involving social, mental, emotional, physical and life-threatening aspects, concluding on impairment and death in cases of extreme anorexia nervosa. It also implies that people suffering an ED need to find psychiatric and psychological help as soon as possible to achieve a fully physical and emotional recovery. Unfortunately, to date, there is a crucial lack of efficient clinical treatment to these disorders. In this review, we present an overview concerning the actual pharmacological and psychological treatments, the knowledge of cells, circuits, neuropeptides, neuromodulators and hormones in the human brain- and other organs- underlying these disorders, the studies in animal models and, finally, the genetic approaches devoted to face this challenge. We will also discuss the need for new perspectives, avenues and strategies to be developed in order to pave the way to novel and more efficient therapeutics.

Posttraumatic Stress Disorder: An Immunological Disorder?

PubMed Central

Wang, Zhewu; Caughron, Blaine; Young, M. Rita I.

2017-01-01

Patients with posttraumatic stress disorder (PTSD) exhibit an increased state of inflammation. Various animal models for PTSD have shown some of the same immune imbalances as have been shown in human subjects with PTSD, and some of these studies are discussed in this review. However, animal studies can only indirectly implicate immune involvement in PTSD in humans. This review of mainly studies with human subjects focuses on dissecting the immunological role in the pathogenesis of PTSD following initial trauma exposure. It addresses both the inflammatory state associated with PTSD and the immune imbalance between stimulatory and inhibitory immune mediators, as well as variables that can lead to discrepancies between analyses. The concept of immunological treatment approaches is proposed for PTSD, as new treatments are needed for this devastating disorder that is affecting unprecedented numbers of Veterans from the long-standing wars in the Middle East and which affects civilians following severe trauma. PMID:29163241

A Deep Learning Approach to Neuroanatomical Characterisation of Alzheimer's Disease.

PubMed

Ambastha, Abhinit Kumar; Leong, Tze-Yun

2017-01-01

Alzheimer's disease (AD) is a neurological degenerative disorder that leads to progressive mental deterioration. This work introduces a computational approach to improve our understanding of the progression of AD. We use ensemble learning methods and deep neural networks to identify salient structural correlations among brain regions that degenerate together in AD; this provides an understanding of how AD progresses in the brain. The proposed technique has a classification accuracy of 81.79% for AD against healthy subjects using a single modality imaging dataset.

Injectible bodily prosthetics employing methacrylic copolymer gels

DOEpatents

Mallapragada, Surya K.; Anderson, Brian C.

2007-02-27

The present invention provides novel block copolymers as structural supplements for injectible bodily prosthetics employed in medical or cosmetic procedures. The invention also includes the use of such block copolymers as nucleus pulposus replacement materials for the treatment of degenerative disc disorders and spinal injuries. The copolymers are constructed by polymerization of a tertiary amine methacrylate with either a (poly(ethylene oxide)-b-poly(propylene oxide)-b-poly(ethylene oxide) polymer, such as the commercially available Pluronic.RTM. polymers, or a poly(ethylene glycol) methyl ether polymer.

Physical Performance Characteristics of Military Aircraft Maintenance Personnel Resistant to Work-Related Musculoskeletal Disorders of the Hand and Wrist

DTIC Science & Technology

2006-01-01

neuropathy . Arthritis is an example of a degenerative condition. Though exact symptoms vary by conditions and the individual, some are common to most...depending upon the part and the access area (J. Warsinske, personal communication, July, 6, 2006). 12 Air Force WMSD iniury data Two jet engine repair...facilities were responsible for receiving, inspecting, and repairing jet engines, tasks that are comparable to the duties of the aircraft maintainers

Acquired degenerative changes of the intervertebral segments at and suprajacent to the lumbosacral junction. A radioanatomic analysis of the nondiskal structures of the spinal column and perispinal soft tissues.

PubMed

Jinkins, J R

2001-01-01

In earlier evolutionary times, mammals were primarily quadrupeds. However, other bipeds have also been represented during the course of the Earth's several billion year history. In many cases, either the bipedal stance yielded a large tail and hypoplastic upper extremities (e.g., Tyrannosaurus rex and the kangaroo), or it culminated in hypoplasia of the tail and further development and specialization of the upper extremities (e.g., nonhuman primates and human beings). In the human species this relatively recently acquired posture resulted in a more or less pronounced lumbosacral kyphosis. In turn, certain compensatory anatomic features have since occurred. These include the normal characteristic posteriorly directed wedge-shape of the L5 vertebral body and the L5-S1 intervertebral disk; the L4 vertebral body and the L4-L5 disk may be similarly visibly affected. These compensatory mechanisms, however, have proved to be functionally inadequate over the long term of the human life span. Upright posture also leads to increased weight bearing in humans that progressively causes excess stresses at and suprajacent to the lumbosacral junction. These combined factors result in accelerated aging and degenerative changes and a predisposition to frank biomechanical failure of the subcomponents of the spinal column in these spinal segments. One other specific problem that occurs at the lumbosacral junction that predisposes toward premature degeneration is the singular relationship that exists between a normally mobile segment of spine (i.e., the lumbar spine) and a normally immobile one (i.e., the sacrum). It is well known that mobile spinal segments adjacent to congenitally or acquired fused segments have a predilection toward accelerated degenerative changes. The only segment of the spine in which this is invariably normally true is at the lumbosacral junction (i.e., the unfused lumbar spine adjoining the fused sacrum). Nevertheless, biomechanical failures of the human spine are not lethal traits; in most cases today, mankind reaches sexual maturity before spinal biomechanical failure precludes sexual reproduction. For this gene-preserving reason, degenerative spinal disorders will likely be a part of modern societies for the foreseeable eternity of the race. The detailed alterations accruing from the interrelated consequences of and phenomena contributing to acquired degenerative changes of the lumbosacral intervertebral segments as detailed in this discussion highlight the extraordinary problems that are associated with degenerative disease in this region of the spine. Further clinicoradiologic research in this area will progressively determine the clinical applications and clinical efficacy of the various traditional and newer methods of therapy in patients presenting with symptomatic acquired collapse of the intervertebral disks at and suprajacent to the lumbosacral junction and the interrelated degenerative alterations of the nondiskal structures of the spine.

Determination of the Oswestry Disability Index score equivalent to a "satisfactory symptom state" in patients undergoing surgery for degenerative disorders of the lumbar spine-a Spine Tango registry-based study.

PubMed

van Hooff, Miranda L; Mannion, Anne F; Staub, Lukas P; Ostelo, Raymond W J G; Fairbank, Jeremy C T

2016-10-01

The achievement of a given change score on a valid outcome instrument is commonly used to indicate whether a clinically relevant change has occurred after spine surgery. However, the achievement of such a change score can be dependent on baseline values and does not necessarily indicate whether the patient is satisfied with the current state. The achievement of an absolute score equivalent to a patient acceptable symptom state (PASS) may be a more stringent measure to indicate treatment success. This study aimed to estimate the score on the Oswestry Disability Index (ODI, version 2.1a; 0-100) corresponding to a PASS in patients who had undergone surgery for degenerative disorders of the lumbar spine. This is a cross-sectional study of diagnostic accuracy using follow-up data from an international spine surgery registry. The sample includes 1,288 patients with degenerative lumbar spine disorders who had undergone elective spine surgery, registered in the EUROSPINE Spine Tango Spine Surgery Registry. The main outcome measure was the ODI (version 2.1a). Surgical data and data from the ODI and Core Outcome Measures Index (COMI) were included to determine the ODI threshold equivalent to PASS at 1 year (±1.5 months; n=780) and 2 years (±2 months; n=508) postoperatively. The symptom-specific well-being item of the COMI was used as the external criterion in the receiver operating characteristic (ROC) analysis to determine the ODI threshold equivalent to PASS. Separate sensitivity analyses were performed based on the different definitions of an "acceptable state" and for subgroups of patients. JF is a copyright holder of the ODI. The ODI threshold for PASS was 22, irrespective of the time of follow-up (area under the curve [AUC]: 0.89 [sensitivity {Se}: 78.3%, specificity {Sp}: 82.1%] and AUC: 0.91 [Se: 80.7%, Sp: 85.6] for the 1- and 2-year follow-ups, respectively). Sensitivity analyses showed that the absolute ODI-22 threshold for the two follow-up time-points were robust. A stricter definition of PASS resulted in lower ODI thresholds, varying from 16 (AUC=0.89; Se: 80.2%, Sp: 82.0%) to 18 (AUC=0.90; Se: 82.4%, Sp: 80.4%) depending on the time of follow-up. An ODI score ≤22 indicates the achievement of an acceptable symptom state and can hence be used as a criterion of treatment success alongside the commonly used change score measures. At the individual level, the threshold could be used to indicate whether or not a patient with a lumbar spine disorder is a "responder" after elective surgery. Copyright © 2016 Elsevier Inc. All rights reserved.

Blood lead levels in children with neurological disorders: a single centre preliminary study.

PubMed

Mahmoudian, Touran; Modaresi, Mohamadreza; Zarei, Ali; Poursafa, Parinaz; Kelishadi, Roya

2009-11-01

Lead poisoning is a potentially devastating problem among young children. Chronic low level lead exposure can lead to learning disabilities and behavior changes such as colic, insomnia, hyperactivity, impaired growth, hearing loss and upper extremity weakness. The purpose of this cross sectional study was to determine the blood lead level in children with neurological disorders in comparison with healthy controls. Blood lead concentrations were measured by flame atomic absorption spectrometry in 100 children aged 1-10 years and suffering from various neurological disorders. One hundred age and sex-matched healthy children served as controls. The mean blood lead concentration was higher in children with neurological disorders than in controls (113.2 + or - 47.5 microg/L vs 84.7 + or - 38.0 microg/L; p<0.01). Overall, 44% of children with neurological disorders and 19% of controls were found to have increased blood lead levels, i.e.>100 microg/L. An increase in blood lead level in children might be related to neurological disorders. The measurement of blood lead level might be included in diagnostic eveluation of children with neurological disorders.

Cytokine Involvement in Biological Inflammation Related to Degenerative Disorders of the Intervertebral Disk: A Narrative Review.

PubMed

De Geer, Christopher M

2018-03-01

The purpose of this narrative literature review is to discuss the literature regarding the potential role that cytokines play in degenerative disk disease. The inclusion criteria were studies that used inflammatory mediators in advancing disk disease processes. Research studies were limited to the last 3 decades that had free full-text available online in English. Exclusion criteria were review articles and articles pertaining to temporomandibular joints and other joints of the body other than the intervertebral disk. The following databases were searched: PubMed, EBSCOhost, and Google Scholar through March 13, 2017. A total of 82 studies were included in this review. The papers were reviewed for complex mechanisms behind the degenerative cascade, emphasizing the role of proinflammatory cytokines, which may be instrumental in processes of inflammation, neurologic pain, and disk degeneration. Interleukin-1β and tumor necrosis factor α were among the more notable cytokines involved in this cascade. Because monocyte chemoattractant protein-1 stimulates and activates macrophages in the event of infiltration, additional proinflammatory cytokines are released to act on molecules to promote blood and nerve ingrowth, resulting in pain signaling and tissue degradation. Excessive inflammation and/or tissue damage initiates a pathologic imbalance between anabolic and catabolic processes. This literature review describes how inflammatory and biochemical changes may trigger disk degeneration. Proinflammatory cytokines stimulate microvascular blood and nerve ingrowth, resulting in pain signaling and tissue degradation. This may sensitize a person to chemical and/or mechanical stimuli, contributing to severe low back pain.

Cell-based therapeutic strategies for replacement and preservation in retinal degenerative diseases

PubMed Central

Jones, Melissa K.; Lu, Bin; Girman, Sergey; Wang, Shaomei

2017-01-01

Cell-based therapeutics offer diverse options for treating retinal degenerative diseases, such as age-related macular degeneration (AMD) and retinitis pigmentosa (RP). AMD is characterized by both genetic and environmental risks factors, whereas RP is mainly a monogenic disorder. Though treatments exist for some patients with neovascular AMD, a majority of retinal degenerative patients have no effective therapeutics, thus indicating a need for universal therapies to target diverse patient populations. Two main cell-based mechanistic approaches are being tested in clinical trials. Replacement therapies utilize cell-derived retinal pigment epithelial (RPE) cells to supplant lost or defective host RPE cells. These cells are similar in morphology and function to native RPE cells and can potentially supplant the responsibilities of RPE in vivo. Preservation therapies utilize supportive cells to aid in visual function and photoreceptor preservation partially by neurotrophic mechanisms. The goal of preservation strategies is to halt or slow the progression of disease and maintain remaining visual function. A number of clinical trials are testing the safety of replacement and preservation cell therapies in patients; however, measures of efficacy will need to be further evaluated. In addition, a number of prevailing concerns with regards to the immune-related response, longevity, and functionality of the grafted cells will need to be addressed in future trials. This review will summarize the current status of cell-based preclinical and clinical studies with a focus on replacement and preservation strategies and the obstacles that remain regarding these types of treatments. PMID:28111323

[Spinocerebellar ataxia type 2 associated to pigmentary retinitis].

PubMed

Jiménez-Caballero, Pedro Enrique; Serviá, Mónica

2010-07-01

Ocular disorders are useful in the characterisation of the different types of spinocerebellar ataxias (SCA); pigmentary retinitis is an alteration that is specifically associated to SCA type 7 and is characterised by night blindness, sensitivity to glare and progressive narrowing of the visual field. A 34-year-old woman with clinical symptoms of progressive ataxia and visual impairment secondary to pigmentary retinitis. The patient had a personal history with an autosomal dominant pattern of a similar disorder in her father and paternal grandmother. In the genetic study she presented a triplet expansion in the SCA type 2 gene. CONCLUSIONS; Although pigmentary retinitis belongs to the SCA type 7 phenotype, our patient presented this retinal disorder, as in other cases of SCA type 2. A genetic study for SCA type 2 must therefore be conducted in patients with a degenerative ataxic clinical picture and who present evidence of pigmentary retinitis.

Current perspectives on the health risks associated with the consumption of advanced glycation end products: recommendations for dietary management

PubMed Central

Palimeri, Sotiria; Palioura, Eleni; Diamanti-Kandarakis, Evanthia

2015-01-01

Advanced glycation end products (AGEs) constitute a complex group of compounds produced endogenously during the aging process and under conditions of hyperglycemia and oxidative stress. AGEs also have an emerging exogenous origin. Cigarette smoke and diet are the two main exogenous sources of AGEs (glycotoxins). Modern Western diets are rich in AGEs which have been implicated in the pathogenesis of several metabolic and degenerative disorders. Accumulating evidence underlies the beneficial effect of the dietary restriction of AGEs not only in animal studies but also in patients with diabetic complications and metabolic diseases. This article reviews the evidence linking dietary glycotoxins to several disorders from diabetic complications and renal failure to liver dysfunction, female reproduction, eye and cognitive disorders as well as cancer. Furthermore, strategies for AGE reduction are discussed with a focus on dietary modification. PMID:26366100

Work-Related Upper Limb Disorders: A Case Report

PubMed Central

Stoyneva, Zlatka Borisova; Dermendjiev, Svetlan; Dermendjiev, Tihomir; Dobrev, Hristo

2015-01-01

In this study the complex interrelationship between physical factors, job stress, lifestyle and genetic factors on symptoms of work-related musculoskeletal disorders of the upper limbs is demonstrated by a case report and discussion of the literature. A 58 year old woman with long lasting complaints of the upper limbs with increasing intensity and duration, generalisation, combined with skin thickness, Raynaud’s phenomenon, joint disorders, arterial and pulmonary hypertension, metabolic lipid dysfunctions is presented. Occupational history proves continuous duration of service at a job with occupational physical static load with numerous repetitive monotonous systematic motions of fingers and hands as a weaver of Persian rugs followed by work at an automated loom and variable labour activities. Though the complaints dated since the time she was a manual weaver, the manifestations of generalized joint degenerative changes, system sclerosis with Raynaud’s phenomenon with similar upper extremities signs and symptoms discount upper limbs musculoskeletal disorder as caused only or mainly by occupational risk factors. The main principles and criteria for occupational diagnosis of musculoskeletal upper limb disorders and legislative requirements for their reglamentation are discussed. PMID:27275213

[Dreams in normal and pathological aging].

PubMed

Guénolé, Fabian; Marcaggi, Geoffrey; Baleyte, Jean-Marc; Garma, Lucile

2010-06-01

Although most of scientific knowledge in dream research is based on young adult studies, this article provides a review of the effects of normal and pathological aging on dream psychology. It starts with preliminary comments about epistemological and methodological principles of dream research, its singularities in aged persons, and the modifications of sleep physiology with age. The whole literature agrees that dream recall progressively decreases from the beginning of adulthood - not in old age - and that dream reports become less intense, perceptually and emotionally. This evolution occurs faster in men than women, with gender differences in the content of dreams. The chronological modifications could be explained partly by changes in lifestyle and attitude towards dreams in early adulthood, but mainly by modifications of sleep physiology, particularly the decrease and qualitative changes of rapid eye movement (REM) sleep. Dreams have usually little subjective importance in the mental life of aged persons. However, working with dreams can be a valuable tool for psychotherapy in the aged. According to the few existing data, patients suffering degenerative dementia dream much less than healthy aged persons. In Alzheimer's disease, this could be linked to the decrease of REM sleep, and atrophy of associative sensory areas of the cerebral cortex. Most studied aspects of dreaming in degenerative cognitive disorders are REM sleep behavior disorders, and nightmares induced by cholinesterase inhibitors. More studies are needed to better characterize the evolution of dreams with age, particularly studies performed in sleep laboratory.

Directed induction of functional motor neuron-like cells from genetically engineered human mesenchymal stem cells.

PubMed

Park, Hwan-Woo; Cho, Jung-Sun; Park, Chul-Kyu; Jung, Sung Jun; Park, Chang-Hwan; Lee, Shin-Jae; Oh, Seog Bae; Park, Young-Seok; Chang, Mi-Sook

2012-01-01

Cell replacement using stem cells is a promising therapeutic approach to treat degenerative motor neuron (MN) disorders, such as amyotrophic lateral sclerosis and spinal cord injury. Human bone marrow-derived mesenchymal stem cells (hMSCs) are a desirable cell source for autologous cell replacement therapy to treat nervous system injury due to their plasticity, low immunogenicity, and a lower risk of tumor formation than embryonic stem cells. However, hMSCs are inefficient with regards to differentiating into MN-like cells. To solve this limitation, we genetically engineered hMSCs to express MN-associated transcription factors, Olig2 and Hb9, and then treat the hMSCs expressing Olig2 and Hb9 with optimal MN induction medium (MNIM). This method of induction led to higher expression (>30% of total cells) of MN markers. Electrophysiological data revealed that the induced hMSCs had the excitable properties of neurons and were able to form functional connections with muscle fibers in vitro. Furthermore, when the induced hMSCs were transplanted into an injured organotypic rat spinal cord slice culture, an ex vivo model of spinal cord injury, they exhibited characteristics of MNs. The data strongly suggest that induced Olig2/Hb9-expressing hMSCs were clearly reprogrammed and directed toward a MN-like lineage. We propose that methods to induce Olig2 and Hb9, followed by further induction with MNIM have therapeutic potential for autologous cell replacement therapy to treat degenerative MN disorders.

[Bone and joint decade--"mile step" in diagnostics and treatment of movement system diseases?].

PubMed

Brongel, Leszek; Lorkowski, Jacek; Hładki, Waldemar; Trybus, Marek

2006-01-01

Musculoskeletal disorders affect hundreds of millions of people across the world and are the most common causes of severe long-term pain and physical disability. The impact from such disorders on the individual and on society let to propose by WHO for the Decade of the Bone and Joint from 2000 to 2010. The goal of the Decade is to improve the health-related quality of life for people with musculoskeletal disorders throughout the world and this could be achieved by raising awareness of the growing burden of bone and joint diseases on society, promoting prevention and treatment and advancing understanding of musculoskeletal disorders through research. The main fields of interest during the Decade are joint diseases, spinal disorders and low back pain, osteoporosis and severe trauma of the extremities. In our Department we study problems concerning on traumatology of old patients, multitrauma injury, biomechanics in spinal disorders, in degenerative joint disease and foot diseases. Apart from contemporary imaging methods like US or CT we use pedobarographic diagnostics and fotogrammetric examination. In this study we present strategic goals and the summary of our ongoing projects in our Department related to the goals of the Bone and Joint Decade.

Sleep and Plasticity in Schizophrenia

PubMed Central

Sprecher, Kate E.; Ferrarelli, Fabio

2016-01-01

Schizophrenia is a devastating mental illness with a worldwide prevalence of approximately 1 %. Although the clinical features of the disorder were described over one hundred years ago, its neurobiology is still largely elusive despite several decades of research. Schizophrenia is associated with marked sleep disturbances and memory impairment. Above and beyond altered sleep architecture, sleep rhythms including slow waves and spindles are disrupted in schizophrenia. In the healthy brain, these rhythms reflect and participate in plastic processes during sleep. This chapter discusses evidence that schizophrenia patients exhibit dysfunction of sleep-mediated plasticity on a behavioral, cellular, and molecular level and offers suggestions on how the study of sleeping brain activity can shed light on the pathophysiological mechanisms of the disorder. PMID:25608723

Transplantation of Human Chorion-Derived Cholinergic Progenitor Cells: a Novel Treatment for Neurological Disorders.

PubMed

Mohammadi, Alireza; Maleki-Jamshid, Ali; Sanooghi, Davood; Milan, Peiman Brouki; Rahmani, Arash; Sefat, Farshid; Shahpasand, Koorosh; Soleimani, Mansoureh; Bakhtiari, Mehrdad; Belali, Rafie; Faghihi, Faezeh; Joghataei, Mohammad Taghi; Perry, George; Mozafari, Masoud

2018-03-16

A neurological disorder is any disorder or abnormality in the nervous system. Among different neurological disorders, Alzheimer's disease (AD) is recognized as the sixth leading cause of death globally. Considerable research has been conducted to find pioneer treatments for this devastating disorder among which cell therapy has attracted remarkable attentions over the last decade. Up to now, targeted differentiation into specific desirable cell types has remained a major obstacle to clinical application of cell therapy. Also, potential risks including uncontrolled growth of stem cells could be disastrous. In our novel protocol, we used basal forebrain cholinergic progenitor cells (BFCN) derived from human chorion-derived mesenchymal stem cells (hC-MSCs) which made it possible to obtain high-quality population of cholinergic neurons and in vivo in much shorter time period than previous established methods. Remarkably, the transplanted progenitors fully differentiated to cholinergic neurons which in turn integrated in higher cortical networks of host brains, resulting in significant improvement in cognitive assessments. This method may have profound implications in cell therapies for any other neurodegenerative disorders. Graphical Abstract ᅟ.

Epigenetic dysregulation in cognitive disorders.

PubMed

Gräff, Johannes; Mansuy, Isabelle M

2009-07-01

Epigenetic mechanisms are not only essential for biological functions requiring stable molecular changes such as the establishment of cell identity and tissue formation, they also constitute dynamic intracellular processes for translating environmental stimuli into modifications in gene expression. Over the past decade it has become increasingly clear that both aspects of epigenetic mechanisms play a pivotal role in complex brain functions. Evidence from patients with neurodegenerative and neurodevelopmental disorders such as Alzheimer's disease and Rett syndrome indicated that epigenetic mechanisms and chromatin remodeling need to be tightly controlled for proper cognitive functions, and their dysregulation can have devastating consequences. However, because they are dynamic, epigenetic mechanisms are also potentially reversible and may provide powerful means for pharmacological intervention. This review outlines major cognitive disorders known to be associated with epigenetic dysregulation, and discusses the potential of 'epigenetic medicine' as a promising cure.

Linkage of early-onset osteoarthritis and chondrocalcinosis to human chromosome 8q

DOE Office of Scientific and Technical Information (OSTI.GOV)

Baldwin, C.T.; Farrer, L.A.; Adair, R.

Calcium pyrophosphate-deposition disease (CPDD), also called {open_quotes}chondrocalcinosis{close_quotes} or {open_quotes}pseudogout{close_quotes}, is a disorder characterized by the deposition of calcium-containing crystals in joint tissue, which leads to arthritis-like symptoms. The presence of these crystals in joint tissue is a common finding in the elderly, and, in this population, there is a poor correlation with joint pain. In contrast, early-onset CPDD has been described in several large families in which the disease progresses to severe degenerative osteoarthritis (OA). In these families, an autosomal dominant mode of inheritance is observed, with an age at onset between the 2nd and 5th decades of life. Inmore » this report, we describe a large New England family with early-onset CPDD and severe degenerative OA. We found genetic linkage between the disease in this family and chromosome 8q, with a multipoint lod score of 4.06. These results suggest that a defective gene at this location causes the disease in this family. 29 refs., 2 figs., 1 tab.« less

Glutaminolysis is Essential for Energy Production and Ion Transport in Human Corneal Endothelium.

PubMed

Zhang, Wenlin; Li, Hongde; Ogando, Diego G; Li, Shimin; Feng, Matthew; Price, Francis W; Tennessen, Jason M; Bonanno, Joseph A

2017-02-01

Corneal endothelium (CE) is among the most metabolically active tissues in the body. This elevated metabolic rate helps the CE maintain corneal transparency by its ion and fluid transport properties, which when disrupted, leads to visual impairment. Here we demonstrate that glutamine catabolism (glutaminolysis) through TCA cycle generates a large fraction of the ATP needed to maintain CE function, and this glutaminolysis is severely disrupted in cells deficient in NH 3 :H + cotransporter Solute Carrier Family 4 Member 11 (SLC4A11). Considering SLC4A11 mutations leads to corneal endothelial dystrophy and sensorineural deafness, our results indicate that SLC4A11-associated developmental and degenerative disorders result from altered glutamine catabolism. Overall, our results describe an important metabolic mechanism that provides CE cells with the energy required to maintain high level transport activity, reveal a direct link between glutamine metabolism and developmental and degenerative neuronal diseases, and suggest an approach for protecting the CE during ophthalmic surgeries. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

The Role of the Photoreceptor ABC Transporter ABCA4 in Lipid Transport and Stargardt Macular Degeneration

PubMed Central

Molday, Robert S.; Zhong, Ming; Quazi, Faraz

2009-01-01

ABCA4 is a member of the ABCA subfamily of ATP binding cassette (ABC) transporters that is expressed in rod and cone photoreceptors of the vertebrate retina. ABCA4, also known as the Rim protein and ABCR, is a large 2273 amino acid glycoprotein organized as two tandem halves, each containing a single membrane spanning segment followed sequentially by a large exocytoplasmic domain, a multispanning membrane domain and a nucleotide binding domain. Over 500 mutations in the gene encoding ABCA4 are associated with a spectrum of related autosomal recessive retinal degenerative diseases including Stargardt macular degeneration, cone-rod dystrophy and a subset of retinitis pigmentosa. Biochemical studies on the purified ABCA4 together with analysis of abca4 knockout mice and patients with Stargardt disease have implicated ABCA4 as a retinylidene-phosphatidylethanolamine transporter that facilitates the removal of potentially reactive retinal derivatives from photoreceptors following photoexcitation. Knowledge of the genetic and molecular basis for ABCA4 related retinal degenerative diseases is being used to develop rationale therapeutic treatments for this set of disorders. PMID:19230850

["Protein of senility" CCL11, "protein of juvenility" GDF11 and their role in age-related pathology].

PubMed

Khavinson, V Kh; Kuznik, B I; Ryzhak, G A; Linkova, N S; Kozina, L S; Sall, T S

2016-01-01

The paper presents the latest literature data on the structure and functions of «protein of juvenility» - CCL11 and «protein of senility» - GDF11. Chemokine CCL11 injected to young animals has been shown to lead to degenerative changes in the central nervous system (CNS), disturb cognitive functions and impede tissue regeneration. CCL11 concentration increases dramatically in schizophrenia, Alzheimer's disease, neuro-inflammatory disorders, cerebral malaria, drug addiction, as well as in atherosclerosis, periodontal disease, macular degeneration, cancer and other pathologies. In contrast to CCL11, differentiation growth factor 11 (GDF11), being administered to old mice, eliminates age-associated hypertrophy of the heart, improves muscle tone and prevents degenerative changes in the CNS, improves cognitive functions and enhances tissue regeneration. Its concentration decreases in cardiovascular disease, osteoporosis, and other «diseases of old age». At the same time, the higher the GDF11 level in the blood, the milder myocardial infarction, stroke and other age-related diseases of the cardiovascular system.

Association of bone marrow edema with temporomandibular joint (TMJ) osteoarthritis and internal derangements.

PubMed

Wahaj, Aiyesha; Hafeez, Kashif; Zafar, Muhammad Sohail

2017-01-01

This study reviewed the dental literature in order to determine the association of bone marrow edema with osteoarthritis and temporomandibular joint (TMJ) internal derangement disorders. A literature search was performed using electronic databases PubMed/Medline (National Library of Medicine, Bethesda, Maryland) and Cochrane for articles published during the last 15 years (January 2000-December 2014). A predetermined inclusion and exclusion criteria were used for filtering the scientific papers. Research articles fulfilling the basic inclusion criteria were included in the review. The reviewed studies showed that bone marrow edema is found in painful joints with osteoarthritis in a majority of cases. A few cases with no pain or significant degenerative changes are reported to have a bone marrow edema pattern as well. Bone marrow edema, increased fluid level, and pain are associated with osteoarthritis in the majority of patients reporting TMJ arthritis. Degenerative and disc displacement conditions are multifactorial and require further investigations. Magnetic resonance imaging can be employed to detect bone marrow edema even in the absence of pain and clinical symptoms in the patients of internal derangements.

Modulating Neurotrophin Receptor Signaling as a Therapeutic Strategy for Huntington’s Disease

PubMed Central

Simmons, Danielle A.

2017-01-01

Huntington’s disease (HD) is an autosomal dominant neurodegenerative disorder caused by CAG repeat expansions in the IT15 gene which encodes the huntingtin (HTT) protein. Currently, no treatments capable of preventing or slowing disease progression exist. Disease modifying therapeutics for HD would be expected to target a comprehensive set of degenerative processes given the diverse mechanisms contributing to HD pathogenesis including neuroinflammation, excitotoxicity, and transcription dysregulation. A major contributor to HD-related degeneration is mutant HTT-induced loss of neurotrophic support. Thus, neurotrophin (NT) receptors have emerged as therapeutic targets in HD. The considerable overlap between NT signaling networks and those dysregulated by mutant HTT provides strong theoretical support for this approach. This review will focus on the contributions of disrupted NT signaling in HD-related neurodegeneration and how targeting NT receptors to augment pro-survival signaling and/or to inhibit degenerative signaling may combat HD pathologies. Therapeutic strategies involving NT delivery, peptidomimetics, and the targeting of specific NT receptors (e.g., Trks or p75NTR), particularly with small molecule ligands, are discussed. PMID:29254102

Role of Low-Level Laser Therapy in Neurorehabilitation

PubMed Central

Hashmi, Javad T.; Huang, Ying-Ying; Osmani, Bushra Z.; Sharma, Sulbha K.; Naeser, Margaret A.; Hamblin, Michael R.

2011-01-01

This year marks the 50th anniversary of the discovery of the laser. The development of lasers for medical use, which became known as low-level laser therapy (LLLT) or photobiomodulation, followed in 1967. In recent years, LLLT has become an increasingly mainstream modality, especially in the areas of physical medicine and rehabilitation. At first used mainly for wound healing and pain relief, the medical applications of LLLT have broadened to include diseases such as stroke, myocardial infarction, and degenerative or traumatic brain disorders. This review will cover the mechanisms of LLLT that operate both on a cellular and a tissue level. Mitochondria are thought to be the principal photoreceptors, and increased adenosine triphosphate, reactive oxygen species, intracellular calcium, and release of nitric oxide are the initial events. Activation of transcription factors then leads to expression of many protective, anti-apoptotic, anti-oxidant, and pro-proliferation gene products. Animal studies and human clinical trials of LLLT for indications with relevance to neurology, such as stroke, traumatic brain injury, degenerative brain disease, spinal cord injury, and peripheral nerve regeneration, will be covered. PMID:21172691

Active Targeted Macrophage-mediated Delivery of Catalase to Affected Brain Regions in Models of Parkinson's Disease.

PubMed

Zhao, Yuling; Haney, Matthew J; Mahajan, Vivek; Reiner, Benjamin C; Dunaevsky, Anna; Mosley, R Lee; Kabanov, Alexander V; Gendelman, Howard E; Batrakova, Elena V

2011-09-10

We previously demonstrated that monocyte-macrophage based drug delivery can be applied to a spectrum of infectious, neoplastic, and degenerative disorders. In particular, bone marrow-derived macrophages (BMM) loaded with nano formulated catalase, "nanozyme", were shown to attenuate neuro inflammation and nigrostriatal degeneration in rodent models of Parkinson's disease (PD). Nonetheless, the pharmacokinetics and biodistribution of BMM-incorporated nanozyme has not been explored. To this end, we now demonstrate that BMM, serving as a "depot" for nanozyme, increased area under the curve(AUC), half-life, and mean residence time in blood circulation of the protein when compared to the nanozyme administered alone. Accordingly, bioavailability of the nanozyme for the brain, spleen, kidney, and liver was substantially increased. Importantly, nanozyme-loaded BMM targeted diseased sites and improved transport across the blood brain barrier. This was seen specifically in affected brain subregions in models of PD. Engaging natural immune cells such as monocyte-macrophages as drug carriers provides a new perspective for therapeutic delivery for PD and also likely a range of other inflammatory and degenerative diseases.

Past, present, and prospects: Reflections 40 years on from the selective impairment of semantic memory (Warrington, 1975).

PubMed

McCarthy, Rosaleen A; Warrington, Elizabeth K

2016-10-01

We summarize the main findings and conclusions of Warrington's (1975) paper, The Selective Impairment of Semantic memory, a neuropsychological paper that described three cases with degenerative neurological conditions [Warrington, E. K. (1975). The selective impairment of semantic memory. The Quarterly Journal of Experimental Psychology, 27, 635-657]. We consider the developments that have followed from its publication and give a selective overview of the field in 2014. The initial impact of the paper was on neuropsychological investigations of semantic loss followed some 14 years later by the identification of Semantic Dementia (the condition shown by the original cases) as a distinctive form of degenerative disease with unique clinical and pathological characteristics. We discuss the distinction between disorders of semantic storage and refractory semantic access, the evidence for category- and modality-specific impairments of semantics, and the light that has been shed on the structure and organization of semantic memory. Finally we consider the relationship between semantic memory and the skills of reading and writing, phonological processing, and autobiographical memory.

The spinocerebellar ataxias.

PubMed

Gilman, S

2000-01-01

The spinocerebellar ataxias (SCAs) are diseases characterized by the progressive degeneration and subsequent loss of neurons accompanied by reactive gliosis, degeneration of fibers from the deteriorating neurons, and clinical symptoms reflecting the locations of the lost neurons. The degenerative changes affect specific neuronal groups while others remain preserved, and these diseases can therefore be viewed as system degenerations. The SCAs result from either genetically transmitted diseases with dominant inheritance or unknown causes with sporadic occurrence. Most of these disorders affect the cerebellum and its pathways, resulting in progressive deterioration of cerebellar function manifested by increasing unsteadiness of gait, incoordination of limb movements with impairment of skilled movements such as handwriting, and a distinctive dysarthria. Other neuronal systems are affected in some of these disorders, notably the corticospinal pathway, basal ganglia, and autonomic nuclei of the brain stem and spinal cord.

Acquired cutis laxa following urticarial vasculitis associated with IgA myeloma.

PubMed

Turner, Ryan B; Haynes, Harley A; Granter, Scott R; Miller, Danielle M

2009-06-01

Cutis laxa (CL) is an inherited or acquired connective tissue disorder characterized clinically by loosely hanging skin folds. There is often preceding cutaneous inflammatory eruption (ie, urticaria, eczema, erythema multiforme), and there is frequently internal organ involvement of the gastrointestinal, urogenital, pulmonary, and cardiovascular systems. Histologically, there are degenerative changes in the dermal elastic fibers. Of the few reports on this rare disorder, authors have speculated about an immune-mediated destruction of elastic fibers, and monoclonal gammopathies, such as multiple myeloma or heavy chain deposition disease, have a recognized association with CL. We report an unusual case of rapidly progressing acquired CL associated with leukocytoclastic vasculitis, IgA myeloma, and an immune complex-mediated glomerulonephritis. Light microscopy of the lax skin revealed complete absence of elastic fibers in areas of vasculitis.

Nature of Tau-Associated Neurodegeneration and the Molecular Mechanisms

PubMed Central

Yang, Ying; Wang, Jian-Zhi

2018-01-01

Neurodegeneration is defined as the progressive loss of structure or function of the neurons. As the nature of degenerative cell loss is currently not clear, there is no specific molecular marker to measure neurodegeneration. Therefore, researchers have been using apoptotic markers to measure neurodegeneration. However, neurodegeneration is completely different from apoptosis by morphology and time course. Lacking specific molecular marker has been the major hindrance in research of neurodegenerative disorders. Alzheimer’s disease (AD) is the most common neurodegenerative disorder, and tau accumulation forming neurofibrillary tangles is a hallmark pathology in the AD brains, suggesting that tau must play a critical role in AD neurodegeneration. Here we review part of our published papers on tau-related studies, and share our thoughts on the nature of tau-associated neurodegeneration in AD. PMID:29562535

[The influence of general magnetic therapy on the psychological status of the patients presenting with osteoarthrosis].

PubMed

Degtiarev, V K; Aleksandrov, A V; Nenasheva, N V; Cherkashina, I V; Nikitin, M V

2013-01-01

The present study was designed to estimate the influence of general magnetic therapy on the psychical conditions of 151 patients presenting with degenerative joint diseases including osteoarthritis (OA). It was shown that the application of general magnetic therapy for the rehabilitative treatment of osteoarthrosis promotes the improvement of the psycho-emotional state of the patients. It is concluded that prescription of general magnetic therapy to the patients with OA suffering from serious psycho-emotional disorders brings about beneficial changes in their anxiety- and depression-related personality traits.

Space Radiation

NASA Technical Reports Server (NTRS)

Wu, Honglu

2006-01-01

Astronauts receive the highest occupational radiation exposure. Effective protections are needed to ensure the safety of astronauts on long duration space missions. Increased cancer morbidity or mortality risk in astronauts may be caused by occupational radiation exposure. Acute and late radiation damage to the central nervous system (CNS) may lead to changes in motor function and behavior, or neurological disorders. Radiation exposure may result in degenerative tissue diseases (non-cancer or non-CNS) such as cardiac, circulatory, or digestive diseases, as well as cataracts. Acute radiation syndromes may occur due to occupational radiation exposure.

Long-chain omega 3 fatty acids: molecular bases of potential antioxidant actions.

PubMed

Giordano, Elena; Visioli, Francesco

2014-01-01

Several lines of investigation are being developed to assess the impact of polyunsaturated fatty acids, namely those of the omega 3 series, intake on oxidative stress. Keeping in mind that there might be a dose-response relation, in vivo and in vitro data strongly suggest that omega 3 fatty acids might act as anti- rather than pro-oxidant in several cells such as vascular cells, hence diminishing inflammation, oxidative stress, and, in turn, the risk of atherosclerosis and degenerative disorders such as cardiovascular disease. © 2013 Published by Elsevier Ltd.

Solar elastosis in its papular form: uncommon, mistakable.

PubMed

Heng, Jun Khee; Aw, Derrick Chen Wee; Tan, Kong Bing

2014-01-01

Solar elastosis is a degenerative condition of elastic tissue in the dermis due to prolonged sun exposure. There are a variety of clinical manifestations of solar elastosis. In its most common form, solar elastosis manifests as yellow, thickened, coarsely wrinkled skin. We report two uncommon cases of severe solar elastosis with a papular morphology. Its presentation can closely mimic a host of cutaneous disorders and thus, although it is helpful to be cognizant of this entity, it is still crucial to biopsy these lesions to avoid missing a more sinister condition.

Obtaining lutein-rich extract from microalgal biomass at preparative scale.

PubMed

Fernández-Sevilla, José M; Fernández, F Gabriel Acién; Grima, Emilio Molina

2012-01-01

Lutein extracts are in increasing demand due to their alleged role in the prevention of degenerative disorders such as age-related macular degeneration (AMD). Lutein extracts are currently obtained from plant sources, but microalgae have been demonstrated to be a competitive source likely to become an alternative. The extraction of lutein from microalgae posesses specific problems that arise from the different structure and composition of the source biomass. Here is presented a method for the recovery of lutein-rich carotenoid extracts from microalgal biomass in the kilogram scale.

The impact of neighborhood factors on the well-being of survivors of intimate partner violence over time.

PubMed

Beeble, Marisa L; Sullivan, Cris M; Bybee, Deborah

2011-06-01

Intimate partner violence (IPV) is a pervasive social problem impacting the psychological well-being of millions of US women annually. The extant literature draws our attention to the devastating mental health effects of IPV, but largely overlooks how ecological factors may further explain survivors' well-being. This study examined how neighborhood disadvantage may contribute to survivors' compromised well-being, in addition to the abuse women experienced. Neighborhood disorder and fear of victimization significantly impacted survivors' well-being, over and above abuse. Although between-women effects of neighborhood disorder and fear were unrelated to change in women's depression or quality of life (QOL), significant within-woman effects were detected. Change in neighborhood disorder was negatively associated with change in QOL, and this relationship was fully mediated by fear. While no direct relationship between change in neighborhood disorder and depression was detected, an indirect effect through survivors' fear was revealed. Implications for future research and practice are discussed.

Alzheimer's Disease and Autistic Spectrum Disorder: Is there any Association?

PubMed

Khan, Sarah A; Khan, Shahida A; Narendra, A R; Mushtaq, Gohar; Zahran, Solafa A; Khan, Shahzad; Kamal, Mohammad A

2016-01-01

Autism spectrum disorder (ASD) and Alzheimer's disease (AD) are neurodevelopmental and neurodegenerative disorders respectively, with devastating effects not only on the individual but also the society. Collectively, a number of factors contribute to the expression of ASD and AD. It is of utmost curiosity that these disorders express at different stages of life and there is an involvement of certain susceptible genes. This genetic basis makes the background of common associations like memory deficits, cognition changes, demyelination, oxidative stress and inflammation, an integral part of both disorders. Modern technology resulting in genetically modified crops and increase in gadgets emitting electromagnetic frequencies have resulted in enhanced risks for neurological dysfunctions and disorders like ASD and AD. Subsequent advances in the psychological, pharmacological, biochemical and nutritional aspects of the disorders have resulted in the development of newer therapeutic approaches. The common clinical features like language impairment, executive functions, and motor problems have been discussed along with the patho-physiological changes, role of DNA methylation, myelin development, and heavy metals in the expression of these disorders. Psychopharmacological and nutritional approaches towards the reduction and management of risk factors have gained attention from the researchers in recent years. Current major therapies either target the inflammatory pathways or reduce cellular oxidative stress. This contribution focuses on the commonalities of the two disorders.

Degenerative joint disease in weight-lifters. Fact or fiction?

PubMed Central

Fitzgerald, B.; McLatchie, G. R.

1980-01-01

A clinical and radiological study of upper and lower limb joints was carried out on 25 experienced weight-lifters to identify the extent of degenerative joint disease (Osteoarthrosis) produced by this sport. Although significant degenerative changes were found in five lifters (20%). This figure is not greater than that found in the general population within the age group studied. There were more degenerative changes found in Olympic style weight-lifters (30.7%) than in power lifters (8.3%). The significance of these figures is discussed. The upper limb joints were almost completely free of degenerative changes. Images p97-a p97-b PMID:7407459

[Contributions of cortisol suppression tests to understanding of psychiatric disorders: a narrative review of literature].

PubMed

Tajima-Pozo, Kazuhiro; Montes-Montero, Ana; Güemes, Itziar; González-Vives, Sara; Díaz-Marsá, Marina; Carrasco, José Luis

2013-01-01

Activity of the hypothalamic-pituitary-adrenal axis had been studied for the past half century, when some researchers noted that some patients with Cushing's syndrome and severe mood disorders had high baseline cortisol levels, which resulted in an inhibited response in the 1mg dexamethasone suppression test. Altered dexamethasone suppression test results were subsequently found in many psychiatric diseases, including anorexia nervosa, obsessive-compulsive disorder, degenerative dementia, bipolar disorders, and schizophrenia. The relationship between high baseline cortisol levels and stress has also been studied. Some researches on the genesis of borderline personality disorder focused on traumatic childhood backgrounds. Other investigations aimed at elucidating the relationship between traumatic backgrounds and some psychiatric disorders noted that patients with post-traumatic stress disorder and borderline personality disorder showed an enhanced cortisol suppression with low cortisol doses (0.5 mg). Recent studies showed that use of an ultra-low dose of cortisol during the dexamethasone suppression test may be helpful for detecting disorders with hyperactivity of the hypothalamic-pituitary-adrenal axis. Recent advances in neuroimaging support the existence of hyperactivity of the hypothalamic-pituitary-adrenal axis in patients with borderline personality disorder, relating a decreased pituitary gland volume to major traumatic backgrounds and suicidal attempts. The purpose of this paper is to make a narrative review of research using dexamethasone suppression test in psychiatric disorders, in order to ascertain its value as a supplemental diagnostic test or as a prognostic marker. Copyright © 2012 SEEN. Published by Elsevier Espana. All rights reserved.

Mitochondrial Translation and Beyond: Processes Implicated in Combined Oxidative Phosphorylation Deficiencies

PubMed Central

Smits, Paulien; Smeitink, Jan; van den Heuvel, Lambert

2010-01-01

Mitochondrial disorders are a heterogeneous group of often multisystemic and early fatal diseases, which are amongst the most common inherited human diseases. These disorders are caused by defects in the oxidative phosphorylation (OXPHOS) system, which comprises five multisubunit enzyme complexes encoded by both the nuclear and the mitochondrial genomes. Due to the multitude of proteins and intricacy of the processes required for a properly functioning OXPHOS system, identifying the genetic defect that underlies an OXPHOS deficiency is not an easy task, especially in the case of combined OXPHOS defects. In the present communication we give an extensive overview of the proteins and processes (in)directly involved in mitochondrial translation and the biogenesis of the OXPHOS system and their roles in combined OXPHOS deficiencies. This knowledge is important for further research into the genetic causes, with the ultimate goal to effectively prevent and cure these complex and often devastating disorders. PMID:20396601

[Gait disorders in geriatric patients. Classification and therapy].

PubMed

Jahn, K; Heinze, C; Selge, C; Heßelbarth, K; Schniepp, R

2015-04-01

Slow walking with reduced body dynamics is a characteristic feature of locomotion in the elderly. Impaired mobility and falls associated with gait disorders significantly contribute to a reduced quality of life in the elderly. A gait disorder is not an inevitable consequence of aging. This article shows that it is worth recognizing specific deficits and differentiating specific aspects in multifactorial disorders because many causes can be well treated. Also provided are the bases for clinical classification and therapeutic principles. Review of recent literature and clinical review based on own experience and own scientific results. Common causes of disturbed gait in the elderly are neurological deficits, including sensory deficits (e.g. peripheral neuropathy and vestibulopathy), neurodegeneration (e.g. cerebellar ataxia and parkinsonian syndromes, cognitive impairment (e.g. degenerative dementia), degeneration of joints (e.g. coxarthrosis) and general loss of muscle mass (sarcopenia). Furthermore, a fear of falling also contributes to the gait disorder. Multimodal therapies are often necessary and the principles are presented. Identification of deficits is a prerequisite for specific therapy. As physical activity protects against cognitive impairment, reduces the risk of falling and improves overall quality of life, a structured assessment of causes for gait impairment is crucial.

Young women with PD: a group work experience.

PubMed

Posen, J; Moore, O; Tassa, D S; Ginzburg, K; Drory, M; Giladi, N

2000-01-01

Parkinson's Disease (PD) prior to the age of 40 affects between 5-10% of the PD population. The psychosocial changes that patients with early PD encounter, may be more devastating and disabling than the actual motor disability. The paper describes a unique experience in groupwork with young female PD patients treated in the Movement Disorders Unit of the Tel Aviv Sourasky Medical Center. The paper focuses on the special issues which characterized this group's experience: stigma, body and sexual image, and personality traits.

Rett Syndrome: Crossing the Threshold to Clinical Translation

PubMed Central

Katz, David M.; Bird, Adrian; Coenraads, Monica; Gray, Steven J.; Menon, Debashish U.; Philpot, Benjamin D.; Tarquinio, Daniel C.

2016-01-01

Lying at the intersection between neurobiology and epigenetics, Rett syndrome (RTT) has garnered intense interest in recent years, not only from a broad range of academic scientists, but also from the pharmaceutical and biotechnology industries. In addition to the critical need for treatments for this devastating disorder, optimism for developing RTT treatments derives from a unique convergence of factors, including a known monogenic cause, reversibility of symptoms in preclinical models, a strong clinical research infrastructure highlighted by an NIH-funded natural history study and well-established clinics with significant patient populations. Here, we review recent advances in understanding the biology of RTT, particularly promising preclinical findings, lessons from past clinical trials, and critical elements of trial design for rare disorders. PMID:26830113

Movement disorders in paraneoplastic and autoimmune disease

PubMed Central

Panzer, Jessica; Dalmau, Josep

2013-01-01

Purpose of review The most relevant advances in immune-mediated movement disorders are described, with emphasis on the clinical–immunological associations, novel antigens, and treatment. Recent findings Many movement disorders previously considered idiopathic or degenerative are now recognized as immune-mediated. Some disorders are paraneoplastic, such as anti-CRMP5-associated chorea, anti-Ma2 hypokinesis and rigidity, anti-Yo cerebellar ataxia and tremor, and anti-Hu ataxia and pesudoathetosis. Other disorders such as Sydenham's chorea, or chorea related to systemic lupus erythematosus and antiphospholipid syndrome occur in association with multiple antibodies, are not paraneoplastic, and are triggered by molecular mimicry or unknown mechanisms. Recent studies have revealed a new category of disorders that can be paraneoplastic or not, and associate with antibodies against cell-surface or synaptic proteins. They include anti-N-methyl-d-aspartate receptor (anti-NMDAR) encephalitis, which may cause dyskinesias, chorea, ballismus or dystonia (NMDAR antibodies), the spectrum of Stiff-person syndrome/muscle rigidity (glutamic acid decarboxylase, amphiphysin, GABAA-receptor-associated protein, or glycine receptor antibodies), neuromyotonia (Caspr2 antibodies), and opsoclonus–myoclonus–ataxia (unknown antigens). Summary Neurologists should be aware that many movement disorders are immune-mediated. Recognition of these disorders is important because it may lead to the diagnosis of an occult cancer, and a substantial number of patients, mainly those with antibodies to cell-surface or synaptic proteins, respond to immunotherapy. PMID:21577108

Somatic diseases in child survivors of the Holocaust with posttraumatic stress disorder: a comparative study.

PubMed

Sperling, Wolfgang; Kreil, Sebastian; Biermann, Teresa

2012-05-01

The incidence of mental and somatic sequelae has been shown to be very high in people who survived the Holocaust. In the current study, 80 Holocaust survivors with posttraumatic stress disorder were examined based on evaluation of their complete record (medical reports, clinical history, medical statements, and handwritten declarations of patients under oath). These survivors were compared with subjects with posttraumatic stress disorder caused by traumata other than the Holocaust. The data were analyzed for the presence of cardiovascular, gastrointestinal, and orthopedic diseases that developed in the time between the earliest medical report (expert opinion) and the latest expert opinion. Analysis revealed an increase in myocardial infarction, chronic degenerative diseases, and cancerous changes in the second expert opinion. No differences between the groups were seen with regard to sex, age at traumatization, or age at examination. Several implications of the data are discussed, including the implication that the survivors examined in this study may comprise a highly resilient group, inasmuch as they had reached an advanced age.

Apigenin-7-diglucuronide protects retinas against bright light-induced photoreceptor degeneration through the inhibition of retinal oxidative stress and inflammation.

PubMed

Bian, Minjuan; Zhang, Yong; Du, Xiaoye; Xu, Jing; Cui, Jingang; Gu, Jiangping; Zhu, Weiliang; Zhang, Teng; Chen, Yu

2017-05-15

Vision impairment in retinal degenerative diseases such as age-related macular degeneration is primarily associated with photoreceptor degeneration, in which oxidative stress and inflammatory responses are mechanistically involved as central players. Therapies with photoreceptor protective properties remain to be developed. Apigenin-7-diglucuronide (A7DG), a flavonoid glycoside, is present in an assortment of medicinal plants with anti-inflammatory or ant-oxidant activities. However, the pharmacological significance of A7DG remains unknown in vivo. The current study isolated A7DG from Glechoma longituba (Nakai) Kuprian and investigated the retinal protective effect A7DG in mice characterized by bright light-induced photoreceptor degeneration. The results showed that A7DG treatment led to remarkable photoreceptor protection in bright light-exposed BALB/c mice. Moreover, A7DG treatment alleviated photoreceptor apoptosis, mitigated oxidative stress, suppressed reactive gliosis and microglial activation and attenuated the expression of proinflammatory genes in bright light-exposed retinas. The results demonstrated for the first time remarkable photoreceptor protective activities of A7DG in vivo. Inhibition of bright light-induced retinal oxidative stress and retinal inflammatory responses was associated with the retinal protection conferred by A7DG. The work here warrants further evaluation of A7DG as a pharmacological candidate for the treatment of vision-threatening retinal degenerative disorders. Moreover, given the general implication of oxidative stress and inflammation in the pathogenesis of neurodegeneration, A7DG could be further tested for the treatment of other neurodegenerative disorders. Copyright © 2017 Elsevier B.V. All rights reserved.

Cow's milk and goat's milk.

PubMed

Turck, Dominique

2013-01-01

Cow's milk is increasingly suggested to play a role in the development of chronic degenerative, non-communicable disorders whereas goat's milk is advocated as having several health benefits. Cow's milk is a rich and cheap source of protein and calcium, and a valuable food for bone health. Despite their high content in saturated fats, consumption of full-fat dairy products does not seem to cause significant changes in cardiovascular disease risk variables. Early introduction of cow's milk is a strong negative determinant of iron status. Unmodified cow's milk does not meet nutritional requirements of infants although it is acceptable to add small volumes of cow's milk to complementary foods. Cow's milk protein allergy has a prevalence ranging from 2 to 7%, and the age of recovery is usually around 2-3 years. The evidence linking cow's milk intake to a later risk of type 1 diabetes or chronic degenerative, non-communicable disorders (obesity, metabolic syndrome, type 2 diabetes, hypertension) is not convincing. Milk probably protects against colorectal cancer, diets high in calcium are a probable cause of prostate cancer, and there is limited evidence suggesting that high consumption of milk and dairy products increases the risk for prostate cancer. There is no evidence to support the use of a cow's milk-free diet as a primary treatment for individuals with autistic spectrum disorders. Unmodified goat's milk is not suitable for infants because of the high protein and minerals content and of a low folate content. Goat's milk has no clear nutritional advantage over cow's milk and is not less allergenic. The European Food Safety Authority recently stated that proteins from goat's milk can be suitable as a protein source for infant and follow-on formula, provided the final product complies with the compositional criteria laid down in Directive 2006/141/EC. Copyright © 2013 S. Karger AG, Basel.

78 FR 65450 - Agency Information Collection (Non-Degenerative Arthritis (Including Inflammatory, Autoimmune...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-10-31

...-Degenerative Arthritis (Including Inflammatory, Autoimmune, Crystalline and Infectious Arthritis) and Dysbaric... Control No. 2900- NEW (Non-Degenerative Arthritis (including inflammatory, autoimmune, crystalline and infectious arthritis) and Dysbaric Osteonecrosis Disability Benefits Questionnaire)'' in any correspondence...

MRI features of cervical articular process degenerative joint disease in Great Dane dogs with cervical spondylomyelopathy.

PubMed

Gutierrez-Quintana, Rodrigo; Penderis, Jacques

2012-01-01

Cervical spondylomyelopathy or Wobbler syndrome commonly affects the cervical vertebral column of Great Dane dogs. Degenerative changes affecting the articular process joints are a frequent finding in these patients; however, the correlation between these changes and other features of cervical spondylomyelopathy are uncertain. We described and graded the degenerative changes evident in the cervical articular process joints from 13 Great Danes dogs with cervical spondylomyelopathy using MR imaging, and evaluated the relationship between individual features of cervical articular process joint degeneration and the presence of spinal cord compression, vertebral foraminal stenosis, intramedullary spinal cord changes, and intervertebral disc degenerative changes. Degenerative changes affecting the articular process joints were common, with only 13 of 94 (14%) having no degenerative changes. The most severe changes were evident between C4-C5 and C7-T1 intervertebral spaces. Reduction or loss of the hyperintense synovial fluid signal on T2-weighted MR images was the most frequent feature associated with articular process joint degenerative changes. Degenerative changes of the articular process joints affecting the synovial fluid or articular surface, or causing lateral hypertrophic tissue, were positively correlated with lateral spinal cord compression and vertebral foraminal stenosis. Dorsal hypertrophic tissue was positively correlated with dorsal spinal cord compression. Disc-associated spinal cord compression was recognized less frequently. © 2011 Veterinary Radiology & Ultrasound.

Diagnostic Validity of Combining History Elements and Physical Examination Tests for Traumatic and Degenerative Symptomatic Meniscal Tears.

PubMed

Décary, Simon; Fallaha, Michel; Frémont, Pierre; Martel-Pelletier, Johanne; Pelletier, Jean-Pierre; Feldman, Debbie E; Sylvestre, Marie-Pierre; Vendittoli, Pascal-André; Desmeules, François

2018-05-01

The current approach to the clinical diagnosis of traumatic and degenerative symptomatic meniscal tears (SMTs) proposes combining history elements and physical examination tests without systematic prescription of imaging investigations, yet the evidence to support this diagnostic approach is scarce. To assess the validity of diagnostic clusters combining history elements and physical examination tests to diagnose or exclude traumatic and degenerative SMT compared with other knee disorders. Prospective diagnostic accuracy study. Patients were recruited from 2 orthopedic clinics, 2 family medicine clinics, and from a university community. A total of 279 consecutive patients who underwent consultation for a new knee complaint. Each patient was assessed independently by 2 evaluators. History elements and standardized physical examination tests performed by a physiotherapist were compared with the reference standard: an expert physicians' composite diagnosis including a clinical examination and confirmatory magnetic resonance imaging. Participating expert physicians were orthopedic surgeons (n = 3) or sport medicine physicians (n = 2). Penalized logistic regression (least absolute shrinkage and selection operator) was used to identify history elements and physical examination tests associated with the diagnosis of SMT and recursive partitioning was used to develop diagnostic clusters. Diagnostic accuracy measures were calculated including sensitivity, specificity, positive and negative predictive values, and positive and negative likelihood ratios (LR+/-) with associated 95% confidence intervals (CIs). Eighty patients had a diagnosis of SMT (28.7%), including 35 traumatic tears and 45 degenerative tears. The combination a history of trauma during a pivot, medial knee pain location, and a positive medial joint line tenderness test was able to diagnose (LR+ = 8.9; 95% CI 6.1-13.1) or exclude (LR- = 0.10; 95% CI 0.03-0.28) a traumatic SMT. Combining a history of progressive onset of pain, medial knee pain location, pain while pivoting, absence of valgus or varus knee misalignment, or full passive knee flexion was able to moderately diagnose (LR+ = 6.4; 95% CI 4.0-10.4) or exclude (LR- = 0.10; 95% CI 0.03-0.31) a degenerative SMT. Internal validation estimates were slightly lower for all clusters but demonstrated positive LR superior to 5 and negative LR inferior to 0.2 indicating moderate shift in posttest probability. Diagnostic clusters combining history elements and physical examination tests can support the differential diagnosis of SMT. These results represent the initial derivation of the clusters and external validation is mandatory. I. Copyright © 2018 American Academy of Physical Medicine and Rehabilitation. Published by Elsevier Inc. All rights reserved.

Radiotherapy for non-malignant disorders: state of the art and update of the evidence-based practice guidelines

PubMed Central

Micke, O; Muecke, R

2015-01-01

Every year in Germany about 50,000 patients are referred and treated by radiotherapy (RT) for “non-malignant disorders”. This highly successful treatment is applied only for specific indications such as preservation or recovery of the quality of life by means of pain reduction or resolution and/or an improvement of formerly impaired physical body function owing to specific disease-related symptoms. Since 1995, German radiation oncologists have treated non-malignant disorders according to national consensus guidelines; these guidelines were updated and further developed over 3 years by implementation of a systematic consensus process to achieve national upgraded and accepted S2e clinical practice guidelines. Throughout this process, international standards of evaluation were implemented. This review summarizes most of the generally accepted indications for the application of RT for non-malignant diseases and presents the special treatment concepts. The following disease groups are addressed: painful degenerative skeletal disorders, hyperproliferative disorders and symptomatic functional disorders. These state of the art guidelines may serve as a platform for daily clinical work; they provide a new starting point for quality assessment, future clinical research, including the design of prospective clinical trials, and outcome research in the underrepresented and less appreciated field of RT for non-malignant disorders. PMID:25955230

Genomic and Epigenomic Insights into Nutrition and Brain Disorders

PubMed Central

Dauncey, Margaret Joy

2013-01-01

Considerable evidence links many neuropsychiatric, neurodevelopmental and neurodegenerative disorders with multiple complex interactions between genetics and environmental factors such as nutrition. Mental health problems, autism, eating disorders, Alzheimer’s disease, schizophrenia, Parkinson’s disease and brain tumours are related to individual variability in numerous protein-coding and non-coding regions of the genome. However, genotype does not necessarily determine neurological phenotype because the epigenome modulates gene expression in response to endogenous and exogenous regulators, throughout the life-cycle. Studies using both genome-wide analysis of multiple genes and comprehensive analysis of specific genes are providing new insights into genetic and epigenetic mechanisms underlying nutrition and neuroscience. This review provides a critical evaluation of the following related areas: (1) recent advances in genomic and epigenomic technologies, and their relevance to brain disorders; (2) the emerging role of non-coding RNAs as key regulators of transcription, epigenetic processes and gene silencing; (3) novel approaches to nutrition, epigenetics and neuroscience; (4) gene-environment interactions, especially in the serotonergic system, as a paradigm of the multiple signalling pathways affected in neuropsychiatric and neurological disorders. Current and future advances in these four areas should contribute significantly to the prevention, amelioration and treatment of multiple devastating brain disorders. PMID:23503168

Rotator cuff disorders: How to write a surgically relevant magnetic resonance imaging report?

PubMed Central

Tawfik, Ahmed M; El-Morsy, Ahmad; Badran, Mohamed Aboelnour

2014-01-01

Evaluation of rotator cuff is a common indication for magnetic resonance imaging (MRI) scanning of the shoulder. Conventional MRI is the most commonly used technique, while magnetic resonance (MR) arthrography is reserved for certain cases. Rotator cuff disorders are thought to be caused by a combination of internal and external mechanisms. A well-structured MRI report should comment on the relevant anatomic structures including the acromial type and orientation, the presence of os acromiale, acromio-clavicular degenerative spurs and fluid in the subacromial subdeltoid bursa. In addition, specific injuries of the rotator cuff tendons and the condition of the long head of biceps should be accurately reported. The size and extent of tendon tears, tendon retraction and fatty degeneration or atrophy of the muscles are all essential components of a surgically relevant MRI report. PMID:24976930

Degenerative Changes of Spine in Helicopter Pilots

PubMed Central

Byeon, Joo Hyeon; Kim, Jung Won; Jeong, Ho Joong; Sim, Young Joo; Kim, Dong Kyu; Choi, Jong Kyoung; Im, Hyoung June

2013-01-01

Objective To determine the relationship between whole body vibration (WBV) induced helicopter flights and degenerative changes of the cervical and lumbar spine. Methods We examined 186 helicopter pilots who were exposed to WBV and 94 military clerical workers at a military hospital. Questionnaires and interviews were completed for 164 of the 186 pilots (response rate, 88.2%) and 88 of the 94 clerical workers (response rate, 93.6%). Radiographic examinations of the cervical and the lumbar spines were performed after obtaining informed consent in both groups. Degenerative changes of the cervical and lumbar spines were determined using four radiographs per subject, and diagnosed by two independent, blinded radiologists. Results There was no significant difference in general and work-related characteristics except for flight hours and frequency between helicopter pilots and clerical workers. Degenerative changes in the cervical spine were significantly more prevalent in the helicopter pilots compared with control group. In the cervical spine multivariate model, accumulated flight hours (per 100 hours) was associated with degenerative changes. And in the lumbar spine multivariate model, accumulated flight hours (per 100 hours) and age were associated with degenerative changes. Conclusion Accumulated flight hours were associated with degenerative changes of the cervical and lumbar spines in helicopter pilots. PMID:24236259

Personality characteristics and individual factors associated with PTSD in firefighters one month after extended wildfires.

PubMed

Psarros, Constantin; Theleritis, Christos; Kokras, Nikolaos; Lyrakos, Dimitris; Koborozos, Angelos; Kakabakou, Olga; Tzanoulinos, Georgios; Katsiki, Panagiota; Bergiannaki, Joanna Despoina

2018-01-01

Firefighters participate in activities with intense physical and psychological stress and are constantly at risk to develop various psychopathological reactions. To investigate psychological reactions in firefighters one month after devastating wildfires in Greece, during August 2007, which lead to the devastation of large areas and the death of 43 people among whom three were firefighters. One month after the wildfires, a joint task force of mental health clinicians was organized in order to provide psychological support and to investigate the psychological consequences of wildfires to firefighters. One hundred and two firefighters, living within the fire-devastated area, who were on duty for the whole period of wildfires were interviewed and assessed with the use of several questionnaires and inventories. Post-traumatic stress disorder (PTSD) was detected in 18.6% of firefighters. Multiple logistic regression found that existence of fear of dying during firefighting, insomnia and increased scores in neuroticism, as well as in depression subscale of the SCL-90, were significantly associated with greater likelihood for having PTSD. Additionally those firefighters who worked permanently had 70% lower probability of having PTSD vs. those seasonally employed. Insomnia, depressive symptoms, as well as personality characteristics as neuroticism and the perception of fear of imminent death during firefighting operations may precipitate the development of PTSD in firefighters. Within this context, mental health clinicians should be aware that the early detection of these predisposing factors may facilitate the prevention and mitigation of PTSD in firefighters particularly those who are seasonally employed.

Use of transfer learning to detect diffuse degenerative hepatic diseases from ultrasound images in dogs: A methodological study.

PubMed

Banzato, T; Bonsembiante, F; Aresu, L; Gelain, M E; Burti, S; Zotti, A

2018-03-01

The aim of this methodological study was to develop a deep convolutional neural network (DNN) to detect degenerative hepatic disease from ultrasound images of the liver in dogs and to compare the diagnostic accuracy of the newly developed DNN with that of serum biochemistry and cytology on the same samples, using histopathology as a standard. Dogs with suspected hepatic disease that had no prior history of neoplastic disease, no hepatic nodular pathology, no ascites and ultrasonography performed 24h prior to death were included in the study (n=52). Ultrasonography and serum biochemistry were performed as part of the routine clinical evaluation. On the basis of histopathology, dogs were categorised as 'normal' (n=8), or having 'vascular abnormalities'(n=8), or 'inflammatory'(n=0), 'neoplastic' (n=4) or 'degenerative'(n=32) disease; dogs with 'neoplastic' disease were excluded from further analysis. On cytological evaluation, dogs were categorised as 'normal' (n=11), or having 'inflammatory' (n=0), 'neoplastic' (n=4) or 'degenerative' (n=37) disease. Dogs were categorised as having 'degenerative' (n=32) or 'non-degenerative' (n=16) liver disease for analysis due to the limited sample size. The DNN was developed using a transfer learning methodology on a pre-trained neural network that was retrained and fine-tuned to our data set. The resultant DNN had a high diagnostic accuracy for degenerative liver disease (area under the curve 0.91; sensitivity 100%; specificity 82.8%). Cytology and serum biochemical markers (alanine transaminase and aspartate transaminase) had poor diagnostic accuracy in the detection of degenerative liver disease. The DNN outperformed all the other non-invasive diagnostic tests in the detection of degenerative liver disease. Copyright © 2018 Elsevier Ltd. All rights reserved.

Myelination, oligodendrocytes, and serious mental illness.

PubMed

Haroutunian, V; Katsel, P; Roussos, P; Davis, K L; Altshuler, L L; Bartzokis, G

2014-11-01

Historically, the human brain has been conceptually segregated from the periphery and further dichotomized into gray matter (GM) and white matter (WM) based on the whitish appearance of the exceptionally high lipid content of the myelin sheaths encasing neuronal axons. These simplistic dichotomies were unfortunately extended to conceptually segregate neurons from glia, cognition from behavior, and have been codified in the separation of clinical and scientific fields into medicine, psychiatry, neurology, pathology, etc. The discrete classifications have helped obscure the importance of continual dynamic communication between all brain cell types (neurons, astrocytes, microglia, oligodendrocytes, and precursor (NG2) cells) as well as between brain and periphery through multiple signaling systems. The signaling systems range from neurotransmitters to insulin, angiotensin, and multiple kinases such a glycogen synthase kinase 3 (GSK-3) that together help integrate metabolism, inflammation, and myelination processes and orchestrate the development, plasticity, maintenance, and repair that continually optimize function of neural networks. A more comprehensive, evolution-based, systems biology approach that integrates brain, body, and environmental interactions may ultimately prove more fruitful in elucidating the complexities of human brain function. The historic focus on neurons/GM is rebalanced herein by highlighting the importance of a systems-level understanding of the interdependent age-related shifts in both central and peripheral homeostatic mechanisms that can lead to remarkably prevalent and devastating neuropsychiatric diseases. Herein we highlight the role of glia, especially the most recently evolved oligodendrocytes and the myelin they produce, in achieving and maintaining optimal brain function. The human brain undergoes exceptionally protracted and pervasive myelination (even throughout its GM) and can thus achieve and maintain the rapid conduction and synchronous timing of neural networks on which optimal function depends. The continuum of increasing myelin vulnerability resulting from the human brain's protracted myelination underlies underappreciated communalities between different disease phenotypes ranging from developmental ones such as schizophrenia (SZ) and bipolar disorder (BD) to degenerative ones such as Alzheimer's disease (AD). These shared vulnerabilities also expose significant yet underexplored opportunities for novel treatment and prevention approaches that have the potential to considerably reduce the tremendous burden of neuropsychiatric disease. © 2014 Wiley Periodicals, Inc.

Fatal degenerative neurologic illnesses in men who participated in wild game feasts--Wisconsin, 2002.

PubMed

2003-02-21

Creutzfeldt-Jakob disease (CJD) is a fatal neurologic disorder in humans. CJD is one of a group of conditions known as transmissible spongiform encephalopathies (TSEs), or prion diseases, that are believed to be caused by abnormally configured, host-encoded prion proteins that accumulate in the central nervous tissue. CJD has an annual incidence of approximately 1 case per million population in the United States and occurs in three forms: sporadic, genetically determined, and acquired by infection. In the latter form, the incubation period is measured typically in years. Recent evidence that prion infection can cross the species barrier between humans and cattle has raised increasing public health concerns about the possible transmission to humans of a TSE among deer and elk known as chronic wasting disease (CWD). During 1993-1999, three men who participated in wild game feasts in northern Wisconsin died of degenerative neurologic illnesses. This report documents the investigation of these deaths, which was initiated in August 2002 and which confirmed the death of only one person from CJD. Although no association between CWD and CJD was found, continued surveillance of both diseases remains important to assess the possible risk for CWD transmission to humans.

Contralateral radiculopathy after transforaminal lumbar interbody fusion in the treatment of lumbar degenerative diseases: A Case Series.

PubMed

Hu, Hong-Tao; Ren, Liang; Sun, Xian-Ze; Liu, Feng-Yu; Yu, Jin-He; Gu, Zhen-Fang

2018-04-01

Transforaminal lumbar interbody fusion (TLIF) is an effective treatment for patients with degenerative lumbar disc disorder. Contralateral radiculopathy, as a complication of TLIF, has been recognized in this institution, but is rarely reported in the literature. In this article, we report 2 cases of contralateral radiculopathy after TLIF in our institution and its associated complications. In the 2 cases, the postoperative computed tomography (CT) and magnetic resonance image (MRI) showed obvious upward movement of the superior articular process, leading to contralateral foraminal stenosis. Revision surgery was done at once to partially resect the opposite superior facet and to relieve nerve root compression. After revision surgery, the contralateral radiculopathy disappeared. Contralateral radiculopathy is an avoidable potential complication. It is very important to create careful preoperative plans and to conscientiously plan the use of intraoperative techniques. In case of postoperative contralateral leg pain, the patients should be examined by CT and MRI. If CT and MRI show that the superior articular process significantly migrated upwards, which leads to contralateral foraminal stenosis, revision surgery should be done at once to partially resect the contralateral superior facet so as to relieve nerve root compression and avoid possible long-term impairment.

Stem cells as a novel tool for drug screening and treatment of degenerative diseases.

PubMed

Zuba-Surma, Ewa K; Wojakowski, Wojciech; Madeja, Zbigniew; Ratajczak, Mariusz Z

2012-01-01

Degenerative diseases similarly as acute tissue injuries lead to massive cell loss and may cause organ failure of vital organs (e.g., heart, central nervous system). Therefore, they belong to a group of disorders that may significantly benefit from stem cells (SCs)-based therapies. Several stem and progenitor cell populations have already been described as valuable tools for developing therapeutic strategies in regenerative medicine. In particular, pluripotent stem cells (PSCs), including adult-tissue-derived PSCs, neonatal-tissue-derived SCs, embryonic stem cells (ESCs), and recently described induced pluripotent stem cells (iPSCs), are the focus of particular attention because of their capacity to differentiate into all the cell lineages. Although PSCs are predominantly envisioned to be applied for organ regeneration, they may be also successfully employed in drug screening and disease modeling. In particular, adult PSCs and iPSCs derived from patient tissues may not only be a source of cells for autologous therapies but also for individual customized in vitro drug testing and studies on the molecular mechanisms of disease. In this review, we will focus on the potential applications of SCs, especially PSCs i) in regenerative medicine therapies, ii) in studying mechanisms of disease, as well as iii) in drug screening and toxicology tests that are crucial in new drug development. In particular, we will discuss the application of SCs in developing new therapeutic approaches to treat degenerative diseases of the neural system and heart. The advantage of adult PSCs in all the above-mentioned settings is that they can be directly harvested from patient tissues and used not only as a safe non-immunogenic source of cells for therapy but also as tools for personalized drug screening and pharmacological therapies.

Intravitreal Autologous Bone Marrow CD34+ Cell Therapy for Ischemic and Degenerative Retinal Disorders: Preliminary Phase 1 Clinical Trial Findings

PubMed Central

Park, Susanna S.; Bauer, Gerhard; Abedi, Mehrdad; Pontow, Suzanne; Panorgias, Athanasios; Jonnal, Ravi; Zawadzki, Robert J.; Werner, John S.; Nolta, Jan

2015-01-01

Purpose. Because human bone marrow (BM) CD34+ stem cells home into damaged tissue and may play an important role in tissue repair, this pilot clinical trial explored the safety and feasibility of intravitreal autologous CD34+ BM cells as potential therapy for ischemic or degenerative retinal conditions. Methods. This prospective study enrolled six subjects (six eyes) with irreversible vision loss from retinal vascular occlusion, hereditary or nonexudative age-related macular degeneration, or retinitis pigmentosa. CD34+ cells were isolated under Good Manufacturing Practice conditions from the mononuclear cellular fraction of the BM aspirate using a CliniMACs magnetic cell sorter. After intravitreal CD34+ cell injection, serial ophthalmic examinations, microperimetry/perimetry, fluorescein angiography, electroretinography (ERG), optical coherence tomography (OCT), and adaptive optics OCT were performed during the 6-month follow-up. Results. A mean of 3.4 million (range, 1–7 million) CD34+ cells were isolated and injected per eye. The therapy was well tolerated with no intraocular inflammation or hyperproliferation. Best-corrected visual acuity and full-field ERG showed no worsening after 6 months. Clinical examination also showed no worsening during follow-up except among age-related macular degeneration subjects in whom mild progression of geographic atrophy was noted in both the study eye and contralateral eye at 6-month follow-up, concurrent with some possible decline on multifocal ERG and microperimetry. Cellular in vivo imaging using adaptive optics OCT showed changes suggestive of new cellular incorporation into the macula of the hereditary macular degeneration study eye. Conclusions. Intravitreal autologous BM CD34+ cell therapy appears feasible and well tolerated in eyes with ischemic or degenerative retinal conditions and merits further exploration. (ClinicalTrials.gov number, NCT01736059.) PMID:25491299

Analysis of lumbar pedicle morphology in degenerative spines using multiplanar reconstruction computed tomography: what can be the reliable index for optimal pedicle screw diameter?

PubMed

Makino, Takahiro; Kaito, Takashi; Fujiwara, Hiroyasu; Yonenobu, Kazuo

2012-08-01

The measurement of transverse pedicle width is still recommended for selecting a screw diameter despite being weakly correlated with the minimum pedicle diameter, except in the upper lumbar spine. The purpose of this study was to reveal the difference between the minimum pedicle diameter and conventional transverse or sagittal pedicle width in degenerative lumbar spines. A total of 50 patients with degenerative lumbar disorders without spondylolysis or lumbar scoliosis of >10° who preoperatively underwent helical CT scans were included. The DICOM data of the scans were reconstructed by imaging software, and the transverse pedicle width (TPW), sagittal pedicle width (SPW), minimum pedicle diameter (MPD), and the cephalocaudal inclination of the pedicles were measured. The mean TPW/SPW/MPD values were 5.46/11.89/5.09 mm at L1, 5.76/10.44/5.39 mm at L2, 7.25/10.23/6.52 mm at L3, 9.01/9.36/6.83 mm at L4, and 12.86/8.95/7.36 mm at L5. There were significant differences between the TPW and MPD at L3, L4, and L5 (p < 0.01) and between the SPW and MPD at all levels (p < 0.01). The MPD was significantly smaller than the TPW and SPW at L3, L4, and L5. The actual measurements of the TPW were not appropriate for use as a direct index for the optimal pedicle screw diameter at these levels. Surgeons should be careful in determining pedicle screw diameter based on plain CT scans especially in the lower lumbar spine.

Visuo-proprioceptive interactions in degenerative cervical spine diseases requiring surgery.

PubMed

Freppel, S; Bisdorff, A; Colnat-Coulbois, S; Ceyte, H; Cian, C; Gauchard, G; Auque, J; Perrin, P

2013-01-01

Cervical proprioception plays a key role in postural control, but its specific contribution is controversial. Postural impairment was shown in whiplash injuries without demonstrating the sole involvement of the cervical spine. The consequences of degenerative cervical spine diseases are underreported in posture-related scientific literature in spite of their high prevalence. No report has focused on the two different mechanisms underlying cervicobrachial pain: herniated discs and spondylosis. This study aimed to evaluate postural control of two groups of patients with degenerative cervical spine diseases with or without optokinetic stimulation before and after surgical treatment. Seventeen patients with radiculopathy were recruited and divided into two groups according to the spondylotic or discal origin of the nerve compression. All patients and a control population of 31 healthy individuals underwent a static posturographic test with 12 recordings; the first four recordings with the head in 0° position: eyes closed, eyes open without optokinetic stimulation, with clockwise and counter clockwise optokinetic stimulations. These four sensorial situations were repeated with the head rotated 30° to the left and to the right. Patients repeated these 12 recordings 6weeks postoperatively. None of the patients reported vertigo or balance disorders before or after surgery. Prior to surgery, in the eyes closed condition, the herniated disc group was more stable than the spondylosis group. After surgery, the contribution of visual input to postural control in a dynamic visual environment was reduced in both cervical spine diseases whereas in a stable visual environment visual contribution was reduced only in the spondylosis group. The relative importance of visual and proprioceptive inputs to postural control varies according to the type of pathology and surgery tends to reduce visual contribution mostly in the spondylosis group. Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.

[Verbal communication disorders and language disorders in cortical dementias (I). The current state of the art in research].

PubMed

Benedet, M J

This is the first part of a research work into primary and secondary language disorders (LD) in the stages of minimum to mild pathological deterioration in the degenerative process of cortical dementias. AIMS. In this first part, in the light of recent models of symbolic computation of language processing, we review the most significant publications on the subject matter. We begin with an introduction to the historical development of the approaches used to deal with the subject. Following that, we briefly describe the components of the language processing system (LPS) in the light of symbolic computation models. We then analyse the publications dealing with those models. Our aim was to determine whether the LD reported in those publications are the result of a primary involvement of any of the LPS components, or whether they are only the result of disorders affecting other components of the cognitive system. In this case, the supposed LD would be secondary and thus a communication, but not language, disorder. Despite the important variations from one individual to another that have been systematically observed by different authors, it seems that only LD belonging to so called primary progressive aphasia are actually cases of this disorder. In all the other dementias in the above mentioned stages of the development process these disorders are secondary to the involvement of other subsystems of the LPS.

Distribution of lactate dehydrogenase in healthy and degenerative canine stifle joint cartilage.

PubMed

Walter, Eveline L C; Spreng, David; Schmöckel, Hugo; Schawalder, Peter; Tschudi, Peter; Friess, Armin E; Stoffel, Michael H

2007-07-01

In dogs, degenerative joint diseases (DJD) have been shown to be associated with increased lactate dehydrogenase (LDH) activity in the synovial fluid. The goal of this study was to examine healthy and degenerative stifle joints in order to clarify the origin of LDH in synovial fluid. In order to assess the distribution of LDH, cartilage samples from healthy and degenerative knee joints were investigated by means of light and transmission electron microscopy in conjunction with immunolabeling and enzyme cytochemistry. Morphological analysis confirmed DJD. All techniques used corroborated the presence of LDH in chondrocytes and in the interterritorial matrix of healthy and degenerative stifle joints. Although enzymatic activity of LDH was clearly demonstrated in the territorial matrix by means of the tetrazolium-formazan reaction, immunolabeling for LDH was missing in this region. With respect to the distribution of LDH in the interterritorial matrix, a striking decrease from superficial to deeper layers was present in healthy dogs but was missing in affected joints. These results support the contention that LDH in synovial fluid of degenerative joints originates from cartilage. Therefore, we suggest that (1) LDH is transferred from chondrocytes to ECM in both healthy dogs and dogs with degenerative joint disease and that (2) in degenerative joints, LDH is released from chondrocytes and the ECM into synovial fluid through abrasion of cartilage as well as through enhanced diffusion as a result of increased water content and degradation of collagen.

Telomeres and age-related disease: how telomere biology informs clinical paradigms

PubMed Central

Armanios, Mary

2013-01-01

Telomere length shortens with age and predicts the onset of replicative senescence. Recently, short telomeres have been linked to the etiology of degenerative diseases such as idiopathic pulmonary fibrosis, bone marrow failure, and cryptogenic liver cirrhosis. These disorders have recognizable clinical manifestations, and the telomere defect explains their genetics and informs the approach to their treatment. Here, I review how telomere biology has become intimately connected to clinical paradigms both for understanding pathophysiology and for individualizing therapy decisions. I also critically examine nuances of interpreting telomere length measurement in clinical studies. PMID:23454763

Inclusion body myositis.

PubMed

Dimachkie, Mazen M; Barohn, Richard J

2014-08-01

The idiopathic inflammatory myopathies (IIMs) are a heterogeneous group of rare disorders that share many similarities. In addition to sporadic inclusion body myositis (IBM), these include dermatomyositis, polymyositis, and autoimmune necrotizing myopathy. IBM is the most common IIM after age 50 years. Muscle histopathology shows endomysial inflammatory exudates surrounding and invading nonnecrotic muscle fibers often accompanied by rimmed vacuoles and protein deposits. It is likely that IBM is has a prominent degenerative component. This article reviews the evolution of knowledge in IBM, with emphasis on recent developments in the field, and discusses ongoing clinical trials. Copyright © 2014 Elsevier Inc. All rights reserved.

Deriving excitatory neurons of the neocortex from pluripotent stem cells

PubMed Central

Hansen, David V.; Rubenstein, John L.R.; Kriegstein, Arnold R.

2011-01-01

The human cerebral cortex is an immensely complex structure that subserves critical functions that can be disrupted in developmental and degenerative disorders. Recent innovations in cellular reprogramming and differentiation techniques have provided new ways to study the cellular components of the cerebral cortex. Here we discuss approaches to generate specific subtypes of excitatory cortical neurons from pluripotent stem cells. We review spatial and temporal aspects of cortical neuron specification that can guide efforts to produce excitatory neuron subtypes with increased resolution. Finally, we discuss distinguishing features of human cortical development and their translational ramifications for cortical stem cell technologies. PMID:21609822

Impulsive Behavior and Associated Clinical Variables in Parkinson's Disease

PubMed Central

Abosch, Aviva; Gupte, Akshay; Eberly, Lynn E.; Tuite, Paul J.; Nance, Martha; Grant, Jon E.

2011-01-01

Parkinson's disease (PD) is a degenerative brain disorder accompanied by the loss of dopaminergic neurons and the presence of motor and non-motor symptoms. We performed a cross-sectional, questionnaire-based analysis of impulsive behavior in our PD clinic population to assess prevalence and associated characteristics. We found a higher prevalence of impulsive behavior (29.7%) than previously reported, and found multiple, concurrent impulsive behaviors in 26% of subjects reporting impulsive behavior. Our findings contribute to the growing awareness of impulsive behavior in PD, and support the need for longitudinal studies to assess changes in impulsive behaviors in Parkinson's patients. PMID:21300194

Professor Eric Can't See: A Project-Based Learning Case for Neurobiology Students.

PubMed

Ogilvie, Judith Mosinger; Ribbens, Eric

2016-01-01

"Professor Eric Can't See" is a semi-biographical case study written for an upper level undergraduate Neurobiology of Disease course. The case is integrated into a unit using a project-based learning approach to investigate the retinal degenerative disorder Retinitis pigmentosa and the visual system. Some case study scenes provide specific questions for student discussion and problem-based learning, while others provide background for student inquiry and related active learning exercises. The case was adapted from "'Chemical Eric' Can't See," and could be adapted for courses in general neuroscience or sensory neuroscience.

Biomedical, translational and clinical research on PDT of TMJ

NASA Astrophysics Data System (ADS)

Kamenoff, J.

2017-02-01

Electromagnetic energy of laser light has some typical properties which are found to be a premise for discussions on laser irradiation abilities to control the severe and chronic disorders in TMJ. In world literature PDT application is recommended when soft tissues in TMJ are damaged, in cases of degenerative diseases of discus articularis, medial and lateral distensions of joint ligaments, chronic inflammatory processes in TMJ, occlusion trauma, etc. The aim of our clinical study was to analyze the theoretical achievements up to now in depth and basing on our clinic al observations suggest new methods guaranteeing high therapeutic efficacy of Photodynamic therapy.

Two novel mutations in the Norrie disease gene associated with the classical ocular phenotype.

PubMed

Caballero, M; Veske, A; Rodriguez, J J; Lugo, N; Schroeder, B; Hesse, L; Gal, A

1996-12-01

Norrie disease (ND) is a rare X-linked recessive disorder characterized by congenital blindness due to a degenerative and proliferative dysplasia of the neuroretina and, occasionally, by deafness and mental handicap. Here, we report two novel mutations detected in patients with the classical eye features of ND. Both the one-base pair insertion in exon II (544/545 insA) and the two-base pair deletion in the start codon (418delTG) of the ND gene predict a functional 'null allele', i.e. the complete absence of the corresponding gene product.

PREPARE: presurgery physiotherapy for patients with degenerative lumbar spine disorder: a randomized controlled trial.

PubMed

Lindbäck, Yvonne; Tropp, Hans; Enthoven, Paul; Abbott, Allan; Öberg, Birgitta

2017-12-15

Surgery because of disc herniation or spinal stenosis results mostly in large improvement in the short-term, but mild to moderate improvements for pain and disability at long-term follow-up. Prehabilitation has been defined as augmenting functional capacity before surgery, which may have beneficial effect on outcome after surgery. The aim was to study if presurgery physiotherapy improves function, pain, and health in patients with degenerative lumbar spine disorder scheduled for surgery. A single-blinded, two-arm, randomized controlled trial (RCT). A total of 197 patients were consecutively included at a spine clinic. The inclusion criteria were patients scheduled for surgery because of disc herniation, spinal stenosis, spondylolisthesis, or degenerative disc disease (DDD), 25-80 years of age. Primary outcome was Oswestry Disability Index (ODI). Secondary outcomes were pain intensity, anxiety, depression, self-efficacy, fear avoidance, physical activity, and treatment effect. Patients were randomized to either presurgery physiotherapy or standardized information, with follow-up after the presurgery intervention as well as 3 and 12 months post surgery. The study was funded by regional research funds for US$77,342. No conflict of interest is declared. The presurgery physiotherapy group had better ODI, visual analog scale (VAS) back pain, EuroQol-5D (EQ-5D), EQ-VAS, Fear Avoidance Belief Questionnaire-Physical Activity (FABQ-PA), Self-Efficacy Scale (SES), and Hospital Anxiety and Depression Scale (HADS) depression scores and activity level compared with the waiting-list group after the presurgery intervention. The improvements were small, but larger than the study-specific minimal clinical important change (MCIC) in VAS back and leg pain, EQ-5D, and FABQ-PA, and almost in line with MCIC in ODI and Physical Component Summary (PCS) in the physiotherapy group. Post surgery, the only difference between the groups was higher activity level in the physiotherapy group compared with the waiting-list group. Presurgery physiotherapy decreases pain, risk of avoidance behavior, and worsening of psychological well-being, and improves quality of life and physical activity levels before surgery compared with waiting-list controls. These results were maintained only for activity levelspost surgery. Still, presurgery selection, content, dosage of exercises, and importance of being active in a presurgery physiotherapy intervention is of interest to study further to improve long-term outcome. Copyright © 2017 Elsevier Inc. All rights reserved.

Label-free characterization of degenerative changes in articular cartilage by Raman spectroscopy

NASA Astrophysics Data System (ADS)

Oshima, Yusuke; Akehi, Mayu; Kiyomatsu, Hiroshi; Miura, Hiromasa

2017-04-01

Osteoarthritis (OA) is very common joint disease in the aging population. Main symptom of OA is accompanied by degenerative changes of articular cartilage. Raman spectroscopy is a label-free technique which enables to analyze molecular composition in degenerative cartilage. We generated an animal OA model surgically induced by knee joint instability and performed Raman spectroscopic analysis for the articular cartilage. In the result, Raman spectral data of the articular cartilage showed drastic changes in comparison between OA and control side. The relative intensity of phosphate band increases in the degenerative cartilage.

Bovine Progressive Degenerative Myeloencephalopathy (Weaver Syndrome) in Brown Swiss Cattle in Canada: A Literature Review and Case Report

PubMed Central

Baird, John D.; Sarmiento, Ulla M.; Basrur, Parvathi K.

1988-01-01

A 15-month-old purebred Brown Swiss heifer was presented because of posterior paresis and ataxia. Histopathological examination of the brain and spinal cord showed evidence of a mild diffuse degenerative myeloencephalopathy. The most severe degenerative lesions were located in the white matter of the thoracic spinal cord. We believe this to be the first documented case of bovine progressive degenerative myeloencephalopathy (“weaver syndrome”) in Canada. ImagesFigure 1.Figure 2., Figure 3., Figure 4.Figure 5. PMID:17423028

Contribution of Microglia-Mediated Neuroinflammation to Retinal Degenerative Diseases

PubMed Central

Madeira, Maria H.; Boia, Raquel; Santos, Paulo F.; Ambrósio, António F.; Santiago, Ana R.

2015-01-01

Retinal degenerative diseases are major causes of vision loss and blindness worldwide and are characterized by chronic and progressive neuronal loss. One common feature of retinal degenerative diseases and brain neurodegenerative diseases is chronic neuroinflammation. There is growing evidence that retinal microglia, as in the brain, become activated in the course of retinal degenerative diseases, having a pivotal role in the initiation and propagation of the neurodegenerative process. A better understanding of the events elicited and mediated by retinal microglia will contribute to the clarification of disease etiology and might open new avenues for potential therapeutic interventions. This review aims at giving an overview of the roles of microglia-mediated neuroinflammation in major retinal degenerative diseases like glaucoma, age-related macular degeneration, and diabetic retinopathy. PMID:25873768

Natural Modulators of Amyloid-Beta Precursor Protein Processing

PubMed Central

Zhang, Can; Tanzi, Rudolph E.

2013-01-01

Alzheimer’s disease (AD) is a devastating neurodegenerative disease and the primary cause of dementia, with no cure currently available. The pathogenesis of AD is believed to be primarily driven by Aβ, the principal component of senile plaques. Aβ is an ~4 kDa peptide generated from the amyloid-β precursor protein (APP) through proteolytic secretases. Natural products, particularly those utilized in traditional Chinese medicine (TCM), have a long history alleviating common clinical disorders, including dementia. However, the cell/molecular pathways mediated by these natural products are largely unknown until recently when the underlying molecular mechanisms of the disorders begin to be elucidated. Here, the mechanisms with which natural products modulate the pathogenesis of AD are discussed, in particular, by focusing on their roles in the processing of APP. PMID:22998566

Proteomic Approaches to Enable Point-of-Care Testing and Personalized Medicine for Psychiatric Disorders.

PubMed

Guest, Francesca L; Guest, Paul C

2017-01-01

This chapter describes how innovations that are driven by proteomic biomarker techniques can facilitate earlier and better treatment of patients who suffer from psychiatric disorders. The application of new micro-fluidic devices along with miniaturized biosensors and transducers will enable the development of handheld point-of-care testing instruments which can analyse a drop of a blood within the time span of a single visit to the doctor's office. It is anticipated that these approaches will incorporate both biochemical and clinical information, resulting in unique profiles for each test subject. These profiles can in turn be used to drive personalized medicine approaches in this devastating disease area. In addition, smartphone applications (apps) for self-monitoring will see increasing use for improved patient outcomes.

Rebalancing the Addicted Brain: Oxytocin Interference with the Neural Substrates of Addiction.

PubMed

Bowen, Michael T; Neumann, Inga D

2017-12-01

Drugs that act on the brain oxytocin (OXT) system may provide a much-needed treatment breakthrough for substance-use disorders. Targeting the brain OXT system has the potential to treat addiction to all major classes of addictive substance and to intervene across all stages of the addiction cycle. Emerging evidence suggests that OXT is able to interfere with such a wide range of addictive behaviours for such a wide range of addictive substances by rebalancing core neural systems that become dysregulated over the course of addiction. By improving our understanding of these interactions between OXT and the neural substrates of addiction, we will not only improve our understanding of addiction, but also our ability to effectively treat these devastating disorders. Copyright © 2017 Elsevier Ltd. All rights reserved.

Lung Fibroblasts, Aging, and Idiopathic Pulmonary Fibrosis.

PubMed

Pardo, Annie; Selman, Moisés

2016-12-01

Idiopathic pulmonary fibrosis (IPF) is an aging-associated, progressive, and irreversible lung disease of unknown etiology, elusive pathogenesis, and very limited therapeutic options. The hallmarks of IPF are aberrant activation of alveolar epithelial cells and accumulation of fibroblasts and myofibroblasts along with excessive production of extracellular matrix. The linkage of aging with this disorder is uncertain, but a number of changes associated with aging, including telomere attrition, cell senescence, and mitochondrial dysfunction, have been revealed in IPF lungs. Also, aging seems to confer a profibrotic phenotype upon fibroblasts and to increase the severity of the fibrogenic response in non-IPF fibrotic lung disorders. Better knowledge of the pathophysiological mechanisms linking aging to IPF will advance understanding of its pathogenesis and may provide new therapeutic windows to treatment of this devastating disease.

[New Forms of Hysteria: Globalization, Market and the Comeback of Hysteria].

PubMed

Ortega, Lucio González

2012-09-01

Hysterical disorder has had different interpretations and therapeutic approaches according to the different cultural contexts. In the Middle Ages, hysteria was conceived as devilish possessions whose symptoms became a sort of veracity certificate for the era's cultural pillar: the Bible. During Renaissance, hysteria obeys a new master: Science, dramatizing the neurological degenerative injuries to give reputation to physicians of the time. There is a kind of consensus: hysteria is an ever less observable disorder in consultation. It has practically disappeared in the North American Diagnosis Manual, DSM-IV. We wonder, has hysteria as such disappeared? Has it gotten new expressions? Psychoanalytic review of hysteria, followed by a qualitative, historical and hermeneutic study. In these days of globalization, science is not the master anymore; instead, science is at the service of computing and market. The market biggest sellers are: depressive and anxious disorders, bulimia, anorexia, fibromyalgia, sexual drawbacks, somatoform disorders and extreme exhaustion disorder. Hysteria, raising bewilderment in modern medicine, comes back, cut up into pieces, in the form of these multiple disorders. Not only hysteria has not disappeared, but it has increased in consultation, almost perfect simulation of the disorders most promoted by capitalistic markets, granting power to the new master. Subsequently, its powerlessness is denounced, nothing alleviates said disorders. As Freud stated, the problem lies in the fact that this word does not have a receiver to decipher it. Copyright © 2012 Asociación Colombiana de Psiquiatría. Publicado por Elsevier España. All rights reserved.

Ocular manifestations of drug and alcohol abuse

PubMed Central

Peragallo, Jason; Biousse, Valérie; Newman, Nancy J.

2015-01-01

Purpose of review To review commonly encountered adverse ocular effects of illicit drug use. Recent findings Drug and alcohol abuse can produce a variety of ocular and neuro-ophthalmic side effects. Novel, so-called “designer,” drugs of abuse can lead to unusual ocular disorders. Legal substances, when used in manners for which they have not been prescribed, can also have devastating ophthalmic consequences. Summary In this review we will systematically evaluate each part of the visual pathways and discuss how individual drugs may affect them. PMID:24100364

Biosafety of Prions.

PubMed

Bistaffa, Edoardo; Rossi, Martina; De Luca, Chiara M G; Moda, Fabio

2017-01-01

Prions are the infectious agents that cause devastating and untreatable disorders known as Transmissible Spongiform Encephalopathies (TSEs). The pathologic events and the infectious nature of these transmissible agents are not completely understood yet. Due to the difficulties in inactivating prions, working with them requires specific recommendations and precautions. Moreover, with the advent of innovative technologies, such as the Protein Misfolding Cyclic Amplification (PMCA) and the Real Time Quaking-Induced Conversion (RT-QuIC), prions could be amplified in vitro and the infectious features of the amplified products need to be carefully assessed. © 2017 Elsevier Inc. All rights reserved.

Teenage constipation: a case study.

PubMed

Streeter, Bonnie L

2002-01-01

Constipation is a problem of significant magnitude. It can have a devastating impact on a patient's personal life. There are many causes of constipation. Among them are dietary factors such as decreased fiber and low fluid intake, decreased activity, lack of privacy for defecation, pharmacologic agents, physiologic problems such as bowel obstruction or metabolic disorders, and psychosocial distress. A young teenage boy is followed through a series of emergency room visits, office visits, and a hospitalization related to his experiences with constipation. A bowel program was identified and instituted with successful outcomes.

Treating pediatric neuromuscular disorders: The future is now

PubMed Central

D. Gonorazky, Hernan; Cohn, Ronald D.; Campbell, Craig

2017-01-01

Pediatric neuromuscular diseases encompass all disorders with onset in childhood and where the primary area of pathology is in the peripheral nervous system. These conditions are largely genetic in etiology, and only those with a genetic underpinning will be presented in this review. This includes disorders of the anterior horn cell (e.g., spinal muscular atrophy), peripheral nerve (e.g., Charcot–Marie–Tooth disease), the neuromuscular junction (e.g., congenital myasthenic syndrome), and the muscle (myopathies and muscular dystrophies). Historically, pediatric neuromuscular disorders have uniformly been considered to be without treatment possibilities and to have dire prognoses. This perception has gradually changed, starting in part with the discovery and widespread application of corticosteroids for Duchenne muscular dystrophy. At present, several exciting therapeutic avenues are under investigation for a range of conditions, offering the potential for significant improvements in patient morbidities and mortality and, in some cases, curative intervention. In this review, we will present the current state of treatment for the most common pediatric neuromuscular conditions, and detail the treatment strategies with the greatest potential for helping with these devastating diseases. PMID:28889642

Models for discovery of targeted therapy in genetic epileptic encephalopathies.

PubMed

Maljevic, Snezana; Reid, Christopher A; Petrou, Steven

2017-10-01

Epileptic encephalopathies are severe disorders emerging in the first days to years of life that commonly include refractory seizures, various types of movement disorders, and different levels of developmental delay. In recent years, many de novo occurring variants have been identified in individuals with these devastating disorders. To unravel disease mechanisms, the functional impact of detected variants associated with epileptic encephalopathies is investigated in a range of cellular and animal models. This review addresses efforts to advance and use such models to identify specific molecular and cellular targets for the development of novel therapies. We focus on ion channels as the best-studied group of epilepsy genes. Given the clinical and genetic heterogeneity of epileptic encephalopathy disorders, experimental models that can reflect this complexity are critical for the development of disease mechanisms-based targeted therapy. The convergence of technological advances in gene sequencing, stem cell biology, genome editing, and high throughput functional screening together with massive unmet clinical needs provides unprecedented opportunities and imperatives for precision medicine in epileptic encephalopathies. © 2017 International Society for Neurochemistry.

Placental Barrier and Autism Spectrum Disorders: The Role of Prolactin and Dopamine on the Developing Fetal Brain.

PubMed

Yarlagadda, Atmaram; Acharya, Ganesh; Kasaraneni, Jayaprada; Hampe, Christiane S; Clayton, Anita H

2015-01-01

Dopamine and prolactin exhibit opposite effects on lactation. However, a possible role for increased prolactin/dopamine ratio in postpartum mood and thought disorders and as a prognostic indicator of the mother's future mental health has not been well investigated. Postpartum depression is a serious condition with potentially devastating outcomes for both the mother and the infant. Early detection and treatment of this condition can have impressive results. Treatment options include antidepressant medications for mood disorders and use of antipsychotics and electroconvulsive therapy to address postpartum psychosis. Although there are obvious benefits of such treatments on the welfare of the mother and her child, broader implications of these treatments on lactation and child growth and development are not known. This review article explores a possible link between in-utero exposure to a high maternal prolactin/dopamine ratio and subsequent development of autism spectrum disorders. We hypothesize that a comprehensive, biologically oriented approach to the use of psychotropics in the regulation of neurotransmission during pre- and postpartum periods may result in better outcomes in this population.

Partitioning heritability analysis reveals a shared genetic basis of brain anatomy and schizophrenia

PubMed Central

Lee, Phil H.; Baker, Justin T.; Holmes, Avram J.; Jahanshad, Neda; Ge, Tian; Jung, Jae-Yoon; Cruz, Yanela; Manoach, Dara S.; Hibar, Derrek P.; Faskowitz, Joshua; McMahon, Katie L.; de Zubicaray, Greig I.; Martin, Nicolas H.; Wright, Margaret J.; Öngür, Dost; Buckner, Randy; Roffman, Joshua; Thompson, Paul M.; Smoller, Jordan W.

2016-01-01

Schizophrenia is a devastating neurodevelopmental disorder with a complex genetic etiology. Widespread cortical gray matter loss has been observed in patients and prodromal samples. However, it remains unresolved whether schizophrenia-associated cortical structure variations arise due to disease etiology or secondary to the illness. Here we address this question using a partitioning-based heritability analysis of genome-wide SNP and neuroimaging data from 1,750 healthy individuals. We find that schizophrenia-associated genetic variants explain a significantly enriched proportion of trait heritability in eight brain phenotypes (FDR=10%). In particular, intracranial volume (ICV) and left superior frontal gyrus thickness exhibit significant and robust associations with schizophrenia genetic risk under varying SNP selection conditions. Cross disorder comparison suggests that the neurogenetic architecture of schizophrenia-associated brain regions is, at least in part, shared with other psychiatric disorders. Our study highlights key neuroanatomical correlates of schizophrenia genetic risk in the general population. These may provide fundamental insights into the complex pathophysiology of the illness, and a potential link to neurocognitive deficits shaping the disorder. PMID:27725656

Partitioning heritability analysis reveals a shared genetic basis of brain anatomy and schizophrenia.

PubMed

Lee, P H; Baker, J T; Holmes, A J; Jahanshad, N; Ge, T; Jung, J-Y; Cruz, Y; Manoach, D S; Hibar, D P; Faskowitz, J; McMahon, K L; de Zubicaray, G I; Martin, N H; Wright, M J; Öngür, D; Buckner, R; Roffman, J; Thompson, P M; Smoller, J W

2016-12-01

Schizophrenia is a devastating neurodevelopmental disorder with a complex genetic etiology. Widespread cortical gray matter loss has been observed in patients and prodromal samples. However, it remains unresolved whether schizophrenia-associated cortical structure variations arise due to disease etiology or secondary to the illness. Here we address this question using a partitioning-based heritability analysis of genome-wide single-nucleotide polymorphism (SNP) and neuroimaging data from 1750 healthy individuals. We find that schizophrenia-associated genetic variants explain a significantly enriched proportion of trait heritability in eight brain phenotypes (false discovery rate=10%). In particular, intracranial volume and left superior frontal gyrus thickness exhibit significant and robust associations with schizophrenia genetic risk under varying SNP selection conditions. Cross-disorder comparison suggests that the neurogenetic architecture of schizophrenia-associated brain regions is, at least in part, shared with other psychiatric disorders. Our study highlights key neuroanatomical correlates of schizophrenia genetic risk in the general population. These may provide fundamental insights into the complex pathophysiology of the illness, and a potential link to neurocognitive deficits shaping the disorder.

Degenerative changes of the canine cervical spine after discectomy procedures, an in vivo study.

PubMed

Grunert, Peter; Moriguchi, Yu; Grossbard, Brian P; Ricart Arbona, Rodolfo J; Bonassar, Lawrence J; Härtl, Roger

2017-06-23

Discectomies are a common surgical treatment for disc herniations in the canine spine. However, the effect of these procedures on intervertebral disc tissue is not fully understood. The objective of this study was to assess degenerative changes of cervical spinal segments undergoing discectomy procedures, in vivo. Discectomies led to a 60% drop in disc height and 24% drop in foraminal height. Segments did not fuse but showed osteophyte formation as well as endplate sclerosis. MR imaging revealed terminal degenerative changes with collapse of the disc space and loss of T2 signal intensity. The endplates showed degenerative type II Modic changes. Quantitative MR imaging revealed that over 95% of Nucleus Pulposus tissue was extracted and that the nuclear as well as overall disc hydration significantly decreased. Histology confirmed terminal degenerative changes with loss of NP tissue, loss of Annulus Fibrosus organization and loss of cartilage endplate tissue. The bony endplate displayed sclerotic changes. Discectomies lead to terminal degenerative changes. Therefore, these procedures should be indicated with caution specifically when performed for prophylactic purposes.

Pattern of eye diseases among welders in a Nigeria community.

PubMed

Ajayi Iyiade, A; Omotoye Olusola, J

2012-06-01

Welders have been identified as a high risk group for eye disorders due to their exposure to ultraviolet radiation. To determine the prevalence and types of eye diseases amongst welders in Ile-Ife, Osun state. This is a cross sectional descriptive study of 405 consenting welders. Information on socio-demographic characteristics was obtained using a pre-tested proforma and all subjects had visual actuity test, anterior and posterior segments examination, test of stereopsis and macular function. Two hundred and seventy five (67.9%) of the respondents were arc welders, 99(22.5%) were gas welders while 39(9.6%) utilized both welding techniques. The age of the respondents ranged from 16 years to 80 years with a mean of 38 ± 13 years. Conjunctival degenerative disorders like pingueculum (50.1%) and pterygium(17.5%) constituted the commonest eye disorders among the welders. There were 6 blind eyes of 5 welders with pigmentary maculopathy accounting for the single case of bilateral blindness. There is a greater odd in developing pingueculum and Pterygium (OR=1.015, 1.039 respectively) in arc welders than in gas welders. Pingueculum, Pterygium, corneal opacity, and pigmentary macular deposits were the common eye disorders among welders.

Drawing Disorders in Alzheimer's Disease and Other Forms of Dementia.

PubMed

Trojano, Luigi; Gainotti, Guido

2016-04-21

Drawing is a multicomponential process that can be impaired by many kinds of brain lesions. Drawing disorders are very common in Alzheimer's disease and other forms of dementia, and can provide clinical information for the distinction of the different dementing diseases. In our review we started from an overview of the neural and cognitive bases of drawing, and from a recollection of the drawing tasks more frequently used for assessing individuals with dementia. Then, we analyzed drawing disorders in dementia, paying special attention to those observed in Alzheimer's disease, from the prodromal stages of the amnesic mild cognitive impairment to the stages of full-blown dementia, both in the sporadic forms with late onset in the entorhino-hippocampal structures and in those with early onset in the posterior neocortical structures. We reviewed the drawing features that could differentiate Alzheimer's disease from vascular dementia and from the most frequent forms of degenerative dementia, namely frontotemporal dementia and Lewy body disease. Finally, we examined some peculiar aspects of drawing disorders in dementia, such as perseverations, rotations, and closing-in. We argue that a careful analysis of drawing errors helps to differentiate the different forms of dementia more than overall accuracy in drawing.

Detection of degenerative change in lateral projection cervical spine x-ray images

NASA Astrophysics Data System (ADS)

Jebri, Beyrem; Phillips, Michael; Knapp, Karen; Appelboam, Andy; Reuben, Adam; Slabaugh, Greg

2015-03-01

Degenerative changes to the cervical spine can be accompanied by neck pain, which can result from narrowing of the intervertebral disc space and growth of osteophytes. In a lateral x-ray image of the cervical spine, degenerative changes are characterized by vertebral bodies that have indistinct boundaries and limited spacing between vertebrae. In this paper, we present a machine learning approach to detect and localize degenerative changes in lateral x-ray images of the cervical spine. Starting from a user-supplied set of points in the center of each vertebral body, we fit a central spline, from which a region of interest is extracted and image features are computed. A Random Forest classifier labels regions as degenerative change or normal. Leave-one-out cross-validation studies performed on a dataset of 103 patients demonstrates performance of above 95% accuracy.

Serum protein profiling and proteomics in autistic spectrum disorder using magnetic bead-assisted mass spectrometry.

PubMed

Taurines, Regina; Dudley, Edward; Conner, Alexander C; Grassl, Julia; Jans, Thomas; Guderian, Frank; Mehler-Wex, Claudia; Warnke, Andreas; Gerlach, Manfred; Thome, Johannes

2010-04-01

The pathophysiology of autistic spectrum disorder (ASD) is not fully understood and there are no diagnostic or predictive biomarkers. Proteomic profiling has been used in the past for biomarker research in several non-psychiatric and psychiatric disorders and could provide new insights, potentially presenting a useful tool for generating such biomarkers in autism. Serum protein pre-fractionation with C8-magnetic beads and protein profiling by matrix-assisted laser desorption/ionisation-time of flight-mass spectrometry (MALDI-ToF-MS) were used to identify possible differences in protein profiles in patients and controls. Serum was obtained from 16 patients (aged 8-18) and age-matched controls. Three peaks in the MALDI-ToF-MS significantly differentiated the ASD sample from the control group. Sub-grouping the ASD patients into children with and without comorbid Attention Deficit and Hyperactivity Disorder, ADHD (ASD/ADHD+ patients, n = 9; ASD/ADHD- patients, n = 7), one peak distinguished the ASD/ADHD+ patients from controls and ASD/ADHD- patients. Our results suggest that altered protein levels in peripheral blood of patients with ASD might represent useful biomarkers for this devastating psychiatric disorder.

Longitudinal assessment of retinal structure and function reveals a rod-cone degeneration in a guinea pig model initially presented as night blind.

PubMed

Racine, Julie; Joly, Sandrine; Lachapelle, Pierre

2011-08-01

We have previously reported a naturally occurring retinopathy in a population of guinea pigs, where the affected animals presented a defect of the rod-mediated vision. The purpose of this study was to investigate if the mutants were affected with a stationary or degenerative retinopathy and to identify the cellular origin of this unique disorder. Electroretinogram (ERG) [postnatal day 1 (P1) to P450], light (LM) and electron microscopy (EM) [P5, P150, P450], and immunohistochemistry [P30, P150, P450] were evaluated from normal and mutant animals. Irrespective of age, the scotopic ERGs of mutants could only be evoked by bright flashes, and the resulting ERGs were of photopic waveform. Interestingly, the amplitude of the cone and the rod/cone a-waves was always of smaller amplitude in mutants, but this difference tended to decrease with age. In contrast, the b-waves were of larger amplitude than normal in photopic ERGs obtained prior to age 25 (days) and prior to age 10 for rod/cone ERGs. LM revealed, in mutants, an absence of the outer segment layer (OSL) with a reduction in the outer nuclear layer (ONL) thickness. EM disclosed the presence of cone outer segment (OS) while no rod OS could be evidenced. Immunohistochemistry revealed the presence of rhodopsin, both cone opsins as well as normal synaptophysin immunoreactivity. Finally, neither the retinal structure nor the function in the mutants achieved normal development. Results suggest that mutant animals are suffering from a degenerative retinal disorder that affects the structure and function of rods and cones.

Transplanting Retinal Cells using Bucky Paper for Support

NASA Technical Reports Server (NTRS)

Loftus, David J.; Cinke, Martin; Meyyappan, Meyya; Fishman, Harvey; Leng, Ted; Huie, Philip; Bilbao, Kalayaan

2004-01-01

A novel treatment for retinal degenerative disorders involving transplantation of cells into the eye is currently under development at NASA Ames Research Center and Stanford University School of Medicine. The technique uses bucky paper as a support material for retinal pigment epithelial (RPE) cells, iris pigment epithelial (IPE) cells, and/or stem cells. This technology is envisioned as a treatment for age-related macular degeneration, which is the leading cause of blindness in persons over age 65 in Western nations. Additionally, patients with other retinal degenerative disorders, such as retinitis pigmentosa, may be treated by this strategy. Bucky paper is a mesh of carbon nanotubes (CNTs), as shown in Figure 1, that can be made from any of the commercial sources of CNTs. Bucky paper is biocompatible and capable of supporting the growth of biological cells. Because bucky paper is highly porous, nutrients, oxygen, carbon dioxide, and waste can readily diffuse through it. The thickness, density, and porosity of bucky paper can be tailored in manufacturing. For transplantation of cells into the retina, bucky paper serves simultaneously as a substrate for cell growth and as a barrier for new blood vessel formation, which can be a problem in the exudative type of macular degeneration. Bucky paper is easily handled during surgical implantation into the eye. Through appropriate choice of manufacturing processes, bucky paper can be made relatively rigid yet able to conform to the retina when the bucky paper is implanted. Bucky paper offers a distinct advantage over other materials that have been investigated for retinal cell transplantation - lens capsule and Descemet's membrane - which are difficult to handle during surgery because they are flimsy and do not stay flat.

High-resolution ultrasonography in assessing temporomandibular joint disc position.

PubMed

Talmaceanu, Daniel; Lenghel, Lavinia Manuela; Bolog, Nicolae; Popa Stanila, Roxana; Buduru, Smaranda; Leucuta, Daniel Corneliu; Rotar, Horatiu; Baciut, Mihaela; Baciut, Grigore

2018-02-04

The purpose of this study was to determine the diagnostic value of high-resolution ultrasonography (US) in temporomandibular joint (TMJ) disc displacements. A number of 74 patients (148 TMJs) with signs and symptoms of TMJ disorders, according to the Research Diagnostic Criteria for Temporomandibular Disorders, were included in this study. All patients received US and magnetic resonance imaging (MRI) of both TMJs 1 to 5 days after the clinical examination. MRI examinations were performed using 1.5 T MRI equipment (Siemens Avanto, Siemens, Erlangen). Ultrasonographic examination was performed on a Hitachi EUB 8500 (Hitachi Medical Corp., Tokyo, Japan) scanner with L 54 M6.5-13 MHz linear transducer. MRI depicted 68 (45.95%) normal joints, 47 (31.76%) with disc displacement with reduction, 33 (22.3%) with disc displacement without reduction and 34 (22.97%) with degenerative changes. US detected 78 (52.7%) normal joints, 37 (25%) with disc displacement with reduction, 33 (22.3%) with disc displacement without reduction and 21 (14.19%) with degenerative changes. Compared to MRI, US showed a sensitivity of 93.1%, specificity of 87.88%, accuracy of 90.32%, a positive predictive value of 87.1% and a negative predictive value of 93.55% for overall diagnosis of disc displacement. The Youden index was 0.81. Based on our results, high-resolution ultrasonography showed high sensitivity, specificity and accuracy in the diagnosis of TMJ disc displacement. It could be a valuable imaging technique in assessing TMJ disc position. The diagnostic value of high-resolution ultrasonography depends strictly on the examiner's skills and on the equipment used.

Friend or foe: high bone mineral density on routine bone density scanning, a review of causes and management.

PubMed

Gregson, Celia L; Hardcastle, Sarah A; Cooper, Cyrus; Tobias, Jonathan H

2013-06-01

A finding of high BMD on routine DXA scanning is not infrequent and most commonly reflects degenerative disease. However, BMD increases may also arise secondary to a range of underlying disorders affecting the skeleton. Although low BMD increases fracture risk, the converse may not hold for high BMD, since elevated BMD may occur in conditions where fracture risk is increased, unaffected or reduced. Here we outline a classification for the causes of raised BMD, based on identification of focal or generalized BMD changes, and discuss an approach to guide appropriate investigation by clinicians after careful interpretation of DXA scan findings within the context of the clinical history. We will also review the mild skeletal dysplasia associated with the currently unexplained high bone mass phenotype and discuss recent advances in osteoporosis therapies arising from improved understanding of rare inherited high BMD disorders.

Antioxidant and anti-inflammatory properties of cancer preventive peptide lunasin in RAW 264.7 macrophages.

PubMed

Hernández-Ledesma, Blanca; Hsieh, Chia-Chien; de Lumen, Ben O

2009-12-18

Oxidative stress and inflammation are two of the most critical factors implicated in carcinogenesis and other degenerative disorders. We have investigated how lunasin, a known anti-cancer seed peptide, affect these factors. This peptide inhibits linoleic acid oxidation and acts as 2,2'-azinobis (3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS) radical scavenger. Furthermore, using LPS-stimulated RAW 264.7 macrophages, we have demonstrated that lunasin reduces, in a significant dose-dependent manner, the production of reactive oxygen species (ROS) by LPS-induced macrophages. Lunasin also inhibits the release of pro-inflammatory cytokines (tumor necrosis factor-alpha [TNF-alpha] and interleukine-6 [IL-6]). On the basis of these potent antioxidant and anti-inflammatory properties, we propose lunasin not only as a cancer preventive and therapeutic agent but also as an agent against other inflammatory-related disorders.

Friend or foe: high bone mineral density on routine bone density scanning, a review of causes and management

PubMed Central

Hardcastle, Sarah A.; Cooper, Cyrus; Tobias, Jonathan H.

2013-01-01

A finding of high BMD on routine DXA scanning is not infrequent and most commonly reflects degenerative disease. However, BMD increases may also arise secondary to a range of underlying disorders affecting the skeleton. Although low BMD increases fracture risk, the converse may not hold for high BMD, since elevated BMD may occur in conditions where fracture risk is increased, unaffected or reduced. Here we outline a classification for the causes of raised BMD, based on identification of focal or generalized BMD changes, and discuss an approach to guide appropriate investigation by clinicians after careful interpretation of DXA scan findings within the context of the clinical history. We will also review the mild skeletal dysplasia associated with the currently unexplained high bone mass phenotype and discuss recent advances in osteoporosis therapies arising from improved understanding of rare inherited high BMD disorders. PMID:23445662

An Analysis of Pathological Activities of CCN Proteins in Joint Disorders: Mechanical Stretch-Mediated CCN2 Expression in Cultured Meniscus Cells.

PubMed

Furumatsu, Takayuki; Ozaki, Toshifumi

2017-01-01

The multifunctional growth factor CYR61/CTGF/NOV (CCN) 2, also known as connective tissue growth factor, regulates cellular proliferation, differentiation, and tissue regeneration. Recent literatures have described important roles of CCN2 in the meniscus metabolism. However, the mechanical stress-mediated transcriptional regulation of CCN2 in the meniscus remains unclear. The meniscus is a fibrocartilaginous tissue that controls complex biomechanics of the knee joint. Therefore, the injured unstable meniscus has a poor healing potential especially in the avascular inner region. In addition, dysfunction of the meniscus correlates with the progression of degenerative knee joint disorders and joint space narrowing. Here, we describe an experimental approach that investigates the distinct cellular behavior of inner and outer meniscus cells in response to mechanical stretch. Our experimental model can analyze the relationships between stretch-induced CCN2 expression and its functional role in the meniscus homeostasis.

[Treatment of multiple sclerosis symptoms and exacerbations].

PubMed

Prieto González, José María

2014-12-01

In the last few years, there has been an explosion of new drugs acting on the clinical course of multiple sclerosis (MS) but less attention has been paid to better knowledge of the symptoms of this disease and their pathogenesis and treatment, which is essential to improve patients' quality of life. Because many patients have numerous concurrent symptoms during their clinical course, their management is complex and consequently it is important to know which symptoms are a direct result of the degenerative lesions of MS. The present article describes all the therapeutic options available for spasticity and its associated pain, paroxystic symptoms, fatigue, genitourinary disorders and sexual dysfunction, tremor, ataxia, gait disorder and cognitive impairment, with special emphasis on novel treatments. The article also defines exacerbations, how to recognize them and the available treatments, mainly oral administration of high-dose methylprednisolone and plasmapheresis. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

Swallowing endoscopy findings in Huntington's disease: a case report.

PubMed

Alves, Thaís Coelho; Cola, Paula Cristina; Santos, Rarissa Rúbia Dallaqua Dos; Motonaga, Suely Mayumi; Silva, Roberta Gonçalves da

2016-01-01

Huntington's disease (HD) is a degenerative genetic disorder with autosomal-dominant transmission. The triad of symptoms of this disease consists of psychiatric disorders, jerky movements, and dementia. Oropharyngeal dysphagia, which is more evident with disease progression, is also present. Few studies have addressed the swallowing characteristics using objective analysis in this population. The purpose of this research was to describe the swallowing endoscopic findings of the pharyngeal phase in HD. This is a cross-sectional study addressing a clinical case which included two individuals of the same family, male, 32 and 63 years old, designated as individual A and individual B, with progression of the disease for five and 13 years, respectively. Consistent liquid, nectar, and puree were offered during the evaluation. There was presence of posterior oral spillage in liquid and nectar, small amount of pharyngeal residues, and no laryngeal penetration or aspiration in the individuals with HD in this study.

Inclusion Body Myositis

PubMed Central

Dimachkie, Mazen M.; Barohn, Richard J.

2012-01-01

The idiopathic inflammatory myopathies are a group of rare disorders that share many similarities. These include dermatomyositis (DM), polymyositis (PM), necrotizing myopathy (NM), and sporadic inclusion body myositis (IBM). Inclusion body myositis is the most common idiopathic inflammatory myopathy after age 50 and it presents with chronic proximal leg and distal arm asymmetric mucle weakness. Despite similarities with PM, it is likely that IBM is primarily a degenerative disorder rather than an inflammatory muscle disease. Inclusion body myositis is associated with a modest degree of creatine kinase (CK) elevation and an abnormal electromyogram demonstrating an irritative myopathy with some chronicity. The muscle histopathology demonstrates inflammatory exudates surrounding and invading nonnecrotic muscle fibers often times accompanied by rimmed vacuoles. In this chapter, we review sporadic IBM. We also examine past, essentially negative, clinical trials in IBM and review ongoing clinical trials. For further details on DM, PM, and NM, the reader is referred to the idiopathic inflammatory myopathies chapter. PMID:23117948

PATTERN OF CUTANEOUS MANIFESTATIONS IN DIABETES MELLITUS

PubMed Central

Goyal, Abhishek; Raina, Sujeet; Kaushal, Satinder S; Mahajan, Vikram; Sharma, Nand Lal

2010-01-01

Background: Diabetes mellitus affects individuals of all ages and socioeconomic status. Skin is affected by the acute metabolic derangements as well as by chronic degenerative complications of diabetes. Aims: To evaluate the prevalence of skin manifestations in patients with diabetes mellitus. To analyze the prevalence and pattern of skin disorders among diabetic patients from this region of Western Himalayas. Materials and Methods: One hundred consecutive patients with the diagnosis of diabetes mellitus and having skin lesions, either attending the diabetic clinic or admitted in medical wards were included in this study. Results: The common skin disorders were: Xerosis (44%), diabetic dermopathy (36%), skin tags (32%), cutaneous infections (31%), and seborrheic keratosis (30%). Conclusion: Skin is involved in diabetes quite often and the manifestations are numerous. High prevalence of xerosis in our diabetic population is perhaps due to cold and dry climatic conditions in the region for most of the time in the year. PMID:20418975

Disorders of the long head of the biceps: tenotomy versus tenodesis.

PubMed

Ribeiro, Fabiano Rebouças; Ursolino, André Petry Sandoval; Ramos, Vinicius Ferreira Lima; Takesian, Fernando Hovaguim; Tenor Júnior, Antonio Carlos; Costa, Miguel Pereira da

2017-01-01

Disorders of the long head of biceps tendon are common in clinical practice. Their causes could be degenerative, inflammatory, instability (subluxation or luxation) or traumatic. They are generally associated to other diseases of the shoulder, mainly rotator cuff injuries. Currently, there is controversy in the literature regarding the indications for surgical treatment and the choice of the best technique for each case, due to the possibility of esthetic deformity, loss of muscle strength, and residual pain. The objective of this study was to identify the indications for surgical treatment, the best surgical technique, and the advantages and disadvantages of each technique described in the orthopedic literature for the treatment of long head of biceps tendon injuries. A revision of the orthopedic medical literature on the following databases: Biblioteca Regional de Medicina (BIREME), Medline, PubMed, Cochrane Library and Google Scholar, comprising articles published in the period from 1991 to 2015.

Intelligent Interfaces to Empower People with Disabilities

NASA Astrophysics Data System (ADS)

Betke, Margrit

Severe motion impairments can result from non-progressive disorders, such as cerebral palsy, or degenerative neurological diseases, such as Amyotrophic Lateral Sclerosis (ALS), Multiple Sclerosis (MS), or muscular dystrophy (MD). They can be due to traumatic brain injuries, for example, due to a traffic accident, or to brainstem strokes [9, 84]. Worldwide, these disorders affect millions of individuals of all races and ethnic backgrounds [4, 75, 52]. Because disease onset of MS and ALS typically occurs in adulthood, afflicted people are usually computer literate. Intelligent interfaces can immensely improve their daily lives by allowing them to communicate and participate in the information society, for example, by browsing the web, posting messages, or emailing friends. However, people with advanced ALS, MS, or MD may reach a point when they cannot control the keyboard and mouse anymore and also cannot rely on automated voice recognition because their speech has become slurred.

Co-morbid depressive disorder is associated with better neurocognitive performance in first episode schizophrenia spectrum.

PubMed

Herniman, Sarah E; Cotton, Sue M; Killackey, Eóin; Hester, Robert; Allott, Kelly A

2018-03-15

Both major depressive disorder (MDD) and first episode schizophrenia spectrum (FES) are associated with significant neurocognitive deficits. However, it remains unclear whether the neurocognitive deficits in individuals with FES are more severe if there is comorbid depressive disorder. The aim of this study was to compare the neurocognitive profiles between those with and without full-threshold depressive disorder in FES. This study involved secondary analysis of baseline data from a randomized controlled trial of vocational intervention for young people with first-episode psychosis (N = 82; age range: 15-25 years). Those with full-threshold depressive disorder (n = 24) had significantly better information processing speed than those without full-threshold depressive disorder. Severity of depressive symptoms was also associated with better information processing speed. In additional to the cross-sectional design, limitations of this study include the absence of assessing insight as a potential mediator. After the first psychotic episode, it could be speculated that those with better information processing speed may be more likely to develop full-threshold depressive disorder, as their ability to efficiently process information may allow them to be more aware of their situations and environments, and consequently to have greater insight into the devastating consequences of FES. Such novel findings support the examination of full-threshold depressive disorder in relation to neurocognitive performance across illness phases in future work. Copyright © 2018 Elsevier B.V. All rights reserved.

2016 update on eating disorders in athletes: A comprehensive narrative review with a focus on clinical assessment and management.

PubMed

Joy, Elizabeth; Kussman, Andrea; Nattiv, Aurelia

2016-02-01

Eating disorders, such as anorexia nervosa and bulimia nervosa, can have devastating effects on both the health and performance of athletes. Compared to non-athletes, both female and male athletes are at higher risk of developing an eating disorder. This is especially true for athletes participating in sports where low body weight or leanness confers a competitive advantage. Screening for disordered eating behaviours, eating disorders and for related health consequences should be a standard component of preparticipation examinations, and team physicians should be knowledgeable of the updated diagnostic criteria for eating disorders in the Diagnostic and Statistical Manual-V. Athletes with eating disorders should undergo thorough evaluation and treatment by an experienced multidisciplinary team. Team physicians play a critical role in decision-making on clearance for participation and return to play. Using evidence-based guidelines for clearance and return to play encourages transparency and accountability between the sports medicine care team and the athlete. Efforts to prevent eating disorders should be aimed at athletes, coaches, parents and athletic administrators, and focused on expanding knowledge of healthy nutrition in support of sport performance and health. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

CRISPR Epigenome Editing of AKAP150 in DRG Neurons Abolishes Degenerative IVD-Induced Neuronal Activation.

PubMed

Stover, Joshua D; Farhang, Niloofar; Berrett, Kristofer C; Gertz, Jason; Lawrence, Brandon; Bowles, Robby D

2017-09-06

Back pain is a major contributor to disability and has significant socioeconomic impacts worldwide. The degenerative intervertebral disc (IVD) has been hypothesized to contribute to back pain, but a better understanding of the interactions between the degenerative IVD and nociceptive neurons innervating the disc and treatment strategies that directly target these interactions is needed to improve our understanding and treatment of back pain. We investigated degenerative IVD-induced changes to dorsal root ganglion (DRG) neuron activity and utilized CRISPR epigenome editing as a neuromodulation strategy. By exposing DRG neurons to degenerative IVD-conditioned media under both normal and pathological IVD pH levels, we demonstrate that degenerative IVDs trigger interleukin (IL)-6-induced increases in neuron activity to thermal stimuli, which is directly mediated by AKAP and enhanced by acidic pH. Utilizing this novel information on AKAP-mediated increases in nociceptive neuron activity, we developed lentiviral CRISPR epigenome editing vectors that modulate endogenous expression of AKAP150 by targeted promoter histone methylation. When delivered to DRG neurons, these epigenome-modifying vectors abolished degenerative IVD-induced DRG-elevated neuron activity while preserving non-pathologic neuron activity. This work elucidates the potential for CRISPR epigenome editing as a targeted gene-based pain neuromodulation strategy. Copyright © 2017 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.

Inherited Retinal Degenerative Clinical Trial Network

DTIC Science & Technology

2009-10-01

ending in blindness. In the United States, the total number of individuals affected by retinitis pigmentosa (RP) and other forms of rare inherited...AD_________________ AWARD NUMBER: W81XWH-07-1-0720 TITLE: Inherited Retinal Degenerative...Final 3. DATES COVERED 27 Sep 2007 – 29 Sep 2009 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Inherited Retinal Degenerative Clinical Trial Network

Optimizing the Use of Aripiprazole Augmentation in the Treatment of Major Depressive Disorder: From Clinical Trials to Clinical Practice

PubMed Central

Han, Changsu; Wang, Sheng-Min; Lee, Soo-Jung; Jun, Tae-Youn

2015-01-01

Major depressive disorder (MDD) is a recurrent, chronic, and devastating disorder leading to serious impairment in functional capacity as well as increasing public health care costs. In the previous decade, switching therapy and dose adjustment of ongoing antidepressants was the most frequently chosen subsequent treatment option for MDD. However, such recommendations were not based on firmly proven efficacy data from well-designed, placebo-controlled, randomized clinical trials (RCTs) but on practical grounds and clinical reasoning. Aripiprazole augmentation has been dramatically increasing in clinical practice owing to its unique action mechanisms as well as proven efficacy and safety from adequately powered and well-controlled RCTs. Despite the increased use of aripiprazole in depression, limited clinical information and knowledge interfere with proper and efficient use of aripiprazole augmentation for MDD. The objective of the present review was to enhance clinicians' current understanding of aripiprazole augmentation and how to optimize the use of this therapy in the treatment of MDD. PMID:26306301

Neuronopathic lysosomal storage disorders: Approaches to treat the central nervous system.

PubMed

Scarpa, Maurizio; Bellettato, Cinzia Maria; Lampe, Christina; Begley, David J

2015-03-01

Pharmacological research has always focused on developing new therapeutic strategies capable of modifying a disease's natural history and improving patients' quality of life. Despite recent advances within the fields of medicine and biology, some diseases still represent a major challenge for successful therapy. Neuronopathic lysosomal storage disorders, in particular, have high rates of morbidity and mortality and a devastating socio-economic effect. Many of the available therapies, such as enzyme replacement therapy, can reverse the natural history of the disease in peripheral organs but, unfortunately, are still unable to reach the central nervous system effectively because they cannot cross the blood-brain barrier that surrounds and protects the brain. Moreover, many lysosomal storage disorders are characterized by a number of blood-brain barrier dysfunctions, which may further contribute to disease neuropathology and accelerate neuronal cell death. These issues, and their context in the development of new therapeutic strategies, will be discussed in detail in this chapter. Copyright © 2014 Elsevier Ltd. All rights reserved.

Autistic spectrum disorders.

PubMed

Singhania, Rajeshree

2005-04-01

Autistic spectrum disorders is a complex developmental disorder with social and communication dysfunction at its core. It has a wide clinical spectrum with a common triad of impairments -- social communication, social interaction and social imagination. Even mild or subtle difficulties can have a profound and devastating impact on the child. To be able to provide suitable treatments and interventions the distinctive way of thinking and learning of autistic children has to be understood. The core areas of social, emotional, communication and language deficits have to be addressed at all levels of functioning. The important goals of assessment include a categorical diagnosis of autism that looks at differential diagnosis, a refined precise documentation of the child's functioning in various developmental domains and ascertaining presence of co-morbid conditions. The interventions have to be adapted to the individual's chronological age, developmental phase and level of functioning. The strategies of curriculum delivery and teaching the child with autism is distinctive and includes presence of structure to increase predictability and strategies to reduce arousal of anxiety.

Nutrition and eating disorders in adolescents.

PubMed

Seidenfeld, Marjorie E Kaplan; Sosin, Elyse; Rickert, Vaughn I

2004-05-01

Adequate nutrition is essential during adolescence, since growth and development during this period play key roles in achieving normal adult size and reproductive capacity. This article briefly reviews recommended caloric intake; the healthy balance of carbohydrates, fat and protein; and the appropriate dietary intake of iron, folic acid and calcium for the adolescent. A major potential obstacle to good nutrition for an adolescent is the development of an eating disorder such as anorexia nervosa or bulimia nervosa. Anorexia nervosa, characterized by severe underweight, fear of gaining weight, and low self-esteem and amenorrhea, is associated with many physiological and psychological complications with which the provider must be familiar. Similarly, bulimia nervosa, which presents with eating binges followed by compensatory behaviors such as vomiting, diet pill abuse and overexercise, may be harder to detect, but can also have devastating consequences, both physically and emotionally, for a young person. Both of these disorders are best treated by a multidisciplinary team of specialists to address the medical, psychological, and nutritional components of these illnesses.

The Role of Personality and Subjective Exposure Experiences in Posttraumatic Stress Disorder and Depression Symptoms among Children Following Wenchuan Earthquake.

PubMed

Chen, Xiacan; Xu, Jiajun; Li, Bin; Li, Na; Guo, Wanjun; Ran, Mao-Sheng; Zhang, Jun; Yang, Yanchun; Hu, Junmei

2017-12-08

This study aims to investigate the role of personality traits and subjective exposure experiences in posttraumatic stress disorder and depression symptoms. In Qingchuan, 21,652 children aged 7 to 15 years were assessed using face-to-face interviews one year after the Wenchuan earthquake in China. The Junior Eysenck Personality Questionnaire, a modified earthquake exposure scale, the UCLA Posttraumatic Stress Disorder Reaction Index (adolescent), and the Adolescent Depression Inventory were used to assess personality characteristics, trauma experiences, posttraumatic stress disorder and depression symptoms, respectively. The measurement was completed with 20,749 children. After adjusting for other factors by multinomial logistic regression analysis, neuroticism, having felt unable to escape from the disaster and having been trapped for a longer time were risk factors of posttraumatic stress disorder and depression symptoms. Socialization was a protective factor of them. Having felt extreme panic or fear was a risk factor of posttraumatic stress disorder symptoms. For depression symptoms, introversion and psychoticism were risk factors, and extraversion was a protective factor. This study was conducted with the largest representative sample of child survivors of a natural, devastating disaster in a developing country. These results could be useful for planning psychological intervention strategies for children and for influencing further research.

Psychiatric considerations in the diagnosis, treatment, and prevention of HIV/AIDS.

PubMed

Ruiz, P; Guynn, R W; Matorin, A A

2000-05-01

HIV/AIDS has the unfortunate distinction of being one of the most devastating epidemics of the twentieth century. By the end of June, 1999, 420,201 deaths in persons with AIDS had been reported in the United States. While HIV/AIDS patients are currently living longer as a result of more effective and complex treatments, no vaccination or cure has yet been discovered. Over the years, the HIV/AIDS epidemic has become multifactorial and currently affects several different special population groups. Individuals who are at high risk for becoming infected with HIV or who already suffer from HIV/AIDS can benefit greatly from the interventions of psychiatrists or other mental health professionals. It is important that psychiatrists collaborate very closely with infectious disease specialists in the management of HIV/AIDS and its psychological sequelae. The authors describe the psychiatric conditions that most often occur in association with HIV/AIDS: mood disorders, anxiety disorders, substance-related disorders, psychotic disorders, insomnia and sleep disorders, delirium, dementia, and pain syndromes. We present guidelines for diagnosis and psychopharmacological and psychotherapeutic treatment of these disorders in patients with HIV/AIDS. The article concludes with a discussion of prevention strategies that can be used in a mental health treatment setting and special issues related to treating HIV/AIDS in certain special population groups.

BRAIN MYELINATION IN PREVALENT NEUROPSYCHIATRIC DEVELOPMENTAL DISORDERS

PubMed Central

BARTZOKIS, GEORGE

2008-01-01

Current concepts of addiction focus on neuronal neurocircuitry and neurotransmitters and are largely based on animal model data, but the human brain is unique in its high myelin content and extended developmental (myelination) phase that continues until middle age. The biology of our exceptional myelination process and factors that influence it have been synthesized into a recently published myelin model of human brain evolution and normal development that cuts across the current symptom-based classification of neuropsychiatric disorders. The developmental perspective of the model suggests that dysregulations in the myelination process contribute to prevalent early-life neuropsychiatric disorders, as well as to addictions. These disorders share deficits in inhibitory control functions that likely contribute to their high rates of comorbidity with addiction and other impulsive behaviors. The model posits that substances such as alcohol and psychostimulants are toxic to the extremely vulnerable myelination process and contribute to the poor outcomes of primary and comorbid addictive disorders in susceptible individuals. By increasing the scientific focus on myelination, the model provides a rational biological framework for the development of novel, myelin-centered treatments that may have widespread efficacy across multiple disease states and could potentially be used in treating, delaying, or even preventing some of the most prevalent and devastating neuropsychiatric disorders. PMID:18668184

Evaluation of Serum Cytokines in Cats with and without Degenerative Joint Disease and Associated Pain

PubMed Central

Gruen, Margaret E.; Messenger, Kristen M.; Thomson, Andrea E.; Griffith, Emily H.; Aldrich, Lauren A.; Vaden, Shelly; Lascelles, BDX

2017-01-01

Degenerative joint disease is common in cats, with signs of pain frequently found on orthopedic examination and radiographs often showing evidence of disease. However, understanding of the pathophysiology of degenerative joint disease and associated pain remains limited. Several cytokines have been identified as having a role in pain in humans, but this has not been investigated in cats. The present study was performed to use a multiplex platform to evaluate the concentration of 19 cytokines and chemokines in serum samples obtained from cats with and without degenerative joint disease and associated pain. Samples from a total of 186 cats were analyzed, with cats representing a range of severity on radiographic and orthopedic evaluations and categorized by degenerative joint disease scores and pain scores. Results showed that cats with higher radiographic degenerative joint disease scores have higher serum concentrations of IL-4 and IL-8, while cats with higher orthopedic exam pain scores have higher concentrations of IL-8, IL-2, and TNF-α increased concentration of IL-8 in degenerative joint disease and pain may be confounded by the association with age. Discriminant analysis was unable to identify one or more cytokines that distinguish between groups of cats classified based on degenerative joint disease score category or pain score category. Finally, cluster analysis driven by analyte concentrations show separation of groups of cats, but features defining the groups remain unknown. Further studies are warranted to investigate any changes in cytokine concentrations in response to analgesic therapies, and further evaluate the elevations in cytokine concentrations found here, particularly focused on studies of local cytokines present in synovial fluid. PMID:28063477

The Coracohumeral Distance in Shoulders With Traumatic and Degenerative Subscapularis Tendon Tears.

PubMed

Balke, Maurice; Banerjee, Marc; Greshake, Oliver; Hoeher, Juergen; Bouillon, Bertil; Liem, Dennis

2016-01-01

A reduced coracohumeral distance (CHD) is thought to be responsible for subcoracoid impingement. This only accounts for degenerative tendon tears. In traumatic tears, the subcoracoid space should be normal. The CHD in patients with traumatic subscapularis tendon tears is larger than that in patients with degenerative tears and does not differ from patients with an intact subscapularis tendon. Cohort study; Level of evidence, 3. A total of 83 patients with arthroscopically certified subscapularis tendon tears were included in the study. Forty-four patients had degenerative causes (group 1), and 39 had traumatic causes (group 2). The control group consisted of 20 patients with traumatic supraspinatus tendon tears and arthroscopically proven, intact subscapularis tendons (group 3). On preoperative axial magnetic resonance imaging, the distance between the CHD was measured, and the values of the 3 groups were compared using the t test. The mean (±SD) CHD in patients with degenerative subscapularis tendon tears was 8.6 ± 2.0 mm (range, 4.0-13.2 mm) and was significantly (P = .0003) smaller than that in patients with traumatic tears (10.2 ± 2.0 mm; range, 6.6-16.2 mm) or controls (10.4 ± 1.8 mm; range, 6.8-14.0 mm). The CHD of controls and patients with traumatic tears did not differ significantly (P = .7875). A CHD of less than 6 mm only occurred in patients with degenerative subscapularis tendon tears. The hypothesis that the CHD in patients with degenerative subscapularis tendon tears is significantly smaller than that in patients with traumatic tears or intact subscapularis tendons was confirmed. The CHD in patients with traumatic tears does not differ from that in controls. A CHD of less than 6 mm only occurs in patients with degenerative subscapularis tendon tears. © 2015 The Author(s).

Radiofrequency neurotomy for treatment of low back pain in patients with minor degenerative spondylolisthesis.

PubMed

Klessinger, Stephan

2012-01-01

Degenerative spondylolisthesis is one of the major causes for low back pain. Morphological abnormalities of the zygapophysial joints are a predisposing factor in the development of degenerative spondylolisthesis. Therefore, radiofrequency neurotomy seems to be a rational therapy. To determine if radiofrequency neurotomy is effective for patients with low back pain and degenerative spondylolisthesis. Retrospective practice audit. Single spine center Charts of all patients with degenerative spondylolisthesis who underwent treatment with radiofrequency neurotomy during a time period of 3 years were reviewed. Only patients with magnetic resonance imaging confirming the diagnosis were included. Patients with a lumbar spine operation in their history, patients with neurological deficits, and patients with a follow-up less than 3 months were excluded. Patients were treated with lumbar radiofrequency neurotomy. Positive treatment response was defined as at least a 50% reduction in pain. A radiofrequency neurotomy was only performed after positive diagnostic medial branch blocks. During a time period of 3 years, 1,490 patients were treated with lumbar radiofrequency neurotomy. Forty of these patients with degenerative spondylolisthesis were included. A significant pain reduction was achieved in 65 % of the patients. This audit is retrospective and observational, and therefore does not represent a high level of evidence. However, to our knowledge, since this information has not been previously reported and no specific nonoperative treatment for lumbar pain in patients with degenerative spondylolisthesis exists, it appears to be the best available research upon which to recommend treatment and to plan higher quality studies. Zygapophysial joints are a possible source of pain in patients with spondylolisthesis. Radiofrequency neurotomy is a rational, specific nonoperative therapy in addition to other nonoperative therapy methods with a success rate of 65%. This is the first study to determine the effect of radiofrequency neurotomy in patients with minor degenerative spondylolisthesis.

Pathological classification of equine recurrent laryngeal neuropathy.

PubMed

Draper, Alexandra C E; Piercy, Richard J

2018-04-24

Recurrent Laryngeal Neuropathy (RLN) is a highly prevalent and predominantly left-sided, degenerative disorder of the recurrent laryngeal nerves (RLn) of tall horses, that causes inspiratory stridor at exercise because of intrinsic laryngeal muscle paresis. The associated laryngeal dysfunction and exercise intolerance in athletic horses commonly leads to surgical intervention, retirement or euthanasia with associated financial and welfare implications. Despite speculation, there is a lack of consensus and conflicting evidence supporting the primary classification of RLN, as either a distal ("dying back") axonopathy or as a primary myelinopathy and as either a (bilateral) mononeuropathy or a polyneuropathy; this uncertainty hinders etiological and pathophysiological research. In this review, we discuss the neuropathological changes and electrophysiological deficits reported in the RLn of affected horses, and the evidence for correct classification of the disorder. In so doing, we summarize and reveal the limitations of much historical research on RLN and propose future directions that might best help identify the etiology and pathophysiology of this enigmatic disorder. Copyright © 2018 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

Early, asymptomatic stage of degenerative joint disease in canine hip joints.

PubMed

Lust, G; Summers, B A

1981-11-01

The early stages of degenerative joint disease were investigated in coxofemoral joints from dogs with a hereditary predisposition to hip dysplasia. Alterations observed included mild nonsuppurative synovitis, increased volume of both synovial fluid and the ligamentum teres, and focal degenerative articular cartilage lesions. On radiologic examination, subluxation of the femoral head was seen, but only in the most severely affected joints. Synovial inflammation with increased synovial fluid and ligament volumes were indicators of early degenerative joint disease in dogs. These changes seemed to coincide with, or perhaps to precede, microscopic evidence for articular cartilage degeneration and occurred before radiologic abnormalities were detected.

Nanotechnology and nanocarrier-based approaches on treatment of degenerative diseases

NASA Astrophysics Data System (ADS)

Chowdhury, Anindita; Kunjiappan, Selvaraj; Panneerselvam, Theivendren; Somasundaram, Balasubramanian; Bhattacharjee, Chiranjib

2017-04-01

Degenerative diseases are results of deterioration of cells and tissues with aging either by unhealthy lifestyle or normal senescence. The degenerative disease likely affects central nervous system and cardiovascular system to a great extent. Certain medications and therapies have emerged for the treatment of degenerative diseases, but in most cases bearing with poor solubility, lower bioavailability, drug resistance, and incapability to cross the blood-brain barrier (BBB). Hence, it has to be overcome with conventional treatment system; in this connection, nanotechnology has gained a great deal of interest in recent years. Moreover, nanotechnology and nanocarrier-based approach drug delivery system could revolutionize the treatment of degenerative diseases by faster absorption of drug, targeted interaction at specific site, and its release in a controlled manner into human body with minimal side effects. The core objective of this review is to customize and formulate therapeutically active molecules with specific site of action and without affecting other organs and tissues to obtain effective result in the improvement of quality of health. In addition, the review provides a concise insight into the recent developments and applications of nanotech and nanocarrier-based drug delivery for the treatment of various degenerative diseases.

Slowly progressive aphasia associated with surface dyslexia.

PubMed

Chiacchio, L; Grossi, D; Stanzione, M; Trojano, L

1993-03-01

We report an Italian patient affected by slowly progressive aphasia (SPA) lasting since four years when he first came to our observation. During the successive four years, we documented a progressive language decline resembling transcortical sensory aphasia, associated with a reading disorder corresponding to surface dyslexia, a form extremely rare in patients with native transparent language. His performance at standard intelligence tasks remained in the normal range, without any variation. CT scan showed left temporal atrophy. We emphasize the heterogeneity of the syndrome of SPA and suggest that it can represent one of the pictures of focal cortical degenerative disease, with variable onset, progression, and evolution.

Mitochondria: A Common Target for Genetic Mutations and Environmental Toxicants in Parkinson’s Disease

PubMed Central

Helley, Martin P.; Pinnell, Jennifer; Sportelli, Carolina; Tieu, Kim

2017-01-01

Parkinson’s disease (PD) is a devastating neurological movement disorder. Since its first discovery 200 years ago, genetic and environmental factors have been identified to play a role in PD development and progression. Although genetic studies have been the predominant driving force in PD research over the last few decades, currently only a small fraction of PD cases can be directly linked to monogenic mutations. The remaining cases have been attributed to other risk associated genes, environmental exposures and gene–environment interactions, making PD a multifactorial disorder with a complex etiology. However, enormous efforts from global research have yielded significant insights into pathogenic mechanisms and potential therapeutic targets for PD. This review will highlight mitochondrial dysfunction as a common pathway involved in both genetic mutations and environmental toxicants linked to PD. PMID:29204154

Slowing the Tide of Alcohol Use Disorders.

PubMed

Chamsi-Pasha, Hassan; Chamsi-Pasha, Majed; Albar, Mohammed Ali

2016-09-28

Alcohol use disorders (AUDs)-a spectrum including at-risk drinking, alcohol abuse, dependence, and addiction-is a highly prevalent problem worldwide with a substantial economic impact. The toll of alcohol on individual health and healthcare systems is devastating. Alcohol is estimated to be the fifth leading risk factor for global disability-adjusted life years. Tackling the problem of AUD requires a comprehensive strategy that includes solid action on price, availability, and marketing of alcohol. Restricting or banning alcohol advertising may reduce exposure to the risk posed by alcohol at the individual and general population level. Warning labels about the cancer risks associated with drinking have a high degree of public support and may be an inexpensive and acceptable way to educate the public. Religiosity may reduce risk behaviors and contribute to health decision making related to alcohol use.

Lumbar paraspinal muscle transverse area and symmetry in dogs with and without degenerative lumbosacral stenosis.

PubMed

Henderson, A L; Hecht, S; Millis, D L

2015-10-01

To investigate whether dogs with degenerative lumbosacral stenosis have decreased lumbar paraspinal muscle transverse area and symmetry compared with control dogs. Retrospective cross-sectional study comparing muscles in transverse T2-weighted magnetic resonance images for nine dogs with and nine dogs without degenerative -lumbosacral stenosis. Mean transverse area was measured for the lumbar multifidus and sacrocaudalis dorsalis lateralis muscles bilaterally and the L7 vertebral body at the level of the caudal endplate. Transverse areas of both muscle groups relative to L7 and asymmetry indices were compared between study populations using independent t tests. Mean muscle-to-L7 transverse area ratios were significantly smaller in the degenerative lumbosacral stenosis group compared with those in the control group in both lumbar multifidus (0·84 ±0·26 versus 1·09 ±0·25; P=0·027) and sacrocaudalis dorsalis lateralis (0·5 ±0·15 versus 0·68 ±0·12; P=0·005) muscles. Mean asymmetry indices were higher for both muscles in the group with degenerative lumbosacral stenosis than in the control group, but highly variable and the difference was not statistically significant. These findings suggest that dogs with degenerative lumbosacral stenosis have decreased lumbar paraspinal muscle mass that may be a cause or consequence of the -syndrome. Understanding altered paraspinal muscle characteristics may improve understanding of the -pathophysiology and management options for degenerative lumbosacral stenosis. © 2015 British Small Animal Veterinary Association.

NF-κB inhibition delays DNA damage–induced senescence and aging in mice

PubMed Central

Tilstra, Jeremy S.; Robinson, Andria R.; Wang, Jin; Gregg, Siobhán Q.; Clauson, Cheryl L.; Reay, Daniel P.; Nasto, Luigi A.; St Croix, Claudette M.; Usas, Arvydas; Vo, Nam; Huard, Johnny; Clemens, Paula R.; Stolz, Donna B.; Guttridge, Denis C.; Watkins, Simon C.; Garinis, George A.; Wang, Yinsheng; Niedernhofer, Laura J.; Robbins, Paul D.

2012-01-01

The accumulation of cellular damage, including DNA damage, is thought to contribute to aging-related degenerative changes, but how damage drives aging is unknown. XFE progeroid syndrome is a disease of accelerated aging caused by a defect in DNA repair. NF-κB, a transcription factor activated by cellular damage and stress, has increased activity with aging and aging-related chronic diseases. To determine whether NF-κB drives aging in response to the accumulation of spontaneous, endogenous DNA damage, we measured the activation of NF-κB in WT and progeroid model mice. As both WT and progeroid mice aged, NF-κB was activated stochastically in a variety of cell types. Genetic depletion of one allele of the p65 subunit of NF-κB or treatment with a pharmacological inhibitor of the NF-κB–activating kinase, IKK, delayed the age-related symptoms and pathologies of progeroid mice. Additionally, inhibition of NF-κB reduced oxidative DNA damage and stress and delayed cellular senescence. These results indicate that the mechanism by which DNA damage drives aging is due in part to NF-κB activation. IKK/NF-κB inhibitors are sufficient to attenuate this damage and could provide clinical benefit for degenerative changes associated with accelerated aging disorders and normal aging. PMID:22706308

A Mitochondrial Paradigm of Metabolic and Degenerative Diseases, Aging, and Cancer: A Dawn for Evolutionary Medicine

PubMed Central

Wallace, Douglas C.

2005-01-01

Life is the interplay between structure and energy, yet the role of energy deficiency in human disease has been poorly explored by modern medicine. Since the mitochondria use oxidative phosphorylation (OXPHOS) to convert dietary calories into usable energy, generating reactive oxygen species (ROS) as a toxic by-product, I hypothesize that mitochondrial dysfunction plays a central role in a wide range of age-related disorders and various forms of cancer. Because mitochondrial DNA (mtDNA) is present in thousands of copies per cell and encodes essential genes for energy production, I propose that the delayed-onset and progressive course of the age-related diseases results from the accumulation of somatic mutations in the mtDNAs of post-mitotic tissues. The tissue-specific manifestations of these diseases may result from the varying energetic roles and needs of the different tissues. The variation in the individual and regional predisposition to degenerative diseases and cancer may result from the interaction of modern dietary caloric intake and ancient mitochondrial genetic polymorphisms. Therefore the mitochondria provide a direct link between our environment and our genes and the mtDNA variants that permitted our forbears to energetically adapt to their ancestral homes are influencing our health today. PMID:16285865

Oxford Shoulder Score: A Cross-Cultural Adaptation and Validation Study of the Persian Version in Iran.

PubMed

Ebrahimzadeh, Mohammad H; Birjandinejad, Ali; Razi, Shiva; Mardani-Kivi, Mohsen; Reza Kachooei, Amir

2015-09-01

Oxford shoulder score is a specific 12-item patient-reported tool for evaluation of patients with inflammatory and degenerative disorders of the shoulder. Since its introduction, it has been translated and culturally adapted in some Western and Eastern countries. The aim of this study was to translate the Oxford Shoulder Score (OSS) in Persian and to test its validity and reliability in Persian speaking population in Iran. One hundred patients with degenerative or inflammatory shoulder problem participated in the survey in 2012. All patients completed the Persian version of OSS, Persian DASH and the SF-36 for testing validity. Randomly, 37 patients filled out the Persian OSS again three days after the initial visit to assess the reliability of the questionnaire. Cronbach's alpha coefficient was 0.93. The intraclass correlation coefficient was 0.93. In terms of validity, there was a significant correlation between the Persian OSS and DASH and SF-36 scores (P < 0.001). The Persian version of the OSS proved to be a valid, reliable, and reproducible tool as demonstrated by high Cronbach's alpha and Pearson's correlation coefficients. The Persian transcript of OSS is administrable to Persian speaking patients with shoulder condition and it is understandable by them.

Oxidation Inhibits Iron-Induced Blood Coagulation

PubMed Central

Pretorius, Etheresia; Bester, Janette; Vermeulen, Natasha; Lipinski, Boguslaw

2013-01-01

Blood coagulation under physiological conditions is activated by thrombin, which converts soluble plasma fibrinogen (FBG) into an insoluble clot. The structure of the enzymatically-generated clot is very characteristic being composed of thick fibrin fibers susceptible to the fibrinolytic degradation. However, in chronic degenerative diseases, such as atherosclerosis, diabetes mellitus, cancer, and neurological disorders, fibrin clots are very different forming dense matted deposits (DMD) that are not effectively removed and thus create a condition known as thrombosis. We have recently shown that trivalent iron (ferric ions) generates hydroxyl radicals, which subsequently convert FBG into abnormal fibrin clots in the form of DMDs. A characteristic feature of DMDs is their remarkable and permanent resistance to the enzymatic degradation. Therefore, in order to prevent thrombotic incidences in the degenerative diseases it is essential to inhibit the iron-induced generation of hydroxyl radicals. This can be achieved by the pretreatment with a direct free radical scavenger (e.g. salicylate), and as shown in this paper by the treatment with oxidizing agents such as hydrogen peroxide, methylene blue, and sodium selenite. Although the actual mechanism of this phenomenon is not yet known, it is possible that hydroxyl radicals are neutralized by their conversion to the molecular oxygen and water, thus inhibiting the formation of dense matted fibrin deposits in human blood. PMID:23170793

Degenerative Nerve Diseases

MedlinePlus

... may include toxins, chemicals, and viruses. Sometimes the cause is not known. Degenerative nerve diseases include Alzheimer's disease Amyotrophic lateral sclerosis Friedreich's ataxia Huntington's disease ...

Dietary Phytochemicals: Natural Swords Combating Inflammation and Oxidation-Mediated Degenerative Diseases.

PubMed

Islam, Md Asiful; Alam, Fahmida; Solayman, Md; Khalil, Md Ibrahim; Kamal, Mohammad Amjad; Gan, Siew Hua

2016-01-01

Cumulatively, degenerative disease is one of the most fatal groups of diseases, and it contributes to the mortality and poor quality of life in the world while increasing the economic burden of the sufferers. Oxidative stress and inflammation are the major pathogenic causes of degenerative diseases such as rheumatoid arthritis (RA), diabetes mellitus (DM), and cardiovascular disease (CVD). Although a number of synthetic medications are used to treat these diseases, none of the current regimens are completely safe. Phytochemicals (polyphenols, carotenoids, anthocyanins, alkaloids, glycosides, saponins, and terpenes) from natural products such as dietary fruits, vegetables, and spices are potential sources of alternative medications to attenuate the oxidative stress and inflammation associated with degenerative diseases. Based on in vitro , in vivo , and clinical trials, some of these active compounds have shown good promise for development into novel agents for treating RA, DM, and CVD by targeting oxidative stress and inflammation. In this review, phytochemicals from natural products with the potential of ameliorating degenerative disease involving the bone, metabolism, and the heart are described.

Changes in rates of arthroscopy due to degenerative knee disease and traumatic meniscal tears in Finland and Sweden

PubMed Central

Mattila, Ville M; Sihvonen, Raine; Paloneva, Juha; Felländer-Tsai, Li

2016-01-01

Background and purpose Knee arthroscopy is commonly performed to treat degenerative knee disease symptoms and traumatic meniscal tears. We evaluated whether the recent high-quality randomized control trials not favoring arthroscopic surgery for degenerative knee disease affected the procedure incidence and trends in Finland and Sweden. Patients and methods We conducted a bi-national registry-based study including all adult (aged ≥18 years) inpatient and outpatient arthroscopic surgeries performed for degenerative knee disease (osteoarthritis (OA) and degenerative meniscal tears) and traumatic meniscal tears in Finland between 1997 and 2012, and in Sweden between 2001 and 2012. Results In Finland, the annual number of operations was 16,389 in 1997, reached 20,432 in 2007, and declined to 15,018 in 2012. In Sweden, the number of operations was 9,944 in 2001, reached 11,711 in 2008, and declined to 8,114 in 2012. The knee arthroscopy incidence for OA was 124 per 105 person-years in 2012 in Finland and it was 51 in Sweden. The incidence of knee arthroscopies for meniscal tears coded as traumatic steadily increased in Finland from 64 per 105 person-years in 1997 to 97 per 105 person-years in 2012, but not in Sweden. Interpretation The incidence of arthroscopies for degenerative knee disease declined after 2008 in both countries. Remarkably, the incidence of arthroscopy for degenerative knee disease and traumatic meniscal tears is 2 to 4 times higher in Finland than in Sweden. Efficient implementation of new high-quality evidence in clinical practice could reduce the number of ineffective surgeries. PMID:26122621

[The modern applications of radon therapy for the medical rehabilitation of the patients].

PubMed

Razumov, A N; Puriga, A O; Yurova, O V

2015-01-01

Radon therapy is one of the methods of physiobalneotherapy the mechanism of action of which is believed to consist of the influence of the small radiation doses of radon and its daughter products on the nervous, vascular, and immune apparatuses of the skin and mucosal membranes that eventually enhances the protective and adaptive potential of the body and thereby its ability to resist pathological impacts. At present, the high effectiveness of radon therapy is universally recognized and this method is widely applied for the combined treatment of various diseases in different fields of medicine. These include (1) diseases of the musculoskeletal system and locomotor disorders in the patients presenting with recurrent rheumatic fever, reactive arthritis, ankylosing spondylitis, post-traumatic osteoarthrosis and knee joint synovitis, the sympathico-tonic course of vegetative dystonia associated with connective tissue dysplasia, etc.; (2) neurological disorders in the patients presenting with cervical dorsopathy, neurological manifedstations of degenerative lesions of the cervical and lumbar spine, etc.; (3) cardiological disorders in the patients presenting with hypertensive disease, coronary heart disease, atherosclerosis of different localization, etc.; (4) gastrointestinal disorders in the patients presenting with gastric and duodenal ulcers, irritated bowel syndrome, etc.; (5) gynecological problems in the patients presenting with primary and secondary dysmenorrhea, genital endometriosis, uterine myoma, dysregulated reproductive function, polycystic ovary - syndrome, polycystic ovary syndrome and ovulatory disorders of proinflammatory origin, etc.

Proteostasis and Diseases of the Motor Unit.

PubMed

Rinaldi, Carlo; Mäger, Imre; Wood, Matthew J

2016-01-01

The accumulation in neurons of aberrant protein species, the pathological hallmark of many neurodegenerative diseases, results from a global impairment of key cellular processes governing protein synthesis/degradation and repair mechanisms, also known as the proteostasis network (PN). The growing number of connections between dysfunction of this intricate network of pathways and diseases of the motor unit, where both motor neurons and muscle are primarily affected, has provided momentum to investigate the muscle- and motor neuron-specific response to physiological and pathological stressors and to explore the therapeutic opportunities that manipulation of this process may offer. Furthermore, these diseases offer an unparalleled opportunity to deepen our understanding of the molecular mechanisms behind the intertissue communication and transfer of signals of proteostasis. The most compelling aspect of these investigations is their immediate potential for therapeutic impact: targeting muscle to stem degeneration of the motor unit would represent a dramatic paradigm therapeutic shift for treating these devastating diseases. Here we will review the current state of the art of the research on the alterations of the PN in diseases of the motor unit and its potential to result in effective treatments for these devastating neuromuscular disorders.

Predicting SF-6D utility scores from the Neck Disability Index and Numeric Rating Scales for Neck and Arm Pain

PubMed Central

Carreon, Leah Y.; Anderson, Paul A.; McDonough, Christine M.; Djurasovic, Mladen; Glassman, Steven D.

2010-01-01

Study Design Cross-sectional cohort Objective This study aims to provide an algorithm estimate SF-6D utilities using data from the NDI, neck pain and arm pain scores. Summary of Background Data Although cost-utility analysis is increasingly used to provide information about the relative value of alternative interventions, health state values or utilities are rarely available from clinical trial data. The Neck Disability Index (NDI) and numeric rating scales for neck and arm pain, are widely used disease-specific measures of symptoms, function and disability in patients with cervical degenerative disorders. The purpose of this study is to provide an algorithm to allow estimation of SF-6D utilities using data from the NDI, and numeric rating scales for neck and arm pain. Methods SF-36, NDI, neck and arm pain rating scale scores were prospectively collected pre-operatively, at 12 and 24 months post-operatively in 2080 patients undergoing cervical fusion for degenerative disorders. SF-6D utilities were computed and Spearman correlation coefficients were calculated for paired observations from multiple time points between NDI, neck and arm pain scores and SF-6D utility scores. SF-6D scores were estimated from the NDI, neck and arm pain scores using a linear regression model. Using a separate, independent dataset of 396 patients in which and NDI scores were available SF-6D was estimated for each subject and compared to their actual SF-6D. Results The mean age for those in the development sample, was 50.4 ± 11.0 years and 33% were male. In the validation sample the mean age was 53.1 ± 9.9 years and 35% were male. Correlations between the SF-6D and the NDI, neck and arm pain scores were statistically significant (p<0.0001) with correlation coefficients of 0.82, 0.62, and 0.50 respectively. The regression equation using NDI alone to predict SF-6D had an R2 of 0.66 and a root mean square error (RMSE) of 0.056. In the validation analysis, there was no statistically significant difference (p=0.961) between actual mean SF-6D (0.49 ± 0.08) and the estimated mean SF-6D score (0.49 ± 0.08) using the NDI regression model. Conclusion This regression-based algorithm may be a useful tool to predict SF-6D scores in studies of cervical degenerative disease that have collected NDI but not utility scores. PMID:20847713

Dysfunctional Metacognitive Beliefs in Body Dysmorphic Disorder

PubMed Central

Zeinodini, Zahra; Sedighi, Sahar; Rahimi, Mandana Baghertork; Noorbakhsh, Simasadat; Esfahani, Sepideh Rajezi

2016-01-01

The present study aims to examine the correlation of body dysmorphic disorder, with metacognitive subscales, metaworry and thought-fusion. The study was conducted in a correlation framework. Sample included 155 high school students in Isfahan, Iran in 2013-2014, gathered through convenience sampling. To gather data about BDD, Yale-Brown Obsessive Compulsive Scale Modified for BDD was applied. Then, Meta Cognitive Questionnaire, Metaworry Questionnaire, and Thought-Fusion Inventory were used to assess metacognitive subscales, metaworry and thought-fusion. Data obtained from this study were analyzed using Pearson correlation and multiple regressions in SPSS 18. Result indicated YBOCS-BDD scores had a significant correlation with scores from MCQ (P<0.05), MWG (P<0.05), and TFI (P<0.05). Also, multiple regressions were run to predict YBOCS from TFI, MWQ, and MCQ-30. These variables significantly predicted YBOCS [F (3,151) =32.393, R2=0.57]. Findings indicated that body dysmorphic disorder was significantly related to metacognitive subscales, metaworry, and thought fusion in high school students in Isfahan, which is in line with previous studies. A deeper understanding of these processes can broaden theory and treatment of BDD, thereby improve the lives of sufferers and potentially protect others from developing this devastating disorder. PMID:26493420

Treating postpartum depression and anxiety naturally.

PubMed

Zauderer, Cheryl; Davis, Wendy

2012-01-01

Postpartum depression and or perinatal mood disorders are complex phenomena with numerous interrelated factors. Approximately 13% of women experience some degree of depression following childbirth. Mental health professionals have described postpartum depression as encompassing a variety of syndromes and as ranging from mild depression and anxiety to more severe forms of emotional disorders. Evidence is accumulating that postpartum depression/perinatal mood disorders may adversely affect the mother-child relationship, and that it may also have long-term effects on the child if the mother does not receive treatment. Postpartum depression and anxiety disorders can have devastating effects on the mother, her baby, and the entire family. Frontline management typically includes medication, therapy, and social support. However, many women feel conflicted about using psychotropic medications during pregnancy and breastfeeding and are interested in learning about alternative therapies. If a pregnant or breastfeeding mother is prescribed psychiatric medications, she may not follow the prescription and may also be afraid to tell her provider. Women may refuse medications, even after weighing the pros and cons and safety issues with health care providers. For mild to moderate depression and anxiety, nonpharmacological choices need to be available for these women to provide them with alternative options and to encourage adherence to treatment.

A developmental and genetic classification for midbrain-hindbrain malformations

PubMed Central

Millen, Kathleen J.; Dobyns, William B.

2009-01-01

Advances in neuroimaging, developmental biology and molecular genetics have increased the understanding of developmental disorders affecting the midbrain and hindbrain, both as isolated anomalies and as part of larger malformation syndromes. However, the understanding of these malformations and their relationships with other malformations, within the central nervous system and in the rest of the body, remains limited. A new classification system is proposed, based wherever possible, upon embryology and genetics. Proposed categories include: (i) malformations secondary to early anteroposterior and dorsoventral patterning defects, or to misspecification of mid-hindbrain germinal zones; (ii) malformations associated with later generalized developmental disorders that significantly affect the brainstem and cerebellum (and have a pathogenesis that is at least partly understood); (iii) localized brain malformations that significantly affect the brain stem and cerebellum (pathogenesis partly or largely understood, includes local proliferation, cell specification, migration and axonal guidance); and (iv) combined hypoplasia and atrophy of putative prenatal onset degenerative disorders. Pertinent embryology is discussed and the classification is justified. This classification will prove useful for both physicians who diagnose and treat patients with these disorders and for clinical scientists who wish to understand better the perturbations of developmental processes that produce them. Importantly, both the classification and its framework remain flexible enough to be easily modified when new embryologic processes are described or new malformations discovered. PMID:19933510

QC operator’s nonneutral posture against musculoskeletal disorder’s (MSDs) risks

NASA Astrophysics Data System (ADS)

Kautsar, F.; Gustopo, D.; Achmadi, F.

2018-04-01

Musculoskeletal disorders refer to a gamut of inflammatory and degenerative disorders aggravated largely by the performance of work. It is the major cause of pain, disability, absenteeism and reduced productivity among workers worldwide. Although it is not fatal, MSDs have the potential to develop into serious injuries in the musculoskeletal system if ignored. QC operators work in nonneutral body posture. This cross-sectional study was condusted in order to investigate correlation between risk assessment results of QEC and body posture calculation of mannequin pro. Statistical analysis was condusted using SPSS version 16.0. Validity test, Reliability test and Regression analysis were conducted to compare the risk assessment output of applied method and nonneutral body posture simulation. All of QEC’s indicator classified as valid and reliable. The result of simple regression anlysis are back (0.326<4.32), shoulder/arm (8.489>4.32), wrist/hand (4.86 >4.32) and neck (1.298 <4.32). Result of this study shows that there is an influence between nonneutral body posture of the QC operator during work with risk of musculoskeletal disorders. The potential risk of musculoskeletal disorders is in the shoulder/arm and wrist/hand of the QC operator, whereas the back and neck are not affected.

Targeting midkine and pleiotrophin signalling pathways in addiction and neurodegenerative disorders: recent progress and perspectives

PubMed Central

Herradón, G; Pérez-García, C

2014-01-01

Midkine (MK) and pleiotrophin (PTN) are two neurotrophic factors that are highly up-regulated in different brain regions after the administration of various drugs of abuse and in degenerative areas of the brain. A deficiency in both MK and PTN has been suggested to be an important genetic factor, which confers vulnerability to the development of the neurodegenerative disorders associated with drugs of abuse in humans. In this review, evidence demonstrating that MK and PTN limit the rewarding effects of drugs of abuse and, potentially, prevent drug relapse is compiled. There is also convincing evidence that MK and PTN have neuroprotective effects against the neurotoxicity and development of neurodegenerative disorders induced by drugs of abuse. Exogenous administration of MK and/or PTN into the CNS by means of non-invasive methods is proposed as a novel therapeutic strategy for addictive and neurodegenerative diseases. Identification of new molecular targets downstream of the MK and PTN signalling pathways or pharmacological modulation of those already known may also provide a more traditional, but probably effective, therapeutic strategy for treating addictive and neurodegenerative disorders. Linked Articles This article is part of a themed section on Midkine. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2014.171.issue-4 PMID:23889475

Childhood obesity case statement.

PubMed

Esposito, Paul W; Caskey, Paul; Heaton, Lisa E; Otsuka, Norman

2013-04-01

The goal of this publication is to raise awareness of the impact of childhood obesity on the musculoskeletal health of children and its potential long-term implications. Relevant articles dealing with musculoskeletal disorders either caused by or worsened by childhood obesity were reviewed through a Pub Med search. Efforts to recognize and combat the childhood obesity epidemic were also identified through Internet search engines. This case statement was then reviewed by the members of the pediatric specialty group of the US Bone and Joint Initiative, which represents an extensive number of organizations dealing with musculoskeletal health. Multiple musculoskeletal disorders are clearly caused by or worsened by childhood obesity. The review of the literature clearly demonstrates the increased frequency and severity of many childhood musculoskeletal disorders. Concerns about the long-term implications of these childhood onset disorders such as pain and degenerative changes into adulthood are clearly recognized by all the member organizations of the US Bone and Joint Initiative. It is imperative to recognize the long-term implications of musculoskeletal disorders caused by or worsened by childhood obesity. It is also important to recognize that the ability to exercise comfortably is a key factor to developing a healthy lifestyle and maintaining a healthy body weight. Efforts to develop reasonable and acceptable programs to increase physical activity by all facets of society should be supported. Further research into the long-term implications of childhood musculoskeletal disorders related to childhood obesity is necessary. Copyright © 2013 Elsevier Inc. All rights reserved.

Autistic spectrum disorder: the challenge for dentists.

PubMed

Berman, Marvin H

2010-10-01

Those who actively work with children are, with increasing frequency, encountering patients who have been diagnosed with autistic disorders. Often, dentists may be the first healthcare providers to recognize that a 1- or 2-year-old child has some type of extraordinary pervasive behavioral disorder that a parent, fearing the worst, may have suspected instinctively and emotionally but never faced objectively. Currently, there are no empirical biological tests (eg, blood tests or brain scans) for ASD that are reliable. The definitive diagnosis of ASD is usually made by pediatricians, psychologists, or psychiatrists who institute a process of analysis which involves a developmental and clinical history, tests for cognitive function, and assessment of receptive and expressive language skills. The etiology of ASD is an enigma. Highly regarded researchers are of the opinion that there is probably more than one cause since the disorder can have such disparate manifestations. Genetics, environmental poisons, neurologic psychopathy, dietary deficiencies, and allergies have all been implicated. Pervasive developmental disorders, Asperger's syndrome, Rett syndrome, and childhood degenerative disorders are all considered a part of the ASD group, but the distinction between the various entities is not always clear. Given the fact that the etiology and the increased incidence of the various ASDs are scientifically puzzling, treatment modalities tend to be wide ranging and very much trial and error, especially since there is no cure. Dental professionals who treat patients with ASDs should be knowledgeable about the special needs of not only these patients, but also of their parents.

Autologous platelet gel for tissue regeneration in degenerative disorders of the knee

PubMed Central

Napolitano, Marcello; Matera, Saverio; Bossio, Marcello; Crescibene, Antonio; Costabile, Enrico; Almolla, Joan; Almolla, Hesham; Togo, Francesco; Giannuzzi, Casimiro; Guido, Giampiero

2012-01-01

Background The refinement of the use of platelet-derived growth factors that has occurred over the last decade has led to a broadening of the fields of use, in particular for new treatments in orthopaedics aimed at improving tissue regeneration. Materials and methods Twenty-seven patients, aged between 18 and 81 years, with a diagnosis of degenerative joint disease lasting for more than 1 year were treated. The patients were divided into two groups, one with arthritis of the knee, the other with degenerative cartilage disease of the knee. Both groups were treated with a therapeutic protocol consisting of a cycle of three infiltrations of platelet-rich plasma at weekly intervals. The extemporaneous preparation was made from a sample of about 8 mL of venous whole blood collected into a specific Fibrin Polymer 2 test-tube from RegenLab® and centrifuged before addition of calcium gluconate. During the initial pre-treatment evaluation, specific questionnaires were administered, the Numerical Rating Scale (NRS) for subjective measurement of pain and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC); these assessments were repeated 7 days after the end of the treatment and at 6 months during the follow-up. Results The parameters evaluated improved in both groups after treatment and there was a further improvement after 6 months of follow-up; furthermore, there was a substantial decrease in pain right after the first infiltration. Discussion The patients were treated on an out-patient basis by a specifically created multidisciplinary team comprising a transfusion specialist, an orthopaedist and a radiologist, who collaborate in a symbiotic manner. The out-patient protocol exploits the regenerative properties of platelet-rich plasma, which is a low cost treatment; in practice, a diagnostic-therapeutic programme of lower intensity, but of high technical and professional quality is created. The strategy also reduces both the number of hospital services and the pharmacological support required, thereby optimising the use of health care resources. PMID:22044954

Novel Molecular Therapies for Heritable Skin Disorders

PubMed Central

Uitto, Jouni; Christiano, Angela M.; Irwin McLean, W. H.; McGrath, John A.

2013-01-01

Tremendous progress has been made in the past two decades in molecular genetics of heritable skin diseases, and pathogenic mutations have been identified in as many as 500 distinct human genes. This progress has resulted in improved diagnosis with prognostic implications, refined genetic counseling, and has formed the basis for prenatal and presymptomatic testing as well as preimplantation genetic diagnosis. However, there has been relatively little progress in developing effective and specific treatments for these often devastating diseases. Very recently, however, a number of novel molecular strategies, including gene therapy, cell-based approaches, and protein replacement therapy have been explored for treatment of these conditions. This overview will focus on the prototypic heritable blistering disorders, epidermolysis bullosa and related keratinopathies, in which significant progress has been recently made towards treatment, and illustrate how some of the translational research therapies have already entered the clinical arena. PMID:22158553

ZIP4 silencing improves bone loss in pancreatic cancer

PubMed Central

Yang, Jingxuan; Ding, Hao; LeBrun, Drake; Ding, Kai; Houchen, Courtney W.; Postier, Russell G.; Ambrose, Catherine G.; Li, Zhaoshen; Bi, Xiaohong; Li, Min

2015-01-01

Metabolic bone disorders are associated with several types of human cancers. Pancreatic cancer patients usually suffer from severe nutrition deficiency, muscle wasting, and loss of bone mass. We have previously found that silencing of a zinc transporter ZIP4 prolongs the survival and reduces the severity of the cachexia in vivo. However, the role of ZIP4 in the pancreatic cancer related bone loss remains unknown. In this study we investigated the effect of ZIP4 knockdown on the bone structure, composition and mechanical properties of femurs in an orthotopic xenograft mouse model. Our data showed that silencing of ZIP4 resulted in increased bone tissue mineral density, decreased bone crystallinity and restoration of bone strength through the RANK/RANKL pathway. The results further support the impact of ZIP4 on the progression of pancreatic cancer, and suggest its potential significance as a therapeutic target for treating patients with such devastating disease and cancer related disorders. PMID:26305676

Neurosurgical Issues in Pregnancy.

PubMed

Can, Anil; Du, Rose

2017-12-01

Although rare, intracranial hemorrhage due to rupture of cerebral vascular malformations or intracranial aneurysms during pregnancy is a potentially devastating and life-threatening disorder, posing a diagnostic and therapeutic challenge to a multidisciplinary team of neurosurgeons, neurologists, obstetricians, and anesthesiologists. Despite the significant risk of morbidity and mortality affecting both the mother and the unborn child, knowledge of the natural history, epidemiology, and appropriate management of cerebral vascular malformations and intracranial aneurysms in pregnant women is limited. Although emergent neurosurgical concerns usually outweigh obstetric considerations, and treatment of these disorders is generally similar in pregnant and nonpregnant women, any necessary and feasible modifications to protect the unborn child should be made. This article reviews the management of ruptured intracranial aneurysms and cerebral vascular malformations, including arteriovenous malformations, cavernous malformations, and moyamoya disease, in women during pregnancy, partus, and puerperium. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

The neurofibromatoses. Part 2: NF2 and schwannomatosis.

PubMed

Lu-Emerson, Christine; Plotkin, Scott R

2009-01-01

The neurofibromatoses, including neurofibromatosis 1 (NF1), neurofibromatosis 2 (NF2), and schwannomatosis, comprise a group of genetically distinct disorders of the nervous system that are unified by the predisposition to nerve sheath tumors. All 3 types of NF have tumor manifestations (consistent with tumor-suppressor status) and nontumor manifestations. In the second part of this 2-part series, the manifestations of NF2 and schwannomatosis are reviewed. NF2 is characterized by bilateral vestibular schwannomas, meningiomas, ependymomas, cataracts, and epiretinal membranes. The combination of complete hearing loss from vestibular schwannomas and blindness from bifacial weakness is a devastating potential outcome of NF2. Schwannomatosis is characterized by multiple nonvestibular, nonintradermal schwannomas and chronic pain. Recently, germline alterations in the SMARCB1/INI1 gene have been implicated in both familial and sporadic forms of this disorder. Neurologists play an important role in the diagnosis and management of the neurofibromatoses.

Gene Expression in Human Meniscal Tears has Limited Association with Early Degenerative Changes in Knee Articular Cartilage

PubMed Central

Brophy, Robert H.; Sandell, Linda J.; Cheverud, James M.; Rai, Muhammad Farooq

2018-01-01

Purpose/Aim Meniscus tears are a common injury to the knee associated with the development of osteoarthritis. Gene expression in the injured meniscus may be associated with early degeneration in the articular cartilage. The purpose of this study was to test the hypothesis that gene expression in meniscus tears is associated with early degenerative changes in the articular cartilage at the time of partial meniscectomy. Materials and Methods Torn meniscus was removed at the time of partial meniscectomy in 63 patients without radiographic osteoarthritis. Meniscal mRNA expression was measured by quantitative PCR for multiple molecular markers of osteoarthritis and cartilage homeostasis. The presence of early degenerative changes in the knee was recorded by X-ray (N=63), magnetic resonance imaging (MRI, N=48) and arthroscopy (N=63). Gene expression was tested for correlation with the presence/absence of degenerative changes after adjusting for age, sex and body mass index. Results Overall gene expression varied significantly with degenerative changes based on X-ray (P=0.047) and MRI (P=0.018). The linear combination of gene variation was also significant. However, only adiponectin (ADIPOQ) (P=0.015) was expressed at a significantly lower level in patients with chondrosis on MRI while the expression of ADIPOQ (P=0.035) and resistin (RETN) (P=0.017) was higher in patients with early degenerative changes on X-ray. Conclusions There is an overall association of gene expression in meniscal tears to early degenerative changes in the knee, but only a limited number of specific genes demonstrate this relationship. The roles of adiponectin and resistin in knee injury and osteoarthritis deserve further study. PMID:27435997

Pedicle screw-rod fixation: a feasible treatment for dogs with severe degenerative lumbosacral stenosis.

PubMed

Tellegen, Anna R; Willems, Nicole; Tryfonidou, Marianna A; Meij, Björn P

2015-12-07

Degenerative lumbosacral stenosis is a common problem in large breed dogs. For severe degenerative lumbosacral stenosis, conservative treatment is often not effective and surgical intervention remains as the last treatment option. The objective of this retrospective study was to assess the middle to long term outcome of treatment of severe degenerative lumbosacral stenosis with pedicle screw-rod fixation with or without evidence of radiological discospondylitis. Twelve client-owned dogs with severe degenerative lumbosacral stenosis underwent pedicle screw-rod fixation of the lumbosacral junction. During long term follow-up, dogs were monitored by clinical evaluation, diagnostic imaging, force plate analysis, and by using questionnaires to owners. Clinical evaluation, force plate data, and responses to questionnaires completed by the owners showed resolution (n = 8) or improvement (n = 4) of clinical signs after pedicle screw-rod fixation in 12 dogs. There were no implant failures, however, no interbody vertebral bone fusion of the lumbosacral junction was observed in the follow-up period. Four dogs developed mild recurrent low back pain that could easily be controlled by pain medication and an altered exercise regime. Pedicle screw-rod fixation offers a surgical treatment option for large breed dogs with severe degenerative lumbosacral stenosis with or without evidence of radiological discospondylitis in which no other treatment is available. Pedicle screw-rod fixation alone does not result in interbody vertebral bone fusion between L7 and S1.

Evaluation of degenerative changes in articular cartilage of osteoarthritis by Raman spectroscopy

NASA Astrophysics Data System (ADS)

Oshima, Yusuke; Ishimaru, Yasumitsu; Kiyomatsu, Hiroshi; Hino, Kazunori; Miura, Hiromasa

2018-02-01

Osteoarthritis (OA) is a very common joint disease in the aging population. Main symptom of OA is accompanied by degenerative changes of articular cartilage. Cartilage contains mostly type II collagen and proteoglycans, so it is difficult to access the quality and morphology of cartilage tissue in situ by conventional diagnostic tools (X-ray, MRI and echography) directly or indirectly. Raman spectroscopy is a label-free technique which enables to analyze molecular composition in degenerative cartilage. In this proposal, we aim to develop Raman spectroscopic system for the quality assessment of articular cartilage during arthroscopic surgery. Toward this goal, we are focusing on the proteoglycan content and collagen fiber alignment in cartilage matrix which may be associated with degenerative changes in OA, and we designed an original Raman device for remote sensing during arthroscopic surgery. In this project, we define the grading system for cartilage defect based on Raman spectroscopy, and we complete the evaluation of the Raman probing system which makes it possible to detect early stage of degenerative cartilage as a novel tool for OA diagnosis using human subject.

Dietary Phytochemicals: Natural Swords Combating Inflammation and Oxidation-Mediated Degenerative Diseases

PubMed Central

2016-01-01

Cumulatively, degenerative disease is one of the most fatal groups of diseases, and it contributes to the mortality and poor quality of life in the world while increasing the economic burden of the sufferers. Oxidative stress and inflammation are the major pathogenic causes of degenerative diseases such as rheumatoid arthritis (RA), diabetes mellitus (DM), and cardiovascular disease (CVD). Although a number of synthetic medications are used to treat these diseases, none of the current regimens are completely safe. Phytochemicals (polyphenols, carotenoids, anthocyanins, alkaloids, glycosides, saponins, and terpenes) from natural products such as dietary fruits, vegetables, and spices are potential sources of alternative medications to attenuate the oxidative stress and inflammation associated with degenerative diseases. Based on in vitro, in vivo, and clinical trials, some of these active compounds have shown good promise for development into novel agents for treating RA, DM, and CVD by targeting oxidative stress and inflammation. In this review, phytochemicals from natural products with the potential of ameliorating degenerative disease involving the bone, metabolism, and the heart are described. PMID:27721914

The provision of mental health services in England for people over 65 years of age, 1970-78.

PubMed

Hilton, Claire

2008-09-01

The twentieth century saw an increasing number of people living into old age, and consequently a higher prevalence of age-related chronic degenerative brain disorders. By 1971 the mental hospitals were almost half full with people over 65 years of age. Thus plans to close the mental hospitals meant that the development of community mental health services for older people was a necessity. Although there was a multi-disciplinary focus on the care of older people, the lead in service development was largely taken by psychiatrists, both individually and through the Group for the Psychiatry of Old Age at the Royal College of Psychiatrists.

Argus II retinal prosthesis system: a review of patient selection criteria, surgical considerations, and post-operative outcomes.

PubMed

Finn, Avni P; Grewal, Dilraj S; Vajzovic, Lejla

2018-01-01

Retinitis pigmentosa (RP) is a group of heterogeneous inherited retinal degenerative disorders characterized by progressive rod and cone dysfunction and ensuing photoreceptor loss. Many patients suffer from legal blindness by their 40s or 50s. Artificial vision is considered once patients have lost all vision to the point of bare light perception or no light perception. The Argus II retinal prosthesis system is one such artificial vision device approved for patients with RP. This review focuses on the factors important for patient selection. Careful pre-operative screening, counseling, and management of patient expectations are critical for the successful implantation and visual rehabilitation of patients with the Argus II device.

Obesity & osteoarthritis

PubMed Central

King, Lauren K.; March, Lyn; Anandacoomarasamy, Ananthila

2013-01-01

The most significant impact of obesity on the musculoskeletal system is associated with osteoarthritis (OA), a disabling degenerative joint disorder characterized by pain, decreased mobility and negative impact on quality of life. OA pathogenesis relates to both excessive joint loading and altered biomechanical patterns together with hormonal and cytokine dysregulation. Obesity is associated with the incidence and progression of OA of both weight-bearing and non weight-bearing joints, to rate of joint replacements as well as operative complications. Weight loss in OA can impart clinically significant improvements in pain and delay progression of joint structural damage. Further work is required to determine the relative contributions of mechanical and metabolic factors in the pathogenesis of OA. PMID:24056594

Effect of Combined Stress on Morphological Changes and Expression of NO Synthases in Rat Ventral Hippocampus.

PubMed

Smirnov, A V; Tyurenkov, I N; Shmidt, M V; Ekova, M R; Mednikov, D S; Borodin, D D

2015-11-01

Adult rats were subjected to 7-day combined stress with stochastic changes of stressors of different modalities (noise, vibration, pulsating bright light) along with mobility restriction and elevated temperature in the chamber during stress exposures (daily 30-min sessions). Circulatory disorders, inhibition of endothelial NO-synthase expression in endothelial cells of the microcirculatory bed, perivascular edema, pronounced degenerative changes, and enhanced expression of inducible NO synthase in CA3 pyramidal neurons in the ventral hippocampus of stressed 12-month-old rats were observed. These findings can attest to the involvement NOdependent mechanisms and different contribution of NO synthase isoforms into the formation of hippocampal neuronal damage.

Choice of valve prosthesis in a rare clinical condition: aortic stenosis due to alkaptonuria.

PubMed

Thakur, Sameer; Markman, Phuong; Cullen, Hugh

2013-10-01

Alkaptonuria is a rare inherited disorder of tyrosine metabolism, which results in deposition of homogentisic acid in the connective tissues. The accumulation of homogentisic acid in connective tissue causes the syndrome known as ochronosis, which is typically manifested by skin pigmentation, degenerative arthropathy and discolouration of urine. Cardiovascular involvement is a much less common complication of alkaptonuria but poses a greater risk to the patient's health. We present the case of a 65 year-old man with aortic stenosis and a previous diagnosis of alkaptonuria who underwent successful aortic valve replacement with a mechanical prosthesis. Crown Copyright © 2013. Published by Elsevier B.V. All rights reserved.

Maintaining the Brain: Insight into Human Neurodegeneration From Drosophila Mutants

PubMed Central

Lessing, Derek; Bonini, Nancy M.

2009-01-01

The fruit fly Drosophila melanogaster has brought significant advances to research in neurodegenerative disease, notably in the identification of genes that are required to maintain the structural integrity of the brain, defined by recessive mutations that cause adult-onset neurodegeneration. Here, we survey these genes in the fly and classify them according to five key cell biological processes. Over half of these genes have counterparts in mouse or human that are also associated with neurodegeneration. Fly genetics continues to be instrumental in the analysis of degenerative disease, with notable recent advances in our understanding of several inherited disorders, as well as Parkinson’s Disease and the central role of mitochondria in neuronal maintenance. PMID:19434080

Basic radiological assessment of synovial diseases: a pictorial essay

PubMed Central

Turan, Aynur; Çeltikçi, Pınar; Tufan, Abdurrahman; Öztürk, Mehmet Akif

2017-01-01

The synovium is a specialized tissue lining the synovial joints, bursae, and tendon sheaths of the body. It is affected by various localized or systemic disorders. Synovial diseases can be classified as inflammatory, infectious, degenerative, traumatic, hemorrhagic, and neoplastic. Damage in other intraarticular structures, particularly cartilages, generally occurs as a part of pathologic processes involving the synovium, leading to irreversible joint destruction. Imaging has an essential role in the early detection of synovial diseases prior to irreversible joint damage. Obtaining and understanding characteristic imaging findings of synovial diseases enables a proper diagnosis for early treatment. This article focuses on the recent literature that is related with the role of imaging in synovial disease. PMID:28638696

The Status of RPE65 Gene Therapy Trials: Safety and Efficacy

PubMed Central

Pierce, Eric A.; Bennett, Jean

2015-01-01

Several groups have reported the results of clinical trials of gene augmentation therapy for Leber congenital amaurosis (LCA) because of mutations in the RPE65 gene. These studies have used subretinal injection of adeno-associated virus (AAV) vectors to deliver the human RPE65 cDNA to the retinal pigment epithelial (RPE) cells of the treated eyes. In all of the studies reported to date, this approach has been shown to be both safe and effective. The successful clinical trials of gene augmentation therapy for retinal degeneration caused by mutations in the RPE65 gene sets the stage for broad application of gene therapy to treat retinal degenerative disorders. PMID:25635059

Subacute sclerosing panencephalitis presenting as neuromyelitis optica.

PubMed

Raut, Tushar Premraj; Singh, Maneesh Kumar; Garg, Ravindra Kumar; Naphade, Pravin Umakant

2012-12-14

Subacute sclerosing panencephalitis (SSPE) is a slowly progressing inflammatory and degenerative disorder of the brain caused by a mutant measles virus. The diagnosis of SSPE is based on characteristic clinical and EEG findings (periodic complexes) and demonstration of elevated antibody titres against measles in cerebrospinal fluid. SSPE can have atypical clinical features at the onset. The authors here report a case of a 3-year-old child who presented with vision loss followed 15 months later by quadriparesis with bladder involvement. These clinical features resembled that of neuromyelitis optica. However, as the disease progressed, appearance of myoclonic jerks, periodic discharges on EEG and positive cerebrospinal fluid serology for measles led to the final diagnosis of SSPE.

Subacute sclerosing panencephalitis presenting as neuromyelitis optica

PubMed Central

Raut, Tushar Premraj; Singh, Maneesh Kumar; Garg, Ravindra Kumar; Naphade, Pravin Umakant

2012-01-01

Subacute sclerosing panencephalitis (SSPE) is a slowly progressing inflammatory and degenerative disorder of the brain caused by a mutant measles virus. The diagnosis of SSPE is based on characteristic clinical and EEG findings (periodic complexes) and demonstration of elevated antibody titres against measles in cerebrospinal fluid. SSPE can have atypical clinical features at the onset. The authors here report a case of a 3-year-old child who presented with vision loss followed 15 months later by quadriparesis with bladder involvement. These clinical features resembled that of neuromyelitis optica. However, as the disease progressed, appearance of myoclonic jerks, periodic discharges on EEG and positive cerebrospinal fluid serology for measles led to the final diagnosis of SSPE. PMID:23242079

Real efficiency of ambulatory laser treatment at the patients with different rheumatic diseases

NASA Astrophysics Data System (ADS)

Sidenco, Elena-Luminita; Ristache, Sanda; Belu, Luminita

2001-06-01

We consulted 189 patients, with different locomotory diseases: degenerative, posttraumatic and chronic inflammatory rheumatic diseases. We followed the main clinical parameters: pain, limitation of mobility, affected function, inflammation and disorders of sensitivity. We applied an infrared LASER source of 100 mW (BTL), daily, for 5 days. The tolerance of the patients at the LASER treatment was excellent (100%). The evolution of the clinical parameters was variated, but inflammation, limitation of mobility and the affected function significantly improved (30-50%). We found a significant diminution of pain (27- 39%). We believe the LASER treatment in ambulatory conditions is essential for the function of the patients with different locomotory diseases.

Posttraumatic stress disorder: a serious post-earthquake complication.

PubMed

Farooqui, Mudassir; Quadri, Syed A; Suriya, Sajid S; Khan, Muhammad Adnan; Ovais, Muhammad; Sohail, Zohaib; Shoaib, Samra; Tohid, Hassaan; Hassan, Muhammad

2017-01-01

Earthquakes are unpredictable and devastating natural disasters. They can cause massive destruction and loss of life and survivors may suffer psychological symptoms of severe intensity. Our goal in this article is to review studies published in the last 20 years to compile what is known about posttraumatic stress disorder (PTSD) occurring after earthquakes. The review also describes other psychiatric complications that can be associated with earthquakes, to provide readers with better overall understanding, and discusses several sociodemographic factors that can be associated with post-earthquake PTSD. A search for literature was conducted on major databases such as MEDLINE, PubMed, EMBASE, and PsycINFO and in neurology and psychiatry journals, and many other medical journals. Terms used for electronic searches included, but were not limited to, posttraumatic stress disorder (PTSD), posttraumatic symptoms, anxiety, depression, major depressive disorder, earthquake, and natural disaster. The relevant information was then utilized to determine the relationships between earthquakes and posttraumatic stress symptoms. It was found that PTSD is the most commonly occurring mental health condition among earthquake survivors. Major depressive disorder, generalized anxiety disorder, obsessive compulsive disorder, social phobia, and specific phobias were also listed. The PTSD prevalence rate varied widely. It was dependent on multiple risk factors in target populations and also on the interval of time that had elapsed between the exposure to the deadly incident and measurement. Females seemed to be the most widely-affected group, while elderly people and young children exhibit considerable psychosocial impact.

Human Amniotic Tissue-derived Allograft, NuCel, in Posteriolateral Lumbar Fusions for Degenerative Disc Disease

ClinicalTrials.gov

2017-09-14

Lumbar Degenerative Disc Disease; Spinal Stenosis; Spondylolisthesis; Spondylosis; Intervertebral Disk Displacement; Intervertebral Disk Degeneration; Spinal Diseases; Bone Diseases; Musculoskeletal Diseases; Spondylolysis

General Anesthetics to Treat Major Depressive Disorder: Clinical Relevance and Underlying Mechanisms.

PubMed

Vutskits, Laszlo

2018-01-01

Major depressive disorder is a frequent and devastating psychological condition with tremendous public health impact. The underlying pathophysiological mechanisms involve abnormal neurotransmission and a relatedly impaired synaptic plasticity. Since general anesthetics are potent modulators of neuronal activity and, thereby, can exert long-term context-dependent impact on neural networks, an intriguing hypothesis is that these drugs could enhance impaired neural plasticity associated with certain psychiatric diseases. Clinical observations over the past few decades appear to confirm this possibility. Indeed, equipotency of general anesthesia alone in comparison with electroconvulsive therapy under general anesthesia has been demonstrated in several clinical trials. Importantly, in the past 15 years, intravenous administration of subanesthetic doses of ketamine have also been demonstrated to have rapid antidepressant effects. The molecular, cellular, and network mechanisms underlying these therapeutic effects have been partially identified. Although several important questions remain to be addressed, the ensemble of these experimental and clinical observations opens new therapeutic possibilities in the treatment of depressive disorders. Importantly, they also suggest a new therapeutic role for anesthetics that goes beyond their principal use in the perioperative period to facilitate surgery.

Idiopathic orthostatic intolerance and postural tachycardia syndromes

NASA Technical Reports Server (NTRS)

Jacob, G.; Biaggioni, I.; Robertson, D. (Principal Investigator)

1999-01-01

Upright posture imposes a substantial gravitational stress on the body, for which we are able to compensate, in large part because of the autonomic nervous system. Alteration in autonomic function, therefore, may lead to orthostatic intolerance. On one extreme, patients with autonomic failure caused by degenerative loss of autonomic function are severely disabled by orthostatic hypotension and may faint whenever they stand up. Fortunately, such patients are relatively rare. On the other hand, disabling orthostatic intolerance can develop in otherwise normal young people. These patients can be severely impaired by symptoms of fatigue, tachycardia, and shortness of breath when they stand up. The actual incidence of this disorder is unknown, but these patients make up the largest group of patients referred to centers that specialize in autonomic disorders. We will review recent advances made in the understanding of this condition, potential pathophysiological mechanisms that contribute to orthostatic intolerance, therapeutic alternatives currently available for the management of these patients, and areas in which more research is needed.

Inclusion body myositis.

PubMed

Dimachkie, Mazen M; Barohn, Richard J

2012-07-01

The idiopathic inflammatory myopathies are a group of rare disorders that share many similarities. These include dermatomyositis (DM), polymyositis (PM), necrotizing myopathy (NM), and sporadic inclusion body myositis (IBM). Inclusion body myositis is the most common idiopathic inflammatory myopathy after age 50 and it presents with chronic proximal leg and distal arm asymmetric mucle weakness. Despite similarities with PM, it is likely that IBM is primarily a degenerative disorder rather than an inflammatory muscle disease. Inclusion body myositis is associated with a modest degree of creatine kinase (CK) elevation and an abnormal electromyogram demonstrating an irritative myopathy with some chronicity. The muscle histopathology demonstrates inflammatory exudates surrounding and invading nonnecrotic muscle fibers often times accompanied by rimmed vacuoles. In this chapter, we review sporadic IBM. We also examine past, essentially negative, clinical trials in IBM and review ongoing clinical trials. For further details on DM, PM, and NM, the reader is referred to the idiopathic inflammatory myopathies chapter. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Inclusion Body Myositis

PubMed Central

Barohn, Richard J.

2014-01-01

The idiopathic inflammatory myopathies (IIM) are a heterogenous group of rare disorders that share many similarities. In addition to sporadic inclusion body myositis (IBM), these include dematomyositis (DM), polymyositis (PM), and autoimmune necrotizing myopathy (NM). For discussion of later three disorders, the reader is referred to the IIM review in this issue. IBM is the most common IIM after age 50. It typically presents with chronic insidious proximal leg and/or distal arm asymmetric muscle weakness leading to recurrent falls and loss of dexterity. Creatine kinase (CK) is up to 15 times elevated in IBM and needle electromyograhy (EMG) mostly shows a chronic irritative myopathy. Muscle histopathology demonstrates endomysial inflammatory exudates surrounding and invading non-necrotic muscle fibers often times accompanied by rimmed vacuoles and protein deposits. Despite inflammatory muscle pathology suggesting similarity with PM, it likely that IBM is has a prominent degenerative component as supported by refractoriness to immunosuppressive therapy. We review the evolution of our knowledge in IBM with emphasis on recent developments in the field and discuss ongoing clinical trials. PMID:25037082

Vessel-associated stem cells from skeletal muscle: From biology to future uses in cell therapy.

PubMed

Sancricca, Cristina; Mirabella, Massimiliano; Gliubizzi, Carla; Broccolini, Aldobrando; Gidaro, Teresa; Morosetti, Roberta

2010-06-26

Over the last years, the existence of different stem cells with myogenic potential has been widely investigated. Besides the classical skeletal muscle progenitors represented by satellite cells, numerous multipotent and embryologically unrelated progenitors with a potential role in muscle differentiation and repair have been identified. In order to conceive a therapeutic approach for degenerative muscle disorders, it is of primary importance to identify an ideal stem cell endowed with all the features for a possible use in vivo. Among all emerging populations, vessel-associated stem cells are a novel and promising class of multipotent progenitors of mesodermal origin and with high myogenic potential which seem to best fit all the requirements for a possible cell therapy. In vitro and in vivostudies have already tested the effectiveness and safety of vessel-associated stem cells in animal models. This leads to the concrete possibility in the future to start pilot human clinical trials, hopefully opening the way to a turning point in the treatment of genetic and acquired muscle disorders.

Intrathoracic tumor of the chest wall: A case of Castleman's disease mimicking myositis of the lower extremities.

PubMed

Tampakis, Athanasios; Tampaki, Ekaterini Christina; Daikeler, Thomas; Lardinois, Didier

2017-11-01

Castleman's disease refers to a group of uncommon lymphoproliferative disorders which exhibit common lymph-node histological features. A 72-year-old male patient presented with signs of lower limb myositis. Detailed work-up focused initially on evaluating hematological malignancies, the presence of a solid tumor, autoimmune diseases and degenerative disorders of the peripheral nerves. Finally, a PET-CT scan was performed to exclude paraneoplastic manifestations of a primary tumor, revealing  however a tumor of the thoracic wall. The definite histological diagnosis confirmed the presence of unicentric Castleman's disease of the chest wall. The manifestations of the present case suggest that a systemic inflammation might occur in the unicentric form of the disease possibly due to cytokine hypersecretion. The unicentric manifestation of the disease should be well distinguished from the multicentric appearance. Unicentric disease is a surgical condition and warrants a follow-up based on the systemic inflammation that might occur.

Homeostatic systems, biocybernetics, and autonomic neuroscience.

PubMed

Goldstein, David S; Kopin, Irwin J

2017-12-01

In this review we describe a series of major concepts introduced during the past 150years that have contributed to our current understanding about how physiological processes required for well-being and survival are regulated. One can theorize that hierarchical networks involving input-output relationships continuously orchestrate and learn adaptive patterns of observable behaviors, cognition, memory, mood, and autonomic systems. Taken together, these networks function as "good regulators" determining levels of internal variables and act as if there were homeostatic comparators ("homeostats"). The consequences of models with vs. without homeostats remain the same in terms of allostatic load and the eventual switch from stabilizing negative feedback loops to destabilizing, pathogenic positive feedback loops. Understanding this switch seems important for comprehending senescence-related, neurodegenerative disorders that involve the autonomic nervous system. Our general proposal is that disintegration of homeostatic systems causes disorders of regulation in degenerative diseases and that medical cybernetics can inspire and rationalize new approaches to treatment and prevention. Published by Elsevier B.V.

Neuroregression as an initial manifestation in a toddler with acquired pernicious anaemia

PubMed Central

Yoganathan, Sangeetha; Thomas, Maya Mary; Mathai, Sarah; Ghosh, Urmi

2015-01-01

The aetiology spectrum for neuroregression in infants and toddlers is diverse. Vitamin B12 deficiency-mediated neuroregression is less commonly considered as a differential. Prevalence of pernicious anaemia in the general population is 0.1% and is extremely rare in children. We describe a 35-month-old toddler with neuroregression, seizures, coarse tremors, bleating cry and neuropathy. His clinical symptomatology mimicked grey matter degenerative illness and infantile tremor syndrome, a nutritional deficiency-mediated movement disorder. His vitamin B12 level was low and serum homocysteine level was elevated. Haematological manifestations were not overt and anti-intrinsic factor antibody was positive. With parenteral vitamin B12 therapy, there was a dramatic response with clinical and laboratory translation. This report emphasises the need for a high index of suspicion and screening for markers of vitamin B12 deficiency in all children with unexplained acute or subacute neuroregression, seizures and movement disorders as it is potentially reversible. PMID:26678841

Neuroregression as an initial manifestation in a toddler with acquired pernicious anaemia.

PubMed

Yoganathan, Sangeetha; Thomas, Maya Mary; Mathai, Sarah; Ghosh, Urmi

2015-12-17

The aetiology spectrum for neuroregression in infants and toddlers is diverse. Vitamin B12 deficiency-mediated neuroregression is less commonly considered as a differential. Prevalence of pernicious anaemia in the general population is 0.1% and is extremely rare in children. We describe a 35-month-old toddler with neuroregression, seizures, coarse tremors, bleating cry and neuropathy. His clinical symptomatology mimicked grey matter degenerative illness and infantile tremor syndrome, a nutritional deficiency-mediated movement disorder. His vitamin B12 level was low and serum homocysteine level was elevated. Haematological manifestations were not overt and anti-intrinsic factor antibody was positive. With parenteral vitamin B12 therapy, there was a dramatic response with clinical and laboratory translation. This report emphasises the need for a high index of suspicion and screening for markers of vitamin B12 deficiency in all children with unexplained acute or subacute neuroregression, seizures and movement disorders as it is potentially reversible. 2015 BMJ Publishing Group Ltd.

Pathophysiology of Degenerative Mitral Regurgitation: New 3-Dimensional Imaging Insights.

PubMed

Antoine, Clemence; Mantovani, Francesca; Benfari, Giovanni; Mankad, Sunil V; Maalouf, Joseph F; Michelena, Hector I; Enriquez-Sarano, Maurice

2018-01-01

Despite its high prevalence, little is known about mechanisms of mitral regurgitation in degenerative mitral valve disease apart from the leaflet prolapse itself. Mitral valve is a complex structure, including mitral annulus, mitral leaflets, papillary muscles, chords, and left ventricular walls. All these structures are involved in physiological and pathological functioning of this valvuloventricular complex but up to now were difficult to analyze because of inherent limitations of 2-dimensional imaging. The advent of 3-dimensional echocardiography, computed tomography, and cardiac magnetic resonance imaging overcoming these limitations provides new insights into mechanistic analysis of degenerative mitral regurgitation. This review will detail the contribution of quantitative and qualitative dynamic analysis of mitral annulus and mitral leaflets by new imaging methods in the understanding of degenerative mitral regurgitation pathophysiology. © 2018 American Heart Association, Inc.

Health survey of 167 pet rabbits (Oryctolagus cuniculus) in Finland.

PubMed

Mäkitaipale, J; Harcourt-Brown, F M; Laitinen-Vapaavuori, O

2015-10-24

Only a limited amount of information is available about health status of pet rabbits. The aim of this study was to obtain data about the health status of pet rabbits considered healthy by the owners in Finland. Physical examination and lateral abdominal and lateral skull radiography were performed on 167 pet rabbits of which 118 (70.7 per cent) had abnormal findings in at least one examination. The most common findings were acquired dental disease (n=67, 40.1 per cent), vertebral column deformities and degenerative lesions (n=52, 31.1 per cent), skin disorders (n=28, 16.8 per cent) and eye disorders (n=12, 7.2 per cent). Vertebral column angulating deformities were significantly more common in dwarf lop rabbits (P≤0.001). The prevalence of health disorders was significantly higher in rabbits over three years of age of which 51 (82.3 per cent) had findings in at least one examination (P<0.05). Rabbits as prey animals hide their illness, which cause difficulties to owners to recognise health problems. Because of the high prevalence of clinical and radiological findings in apparently healthy pet rabbits, regular physical examinations are advised, especially for animals over three years old. British Veterinary Association.

Contribution of Inhibitor of DNA Binding/Differentiation-3 and Endocrine Disrupting Chemicals to Pathophysiological Aspects of Chronic Disease

PubMed Central

2017-01-01

The overwhelming increase in the global incidence of obesity and its associated complications such as insulin resistance, atherosclerosis, pulmonary disease, and degenerative disorders including dementia constitutes a serious public health problem. The Inhibitor of DNA Binding/Differentiation-3 (ID3), a member of the ID family of transcriptional regulators, has been shown to play a role in adipogenesis and therefore ID3 may influence obesity and metabolic health in response to environmental factors. This review will highlight the current understanding of how ID3 may contribute to complex chronic diseases via metabolic perturbations. Based on the increasing number of reports that suggest chronic exposure to and accumulation of endocrine disrupting chemicals (EDCs) within the human body are associated with metabolic disorders, we will also consider the impact of these chemicals on ID3. Improved understanding of the ID3 pathways by which exposure to EDCs can potentiate complex chronic diseases in populations with metabolic disorders (obesity, metabolic syndrome, and glucose intolerance) will likely provide useful knowledge in the prevention and control of complex chronic diseases associated with exposure to environmental pollutants. PMID:28785583

The role for IGF-1-derived small neuropeptides as a therapeutic target for neurological disorders.

PubMed

Guan, Jian; Harris, Paul; Brimble, Margaret; Lei, Yang; Lu, Jun; Yang, Yang; Gunn, Alistair J

2015-06-01

Exogenous IGF-1 protects the brain from ischemic injury and improves function. However, its clinical application to neurological disorders is limited by its large molecular size, poor central uptake and mitogenic potential. In this review, the authors have discussed the efficacy, pharmacokinetics and mechanisms of IGF-1 derivatives on protecting acute brain injury, preventing memory impairment and improving recovery from neurological degenerative conditions evaluated in various animal models. We have included natural metabolites of IGF-1, glycine-proline-glutamate (GPE), cleaved from N-terminal IGF-1 and cyclic glycine-proline (cGP) as well as the structural analogues of GPE and cGP, glycine-2-methyl-proline-glutamate and cyclo-l-glycyl-l-2-allylproline, respectively. In addition, the regulatory role for cGP in bioavailability of IGF-1 has also been discussed. These small neuropeptides provide effective neuroprotection by offering an improved pharmacokinetic profile and more practical route of administration compared with IGF-1 administration. Developing modified neuropeptides to overcome the limitations of their endogenous counterparts represents a novel strategy of pharmaceutical discovery for neurological disorders. The mechanism of action may involve a regulation of IGF-1 bioavailability.

Peroxisome biogenesis disorders in the Zellweger spectrum: An overview of current diagnosis, clinical manifestations, and treatment guidelines.

PubMed

Braverman, Nancy E; Raymond, Gerald V; Rizzo, William B; Moser, Ann B; Wilkinson, Mark E; Stone, Edwin M; Steinberg, Steven J; Wangler, Michael F; Rush, Eric T; Hacia, Joseph G; Bose, Mousumi

2016-03-01

Peroxisome biogenesis disorders in the Zellweger spectrum (PBD-ZSD) are a heterogeneous group of genetic disorders caused by mutations in PEX genes responsible for normal peroxisome assembly and functions. As a result of impaired peroxisomal activities, individuals with PBD-ZSD can manifest a complex spectrum of clinical phenotypes that typically result in shortened life spans. The extreme variability in disease manifestation ranging from onset of profound neurologic symptoms in newborns to progressive degenerative disease in adults presents practical challenges in disease diagnosis and medical management. Recent advances in biochemical methods for newborn screening and genetic testing have provided unprecedented opportunities for identifying patients at the earliest possible time and defining the molecular bases for their diseases. Here, we provide an overview of current clinical approaches for the diagnosis of PBD-ZSD and provide broad guidelines for the treatment of disease in its wide variety of forms. Although we anticipate future progress in the development of more effective targeted interventions, the current guidelines are meant to provide a starting point for the management of these complex conditions in the context of personalized health care. Copyright © 2015 Elsevier Inc. All rights reserved.

Reconstructive surgery for patellofemoral joint incongruency.

PubMed

Neumann, M V; Stalder, M; Schuster, A J

2016-03-01

A retrospective analysis of a heterogeneous patient cohort was performed to determine the outcome and eligibility of a combined trochleaplasty and soft tissue-balancing technique for repair of patellofemoral joint disorders. A strict surgical treatment algorithm including trochleaplasty and reconstruction of the medial patellofemoral ligament and vastus medialis oblique muscle was implemented to restore the patellofemoral joint. A heterogeneous patient cohort including 46 consecutively treated symptomatic knees was reviewed. The median follow-up period was 4.7 years (range 24-109 months). No patellar redislocation occurred post-operatively, and the median Kujala score improved from 62 (9-96) to 88 (47-100) points (p < 0.001) at follow-up. Radiological signs of trochlear dysplasia were corrected, and both patellar height and trochlear depth were significantly restored after surgery. In total, 16% of affected patients with pre-existing patellofemoral degenerative changes showed progression of osteoarthrosis according to the Kellgren and Lawrence classification. The surgical combination of trochleaplasty and reconstruction of the medial patellofemoral ligament and vastus medialis oblique muscle offers excellent clinical and radiological results. The overall results of the present study showed significant improvement of the Kujala score in patients with Dejour grades C and D dysplasia. These results outline the clinical relevance of trochleaplasty with additional soft tissue balancing as an effective joint-preserving method with satisfying results in patients with pre-existing degenerative changes. IV.

Loss of cIAP1 attenuates soleus muscle pathology and improves diaphragm function in mdx mice

PubMed Central

Enwere, Emeka K.; Boudreault, Louise; Holbrook, Janelle; Timusk, Kristen; Earl, Nathalie; LaCasse, Eric; Renaud, Jean-Marc; Korneluk, Robert G.

2013-01-01

The cellular inhibitor of apoptosis 1 (cIAP1) protein is an essential regulator of canonical and noncanonical nuclear factor κB (NF-κB) signaling pathways. NF-κB signaling is known to play important roles in myogenesis and degenerative muscle disorders such as Duchenne muscular dystrophy (DMD), but the involvement of cIAP1 in muscle disease has not been studied directly. Here, we asked whether the loss of cIAP1 would influence the pathology of skeletal muscle in the mdx mouse model of DMD. Double-mutant cIAP1−/−;mdx mice exhibited reduced muscle damage and decreased fiber centronucleation in the soleus, compared with single-mutant cIAP1+/+;mdx mice. This improvement in pathology was associated with a reduction in muscle infiltration by macrophages and diminished expression of inflammatory cytokines such as IL-6 and tumor necrosis factor-α. Furthermore, the cIAP1−/−;mdx mice exhibited reduced serum creatine kinase, and improved exercise endurance associated with improved exercise resilience by the diaphragm. Mechanistically, the loss of cIAP1 was sufficient to drive constitutive activation of the noncanonical NF-κB pathway, which led to increased myoblast fusion in vitro and in vivo. Collectively, these results show that the loss of cIAP1 protects skeletal muscle from the degenerative pathology resulting from systemic loss of dystrophin. PMID:23184147

GPER1 mediates estrogen-induced neuroprotection against oxygen-glucose deprivation in the primary hippocampal neurons.

PubMed

Zhao, Tian-Zhi; Shi, Fei; Hu, Jun; He, Shi-Ming; Ding, Qian; Ma, Lian-Ting

2016-07-22

It is well-known that the neuroprotective effects of estrogen have potential in the prevention and amelioration of ischemic and degenerative neurological disorders, while the underlying mechanisms for estrogen actions are undefined. As an important mediator for the non-genomic functions of estrogen, GPER1 (G Protein-coupled Estrogen Receptor 1) has been suggested to involve in the beneficial roles of estrogen in neural cells. Here our studies on primary hippocampal neurons have focused on GPER1 in an in vitro model of ischemia using oxygen-glucose deprivation (OGD). GPER1 expression in the primary hippocampal neurons was stimulated by the OGD treatments. Both E2 (estradiol) and E2-BSA (membrane impermeable estradiol by covalent conjugation of bovine serum albumin) attenuated OGD-induced cell death in primary cultures of hippocampal neurons. Importantly, this membrane-mediated estrogen function requires GPER1 protein. Knocking down of GPER1 diminished, while overexpression of GPER1 potentiated, the protective roles of E2/E2-BSA following OGD. Additionally, the downstream mechanisms employed by membrane-associated estrogen signaling were found to include PI3K/Akt-dependent Ask1 inhibition in the primary hippocampal neurons. Overall, these research results could enhance our understanding of the neuroprotective actions for estrogen, and provide a new therapeutic target for improving stroke outcome and ameliorating degenerative neurological diseases. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

Chronic administration of thiamine pyrophosphate decreases age-related histological atrophic testicular changes and improves sexual behavior in male Wistar rats.

PubMed

Hernández-Montiel, H L; Vásquez López, C M; González-Loyola, J G; Vega-Anaya, G C; Villagrán-Herrera, M E; Gallegos-Corona, M A; Saldaña, C; Ramos Gómez, M; García Horshman, P; García Solís, P; Solís-S, J C; Robles-Osorio, M L; Ávila Morales, J; Varela-Echavarría, A; Paredes Guerrero, R

2014-06-01

Aging is a multifactorial universal process and constitutes the most important risk factor for chronic-degenerative diseases. Although it is a natural process, pathological aging arises when these changes occur quickly and the body is not able to adapt. This is often associated with the generation of reactive oxygen species (ROS), inflammation, and a decrease in the endogenous antioxidant systems, constituting a physiopathological state commonly found in chronic-degenerative diseases. At the testicular level, aging is associated with tissue atrophy, decreased steroidogenesis and spermatogenesis, and sexual behavior disorders. This situation, in addition to the elevated generation of ROS in the testicular steroidogenesis, provides a critical cellular environment causing oxidative damage at diverse cellular levels. To assess the effects of a reduction in the levels of ROS, thiamine pyrophosphate (TPP) was chronically administered in senile Wistar rats. TPP causes an activation of intermediate metabolism routes, enhancing cellular respiration and decreasing the generation of ROS. Our results show an overall decrease of atrophic histological changes linked to aging, with higher levels of serum testosterone, sexual activity, and an increase in the levels of endogenous antioxidant enzymes in TPP-treated animals. These results suggest that TPP chronic administration decreases the progression of age-related atrophic changes by improving the intermediate metabolism, and by increasing the levels of antioxidant enzymes.

Running Exercise Alleviates Pain and Promotes Cell Proliferation in a Rat Model of Intervertebral Disc Degeneration

PubMed Central

Luan, Shuo; Wan, Qing; Luo, Haijie; Li, Xiao; Ke, Songjian; Lin, Caina; Wu, Yuanyuan; Wu, Shaoling; Ma, Chao

2015-01-01

Chronic low back pain accompanied by intervertebral disk degeneration is a common musculoskeletal disorder. Physical exercise, which is clinically recommended by international guidelines, has proven to be effective for degenerative disc disease (DDD) patients. However, the mechanism underlying the analgesic effects of physical exercise on DDD remains largely unclear. The results of the present study showed that mechanical withdrawal thresholds of bilateral hindpaw were significantly decreased beginning on day three after intradiscal complete Freund’s adjuvant (CFA) injection and daily running exercise remarkably reduced allodynia in the CFA exercise group beginning at day 28 compared to the spontaneous recovery group (controls). The hindpaw withdrawal thresholds of the exercise group returned nearly to baseline at the end of experiment, but severe pain persisted in the control group. Histological examinations performed on day 70 revealed that running exercise restored the degenerative discs and increased the cell densities of the annulus fibrosus (AF) and nucleus pulposus (NP). Furthermore, immunofluorescence labeling revealed significantly higher numbers of 5-bromo-2-deoxyuridine (BrdU)-positive cells in the exercise group on days 28, 42, 56 and 70, which indicated more rapid proliferation compared to the control at the corresponding time points. Taken together, these results suggest that running exercise might alleviate the mechanical allodynia induced by intradiscal CFA injection via disc repair and cell proliferation, which provides new evidence for future clinical use. PMID:25607736

Peripheral Nerve Fibers and Their Neurotransmitters in Osteoarthritis Pathology

PubMed Central

Grässel, Susanne; Muschter, Dominique

2017-01-01

The importance of the nociceptive nervous system for maintaining tissue homeostasis has been known for some time, and it has also been suggested that organogenesis and tissue repair are under neuronal control. Changes in peripheral joint innervation are supposed to be partly responsible for degenerative alterations in joint tissues which contribute to development of osteoarthritis. Various resident cell types of the musculoskeletal system express receptors for sensory and sympathetic neurotransmitters, allowing response to peripheral neuronal stimuli. Among them are mesenchymal stem cells, synovial fibroblasts, bone cells and chondrocytes of different origin, which express distinct subtypes of adrenoceptors (AR), receptors for vasoactive intestinal peptide (VIP), substance P (SP) and calcitonin gene-related peptide (CGRP). Some of these cell types synthesize and secrete neuropeptides such as SP, and they are positive for tyrosine-hydroxylase (TH), the rate limiting enzyme for biosynthesis of catecholamines. Sensory and sympathetic neurotransmitters are involved in the pathology of inflammatory diseases such as rheumatoid arthritis (RA) which manifests mainly in the joints. In addition, they seem to play a role in pathogenesis of priori degenerative joint disorders such as osteoarthritis (OA). Altogether it is evident that sensory and sympathetic neurotransmitters have crucial trophic effects which are critical for joint tissue and bone homeostasis. They modulate articular cartilage, subchondral bone and synovial tissue properties in physiological and pathophysiological conditions, in addition to their classical neurological features. PMID:28452955

Effects of Curculigoside on Memory Impairment and Bone Loss via Anti-Oxidative Character in APP/PS1 Mutated Transgenic Mice.

PubMed

Zhao, Lu; Liu, Sha; Wang, Yin; Zhang, Qiaoyan; Zhao, Wenjuan; Wang, Zejian; Yin, Ming

2015-01-01

Alzheimer's disease (AD) and osteoporosis are two closely related multifactorial progressively degenerative diseases that predominantly affect aged people. These two diseases share many common risk factors, including old age, being female, smoking, excessive drinking, low estrogen, and vitamin D3 levels. Additionally, oxidative damage and the dysfunction of the antioxidant system play important roles in the pathogenesis of osteoporosis and AD. Aβ not only leads to impaired memory but also plays a crucial role in the demineralization process of bone tissues of older people and women with menopause. Curculigoside can promote calcium deposition and increase the levels of ALP and Runx2 in osteoblasts under oxidative stress via anti-oxidative character. Therefore, we investigated the effects of CUR on the spatial learning and memory by the Morris water maze and brain immunohistochemistry, and bone microstructure and material properties of femurs by micro-computed tomography and mechanical testing in APP/PS1 mutated transgenic mice. Oral administration of CUR can significantly enhance learning performance and ameliorate bone loss in APP/PS1 mutated transgenic mice, and the mechanism may be related to its antioxidant effect. Based on these results, CUR has real potential as a new natural resource for developing medicines or dietary supplements for the prevention and treatment of the two closely linked multifactorial progressive degenerative disorders, AD and osteoporosis.

Artificial chordae for degenerative mitral valve disease: critical analysis of current techniques

PubMed Central

Ibrahim, Michael; Rao, Christopher; Athanasiou, Thanos

2012-01-01

The surgical repair of degenerative mitral valve disease involves a number of technical points of importance. The use of artificial chordae for the repair of degenerative disease has increased as a part of the move from mitral valve replacement to repair of the mitral valve. The use of artificial chordae provides an alternative to the techniques pioneered by Carpentier (including the quadrangular resection, transfer of native chordae and papillary muscle shortening/plasty), which can be more technically difficult. Despite a growth in their uptake and the indications for their use, a number of challenges remain for the use of artificial chordae in mitral valve repair, particularly in the determination of the correct length to ensure optimal leaflet coaptation. Here, we analyse over 40 techniques described for artificial chordae mitral valve repair in the setting of degenerative disease. PMID:22962321

Selective muscle fiber loss and molecular compensation in mitochondrial myopathy due to TK2 deficiency.

PubMed

Vilà, Maya R; Villarroya, Joan; García-Arumí, Elena; Castellote, Amparo; Meseguer, Anna; Hirano, Michio; Roig, Manuel

2008-04-15

A 12-year-old patient with mitochondrial DNA (mtDNA) depletion syndrome due to TK2 gene mutations has been evaluated serially over the last 10 years. We observed progressive muscle atrophy with selective loss of type 2 muscle fibers and, despite severe depletion of mtDNA, normal activities of respiratory chain (RC) complexes and levels of COX II mitochondrial protein in the remaining muscle fibers. These results indicate that compensatory mechanisms account for the slow progression of the disease. Identification of factors that ameliorate mtDNA depletion may reveal new therapeutic targets for these devastating disorders.

Dietary copper: a novel predisposing factor for oral submucous fibrosis?

PubMed

Arakeri, Gururaj; Brennan, Peter A

2013-03-01

Oral submucous fibrosis (OSMF) is known devastating disorder commonly seen in South Asian developing countries. It is directly linked to areca nut chewing and the contents of areca are subjected to multitude of investigations. Among all the contents of areca nut, the copper element has been extensively studied. Most of the published studies have validated its association with OSMF because of its local action. In this paper we postulate a novel biological pathway through which copper is thought to predispose oral mucosa to OSMF. The hypothesis is instructive in explaining various unexplored aspects of the disease. Copyright © 2012 Elsevier Ltd. All rights reserved.

Ferritin for the Clinician

PubMed Central

Knovich, Mary Ann; Storey, Jonathan A.; Coffman, Lan G.; Torti, Suzy V.

2009-01-01

Ferritin, a major iron storage protein, is essential to iron homeostasis and is involved in a wide range of physiologic and pathologic processes. In clinical medicine, ferritin is predominantly utilized as a serum marker of total body iron stores. In cases of iron deficiency and overload, serum ferritin serves a critical role in both diagnosis and management. Elevated serum and tissue ferritin are linked to coronary artery disease, malignancy, and poor outcomes following stem cell transplantation. Ferritin is directly implicated in less common but potentially devastating human diseases including sideroblastic anemias, neurodegenerative disorders, and hemophagocytic syndrome. Additionally, recent research describes novel functions of ferritin independent of iron storage. PMID:18835072

Exposure to styrene and chronic health effects: mortality and incidence of solid cancers in the Danish reinforced plastics industry.

PubMed Central

Kolstad, H A; Juel, K; Olsen, J; Lynge, E

1995-01-01

OBJECTIVES--To study the occurrence of non-malignant diseases and solid cancers in workers exposed to styrene in the Danish reinforced plastics industry. METHODS--All 36,610 workers of 386 reinforced plastics companies and 14,293 workers not exposed to styrene from similar industries were followed up from 1970 to 1990. This industry is characterised by simple exposure conditions, exposure to high concentrations of styrene, and a high proportion of small companies, and the exposure assessment was based on experts' classification on a company level. The mortality from non-malignant causes and the incidence of solid cancers were compared with the national rates. Poisson models were used for internal comparisons. RESULTS--A total of 3031 deaths and 1134 newly diagnosed cases of solid cancer were reported in the workers in the reinforced plastics industry. In companies where 50% or more of the workers produced reinforced plastics an increased mortality rate ratio (MRR) for degenerative disorders of the nervous system (multiple sclerosis, parkinsonism, and motor neurone disease; MRR 1.8, 16 cases, 95% confidence interval (95% CI) 0.9-3.8) and an increased incidence rate ratio (IRR) for pancreatic cancer (IRR 2.2, 17 cases, 95% CI 1.1-4.5) was found. For both disease categories increased occurrence was also found among long term workers, workers of the 1960s (the period with the highest exposure to styrene), and workers with a latent period of more than 10 years after the start of employment. No other non-malignant diseases or solid cancers showed these patterns. CONCLUSION--The findings have to be interpreted with caution, due to the company based exposure assessment, but the possible association between exposures in the reinforced plastics industry, mainly styrene, and degenerative disorders of the nervous system and pancreatic cancer, deserves attention. PMID:7795754

The evaluation of lumbar paraspinal muscle quantity and quality using the Goutallier classification and lumbar indentation value.

PubMed

Tamai, Koji; Chen, Jessica; Stone, Michael; Arakelyan, Anush; Paholpak, Permsak; Nakamura, Hiroaki; Buser, Zorica; Wang, Jeffrey C

2018-05-01

The cross-sectional area and fat infiltration are accepted as standard parameters for quantitative and qualitative evaluation of muscle degeneration. However, they are time-consuming, which prevents them from being used in a clinical setting. The aim of this study was to analyze the relationship between lumbar muscle degeneration and spinal degenerative disorders, using lumbar indentation value (LIV) as quantitative and Goutallier classification as qualitative measures. This is a retrospective analysis of kinematic magnetic resonance images (kMRI). Two-hundred and thirty patients with kMRIs taken in weight-bearing positions were selected randomly. The LIV and Goutallier classification were evaluated at L4-5. The correlation of these two parameters with patients' age, gender, lumbar lordosis (LL), range of motion, disc degeneration, disc height, and Modic change were analyzed. There was no significant trend of LIV among the different grades of Goutallier classification (p = 0.943). There was a significant increase in age with higher grades of Goutallier classification (p < 0.001). In contrast, there was no correlation between LIV and age (p = 0.799). The Goutallier classification positively correlated with LL (r = 0.377) and severe disc degeneration (r = 0.249). The LIV positively correlated with LL (r = 0.476) and degenerative spondylolisthesis (r = 0.184). Multinomial logistic regression analysis showed that age (p = 0.026), gender (p = 0.003), and LIV (p < 0.001) were significant predictors for patients with low LL (< 10°). Lumbar muscle quantity and quality showed specific correlation with age and spine disorders. Additionally, LL can be predicted by the muscle quantity, but not the quality. These time-saving evaluation tools potentially accelerate the study of lumbar muscles. These slides can be retrieved under Electronic Supplementary Material.

An in vivo comparison study in goats for a novel motion-preserving cervical joint system

PubMed Central

Qin, Jie; Zhao, Chenguang; Wang, Dong; Zhao, Bo; Dong, Jun; Li, Haopeng; Sang, Rongxia; Wang, Shuang; Fu, Jiao; Kong, Rangrang

2017-01-01

Cervical degenerative disease is one of the most common spinal disorders worldwide, especially in older people. Anterior cervical corpectomy and fusion (ACCF) is a useful method for the surgical treatment of multi-level cervical degenerative disease. Anterior cervical disc replacement (ACDR) is considered as an alternative surgical method. However, both methods have drawbacks, particularly the neck motion decrease observed after arthrodesis, and arthroplasty should only be performed on patients presenting with cervical disc disease but without any vertebral body disease. Therefore, we designed a non-fusion cervical joint system, namely an artificial cervical vertebra and intervertebral complex (ACVC), to provide a novel treatment for multi-level cervical degenerative disease. To enhance the long-term stability of ACVC, we applied a hydroxyapatite (HA) biocoating on the surface of the artificial joint. Thirty-two goats were randomly divided into four groups: a sham control group, an ACVC group, an ACVC-HA group, and an ACCF group (titanium and plate fixation group). We performed the prosthesis implantation in our previously established goat model. We compared the clinical, radiological, biomechanical, and histological outcomes among these four different groups for 24 weeks post surgery. The goats successfully tolerated the entire experimental procedure. The kinematics data for the ACVC and ACVC-HA groups were similar. The range of motion (ROM) in adjacent level increased after ACCF but was not altered after ACVC or ACVC-HA implantation. Compared with the control group, no significant difference was found in ROM and neutral zone (NZ) in flexion-extension or lateral bending for the ACVC and ACVC-HA groups, whereas the ROM and NZ in rotation were significantly greater. Compared with the ACCF group, the ROM and NZ significantly increased in all directions. Overall, stiffness was significantly decreased in the ACVC and ACVC-HA groups compared with the control group and the ACCF group. Similar results were found after a fatigue test of 5,000 repetitions of axial rotation. The histological results showed more new bone formation and better bone implant contact in the ACVC-HA group than the ACVC group. Goat is an excellent animal model for cervical spine biomechanical study. Compared with the intact state and the ACCF group, ACVC could provide immediate stability and preserve segmental movement after discectomy and corpectomy. Besides, HA biocoating provide a better bone ingrowth, which is essential for long-term stability. In conclusion, ACVC-HA brings new insight to treat cervical degenerative disease. PMID:28582418

Birth and mortality of maned wolves Chrysocyon brachyurus (Illiger, 1811) in captivity.

PubMed

Maia, O B; Gouveia, A M G

2002-02-01

The aims of this study were to verify the distribution of births of captive maned wolves Chrysocyon brachyurus and the causes of their deaths during the period from 1980 to 1998, based on the registry of births and deaths in the International Studbook for Maned Wolves. To determine birth distribution and average litter size, 361 parturitions were analyzed for the 1989-98 period. To analyze causes of mortality, the animals were divided into four groups: 1. pups born in captivity that died prior to one year of age; 2. animals born in captivity that died at more than one year of age; 3. animals captured in the wild that died at any age; and 4. all animals that died during the 1980-98 period. In group 1, the main causes of mortality were parental incompetence (67%), infectious diseases, (9%) and digestive system disorders (5%). The average mortality rate for pups was 56%. Parental incompetence was responsible for 95% of pup deaths during the first week of life. In group 2, the main causes were euthanasia (18%) and disorders of the genitourinary (10%) and digestive systems (8%). Euthanasia was implemented due to senility, congenital disorders, degenerative diseases, and trauma. In group 3, the main causes were digestive system disorders (12%), infectious diseases (10%), and lesions or accidents (10%). The main causes of mortality of maned wolves in captivity (group 4) were parental incompetence (38%), infectious diseases (9%), and digestive system disorders (7%).

Long-term Outcomes of Mitral Valve Repair Versus Replacement for Degenerative Disease: A Systematic Review

PubMed Central

McNeely, Christian A; Vassileva, Christina M

2015-01-01

The short-term advantage of mitral valve repair versus replacement for degenerative disease has been extensively documented. These advantages include lower operative mortality, improved survival, better preservation of left-ventricular function, shorter post-operative hospital stay, lower total costs, and fewer valve-related complications, including thromboembolism, anticoagulation-related bleeding events and late prosthetic dysfunction. More recent written data are available indicating the long-term advantage of repair versus replacement. While at some institutions, the repair rate for degenerative disease may exceed 90%, the national average in 2007 was only 69%. Making direct comparisons between mitral valve repair and replacement using the available studies does present some challenges however, as there are often differences in baseline characteristics between patient groups as well as other dissimilarities between studies. The purpose of this review is to systematically summarize the long-term survival and reoperation data of mitral valve repair versus replacement for degenerative disease. A PubMed search was done and resulted in 12 studies that met our study criteria for comparing mitral valve repair versus replacement for degenerative disease. A systematic review was then conducted abstracting survival and reoperation data. PMID:25158683

Plasma and tissue oxidative stress index in patients with rheumatic and degenerative heart valve disease.

PubMed

Rabus, Murat; Demirbağ, Recep; Sezen, Yusuf; Konukoğlu, Oğuz; Yildiz, Ali; Erel, Ozcan; Zeybek, Rahmi; Yakut, Cevat

2008-12-01

We investigated whether patients with rheumatic and degenerative heart valve disease (HVD) differed with regard to plasma and tissue oxidative stress index (OSI). The study included 56 patients who underwent valve replacement due to rheumatic (n=32; 15 males; mean age 47+/-10 years) and degenerative (n=24; 13 males; mean age 55+/-12 years) HVD. Plasma and tissue total oxidative status (TOS) and total antioxidative capacity (TAC) levels were measured and OSI was calculated. Patients with degenerative HVD had significantly higher age, increased interventricular septum thickness, and higher frequency of aortic stenosis, whereas the incidence of mitral stenosis was higher in patients with rheumatic HVD (p<0.05). Plasma oxidative characteristics did not differ between the two HVD groups (p>0.05). Tissue TAC was significantly lower in patients with rheumatic HVD (p=0.027), whereas tissue TOS and OSI were similar between the two HVD groups (p>0.05). In bivariate analysis, plasma OSI did not show any correlation with clinical, laboratory, and echocardiographic variables (p>0.05). Our data show that plasma and tissue OSI levels are similar in patients with rheumatic and degenerative HVD.

Anterior Cervical Spine Surgery for Degenerative Disease: A Review

PubMed Central

SUGAWARA, Taku

Anterior cervical spine surgery is an established surgical intervention for cervical degenerative disease and high success rate with excellent long-term outcomes have been reported. However, indications of surgical procedures for certain conditions are still controversial and severe complications to cause neurological dysfunction or deaths may occur. This review is focused mainly on five widely performed procedures by anterior approach for cervical degenerative disease; anterior cervical discectomy, anterior cervical discectomy and fusion, anterior cervical corpectomy and fusion, anterior cervical foraminotomy, and arthroplasty. Indications, procedures, outcomes, and complications of these surgeries are discussed. PMID:26119899

Prevalence of psychiatric disorders and functional impairment after loss of a family member: a longitudinal study after the 2004 Tsunami.

PubMed

Kristensen, Pål; Weisaeth, Lars; Hussain, Ajmal; Heir, Trond

2015-01-01

Bereavement following disasters is a devastating experience for family members. The aim of this study was to examine the long-term mental health effects of losing a loved one in a natural disaster. Ninety-four Norwegians aged 18-80 years who lost close family members in the 2004 Southeast Asian tsunami were evaluated 2 and 6 years after the disaster. The participants were either staying in an affected area at the time of the disaster (i.e., directly exposed) or not (i.e., not directly exposed). The prevalence of psychiatric disorders was assessed by the MINI International Neuropsychiatric Interview (M.I.N.I). Prolonged grief disorder (PGD) was self-reported using the Inventory of Complicated Grief (ICG), and functional impairment was self-reported using the Work and Social Adjustment Scale (WSAS). We did not identify a significant decrease in the prevalence of PGD, posttraumatic stress disorder (PTSD), or major depressive disorder (MDD) from 2 to 6 years. Approximately, one-third of the bereaved (36%) had a psychiatric disorder 6 years after the tsunami. The most common disorder was PGD (12%) followed by general anxiety disorder (GAD, 11%), agoraphobia (11%), and MDD (10%). The prevalence of PTSD and MDD was higher among family members who were directly exposed to the disaster compared to those who were not (21 vs. 0%, and 25 vs. 3%). PGD was associated with functional impairment independent of other disorders. Loss of a close family member in a natural disaster can have a substantial adverse long-term effect on mental health and everyday functioning. © 2014 Wiley Periodicals, Inc.

Quantitative analysis of 18F-NaF dynamic PET/CT cannot differentiate malignant from benign lesions in multiple myeloma

PubMed Central

Sachpekidis, Christos; Hillengass, Jens; Goldschmidt, Hartmut; Anwar, Hoda; Haberkorn, Uwe; Dimitrakopoulou-Strauss, Antonia

2017-01-01

A renewed interest has been recently developed for the highly sensitive bone-seeking radiopharmaceutical 18F-NaF. Aim of the present study is to evaluate the potential utility of quantitative analysis of 18F-NaF dynamic PET/CT data in differentiating malignant from benign degenerative lesions in multiple myeloma (MM). 80 MM patients underwent whole-body PET/CT and dynamic PET/CT scanning of the pelvis with 18F-NaF. PET/CT data evaluation was based on visual (qualitative) assessment, semi-quantitative (SUV) calculations, and absolute quantitative estimations after application of a 2-tissue compartment model and a non-compartmental approach leading to the extraction of fractal dimension (FD). In total 263 MM lesions were demonstrated on 18F-NaF PET/CT. Semi-quantitative and quantitative evaluations were performed for 25 MM lesions as well as for 25 benign, degenerative and traumatic lesions. Mean SUVaverage for MM lesions was 11.9 and mean SUVmax was 23.2. Respectively, SUVaverage and SUVmax for degenerative lesions were 13.5 and 20.2. Kinetic analysis of 18F-NaF revealed the following mean values for MM lesions: K1 = 0.248 (1/min), k3 = 0.359 (1/min), influx (Ki) = 0.107 (1/min), FD = 1.382, while the respective values for degenerative lesions were: K1 = 0.169 (1/min), k3 = 0.422 (1/min), influx (Ki) = 0.095 (1/min), FD = 1. 411. No statistically significant differences between MM and benign degenerative disease regarding SUVaverage, SUVmax, K1, k3 and influx (Ki) were demonstrated. FD was significantly higher in degenerative than in malignant lesions. The present findings show that quantitative analysis of 18F-NaF PET data cannot differentiate malignant from benign degenerative lesions in MM patients, supporting previously published results, which reflect the limited role of 18F-NaF PET/CT in the diagnostic workup of MM. PMID:28913153

Lumbar degenerative spinal deformity: Surgical options of PLIF, TLIF and MI-TLIF

PubMed Central

Hey, Hwee Weng Dennis; Hee, Hwan Tak

2010-01-01

Degenerative disease of the lumbar spine is common in ageing populations. It causes disturbing back pain, radicular symptoms and lowers the quality of life. We will focus our discussion on the surgical options of posterior lumbar interbody fusion (PLIF) and transforaminal lumbar interbody fusion (TLIF) and minimally invasive transforaminal lumbar interbody fusion (MI-TLIF) for lumbar degenerative spinal deformities, which include symptomatic spondylolisthesis and degenerative scoliosis. Through a description of each procedure, we hope to illustrate the potential benefits of TLIF over PLIF. In a retrospective study of 53 ALIF/PLIF patients and 111 TLIF patients we found reduced risk of vessel and nerve injury in TLIF patients due to less exposure of these structures, shortened operative time and reduced intra-operative bleeding. These advantages could be translated to shortened hospital stay, faster recovery period and earlier return to work. The disadvantages of TLIF such as incomplete intervertebral disc and vertebral end-plate removal and potential occult injury to exiting nerve root when under experienced hands are rare. Hence TLIF remains the mainstay of treatment in degenerative deformities of the lumbar spine. However, TLIF being a unilateral transforaminal approach, is unable to decompress the opposite nerve root. This may require contralateral laminotomy, which is a fairly simple procedure. The use of minimally invasive transforaminal lumbar interbody fusion (MI-TLIF) to treat degenerative lumbar spinal deformity is still in its early stages. Although the initial results appear promising, it remains a difficult operative procedure to master with a steep learning curve. In a recent study comparing 29 MI-TLIF patients and 29 open TLIF, MI-TLIF was associated with longer operative time, less blood loss, shorter hospital stay, with no difference in SF-36 scores at six months and two years. Whether it can replace traditional TLIF as the surgery of choice for degenerative lumbar deformity remains unknown and more studies are required to validate the safety and efficiency. PMID:20419002

Stem cells: a revolution in therapeutics-recent advances in stem cell biology and their therapeutic applications in regenerative medicine and cancer therapies.

PubMed

Mimeault, M; Hauke, R; Batra, S K

2007-09-01

Basic and clinical research accomplished during the last few years on embryonic, fetal, amniotic, umbilical cord blood, and adult stem cells has constituted a revolution in regenerative medicine and cancer therapies by providing the possibility of generating multiple therapeutically useful cell types. These new cells could be used for treating numerous genetic and degenerative disorders. Among them, age-related functional defects, hematopoietic and immune system disorders, heart failures, chronic liver injuries, diabetes, Parkinson's and Alzheimer's diseases, arthritis, and muscular, skin, lung, eye, and digestive disorders as well as aggressive and recurrent cancers could be successfully treated by stem cell-based therapies. This review focuses on the recent advancements in adult stem cell biology in normal and pathological conditions. We describe how these results have improved our understanding on critical and unique functions of these rare sub-populations of multipotent and undifferentiated cells with an unlimited self-renewal capacity and high plasticity. Finally, we discuss some major advances to translate the experimental models on ex vivo and in vivo expanded and/or differentiated stem cells into clinical applications for the development of novel cellular therapies aimed at repairing genetically altered or damaged tissues/organs in humans. A particular emphasis is made on the therapeutic potential of different tissue-resident adult stem cell types and their in vivo modulation for treating and curing specific pathological disorders.

Low dose of caffeine enhances the efficacy of antidepressants in major depressive disorder and the underlying neural substrates.

PubMed

Liu, Qing-Shan; Deng, Ran; Fan, Yuyan; Li, Keqin; Meng, Fangang; Li, Xueli; Liu, Rui

2017-08-01

Caffeine is one of the most frequently used psychoactive substances ingested mainly via beverage or food products. Major depressive disorder is a serious and devastating psychiatric disorder. Emerging evidence indicates that caffeine enhances the antidepressant-like activity of common antidepressant drugs in rodents. However, whether joint administration of low dose of caffeine enhances the antidepressant actions in depressed patients remains unclear. A total of 95 male inpatients were assigned to three groups and were asked to take either caffeine (60, 120 mg) or placebo (soymilk powder) daily for 4 wk on the basis of their current antidepressant medications. Results showed that chronic supplementation with low dose of caffeine (60 mg) produced rapid antidepressant action by reduction of depressive scores. Furthermore, low dose of caffeine improved cognitive performance in depressed patients. However, caffeine did not affect sleep as measured by overnight polysomnography. Moreover, chronic caffeine consumption elicited inhibition of hypothalamic-pituitary-adrenal axis activation by normalization of salivary cortisol induced by Trier social stress test. These findings indicated the potential benefits of further implications of supplementary administration of caffeine to reverse the development of depression and enhance the outcome of antidepressants treatment in major depressive disorder. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Genes and Schizophrenia: Beyond Schizophrenia: The Role of DISC1 in Major Mental Illness

PubMed Central

Hennah, William; Thomson, Pippa; Peltonen, Leena; Porteous, David

2006-01-01

Schizophrenia and related disorders have a major genetic component, but despite much effort and many claims, few genes have been consistently replicated and fewer have biological support. One recent exception is “Disrupted in Schizophrenia 1” (DISC1), which was identified at the breakpoint on chromosome 1 of the balanced translocation (1;11)(q42.1;q14.3) that co-segregated in a large Scottish family with a wide spectrum of major mental illnesses. Since then, genetic analysis has implicated DISC1 in schizophrenia, schizoaffective disorder, bipolar affective disorder, and major depression. Importantly, evidence is emerging from genetic studies for a causal relationship between DISC1 and directly measurable trait variables such as working memory, cognitive aging, and decreased gray matter volume in the prefrontal cortex, abnormalities in hippocampal structure and function, and reduction in the amplitude of the P300 event-related potential. Further, DISC1 binds a number of proteins known to be involved in essential processes of neuronal function, including neuronal migration, neurite outgrowth, cytoskeletal modulation, and signal transduction. Thus, both genetic and functional data provide evidence for a critical role for DISC1 in schizophrenia and related disorders, supporting the neurodevelopmental hypothesis for the molecular pathogenesis of these devastating illnesses. PMID:16699061

Regulation of cellular plasticity and resilience by mood stabilizers: the role of AMPA receptor trafficking

PubMed Central

Du, Jing; Quiroz, Jorge A.; Gray, Neil A.; Szabo, Steve T.; Zarate Jr, Carlos A.; Manji, Husseini K.

2004-01-01

There is increasing evidence from a variety of sources that severe mood disorders are associated with regional reductions in brain volume, as well as reductions in the number, size, and density of glia and neurons in discrete brain areas. Although the precise pathophysiology underlying these morphometric changes remains to be fully elucidated, the data suggest that severe mood disorders are associated with impairments of structural plasticity and cellular resilience. In this context, it is noteworthy that a growing body of data suggests that the glutamaiergic system (which is known to play a major role in neuronal plasticity and cellular resilience) may be involved in the pathophysiology and treatment of mood disorders. Glutamate α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) GluR1 receptor trafficking plays a critical role in regulating various forms of neural plasticity. It is thus noteworthy that recent studies have shown that structurally dissimilar mood stabilizers lithium and valproate regulate GluR1 receptor subunit trafficking and localization at synapses. These studies suggest that regulation of glutamatergically mediated synaptic plasticity may play a role in the treatment of mood disorders, and raises the possibility that agents more directly affecting synaptic GluR1 represent novel therapies for these devastating illnesses. PMID:22034247

The immediate effects of taping therapy on knee pain and depression in patients with degenerative arthritis.

PubMed

Han, Ji-Won; Lee, Dong-Kyu; Park, Chi-Bok

2018-05-01

[Purpose] This study aims to identify the immediate effects of taping therapy on knee pain and depression among patients with degenerative arthritis. [Subjects and Methods] In total, 32 patients with degenerative arthritis were randomly assigned to one of two groups: the experimental group that underwent taping therapy and the control group that underwent regular treatment (16 patients per group). In the experimental group, therapeutic tape was wrapped all around the knee joint. Pain and depression were measured using the visual analogue scale (VAS) and the Beck Depression Inventory (BDI), respectively. [Results] The intra-group comparison showed significant differences in VAS and BDI for the experimental group. The intergroup comparison showed that the differences in VAS and BDI within the experimental group appeared significant relative to the control group. [Conclusion] It was observed that taping therapy showed an immediate effect in decreasing knee pain and depression among patients with degenerative arthritis.

Three decades of neoliberalism in Mexico: the destruction of society.

PubMed

Laurell, Asa Cristina

2015-01-01

Neoliberalism has been implemented in Latin America for about three decades. This article reviews Mexico's neoliberal trajectory to illustrate the political, economic, and social alterations that have resulted from this process. It finds that representative democracy has been perverted through fear, putting central political decisions in the hands of power groups with special interests. The border between the state of law and the state of exception is blurred. Economic structural adjustment with liberalization and privatization has provoked recurrent crisis, but has been maintained, leading to the destruction of the national productive structure in favor of supranational corporations, particularly financial capital. The association between criminal economy and economic criminality is also discussed. The privatization of social benefits and services requires state subsidies and allows the privatization of profits and the socialization of losses. The social impact of this process has been devastating, with a polarized income distribution, falling wages, increased precarious jobs, rising inequality, and extreme violence. Health conditions have also deteriorated and disorders associated with violence, chronic stress, and a changing nutritional culture have become dominating. However, in Latin America, massive, organized political and social mobilization has broken the vicious neoliberal circle and elected progressive governments that are struggling to reverse social and economic devastation. © The Author(s) 2015 Reprints and permissions:]br]sagepub.co.uk/journalsPermissions.nav.

Prevalence of disorders recorded in dogs attending primary-care veterinary practices in England.

PubMed

O Neill, Dan G; Church, David B; McGreevy, Paul D; Thomson, Peter C; Brodbelt, Dave C

2014-01-01

Purebred dog health is thought to be compromised by an increasing occurence of inherited diseases but inadequate prevalence data on common disorders have hampered efforts to prioritise health reforms. Analysis of primary veterinary practice clinical data has been proposed for reliable estimation of disorder prevalence in dogs. Electronic patient record (EPR) data were collected on 148,741 dogs attending 93 clinics across central and south-eastern England. Analysis in detail of a random sample of EPRs relating to 3,884 dogs from 89 clinics identified the most frequently recorded disorders as otitis externa (prevalence 10.2%, 95% CI: 9.1-11.3), periodontal disease (9.3%, 95% CI: 8.3-10.3) and anal sac impaction (7.1%, 95% CI: 6.1-8.1). Using syndromic classification, the most prevalent body location affected was the head-and-neck (32.8%, 95% CI: 30.7-34.9), the most prevalent organ system affected was the integument (36.3%, 95% CI: 33.9-38.6) and the most prevalent pathophysiologic process diagnosed was inflammation (32.1%, 95% CI: 29.8-34.3). Among the twenty most-frequently recorded disorders, purebred dogs had a significantly higher prevalence compared with crossbreds for three: otitis externa (P = 0.001), obesity (P = 0.006) and skin mass lesion (P = 0.033), and popular breeds differed significantly from each other in their prevalence for five: periodontal disease (P = 0.002), overgrown nails (P = 0.004), degenerative joint disease (P = 0.005), obesity (P = 0.001) and lipoma (P = 0.003). These results fill a crucial data gap in disorder prevalence information and assist with disorder prioritisation. The results suggest that, for maximal impact, breeding reforms should target commonly-diagnosed complex disorders that are amenable to genetic improvement and should place special focus on at-risk breeds. Future studies evaluating disorder severity and duration will augment the usefulness of the disorder prevalence information reported herein.

Scenes of Devastation: Chasing Hawaii's Deadly Ohia Fungus | Hawaii Public

Science.gov Websites

Scenes of Devastation: Chasing Hawaii's Deadly Ohia Fungus By Molly Solomon * Mar 25, 2016 TweetShareGoogle+Email Molly Solomon Rapid Ohia Death has devastated native forests on Hawaii Island, especially in Lower Puna subdivisions like Leilani Estates. Credit Molly Solomon One of Hawai'i's oldest and most

Comparative effectiveness of platelet-rich plasma injections for treating knee joint cartilage degenerative pathology: a systematic review and meta-analysis.

PubMed

Chang, Ke-Vin; Hung, Chen-Yu; Aliwarga, Fanny; Wang, Tyng-Guey; Han, Der-Sheng; Chen, Wen-Shiang

2014-03-01

To explore the effectiveness of platelet-rich plasma (PRP) in treating cartilage degenerative pathology in knee joints. Electronic databases, including PubMed and Scopus, were searched from the earliest record to September 2013. We included single-arm prospective studies, quasi-experimental studies, and randomized controlled trials that used PRP to treat knee chondral degenerative lesions. Eight single-arm studies, 3 quasi-experimental studies, and 5 randomized controlled trials were identified, comprising 1543 participants. We determined effect sizes for the selected studies by extracting changes in functional scales after the interventions and compared the PRP group pooled values with the pretreatment baseline and the groups receiving placebo or hyaluronic acid (HA) injections. PRP injections in patients with knee degenerative pathology showed continual efficacy for 12 months compared with their pretreatment condition. The effectiveness of PRP was likely better and more prolonged than that of HA. Injection doses ≤2, the use of a single-spinning approach, and lack of additional activators led to an uncertainty in the treatment effects. Patients with lower degrees of cartilage degeneration achieved superior outcomes as opposed to those affected by advanced osteoarthritis. PRP application improves function from basal evaluations in patients with knee joint cartilage degenerative pathology and tends to be more effective than HA administration. Discrepancy in the degenerative severity modifies the treatment responses, leading to participants with lower degrees of degeneration benefiting more from PRP injections. Copyright © 2014 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Do the disc degeneration and osteophyte contribute to the curve rigidity of degenerative scoliosis?

PubMed

Zhu, Feng; Bao, Hongda; Yan, Peng; Liu, Shunan; Bao, Mike; Zhu, Zezhang; Liu, Zhen; Qiu, Yong

2017-03-29

The factors associated with lateral curve flexibility in degenerative scoliosis have not been well documented. Disc degeneration could result in significant change in stiffness and range of motion in lateral bending films. The osteophytes could be commonly observed in degenerative spine but the relationship between osteophyte formation and curve flexibility remains controversial. The aim of the current study is to clarify if the disc degeneration and osteophyte formation were both associated with curve flexibility of degenerative scoliosis. A total of 85 patients were retrospectively analyzed. The inclusion criteria were as follow: age greater than 45 years, diagnosed as degenerative scoliosis and coronal Cobb angle greater than 20°. Curve flexibility was calculated based on Cobb angle, and range of motion (ROM) was based on disc angle evaluation. Regional disc degeneration score (RDS) was obtained according to Pfirrmann classification and osteophyte formation score (OFS) was based on Nanthan classification. Spearman correlation was performed to analyze the relationship between curve flexibility and RDS as well as OFS. Moderate correlation was found between RDS and curve flexibility with a Spearman coefficient of -0.487 (P = 0.009). Similarly, moderate correlation was observed between curve flexibility and OFS with a Spearman coefficient of -0.429 (P = 0.012). Strong correlation was found between apical ROM and OFS compared to the relationship between curve flexibility and OFS with a Spearman coefficient of -0.627 (P < 0.001). Both disc degeneration and osteophytes formation correlated with curve rigidity. The pre-operative evaluation of both features may aid in the surgical decision-making in degenerative scoliosis patients.

Lumbar scoliosis associated with spinal stenosis in idiopathic and degenerative cases.

PubMed

Le Huec, J C; Cogniet, A; Mazas, S; Faundez, A

2016-10-01

Degenerative de novo scoliosis is commonly present in older adult patients. The degenerative process including disc bulging, facet arthritis, and ligamentum flavum hypertrophy contributes to the appearance of symptoms of spinal stenosis. Idiopathic scoliosis has also degenerative changes that can lead to spinal stenosis. The aetiology, prevalence, biomechanics, classification, symptomatology, and treatment of idiopathic and degenerative lumbar scoliosis in association with spinal stenosis are reviewed. Review study is based on a review of pertinent but non-exhaustive literature of the last 20 years in PubMed in English language. Retrospective analysis of studies focused on all parameters concerning scoliosis associated with stenosis. Very few publications have focused specifically on idiopathic scoliosis and stenosis, and this was before the advent of modern segmental instrumentation. On the other hand, many papers were found for degenerative scoliosis and stenosis with treatment methods based on aetiology of spinal canal stenosis and analysis of global sagittal and frontal parameters. Satisfactory clinical results after operative treatment range from 83 to 96 % but with increased percentage of complications. Recent literature analysed the importance of stabilizing or not the spine after decompression in such situation knowing the increasing risk of instability after facet resection. No prospective randomized studies were found to support short instrumentation. Long instrumentation and fusion to prevent distabilization after decompression were always associated with higher complication rates. Imbalance patients with unsatisfactory compensation capacities were at risk of complications. Operative treatment using newly proposed classification system of lumbar scoliosis with associated canal stenosis is useful. Sagittal balance and rotatory dislocation are the main parameters to analyse to determine the length of fusion.

Cartilage repair in the degenerative ageing knee

PubMed Central

Brittberg, Mats; Gomoll, Andreas H; Canseco, José A; Far, Jack; Lind, Martin; Hui, James

2016-01-01

Background and purpose Cartilage damage can develop due to trauma, resulting in focal chondral or osteochondral defects, or as more diffuse loss of cartilage in a generalized organ disease such as osteoarthritis. A loss of cartilage function and quality is also seen with increasing age. There is a spectrum of diseases ranging from focal cartilage defects with healthy surrounding cartilage to focal lesions in degenerative cartilage, to multiple and diffuse lesions in osteoarthritic cartilage. At the recent Aarhus Regenerative Orthopaedics Symposium (AROS) 2015, regenerative challenges in an ageing population were discussed by clinicians and basic scientists. A group of clinicians was given the task of discussing the role of tissue engineering in the treatment of degenerative cartilage lesions in ageing patients. We present the outcomes of our discussions on current treatment options for such lesions, with particular emphasis on different biological repair techniques and their supporting level of evidence. Results and interpretation Based on the studies on treatment of degenerative lesions and early OA, there is low-level evidence to suggest that cartilage repair is a possible treatment for such lesions, but there are conflicting results regarding the effect of advanced age on the outcome. We concluded that further improvements are needed for direct repair of focal, purely traumatic defects before we can routinely use such repair techniques for the more challenging degenerative lesions. Furthermore, we need to identify trigger mechanisms that start generalized loss of cartilage matrix, and induce subchondral bone changes and concomitant synovial pathology, to maximize our treatment methods for biological repair in degenerative ageing joints. PMID:27910738

Corrosion and Tribology of Materials Used in a Novel Reverse Hip Replacement.

PubMed

Braddon, Linda; Termanini, Zafer; MacDonald, Steven; Parvizi, Jay; Lieberman, Jay; Frankel, Victor; Zuckerman, Joseph

2017-07-05

Total hip arthroplasty has been utilized for the past 50 years as an effective treatment for degenerative, inflammatory and traumatic disorders of the hip. The design of these implants has generally followed the anatomy of the hip as a ball and socket joint with the femoral head representing the ball and the acetabulum representing the socket. We describe a novel hip arthroplasty design in which the "ball" is located on the acetabular side and the "socket" is located on the femoral side. The results of extensive biomechanical testing are described and document wear and corrosion characteristics that are at least equivalent to standard designs. These results support clinical assessment as the next step of the evaluation.

Abdominal aortic aneurysms: an autoimmune disease?

PubMed

Jagadesham, Vamshi P; Scott, D Julian A; Carding, Simon R

2008-12-01

Abdominal aortic aneurysms (AAAs) are a multifactorial degenerative vascular disorder. One of the defining features of the pathophysiology of aneurysmal disease is inflammation. Recent developments in vascular and molecular cell biology have increased our knowledge on the role of the adaptive and innate immune systems in the initiation and propagation of the inflammatory response in aortic tissue. AAAs share many features of autoimmune disease, including genetic predisposition, organ specificity and chronic inflammation. Here, this evidence is used to propose that the chronic inflammation observed in AAAs is a consequence of a dysregulated autoimmune response against autologous components of the aortic wall that persists inappropriately. Identification of the molecular and cellular targets involved in AAA formation will allow the development of therapeutic agents for the treatment of AAA.

Corrosion and Tribology of Materials Used in a Novel Reverse Hip Replacement

PubMed Central

Braddon, Linda; Termanini, Zafer; MacDonald, Steven; Parvizi, Jay; Lieberman, Jay; Frankel, Victor; Zuckerman, Joseph

2017-01-01

Total hip arthroplasty has been utilized for the past 50 years as an effective treatment for degenerative, inflammatory and traumatic disorders of the hip. The design of these implants has generally followed the anatomy of the hip as a ball and socket joint with the femoral head representing the ball and the acetabulum representing the socket. We describe a novel hip arthroplasty design in which the “ball” is located on the acetabular side and the “socket” is located on the femoral side. The results of extensive biomechanical testing are described and document wear and corrosion characteristics that are at least equivalent to standard designs. These results support clinical assessment as the next step of the evaluation. PMID:28773112

Force wave transmission through the human locomotor system.

PubMed

Voloshin, A; Wosk, J; Brull, M

1981-02-01

A method to measure the capability of the human shock absorber system to attenuate input dynamic loading during the gait is presented. The experiments were carried out with two groups: healthy subjects and subjects with various pathological conditions. The results of the experiments show a considerable difference in the capability of each group's shock absorbers to attenuate force transmitted through the locomotor system. Comparison shows that healthy subjects definitely possess a more efficient shock-absorbing capacity than do those subjects with joint disorders. Presented results show that degenerative changes in joints reduce their shock absorbing capacity, which leads to overloading of the next shock absorber in the locomotor system. So, the development of osteoarthritis may be expected to result from overloading of a shock absorber's functional capacity.

Deep Brain Stimulation

PubMed Central

Lyketsos, Constantine G.; Pendergrass, Jo Cara; Lozano, Andres M.

2012-01-01

Recent studies have identified an association between memory deficits and defects of the integrated neuronal cortical areas known collectively as the default mode network. It is conceivable that the amyloid deposition or other molecular abnormalities seen in patients with Alzheimer’s disease may interfere with this network and disrupt neuronal circuits beyond the localized brain areas. Therefore, Alzheimer’s disease may be both a degenerative disease and a broader system-level disorder affecting integrated neuronal pathways involved in memory. In this paper, we describe the rationale and provide some evidence to support the study of deep brain stimulation of the hippocampal fornix as a novel treatment to improve neuronal circuitry within these integrated networks and thereby sustain memory function in early Alzheimer’s disease. PMID:23346514

Natural and synthetic saponin adjuvant QS-21 for vaccines against cancer

PubMed Central

Ragupathi, Govind; Gardner, Jeffrey R; Livingston, Philip O; Gin, David Y

2013-01-01

One of the most widely used and potent immunological adjuvants is a mixture of soluble triterpene glycosides purified from the soap bark tree (Quillaja saponaria). Despite challenges in production, quality control, stability and toxicity, the QS-21 fraction from this extract has exhibited exceptional adjuvant properties for a range of antigens. It possesses an ability to augment clinically significant antibody and T-cell responses to vaccine antigens against a variety of infectious diseases, degenerative disorders and cancers. The recent synthesis of active molecules of QS-21 has provided a robust method to produce this leading vaccine adjuvant in high purity as well as to produce novel synthetic QS-21 congeners designed to induce increased immune responsiveness and decreased toxicity. PMID:21506644

Lateral epicondylitis of the elbow.

PubMed

Tosti, Rick; Jennings, John; Sewards, J Milo

2013-04-01

Lateral epicondylitis, or "tennis elbow," is a common musculotendinous degenerative disorder of the extensor origin at the lateral humeral epicondyle. Repetitive occupational or athletic activities involving wrist extension and supination are thought to be causative. The typical symptoms include lateral elbow pain, pain with wrist extension, and weakened grip strength. The diagnosis is made clinically through history and physical examination; however, a thorough understanding of the differential diagnosis is imperative to prevent unnecessary testing and therapies. Most patients improve with nonoperative measures, such as activity modification, physical therapy, and injections. A small percentage of patients will require surgical release of the extensor carpi radialis brevis tendon. Common methods of release may be performed via percutaneous, arthroscopic, or open approaches. Copyright © 2013 Elsevier Inc. All rights reserved.

Analysis of Brain Recurrence

NASA Astrophysics Data System (ADS)

Frilot, Clifton; Kim, Paul Y.; Carrubba, Simona; McCarty, David E.; Chesson, Andrew L.; Marino, Andrew A.

Analysis of Brain Recurrence (ABR) is a method for extracting physiologically significant information from the electroencephalogram (EEG), a non-stationary electrical output of the brain, the ultimate complex dynamical system. ABR permits quantification of temporal patterns in the EEG produced by the non-autonomous differential laws that govern brain metabolism. In the context of appropriate experimental and statistical designs, ABR is ideally suited to the task of interpreting the EEG. Present applications of ABR include discovery of a human magnetic sense, increased mechanistic understanding of neuronal membrane processes, diagnosis of degenerative neurological disease, detection of changes in brain metabolism caused by weak environmental electromagnetic fields, objective characterization of the quality of human sleep, and evaluation of sleep disorders. ABR has important beneficial implications for the development of clinical and experimental neuroscience.

Toward a model for improved targeting of aged at risk of institutionalization.

PubMed Central

Weissert, W G; Cready, C M

1989-01-01

A national sample of institutionalized and noninstitutionalized aged was created by merging the 1977 National Nursing Home Survey and its counterpart, the National Health Interview Survey for the same year. A weighted logistic regression analysis was conducted to identify factors that might be useful in calculating home- and community-based long-term care clients' risk of institutionalization. A model containing patient characteristics, nursing home bed supply, and a climate variable correctly classified 98.2 percent of cases residing in nursing homes or the community. Physical dependency, mental disorder and degenerative disease, lack of spouse, being white, poverty, old age, unoccupied nursing home beds, and climate all appear to be determinants of institutional residency among the aged. PMID:2807934

Role for excitatory amino acids in methamphetamine-induced nigrostriatal dopaminergic toxicity.

PubMed

Sonsalla, P K; Nicklas, W J; Heikkila, R E

1989-01-20

The systemic administration of either methamphetamine or 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to experimental animals produces degenerative changes in nigrostriatal dopaminergic neurons or their axon terminals. This study was conducted to determine if excitatory amino acids, which appear to be involved in various neurodegenerative disorders, might also contribute to the dopaminergic neurotoxicity produced in mice by either methamphetamine or MPTP. MK-801, phencyclidine, and ketamine, noncompetitive antagonists of one subtype of excitatory amino acid receptor, the N-methyl-D-aspartate receptor, provided substantial protection against neurotoxicity produced by methamphetamine but not that produced by MPTP. These findings indicate that excitatory amino acids play an important role in the nigrostriatal dopaminergic damage induced by methamphetamine.

21 CFR 888.3580 - Knee joint patellar (hemi-knee) metallic resurfacing uncemented prosthesis.

Code of Federal Regulations, 2012 CFR

2012-04-01

... degenerative and posttraumatic patellar arthritis. (2) Class III when intended for uses other than treatment of degenerative and posttraumatic patellar arthritis. (c) Date PMA or notice of completion of a PDP is required. A...

21 CFR 888.3580 - Knee joint patellar (hemi-knee) metallic resurfacing uncemented prosthesis.

Code of Federal Regulations, 2014 CFR

2014-04-01

... degenerative and posttraumatic patellar arthritis. (2) Class III when intended for uses other than treatment of degenerative and posttraumatic patellar arthritis. (c) Date PMA or notice of completion of a PDP is required. A...

21 CFR 888.3580 - Knee joint patellar (hemi-knee) metallic resurfacing uncemented prosthesis.

Code of Federal Regulations, 2011 CFR

2011-04-01

... degenerative and posttraumatic patellar arthritis. (2) Class III when intended for uses other than treatment of degenerative and posttraumatic patellar arthritis. (c) Date PMA or notice of completion of a PDP is required. A...

21 CFR 888.3580 - Knee joint patellar (hemi-knee) metallic resurfacing uncemented prosthesis.

Code of Federal Regulations, 2013 CFR

2013-04-01

... degenerative and posttraumatic patellar arthritis. (2) Class III when intended for uses other than treatment of degenerative and posttraumatic patellar arthritis. (c) Date PMA or notice of completion of a PDP is required. A...

Predicting SF-6D utility scores from the Oswestry disability index and numeric rating scales for back and leg pain.

PubMed

Carreon, Leah Y; Glassman, Steven D; McDonough, Christine M; Rampersaud, Raja; Berven, Sigurd; Shainline, Michael

2009-09-01

Cross-sectional cohort. The purpose of this study is to provide a model to allow estimation of utility from the Short Form (SF)-6D using data from the Oswestry Disability Index (ODI), Back Pain Numeric Rating Scale (BPNRS), and the Leg Pain Numeric Rating Scale (LPNRS). Cost-utility analysis provides important information about the relative value of interventions and requires a measure of utility not often available from clinical trial data. The ODI and numeric rating scales for back (BPNRS) and leg pain (LPNRS), are widely used disease-specific measures for health-related quality of life in patients with lumbar degenerative disorders. The purpose of this study is to provide a model to allow estimation of utility from the SF-6D using data from the ODI, BPNRS, and the LPNRS. SF-36, ODI, BPNRS, and LPNRS were prospectively collected before surgery, at 12 and 24 months after surgery in 2640 patients undergoing lumbar fusion for degenerative disorders. Spearman correlation coefficients for paired observations from multiple time points between ODI, BPNRS, and LPNRS, and SF-6D utility scores were determined. Regression modeling was done to compute the SF-6D score from the ODI, BPNRS, and LPNRS. Using a separate, independent dataset of 2174 patients in which actual SF-6D and ODI scores were available, the SF-6D was estimated for each subject and compared to their actual SF-6D. In the development sample, the mean age was 52.5 +/- 15 years and 34% were male. In the validation sample, the mean age was 52.9 +/- 14.2 years and 44% were male. Correlations between the SF-6D and the ODI, BPNRS, and LPNRS were statistically significant (P < 0.0001) with correlation coefficients of 0.82, 0.78, and 0.72, respectively. The regression equation using ODI, BPNRS,and LPNRS to predict SF-6D had an R of 0.69 and a root mean square error of 0.076. The model using ODI alone had an R of 0.67 and a root mean square error of 0.078. The correlation coefficient between the observed and estimated SF-6D score was 0.80. In the validation analysis, there was no statistically significant difference (P = 0.11) between actual mean SF-6D (0.55 +/- 0.12) and the estimated mean SF-6D score (0.55 +/- 0.10) using the ODI regression model. This regression-based algorithm may be used to predict SF-6D scores in studies of lumbar degenerative disease that have collected ODI but not utility scores.

Predicting SF-6D utility scores from the Oswestry Disability Index and Numeric Rating Scales for Back and Leg Pain

PubMed Central

Carreon, Leah Y.; Glassman, Steven D.; McDonough, Christine M.; Rampersaud, Raja; Berven, Sigurd; Shainline, Michael

2012-01-01

Study Design Cross-sectional cohort Objective The purpose of this study is to provide a model to allow estimation of utility from the SF-6D using data from the ODI, BPNRS, and the LPNRS. Summary of Background Data Cost-utility analysis provides important information about the relative value of interventions and requires a measure of utility not often available from clinical trial data. The Oswestry Disability Index (ODI) and numeric rating scales for back (BPNRS) and leg pain (LPNRS), are widely used disease-specific measures for health-related quality of life in patients with lumbar degenerative disorders. The purpose of this study is to provide a model to allow estimation of utility from the SF-6D using data from the ODI, BPNRS, and the LPNRS. Methods SF-36, ODI, BPNRS and LPNRS were prospectively collected pre-operatively, at 12 and 24 months post-operatively in 2640 patients undergoing lumbar fusion for degenerative disorders. Spearman correlation coefficients for paired observations from multiple time points between ODI, BPNRS and LPNRS and SF-6D utility scores were determined. Regression modeling was done to compute the SF-6D score from the ODI, BPNRS and LPNRS. Using a separate, independent dataset of 2174 patients in which actual SF-6D and ODI scores were available, the SF-6D was estimated for each subject and compared to their actual SF-6D. Results In the development sample, the mean age was 52.5 ± 15 years and 34% were male. In the validation sample the mean age was 52.9 ± 14.2 years and 44% were male. Correlations between the SF-6D and the ODI, BPNRS and LPNRS were statistically significant (p<0.0001) with correlation coefficients of 0.82, 0.78, and 0.72 respectively. The regression equation using ODI, BPNRS and LPNRS to predict SF-6D had an R2 of 0.69 and a root mean square error (RMSE) of 0.076. The model using ODI alone had an R2 of 0.67 and a RMSE of 0.078. The correlation coefficient between the observed and estimated SF-6D score was 0.80. In the validation analysis, there was no statistically significant difference (p=0.11) between actual mean SF-6D (0.55 ± 0.12) and the estimated mean SF-6D score (0.55 ± 0.10) using the ODI regression model. Conclusion This regression-based algorithm may be used to predict SF-6D scores in studies of lumbar degenerative disease that have collected ODI but not utility scores. PMID:19730215

Degenerative Pannus Mimicking Clival Chordoma Resected via an Endoscopic Transnasal Approach.

PubMed

Khaldi, Ahmad; Griauzde, Julius; Duckworth, Edward A M

2011-05-01

Lesions of the lower clivus represent a technically challenging subset of skull base disease that requires careful treatment. A 75-year-old woman with tongue atrophy was referred for resection of a presumed clival chordoma. The lesion was resected via an endoscopic transnasal transclival approach with no complications. Pathology revealed only chronic inflammatory tissue consistent with a degenerative pannus. Degenerative pannus should be included in the differential diagnosis of lower clival extradural lesions. The endoscopic transnasal transclival corridor should be considered for resection of such lesions as an alternative to larger, more morbid, traditional skull base approaches.

Degenerative Pannus Mimicking Clival Chordoma Resected via an Endoscopic Transnasal Approach

PubMed Central

Khaldi, Ahmad; Griauzde, Julius; Duckworth, Edward A.M.

2011-01-01

Lesions of the lower clivus represent a technically challenging subset of skull base disease that requires careful treatment. A 75-year-old woman with tongue atrophy was referred for resection of a presumed clival chordoma. The lesion was resected via an endoscopic transnasal transclival approach with no complications. Pathology revealed only chronic inflammatory tissue consistent with a degenerative pannus. Degenerative pannus should be included in the differential diagnosis of lower clival extradural lesions. The endoscopic transnasal transclival corridor should be considered for resection of such lesions as an alternative to larger, more morbid, traditional skull base approaches. PMID:23984195

Motor Training in Degenerative Spinocerebellar Disease: Ataxia-Specific Improvements by Intensive Physiotherapy and Exergames

PubMed Central

2014-01-01

The cerebellum is essentially involved in movement control and plays a critical role in motor learning. It has remained controversial whether patients with degenerative cerebellar disease benefit from high-intensity coordinative training. Moreover, it remains unclear by which training methods and mechanisms these patients might improve their motor performance. Here, we review evidence from different high-intensity training studies in patients with degenerative spinocerebellar disease. These studies demonstrate that high-intensity coordinative training might lead to a significant benefit in patients with degenerative ataxia. This training might be based either on physiotherapy or on whole-body controlled videogames (“exergames”). The benefit shown in these studies is equal to regaining one or more years of natural disease progression. In addition, first case studies indicate that even subjects with advanced neurodegeneration might benefit from such training programs. For both types of training, the observed clinical improvements are paralleled by recoveries in ataxia-specific dysfunctions (e.g., multijoint coordination and dynamic stability). Importantly, for both types of training, the retention of the effects seems to depend on the frequency and continuity of training. Based on these studies, we here present preliminary recommendations for clinical practice, and articulate open questions that might guide future studies on neurorehabilitation in degenerative spinocerebellar disease. PMID:24877117

Characterization of Individuals with Sacroiliac Joint Bridging in a Skeletal Population: Analysis of Degenerative Changes in Spinal Vertebrae

PubMed Central

Imamura, Takeshi; Saiki, Kazunobu; Okamoto, Keishi; Maeda, Junichiro; Matsuo, Hiroaki; Wakebe, Tetsuaki; Ogami, Keiko; Tomita, Masato; Tagami, Atsushi; Shindo, Hiroyuki; Tsurumoto, Toshiyuki

2014-01-01

The aim of this study was to characterize the individuals with sacroiliac joint bridging (SIB) by analyzing the degenerative changes in their whole vertebral column and comparing them with the controls. A total of 291 modern Japanese male skeletons, with an average age at death of 60.8 years, were examined macroscopically. They were divided into two groups: individuals with SIB and those without bridging (Non-SIB). The degenerative changes in their whole vertebral column were evaluated, and marginal osteophyte scores (MOS) of the vertebral bodies and degenerative joint scores in zygapophyseal joints were calculated. SIB was recognized in 30 individuals from a total of 291 males (10.3%). The average of age at death in SIB group was significantly higher than that in Non-SIB group. The values of MOS in the thoracic spines, particularly in the anterior part of the vertebral bodies, were consecutively higher in SIB group than in Non-SIB group. Incidence of fused vertebral bodies intervertebral levels was obviously higher in SIB group than in Non-SIB group. SIB and marginal osteophyte formation in vertebral bodies could coexist in a skeletal population of men. Some systemic factors might act on these degenerative changes simultaneously both in sacroiliac joint and in vertebral column. PMID:25276825

Degenerative joint disease: multiple joint involvement in young and mature dogs.

PubMed

Olsewski, J M; Lust, G; Rendano, V T; Summers, B A

1983-07-01

Radiologic, pathologic, and ancillary methods were used to determine the occurrence of degenerative joint disease involving multiple joints of immature and adult dogs. Animals were selected for the development of hip joint dysplasia and chronic degenerative joint disease. Of disease-prone dogs, 82% (45 of 55 dogs) had radiologic changes, indicative of hip dysplasia, by 1 year of age. At necropsy, more abnormal joints were identified than by radiographic examination. Among 92 dogs between 3 to 11 months of age that had joint abnormalities, 71% had hip joint involvement; 38%, shoulder joint involvement; 22%, stifle joint involvement; and 40% had multiple joint involvement. Polyarthritis was asymptomatic and unexpected. Radiographic examination of older dogs also revealed evidence of degenerative joint disease in many joints. Multiple joint involvement was substantiated at necropsy of young and mature dogs. A similar pattern of polyarticular osteoarthritis was revealed in a survey (computer search) of necropsy reports from medical case records of 100 adult and elderly dogs. Usually, the joint disease was an incidental observation, unrelated to the clinical disease or to the cause of death. The frequent occurrence of degenerative changes in several joints of dogs aged 6 months to 17 years indicated that osteoarthritis may be progressive in these joints and raises the possibility that systemic factors are involved in the disease process.

Autism in 2016: the need for answers.

PubMed

Posar, Annio; Visconti, Paola

Autism spectrum disorders are lifelong and often devastating conditions that severely affect social functioning and self-sufficiency. The etiopathogenesis is presumably multifactorial, resulting from a very complex interaction between genetic and environmental factors. The dramatic increase in autism spectrum disorder prevalence observed during the last decades has led to placing more emphasis on the role of environmental factors in the etiopathogenesis. The objective of this narrative biomedical review was to summarize and discuss the results of the most recent and relevant studies about the environmental factors hypothetically involved in autism spectrum disorder etiopathogenesis. A search was performed in PubMed (United States National Library of Medicine) about the environmental factors hypothetically involved in the non-syndromic autism spectrum disorder etiopathogenesis, including: air pollutants, pesticides and other endocrine-disrupting chemicals, electromagnetic pollution, vaccinations, and diet modifications. While the association between air pollutants, pesticides and other endocrine-disrupting chemicals, and risk for autism spectrum disorder is receiving increasing confirmation, the hypothesis of a real causal relation between them needs further data. The possible pathogenic mechanisms by which environmental factors can lead to autism spectrum disorder in genetically predisposed individuals were summarized, giving particular emphasis to the increasingly important role of epigenetics. Future research should investigate whether there is a significant difference in the prevalence of autism spectrum disorder among nations with high and low levels of the various types of pollution. A very important goal of the research concerning the interactions between genetic and environmental factors in autism spectrum disorder etiopathogenesis is the identification of vulnerable populations, also in view of proper prevention. Copyright © 2016 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

Guideline summary review: An evidence-based clinical guideline for the diagnosis and treatment of degenerative lumbar spondylolisthesis.

PubMed

Matz, Paul G; Meagher, R J; Lamer, Tim; Tontz, William L; Annaswamy, Thiru M; Cassidy, R Carter; Cho, Charles H; Dougherty, Paul; Easa, John E; Enix, Dennis E; Gunnoe, Bryan A; Jallo, Jack; Julien, Terrence D; Maserati, Matthew B; Nucci, Robert C; O'Toole, John E; Rosolowski, Karie; Sembrano, Jonathan N; Villavicencio, Alan T; Witt, Jens-Peter

2016-03-01

The North American Spine Society's (NASS) Evidence-Based Clinical Guideline for the Diagnosis and Treatment of Degenerative Lumbar Spondylolisthesis features evidence-based recommendations for diagnosing and treating degenerative lumbar spondylolisthesis. The guideline updates the 2008 guideline on this topic and is intended to reflect contemporary treatment concepts for symptomatic degenerative lumbar spondylolisthesis as reflected in the highest quality clinical literature available on this subject as of May 2013. The NASS guideline on this topic is the only guideline on degenerative lumbar spondylolisthesis included in the Agency for Healthcare Research and Quality's National Guideline Clearinghouse (NGC). The purpose of this guideline is to provide an evidence-based educational tool to assist spine specialists when making clinical decisions for patients with degenerative lumbar spondylolisthesis. This article provides a brief summary of the evidence-based guideline recommendations for diagnosing and treating patients with this condition. A systematic review of clinical studies relevant to degenerative spondylolisthesis was carried out. This NASS spondyolisthesis guideline is the product of the Degenerative Lumbar Spondylolisthesis Work Group of NASS' Evidence-Based Guideline Development Committee. The methods used to develop this guideline are detailed in the complete guideline and technical report available on the NASS website. In brief, a multidisciplinary work group of spine care specialists convened to identify clinical questions to address in the guideline. The literature search strategy was developed in consultation with medical librarians. Upon completion of the systematic literature search, evidence relevant to the clinical questions posed in the guideline was reviewed. Work group members used the NASS evidentiary table templates to summarize study conclusions, identify study strengths and weaknesses, and assign levels of evidence. Work group members participated in webcasts and in-person recommendation meetings to update and formulate evidence-based recommendations and incorporate expert opinion when necessary. The draft guidelines were submitted to an internal peer review process and ultimately approved by the NASS Board of Directors. Upon publication, the Degenerative Lumbar Spondylolisthesis guideline was accepted into the NGC and will be updated approximately every 5 years. Twenty-seven clinical questions were addressed in this guideline update, including 15 clinical questions from the original guideline and 12 new clinical questions. The respective recommendations were graded by strength of the supporting literature, which was stratified by levels of evidence. Twenty-one new or updated recommendations or consensus statements were issued and 13 recommendations or consensus statements were maintained from the original guideline. The clinical guideline was created using the techniques of evidence-based medicine and best available evidence to aid practitioners in the care of patients with degenerative lumbar spondylolisthesis. The entire guideline document, including the evidentiary tables, literature search parameters, literature attrition flow chart, suggestions for future research, and all of the references, is available electronically on the NASS website at https://www.spine.org/Pages/ResearchClinicalCare/QualityImprovement/ClinicalGuidelines.aspx and will remain updated on a timely schedule. Copyright © 2016 Elsevier Inc. All rights reserved.

First sternocostal degenerative arthritis with intrarticular fluid collection. A case report.

PubMed

Chalazonitis, Athanasios N; Condilis, Nicolas; Tilentzoglou, Anastasia C; Pontikis, John; Tzovara, Joannie

2006-01-01

A rare case with clinical condition of first sternocostal degenerative arthritis with intra-articular fluid collection that developed after long-lasting intense exercise (weight-lifting) for twenty years is reported. Imaging findings and differential diagnoses of the case are presented.

Gene therapy restores auditory and vestibular function in a mouse model of Usher syndrome type 1c.

PubMed

Pan, Bifeng; Askew, Charles; Galvin, Alice; Heman-Ackah, Selena; Asai, Yukako; Indzhykulian, Artur A; Jodelka, Francine M; Hastings, Michelle L; Lentz, Jennifer J; Vandenberghe, Luk H; Holt, Jeffrey R; Géléoc, Gwenaëlle S

2017-03-01

Because there are currently no biological treatments for hearing loss, we sought to advance gene therapy approaches to treat genetic deafness. We focused on Usher syndrome, a devastating genetic disorder that causes blindness, balance disorders and profound deafness, and studied a knock-in mouse model, Ush1c c.216G>A, for Usher syndrome type IC (USH1C). As restoration of complex auditory and balance function is likely to require gene delivery systems that target auditory and vestibular sensory cells with high efficiency, we delivered wild-type Ush1c into the inner ear of Ush1c c.216G>A mice using a synthetic adeno-associated viral vector, Anc80L65, shown to transduce 80-90% of sensory hair cells. We demonstrate recovery of gene and protein expression, restoration of sensory cell function, rescue of complex auditory function and recovery of hearing and balance behavior to near wild-type levels. The data represent unprecedented recovery of inner ear function and suggest that biological therapies to treat deafness may be suitable for translation to humans with genetic inner ear disorders.

Altered heavy metals and transketolase found in autistic spectrum disorder.

PubMed

Obrenovich, Mark E; Shamberger, Raymond J; Lonsdale, Derrick

2011-12-01

Autism and autism spectrum disorder (ASD) are developmental brain disorders with complex, obscure, and multifactorial etiology. Our recent clinical survey of patient records from ASD children under the age of 6 years and their age-matched controls revealed evidence of abnormal markers of thiol metabolism, as well as a significant alteration in deposition of several heavy metal species, particularly arsenic, mercury, copper, and iron in hair samples between the groups. Altered thiol metabolism from heavy metal toxicity may be responsible for the biochemical alterations in transketolase, and are mechanisms for oxidative stress production, dysautonomia, and abnormal thiamine homeostasis. It is unknown why the particular metals accumulate, but we suspect that children with ASD may have particular trouble excreting thiol-toxic heavy metal species, many of which exist as divalent cations. Accumulation or altered mercury clearance, as well as concomitant oxidative stress, arising from redox-active metal and arsenic toxicity, offers an intriguing component or possible mechanism for oxidative stress-mediated neurodegeneration in ASD patients. Taken together, these factors may be more important to the etiology of this symptomatically diverse disease spectrum and may offer insights into new treatment approaches and avenues of exploration for this devastating and growing disease.

Functional Implications of the IL-23/IL-17 Immune Axis in Schizophrenia.

PubMed

Debnath, Monojit; Berk, Michael

2017-12-01

The aetiology of schizophrenia seems to stem from complex interactions amongst environmental, genetic, metabolic, immunologic and oxidative components. Chronic low-grade inflammation has been persistently linked to schizophrenia, and this has primarily been based on the findings derived from Th1/Th2 cytokine balance. While the IL-23/IL-17 axis plays crucial role in the pathogenesis of several immune-mediated disorders, it has remained relatively unexplored in neuropsychiatric disorders. Altered levels of cytokines related to IL-23/IL-17 axis have been observed in schizophrenia patients in a few studies. In addition, other indirect factors known to confer schizophrenia risk like complement activation and altered gut microbiota are shown to modulate the IL-23/IL-17 axis. These preliminary observations provide crucial clues about the functional implications of IL-23/IL-17 axis in schizophrenia. In this review, an attempt has been made to highlight the biology of IL-23/IL-17 axis and its relevance to schizophrenia risk and pathogenesis. Given the pathogenic potential of the IL-23/IL-17 axis, therapeutic targeting of this axis may be a promising approach to benefit patients suffering from this devastating disorder.

Reduced striatal dopamine transporters in people with internet addiction disorder.

PubMed

Hou, Haifeng; Jia, Shaowe; Hu, Shu; Fan, Rong; Sun, Wen; Sun, Taotao; Zhang, Hong

2012-01-01

In recent years, internet addiction disorder (IAD) has become more prevalent worldwide and the recognition of its devastating impact on the users and society has rapidly increased. However, the neurobiological mechanism of IAD has not bee fully expressed. The present study was designed to determine if the striatal dopamine transporter (DAT) levels measured by (99m)Tc-TRODAT-1 single photon emission computed tomography (SPECT) brain scans were altered in individuals with IAD. SPECT brain scans were acquired on 5 male IAD subjects and 9 healthy age-matched controls. The volume (V) and weight (W) of bilateral corpus striatum as well as the (99m)Tc-TRODAT-1 uptake ratio of corpus striatum/the whole brain (Ra) were calculated using mathematical models. It was displayed that DAT expression level of striatum was significantly decreased and the V, W, and Ra were greatly reduced in the individuals with IAD compared to controls. Taken together, these results suggest that IAD may cause serious damages to the brain and the neuroimaging findings further illustrate IAD is associated with dysfunctions in the dopaminergic brain systems. Our findings also support the claim that IAD may share similar neurobiological abnormalities with other addictive disorders.

Opioid Use Disorders

PubMed Central

Sharma, Bikash; Bruner, Ann; Barnett, Gabrielle; Fishman, Marc

2016-01-01

Opioid use and addiction in adolescents and young adults, including heroin and non-medical use of prescription opioids, is a serious and growing health problem of epidemic proportions. Opioid use has devastating consequences for youth and their families, including: progression to full addiction, severe psychosocial impairment, HCV and HIV transmission with injection use, exacerbation of co-occurring psychiatric disorders, overdose, and death. This chapter will provide an overview of opioid use disorders (OUDs) in youth, including: etiologic factors, epidemiology, consequences, clinical presentation and course, assessment and diagnosis, overdose, detoxification, and treatment. Opioid overdose is a life-threatening emergency. Respiratory depression should be treated with naloxone, and respiratory support if necessary. Overdose should always be utilized as an opportunity to initiate addiction treatment. Opioid withdrawal management (detoxification) is often a necessary, but never sufficient, component of treatment for OUDs. Medications used in the treatment of withdrawal may include buprenorphine, clonidine and others for relief of symptoms. Treatment for OUDs is effective but treatment capacity is alarmingly limited and under-developed. Although there is a limited evidence base for youth specific treatment, emerging consensus supports the incorporation of relapse prevention medications such as buprenorphine and extended release naltrexone into comprehensive psychosocial treatment including counseling and family involvement. PMID:27338968

The Bad, the Good, and the Ugly about Oxidative Stress

PubMed Central

Jimenez-Del-Rio, Marlene; Velez-Pardo, Carlos

2012-01-01

Alzheimer's disease (AD), Parkinson's disease (PD), and cancer (e.g., leukemia) are the most devastating disorders affecting millions of people worldwide. Except for some kind of cancers, no effective and/or definitive therapeutic treatment aimed to reduce or to retard the clinic and pathologic symptoms induced by AD and PD is presently available. Therefore, it is urgently needed to understand the molecular basis of these disorders. Since oxidative stress (OS) is an important etiologic factor of the pathologic process of AD, PD, and cancer, understanding how intracellular signaling pathways respond to OS will have a significant implication in the therapy of these diseases. Here, we propose a model of minimal completeness of cell death signaling induced by OS as a mechanistic explanation of neuronal and cancer cell demise. This mechanism might provide the basis for therapeutic design strategies. Finally, we will attempt to associate PD, cancer, and OS. This paper critically analyzes the evidence that support the “oxidative stress model” in neurodegeneration and cancer. PMID:22619696

The genetics of Leigh syndrome and its implications for clinical practice and risk management.

PubMed

Ruhoy, Ilene S; Saneto, Russell P

2014-01-01

Leigh syndrome, also referred to as subacute necrotizing encephalomyelopathy, is a severe, early-onset neurodegenerative disorder that is relentlessly progressive and devastating to both the patient and the patient's family. Attributed to the ultimate failure of the mitochondrial respiratory chain, once it starts, the disease often results in the regression of both mental and motor skills, leading to disability and rapid progression to death. It is a mitochondrial disorder with both phenotypic and genetic heterogeneity. The cause of death is most often respiratory failure, but there are a whole host of complications, including refractory seizures, that may further complicate morbidity and mortality. The symptoms may develop slowly or with rapid progression, usually associated with age of onset. Although the disease is usually diagnosed within the first year of life, it is important to note that recent studies reveal phenotypic heterogeneity, with some patients having evidence of in utero presentation and others having adult-onset symptoms.

Brain/MINDS: brain-mapping project in Japan

PubMed Central

Okano, Hideyuki; Miyawaki, Atsushi; Kasai, Kiyoto

2015-01-01

There is an emerging interest in brain-mapping projects in countries across the world, including the USA, Europe, Australia and China. In 2014, Japan started a brain-mapping project called Brain Mapping by Integrated Neurotechnologies for Disease Studies (Brain/MINDS). Brain/MINDS aims to map the structure and function of neuronal circuits to ultimately understand the vast complexity of the human brain, and takes advantage of a unique non-human primate animal model, the common marmoset (Callithrix jacchus). In Brain/MINDS, the RIKEN Brain Science Institute acts as a central institute. The objectives of Brain/MINDS can be categorized into the following three major subject areas: (i) structure and functional mapping of a non-human primate brain (the marmoset brain); (ii) development of innovative neurotechnologies for brain mapping; and (iii) human brain mapping; and clinical research. Brain/MINDS researchers are highly motivated to identify the neuronal circuits responsible for the phenotype of neurological and psychiatric disorders, and to understand the development of these devastating disorders through the integration of these three subject areas. PMID:25823872

THE USE OF POSITRON EMISSION TOMOGRAPHY IN IDENTIFYING AND QUANTIFYING RECEPTORS INVOLVED IN SCHIZOPHRENIA.

DOE Office of Scientific and Technical Information (OSTI.GOV)

VOLKOW,N.D.; WOLF,A.P.

1991-01-01

Schizophrenia is a devasting mental disorder that is the focus of a great deal of research. Some symptoms of the disease, such as auditory hallucinations and delusions, can be ameliorated with drug treatment, whereas other symptoms, such as social withdrawal and cognitive decline, remain uncontrolled. It is possible that these latter symptoms that are often termed ''negative symptoms'' are the result of anatomical and neurochemical abnormalities, whereas those symptoms of the disease such as auditory hallucinations that are termed ''positive symptoms'' may be a result of only neurochemical disorders. The drugs used to treat schizophrenia are designated neuroleptics. The termmore » neuroleptic was chosen to emphasize the similarity of pharmacological profiles of drugs with entirely different chemical structures. Especially prominent features of the effects of neuroleptics include the following: a state of affective indifference; a decrease in locomotor activity; a decrease in excitation, agitation, and aggressiveness; and an antipsychotic action in patients with acute as well as chronic psychoses.« less

The genetics of Leigh syndrome and its implications for clinical practice and risk management

PubMed Central

Ruhoy, Ilene S; Saneto, Russell P

2014-01-01

Leigh syndrome, also referred to as subacute necrotizing encephalomyelopathy, is a severe, early-onset neurodegenerative disorder that is relentlessly progressive and devastating to both the patient and the patient’s family. Attributed to the ultimate failure of the mitochondrial respiratory chain, once it starts, the disease often results in the regression of both mental and motor skills, leading to disability and rapid progression to death. It is a mitochondrial disorder with both phenotypic and genetic heterogeneity. The cause of death is most often respiratory failure, but there are a whole host of complications, including refractory seizures, that may further complicate morbidity and mortality. The symptoms may develop slowly or with rapid progression, usually associated with age of onset. Although the disease is usually diagnosed within the first year of life, it is important to note that recent studies reveal phenotypic heterogeneity, with some patients having evidence of in utero presentation and others having adult-onset symptoms. PMID:25419155

The bad, the good, and the ugly about oxidative stress.

PubMed

Jimenez-Del-Rio, Marlene; Velez-Pardo, Carlos

2012-01-01

Alzheimer's disease (AD), Parkinson's disease (PD), and cancer (e.g., leukemia) are the most devastating disorders affecting millions of people worldwide. Except for some kind of cancers, no effective and/or definitive therapeutic treatment aimed to reduce or to retard the clinic and pathologic symptoms induced by AD and PD is presently available. Therefore, it is urgently needed to understand the molecular basis of these disorders. Since oxidative stress (OS) is an important etiologic factor of the pathologic process of AD, PD, and cancer, understanding how intracellular signaling pathways respond to OS will have a significant implication in the therapy of these diseases. Here, we propose a model of minimal completeness of cell death signaling induced by OS as a mechanistic explanation of neuronal and cancer cell demise. This mechanism might provide the basis for therapeutic design strategies. Finally, we will attempt to associate PD, cancer, and OS. This paper critically analyzes the evidence that support the "oxidative stress model" in neurodegeneration and cancer.

Shaping vulnerability to addiction - the contribution of behavior, neural circuits and molecular mechanisms.

PubMed

Egervari, Gabor; Ciccocioppo, Roberto; Jentsch, J David; Hurd, Yasmin L

2018-02-01

Substance use disorders continue to impose increasing medical, financial and emotional burdens on society in the form of morbidity and overdose, family disintegration, loss of employment and crime, while advances in prevention and treatment options remain limited. Importantly, not all individuals exposed to abused substances effectively develop the disease. Genetic factors play a significant role in determining addiction vulnerability and interactions between innate predisposition, environmental factors and personal experiences are also critical. Thus, understanding individual differences that contribute to the initiation of substance use as well as on long-term maladaptations driving compulsive drug use and relapse propensity is of critical importance to reduce this devastating disorder. In this paper, we discuss current topics in the field of addiction regarding individual vulnerability related to behavioral endophenotypes, neural circuits, as well as genetics and epigenetic mechanisms. Expanded knowledge of these factors is of importance to improve and personalize prevention and treatment interventions in the future. Copyright © 2017 Elsevier Ltd. All rights reserved.

Medical management of ischemic stuttering priapism: a contemporary review of the literature.

PubMed

Levey, Helen R; Kutlu, Omer; Bivalacqua, Trinity J

2012-01-01

Priapism is defined as a prolonged and persistent erection of the penis without sexual stimulation. This is a poorly understood disease process with little information on the pathophysiology of this erectile disorder. Complications from this disorder are devastating due to the irreversible erectile damage and resultant erectile dysfunction (ED). Stuttering priapism, though relatively rare, affects a high prevalence of men with sickle-cell disease (SCD) and presents a challenging problem with guidelines for treatment lacking or resulting in permanent ED. The mechanisms involved in the development of priapism in this cohort are poorly characterized; therefore, medical management of priapism represents a therapeutic challenge to urologists. Additional research is warranted, so we can effectively target treatments for these patients with prevention as the goal. This review gives an introduction to stuttering priapism and its clinical significance, specifically with regards to the patient with SCD. Additionally, the proposed mechanisms behind its pathophysiology and a summary of the current and future targets for medical management are discussed.

Does restoration of focal lumbar lordosis for single level degenerative spondylolisthesis result in better patient-reported clinical outcomes? A systematic literature review.

PubMed

Rhee, Chanseok; Visintini, Sarah; Dunning, Cynthia E; Oxner, William M; Glennie, R Andrew

2017-10-01

It is controversial whether the surgical restoration of sagittal balance and spinopelvic angulation in a single level lumbar degenerative spondylolisthesis results in clinical improvements. The purpose of this study to systematically review the available literature to determine whether the surgical correction of malalignment in lumbar degenerative spondylolisthesis correlates with improvements in patient-reported clinical outcomes. Literature searches were performed via Ovid Medline, Embase, CENTRAL and Web of Science using search terms "lumbar," "degenerative/spondylolisthesis" and "surgery/surgical/surgeries/fusion". This resulted in 844 articles and after reviewing the abstracts and full-texts, 13 articles were included for summary and final analysis. There were two Level II articles, four Level III articles and five Level IV articles. Most commonly used patient-reported outcome measures (PROMs) were Oswestery disability index (ODI) and visual analogue scale (VAS). Four articles were included for the final statistical analysis. There was no statistically significant difference between the patient groups who achieved successful surgical correction of malalignment and those who did not for either ODI (mean difference -0.94, CI -8.89-7.00) or VAS (mean difference 1.57, CI -3.16-6.30). Two studies assessed the efficacy of manual reduction of lumbar degenerative spondylolisthesis and their clinical outcomes after the operation, and there was no statistically significant improvement. Overall, the restoration of focal lumbar lordosis and restoration of sagittal balance for single-level lumbar degenerative spondylolisthesis does not seem to yield clinical improvements but well-powered studies on this specific topic is lacking in the current literature. Future well-powered studies are needed for a more definitive conclusion. Copyright © 2017 Elsevier Ltd. All rights reserved.

Disorders of the lower cranial nerves

PubMed Central

Finsterer, Josef; Grisold, Wolfgang

2015-01-01

Lesions of the lower cranial nerves (LCN) are due to numerous causes, which need to be differentiated to optimize management and outcome. This review aims at summarizing and discussing diseases affecting LCN. Review of publications dealing with disorders of the LCN in humans. Affection of multiple LCN is much more frequent than the affection of a single LCN. LCN may be affected solely or together with more proximal cranial nerves, with central nervous system disease, or with nonneurological disorders. LCN lesions have to be suspected if there are typical symptoms or signs attributable to a LCN. Causes of LCN lesions can be classified as genetic, vascular, traumatic, iatrogenic, infectious, immunologic, metabolic, nutritional, degenerative, or neoplastic. Treatment of LCN lesions depends on the underlying cause. An effective treatment is available in the majority of the cases, but a prerequisite for complete recovery is the prompt and correct diagnosis. LCN lesions need to be considered in case of disturbed speech, swallowing, coughing, deglutition, sensory functions, taste, or autonomic functions, neuralgic pain, dysphagia, head, pharyngeal, or neck pain, cardiac or gastrointestinal compromise, or weakness of the trapezius, sternocleidomastoid, or the tongue muscles. To correctly assess manifestations of LCN lesions, precise knowledge of the anatomy and physiology of the area is required. PMID:26167022

Movement disorders: role of imaging in diagnosis.

PubMed

Mascalchi, Mario; Vella, Alessandra; Ceravolo, Roberto

2012-02-01

Magnetic resonance imaging (MRI and single-photon emission computed tomography (SPECT) have a considerable role in the diagnosis of the single patient with movement disorders. Conventional MRI demonstrates symptomatic causes of parkinsonism but does not show any specific finding in Parkinson's disease (PD). However, SPECT using tracers of the dopamine transporter (DAT) demonstrates an asymmetric decrease of the uptake in the putamen and caudate from the earliest clinical stages. In other degenerative forms of parkinsonism, including progressive supranuclear palsy (PSP), multisystem atrophy (MSA), and corticobasal degeneration (CBD), MRI reveals characteristic patterns of regional atrophy combined with signal changes or microstructural changes in the basal ganglia, pons, middle and superior cerebellar peduncles, and cerebral subcortical white matter. SPECT demonstrates a decreased uptake of tracers of the dopamine D2 receptors in the striata of patients with PSP and MSA, which is not observed in early PD. MRI also significantly contributes to the diagnosis of some inherited hyperkinetic conditions including neurodegeneration with brain iron accumulation and fragile-X tremor/ataxia syndrome by revealing characteristic symmetric signal changes in the basal ganglia and middle cerebellar peduncles, respectively. A combination of the clinical features with MRI and SPECT is recommended for optimization of the diagnostic algorithm in movement disorders. Copyright © 2011 Wiley Periodicals, Inc.

Potential of Induced Pluripotent Stem Cells (iPSCs) for Treating Age-Related Macular Degeneration (AMD).

PubMed

Fields, Mark; Cai, Hui; Gong, Jie; Del Priore, Lucian

2016-12-08

The field of stem cell biology has rapidly evolved in the last few decades. In the area of regenerative medicine, clinical applications using stem cells hold the potential to be a powerful tool in the treatment of a wide variety of diseases, in particular, disorders of the eye. Embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) are promising technologies that can potentially provide an unlimited source of cells for cell replacement therapy in the treatment of retinal degenerative disorders such as age-related macular degeneration (AMD), Stargardt disease, and other disorders. ESCs and iPSCs have been used to generate retinal pigment epithelium (RPE) cells and their functional behavior has been tested in vitro and in vivo in animal models. Additionally, iPSC-derived RPE cells provide an autologous source of cells for therapeutic use, as well as allow for novel approaches in disease modeling and drug development platforms. Clinical trials are currently testing the safety and efficacy of these cells in patients with AMD. In this review, the current status of iPSC disease modeling of AMD is discussed, as well as the challenges and potential of this technology as a viable option for cell replacement therapy in retinal degeneration.

[Disorders of locomotor system and effectiveness of physiotherapy in coal miners].

PubMed

Bilski, Bartosz; Bednarek, Agata

2003-01-01

The aim of the survey was to analyze the efficacy of physiotherapy applied in coal miners as well as to assess their locomotor system load and the effects of working conditions in mines. The questionnaire survey covered a group of 51 miners, aged 28-76 years (mean, 54 years), undergoing physiotherapeutic procedures in the mine out-patient clinic during the first quarter of 2003. The survey revealed that lumbosacral disorders were the most frequent locomotor system complaints reported by miners, especially those who work in a bending down position. According to the clinical data, spondylosis and allied disorders were the main reasons for pain in this part of the body. Having analyzed the relationship between age and occurrence of back pains, the majority of complaints were found in the 46-55 age group (two complaints per one respondent). The analysis of the association between back pains and duration of employment revealed that the complaints for the locomotor system occurred already after a five-year employment. The survey showed that the application of physiotherapeutic procedures diminished the back pain in the study group by 2.83 on average on the 0-10 scale. It was also found that magnetotherapy proved to be the most effective method in treating the spinal degenerative changes.

Neurologic manifestations of chronic methamphetamine abuse

PubMed Central

Rusyniak, Daniel E.

2011-01-01

Summary Chronic methamphetamine abuse has devastating effects on the central nervous system. The degree to which addicts will tolerate the dysfunction in the way they think, feel, move, and even look, is a powerful testimony to the addictive properties of this drug. While the mechanisms behind these disorders are complex, at their heart they involve the recurring increase in the concentrations of central monoamines with subsequent dysfunction in dopaminergic neurotransmission. The mainstay of treatment for the problems associated with chronic methamphetamine abuse is abstinence. However, by recognizing the manifestations of chronic abuse, clinicians will be better able to help their patients get treatment for their addiction and to deal with the neurologic complications related to chronic abuse. PMID:21803215

Probing amyloid protein aggregation with optical superresolution methods: from the test tube to models of disease

PubMed Central

Kaminski, Clemens F.; Kaminski Schierle, Gabriele S.

2016-01-01

Abstract. The misfolding and self-assembly of intrinsically disordered proteins into insoluble amyloid structures are central to many neurodegenerative diseases such as Alzheimer’s and Parkinson’s diseases. Optical imaging of this self-assembly process in vitro and in cells is revolutionizing our understanding of the molecular mechanisms behind these devastating conditions. In contrast to conventional biophysical methods, optical imaging and, in particular, optical superresolution imaging, permits the dynamic investigation of the molecular self-assembly process in vitro and in cells, at molecular-level resolution. In this article, current state-of-the-art imaging methods are reviewed and discussed in the context of research into neurodegeneration. PMID:27413767

Software support for Huntingtons disease research.

PubMed

Conneally, P M; Gersting, J M; Gray, J M; Beidleman, K; Wexler, N S; Smith, C L

1991-01-01

Huntingtons disease (HD) is a hereditary disorder involving the central nervous system. Its effects are devastating, to the affected person as well as his family. The Department of Medical and Molecular Genetics at Indiana University (IU) plays an integral part in Huntingtons research by providing computerized repositories of HD family information for researchers and families. The National Huntingtons Disease Research Roster, founded in 1979 at IU, and the Huntingtons Disease in Venezuela Project database contain information that has proven to be invaluable in the worldwide field of HD research. This paper addresses the types of information stored in each database, the pedigree database program (MEGADATS) used to manage the data, and significant findings that have resulted from access to the data.

Update in the treatment of schizophrenia.

PubMed

Katz, I; Kac, M

1993-04-01

The large number of drugs available to treat schizophrenia and the emergence of atypical and newer agents that provide efficiency with lessening of side effects may not only serve to provide more amelioration against this disease, but may also help us to unravel the neurochemical defects of the disorder. Despite these encouraging trends, the reality is that schizophrenia is still a devastating illness for a sizeable minority affected with the condition, that a 'cure' is not yet possible, and that drug therapies alone will not provide all that is required in acute or continuing management. Supporting care in the community for patient and family are just as important as pharmacotherapy in managing this problem.

The Role of Histone Deacetylases in Neurodegenerative Diseases and Small-Molecule Inhibitors as a Potential Therapeutic Approach

NASA Astrophysics Data System (ADS)

Bürli, Roland W.; Thomas, Elizabeth; Beaumont, Vahri

Neurodegenerative disorders are devastating for patients and their social environment. Their etiology is poorly understood and complex. As a result, there is clearly an urgent need for therapeutic agents that slow down disease progress and alleviate symptoms. In this respect, interference with expression and function of multiple gene products at the epigenetic level has offered much promise, and histone deacetylases play a crucial role in these processes. This review presents an overview of the biological pathways in which these enzymes are involved and illustrates the complex network of proteins that governs their activity. An overview of small molecules that interfere with histone deacetylase function is provided.

Idiopathic intracranial hypertension and sickle cell disease: two case reports.

PubMed

Segal, Laura; Discepola, Marino

2005-12-01

Two patients with sickle cell disease presented with headaches and visual disturbances, typical complaints of this disorder. However, prompt diagnosis of idiopathic intracranial hypertension and initiation of medical therapy lead to improved symptoms and restored vision. Ophthalmologists should consider sickle cell disease to be an independent risk factor for idiopathic intracranial hypertension when a patient is being assessed for visual disturbances. Although a rare condition, idiopathic intracranial hypertension has several key signs useful in establishing a diagnosis. It is critical to recognize the warning signs and symptoms to prevent devastating ophthalmologic complications. We report the first cases of idiopathic intracranial hypertension in patients with the novel Quebec-Chori beta-chain variant of sickle cell disease.

Thyroid storm with multiple organ failure, disseminated intravascular coagulation, and stroke with a normal serum FT3 level.

PubMed

Harada, Yuko; Akiyama, Hisanao; Yoshimoto, Tatsuji; Urao, Yasuko; Ryuzaki, Munekazu; Handa, Michiko

2012-01-01

Thyroid storm is a rare disorder with a sudden onset, rapid progression and high mortality. We experienced a case of thyroid storm which had a devastating course, including multiple organ failure (MOF), severe hypoglycemia, disseminated intravascular coagulation (DIC), and stroke. It was difficult to make a diagnosis of thyroid storm in the present patient, because she did not have a history of thyroid disease and her serum FT3 level was normal. Clinicians should be aware that thyroid storm can occur even when there is an almost normal level of thyroid hormones, and that intensive anticoagulation is required for patients with atrial fibrillation to prevent stroke after thyroid storm.

ATP Synthase Diseases of Mitochondrial Genetic Origin

PubMed Central

Dautant, Alain; Meier, Thomas; Hahn, Alexander; Tribouillard-Tanvier, Déborah; di Rago, Jean-Paul; Kucharczyk, Roza

2018-01-01

Devastating human neuromuscular disorders have been associated to defects in the ATP synthase. This enzyme is found in the inner mitochondrial membrane and catalyzes the last step in oxidative phosphorylation, which provides aerobic eukaryotes with ATP. With the advent of structures of complete ATP synthases, and the availability of genetically approachable systems such as the yeast Saccharomyces cerevisiae, we can begin to understand these molecular machines and their associated defects at the molecular level. In this review, we describe what is known about the clinical syndromes induced by 58 different mutations found in the mitochondrial genes encoding membrane subunits 8 and a of ATP synthase, and evaluate their functional consequences with respect to recently described cryo-EM structures. PMID:29670542

Cell therapy for spinal cord injury informed by electromagnetic waves.

PubMed

Finnegan, Jack; Ye, Hui

2016-10-01

Spinal cord injury devastates the CNS, besetting patients with symptoms including but not limited to: paralysis, autonomic nervous dysfunction, pain disorders and depression. Despite the identification of several molecular and genetic factors, a reliable regenerative therapy has yet to be produced for this terminal disease. Perhaps the missing piece of this puzzle will be discovered within endogenous electrotactic cellular behaviors. Neurons and stem cells both show mediated responses (growth rate, migration, differentiation) to electromagnetic waves, including direct current electric fields. This review analyzes the pathophysiology of spinal cord injury, the rationale for regenerative cell therapy and the evidence for directing cell therapy via electromagnetic waves shown by in vitro experiments.

Bilateral coxofemoral degenerative joint disease in a juvenile male yellow-eyed penguin (Megadyptes antipodes).

PubMed

Buckle, Kelly N; Alley, Maurice R

2011-08-01

A juvenile, male, yellow-eyed penguin (Megadyptes antipodes) with abnormal stance and decreased mobility was captured, held in captivity for approximately 6 weeks, and euthanized due to continued clinical signs. Radiographically, there was bilateral degenerative joint disease with coxofemoral periarticular osteophyte formation. Grossly, the bird had bilaterally distended, thickened coxofemoral joints with increased laxity, and small, roughened and angular femoral heads. Histologically, the left femoral articular cartilage and subchondral bone were absent, and the remaining femoral head consisted of trabecular bone overlain by fibrin and granulation tissue. There was no gross or histological evidence of infection. The historic, gross, radiographic, and histopathologic findings were most consistent with bilateral aseptic femoral head degeneration resulting in degenerative joint disease. Although the chronicity of the lesions masked the initiating cause, the probable underlying causes of aseptic bilateral femoral head degeneration in a young animal are osteonecrosis and osteochondrosis of the femoral head. To our knowledge, this is the first reported case of bilateral coxofemoral degenerative joint disease in a penguin.

The cervical spine of professional front-row rugby players: correlation between degenerative changes and symptoms.

PubMed

Hogan, B A; Hogan, N A; Vos, P M; Eustace, S J; Kenny, P J

2010-06-01

Injuries to the cervical spine (C-spine) are among the most serious in rugby and are well documented. Front-row players are particularly at risk due to repetitive high-intensity collisions in the scrum. This study evaluates degenerative changes of the C-spine and associated symptomatology in front-row rugby players. C-spine radiographs from 14 professional rugby players and controls were compared. Players averaged 23 years of playing competitive rugby. Two consultant radiologists performed a blind review of radiographs evaluating degeneration of disc spaces and apophyseal joints. Clinical status was assessed using a modified AAOS/NASS/COSS cervical spine outcomes questionnaire. Front-row rugby players exhibited significant radiographic evidence of C-spine degenerative changes compared to the non-rugby playing controls (P < 0.005). Despite these findings the rugby players did not exhibit increased symptoms. This highlights the radiologic degenerative changes of the C-spine of front-row rugby players. However, these changes do not manifest themselves clinically or affect activities of daily living.

Effects of Fe particle irradiation on human endothelial barrier structure and function

NASA Astrophysics Data System (ADS)

Sharma, Preety; Guida, Peter; Grabham, Peter

2014-07-01

Space travel involves exposure to biologically effective heavy ion radiation and there is consequently a concern for possible degenerative disorders in humans. A significant target for radiation effects is the microvascular system, which is crucial to healthy functioning of the tissues. Its pathology is linked to disrupted endothelial barrier function and is not only a primary event in a range of degenerative diseases but also an important influencing factor in many others. Thus, an assessment of the effects of heavy ion radiation on endothelial barrier function would be useful for estimating the risks of space travel. This study was aimed at understanding the effects of high LET Fe particles (1 GeV/n) and is the first investigation of the effects of charged particles on the function of the human endothelial barrier. We used a set of established and novel endpoints to assess barrier function after exposure. These include, trans-endothelial electrical resistance (TEER), morphological effects, localization of adhesion and cell junction proteins (in 2D monolayers and in 3D tissue models), and permeability of molecules through the endothelial barrier. A dose of 0.50 Gy was sufficient to cause a progressive reduction in TEER measurements that were significant 48 hours after exposure. Concurrently, there were morphological changes and a 14% loss of cells from monolayers. Gaps also appeared in the normally continuous cell-border localization of the tight junction protein - ZO-1 but not the Platelet endothelial cell adhesion molecule (PECAM-1) in both monolayers and in 3D vessel models. Disruption of barrier function was confirmed by increased permeability to 3 kDa and 10 kDa dextran molecules. A dose of 0.25 Gy caused no detectible change in cell number, morphology, or TEER, but did cause barrier disruption since there were gaps in the cell border localization of ZO-1 and an increased permeability to 3 kDa dextran. These results indicate that Fe particles potently have impact on human endothelial barrier function and represent a risk for degenerative diseases in the space environment.

Integrative genomic and proteomic profiling of human neuroblastoma SH-SY5Y cells reveals signatures of endosulfan exposure.

PubMed

Gandhi, Deepa; Tarale, Prashant; Naoghare, Pravin K; Bafana, Amit; Kannan, Krishnamurthi; Sivanesan, Saravanadevi

2016-01-01

Endosulfan, an organochlorine pesticide, is known to induce multiple disorders/abnormalities including neuro-degenerative disorders in many animal species. However, the molecular mechanism of endosulfan induced neuronal alterations is still not well understood. In the present study, the effect of sub-lethal concentration of endosulfan (3 μM) on human neuroblastoma cells (SH-SY5Y) was investigated using genomic and proteomic approaches. Microarray and 2D-PAGE followed by MALDI-TOF-MS analysis revealed differential expression of 831 transcripts and 16 proteins in exposed cells. A gene ontology enrichment analysis revealed that the differentially expressed genes and proteins were involved in variety of cellular events such as neuronal developmental pathway, immune response, cell differentiation, apoptosis, transmission of nerve impulse, axonogenesis, etc. The present study attempted to explore the possible molecular mechanism of endosulfan induced neuronal alterations in SH-SY5Y cells using an integrated genomic and proteomic approach. Based on the gene and protein profile possible mechanisms underlying endosulfan neurotoxicity were predicted. Copyright © 2015 Elsevier B.V. All rights reserved.

Whole-exome sequencing identifies USH2A mutations in a pseudo-dominant Usher syndrome family.

PubMed

Zheng, Sui-Lian; Zhang, Hong-Liang; Lin, Zhen-Lang; Kang, Qian-Yan

2015-10-01

Usher syndrome (USH) is an autosomal recessive (AR) multi-sensory degenerative disorder leading to deaf-blindness. USH is clinically subdivided into three subclasses, and 10 genes have been identified thus far. Clinical and genetic heterogeneities in USH make a precise diagnosis difficult. A dominant‑like USH family in successive generations was identified, and the present study aimed to determine the genetic predisposition of this family. Whole‑exome sequencing was performed in two affected patients and an unaffected relative. Systematic data were analyzed by bioinformatic analysis to remove the candidate mutations via step‑wise filtering. Direct Sanger sequencing and co‑segregation analysis were performed in the pedigree. One novel and two known mutations in the USH2A gene were identified, and were further confirmed by direct sequencing and co‑segregation analysis. The affected mother carried compound mutations in the USH2A gene, while the unaffected father carried a heterozygous mutation. The present study demonstrates that whole‑exome sequencing is a robust approach for the molecular diagnosis of disorders with high levels of genetic heterogeneity.

Interplay between cancer cell cycle and metabolism: Challenges, targets and therapeutic opportunities.

PubMed

Roy, Debmalya; Sheng, Gao Ying; Herve, Semukunzi; Carvalho, Evandro; Mahanty, Arpan; Yuan, Shengtao; Sun, Li

2017-05-01

A growing interest has emerged in the field of studying the cross-talk between cancer cell cycle and metabolism. In this review, we aimed to present how metabolism and cell cycle are correlated and how cancer cells get energy to drive cell cycle. Cell proliferation and cell death largely depend on the metabolic activity of the cell. Cell cycle proteins, e.g. cyclin D, cyclin dependent kinase (CDK), some pro-apoptotic and anti-apoptotic proteins, and P53 have been shown to be regulated by metabolic crosstalk. Dysregulation of this cross-talk between metabolism and cell cycle leads to degenerative disorder(s) and cancer. It is not fully understood the actual reason of aberration between metabolism and cell cycle, but it is a hallmark of cancer research. Herein, we discussed the role of some regulatory molecules relative of cell cycle and metabolism and highlight how they control the function of each other. We also pointed out, current therapeutic opportunities and some additional crucial therapeutic targets on these fields that could be a breakthrough in cancer research. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Analysis of Nucleotide Variations in Genes of Iron Management in Patients of Parkinson's Disease and Other Movement Disorders

PubMed Central

Castiglioni, Emanuela; Finazzi, Dario; Goldwurm, Stefano; Pezzoli, Gianni; Forni, Gianluca; Girelli, Domenico; Maccarinelli, Federica; Poli, Maura; Ferrari, Maurizio; Cremonesi, Laura; Arosio, Paolo

2011-01-01

The capacity to act as an electron donor and acceptor makes iron an essential cofactor of many vital processes. Its balance in the body has to be tightly regulated since its excess can be harmful by favouring oxidative damage, while its deficiency can impair fundamental activities like erythropoiesis. In the brain, an accumulation of iron or an increase in its availability has been associated with the development and/or progression of different degenerative processes, including Parkinson's disease, while iron paucity seems to be associated with cognitive deficits, motor dysfunction, and restless legs syndrome. In the search of DNA sequence variations affecting the individual predisposition to develop movement disorders, we scanned by DHPLC the exons and intronic boundary regions of ceruloplasmin, iron regulatory protein 2, hemopexin, hepcidin and hemojuvelin genes in cohorts of subjects affected by Parkinson's disease and idiopathic neurodegeneration with brain iron accumulation (NBIA). Both novel and known sequence variations were identified in most of the genes, but none of them seemed to be significantly associated to the movement diseases of interest. PMID:20981230

Dental stem cells: a future asset of ocular cell therapy.

PubMed

Yam, Gary Hin-Fai; Peh, Gary Swee-Lim; Singhal, Shweta; Goh, Bee-Tin; Mehta, Jodhbir S

2015-11-10

Regenerative medicine using patient's own stem cells (SCs) to repair dysfunctional tissues is an attractive approach to complement surgical and pharmacological treatments for aging and degenerative disorders. Recently, dental SCs have drawn much attention owing to their accessibility, plasticity and applicability for regenerative use not only for dental, but also other body tissues. In ophthalmology, there has been increasing interest to differentiate dental pulp SC and periodontal ligament SC (PDLSC) towards ocular lineage. Both can commit to retinal fate expressing eye field transcription factors and generate rhodopsin-positive photoreceptor-like cells. This proposes a novel therapeutic alternative for retinal degeneration diseases. Moreover, as PDLSC shares similar cranial neural crest origin and proteoglycan secretion with corneal stromal keratoctyes and corneal endothelial cells, this offers the possibility of differentiating PDLSC to these corneal cell types. The advance could lead to a shift in the medical management of corneal opacities and endothelial disorders from highly invasive corneal transplantation using limited donor tissue to cell therapy utilizing autologous cells. This article provides an overview of dental SC research and the perspective of utilizing dental SCs for ocular regenerative medicine.

Vessel-associated stem cells from skeletal muscle: From biology to future uses in cell therapy

PubMed Central

Sancricca, Cristina; Mirabella, Massimiliano; Gliubizzi, Carla; Broccolini, Aldobrando; Gidaro, Teresa; Morosetti, Roberta

2010-01-01

Over the last years, the existence of different stem cells with myogenic potential has been widely investigated. Besides the classical skeletal muscle progenitors represented by satellite cells, numerous multipotent and embryologically unrelated progenitors with a potential role in muscle differentiation and repair have been identified. In order to conceive a therapeutic approach for degenerative muscle disorders, it is of primary importance to identify an ideal stem cell endowed with all the features for a possible use in vivo. Among all emerging populations, vessel-associated stem cells are a novel and promising class of multipotent progenitors of mesodermal origin and with high myogenic potential which seem to best fit all the requirements for a possible cell therapy. In vitro and in vivo studies have already tested the effectiveness and safety of vessel-associated stem cells in animal models. This leads to the concrete possibility in the future to start pilot human clinical trials, hopefully opening the way to a turning point in the treatment of genetic and acquired muscle disorders. PMID:21607121

Fatal CNS vasculopathy in a patient with refractory celiac disease and lymph node cavitation.

PubMed

Keller, Christian E; Gamboa, Eugenia T; Hays, Arthur P; Karlitz, Jordan; Lowe, Gina; Green, Peter H R; Bhagat, Govind

2006-02-01

Celiac disease is an enteropathy occurring in genetically predisposed individuals due to a dietary intolerance to gluten. Patients with celiac disease may develop a neurological disorder of unknown cause, although autoimmune mechanisms are suspected. We report on a 56-year-old man with celiac disease, who became refractory to a gluten-free diet and died of a rapidly progressive encephalopathy. Magnetic resonance imaging indicated focal lesions of the cerebellum and brainstem, and electrodiagnostic studies suggested an axonal neuropathy. Autopsy revealed a flattened small-bowel mucosa with intraepithelial lymphocytosis, a spectrum of degenerative changes of the intra-abdominal and mediastinal lymph nodes, including cavitary degeneration, and splenomegaly. Histologically, the lymph nodes showed pseudocyst formation and lymphocytic vasculitis with fibrinoid necrosis, and sections of the brain exhibited fibrinoid degeneration of small blood vessels, sparse perivascular lymphocytic infiltrates, and perivascular ischemic lesions. Identical T-cell clones were identified in the duodenum, stomach, lymph nodes, and spleen. This patient had an unusual neurological disorder related to a vasculopathy, probably mediated by a circulating neoplastic clone of activated T cells.

Laughing as a manifestation of rapid eye movement sleep behavior disorder.

PubMed

Siclari, F; Wienecke, M; Poryazova, R; Bassetti, C L; Baumann, C R

2011-06-01

Among the range of sleep-related behavior displayed by patients with rapid eye movement (REM) sleep behavior disorder (RBD), aggressive acts are particularly common, while pleasant behaviors have rarely been reported. We aimed at identifying the frequency and characteristics of patients who displayed laughing as a pleasant, nonviolent manifestation of RBD. We reviewed 67 consecutive polysomnographic recordings of patients with RBD, obtained in our sleep laboratory between July 2004 and July 2009. We identified 14 patients (21% of our RBD patients with degenerative parkinsonism: 10 males, mean age 63 ± 11 years) who repeatedly laughed during REM sleep. Ten patients had idiopathic Parkinson's disease, 3 suffered from multisystem atrophy and 1 patient was diagnosed with dementia with Lewy bodies. Other RBD-associated behaviors included smiling, crying, aggressive behavior, screaming, and somniloquia. Nine of the 14 patients were depressed during daytime. Laughing belongs to the spectrum of behavioral manifestations of RBD. Many of our patients with RBD-associated laughter were depressed, suggesting a dissociation between emotional expression during daytime and REM sleep. Copyright © 2011 Elsevier Ltd. All rights reserved.

Disorders of emotional processing in amyotrophic lateral sclerosis.

PubMed

Sedda, Anna

2014-12-01

Amyotrophic lateral sclerosis (ALS) is a degenerative brain disease characterized by motor, behavioural and cognitive deficits. Only recently, emotional processing disorders have been shown in this disease. The interest in affective processing in ALS is growing given that basic emotion impairments could impact copying strategies and mood. Studies explore both basic emotion recognition and social cognition. Results are congruent on arousal and valence detection impairments, independently from the stimulus modality (verbal or visual). Further, recognition of facial expressions of anger, sadness and disgust is impaired in ALS, even when cognition is preserved. Clinical features such as type of onset and severity of the disease could be the cause of the heterogeneity in emotional deficits profiles between patients. Finally, a study employing diffusion tensor imaging showed that emotional dysfunctions in ALS are related to right hemispheric connective bundles impairments, involving the inferior longitudinal fasciculus and the inferior frontal occipital fasciculus. Research on emotional processing in ALS is still in its infancy and results are mixed. Future research including more detailed clinical profiles of patients and measures of brain connectivity will provide useful information to understand heterogeneity of results in ALS.

Disruption of neurogenesis by hypothalamic inflammation in obesity or aging.

PubMed

Purkayastha, Sudarshana; Cai, Dongsheng

2013-12-01

Adult neural stem cells contribute to neurogenesis and plasticity of the brain which is essential for central regulation of systemic homeostasis. Damage to these homeostatic components, depending on locations in the brain, poses threat to impaired neurogenesis, neurodegeneration, cognitive loss and energy imbalance. Recent research has identified brain metabolic inflammation via proinflammatory IκB kinase-β (IKKβ) and its downstream nuclear transcription factor NF-κB pathway as a non-classical linker of metabolic and neurodegenerative disorders. Chronic activation of the pathway results in impairment of energy balance and nutrient metabolism, impediment of neurogenesis, neural stem cell proliferation and differentiation, collectively converging on metabolic and cognitive decline. Hypothalamic IKKβ/NF-κB via inflammatory crosstalk between microglia and neurons has been discovered to direct systemic aging by inhibiting the production of gonadotropin-releasing hormone (GnRH) and inhibition of inflammation or GnRH therapy could revert aging related degenerative symptoms at least in part. This article reviews the crucial role of hypothalamic inflammation in affecting neural stem cells which mediates the neurodegenerative mechanisms of causing metabolic derangements as well as aging-associated disorders or diseases.

Stem Cell Applications in Tendon Disorders: A Clinical Perspective

PubMed Central

Young, Mark

2012-01-01

Tendon injuries are a common cause of morbidity and a significant health burden on society. Tendons are structural tissues connecting muscle to bone and are prone to tearing and tendinopathy, an overuse or degenerative condition that is characterized by failed healing and cellular depletion. Current treatments, for tendon tear are conservative, surgical repair or surgical scaffold reconstruction. Tendinopathy is treated by exercises, injection therapies, shock wave treatments or surgical tendon debridement. However, tendons usually heal with fibrosis and scar tissue, which has suboptimal tensile strength and is prone to reinjury, resulting in lifestyle changes with activity restriction. Preclinical studies show that cell therapies have the potential to regenerate rather than repair tendon tissue, a process termed tenogenesis. A number of different cell lines, with varying degrees of differentiation, have being evaluated including stem cells, tendon derived cells and dermal fibroblasts. Even though cellular therapies offer some potential in treating tendon disorders, there have been few published clinical trials to determine the ideal cell source, the number of cells to administer, or the optimal bioscaffold for clinical use. PMID:22448174

[Age-related changes in swallowing. Physiology and pathophysiology].

PubMed

Muhle, P; Wirth, R; Glahn, J; Dziewas, R

2015-04-01

The term presbyphagia refers to all changes of swallowing physiology that are manifested with increasing age. Alterations in the pattern of deglutition that are part of healthy aging are called primary presbyphagia. Primary presbyphagia is not an illness in itself but contributes to a more pervasive naturally diminished functional reserve, making older adults more susceptible to dysphagia. If disorders in swallowing occur in the elderly as a comorbidity of a specific disease, for example stroke or neurodegenerative disorders, this is called secondary presbyphagia. Increasing age has an impact on each stage of deglutition. In the oral preparatory phase a diminished input for smell and taste as well as a usually multifactorial cause of dry mouth are the most important influencing factors. Sarcopenia, the degenerative loss of skeletal muscle mass, strength and quality associated with aging, interferes in particular with the oropharyngeal phase. A decreased sensory feedback from the oropharyngeal mucosa leads to a delayed triggering of the swallowing reflex. Finally, a reduction in connective tissue elasticity and changes of the axial skeleton lead to various modifications of the swallowing pattern with advanced age.

Level of Education as a Risk Factor for Extensive Prevalence of Cervical Intervertebral Disc Degenerative Changes and Chronic Neck Pain.

PubMed

Markotić, Vedran; Zubac, Damir; Miljko, Miro; Šimić, Goran; Zalihić, Amra; Bogdan, Gojko; Radančević, Dorijan; Šimić, Ana Dugandžić; Mašković, Josip

2017-09-01

The aim of this study was to document the prevalence of degenerative intervertebral disc changes in the patients who previously reported symptoms of neck pain and to determine the influence of education level on degenerative intervertebral disc changes and subsequent chronic neck pain. One hundred and twelve patients were randomly selected from the University Hospital in Mostar, Bosna and Herzegovina, (aged 48.5±12.7 years) and submitted to magnetic resonance imaging (MRI) of the cervical spine. MRI of 3.0 T (Siemens, Skyrim, Erlangen, Germany) was used to obtain cervical spine images. Patients were separated into two groups based on their education level: low education level (LLE) and high education level (HLE). Pfirrmann classification was used to document intervertebral disc degeneration, while self-reported chronic neck pain was evaluated using the previously validated Oswestry questionnaire. The entire logistic regression model containing all predictors was statistically significant, (χ 2 (3)=12.2, p=0.02), and was able to distinguish between respondents who had chronic neck pain and vice versa. The model explained between 10.0% (Cox-Snell R 2 ) and 13.8% (Nagelkerke R 2 ) of common variance with Pfirrmann classification, and it had the strength to discriminate and correctly classify 69.6% of patients. The probability of a patient being classified in the high or low group of degenerative disc changes according to the Pfirrmann scale was associated with the education level (Wald test: 5.5, p=0.02). Based on the Pfirrmann assessment scale, the HLE group was significantly different from the LLE group in the degree of degenerative changes of the cervical intervertebral discs (U=1,077.5, p=0.001). A moderate level of intervertebral disc degenerative changes (grade II and III) was equally matched among all patients, while the overall results suggest a higher level of education as a risk factor leading to cervical disc degenerative changes, regardless of age differences among respondents. Copyright© by the National Institute of Public Health, Prague 2017

Quantitative analysis of 18F-NaF dynamic PET/CT cannot differentiate malignant from benign lesions in multiple myeloma.

PubMed

Sachpekidis, Christos; Hillengass, Jens; Goldschmidt, Hartmut; Anwar, Hoda; Haberkorn, Uwe; Dimitrakopoulou-Strauss, Antonia

2017-01-01

A renewed interest has been recently developed for the highly sensitive bone-seeking radiopharmaceutical 18 F-NaF. Aim of the present study is to evaluate the potential utility of quantitative analysis of 18 F-NaF dynamic PET/CT data in differentiating malignant from benign degenerative lesions in multiple myeloma (MM). 80 MM patients underwent whole-body PET/CT and dynamic PET/CT scanning of the pelvis with 18 F-NaF. PET/CT data evaluation was based on visual (qualitative) assessment, semi-quantitative (SUV) calculations, and absolute quantitative estimations after application of a 2-tissue compartment model and a non-compartmental approach leading to the extraction of fractal dimension (FD). In total 263 MM lesions were demonstrated on 18 F-NaF PET/CT. Semi-quantitative and quantitative evaluations were performed for 25 MM lesions as well as for 25 benign, degenerative and traumatic lesions. Mean SUV average for MM lesions was 11.9 and mean SUV max was 23.2. Respectively, SUV average and SUV max for degenerative lesions were 13.5 and 20.2. Kinetic analysis of 18 F-NaF revealed the following mean values for MM lesions: K 1 = 0.248 (1/min), k 3 = 0.359 (1/min), influx (K i ) = 0.107 (1/min), FD = 1.382, while the respective values for degenerative lesions were: K 1 = 0.169 (1/min), k 3 = 0.422 (1/min), influx (K i ) = 0.095 (1/min), FD = 1. 411. No statistically significant differences between MM and benign degenerative disease regarding SUV average , SUV max , K 1 , k 3 and influx (K i ) were demonstrated. FD was significantly higher in degenerative than in malignant lesions. The present findings show that quantitative analysis of 18 F-NaF PET data cannot differentiate malignant from benign degenerative lesions in MM patients, supporting previously published results, which reflect the limited role of 18 F-NaF PET/CT in the diagnostic workup of MM.

The comparison of measurement between ultrasound and computed tomography for abnormal degenerative facet joints: A STROBE-compliant article.

PubMed

Shi, Wen; Tian, Dan; Liu, Da; Yin, Jing; Huang, Ying

2017-08-01

Besides the study on examining facet joints of lumbar spine by ultrasound in normal population, there has not been any related report about examining normal facet joints of lumbar spine by ultrasound so far. This study was aimed to explore the feasibility of ultrasound assessment of lumber spine facet joints by comparing ultrasound measure values of normal and degenerative lumber spine facet joints, and by comparing measure values of ultrasound and computed tomography (CT) of degenerative lumber spine facet joints.This study included 15 patients who had chronic low back pain because of degenerative change in lumbar vertebrae, and 19 volunteers who did not have low back pain or pain in the lower limb. The ultrasound measure values (height [H] and width [W]) of normal and degenerative lumber spine facet joints were compared. And the differentiation between measure values (H and W) of ultrasound and CT of degenerative lumber spine facet joints was also analyzed.The ultrasound clearly showed abnormal facet joints lesion, which was characterized by hyperostosis on the edge of joints, bone destruction under joints, and thinner or thicker articular cartilage. There were significant differences between the ultrasound measure values of the normal (H: 1.26 ± 0.03 cm, W: 0.18 ± 0.01 cm) and abnormal facet joints (H: 1.43 ± 0.05 cm, W: 0.15 ± 0.02 cm) (all P < .05). However, there were no significant differences between the measure values of the ultrasound (H: 1.43 ± 0.17 cm, W: 0.15 ± 0.03 cm) and CT (H: 1.42 ± 0.16, W: 0.14 ± 0.03) of the degenerative lumber spine facet joints (all P > .05).Ultrasound can clearly show the structure of facet joints of lumbar spine. It is precise and feasible to assess facet joints of lumbar spine by ultrasound. This study has important significance for the diagnosis of lumbar facet joint degeneration.

Surgical Treatment of Spinal Stenosis with and without Degenerative Spondylolisthesis: Cost-Effectiveness after 2 Years

PubMed Central

Tosteson, Anna N.A.; Lurie, Jon D.; Tosteson, Tor D.; Skinner, Jonathan S.; Herkowitz, Harry; Albert, Todd; Boden, Scott D.; Bridwell, Keith; Longley, Michael; Andersson, Gunnar B.; Blood, Emily A.; Grove, Margaret R.; Weinstein, James N.

2009-01-01

Background The SPORT (Spine Patient Outcomes Research Trial) reported favorable surgery outcomes over 2 years among patients with stenosis with and without degenerative spondylolisthesis, but the economic value of these surgeries is uncertain. Objective To assess the short-term cost-effectiveness of spine surgery relative to nonoperative care for stenosis alone and for stenosis with spondylolisthesis. Design Prospective cohort study. Data Sources Resource utilization, productivity, and EuroQol EQ-5D score measured at 6 weeks and at 3, 6, 12, and 24 months after treatment among SPORT participants. Target Population Patients with image-confirmed spinal stenosis, with and without degenerative spondylolisthesis. Time Horizon 2 years. Perspective Societal. Intervention Nonoperative care or surgery (primarily decompressive laminectomy for stenosis and decompressive laminectomy with fusion for stenosis associated with degenerative spondylolisthesis). Outcome Measures Cost per quality-adjusted life-year (QALY) gained. Results of Base-Case Analysis Among 634 patients with stenosis, 394 (62%) had surgery, most often decompressive laminectomy (320 of 394 [81%]). Stenosis surgeries improved health to a greater extent than nonoperative care (QALY gain, 0.17 [95% CI, 0.12 to 0.22]) at a cost of $77 600 (CI, $49 600 to $120 000) per QALY gained. Among 601 patients with degenerative spondylolisthesis, 368 (61%) had surgery, most including fusion (344 of 368 [93%]) and most with instrumentation (269 of 344 [78%]). Degenerative spondylolisthesis surgeries significantly improved health versus non-operative care (QALY gain, 0.23 [CI, 0.19 to 0.27]), at a cost of $115 600 (CI, $90 800 to $144 900) per QALY gained. Result of Sensitivity Analysis Surgery cost markedly affected the value of surgery. Limitation The study used self-reported utilization data, 2-year time horizon, and as-treated analysis to address treatment non-adherence among randomly assigned participants. Conclusion The economic value of spinal stenosis surgery at 2 years compares favorably with many health interventions. Degenerative spondylolisthesis surgery is not highly cost-effective over 2 years but could show value over a longer time horizon. PMID:19075203

Age-related differences in temporomandibular disorder diagnoses.

PubMed

Guarda-Nardini, Luca; Piccotti, Fabio; Mogno, Giorgia; Favero, Lorenzo; Manfredini, Daniele

2012-04-01

The purpose of the current study was to evaluate the pattern of age distribution of temporomandibular disorders (TMD) and to identify prevalence peaks for the different diagnoses. The study sample (N = 383; F:M ratio = 3.9; mean age range 41.7 +/- 17 years) consisted of patients seeking treatment for TMD and who were assessed in accordance with the Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD) version 1.0 guidelines. The sample was divided into four age groups on the basis of percentile-derived intervals to compare prevalence of different diagnoses in relation to age. The pattern of clinical diagnoses changed with increasing age. The peculiar distribution of RDC/TMD axis I diagnoses, with relation to age, mainly affected the disorders trend of groups II and III, with the former decreasing with age from about 62% to 40% and the latter increasing from 75% to almost 95%. Two distinct age peaks were identified for the prevalence of the main clinical marker of group III diagnosis of arthrosis/arthritis, viz., joint crepitus sounds (N = 104, mean age range 51.9 +/- 14.5), and for the prevalence of all other diagnoses in patients without joint crepitus (N = 279, mean age range 37.9 +/- 16.4). The hypothesis that TMD patient populations may be composed of at least two diagnostic subgroups in relation to age, and that the presence of clinically diagnosed degenerative joint disorders may be a key discriminating factor, was supported. The external validity of the results from this investigation needs to be confirmed by multicenter and cross-cultural studies.

Low pacemaker incidence with continuous-sutured valves: a retrospective analysis.

PubMed

Niclauss, Lars; Delay, Dominique; Pfister, Raymond; Colombier, Sebastien; Kirsch, Matthias; Prêtre, René

2017-06-01

Background Permanent pacemaker implantation after surgical aortic valve replacement depends on patient selection and risk factors for conduction disorders. We aimed to identify risk criteria and obtain a selected group comparable to patients assigned to transcatheter aortic valve implantation. Methods Isolated sutured aortic valve replacements in 994 patients treated from 2007 to 2015 were reviewed. Demographics, hospital stay, preexisting conduction disorders, surgical technique, and etiology in patients with and without permanent pacemaker implantation were compared. Reported outcomes after transcatheter aortic valve implantation were compared with those of a subgroup including only degenerative valve disease and first redo. Results The incidence of permanent pacemaker implantation was 2.9%. Longer hospital stay ( p = 0.01), preexisting rhythm disorders ( p < 0.001), complex prosthetic endocarditis ( p = 0.01), and complex redo ( p < 0.001) were associated with permanent pacemaker implantation. Although prostheses were sutured with continuous monofilament in the majority of cases (86%), interrupted pledgetted sutures were used more often in the pacemaker group ( p = 0.002). In the subgroup analysis, the incidence of permanent pacemaker implantation was 2%; preexisting rhythm disorders and the suture technique were still major risk factors. Conclusion Permanent pacemaker implantation depends on etiology, preexisting rhythm disorders, and suture technique, and the 2% incidence compares favorably with the reported 5- to 10-fold higher incidence after transcatheter aortic valve implantation. Cost analysis should take this into account. Often dismissed as minor complication, permanent pacemaker implantation increases the risks of endocarditis, impaired myocardial recovery, and higher mortality if associated with prosthesis regurgitation.

Neuronal regulation of tendon homoeostasis

PubMed Central

Ackermann, Paul W

2013-01-01

The regulation of tendon homoeostasis, including adaptation to loading, is still not fully understood. Accumulating data, however, demonstrates that in addition to afferent (sensory) functions, the nervous system, via efferent pathways which are associated with through specific neuronal mediators plays an active role in regulating pain, inflammation and tendon homeostasis. This neuronal regulation of intact-, healing- and tendinopathic tendons has been shown to be mediated by three major groups of molecules including opioid, autonomic and excitatory glutamatergic neuroregulators. In intact healthy tendons the neuromediators are found in the surrounding structures: paratenon, endotenon and epitenon, whereas the proper tendon itself is practically devoid of neurovascular supply. This neuroanatomy reflects that normal tendon homoeostasis is regulated from the tendon surroundings. After injury and during tendon repair, however, there is extensive nerve ingrowth into the tendon proper, followed by a time-dependent emergence of sensory, autonomic and glutamatergic mediators, which amplify and fine-tune inflammation and regulate tendon regeneration. In tendinopathic condition, excessive and protracted presence of sensory and glutamatergic neuromediators has been identified, suggesting involvement in inflammatory, nociceptive and hypertrophic (degenerative) tissue responses. Under experimental and clinical conditions of impaired (e.g. diabetes) as well as excessive (e.g. tendinopathy) neuromediator release, dysfunctional tendon homoeostasis develops resulting in chronic pain and gradual degeneration. Thus there is a prospect that in the future pharmacotherapy and tissue engineering approaches targeting neuronal mediators and their receptors may prove to be effective therapies for painful, degenerative and traumatic tendon disorders. PMID:23718724

Destructive discovertebral degenerative disease of the lumbar spine.

PubMed

Charran, A K; Tony, G; Lalam, R; Tyrrell, P N M; Tins, B; Singh, J; Eisenstein, S M; Balain, B; Trivedi, J M; Cassar-Pullicino, V N

2012-09-01

The uncommon variant of degenerative hip joint disease, termed rapidly progressive osteoarthritis, and highlighted by severe joint space loss and osteochondral disintegration, is well established. We present a similar unusual subset in the lumbar spine termed destructive discovertebral degenerative disease (DDDD) with radiological features of vertebral malalignment, severe disc resorption, and "bone sand" formation secondary to vertebral fragmentation. Co-existing metabolic bone disease is likely to promote the development of DDDD of the lumbar spine, which presents with back pain and sciatica due to nerve root compression by the "bone sand" in the epidural space. MRI and CT play a complimentary role in making the diagnosis.

Genetic modifiers of Huntington's disease.

PubMed

Gusella, James F; MacDonald, Marcy E; Lee, Jong-Min

2014-09-15

Huntington's disease (HD) is a devastating neurodegenerative disorder that directly affects more than 1 in 10,000 persons in Western societies but, as a family disorder with a long, costly, debilitating course, it has an indirect impact on a far greater proportion of the population. Although some palliative treatments are used, no effective treatment exists for preventing clinical onset of the disorder or for delaying its inevitable progression toward premature death, approximately 15 years after diagnosis. Huntington's disease involves a movement disorder characterized by chorea, as well as a variety of psychiatric disturbances and intellectual decline, with a gradual loss of independence. A dire need exists for effective HD therapies to alleviate the suffering and costs to the individual, family, and health care system. In past decades, genetics, the study of DNA sequence variation and its consequences, provided the tools to map the HD gene to chromosome 4 and ultimately to identify its mutation as an expanded CAG trinucleotide repeat in the coding sequence of a large protein, dubbed huntingtin. Now, advances in genetic technology offer an unbiased route to the identification of genetic factors that are disease-modifying agents in human patients. Such genetic modifiers are expected to highlight processes capable of altering the course of HD and therefore to provide new, human-validated targets for traditional drug development, with the goal of developing rational treatments to delay or prevent onset of HD clinical signs. © 2014 International Parkinson and Movement Disorder Society.

Adult's Degenerative Scoliosis: Midterm Results of Dynamic Stabilization without Fusion in Elderly Patients—Is It Effective?

PubMed Central

Di Silvestre, Mario; Lolli, Francesco; Greggi, Tiziana; Vommaro, Francesco; Baioni, Andrea

2013-01-01

Study Design. A retrospective study. Purpose. Posterolateral fusion with pedicle screw instrumentation used for degenerative lumbar scoliosis can lead to several complications. In elderly patients without sagittal imbalance, dynamic stabilization could represent an option to avoid these adverse events. Methods. 57 patients treated by dynamic stabilization without fusion were included. All patients had degenerative lumbar de novo scoliosis (average Cobb angle 17.2°), without sagittal imbalance, associated in 52 cases (91%) with vertebral canal stenosis and in 24 (42%) with degenerative spondylolisthesis. Nineteen patients (33%) had previously undergone lumbar spinal surgery. Results. At an average followup of 77 months, clinical results improved with statistical significance. Scoliosis Cobb angle was 17.2° (range, 12° to 38°) before surgery and 11.3° (range, 4° to 26°) at last follow-up. In the patients with associated spondylolisthesis, anterior vertebral translation was 19.5% (range, 12% to 27%) before surgery, 16.7% (range, 0% to 25%) after surgery, and 17.5% (range, 0% to 27%) at followup. Complications incidence was low (14%), and few patients required revision surgery (4%). Conclusions. In elderly patients with mild degenerative lumbar scoliosis without sagittal imbalance, pedicle screw-based dynamic stabilization is an effective option, with low complications incidence, granting curve stabilization during time and satisfying clinical results. PMID:23781342

Prevalence of Late Functional Tricuspid Regurgitation in Degenerative Mitral Regurgitation Surgery.

PubMed

Vaturi, Mordehay; Kotler, Tali; Shapira, Yaron; Weisenberg, Daniel; Monakier, Daniel; Sagie, Alexander

2016-03-01

Although significant late tricuspid regurgitation (TR) may develop after surgery for degenerative mitral regurgitation (MR), the use of routine tricuspid annuloplasty is debatable. The study aim was to determine the prevalence and predictors of significant late TR after surgery for degenerative MR. A total of 112 patients who had undergone surgery for degenerative MR without concomitant tricuspid valve repair (average follow up 7.7 ± 4.0 years) was studied retrospectively. The prevalence of post-surgical TR and predictors of progression were determined. The majority of patients (97%) had non-significant TR (less than moderate) prior to surgery, although an overall trend of progression towards significant TR (grades 2 or 3) was noted in 17 patients (p = 0.0006). Of the 18 patients (16%) with late postoperative significant TR, only nine (8%) had severe TR with only a single referral to surgery. New-onset post-surgical atrial fibrillation was more common in patients who developed late significant TR (p = 0.002). Multivariate analysis of the pre-surgery variables, age >65 years and left ventricular dysfunction were shown to be independent predictors of late functional TR. Significant progression in TR after surgery for degenerative MR was rare in this patient cohort. The impact of older age and left ventricular dysfunction at the time of surgery showed a strong association with post-surgical atrial fibrillation.

Effectiveness of Biologic Factors in Shoulder Disorders

PubMed Central

Giotis, Dimitrios; Aryaei, Ashkan; Vasilakakos, Theofanis; Paschos, Nikolaos K.

2017-01-01

Background: Shoulder pathology can cause significant pain, discomfort, and loss of function that all interfere with activities of daily living and may lead to poor quality of life. Primary osteoarthritis and rotator cuff diseases with its sequalae are the main culprits. Management of shoulder disorders using biological factors gained an increasing interest over the last years. This interest reveals the need of effective treatments for shoulder degenerative disorders, and highlights the importance of a comprehensive and detailed understanding of the rapidly increasing knowledge in the field. Methods: This study will describe most of the available biology-based strategies that have been recently developed, focusing on their effectiveness in animal and clinical studies. Results: Data from in vitro work will also be briefly presented; in order to further elucidate newly acquired knowledge regarding mechanisms of tissue degeneration and repair that would probably drive translational work in the next decade. The role of platelet rich-plasma, growth factors, stem cells and other alternative treatments will be described in an evidence-based approach, in an attempt to provide guidelines for their clinical application. Finally, certain challenges that biologic treatments face today will be described as an initiative for future strategies. Conclusion: The application of different growth factors and mesenchymal stem cells appears as promising approaches for enhancing biologic repair. However, data from clinical studies are still limited, and future studies need to improve understanding of the repair process in cellular and molecular level and evaluate the effectiveness of biologic factors in the management of shoulder disorders. PMID:28400884

Pick's disease: a modern approach.

PubMed

Dickson, D W

1998-04-01

Pick's disease is a rare dementing disorder that is sometimes familial. The cardinal features are circumscribed cortical atrophy most often affecting the frontal and temporal poles and argyrophilic, round intraneuronal inclusions (Pick bodies). Clinical manifestations reflect the distribution of cortical degeneration, and personality deterioration and memory deficits are often more severe than visuospatial and apraxic disorders that are common in Alzheimer's disease, but clinical overlap with other non-Alzheimer degenerative disorders is increasingly recognized. Neuronal loss and degeneration are usually maximal in the limbic system, including hippocampus, entorhinal cortex and amygdala. Numerous Pick bodies are often present in the dentate fascia of the hippocampus. Less specific features include leukoencephalopathy and ballooned cortical neurons (Pick cells). Glial reaction is often pronounced in affected cerebral gray and white matter. Tau-immunoreactive glial inclusions are a recently recognized finding in Pick's disease, and neuritic changes have also recently been described. Variable involvement of the deep gray matter and the brainstem is typical, with a predilection for the monoaminergic nuclei and nuclei of the pontine base. Neurochemical studies demonstrate deficits in intrinsic cortical neurotransmitter systems (e.g., somatostatin), but inconsistent loss of transmitters in systems projecting to the cortex (e.g., cholinergic neurons of the basal nucleus). Biochemical and immunocytochemical studies have demonstrated that abnormal tau proteins are the major structural components of Pick bodies. A specific tau protein immunoblotting pattern different from that seen in Alzheimer's disease and certain other disorders has been suggested in some studies. A specific molecular marker and a genetic locus for familial cases are not known.

Reduced NAA levels in the dorsolateral prefrontal cortex of young bipolar patients.

PubMed

Sassi, Roberto B; Stanley, Jeffrey A; Axelson, David; Brambilla, Paolo; Nicoletti, Mark A; Keshavan, Matcheri S; Ramos, Renato T; Ryan, Neal; Birmaher, Boris; Soares, Jair C

2005-11-01

Converging evidence implicates prefrontal circuits in the pathophysiology of bipolar disorder. Proton spectroscopy studies performed in adult bipolar patients assessing prefrontal regions have suggested decreased levels of N-acetylaspartate (NAA), a putative marker of neuronal integrity. In order to examine whether such abnormalities would also be found in younger patients, a 1H spectroscopy study was conducted that focused on the dorsolateral prefrontal cortex of children and adolescents with bipolar disorder. The authors examined the levels of NAA, creatine plus phosphocreatine, and choline-containing molecules in the left dorsolateral prefrontal cortex of 14 bipolar disorder patients (mean age=15.5 years, SD=3, eight female) and 18 healthy comparison subjects (mean age=17.3, SD=3.7, seven female) using short echo time, single-voxel in vivo 1H spectroscopy. Absolute metabolite levels were determined using the water signal as an internal reference. Bipolar patients presented significantly lower NAA levels and a significant inverse correlation between choline-containing molecules and number of previous affective episodes. No differences were found for other metabolites. These findings suggest that young bipolar patients have decreased NAA levels in the dorsolateral prefrontal cortex, similar to what was previously reported in adult patients. Such changes may reflect an underdevelopment of dendritic arborizations and synaptic connections. These neuronal abnormalities in the dorsolateral prefrontal cortex of bipolar disorder youth are unlikely to represent long-term degenerative processes, at least in the subgroup of patients where the illness had relatively early onset.

Progress on gene therapy, cell therapy, and pharmacological strategies toward the treatment of oculopharyngeal muscular dystrophy.

PubMed

Harish, Pradeep; Malerba, Alberto; Dickson, George; Bachtarzi, Houria

2015-05-01

Oculopharyngeal muscular dystrophy (OPMD) is a muscle-specific, late-onset degenerative disorder whereby muscles of the eyes (causing ptosis), throat (leading to dysphagia), and limbs (causing proximal limb weakness) are mostly affected. The disease is characterized by a mutation in the poly(A)-binding protein nuclear-1 (PABPN1) gene, resulting in a short GCG expansion in the polyalanine tract of PABPN1 protein. Accumulation of filamentous intranuclear inclusions in affected skeletal muscle cells constitutes the pathological hallmark of OPMD. This review highlights the current translational research advances in the treatment of OPMD. In vitro and in vivo disease models are described. Conventional and experimental therapeutic approaches are discussed with emphasis on novel molecular therapies including the use of intrabodies, gene therapy, and myoblast transfer therapy.

Neurodegeneration and Neuroprotection in Glaucoma

PubMed Central

Gauthier, Angela C.; Liu, Ji

2016-01-01

Glaucoma is the principal cause of irreversible blindness in the world. The disease leads to progressive optic nerve degeneration with a gradual loss of retinal ganglion cells. Neurodegeneration in glaucoma extends beyond the eye into the lateral geniculate nucleus and visual cortex, and the disease even shares some characteristics with other central nervous system degenerative disorders. Glaucoma destroys neurons through oxidative stress, impairment in axonal transport, neuroinflammation, and excitotoxicity. Autophagy may promote or inhibit disease progression. Currently, lowering intraocular pressure is the only way proven to delay glaucoma advancement. However, many new therapies are being developed, including antioxidants, adenosine receptor antagonists, Rho-pathway inhibitors, stem cell therapy, and neurotrophic factors. These therapies focus on neuroprotection, and they may eventually halt glaucoma progression or reverse the process of the disease itself. PMID:27505018

Curcumin, a potential therapeutic candidate for retinal diseases.

PubMed

Wang, Lei-Lei; Sun, Yue; Huang, Kun; Zheng, Ling

2013-09-01

Curcumin, the major extraction of turmeric, has been widely used in many countries for centuries both as a spice and as a medicine. In the last decade, researchers have found the beneficial effects of curcumin on multiple disorders are due to its antioxidative, anti-inflammatory, and antiproliferative properties, as well as its novel function as an inhibitor of histone aectyltransferases. In this review, we summarize the recent progress made on studying the beneficial effects of curcumin on multiple retinal diseases, including diabetic retinopathy, glaucoma, and age-related macular degeneration. Recent clinical trials on the effectiveness of phosphatidylcholine formulated curcumin in treating eye diseases have also shown promising results, making curcumin a potent therapeutic drug candidate for inflammatory and degenerative retinal and eye diseases. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Establishment and rapid detection of a heterozygous missense mutation in the CACNA1F gene by ARMS technique with double-base mismatched primers.

PubMed

Yang, W C; Zhu, L; Zhou, B X; Tania, S; Zhou, Q; Khan, M A; Fu, X L; Cheng, J L; Lv, H B; Fu, J J

2015-09-25

Retinitis pigmentosa (RP) is a retinal degenerative disorder that often causes complete blindness. Mutations of more than 50 genes have been identified as associated with RP, including the CACNA1F gene. In a recent study, by employing next-generation sequencing, we identified a novel mutation in the CACNA1F gene. In this study, we used the amplification refractory mutation system (ARMS) and identified a single nucleotide change c.1555C>T in exon 13 of the CACNA1F gene, leading to the substitution of arginine by tryptophan (p.R519W) in a Chinese individual affected by RP. This study actually confirms this novel mutation, and establishes the ARMS technique for the detection of mutations in RP.

Structure and function of the interphotoreceptor matrix surrounding retinal photoreceptor cells.

PubMed

Ishikawa, Makoto; Sawada, Yu; Yoshitomi, Takeshi

2015-04-01

The interphotoreceptor matrix (IPM) is a highly organized structure with interconnected domains surrounding cone and rod photoreceptor cells and extends throughout the subretinal space. Based on known roles of the extracellular matrix in other tissues, the IPM is thought to have several prominent functions including serving as a receptor for growth factors, regulating retinoid transport, participating in cytoskeletal organization in surrounding cells, and regulation of oxygen and nutrient transport. In addition, a number of studies suggest that the IPM also may play a significant role in the etiology of retinal degenerative disorders. In this review, we describe the present knowledge concerning the structure and function of the IPM under physiological and pathological conditions. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Neuroleptic malignant syndrome as a presenting feature of subacute sclerosing panencephalitis.

PubMed

Garg, Divyani; Reddy, Varun; Singh, Rajesh Kumar; Dash, Deepa; Bhatia, Rohit; Tripathi, Manjari

2018-02-01

Subacute sclerosing panencephalitis (SSPE) is a slowly progressive degenerative disorder caused by measles virus. It is characterised by typical clinical and electrophysiological features in the form of slow myoclonic jerks, with progressive cognitive impairment, visual symptoms, and periodic complexes on EEG, with raised titres of anti-measles antibodies in CSF and serum. Atypical presentations of SSPE have been reported including brainstem involvement, ADEM-like presentation, acute encephalitis, and cerebellar ataxia. Presentation with predominant extrapyramidal features is uncommon. We describe a case of SSPE presenting with extensive rigidity with highly elevated CPK values, mimicking neuroleptic malignant syndrome (NMS) which was most probably due to central dopaminergic blockade induced by the disease process. To our knowledge, this is the first case of SSPE presenting with a NMS-like syndrome.

Nutritional issues for older adults: addressing degenerative ageing with long-term studies.

PubMed

de Groot, Lisette C P G M

2016-05-01

The ageing process is influenced by a variety of factors, including extrinsic, malleable lifestyle variables. The present paper deals with the epidemiological evidence for the role of dietary patterns and key nutritional concerns in relation to survival and ageing-related disorders that present themselves in later life. Healthful dietary patterns appear to be most relevant in old age. Specific nutritional concerns are related to vitamin D, vitamin B12 and protein malnutrition. An important challenge to further expand the knowledge base is currently addressed by the NuAge project, acknowledging the complexity of the ageing process and integrating different dimensions of research into human healthy ageing. In the meantime, reversing poor adherence to existing guidelines for a healthy diet remains a first challenge in public health nutritional practices.

The menopausal mouse: a new neural paradigm of a distressing human condition.

PubMed

Danilovich, Natalia; Sairam, M Ram; Maysinger, Dusica

2003-08-26

Progressive and long-term sex hormone imbalance in the FSH-R haploinsufficient menopausal mouse leads to degenerative changes in the CNS associated with increased anxiety. The brain region most affected by aging in these mice is the hippocampus. Choline acetyltransferase (ChAT) enzymatic activity and synapsin immunoreactivity are reduced at 20 months of age. Neurons in the dentate gyrus show signs of progressive degenerative changes, hypertrophy and glyosis, and subsequent cell shrinkage and death. These results suggest that the menopausal mouse mimics degenerative changes in the hippocampus of hormonally imbalanced aging humans. We propose using this animal model to test the effectiveness of potential therapeutics in paradigms of accelerated aging.

Teaching Early Braille Literacy Skills within a Stimulus Equivalence Paradigm to Children with Degenerative Visual Impairments

ERIC Educational Resources Information Center

Toussaint, Karen A.; Tiger, Jeffrey H.

2010-01-01

Despite the need for braille literacy, there has been little attempt to systematically evaluate braille-instruction programs. The current study evaluated an instructive procedure for teaching early braille-reading skills with 4 school-aged children with degenerative visual impairments. Following a series of pretests, braille instruction involved…

The development of biomarkers for degenerative musculoskeletal conditions.

PubMed

Jayabalan, Prakash; Sowa, Gwendolyn A

2014-02-01

With an aging population, degenerative musculoskeletal conditions will become more prevalent with significantly increasing costs to society over the next several decades. The majority of these conditions are diagnosed radiographically, at which point the disease process is often more advanced and challenging to treat. The commonly available radiographic studies also do not adequately provide information as to the exact pain generator and findings often do not correlate either to patient symptoms or function. Personalized medicine involves formulating treatments based on a patient's own biology. The development of biological markers (biomarkers) pertaining to disease is a rapidly growing area within this field of medicine. For degenerative musculoskeletal conditions, biomarkers have the potential to provide an early non-invasive method of assessing the location and severity of tissue damage and presence of inflammation. By outlining mechanisms of disease they could allow the formulation of further treatment targets and through sub-categorizing patients into different groups based on their biomarker profile, one could provide more efficacious treatments for patients. The present article is a review of the development of biomarkers for these purposes specifically as they pertain to degenerative musculoskeletal conditions.

Stem cells in degenerative orthopaedic pathologies: effects of aging on therapeutic potential.

PubMed

Atesok, Kivanc; Fu, Freddie H; Sekiya, Ichiro; Stolzing, Alexandra; Ochi, Mitsuo; Rodeo, Scott A

2017-02-01

The purpose of this study was to summarize the current evidence on the use of stem cells in the elderly population with degenerative orthopaedic pathologies and to highlight the pathophysiologic mechanisms behind today's therapeutic challenges in stem cell-based regeneration of destructed tissues in the elderly patients with osteoarthritis (OA), degenerative disc disease (DDD), and tendinopathies. Clinical and basic science studies that report the use of stem cells in the elderly patients with OA, DDD, and tendinopathies were identified using a PubMed search. The studies published in English have been assessed, and the best and most recent evidence was included in the current study. Evidence suggests that, although short-term results regarding the effects of stem cell therapy in degenerative orthopaedic pathologies can be promising, stem cell therapies do not appear to reverse age-related tissue degeneration. Causes of suboptimal outcomes can be attributed to the decrease in the therapeutic potential of aged stem cell populations and the regenerative capacity of these cells, which might be negatively influenced in an aged microenvironment within the degenerated tissues of elderly patients with OA, DDD, and tendinopathies. Clinical protocols guiding the use of stem cells in the elderly patient population are still under development, and high-level randomized controlled trials with long-term outcomes are lacking. Understanding the consequences of age-related changes in stem cell function and responsiveness of the in vivo microenvironment to stem cells is critical when designing cell-based therapies for elderly patients with degenerative orthopaedic pathologies.

Restoring Segmental Biomechanics Through Nucleus Augmentation: An In Vitro Study.

PubMed

Pelletier, Matthew H; Cohen, Charles S; Ducheyne, Paul; Walsh, William R

2016-12-01

In vitro biomechanical laboratory study. The purpose of this study is to evaluate a mechanical treatment to create a degenerative motion segment and the ability of nucleus augmentation to restore biomechanics. In cases with an intact annulus fibrosus, the replacement or augmentation of the nucleus pulposus alone may provide a less invasive option to restore normal biomechanics and disk height when compared with spinal fusion or total disk replacement. Laboratory testing allows these changes to be fully characterized. However, without preexisting pathology, nucleus augmentation therapies are difficult to evaluate in vitro. The present study evaluated pure moment bending and compressive biomechanics in 3 states (n=6): (1) intact, (2) after creep loading and nucleus disruption to induce degenerative biomechanical changes, and (3) after nucleus augmentation through an injectable polymer (DiscCell). Neutral zone and ROM were increased in all modes of bending after the degenerative treatment. The most sensitive mode of bending was lateral bending, with intact ROM (20.0±2.9 degrees) increased to 22.3±2.6 degrees after degenerative treatment and reduced to 18.4±1.6 degrees after injection of the polymer. All bending ROM and NZ changes induced by the degenerative treatment were reversed by nucleus augmentation. This material was shown to be effective at altering motion segment biomechanics and restoring disk height during time zero tests. This technique may provide a model to examine the time zero performance of a nucleus augmentation device/material.

Correlation between degenerative spine disease and bone marrow density: a retrospective investigation.

PubMed

Grams, Astrid Ellen; Rehwald, Rafael; Bartsch, Alexander; Honold, Sarah; Freyschlag, Christian Franz; Knoflach, Michael; Gizewski, Elke Ruth; Glodny, Bernhard

2016-02-24

Spondylosis leads to an overestimation of bone mineral density (BMD) with dual-energy x-ray absorptiometry (DXA) but not with quantitative computed tomography (QCT). The correlation between degenerative changes of the spine and QCT-BMD was therefore investigated for the first time. One hundred thirty-four patients (66 female and 68 male) with a mean age of 49.0 ± 14.6 years (range: 19-88 years) who received a CT scan and QCT-BMD measurements of spine and hip were evaluated retrospectively. The occurrence and severity of spondylosis, osteochondrosis, and spondylarthrosis and the height of the vertebral bodies were assessed. A negative correlation was found between spinal BMD and number of spondylophytes (ρ = -0.35; p < 0.01), disc heights (r = -0.33; p < 0.01), number of discal air inclusions (ρ = -0.34; p < 0.01), the number of Schmorl nodules (ρ = -0.25; p < 0.01), the number (ρ = -0.219; p < 0.05) and the degree (ρ = -0.220; p < 0.05) of spondylarthrosis. Spinal and hip BMD correlated moderately, but the latter did not correlate with degenerative changes of the spine. In linear regression models age, osteochondrosis and spondylarthrosis were factors influencing spinal BMD. Degenerative spinal changes may be associated with reduced regional spinal mineralization. This knowledge could lead to a modification of treatment of degenerative spine disease with early treatment of osteopenia to prevent secondary fractures.

The Effects of Anti-Dementia and Nootropic Treatments on the Mortality of Patients with Dementia: A Population-Based Cohort Study in Taiwan.

PubMed

Wu, Chen-Yi; Hu, Hsiao-Yun; Chow, Lok-Hi; Chou, Yiing-Jenq; Huang, Nicole; Wang, Pei-Ning; Li, Chung-Pin

2015-01-01

Few studies have examined the contribution of treatment on the mortality of dementia based on a population-based study. To investigate the effects of anti-dementia and nootropic treatments on the mortality of dementia using a population-based cohort study. 12,193 incident dementia patients were found from 2000 to 2010. Their data were compared with 12,193 age- and sex-matched non-dementia controls that were randomly selected from the same database. Dementia was classified into vascular (VaD) and degenerative dementia. Mortality incidence and hazard ratios (HRs) were calculated. The median survival time was 3.39 years (95% confidence interval [CI]: 2.88-3.79) for VaD without medication, 6.62 years (95% CI: 6.24-7.21) for VaD with nootropics, 3.01 years (95% CI: 2.85-3.21) for degenerative dementia without medication, 8.11 years (95% CI: 6.30-8.55) for degenerative dementia with anti-dementia medication, 6.00 years (95% CI: 5.73-6.17) for degenerative dementia with nootropics, and 9.03 years (95% CI: 8.02-9.87) for degenerative dementia with both anti-dementia and nootropic medications. Compared to the non-dementia group, the HRs among individuals with degenerative dementia were 2.69 (95% CI: 2.55-2.83) without medication, 1.46 (95% CI: 1.39-1.54) with nootropics, 1.05 (95% CI: 0.82-1.34) with anti-dementia medication, and 0.92 (95% CI: 0.80-1.05) with both nootropic and anti-dementia medications. VaD with nootropics had a lower mortality (HR: 1.25, 95% CI: 1.15-1.37) than VaD without medication (HR: 2.46, 95% CI: 2.22-2.72). Pharmacological treatments have beneficial effects for patients with dementia in prolonging their survival.

Prevalence, Comorbidities, and Risk of Perioperative Complications in Human Immunodeficiency Virus-Positive Patients Undergoing Cervical Spine Surgery.

PubMed

Lovy, Andrew J; Guzman, Javier Z; Skovrlj, Branko; Cho, Samuel K; Hecht, Andrew C; Qureshi, Sheeraz A

2015-11-01

Retrospective database analysis. To evaluate outcomes of human immunodeficiency virus (HIV) positive patients after cervical spine surgery. Highly active antiretroviral medications have qualitatively altered the natural history of HIV, thus increasing the number of HIV-positive patients seeking treatment for chronic degenerative conditions. Minimal data exist on HIV patients undergoing degenerative cervical spine surgery. The Nationwide Inpatient Sample was examined from 2002 to 2011. Hospitalizations were identified using International Classification of Diseases Ninth Revision, Clinical Modification (ICD-9-CM) procedural codes for cervical spine surgery and diagnoses codes for degenerative conditions of the cervical spine, and HIV. Statistical analysis was conducted to evaluate associations between HIV status and perioperative complications. A total of 1,602,129 patients underwent degenerative cervical spine surgery, of which 3700 patients (0.23%) had HIV. The prevalence of HIV increased over the study period from 0.19% to 0.33% (P < 0.001). Patients with HIV were younger (48.6 yrs vs. 53.4 yrs, P < 0.001) and more likely to be male (P < 0.001). HIV patients had significantly greater odds of having chronic pulmonary disease, liver disease, and drug abuse. Unadjusted analysis did not reveal increased rate of acute complications among HIV-positive patients compared with negative controls (3.8% vs. 3.7%, P = 0.62). Multivariate analysis did not identify HIV as a significant predictor of complication (odds ratio = 1.04, P = 0.84). HIV was associated with a 1.5 day increased length of stay AND 1.29 fold increase in median costs compared with controls ($14,551 vs. 18,846, P < 0.001). The prevalence of HIV patients undergoing degenerative cervical spine surgery is increasing. A diagnosis of HIV was not associated with an increased risk of perioperative complication among patients undergoing degenerative cervical spine surgery. Further clinical studies are needed to evaluate predictors of complications among HIV patients and long-term outcomes. 4.

A 20-Year Prospective Longitudinal Study of Degeneration of the Cervical Spine in a Volunteer Cohort Assessed Using MRI: Follow-up of a Cross-Sectional Study.

PubMed

Daimon, Kenshi; Fujiwara, Hirokazu; Nishiwaki, Yuji; Okada, Eijiro; Nojiri, Kenya; Watanabe, Masahiko; Katoh, Hiroyuki; Shimizu, Kentaro; Ishihama, Hiroko; Fujita, Nobuyuki; Tsuji, Takashi; Nakamura, Masaya; Matsumoto, Morio; Watanabe, Kota

2018-05-16

Few studies have addressed in detail long-term degenerative changes in the cervical spine. In this study, we evaluated the progression of degenerative changes of the cervical spine that occurred over a 20-year period in an originally healthy cohort. We also sought to clarify the relationship between the progression of cervical degenerative changes and the development of clinical symptoms. For this prospective follow-up investigation, we recruited 193 subjects from an original cohort of 497 participants who had undergone magnetic resonance imaging (MRI) of the cervical spine between 1993 and 1996. The subjects were asked about the presence or absence of cervical spine-related symptoms. Degenerative changes of the cervical spine were assessed on MRI using an original numerical grading system. The relationship between the progression of degenerative changes and the onset of clinical symptoms was evaluated by logistic regression analysis. Degeneration in the cervical spine was found to have progressed in 95% of the subjects during the 20-year period. The finding of a decrease in signal intensity of the intervertebral disc progressed in a relatively high proportion of the subjects in all age groups and occurred with similar frequency (around 60%) at all intervertebral disc levels. The rate of progression of other structural failures on MRI increased with age and was highest at C5-C6. The progression of foraminal stenosis was associated with the onset of upper-limb pain (odds ratio, 4.71 [95% confidence interval, 1.02 to 21.7]). A progression of degenerative changes in the cervical spine on MRI over the 20-year period was detected in nearly all subjects. There was no relationship between the progression of degeneration on MRI and the development of clinical symptoms, with the exception of an association found between foraminal stenosis and upper-limb pain. Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

The change in the diffusion of water in normal and degenerative lumbar intervertebral discs following joint mobilization compared to prone lying.

PubMed

Beattie, Paul F; Donley, Jonathan W; Arnot, Cathy F; Miller, Ronald

2009-01-01

Prospective, repeated measures obtained under treatment and control conditions. The purposes of this study were to provide preliminary evidence regarding the immediate change in the diffusion of water in the nuclear region of normal and degenerative lumbar intervertebral discs (IVDs) following a single session of lumbar joint mobilization, and to compare these findings to the immediate change in the diffusion of water following a 10-minute session of prone lying. There is conflicting evidence regarding the effectiveness and efficacy of lumbar joint mobilization. Increased knowledge of the physiologic effects of lumbar joint mobilization can lead to refinement of its clinical application. A total of 24 people (15 males and 9 females), ranging in age from 22 to 58 years, participated in this study. All subjects had a history of activity-limiting low back pain. Diffusion-weighted magnetic resonance images (DW-MRIs) were obtained immediately before and after a 10-minute session of lumbar joint mobilization. At least 1 month later, a second session was performed in which DW-MRIs were obtained immediately before and after a 10-minute session of prone lying. Following lumbar joint mobilization, a significant increase (P = .002) in the mean values for diffusion of water was observed within degenerative IVDs at L5-S1 (22.2% increase; effect size, 0.97). Degenerative IVDs at L1-2 to L4-5 and normal IVDs at L1-2 to L5-S1 did not demonstrate a change in diffusion following joint mobilization. Prone lying was not associated with a change in diffusion for normal or degenerative IVDs. The stimulus provided by lumbar joint mobilization may influence the diffusion of water in degenerative IVDs at L5-S1; however, these are preliminary findings and the relationship of these findings to pain and function needs further investigation.

The Effects of Anti-Dementia and Nootropic Treatments on the Mortality of Patients with Dementia: A Population-Based Cohort Study in Taiwan

PubMed Central

Wu, Chen-Yi; Hu, Hsiao-Yun; Chow, Lok-Hi; Chou, Yiing-Jenq; Huang, Nicole; Wang, Pei-Ning; Li, Chung-Pin

2015-01-01

Background Few studies have examined the contribution of treatment on the mortality of dementia based on a population-based study. Objective To investigate the effects of anti-dementia and nootropic treatments on the mortality of dementia using a population-based cohort study. Methods 12,193 incident dementia patients were found from 2000 to 2010. Their data were compared with 12,193 age- and sex-matched non-dementia controls that were randomly selected from the same database. Dementia was classified into vascular (VaD) and degenerative dementia. Mortality incidence and hazard ratios (HRs) were calculated. Results The median survival time was 3.39 years (95% confidence interval [CI]: 2.88–3.79) for VaD without medication, 6.62 years (95% CI: 6.24–7.21) for VaD with nootropics, 3.01 years (95% CI: 2.85–3.21) for degenerative dementia without medication, 8.11 years (95% CI: 6.30–8.55) for degenerative dementia with anti-dementia medication, 6.00 years (95% CI: 5.73–6.17) for degenerative dementia with nootropics, and 9.03 years (95% CI: 8.02–9.87) for degenerative dementia with both anti-dementia and nootropic medications. Compared to the non-dementia group, the HRs among individuals with degenerative dementia were 2.69 (95% CI: 2.55–2.83) without medication, 1.46 (95% CI: 1.39–1.54) with nootropics, 1.05 (95% CI: 0.82–1.34) with anti-dementia medication, and 0.92 (95% CI: 0.80–1.05) with both nootropic and anti-dementia medications. VaD with nootropics had a lower mortality (HR: 1.25, 95% CI: 1.15–1.37) than VaD without medication (HR: 2.46, 95% CI: 2.22–2.72). Conclusion Pharmacological treatments have beneficial effects for patients with dementia in prolonging their survival. PMID:26098910

Descriptive analysis of spinal neuroaxial injections, surgical interventions and physical therapy utilization for degenerative lumbar spondylolisthesis within Medicare beneficiaries from 2000–2011

PubMed Central

Sclafani, Joseph A.; Constantin, Alexandra; Ho, Pei-Shu; Akuthota, Venu; Chan, Leighton

2016-01-01

Study Design Retrospective, observational study. Objective To determine the utilization of various treatment modalities in the management of degenerative spondylolisthesis within Medicare beneficiaries. Summary of Background Data Degenerative lumbar spondylolisthesis is a condition often identified in symptomatic low back pain. A variety of treatment algorithms including physical therapy and interventional techniques can be used to manage clinically significant degenerative spondylolisthesis. Methods This study utilized the 5% national sample of Medicare carrier claims from 2000 through 2011. A cohort of beneficiaries with a new ICD-9 diagnosis code for degenerative lumbar spondylolisthesis was identified. Current procedural terminology codes were used to identify the number of procedures performed each year by specialty on this cohort. Results A total of 95,647 individuals were included in the analysis. Average age at the time of initial diagnosis was 72.8 ± 9.8 years. Within this study cohort, spondylolisthesis was more prevalent in females (69%) than males and in Caucasians (88%) compared to other racial demographics. Over 40% of beneficiaries underwent at least one injection, approximately one third (37%) participated in physical therapy, one in five (22%) underwent spinal surgery, and one third (36%) did not utilize any of these interventions. Greater than half of all procedures (124,280/216,088) occurred within 2 years of diagnosis. The ratio of focal interventions (transforaminal and facet interventions) to less selective (interlaminar) procedures was greater for the specialty of Physical Medicine and Rehabilitation compared to the specialties of Anesthesiology, Interventional Radiology, Neurosurgery, and Orthopedic Surgery. The majority of physical therapy was dedicated to passive treatment modalities and range of motion exercises rather than active strengthening modalities within this cohort. Conclusion Interventional techniques and physical therapy are frequently used treatment modalities for symptomatic degenerative spondylolisthesis. Understanding utilization of these techniques is important to determine relative clinical efficacies and to optimize future health care expenditures. PMID:28207664

Comparison of 368 patients undergoing surgery for lumbar degenerative spondylolisthesis from the SPORT trial with 955 from the NSQIP database.

PubMed

Golinvaux, Nicholas S; Basques, Bryce A; Bohl, Daniel D; Yacob, Alem; Grauer, Jonathan N

2015-03-01

Retrospective cohort. To compare demographics and perioperative outcomes between the Spine Patient Outcomes Research Trial (SPORT) lumbar degenerative spondylolisthesis arm and a similar population from the National Surgical Quality Improvement Program (NSQIP) database. SPORT is a well-known surgical trial that investigated the benefits of surgical versus nonsurgical treatment in patients with various lumbar pathologies. However, the external validity of SPORT demographics and outcomes has not been fully established. Surgical degenerative spondylolisthesis cases were identified from NSQIP between 2010 and 2012. This population was then compared with the SPORT degenerative spondylolisthesis study. These comparisons were based on published data from SPORT and included analyses of demographics, perioperative factors, and complications. The 368 surgical patients with degenerative spondylolisthesis in SPORT were compared with 955 patients identified in NSQIP. Demographic comparisons were as follows: average age and race (no difference; P > 0.05 for each), sex (9.1% more female patients in SPORT; P = 0.002), smoking status (6.6% more smokers in NSQIP; P = 0.002), and average body mass index (1.1 kg/m greater in NSQIP; P = 0.005). Larger differences were noted in what surgical procedure was performed (P < 0.001), with the most notable difference being that the NSQIP population was much more likely to include interbody fusion than the SPORT population (52.4% vs. 12.5%). Most perioperative factors and complication rates were similar, including average operative time, wound infection, wound dehiscence, postoperative transfusion, and postoperative mortality (no differences; P > 0.05 for each). Average length of stay was shorter in NSQIP compared with SPORT (3.7 vs. 5.8 d; P = 0.042). Though important differences in the distribution of surgical procedures were identified, this study supports the greater generalizability of the surgical SPORT degenerative spondylolisthesis study based on similar demographics and perioperative outcomes when compared with patients from the NSQIP database. 3.

Prevalence of Disorders Recorded in Dogs Attending Primary-Care Veterinary Practices in England

PubMed Central

O′Neill, Dan G.; Church, David B.; McGreevy, Paul D.; Thomson, Peter C.; Brodbelt, Dave C.

2014-01-01

Purebred dog health is thought to be compromised by an increasing occurence of inherited diseases but inadequate prevalence data on common disorders have hampered efforts to prioritise health reforms. Analysis of primary veterinary practice clinical data has been proposed for reliable estimation of disorder prevalence in dogs. Electronic patient record (EPR) data were collected on 148,741 dogs attending 93 clinics across central and south-eastern England. Analysis in detail of a random sample of EPRs relating to 3,884 dogs from 89 clinics identified the most frequently recorded disorders as otitis externa (prevalence 10.2%, 95% CI: 9.1–11.3), periodontal disease (9.3%, 95% CI: 8.3–10.3) and anal sac impaction (7.1%, 95% CI: 6.1–8.1). Using syndromic classification, the most prevalent body location affected was the head-and-neck (32.8%, 95% CI: 30.7–34.9), the most prevalent organ system affected was the integument (36.3%, 95% CI: 33.9–38.6) and the most prevalent pathophysiologic process diagnosed was inflammation (32.1%, 95% CI: 29.8–34.3). Among the twenty most-frequently recorded disorders, purebred dogs had a significantly higher prevalence compared with crossbreds for three: otitis externa (P = 0.001), obesity (P = 0.006) and skin mass lesion (P = 0.033), and popular breeds differed significantly from each other in their prevalence for five: periodontal disease (P = 0.002), overgrown nails (P = 0.004), degenerative joint disease (P = 0.005), obesity (P = 0.001) and lipoma (P = 0.003). These results fill a crucial data gap in disorder prevalence information and assist with disorder prioritisation. The results suggest that, for maximal impact, breeding reforms should target commonly-diagnosed complex disorders that are amenable to genetic improvement and should place special focus on at-risk breeds. Future studies evaluating disorder severity and duration will augment the usefulness of the disorder prevalence information reported herein. PMID:24594665

Surgical outcomes of degenerative spondylolisthesis with L5-S1 disc degeneration: comparison between lumbar floating fusion and lumbosacral fusion at a minimum 5-year follow-up.

PubMed

Liao, Jen-Chung; Chen, Wen-Jer; Chen, Lih-Hui; Niu, Chi-Chien; Keorochana, Gun

2011-09-01

A retrospective clinical and radiographic study was performed. The purpose of this study was to compare outcomes of patients with degenerative spondylolisthesis and a preexisting degenerative L5-S1 disc treated with a lumbar floating fusion (LFF) versus lumbosacral fusion (LSF). Fusion for treatment of degenerative spondylolisthesis often ends at the L5 level. These patients usually had a preexisting L5-S1 disc degeneration; however, no literature mentions the role of prophylactic LSF in degenerative spondylolisthesis associated with L5-S1 disc degeneration. A total of 107 patients with a minimum 5-year follow-up who had lumbosacral or LFF with pedicle instrumentation for degenerative spondylolisthesis were included. UCLA (University of California, Los Angeles) classification was used to evaluate the radiographic results of the L5-S1 segment. The Oswestry Disability Index (ODI) and modified Brodsky's criteria were used to evaluate patients' clinical results. The incidence of adjacent segment disease (ASD) (includes radiographic and clinical ASD) of both ends was recorded. There were no statistically significant differences in sex, age distribution, or amount of follow-up between the LFF and LSF groups. The LSF group had a higher percentage of patients that underwent total L5 laminectomy with loss of L5-S1 posterior ligament integrity (LSF = 92% vs. LFF = 67%, P = 0.019). The higher incidence of cephalic ASD in the LSF group was statistically significant (LSF = 25% vs. LFF = 9.7%, P = 0.049). Although no patient in the LSF group developed L5-S1 ASD, need for L5-S1 segment revision surgery was not prevented with LSF. Clinical outcomes on the basis of the success rate (LFF = 85.5% vs.LSF = 70.8%, P = 0.103) and ODI difference (LFF = 28.97 ± 15.82 vs. LSF = 23.04 ± 10.97, P = 0.109), there were no statistically significant difference between these two groups. Posterior instrumentation with posterolateral LFF for the treatment of degenerative spondylolisthesis with concomitant L5-S1 disc degeneration results in a high percentage of satisfactory clinical results. Extended fusion to the sacrum did not provide a better clinical result. LSF could not reduce the incidence of revision surgery at the L5-S1 segment and involved greater incidence of cephalic ASD.

Anti-inflammatory Chitosan/Poly-γ-glutamic acid nanoparticles control inflammation while remodeling extracellular matrix in degenerated intervertebral disc.

PubMed

Teixeira, Graciosa Q; Leite Pereira, Catarina; Castro, Flávia; Ferreira, Joana R; Gomez-Lazaro, Maria; Aguiar, Paulo; Barbosa, Mário A; Neidlinger-Wilke, Cornelia; Goncalves, Raquel M

2016-09-15

Intervertebral disc (IVD) degeneration is one of the most common causes of low back pain (LBP), the leading disorder in terms of years lived with disability. Inflammation can play a role in LPB, while impairs IVD regeneration. In spite of this, different inflammatory targets have been purposed in the context of IVD regeneration. Anti-inflammatory nanoparticles (NPs) of Chitosan and Poly-(γ-glutamic acid) with a non-steroidal anti-inflammatory drug, diclofenac (Df), were previously shown to counteract a pro-inflammatory response of human macrophages. Here, the effect of intradiscal injection of Df-NPs in degenerated IVD was evaluated. For that, Df-NPs were injected in a bovine IVD organ culture in pro-inflammatory/degenerative conditions, upon stimulation with needle-puncture and interleukin (IL)-1β. Df-NPs were internalized by IVD cells, down-regulating IL-6, IL-8, MMP1 and MMP3, and decreasing PGE2 production, compared with IL-1β-stimulated IVD punches. Interestingly, at the same time, Df-NPs promoted an up-regulation of extracellular matrix (ECM) proteins, namely collagen type II and aggrecan. Allover, this study suggests that IVD treatment with Df-NPs not only reduces inflammation, but also delays and/or decreases ECM degradation, opening perspectives to new intradiscal therapies for IVD degeneration, based on the modulation of inflammation. Degeneration of the IVD is an age-related progressive process considered to be the major cause of spine disorders. The pro-inflammatory environment and biomechanics of the degenerated IVD is a challenge for regenerative therapies. The novelty of this work is the intradiscal injection of an anti-inflammatory therapy based on Chitosan (Ch)/Poly-(γ-glutamic acid) (γ-PGA) nanoparticles (NPs) with an anti-inflammatory drug (diclofenac, Df), previously developed by us. This drug delivery system was tested in a pro-inflammatory/degenerative intervertebral disc ex vivo model. The main findings support the success of an anti-inflammatory therapy for degenerated IVD that not only reduces inflammation but also promotes native IVD matrix production. Copyright © 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Functional Mitochondria in Health and Disease.

PubMed

Herst, Patries M; Rowe, Matthew R; Carson, Georgia M; Berridge, Michael V

2017-01-01

The ability to rapidly adapt cellular bioenergetic capabilities to meet rapidly changing environmental conditions is mandatory for normal cellular function and for cancer progression. Any loss of this adaptive response has the potential to compromise cellular function and render the cell more susceptible to external stressors such as oxidative stress, radiation, chemotherapeutic drugs, and hypoxia. Mitochondria play a vital role in bioenergetic and biosynthetic pathways and can rapidly adjust to meet the metabolic needs of the cell. Increased demand is met by mitochondrial biogenesis and fusion of individual mitochondria into dynamic networks, whereas a decrease in demand results in the removal of superfluous mitochondria through fission and mitophagy. Effective communication between nucleus and mitochondria (mito-nuclear cross talk), involving the generation of different mitochondrial stress signals as well as the nuclear stress response pathways to deal with these stressors, maintains bioenergetic homeostasis under most conditions. However, when mitochondrial DNA (mtDNA) mutations accumulate and mito-nuclear cross talk falters, mitochondria fail to deliver critical functional outputs. Mutations in mtDNA have been implicated in neuromuscular and neurodegenerative mitochondriopathies and complex diseases such as diabetes, cardiovascular diseases, gastrointestinal disorders, skin disorders, aging, and cancer. In some cases, drastic measures such as acquisition of new mitochondria from donor cells occurs to ensure cell survival. This review starts with a brief discussion of the evolutionary origin of mitochondria and summarizes how mutations in mtDNA lead to mitochondriopathies and other degenerative diseases. Mito-nuclear cross talk, including various stress signals generated by mitochondria and corresponding stress response pathways activated by the nucleus are summarized. We also introduce and discuss a small family of recently discovered hormone-like mitopeptides that modulate body metabolism. Under conditions of severe mitochondrial stress, mitochondria have been shown to traffic between cells, replacing mitochondria in cells with damaged and malfunctional mtDNA. Understanding the processes involved in cellular bioenergetics and metabolic adaptation has the potential to generate new knowledge that will lead to improved treatment of many of the metabolic, degenerative, and age-related inflammatory diseases that characterize modern societies.

Survival, differentiation, and neuroprotective mechanisms of human stem cells complexed with neurotrophin-3-releasing pharmacologically active microcarriers in an ex vivo model of Parkinson's disease.

PubMed

Daviaud, Nicolas; Garbayo, Elisa; Sindji, Laurence; Martínez-Serrano, Alberto; Schiller, Paul C; Montero-Menei, Claudia N

2015-06-01

Stem cell-based regenerative therapies hold great potential for the treatment of degenerative disorders such as Parkinson's disease (PD). We recently reported the repair and functional recovery after treatment with human marrow-isolated adult multilineage inducible (MIAMI) cells adhered to neurotrophin-3 (NT3) releasing pharmacologically active microcarriers (PAMs) in hemiparkinsonian rats. In order to comprehend this effect, the goal of the present work was to elucidate the survival, differentiation, and neuroprotective mechanisms of MIAMI cells and human neural stem cells (NSCs), both adhering to NT3-releasing PAMs in an ex vivo organotypic model of nigrostriatal degeneration made from brain sagittal slices. It was shown that PAMs led to a marked increase in MIAMI cell survival and neuronal differentiation when releasing NT3. A significant neuroprotective effect of MIAMI cells adhering to PAMs was also demonstrated. NSCs barely had a neuroprotective effect and differentiated mostly into dopaminergic neuronal cells when adhering to PAM-NT3. Moreover, those cells were able to release dopamine in a sufficient amount to induce a return to baseline levels. Reverse transcription-quantitative polymerase chain reaction and enzyme-linked immunosorbent assay analyses identified vascular endothelial growth factor (VEGF) and stanniocalcin-1 as potential mediators of the neuroprotective effect of MIAMI cells and NSCs, respectively. It was also shown that VEGF locally stimulated tissue vascularization, which might improve graft survival, without excluding a direct neuroprotective effect of VEGF on dopaminergic neurons. These results indicate a prospective interest of human NSC/PAM and MIAMI cell/PAM complexes in tissue engineering for PD. Stem cell-based regenerative therapies hold great potential for the treatment of degenerative disorders such as Parkinson's disease (PD). The present work elucidates and compares the survival, differentiation, and neuroprotective mechanisms of marrow-isolated adult multilineage inducible cells and human neural stem cells both adhered to neurotrophin-3-releasing pharmacologically active microcarriers in an ex vivo organotypic model of PD made from brain sagittal slices. ©AlphaMed Press.

Forkhead Transcription Factors: Formulating a FOXO Target for Cognitive Loss.

PubMed

Maiese, Kenneth

2017-01-01

With almost 47 million individuals worldwide suffering from some aspect of dementia, it is clear that cognitive loss impacts a significant proportion of the global population. Unfortunately, definitive treatments to resolve or prevent the onset of cognitive loss are limited. In most cases such care is currently non-existent prompting the need for novel treatment strategies. Mammalian forkhead transcription factors of the O class (FoxO) are one such avenue of investigation that offer an exciting potential to bring new treatments forward for disorders that involve cognitive loss. Here we examine the background, structure, expression, and function of FoxO transcription factors and their role in cognitive loss, programmed cell death in the nervous system with apoptosis and autophagy, and areas to target FoxOs for dementia and specific disorders such as Alzheimer's disease. FoxO proteins work in concert with a number of other cell survival pathways that involve growth factors, such as erythropoietin and neurotrophins, silent mating type information regulation 2 homolog 1 (Saccharomyces cerevisiae) (SIRT1), Wnt1 inducible signaling pathway protein 1 (WISP1), Wnt signaling, and cancer-related pathways. FoxO transcription factors oversee proinflammatory pathways, affect nervous system amyloid (Aβ) production and toxicity, lead to mitochondrial dysfunction, foster neuronal apoptotic cell death, and accelerate the progression of degenerative disease. However, under some scenarios such as those involving autophagy, FoxOs also can offer protection in the nervous system and reduce toxic intracellular protein accumulations and potentially limit Aβ toxicity. Given the ability of FoxOs to not only promote apoptotic cell death in the nervous system, but also through the induction of autophagy offer protection against degenerative disease that can lead to dementia, a fine balance in the activity of FoxOs may be required to target cognitive loss in individuals. Future work should yield exciting new prospects for FoxO proteins as new targets to treat the onset and progression of cognitive loss and dementia. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

[X-linked adrenoleukodystrophy: a report of three cases. The importance of early diagnosis].

PubMed

López Úbeda, Marta; de Arriba Muñoz, Antonio; Ferrer Lozano, Marta; Labarta Aizpún, José I; García Jiménez, María C

2017-10-01

X-linked adrenoleukodystrophy is the most common peroxisomal disorder. This disease is caused by a defect in the ABCD1 gen. Saturated very long chain fatty acids are accumulated in serum, adrenal cortex and central nervous system white matter. The clinical spectrum is characterized by progressive neurological dysfunction and adrenal insufficiency with a devastating prognosis. We report a first case of X-linked adrenoleukodystrophy with fatal evolution which identified two asymptomatic family members and established a preventive treatment. Although there is no definitive cure, we stress the importance of family study and evaluation of the individual in situation of risk to establish an early preventive treatment and to give in each particular situation suitable professional advice. Sociedad Argentina de Pediatría.

Neuroimaging Findings of Zika Virus-Associated Neurologic Complications in Adults.

PubMed

Hygino da Cruz, L C; Nascimento, O J M; Lopes, F P P L; da Silva, I R F

2018-05-17

When the first suspected cases of neurologic disorders associated with the Zika virus were noticed in Brazil in late 2015, several studies had been conducted to understand the pathophysiology of the disease and its associated complications. In addition to its well-established association with microcephaly in neonates, the Zika virus infection has also been suggested to trigger other severe neurologic complications in adults, such as Guillain-Barré syndrome, radiculomyelitis, and meningoencephalitis. Hence, the Zika virus should be deemed a global threat that can cause devastating neurologic complications among individuals in all age ranges. The aim of this review was to further describe neuroimaging findings of Zika virus infection and associated neurologic complications found in adults. © 2018 by American Journal of Neuroradiology.

Software support for Huntingtons disease research.

PubMed Central

Conneally, P. M.; Gersting, J. M.; Gray, J. M.; Beidleman, K.; Wexler, N. S.; Smith, C. L.

1991-01-01

Huntingtons disease (HD) is a hereditary disorder involving the central nervous system. Its effects are devastating, to the affected person as well as his family. The Department of Medical and Molecular Genetics at Indiana University (IU) plays an integral part in Huntingtons research by providing computerized repositories of HD family information for researchers and families. The National Huntingtons Disease Research Roster, founded in 1979 at IU, and the Huntingtons Disease in Venezuela Project database contain information that has proven to be invaluable in the worldwide field of HD research. This paper addresses the types of information stored in each database, the pedigree database program (MEGADATS) used to manage the data, and significant findings that have resulted from access to the data. PMID:1839672

The intricate mechanisms of neurodegeneration in prion diseases

PubMed Central

Soto, Claudio; Satani, Nikunj

2010-01-01

Prion diseases are a group of infectious neurodegenerative diseases with an entirely novel mechanism of transmission, involving a protein-only infectious agent that propagates the disease by transmitting protein conformational changes. The disease results from extensive and progressive brain degeneration. The molecular mechanisms involved in neurodegeneration are not entirely known but involve multiple processes operating simultaneously and synergistically in the brain, including spongiform degeneration, synaptic alterations, brain inflammation, neuronal death and the accumulation of protein aggregates. Here, we review the pathways implicated in prion-induced brain damage and put the pieces together into a possible model of neurodegeneration in prion disorders. A more comprehensive understanding of the molecular basis of brain degeneration is essential to develop a much needed therapy for these devastating diseases. PMID:20889378

Surgical Treatment of Pediatric Epileptic Encephalopathies

PubMed Central

Fridley, J.; Reddy, G.; Curry, D.; Agadi, S.

2013-01-01

Pediatric epileptiform encephalopathies are a group of neurologically devastating disorders related to uncontrolled ictal and interictal epileptic activity, with a poor prognosis. Despite the number of pharmacological options for treatment of epilepsy, many of these patients are drug resistant. For these patients with uncontrolled epilepsy, motor and/or neuropsychological deterioration is common. To prevent these secondary consequences, surgery is often considered as either a curative or a palliative option. Magnetic resonance imaging to look for epileptic lesions that may be surgically treated is an essential part of the workup for these patients. Many surgical procedures for the treatment of epileptiform encephalopathies have been reported in the literature. In this paper the evidence for these procedures for the treatment of pediatric epileptiform encephalopathies is reviewed. PMID:24288601

Elucidating the triggers, progression, and effects of Alzheimer's disease.

PubMed

Medeiros, Rodrigo; Chabrier, Meredith A; LaFerla, Frank M

2013-01-01

As the number of patients with Alzheimer's disease (AD) continues to rise, the need for efficacious therapeutics is becoming more and more urgent. Understanding the molecular relationship and interactions between Aβ and tau and their contribution to cognitive decline remain one of the most fundamental and unresolved questions in the AD field. Likewise, elucidating the initial triggers of disease pathology, as well as the impact of various factors such as stress and inflammation on disease progression, are equally important to fully understand this devastating disorder. Here we discuss recent studies that have illuminated the importance of key facilitators of disease progression using the 3xTg-AD and CaM/Tet-DTA mouse models, and suggest viable targets for ameliorating both molecular pathology and cognitive decline.

Parental social support, coping strategies, resilience factors, stress, anxiety and depression levels in parents of children with MPS III (Sanfilippo syndrome) or children with intellectual disabilities (ID).

PubMed

Grant, Sheena; Cross, Elaine; Wraith, James Edmond; Jones, Simon; Mahon, Louise; Lomax, Michelle; Bigger, Brian; Hare, Dougal

2013-03-01

Mucopolysaccharidosis type III (MPS III, Sanfilippo syndrome) is a lysosomal storage disorder, caused by a deficiency in one of four enzymes involved in the catabolism of the glycosaminoglycan heparan sulphate. It is a degenerative disorder, with a progressive decline in children's intellectual and physical functioning. There is currently no cure for the disorder. To date there is a paucity of research on how this disorder impacts parents psychological functioning. Specifically, research in the area has failed to employ adequate control groups to assess if the impact of this disorder on parents psychological functioning differs from parenting a child with intellectual disability (ID). The current study examined child behaviour and parental psychological functioning in 23 parents of children with MPS III and 23 parents of children with ID. Parents completed postal questionnaires about their child's behaviour and abilities and their own psychological functioning. Parents of children with MPS III reported fewer behavioural difficulties as their child aged, more severe level of intellectual disability, and similar levels of perceived social support, coping techniques, stress, anxiety and depression levels as parents of children with ID. Both groups of parents scored above the clinical cut off for anxiety and depression. Parents of children with MPS III rated themselves as significantly less future-orientated and goal directed than parents of children with ID. Services should develop support packages for parents of children with MPS III that incorporate an understanding of the unique stressors and current-difficulty approach of this population. Future research should examine gender differences between parental psychological functioning, using mixed qualitative and quantitative approaches, and utilise matched developmental level and typically developing control groups.

Inherited Retinal Degenerative Disease Clinical Trial Network

DTIC Science & Technology

2012-10-01

strategies can be designed , tested and adopted as standard care. 2 While repeat evaluation and study of affected patients are vital to rigorously...following document is a summary of our experience and research in testing retinal structure and function in eyes with degenerative retinal diseases...Network PRINCIPAL INVESTIGATOR: Patricia Zilliox, Ph.D. CONTRACTING ORGANIZATION: National Neurovision Research Institute Owings

Studies on carcinogenic and toxic effects of ochratoxin A in chicks.

PubMed

Stoev, Stoycho D

2010-04-01

Carcinogenic/toxic effects of ochratoxin A (OTA) in various internal organs of Plymouth Rock chicks were determined. The number of OTA-induced neoplasms was similar in chicks given 25 ppm L-β-phenylalanine (PHE) in addition to 5 ppm OTA compared to chicks given only 5 ppm OTA, which showed that PHE cannot be used as a real protector against the carcinogenic or toxic effects of OTA in chicks. OTA was found to provoke strong degenerative changes in liver and kidneys, degenerative changes and depletion of cells in lymphoid organs, oedematous and degenerative changes in the brain, muscular haemorrhages and fatty changes in the bone marrow. The target organs for carcinogenic effect of OTA in chicks were found to be kidneys and liver.

Effectiveness of Acceptance and Commitment Therapy on Interpersonal Problemsand Psychological Flexibility in Female High School Students With Social Anxiety Disorder

PubMed Central

Azadeh, Sayedeh Monireh; Kazemi-Zahrani, Hamid; Besharat, Mohammad Ali

2016-01-01

Social anxiety is a psychological disorder which has devastative and pernicious effects on interpersonal relationships and one's psychological flexibility. The aim of this research was to determine the effectiveness of Acceptance and Commitment Therapy on interpersonal problems and psychological flexibility in female high school students with social anxiety disorder. With a semi-experimental design, the subjects were assessed using the Social Anxiety Scale and clinical interview. The statistical population of the research was high school female students studying in 5 areas of Isfahan. 30 individuals were purposively selected as the sample. The subjects of the research were randomly assigned to the experimental and control groups. Acceptance and Commitment Therapy was given in 10 sessions of 90 minutes in the experimental group and the control group did not receive any treatment. Pre-test and post-test scores of Inventory of Interpersonal Problems, and Acceptance and Action Questionnaire were analyzed using multivariate analysis of variance & the results showed that after the intervention, there was a significant difference between the scores of the subjects in the experimental and control groups. This means that Acceptance and Commitment Therapy can influence interpersonal problems and their six dimensions and psychological flexibility as well. PMID:26493425

A Neurophysiological Perspective on a Preventive Treatment against Schizophrenia Using Transcranial Electric Stimulation of the Corticothalamic Pathway

PubMed Central

Pinault, Didier

2017-01-01

Schizophrenia patients are waiting for a treatment free of detrimental effects. Psychotic disorders are devastating mental illnesses associated with dysfunctional brain networks. Ongoing brain network gamma frequency (30–80 Hz) oscillations, naturally implicated in integrative function, are excessively amplified during hallucinations, in at-risk mental states for psychosis and first-episode psychosis. So, gamma oscillations represent a bioelectrical marker for cerebral network disorders with prognostic and therapeutic potential. They accompany sensorimotor and cognitive deficits already present in prodromal schizophrenia. Abnormally amplified gamma oscillations are reproduced in the corticothalamic systems of healthy humans and rodents after a single systemic administration, at a psychotomimetic dose, of the glutamate N-methyl-d-aspartate receptor antagonist ketamine. These translational ketamine models of prodromal schizophrenia are thus promising to work out a preventive noninvasive treatment against first-episode psychosis and chronic schizophrenia. In the present essay, transcranial electric stimulation (TES) is considered an appropriate preventive therapeutic modality because it can influence cognitive performance and neural oscillations. Here, I highlight clinical and experimental findings showing that, together, the corticothalamic pathway, the thalamus, and the glutamatergic synaptic transmission form an etiopathophysiological backbone for schizophrenia and represent a potential therapeutic target for preventive TES of dysfunctional brain networks in at-risk mental state patients against psychotic disorders. PMID:28350371

A Neurophysiological Perspective on a Preventive Treatment against Schizophrenia Using Transcranial Electric Stimulation of the Corticothalamic Pathway.

PubMed

Pinault, Didier

2017-03-28

Schizophrenia patients are waiting for a treatment free of detrimental effects. Psychotic disorders are devastating mental illnesses associated with dysfunctional brain networks. Ongoing brain network gamma frequency (30-80 Hz) oscillations, naturally implicated in integrative function, are excessively amplified during hallucinations, in at-risk mental states for psychosis and first-episode psychosis. So, gamma oscillations represent a bioelectrical marker for cerebral network disorders with prognostic and therapeutic potential. They accompany sensorimotor and cognitive deficits already present in prodromal schizophrenia. Abnormally amplified gamma oscillations are reproduced in the corticothalamic systems of healthy humans and rodents after a single systemic administration, at a psychotomimetic dose, of the glutamate N - methyl -d-aspartate receptor antagonist ketamine. These translational ketamine models of prodromal schizophrenia are thus promising to work out a preventive noninvasive treatment against first-episode psychosis and chronic schizophrenia. In the present essay, transcranial electric stimulation (TES) is considered an appropriate preventive therapeutic modality because it can influence cognitive performance and neural oscillations. Here, I highlight clinical and experimental findings showing that, together, the corticothalamic pathway, the thalamus, and the glutamatergic synaptic transmission form an etiopathophysiological backbone for schizophrenia and represent a potential therapeutic target for preventive TES of dysfunctional brain networks in at-risk mental state patients against psychotic disorders.

Anxiety and its disorders as risk factors for suicidal thoughts and behaviors: A meta-analytic review

PubMed Central

Bentley, Kate H.; Franklin, Joseph C.; Ribeiro, Jessica D.; Kleiman, Evan M.; Fox, Kathryn R.; Nock, Matthew K.

2016-01-01

Suicidal thoughts and behaviors are highly prevalent public health problems with devastating consequences. There is an urgent need to improve our understanding of risk factors for suicide to identify effective intervention targets. The aim of this meta-analysis was to examine the magnitude and clinical utility of anxiety and its disorders as risk factors for suicide ideation, attempts, and deaths. We conducted a literature search through December 2014; of the 65 articles meeting our inclusion criteria, we extracted 180 cases in which an anxiety-specific variable was used to longitudinally predict a suicide-related outcome. Results indicated that anxiety is a statistically significant, yet weak, predictor of suicide ideation (OR=1.49, 95% CI: 1.18, 1.88) and attempts (OR=1.64, 95% CI: 1.47, 1.83), but not deaths (OR=1.01, 95% CI: 0.87, 1.18). The strongest associations were observed for PTSD. Estimates were reduced after accounting for publication bias, and diagnostic accuracy analyses indicated acceptable specificity but poor sensitivity. Overall, the extant literature suggests that anxiety and its disorders, at least when these constructs are measured in isolation and as trait-like constructs, are relatively weak predictors of suicidal thoughts and behaviors over long follow-up periods. Implications for future research priorities are discussed. PMID:26688478

A systematic literature review of synovial chondromatosis and pigmented villonodular synovitis of the hip.

PubMed

Startzman, Ashley; Collins, Devin; Carreira, Dominic

2016-11-01

Benign synovial diseases of the hip including Synovial Chondromatosis (SC) and Pigmented Villonodular Synovitis (PVNS) are devastating diseases. Initially, patients present with hip pain unrelieved by conservative measures. The diagnosis of PVNS and SC are often delayed, leading to progression of joint damage. The purpose of this review is to present the latest on the diagnosis, management, and prognosis of SC and PVNS of the hip. An extensive systematic search of MEDLINE and PUBMED Databases was performed. Data parameters were set from 2005 to present day with set inclusion criteria. Systematic reviews were excluded. 427 abstracts were identified, with 12 articles meeting all inclusion criteria. Eight studies focused on SC, and 5 on PVNS. 233 patients with SC of the hip and 98 patients with PVNS of the hip were identified, a total of 331 patients. Benign Synovial disorders of the hip are rare. In patients with chronic hip pain secondary to benign synovial disorders, early diagnosis and surgical intervention demonstrate good outcomes, and patients may benefit due to prevention of morbidity from further joint destruction. There is no clear consensus between higher successes through open versus arthroscopic surgical debridement. In the final phase of benign synovial disorders of the hip, THA of different types based on the patient's age should be considered.

Impact of Microbes on the Pathogenesis of Primary Biliary Cirrhosis (PBC) and Primary Sclerosing Cholangitis (PSC)

PubMed Central

Mattner, Jochen

2016-01-01

Primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC) represent the major clinical entities of chronic cholestatic liver diseases. Both disorders are characterized by portal inflammation and slowly progress to obliterative fibrosis and eventually liver cirrhosis. Although immune-pathogenic mechanisms have been implicated in the pathogenesis of PBC and PSC, neither disorder is considered to be a classical autoimmune disease, as PSC and PBC patients do not respond to immune-suppressants. Furthermore, the decreased bile flow resulting from the immune-mediated tissue assault and the subsequent accumulation of toxic bile products in PBC and PSC not only perpetuates biliary epithelial damage, but also alters the composition of the intestinal and biliary microbiota and its mutual interactions with the host. Consistent with the close association of PSC and inflammatory bowel disease (IBD), the polyclonal hyper IgM response in PBC and (auto-)antibodies which cross-react to microbial antigens in both diseases, an expansion of individual microbes leads to shifts in the composition of the intestinal or biliary microbiota and a subsequent altered integrity of epithelial layers, promoting microbial translocation. These changes have been implicated in the pathogenesis of both devastating disorders. Thus, we will discuss here these recent findings in the context of novel and alternative therapeutic options. PMID:27834858

A phonology-free mobile communication app.

PubMed

Kondapalli, Ananya; Zhang, Lee R; Patel, Shreya; Han, Xiao; Kim, Hee Jin; Li, Xintong; Altschuler, Eric L

2016-11-01

Aphasia - loss of comprehension or expression of language - is a devastating functional sequela of stroke. There are as yet no effective methods for rehabilitation of aphasia. An assistive device that allows aphasia patients to communicate and interact at speeds approaching real time is urgently needed. Behavioral and linguistic studies of aphasia patients show that they retain normal thinking processes and most aspects of language. They lack only phonology: the ability to translate (input) and/or output sounds (or written words) such as "ta-ble" into the image of a four-legged object with a top at which one works or eats. We have made a phonology-free communication mobile app that may be useful for patients with aphasia and other communication disorders. Particular innovations of our app include calling Google Images as a "subroutine" to allow a near-infinite number of choices (e.g. food or clothing items) for patients without having to make countless images, and by the use of animation for words, phrases or concepts that cannot be represented by a single image. We have tested our app successfully in one patient. The app may be of great benefit to patients with aphasia and other communication disorders. Implications for Rehabilitation We have made a phonology-free mobile communication app. This app may facilitate communication for patients with aphasia and other communication disorders.

HDL and Cognition in Neurodegenerative Disorders

PubMed Central

Hottman, David A.; Chernick, Dustin; Cheng, Shaowu; Wang, Zhe; Li, Ling

2014-01-01

High-density lipoproteins (HDL) are a heterogeneous group of lipoproteins composed of various lipids and proteins. HDL is formed both in the systemic circulation and in the brain. In addition to being a crucial player in the reverse cholesterol transport pathway, HDL possesses a wide range of other functions including anti-oxidation, anti-inflammation, pro-endothelial function, anti-thrombosis, and modulation of immune function. It has been firmly established that high plasma levels of HDL protect against cardiovascular disease. Accumulating evidence indicates that the beneficial role of HDL extends to many other systems including the central nervous system. Cognition is a complex brain function that includes all aspects of perception, thought, and memory. Cognitive function often declines during aging and this decline manifests as cognitive impairment/dementia in age-related and progressive neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis. A growing concern is that no effective therapy is currently available to prevent or treat these devastating diseases. Emerging evidence suggests that HDL may play a pivotal role in preserving cognitive function under normal and pathological conditions. This review attempts to summarize recent genetic, clinical and experimental evidence for the impact of HDL on cognition in aging and in neurodegenerative disorders as well as the potential of HDL-enhancing approaches to improve cognitive function. PMID:25131449

Biochemical markers and neuropsychological functioning in distal urea cycle disorders.

PubMed

Waisbren, Susan E; Cuthbertson, David; Burgard, Peter; Holbert, Amy; McCarter, Robert; Cederbaum, Stephen

2018-02-08

Urea cycle disorders often present as devastating metabolic conditions, resulting in high mortality and significant neuropsychological damage, despite treatment. The Urea Cycle Disorders Longitudinal Study is a natural history study that collects data from regular clinical follow-up and neuropsychological testing. This report examines links between biochemical markers (ammonia, glutamine, arginine, citrulline) and primary neuropsychological endpoints in three distal disorders, argininosuccinic acid synthetase deficiency (ASD or citrullinemia type I), argininosuccinic acid lyase deficiency (ASA or ALD), and arginase deficiency (ARGD). Laboratory results and test scores from neuropsychological evaluations were assessed in 145 study participants, ages 3 years and older, with ASD (n = 64), ASA (n = 65) and ARGD (n = 16). Mean full scale IQ was below the population mean of 100 ± 15 for all groups: (ASD = 79 ± 24; ASA = 71 ± 21; ARGD = 65 ± 19). The greatest deficits were noted in visual performance and motor skills for all groups. While ammonia levels remain prominent as prognostic biomarkers, other biomarkers may be equally valuable as correlates of neuropsychological functioning. Cumulative exposure to the biomarkers included in the study proved to be highly sensitive indicators of neuropsychological outcomes, even when below the cut-off levels generally considered toxic. Blood levels of biomarkers obtained on the day of neuropsychological evaluations were not correlated with measures of functioning for any disorder in any domain. The importance of cumulative exposure supports early identification and confirms the need for well-controlled management of all biochemical abnormalities (and not just ammonia) that occur in urea cycle disorders.