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Sample records for exacerbates motor dysfunction

  1. Loss of ALS2/Alsin exacerbates motor dysfunction in a SOD1-expressing mouse ALS model by disturbing endolysosomal trafficking.

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    Shinji Hadano

    Full Text Available BACKGROUND: ALS2/alsin is a guanine nucleotide exchange factor for the small GTPase Rab5 and involved in macropinocytosis-associated endosome fusion and trafficking, and neurite outgrowth. ALS2 deficiency accounts for a number of juvenile recessive motor neuron diseases (MNDs. Recently, it has been shown that ALS2 plays a role in neuroprotection against MND-associated pathological insults, such as toxicity induced by mutant Cu/Zn superoxide dismutase (SOD1. However, molecular mechanisms underlying the relationship between ALS2-associated cellular function and its neuroprotective role remain unclear. METHODOLOGY/PRINCIPAL FINDINGS: To address this issue, we investigated the molecular and pathological basis for the phenotypic modification of mutant SOD1-expressing mice by ALS2 loss. Genetic ablation of Als2 in SOD1(H46R, but not SOD1(G93A, transgenic mice aggravated the mutant SOD1-associated disease symptoms such as body weight loss and motor dysfunction, leading to the earlier death. Light and electron microscopic examinations revealed the presence of degenerating and/or swollen spinal axons accumulating granular aggregates and autophagosome-like vesicles in early- and even pre-symptomatic SOD1(H46R mice. Further, enhanced accumulation of insoluble high molecular weight SOD1, poly-ubiquitinated proteins, and macroautophagy-associated proteins such as polyubiquitin-binding protein p62/SQSTM1 and a lipidated form of light chain 3 (LC3-II, emerged in ALS2-deficient SOD1(H46R mice. Intriguingly, ALS2 was colocalized with LC3 and p62, and partly with SOD1 on autophagosome/endosome hybrid compartments, and loss of ALS2 significantly lowered the lysosome-dependent clearance of LC3 and p62 in cultured cells. CONCLUSIONS/SIGNIFICANCE: Based on these observations, although molecular basis for the distinctive susceptibilities to ALS2 loss in different mutant SOD1-expressing ALS models is still elusive, disturbance of the endolysosomal system by ALS2 loss

  2. Overexpression of Hypoxia-Inducible Factor-1α Exacerbates Endothelial Barrier Dysfunction Induced by Hypoxia

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    Pei Wang

    2013-09-01

    Full Text Available Background/Aims: The mechanisms involved in endothelial barrier dysfunction induced by hypoxia are incompletely understood. There is debate about the role of hypoxia-inducible factor-1α (HIF-1α in endothelial barrier disruption. The aim of this study was to investigate the effect of genetic overexpression of HIF-1α on barrier function and the underlying mechanisms in hypoxic endothelial cells. Methods: The plasmid pcDNA3.1/V5-His-HIF-1α was stably transfected into human endothelial cells. The cells were exposed to normoxia or hypoxia. The mRNA and protein expressions of HIF-1α were detected by RT-PCR and Western blot respectively. The barrier function was assessed by measuring the transendothelial electrical resistance (TER. The Western blot analysis was used to determine the protein expression of glucose transporter-1 (GLUT-1, zonular occludens-1 (ZO-1, occludin, and myosin light chain kinase (MLCK in endothelial cells. The mRNA expression of proinflammatory cytokines was detected by qRT-PCR. Results: Genetic overexpression of HIF-1α significantly increased the mRNA and protein expression of HIF-1α in endothelial cells. The overexpression of HIF-1α enhanced the hypoxia-induced increase of HIF-1α and GLUT-1 protein expression. HIF-1α overexpression not only exacerbated hypoxia-induced endothelial barrier dysfunction but also augmented hypoxia-induced up-regulation of MLCK protein expression. HIF-1α overexpression also enhanced IL-1β, IL-6 and TNF-α mRNA expression. Conclusion: We provide evidence that genetic overexpression of HIF-1α aggravates the hypoxia-induced endothelial barrier dysfunction via enhancing the up-regulation of MLCK protein expression caused by hypoxia, suggesting a potential role for HIF-1α in the pathogenesis of endothelial barrier dysfunction in hypoxia.

  3. Timed motor tests can detect subtle motor dysfunction in early Parkinson's disease.

    NARCIS (Netherlands)

    Haaxma, C.A.; Bloem, B.R.; Overeem, S.; Borm, G.F.; Horstink, M.W.I.M.

    2010-01-01

    Early diagnosis of Parkinson's disease (PD) is important for putative neuroprotective therapies to be initiated in the earliest stage of the disease. We investigated whether a previously validated timed motor test (TMT) battery could detect subtle motor dysfunction in early PD patients and even in

  4. Limb motor nerve dysfunction in Miller Fisher syndrome.

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    Drenthen, Judith; Maathuis, Ellen M; Visser, Gerhard H; van Doorn, Pieter A; Blok, Joleen H; Jacobs, Bart C

    2013-03-01

    Typical Miller Fisher syndrome (MFS) lacks limb muscle weakness, but some patients may unpredictably progress to severe Guillain-Barré syndrome. The compound muscle action potential (CMAP) scan is a recently developed non-invasive, painless, and reproducible method for detecting early changes in motor nerve excitability. This technique was used to monitor subclinical limb motor nerve dysfunction during disease course in typical MFS. Three Miller Fisher patients with preserved limb muscle strength and normal routine nerve conduction studies were included. Frequent serial CMAP scanning of the median nerve was performed during acute phase and follow-up and was related to clinical course and outcome. All patients showed an abnormal increase in the range of stimulus intensities at the day of hospital admission, indicating reduced motor nerve excitability already at the earliest stage of disease. Median nerve dysfunction progressed in parallel or even before clinical deterioration, and improved with clinical recovery. Our study shows that typical MFS is a more general neuropathy, affecting peripheral motor nerves even in patients with preserved limb strength and conduction velocity. CMAP scanning is a sensitive technique for early detection of subclinical motor nerve dysfunction and for monitoring disease activity in immune-mediated neuropathies. © 2013 Peripheral Nerve Society.

  5. High-sugar intake does not exacerbate metabolic abnormalities or cardiac dysfunction in genetic cardiomyopathy.

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    Hecker, Peter A; Galvao, Tatiana F; O'Shea, Karen M; Brown, Bethany H; Henderson, Reney; Riggle, Heather; Gupte, Sachin A; Stanley, William C

    2012-05-01

    A high-sugar intake increases heart disease risk in humans. In animals, sugar intake accelerates heart failure development by increased reactive oxygen species (ROS). Glucose-6-phosphate dehydrogenase (G6PD) can fuel ROS production by providing reduced nicotinamide adenine dinucleotide phosphate (NADPH) for superoxide generation by NADPH oxidase. Conversely, G6PD also facilitates ROS scavenging using the glutathione pathway. We hypothesized that a high-sugar intake would increase flux through G6PD to increase myocardial NADPH and ROS and accelerate cardiac dysfunction and death. Six-week-old TO-2 hamsters, a non-hypertensive model of genetic cardiomyopathy caused by a δ-sarcoglycan mutation, were fed a long-term diet of high starch or high sugar (57% of energy from sucrose plus fructose). After 24 wk, the δ-sarcoglycan-deficient animals displayed expected decreases in survival and cardiac function associated with cardiomyopathy (ejection fraction: control 68.7 ± 4.5%, TO-2 starch 46.1 ± 3.7%, P sugar 58.0 ± 4.2%, NS, versus TO-2 starch or control; median survival: TO-2 starch 278 d, TO-2 sugar 318 d, P = 0.133). Although the high-sugar intake was expected to exacerbate cardiomyopathy, surprisingly, there was no further decrease in ejection fraction or survival with high sugar compared with starch in cardiomyopathic animals. Cardiomyopathic animals had systemic and cardiac metabolic abnormalities (increased serum lipids and glucose and decreased myocardial oxidative enzymes) that were unaffected by diet. The high-sugar intake increased myocardial superoxide, but NADPH and lipid peroxidation were unaffected. A sugar-enriched diet did not exacerbate ventricular function, metabolic abnormalities, or survival in heart failure despite an increase in superoxide production. Copyright © 2012 Elsevier Inc. All rights reserved.

  6. Motor neuron degeneration correlates with respiratory dysfunction in SCA1.

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    Orengo, James P; van der Heijden, Meike E; Hao, Shuang; Tang, Jianrong; Orr, Harry T; Zoghbi, Huda Y

    2018-01-29

    Spinocerebellar ataxia type 1 (SCA1) is characterized by adult-onset cerebellar degeneration with attendant loss of motor coordination. Bulbar function is eventually impaired, and patients tend to die from inability to clear the airway. We asked whether motor neuron degeneration is at the root of bulbar dysfunction by studying SCA1 knock-in mice. We analyzed spinal cord and brainstem motor neurons in SCA1 knock-in (Atxn1 154Q ) mice at 1, 3, and 6 months of age. Specifically, we assessed breathing physiology, diaphragm histology and electromyography, and motor neuron histology and immunohistochemistry. Atxn1 154Q mice show progressive neuromuscular respiratory abnormalities, neurogenic changes in diaphragm, and motor neuron degeneration in the spinal cord and brainstem. The latter is accompanied by reactive astrocytosis and accumulation of Atxn1 aggregates in the motor neuron nuclei. This dovetails with previous observations in SCA1 patient tissue. Atxn1 154Q mice develop bulbar dysfunction because of motor neuron degeneration. These findings confirm the Atxn1 154Q line as a SCA1 model with face and construct validity for this understudied disease feature. Furthermore, this model is suitable to study the pathogenic mechanism driving motor neuron degeneration in SCA1 and perhaps other degenerative motor neuron diseases. From a clinical standpoint, the data indicate that pulmonary function testing and employment of non-invasive ventilator support could be beneficial in SCA1 patients. The physiological tests used in this study may serve as valuable biomarkers for future therapeutic interventions and clinical trials. © 2018. Published by The Company of Biologists Ltd.

  7. Coronary arterial BK channel dysfunction exacerbates ischemia/reperfusion-induced myocardial injury in diabetic mice.

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    Lu, Tong; Jiang, Bin; Wang, Xiao-Li; Lee, Hon-Chi

    2016-09-01

    The large conductance Ca(2+)-activated K(+) (BK) channels, abundantly expressed in coronary artery smooth muscle cells (SMCs), play a pivotal role in regulating coronary circulation. A large body of evidence indicates that coronary arterial BK channel function is diminished in both type 1 and type 2 diabetes. However, the consequence of coronary BK channel dysfunction in diabetes is not clear. We hypothesized that impaired coronary BK channel function exacerbates myocardial ischemia/reperfusion (I/R) injury in streptozotocin-induced diabetic mice. Combining patch-clamp techniques and cellular biological approaches, we found that diabetes facilitated the colocalization of angiotensin II (Ang II) type 1 receptors and BK channel α-subunits (BK-α), but not BK channel β1-subunits (BK-β1), in the caveolae of coronary SMCs. This caveolar compartmentation in vascular SMCs not only enhanced Ang II-mediated inhibition of BK-α but also produced a physical disassociation between BK-α and BK-β1, leading to increased infarct size in diabetic hearts. Most importantly, genetic ablation of caveolae integrity or pharmacological activation of coronary BK channels protected the cardiac function of diabetic mice from experimental I/R injury in both in vivo and ex vivo preparations. Our results demonstrate a vascular ionic mechanism underlying the poor outcome of myocardial injury in diabetes. Hence, activation of coronary BK channels may serve as a therapeutic target for cardiovascular complications of diabetes.

  8. Imaging of muscular denervation secondary to motor cranial nerve dysfunction

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    Connor, S.E.J. [Neuroradiology Department, Kings College Hospital, Denmark Hill, London SE5 9RS (United Kingdom)]. E-mail: sejconnor@tiscali.co.uk; Chaudhary, N. [Neuroradiology Department, Kings College Hospital, Denmark Hill, London SE5 9RS (United Kingdom); Fareedi, S. [Neuroradiology Department, Kings College Hospital, Denmark Hill, London SE5 9RS (United Kingdom); Woo, E.K. [Neuroradiology Department, Kings College Hospital, Denmark Hill, London SE5 9RS (United Kingdom)

    2006-08-15

    The effects of motor cranial nerve dysfunction on the computed tomography (CT) and magnetic resonance imaging (MRI) appearances of head and neck muscles are reviewed. Patterns of denervation changes are described and illustrated for V, VII, X, XI and XII cranial nerves. Recognition of the range of imaging manifestations, including the temporal changes in muscular appearances and associated muscular grafting or compensatory hypertrophy, will avoid misinterpretation as local disease. It will also prompt the radiologist to search for underlying cranial nerve pathology, which may be clinically occult. The relevant cranial nerve motor division anatomy will be described to enable a focussed search for such a structural abnormality.

  9. CD200-CD200R dysfunction exacerbates microglial activation and dopaminergic neurodegeneration in a rat model of Parkinson's disease

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    Zhang Shi

    2011-11-01

    study shows that deficits in the CD200-CD200R system exacerbate microglial activation and dopaminergic neurodegeneration in a 6-OHDA-induced rat model of PD. Our results suggest that dysfunction of CD200-CD200R signalling may be involved in the aetiopathogenesis of PD.

  10. Transient Cerebral Ischemia Promotes Brain Mitochondrial Dysfunction and Exacerbates Cognitive Impairments in Young 5xFAD Mice

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    Lu, Lin; Guo, Lan; Gauba, Esha; Tian, Jing; Wang, Lu; Tandon, Neha; Shankar, Malini; Beck, Simon J.; Du, Yifeng; Du, Heng

    2015-01-01

    Alzheimer's disease (AD) is heterogeneous and multifactorial neurological disorder; and the risk factors of AD still remain elusive. Recent studies have highlighted the role of vascular factors in promoting the progression of AD and have suggested that ischemic events increase the incidence of AD. However, the detailed mechanisms linking ischemic insult to the progression of AD is still largely undetermined. In this study, we have established a transient cerebral ischemia model on young 5xFAD mice and their non-transgenic (nonTg) littermates by the transient occlusion of bilateral common carotid arteries. We have found that transient cerebral ischemia significantly exacerbates brain mitochondrial dysfunction including mitochondrial respiration deficits, oxidative stress as well as suppressed levels of mitochondrial fusion proteins including optic atrophy 1 (OPA1) and mitofusin 2 (MFN2) in young 5xFAD mice resulting in aggravated spatial learning and memory. Intriguingly, transient cerebral ischemia did not induce elevation in the levels of cortical or mitochondrial Amyloid beta (Aβ)1-40 or 1–42 levels in 5xFAD mice. In addition, the glucose- and oxygen-deprivation-induced apoptotic neuronal death in Aβ-treated neurons was significantly mitigated by mitochondria-targeted antioxidant mitotempo which suppresses mitochondrial superoxide levels. Therefore, the simplest interpretation of our results is that young 5xFAD mice with pre-existing AD-like mitochondrial dysfunction are more susceptible to the effects of transient cerebral ischemia; and ischemic events may exacerbate dementia and worsen the outcome of AD patients by exacerbating mitochondrial dysfunction. PMID:26632816

  11. Bromide supplementation exacerbated the renal dysfunction, injury and fibrosis in a mouse model of Alport syndrome.

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    Tsubasa Yokota

    Full Text Available A seminal study recently demonstrated that bromide (Br- has a critical function in the assembly of type IV collagen in basement membrane (BM, and suggested that Br- supplementation has therapeutic potential for BM diseases. Because salts of bromide (KBr and NaBr have been used as antiepileptic drugs for several decades, repositioning of Br- for BM diseases is probable. However, the effects of Br- on glomerular basement membrane (GBM disease such as Alport syndrome (AS and its impact on the kidney are still unknown. In this study, we administered daily for 16 weeks 75 mg/kg or 250 mg/kg (within clinical dosage NaBr or NaCl (control via drinking water to 6-week-old AS mice (mouse model of X-linked AS. Treatment with 75 mg/kg NaBr had no effect on AS progression. Surprisingly, compared with 250 mg/kg NaCl, 250 mg/kg NaBr exacerbated the progressive proteinuria and increased the serum creatinine and blood urea nitrogen in AS mice. Histological analysis revealed that glomerular injury, renal inflammation and fibrosis were exacerbated in mice treated with 250 mg/kg NaBr compared with NaCl. The expressions of renal injury markers (Lcn2, Lysozyme, matrix metalloproteinase (Mmp-12, pro-inflammatory cytokines (Il-6, Il-8, Tnf-α, Il-1β and pro-fibrotic genes (Tgf-β, Col1a1, α-Sma were also exacerbated by 250 mg/kg NaBr treatment. Notably, the exacerbating effects of Br- were not observed in wild-type mice. These findings suggest that Br- supplementation needs to be carefully evaluated for real positive health benefits and for the absence of adverse side effects especially in GBM diseases such as AS.

  12. Global muscle dysfunction as a risk factor of readmission to hospital due to COPD exacerbations

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    Vilaró, Jordi; Ramirez-Sarmiento, Alba; Martínez-Llorens, Juana Ma; Mendoza, Teresa; Alvarez, Miguel; Sánchez-Cayado, Natalia; Vega, Ángeles; Gimeno, Elena; Coronell, Carlos; Gea, Joaquim; Roca, Josep; Orozco-Levi, Mauricio

    2010-01-01

    Exacerbations of chronic obstructive pulmonary disease (COPD) are associated with several modifiable (sedentary life-style, smoking, malnutrition, hypoxemia) and non-modifiable (age, co-morbidities, severity of pulmonary function, respiratory infections) risk factors. We hypothesise that most of these risk factors may have a converging and deleterious effects on both respiratory and peripheral muscle function in COPD patients. METHODS: A multicentre study was carried out in 121 COPD patients ...

  13. Motor dysfunction and touch-slang in user interface data.

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    Klein, Yoni; Djaldetti, Ruth; Keller, Yosi; Bachelet, Ido

    2017-07-05

    The recent proliferation in mobile touch-based devices paves the way for increasingly efficient, easy to use natural user interfaces (NUI). Unfortunately, touch-based NUIs might prove difficult, or even impossible to operate, in certain conditions e.g. when suffering from motor dysfunction such as Parkinson's Disease (PD). Yet, the prevalence of such devices makes them particularly suitable for acquiring motor function data, and enabling the early detection of PD symptoms and other conditions. In this work we acquired a unique database of more than 12,500 annotated NUI multi-touch gestures, collected from PD patients and healthy volunteers, that were analyzed by applying advanced shape analysis and statistical inference schemes. The proposed analysis leads to a novel detection scheme for early stages of PD. Moreover, our computational analysis revealed that young subjects may be using a 'slang' form of gesture-making to reduce effort and attention cost while maintaining meaning, whereas older subjects put an emphasis on content and precise performance.

  14. Motor dysfunction in complex regional pain syndrome : the role of sensory processing and sensory-motor integration

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    Bank, Paulina Johanna Maria

    2014-01-01

    In the chronic stage of Complex Regional Pain Syndrome (CRPS), motor disturbances are common and cause significant disability. The motor dysfunction of CRPS is a poorly understood phenomenon that is characterized predominantly by a decrease or loss of voluntary muscle control. This thesis aims to

  15. Severity of motor dysfunction in children with cerebral palsy seen in ...

    African Journals Online (AJOL)

    Abstract. Introduction: Children with cerebral palsy (CP) have gross motor dysfunction (GMD) of varying degrees of severity. The Gross Motor Function Classification System (GMFCS) is widely used internationally to classify children with CP into functional severity levels. There are few reports on the use of GMFCS in Nigeria ...

  16. Remote Traumatic Brain Injury Is Associated with Motor Dysfunction in Older Military Veterans.

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    Gardner, Raquel C; Peltz, Carrie B; Kenney, Kimbra; Covinsky, Kenneth E; Diaz-Arrastia, Ramon; Yaffe, Kristine

    2017-09-01

    Traumatic brain injury (TBI) has been identified as a risk factor for Parkinson's disease (PD). Motor dysfunction among TBI-exposed elders without PD has not been well characterized. We sought to determine whether remote TBI is a risk factor for motor dysfunction on exam and functionally relevant motor dysfunction in day-to-day life among independently living elders without PD. This is a cross-sectional cohort study of independently living retired military veterans aged 50 or older with (n = 78) and without (n = 85) prior TBI-all without diagnosed PD. To characterize multidimensional aspects of motor function on exam, the Unified Parkinson's Disease Rating Scale (UPDRS) Motor Examination was performed by a board-certified neurologist and used to calculate a modified UPDRS (mUPDRS) global motor score and four domain scores (tremor, rigidity, bradykinesia, and posture/gait). Functionally relevant motor dysfunction was assessed via self-report of falls within the past year. In analyses adjusted for demographics and comorbidities that differed between groups, compared with veterans without TBI, those with moderate-to-severe TBI were more likely to have fallen in past year (33% vs. 14%, risk ratio 2.5 [95% confidence interval 1.1-5.4]), had higher (worse) mUPDRS global motor (p = .03) and posture/gait scores (p = .02), but not higher tremor (p = .70), rigidity (p = .21), or bradykinesia scores (p = .22). Mild TBI was not associated with worse motor function. Remote moderate-to-severe TBI is a risk factor for motor dysfunction-defined as recent falls and impaired posture/gait-among older veterans. TBI-exposed older adults may be ideal candidates for aggressive fall-screening and prevention strategies.

  17. Motor dysfunction as research domain in the period preceding manifest schizophrenia: A systematic review.

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    Hirjak, Dusan; Meyer-Lindenberg, Andreas; Kubera, Katharina M; Thomann, Philipp A; Wolf, Robert C

    2018-02-09

    Schizophrenia is a severe behavioral syndrome of neurodevelopmental nature marked by primary or genuine motor abnormalities (GMA), which refer to spontaneous and medication-independent motor phenomena. Since motor dysfunction thus might be a consequence of events occurring during early childhood and adolescence, GMA can be detected in the period preceding manifest schizophrenia. However, the question whether motor system dysfunction might be a promising motor intermediate phenotype for schizophrenia remains unanswered. In this review, we systematically evaluate the evidence on GMA in healthy persons, individuals with schizotypal personality traits, persons at ultra-high risk for psychosis, and unaffected first-degree relatives of schizophrenia patients. What becomes evident is a continuum of GMA expression, which appears to be linked to abnormalities of cerebello-thalamo-cortical, fronto-parietal, and cortico-subcortical motor circuits. According to current evidence, motor dysfunction is a key aspect of the neurodevelopmental risk factor model of schizophrenia. Insights provided by this research will help promoting the RDoC Motor System construct and expand the clinical relevance of the motor domain in the period preceding manifest schizophrenia. Copyright © 2018 Elsevier Ltd. All rights reserved.

  18. Blue light therapy improves circadian dysfunction as well as motor symptoms in two mouse models of Huntington's disease

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    Huei-Bin Wang

    2017-01-01

    Full Text Available Patients with Huntington's disease (HD exhibit movement disorders, psychiatric disturbance and cognitive impairments as the disease progresses. Abnormal sleep/wake cycles are common among HD patients with reports of delayed sleep onset, fatigue during the day, and a delayed pattern of melatonin secretion all of which suggest circadian dysfunction. Mouse models of HD confirm disrupted circadian rhythms with pathophysiology found in the central circadian clock (suprachiasmatic nucleus. Importantly, circadian dysfunction manifests early in disease, even before the classic motor symptoms, in both patients and mouse models. Therefore, we hypothesize that the circadian dysfunction may interact with the disease pathology and exacerbate the HD symptoms. If correct, early intervention may benefit patients and delay disease progression. One test of this hypothesis is to determine whether light therapy designed to strengthen this intrinsic timing system can delay the disease progression in mouse models. Therefore, we determined the impact of blue wavelength-enriched light on two HD models: the BACHD and Q175 mice. Both models received 6 h of blue-light at the beginning of their daily light cycle for 3 months. After treatment, both genotypes showed improvements in their locomotor activity rhythm without significant change to their sleep behavior. Critically, treated mice of both lines exhibited improved motor performance compared to untreated controls. Focusing on the Q175 genotype, we sought to determine whether the treatment altered signaling pathways in brain regions known to be impacted by HD using NanoString gene expression assays. We found that the expression of several HD relevant markers was altered in the striatum and cortex of the treated mice. Our study demonstrates that strengthening the circadian system can delay the progression of HD in pre-clinical models. This work suggests that lighting conditions should be considered when managing

  19. Focal dystonia in musicians: Linking motor symptoms to somatosensory dysfunction

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    Juergen eKonczak

    2013-06-01

    Full Text Available Musician’s dystonia (MD is a neurological motor disorder characterized by involuntary contractions of those muscles involved in the play of a musical instrument. It is task-specific and initially only impairs the voluntary control of highly practiced musical motor skills. MD can lead to a severe decrement in a musician’s ability to perform. While the etiology and the neurological pathomechanism of the disease remain unknown, it is known that MD like others forms of focal dystonia is associated with somatosensory deficits, specifically a decreased precision of tactile and proprioceptive perception. The sensory component of the disease becomes also evident by the patients’ use sensory tricks such as touching dystonic muscles to alleviate motor symptoms. The central premise of this paper is that the motor symptoms of MD have a somatosensory origin and are not fully explained as a problem of motor execution. We outline how altered proprioceptive feedback ultimately leads to a loss of voluntary motor control and propose two scenarios that explain why sensory tricks are effective. Sensory tricks are effective, because the sensorimotor system either recruits neural resources normally involved in tactile-proprioceptive (sensory integration, or utilizes a fully functioning motor efference copy mechanism to align experienced with expected sensory feedback. We argue that an enhanced understanding of how a primary sensory deficit interacts with mechanisms of sensorimotor integration in musician’s dystonia provides helpful insights for the design of more effective behavioral therapies.

  20. The Identification of Children with Perceptual-Motor Dysfunction; A Study of Perceptual-Motor Dysfunction among Emotionally Disturbed, Educable Mentally Retarded and Normal Children in the Pittsburgh Public Schools.

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    Rosner, Jerome; And Others

    The Rosner Perceptual Survey (RPS) and the Rosner-Richman Perceptual Survey (RRPS) were developed for screening perceptual motor dysfunction. The RPS consisted of 17 subtests of visual motor and auditory motor functions, general motor skills, self awareness, and integrative function; the RRPS, intended for teacher or paraprofessional use, included…

  1. Dysfunctional lipoproteins from young smokers exacerbate cellular senescence and atherogenesis with smaller particle size and severe oxidation and glycation.

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    Park, Ki-Hoon; Shin, Dong-Gu; Cho, Kyung-Hyun

    2014-07-01

    Until now, there has been limited information on the effects of smoking on atherogenesis and senescence in the context of lipoprotein parameters, particularly in young smokers who have smoked fewer than 10 cigarettes per day for 3 years. In this study, lipoprotein profiles and functions were compared between smoker (n = 21) and control groups (n = 20). In the smoking group, ferric ion reduction abilities of serum and high-density lipoprotein (HDL) fractions were significantly reduced, and low-density lipoprotein (LDL) was severely oxidized. All lipoprotein particles from the smoker group showed higher advanced glycated end products with more triglyceride (TG) content compared with the control group. Lipoproteins from smokers showed faster agarose gel electromobility as well as greater smear band intensity in SDS-PAGE due to oxidation and glycation. LDL from smokers was more sensitive to oxidation and promoted foam cell forma-tion in macrophages. Gel filtration column chromatography revealed that the protein and cholesterol peaks of VLDL and LDL were elevated in the smoker group, whereas those of HDL were reduced. Human dermal fibroblast cells from the smoker group showed severe senescence following treatment with HDL2 and HDL3. Although HDL from young smokers showed impaired antioxidant ability, smaller particle size, and increased TG content, cholesteryl ester transfer protein activities were greatly enhanced in the serum and HDL fractions of the smoker group. In conclusion, smoking can cause production of dysfunctional lipoproteins having a smaller particle size that exacerbate senescence and atherogenic progress due to oxidation and glycation. © The Author 2014. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  2. Colonic Motor Dysfunction in Children with Chronicle Constipation: Electrophysiological Aspects

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    T.V. Zimnitskaia

    2015-09-01

    Conclusions. Different types of violations in colonic electrical activity require a differentiated approach to the correction of its motor function. The principles of treatment for chronic constipation in children at every type of violation in colonic electrical activity were offered.

  3. At the interface of sensory and motor dysfunctions and Alzheimer’s Disease

    Science.gov (United States)

    Albers, Mark W.; Gilmore, Grover C.; Kaye, Jeffrey; Murphy, Claire; Wingfield, Arthur; Bennett, David A.; Boxer, Adam L.; Buchman, Aron S.; Cruickshanks, Karen J.; Devanand, Davangere P.; Duffy, Charles J.; Gall, Christine M.; Gates, George A.; Granholm, Ann-Charlotte; Hensch, Takao; Holtzer, Roee; Hyman, Bradley T.; Lin, Frank R.; McKee, Ann C.; Morris, John C.; Petersen, Ronald C.; Silbert, Lisa C.; Struble, Robert G.; Trojanowski, John Q.; Verghese, Joe; Wilson, Donald A.; Xu, Shunbin; Zhang, Li I.

    2014-01-01

    Recent evidence indicates that sensory and motor changes may precede the cognitive symptoms of Alzheimer’s disease (AD) by several years and may signify increased risk of developing AD. Traditionally, sensory and motor dysfunctions in aging and AD have been studied separately. To ascertain the evidence supporting the relationship between age-related changes in sensory and motor systems and the development of AD and to facilitate communication between several disciplines, the National Institute on Aging held an exploratory workshop titled “Sensory and Motor Dysfunctions in Aging and Alzheimer’s Disease”. The scientific sessions of the workshop focused on age-related and neuropathological changes in the olfactory, visual, auditory, and motor systems, followed by extensive discussion and hypothesis generation related to the possible links among sensory, cognitive, and motor domains in aging and AD. Based on the data presented and discussed at this workshop, it is clear that sensory and motor regions of the CNS are affected by Alzheimer pathology and that interventions targeting amelioration of sensory-motor deficits in AD may enhance patient function as AD progresses. PMID:25022540

  4. Timing Deficits Are Implicated in Motor Dysfunction in Asperger's Syndrome

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    Price, Kelly J.; Edgell, Dorothy; Kerns, Kimberly A.

    2012-01-01

    This study addressed what role movement timing irregularities have in producing the motor deficits documented in Asperger's Syndrome (AS). Participants included males with AS (n = 14) and without (n = 16), matched by age (7-23 years) and with no significant IQ differences. They completed measures of timing perception (comparisons of tempo of…

  5. Assessing Upper Extremity Motor Dysfunction Using an Augmented Reality Game

    NARCIS (Netherlands)

    Cidota, M.A.; Bank, Paulina J.M.; Ouwehand, P.W.; Lukosch, S.G.

    2017-01-01

    Advances in technology offer new opportunities for a better understanding of how different disorders affect motor function. In this paper, we explore the potential of an augmented reality (AR) game implemented using free hand and body tracking to develop a uniform, cost-effective and objective

  6. Neural substrates of motor and cognitive dysfunctions in SCA2 patients: A network based statistics analysis

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    G. Olivito

    2017-01-01

    In the present study, the network-based statistics (NBS approach was used to assess differences in functional connectivity between specific cerebellar and cerebral “nodes” in SCA2 patients. Altered inter-nodal connectivity was found between more posterior regions in the cerebellum and regions in the cerebral cortex clearly related to cognition and emotion. Furthermore, more anterior cerebellar lobules showed altered inter-nodal connectivity with motor and somatosensory cerebral regions. The present data suggest that in SCA2 a cerebellar dysfunction affects long-distance cerebral regions and that the clinical symptoms may be specifically related with connectivity changes between motor and non-motor cerebello-cortical nodes.

  7. Specific postural support promotes variation in motor behaviour of infants with minor neurological dysfunction

    NARCIS (Netherlands)

    de Graaf-Peters, Victorine B.; De Groot-Hornstra, Agnes H.; Dirks, Tineke; Hadders-Algra, Mijna

    2006-01-01

    This study evaluated the effect of specific postural support on motor behaviour of infants with and without minor neurological dysfunction (MND). The following questions were addressed: (1) Does application of supportive pillows affect the time during which the infant exhibits general movements

  8. N-terminal proB-type natriuretic peptide levels aid the diagnosis of left ventricular dysfunction in patients with severe acute exacerbations of chronic obstructive pulmonary disease and renal dysfunction.

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    Ouanes, Islem; Jalloul, Faten; Ayed, Samia; Dachraoui, Fahmi; Ouanes-Besbes, Lamia; Fekih Hassen, Mohamed; Elatrous, Souheil; Abroug, Fekri

    2012-05-01

    The aim of this study was to assess the performance of N-terminal proB-type natriuretic peptide (NT-proBNP) levels for the diagnosis of left ventricular dysfunction in patients with severe acute exacerbations of chronic obstructive pulmonary disease (COPD) and renal dysfunction. NT-proBNP levels at admission were measured in consecutive patients admitted to two participating intensive care units with acute exacerbations of COPD. Left ventricular dysfunction was assessed on the basis of clinical and echocardiographic criteria. The performance of NT-proBNP levels was evaluated in patients with or without renal dysfunction. Among the 120 patients included in the study, 70 had impaired renal function, defined as a glomerular filtration rate of <90 mL/min/1.73 m(2). NT-proBNP levels were inversely correlated with glomerular filtration rate (Spearman's correlation coefficient = -0.457, P < 0.001). Overall, left ventricular dysfunction was diagnosed in 58 patients (48.3%). Median NT-proBNP levels were significantly higher in these patients, irrespective of whether their renal function was normal (3313 (interquartile range (IQR) 4603) vs 337 (IQR 695) pg/mL, P < 0.001) or impaired (5692 (IQR 10714) vs 887 (IQR 1165) pg/mL, P < 0.001). The areas under the receiver operating characteristic curves were 0.87 and 0.78, respectively. The threshold NT-proBNP value with the highest diagnostic accuracy was greater in the setting of renal dysfunction (2000 pg/mL; sensitivity 71%, specificity 82%, compared with 1000 pg/mL in patients with normal renal function; sensitivity 94%, specificity 82%). Multivariate analysis showed that left ventricular dysfunction and glomerular filtration rate were independently associated with elevated NT-proBNP levels. NT-proBNP remains an accurate biomarker for the diagnosis of left ventricular dysfunction associated with acute exacerbations of COPD. Threshold values of NT-proBNP were higher in patients with impaired renal function than in those with

  9. Severity of motor dysfunction in children with cerebral palsy seen in Enugu, Nigeria.

    Science.gov (United States)

    Ogoke, Christian Chukwukere; Iloeje, Sylvester Onabeke

    2017-01-01

    Children with cerebral palsy (CP) have gross motor dysfunction (GMD) of varying degrees of severity. The Gross Motor Function Classification System (GMFCS) is widely used internationally to classify children with CP into functional severity levels. There are few reports on the use of GMFCS in Nigeria to determine the severity of motor dysfunction in children with CP. This study aims to classify children with CP in Enugu on the basis of severity of their GMD in order to ascertain their management needs. The study was a cross sectional observational study and sample selection was by consecutive recruitment. One hundred (100) children with CP aged 9 - 96 months, attending two Pediatric Neurology Clinics in Enugu, were consecutively recruited. Relevant history was taken including modalities of treatment received. Neurological examination was done and the GMFCS manual was used to classify the children into levels of severity. GMD varied in severity in the patients from mild (47%) (GMFCS levels I & II) to moderate (7%) (GMFCS levels III) and to severe (46%) (GMFCS levels IV & V). Those in levels I - III (54%) were ambulatory while those in levels IV & V (46%) were non-ambulatory. Of the 53 that required mobility assistive device, only 6 (11.3%) were using one. More than half of CP patients seen in Enugu were ambulatory with mild to moderate motor dysfunction based on the GMFCS. Only a few of our patients are appropriately rehabilitated with augmentative interventions.

  10. The quality of the early motor repertoire in preterm infants predicts minor neurologic dysfunction at school age

    NARCIS (Netherlands)

    Bruggink, Janneke L. M.; Einspieler, Christa; Butcher, Phillipa R.; Van Braeckel, Koenraad N. J. A.; Prechtl, Heinz F. R.; Bos, Arend F.

    Objective The quality of a child's motor repertoire at age 3 to 4 months postterm is predictive of later cerebral palsy (CP). Its predictive power for minor neurologic dysfunction (MND) is unclear. This study aimed to investigate the predictive value of the quality of the early motor repertoire for

  11. Clinical biomechanic correlates of cervical dysfunction: Part 4. Altered regional motor behavior.

    Science.gov (United States)

    Vorro, J; Johnston, W L

    1998-06-01

    The present study examined organizational patterns of individual muscular contributions to head and neck motion. Previous studies of asymptomatic subjects with cervical motor asymmetry identified significant kinematic and myoelectric alterations. The current study evaluated 34 asymptomatic subjects categorized as to symmetry group based on initial palpatory test comparing regional motion responses of the head and neck to sidebending right and left. Electromyographic techniques were used to study muscular activity, indicating contraction frequency for each muscle monitored during active and passive test motions. Subjects with diagnosed regional motion asymmetry exhibited a significantly altered organization of electrically active and electrically silent muscles. Their pattern of muscle contraction was compromised just as frequently in the passive as in the active phases of motion. A positive sign of motion asymmetry on physical examination of the cervical region alerts the physician early to the presence of significant dysfunction in motor organization for efficient head/neck movement. The adaptive motor patterning in dysfunction can occur before the appearance of subjective pain.

  12. Candesartan, rather than losartan, improves motor dysfunction in thioacetamide-induced chronic liver failure in rats

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    H.A. Murad

    2017-09-01

    Full Text Available Minimal hepatic encephalopathy is more common than the acute syndrome. Losartan, the first angiotensin-II receptor blocker (ARB, and candesartan, another widely-used ARB, have protected against developing fibrogenesis, but there is no clear data about their curative antifibrotic effects. The current study was designed to examine their effects in an already-established model of hepatic fibrosis and also their effects on the associated motor dysfunction. Low-grade chronic liver failure (CLF was induced in 3-month old Sprague-Dawley male rats using thioacetamide (TAA, 50 mg·kg−1·day−1 intraperitoneally for 2 weeks. The TAA-CLF rats were randomly divided into five groups (n=8 treated orally for 14 days (mg·kg−1·day−1 as follows: TAA (distilled water, losartan (5 and 10 mg/kg, and candesartan (0.1 and 0.3 mg/kg. Rats were tested for rotarod and open-field tests. Serum and hepatic biochemical markers, and hepatic histopathological changes were evaluated by H&E and Masson's staining. The TAA-CLF rats showed significant increases of hepatic malondialdehyde, hepatic expression of tumor necrosis factor-α (TNF-α, and serum ammonia, alanine aminotransferase, γ-glutamyl transferase, TNF-α, and malondialdehyde levels as well as significant decreases of hepatic and serum glutathione levels. All treatments significantly reversed these changes. The histopathological changes were moderate in losartan-5 and candesartan-0.1 groups and mild in losartan-10 and candesartan-0.3 groups. Only candesartan significantly improved TAA-induced motor dysfunction. In conclusion, therapeutic antifibrotic effects of losartan and candesartan in thioacetamide-induced hepatic fibrosis in rats are possibly through angiotensin-II receptor blocking, antioxidant, and anti-inflammatory activities. Improved motor dysfunction by candesartan could be attributed to better brain penetration and slower “off-rate” from angiotensin-II receptors. Clinical trials are

  13. Candesartan, rather than losartan, improves motor dysfunction in thioacetamide-induced chronic liver failure in rats.

    Science.gov (United States)

    Murad, H A; Gazzaz, Z J; Ali, S S; Ibraheem, M S

    2017-09-21

    Minimal hepatic encephalopathy is more common than the acute syndrome. Losartan, the first angiotensin-II receptor blocker (ARB), and candesartan, another widely-used ARB, have protected against developing fibrogenesis, but there is no clear data about their curative antifibrotic effects. The current study was designed to examine their effects in an already-established model of hepatic fibrosis and also their effects on the associated motor dysfunction. Low-grade chronic liver failure (CLF) was induced in 3-month old Sprague-Dawley male rats using thioacetamide (TAA, 50 mg·kg-1·day-1) intraperitoneally for 2 weeks. The TAA-CLF rats were randomly divided into five groups (n=8) treated orally for 14 days (mg·kg-1·day-1) as follows: TAA (distilled water), losartan (5 and 10 mg/kg), and candesartan (0.1 and 0.3 mg/kg). Rats were tested for rotarod and open-field tests. Serum and hepatic biochemical markers, and hepatic histopathological changes were evaluated by H&E and Masson's staining. The TAA-CLF rats showed significant increases of hepatic malondialdehyde, hepatic expression of tumor necrosis factor-α (TNF-α), and serum ammonia, alanine aminotransferase, γ-glutamyl transferase, TNF-α, and malondialdehyde levels as well as significant decreases of hepatic and serum glutathione levels. All treatments significantly reversed these changes. The histopathological changes were moderate in losartan-5 and candesartan-0.1 groups and mild in losartan-10 and candesartan-0.3 groups. Only candesartan significantly improved TAA-induced motor dysfunction. In conclusion, therapeutic antifibrotic effects of losartan and candesartan in thioacetamide-induced hepatic fibrosis in rats are possibly through angiotensin-II receptor blocking, antioxidant, and anti-inflammatory activities. Improved motor dysfunction by candesartan could be attributed to better brain penetration and slower "off-rate" from angiotensin-II receptors. Clinical trials are recommended.

  14. Synergistic exacerbation of mitochondrial and synaptic dysfunction and resultant learning and memory deficit in a mouse model of diabetic Alzheimer's disease.

    Science.gov (United States)

    Wang, Yongfu; Wu, Long; Li, Jianping; Fang, Du; Zhong, Changjia; Chen, John Xi; Yan, Shirley ShiDu

    2015-01-01

    Diabetes is considered to be a risk factor in Alzheimer's disease (AD) pathogenesis. Although recent evidence indicates that diabetes exaggerates pathologic features of AD, the underlying mechanisms are not well understood. To determine whether mitochondrial perturbation is associated with the contribution of diabetes to AD progression, we characterized mouse models of streptozotocin (STZ)-induced type 1 diabetes and transgenic AD mouse models with diabetes. Brains from mice with STZ-induced diabetes revealed a significant increase of cyclophilin D (CypD) expression, reduced respiratory function, and decreased hippocampal long-term potentiation (LTP); these animals had impaired spatial learning and memory. Hyperglycemia exacerbated the upregulation of CypD, mitochondrial defects, synaptic injury, and cognitive dysfunction in the brains of transgenic AD mice overexpressing amyloid-β as shown by decreased mitochondrial respiratory complex I and IV enzyme activity and greatly decreased mitochondrial respiratory rate. Concomitantly, hippocampal LTP reduction and spatial learning and memory decline, two early pathologic indicators of AD, were enhanced in the brains of diabetic AD mice. Our results suggest that the synergistic interaction between effects of diabetes and AD on mitochondria may be responsible for brain dysfunction that is in common in both diabetes and AD.

  15. Synergistic Exacerbation of Mitochondrial and Synaptic Dysfunction and Resultant Learning and Memory Deficit in a Mouse Model of Diabetic Alzheimer’s Disease

    Science.gov (United States)

    Wang, Yongfu; Wu, Long; Li, Jianping; Fang, Du; Zhong, Changjia; Chen, John Xi; Yan, Shirley ShiDu

    2015-01-01

    Diabetes is considered to be a risk factor in Alzheimer’s disease (AD) pathogenesis. Although recent evidence indicates that diabetes exaggerates pathologic features of AD, the underlying mechanisms are not well understood. To determine whether mitochondrial perturbation is associated with the contribution of diabetes to AD progression, we characterized mouse models of streptozotocin (STZ)-induced type 1 diabetes and transgenic AD mouse models with diabetes. Brains from mice with STZ-induced diabetes revealed a significant increase of cyclophilin D (CypD) expression, reduced respiratory function, and decreased hippocampal long-term potentiation (LTP); these animals had impaired spatial learning and memory. Hyperglycemia exacerbated the upregulation of CypD, mitochondrial defects, synaptic injury, and cognitive dysfunction in the brains of transgenic AD mice overexpressing amyloid-β as shown by decreased mitochondrial respiratory complex I and IV enzyme activity and greatly decreased mitochondrial respiratory rate. Concomitantly, hippocampal LTP reduction and spatial learning and memory decline, two early pathologic indicators of AD, were enhanced in the brains of diabetic AD mice. Our results suggest that the synergistic interaction between effects of diabetes and AD on mitochondria may be responsible for brain dysfunction that is in common in both diabetes and AD. PMID:25096625

  16. Significance of NT-pro-BNP in acute exacerbation of COPD patients without underlying left ventricular dysfunction

    Directory of Open Access Journals (Sweden)

    Adrish M

    2017-04-01

    Full Text Available Muhammad Adrish,1 Varalaxmi Bhavani Nannaka,2 Edison J Cano,3 Bharat Bajantri,1 Gilda Diaz-Fuentes1 1Division of Pulmonary and Critical Care Medicine, Bronx-Lebanon Hospital Center, Icahn School of Medicine at Mount Sinai, 2Department of Critical Care Medicine, Montefiore Medical Center, The University Hospital for Albert Einstein College of Medicine, 3Department of Medicine, Bronx-Lebanon Hospital Center, Icahn School of Medicine at Mount Sinai, Bronx, NY, USA Background: B-type natriuretic peptide (BNP and the N-terminal fragment of pro-BNP (NT-pro-BNP are established biomarkers of heart failure. Increased levels of natriuretic peptide (NP have been associated with poor outcomes in acute exacerbation of COPD (AECOPD; however, most studies did not address the conditions that can also increase NT-pro-BNP levels. We aimed to determine if NT-pro-BNP levels correlate with outcomes of AECOPD in patients without heart failure and other conditions that can affect NT-pro-BNP levels.Methods: We conducted a retrospective study in patients hospitalized for AECOPD with available NT-pro-BNP levels and normal left ventricular ejection fraction. We compared patients with normal and elevated NT-pro-BNP levels and analyzed the clinical and outcome data.Results: A total of 167 of 1,420 (11.7% patients met the study criteria. A total of 77% of male patients and 53% of female patients had elevated NT-pro-BNP levels (P=0.0031. NT-pro-BNP levels were not associated with COPD severity and comorbid illnesses. Log-transformed NT-pro-BNP levels were positively associated with echocardiographically estimated right ventricular systolic pressure (r=0.3658; 95% confidence interval [CI]: 0.2060–0.5067; P<0.0001. Patients with elevated NT-pro-BNP levels were more likely to require intensive care (63% vs 43%; P=0.0207 and had a longer hospital length of stay (P=0.0052. There were no differences in the need for noninvasive positive pressure ventilation (P=0.1245 or mechanical

  17. Comparative analysis of speech impairment and upper limb motor dysfunction in Parkinson's disease.

    Science.gov (United States)

    Rusz, Jan; Tykalová, Tereza; Krupička, Radim; Zárubová, Kateřina; Novotný, Michal; Jech, Robert; Szabó, Zoltán; Růžička, Evžen

    2017-04-01

    It is currently unknown whether speech and limb motor effectors in Parkinson's disease (PD) are controlled by similar underlying brain processes. Based on computerized objective analysis, the aim of this study was to evaluate potential correlation between speech and mechanical tests of upper limb motor function. Speech and upper limb motor tests were performed in 22 PD patients and 22 healthy controls. Quantitative acoustic analyses of eight key speech dimensions of hypokinetic dysarthria, including quality of voice, sequential motion rates, consonant articulation, vowel articulation, average loudness, loudness variability, pitch variability, and number of pauses, were performed. Upper limb movements were assessed using the motor part of the Unified Parkinson's Disease Rating Scale, contactless three-dimensional motion capture system, blinded expert evaluation, and the Purdue Pegboard Test. Significant relationships were observed between the quality of voice assessed by jitter and amplitude decrement of finger tapping (r = 0.61, p = 0.003), consonant articulation evaluated using voice onset time and expert rating of finger tapping (r = 0.60, p = 0.003), and number of pauses and Purdue Pegboard Test score (r = 0.60, p = 0.004). The current study supports the hypothesis that speech impairment in PD shares, at least partially, similar pathophysiological processes with limb motor dysfunction. Vocal fold vibration irregularities appeared to be influenced by mechanisms similar to amplitude decrement during repetitive limb movements. Consonant articulation deficits were associated with decreased manual dexterity and movement speed, likely reflecting fine motor control involvement in PD.

  18. Selective loss of noradrenaline exacerbates early cognitive dysfunction and synaptic deficits in APP/PS1 mice

    Science.gov (United States)

    Hammerschmidt, Thea; Kummer, Markus P.; Terwel, Dick; Martinez, Ana; Gorji, Ali; Pape, Hans-Christian; Rommelfanger, Karen S.; Schroeder, Jason P.; Stoll, Monika; Schultze, Joachim; Weinshenker, David; Heneka, Michael T.

    2016-01-01

    Background Degeneration of the locus ceruleus (LC), the major noradrenergic nucleus in the brain, occurs early and is ubiquitous in Alzheimer’s disease. Experimental lesions to the LC exacerbate AD-like neuropathology and cognitive deficits in several transgenic mouse models of AD. Because the LC contains multiple neuromodulators known to affect Aβ toxicity and cognitive function, the specific role of noradrenaline (NA) in AD is not well understood. Methods To determine the consequences of selective NA deficiency in an AD mouse model, we crossed dopamine β-hydroxylase (DBH) knock-out mice with APP/PS1 mice, overexpressing mutant amyloid precursor protein and presenilin-1. DBH (−/−) mice are unable to synthesize NA but otherwise have normal LC neurons and co-transmitters. Spatial memory, hippocampal long-term potentiation (LTP), and synaptic protein levels were assessed. Results The modest impairments in spatial memory and hippocampal LTP displayed by young APP/PS1 or DBH(−/−) single mutant mice were augmented in DBH(−/−)/APP/PS1 double mutant mice. Deficits were associated with reduced levels of total Ca2+/calmodulin-dependent protein kinases II (CaMKII) and N-Methyl-D-aspartate receptor 2A (NR2A), increased N-Methyl-D-aspartate receptor 2B (NR2B) levels and were independent of Aβ accumulation. Spatial memory performance was partly improved by treatment with the NA precursor drug L-threo-DOPS. Conclusions These results indicate that early LC degeneration and subsequent NA deficiency in AD may contribute to cognitive deficits via altered levels of CaMKII and N-Methyl-D-aspartate receptors, and suggest that NA supplementation could be beneficial in early AD. PMID:22883210

  19. In vivo impact of presynaptic calcium channel dysfunction on motor axons in episodic ataxia type 2.

    Science.gov (United States)

    Tomlinson, Susan E; Tan, S Veronica; Burke, David; Labrum, Robyn W; Haworth, Andrea; Gibbons, Vaneesha S; Sweeney, Mary G; Griggs, Robert C; Kullmann, Dimitri M; Bostock, Hugh; Hanna, Michael G

    2016-02-01

    Ion channel dysfunction causes a range of neurological disorders by altering transmembrane ion fluxes, neuronal or muscle excitability, and neurotransmitter release. Genetic neuronal channelopathies affecting peripheral axons provide a unique opportunity to examine the impact of dysfunction of a single channel subtype in detail in vivo. Episodic ataxia type 2 is caused by mutations in CACNA1A, which encodes the pore-forming subunit of the neuronal voltage-gated calcium channel Cav2.1. In peripheral motor axons, this channel is highly expressed at the presynaptic neuromuscular junction where it contributes to action potential-evoked neurotransmitter release, but it is not expressed mid-axon or thought to contribute to action potential generation. Eight patients from five families with genetically confirmed episodic ataxia type 2 underwent neurophysiological assessment to determine whether axonal excitability was normal and, if not, whether changes could be explained by Cav2.1 dysfunction. New mutations in the CACNA1A gene were identified in two families. Nerve conduction studies were normal, but increased jitter in single-fibre EMG studies indicated unstable neuromuscular transmission in two patients. Excitability properties of median motor axons were compared with those in 30 age-matched healthy control subjects. All patients had similar excitability abnormalities, including a high electrical threshold and increased responses to hyperpolarizing (P ataxia type 2 thus has unexpected effects on axon excitability, which may reflect an indirect effect of abnormal calcium current fluxes during development. © The Author (2016). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved.

  20. Dysfunctional HDL containing L159R ApoA-I leads to exacerbation of atherosclerosis in hyperlipidemic mice.

    Science.gov (United States)

    Sorci-Thomas, Mary G; Zabalawi, Manal; Bharadwaj, Manish S; Wilhelm, Ashley J; Owen, John S; Asztalos, Bela F; Bhat, Shaila; Thomas, Michael J

    2012-03-01

    The mutation L159R apoA-I or apoA-I(L159R) (FIN) is a single amino acid substitution within the sixth helical repeat of apoA-I. It is associated with a dominant negative phenotype, displaying hypoalphaproteinemia and an increased risk for atherosclerosis in humans. Mice lacking both mouse apoA-I and LDL receptor (LDL(-/-), apoA-I(-/-)) (double knockout or DKO) were crossed>9 generations with mice transgenic for human FIN to obtain L159R apoA-I, LDLr(-/-), ApoA-I(-/-) (FIN-DKO) mice. A similar cross was also performed with human wild-type (WT) apoA-I (WT-DKO). In addition, FIN-DKO and WT-DKO were crossed to obtain WT/FIN-DKO mice. To determine the effects of the apoA-I mutations on atherosclerosis, groups of each genotype were fed either chow or an atherogenic diet for 12weeks. Interestingly, the production of dysfunctional HDL-like particles occurred in DKO and FIN-DKO mice. These particles were distinct with respect to size, and their enrichment in apoE and cholesterol esters. Two-dimensional gel electrophoresis indicated that particles found in the plasma of FIN-DKO mice migrated as large α(3)-HDL. Atherosclerosis analysis showed that FIN-DKO mice developed the greatest extent of aortic cholesterol accumulation compared to all other genotypes, including DKO mice which lack any apoA-I. Taken together these data suggest that the presence of large apoE enriched HDL particles containing apoA-I L159R lack the normal cholesterol efflux promoting properties of HDL, rendering them dysfunctional and pro-atherogenic. In conclusion, large HDL-like particles containing apoE and apoA-I(L159R) contribute rather than protect against atherosclerosis, possibly through defective efflux properties and their potential for aggregation at their site of interaction in the aorta. This article is part of a Special Issue entitled Advances in High Density Lipoprotein Formation and Metabolism: A Tribute to John F. Oram (1945-2010). Copyright © 2011 Elsevier B.V. All rights reserved.

  1. Overexpression myocardial inducible nitric oxide synthase exacerbates cardiac dysfunction and beta-adrenergic desensitization in experimental hypothyroidism.

    Science.gov (United States)

    Shao, Qun; Cheng, Heng-Jie; Callahan, Michael F; Kitzman, Dalane W; Li, Wei-Min; Cheng, Che Ping

    2016-02-01

    Altered nitric oxide synthase (NOS) has been implicated in the pathophysiology of heart failure (HF). Recent evidence links hypothyroidism to the pathology of HF. However, the precise mechanisms are incompletely understood. The alterations and functional effects of cardiac NOS in hypothyroidism are unknown. We tested the hypothesis that hypothyroidism increases cardiomyocyte inducible NOS (iNOS) expression, which plays an important role in hypothyroidism-induced depression of cardiomyocyte contractile properties, [Ca(2+)]i transient ([Ca(2+)]iT), and β-adrenergic hyporesponsiveness. We simultaneously evaluated LV functional performance and compared myocyte three NOS, β-adrenergic receptors (AR) and SERCA2a expressions and assessed cardiomyocyte contractile and [Ca(2+)]iT responses to β-AR stimulation with and without pretreatment of iNOS inhibitor (1400 W, 10(-5)mol/L) in 26 controls and 26 rats with hypothyroidism induced by methimazole (~30 mg/kg/day for 8 weeks in the drinking water). Compared with controls, in hypothyroidism, total serum T3 and T4 were significantly reduced followed by significantly decreased LV contractility (EES) with increased LV time constant of relaxation. These LV abnormalities were accompanied by concomitant significant decreases in myocyte contraction (dL/dtmax), relaxation (dR/dtmax), and [Ca(2+)]iT. In hypothyroidism, isoproterenol (10(-8)M) produced significantly smaller increases in dL/dtmax, dR/dtmax and [Ca(2+)]iT. These changes were associated with decreased β1-AR and SERCA2a, but significantly increased iNOS. Moreover, only in hypothyroidism, pretreatment with iNOS inhibitor significantly improved basal and isoproterenol-stimulated myocyte contraction, relaxation and [Ca(2+)]iT. Hypothyroidism produces intrinsic defects of LV myocyte force-generating capacity and relaxation with β-AR desensitization. Up-regulation of cardiomyocyte iNOS may promote progressive cardiac dysfunction in hypothyroidism. Copyright © 2015 Elsevier

  2. Overexpression Myocardial Inducible Nitric Oxide Synthase Exacerbates Cardiac Dysfunction and Beta-Adrenergic Desensitization in Experimental Hypothyroidism☆,☆☆

    Science.gov (United States)

    Shao, Qun; Cheng, Heng-Jie; Callahan, Michael F.; Kitzman, Dalane W; Li, Wei-Min; Cheng, Che Ping

    2015-01-01

    Background Altered nitric oxide synthase (NOS) has been implicated in the pathophysiology of heart failure (HF). Recent evidence links hypothyroidism to the pathology of HF. However, the precise mechanisms are incompletely understood. The alterations and functional effects of cardiac NOS in hypothyroidism are unknown. We tested the hypothesis that hypothyroidism increases cadiomyocyte inducible NOS (iNOS) expression, which plays an important role in hypothyroidism-induced depression of cardiomyocyte contractile properties, [Ca2+]i transient ([Ca2+]iT), and β-adrenergic hyporesponsiveness. Methods and Results We simultaneously evaluated LV functional performance and compared myocyte three NOS, β-adrenergic receptors (AR) and SERCA2a expressions and assessed cardiomyocyte contractile and [Ca2+]iT responses to β-AR stimulation with and without pretreatment of iNOS inhibitor (1400W, 10−5 mol/L) in 26 controls and 26 rats with hypothyroidism induced by methimazole (~30 mg/kg/day for 8 weeks in the drinking water). Compared with controls, in hypothyroidism, total serum T3 and T4 were significantly reduced followed by significantly decreased LV contractility (EES) with increased LV time constant of relaxation. These LV abnormalities were accompanied by concomitant significant decreases in myocyte contraction (dL/dtmax), relaxation (dR/dtmax), and [Ca2+]iT. In hypothyroidism, isoproterenol (10−8 M) produced significantly smaller increases in dL/dtmax, dR/dtmax and [Ca2+]iT. These changes were associated with decreased β1-AR and SERCA2a, but significantly increased iNOS. Moreover, only in hypothyroidism, pretreatment with iNOS inhibitor significantly improved basal and isoproterenol-stimulated myocyte contraction, relaxation and [Ca2+]iT. Conclusions Hypothyroidism produces intrinsic defects of LV myocyte force-generating capacity and relaxation with β-AR desensitization. Up-regulation of cadiomyocyte iNOS may promote progressive cardiac dysfunction in

  3. Pathophysiology of Motor Dysfunction in Parkinson’s Disease as the Rationale for Drug Treatment and Rehabilitation

    Directory of Open Access Journals (Sweden)

    Francesca Magrinelli

    2016-01-01

    Full Text Available Cardinal motor features of Parkinson’s disease (PD include bradykinesia, rest tremor, and rigidity, which appear in the early stages of the disease and largely depend on dopaminergic nigrostriatal denervation. Intermediate and advanced PD stages are characterized by motor fluctuations and dyskinesia, which depend on complex mechanisms secondary to severe nigrostriatal loss and to the problems related to oral levodopa absorption, and motor and nonmotor symptoms and signs that are secondary to marked dopaminergic loss and multisystem neurodegeneration with damage to nondopaminergic pathways. Nondopaminergic dysfunction results in motor problems, including posture, balance and gait disturbances, and fatigue, and nonmotor problems, encompassing depression, apathy, cognitive impairment, sleep disturbances, pain, and autonomic dysfunction. There are a number of symptomatic drugs for PD motor signs, but the pharmacological resources for nonmotor signs and symptoms are limited, and rehabilitation may contribute to their treatment. The present review will focus on classical notions and recent insights into the neuropathology, neuropharmacology, and neurophysiology of motor dysfunction of PD. These pieces of information represent the basis for the pharmacological, neurosurgical, and rehabilitative approaches to PD.

  4. Relationships linking emotional, motor, cognitive and GABAergic dysfunctions in dystrophin-deficient mdx mice.

    Science.gov (United States)

    Vaillend, Cyrille; Chaussenot, Rémi

    2017-03-15

    Alterations in the Duchenne muscular dystrophy (DMD) gene have been associated with enhanced stress reactivity in vertebrate species, suggesting a role for brain dystrophin in fear-related behavioral and cognitive processes. Because the loss of dystrophin (Dp427) reduces clustering of central γ-aminobutyric acid (GABAA) receptors, it is suspected that local inhibitory tuning and modulation of neuronal excitability are perturbed in a distributed brain circuit that normally controls such critical behavioral functions. In this study, we undertook a large-scale behavioral study to evaluate fear-related behavioral disturbances in dystrophin-deficient mdx mice. We first characterized the behavioral determinants of the enhanced fearfulness displayed by mdx mice following mild acute stress and its association with increased anxiety and altered fear memories. We further demonstrated that this enhanced fearfulness induces long-lasting motor inhibition, suggesting that neurobehavioral dysfunctions significantly influence motor outcome measures in this model. We also found that mdx mice are more sensitive to the sedative and hypnotic effects of 4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol hydrochlorid (THIP), a selective pharmacological activator of extrasynaptic GABAA receptors involved in central tonic inhibition. Our results highlight that information on the emotional aspects of mdx mice are important to better understand the bases of intellectual and neuropsychiatric defects in DMD and to better define valuable functional readouts for preclinical studies. Our data also support the hypothesis that altered spatial localization of GABAA receptors due to Dp427 loss is a pathological mechanism associated with brain dysfunction in DMD, suggesting that extrasynaptic GABAA receptors might be candidate targets for future therapeutic developments. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  5. Dysfunctions of the basal ganglia-cerebellar-thalamo-cortical system produce motor tics in Tourette syndrome.

    Directory of Open Access Journals (Sweden)

    Daniele Caligiore

    2017-03-01

    Full Text Available Motor tics are a cardinal feature of Tourette syndrome and are traditionally associated with an excess of striatal dopamine in the basal ganglia. Recent evidence increasingly supports a more articulated view where cerebellum and cortex, working closely in concert with basal ganglia, are also involved in tic production. Building on such evidence, this article proposes a computational model of the basal ganglia-cerebellar-thalamo-cortical system to study how motor tics are generated in Tourette syndrome. In particular, the model: (i reproduces the main results of recent experiments about the involvement of the basal ganglia-cerebellar-thalamo-cortical system in tic generation; (ii suggests an explanation of the system-level mechanisms underlying motor tic production: in this respect, the model predicts that the interplay between dopaminergic signal and cortical activity contributes to triggering the tic event and that the recently discovered basal ganglia-cerebellar anatomical pathway may support the involvement of the cerebellum in tic production; (iii furnishes predictions on the amount of tics generated when striatal dopamine increases and when the cortex is externally stimulated. These predictions could be important in identifying new brain target areas for future therapies. Finally, the model represents the first computational attempt to study the role of the recently discovered basal ganglia-cerebellar anatomical links. Studying this non-cortex-mediated basal ganglia-cerebellar interaction could radically change our perspective about how these areas interact with each other and with the cortex. Overall, the model also shows the utility of casting Tourette syndrome within a system-level perspective rather than viewing it as related to the dysfunction of a single brain area.

  6. Detecting neuronal dysfunction of hand motor cortex in ALS: A MRSI study.

    Science.gov (United States)

    Wang, Yuzhou; Li, Xiaodi; Chen, Wenming; Wang, Zhanhang; Xu, Yan; Luo, Jingpan; Lin, Hanbo; Sun, Guijun

    2017-03-01

    Although hand motor cortex (HMC) has been constantly used for identification of primary motor cortex in magnetic resonance spectroscopy (MRS) studies of amyotrophic lateral sclerosis (ALS), neurochemical profiles of HMC have never been assessed independently. As HMC has a constant location and the clinic-anatomic correlation between hand motor function and HMC has been established, we hypothesize that HMC may serve as a promising region of interest in diagnosing ALS. Fourteen ALS patients and 14 age- and gender-matched healthy controls (HC) were recruited in this study. An optimized magnetic resonance spectroscopic imaging (MRSI) method was developed and for each subject bilateral HMC areas were scanned separately (two-dimensional multi-voxel MRSI, voxel size 0.56 cm(3)). N-acetyl aspartate (NAA)-creatine (Cr) ratio was measured from HMC and the adjacent postcentral gyrus. Compared with HC, NAA/Cr ratios from HMC and the postcentral gyrus were significantly reduced in ALS. However, in each group the difference of NAA/Cr ratios between HMC and the postcentral gyrus was not significant. Limb predominance of HMC was not found in either ALS or HC. In ALS, there was a significant difference in NAA/Cr ratio between the most affected HMC and the less affected HMC. A positive relationship between NAA/Cr ratio of HMC and the severity of hand strength (assessed by finger tapping speed) was demonstrated. Neuronal dysfunction of HMC can differentiate ALS patients from HC when represented as reduced NAA/Cr ratio. Postcentral gyrus could not serve as normal internal reference tissue in diagnosing ALS. Asymmetrical NAA/Cr ratios from bilateral HMC may serve as a promising diagnostic biomarker of ALS at the individual level.

  7. Is gut the "motor" for producing hepatocellular dysfunction after trauma and hemorrhagic shock?

    Science.gov (United States)

    Wang, P; Ba, Z F; Cioffi, W G; Bland, K I; Chaudry, I H

    1998-02-01

    Although studies suggest that the gut may be the "motor" responsible for producing sepsis and multiple organ failure after injury, it is not known whether enterectomy prior to the onset of hemorrhage alters proinflammatory cytokines TNF and IL-6 and, if so, whether hepatocellular dysfunction and damage are prevented or attenuated under such conditions. Under methoxyflurane anesthesia, an enterectomy in the rat was performed by excision of the duodenum, jejunum, and ileum. The rats were then bled to and maintained at a mean arterial pressure of 40 mm Hg until 40% of the maximal shed volume was returned in the form of Ringer's lactate. The animals were then resuscitated with four times the volume of shed blood with Ringer's lactate over 1 h. At 1.5 h after the completion of resuscitation, hepatocellular function [i.e., the maximal velocity (Vmax) and transport efficiency (Km) of indocyanine green (ICG) clearance] was assessed by an in vivo ICG clearance technique. Blood samples were taken for the measurement of TNF, IL-6, and liver enzymes (i.e., SGPT and SGOT). Cardiac output and microvascular blood flow were determined by ICG dilution and laser Doppler flowmetry, respectively. The increase in circulating levels of TNF but not IL-6 was prevented by enterectomy prior to hemorrhage. The reduced Vmax and K(m) and elevated SGPT and SGOT following hemorrhage and resuscitation, however, were not significantly affected by prior enterectomy. Moreover, enterectomy before hemorrhage further reduced hepatic perfusion. Since enterectomy prior to the onset of hemorrhage does not prevent or attenuate the reduced ICG clearance and elevated liver enzymes despite downregulation of TNF production, it appears that the small intestine does not play a significant role in producing hepatocellular dysfunction and injury following trauma and hemorrhagic shock.

  8. [Motor dysfunction in stroke of subacute stage treated with acupuncture: multi-central randomized controlled study].

    Science.gov (United States)

    Chen, Li-Fang; Fang, Jian-Qiao; Wu, Yuan-Yuan; Ma, Rui-Jie; Xu, Shou-Yu; Shen, Lai-Hua; Luo, Kai-Tao; Gao, Feng; Bao, Ye-Hua; Ni, Ke-Feng; Li, Li-Ping

    2014-04-01

    To verify the clinical efficacy of acupuncture on motor dysfunction in ischemic stroke of subacute stage. The multi-central randomized controlled trial was adopted. One hundred and twenty-six cases of ischemic stroke of subacute stage were randomized into an acupuncture group (61 cases) and a conventional treatment group (65 cases). The basic treatment of western internal medicine and rehabilitation training were applied to the patients of the two groups. In the acupuncture group, acupuncture was supplemented at the body points located on the extensor of the upper limbs and the flexor of the lower limbs. In combination, scalp acupuncture was applied to NS5, MS6 and MS6 on the affected side. The treatment was given 5 times a week and totally 8 weeks were required. The follow-up observation lasted for 3 months. The scores in Fugl-Meyer scale and NIHSS scale and Barthel index were compared between the two groups before treatment, in 4 and 8 weeks of treatment and the 3-month follow-up observation after treatment separately. In 4 and 8 weeks of treatment and the follow-up observation, Fugl-Meyer scale score was improved obviously in the patients of the two groups (all Pacupuncture groupwas im proved much apparently as compared with that in the conventional treatment group [68. 0 (43. 0,86. 5) vs 52. 5 (30.3, 77.0), 77.0 (49.5, 89.0) vs 63. 0 (33.0, 84.0), both P0.05), the results of NIHSS scale at the other time points were all decreased obviously as compared with those before treatment in the patients of the two groups (all Pacupuncture group were reduced much apparently as compared with those in the conventional treatment group [5. 0 (3.0,8.0) vs 7. 0 (3.0,13.8), 4. 0 (1.5,7.0) vs 6.0 (2.0,11.7) ,both Pacupuncture group was much more significant as compared with the conventional treatment group [75. 0 (60. 0,87. 5) vs 65. O (36. 3, 87. 5), PAcupuncture achieves the satisfactory clinical efficacy on motor dysfunction in ischemic stroke of subacute stage.

  9. Transcranial magnetic stimulation as an investigative tool for motor dysfunction and recovery in stroke: an overview for neurorehabilitation clinicians

    Science.gov (United States)

    Cortes, Mar; Black-Schaffer, Randie M; Edwards, Dylan J

    2012-01-01

    Rationale An improved understanding of motor dysfunction and recovery after stroke has important clinical implications that may lead to the design of more effective rehabilitation strategies for patients with hemiparesis. Scope Transcranial magnetic stimulation (TMS) is a safe and painless tool that has been used in conjunction with other existing diagnostic tools to investigate motor pathophysiology in stroke patients. Since TMS emerged over two decades ago, its application in clinical and basic neuroscience has expanded worldwide. TMS can quantify the corticomotor excitability properties of clinically affected and unaffected muscles, and probe local cortical networks, as well as remote but functionally related areas. This provides novel insight into the physiology of neural circuits underlying motor dysfunction, and brain reorganization during the motor recovery process. This important tool needs to be used with caution by clinical investigators, its limitations need to be understood and the results should be interpreted along with clinical evaluation in this patient population. Summary In this review, we provide an overview of the rationale, implementation and limitations of TMS to study stroke motor physiology. This knowledge may be useful to guide future rehabilitation treatments by assessing and promoting functional plasticity. PMID:22624621

  10. Optimising the detection of upper motor neuron function dysfunction in amyotrophic lateral sclerosis--a transcranial magnetic stimulation study.

    Science.gov (United States)

    Osei-Lah, Abena D; Mills, Kerry R

    2004-11-01

    Evidence of upper motor neuron (UMN) dysfunction is essential in making the diagnosis of amyotrophic lateral sclerosis (ALS). Central motor conduction (CMC) abnormalities detected using transcranial magnetic stimulation (TMS) are presumed to reflect UMN dysfunction. CMC is, however, often normal in patients with classical sporadic ALS. The aim of the study was to determine whether the utility of the CMC measure in ALS could be enhanced. We measured CMC to four pairs of muscles (abductor digiti minimi (ADM), biceps, vastus medialis (VM) and abductor hallucis (AH) in 20 controls and 25 ALS patients. The commonest abnormality detected in the ALS patients was an absent MEP, found in 11 patients (44 %) and in 25 of 200 muscles examined. Studying a minimum of three muscles increased the probability of detecting UMN dysfunction. Weakness in the muscle as well as selecting a distal rather than a proximal muscle was significantly associated with an abnormal CMC. Interside differences in CMC were significantly more pronounced in the patient group. In 30% of patients a significant interside difference in AH CMC time was the sole abnormality, suggesting mild UMN dysfunction on the side with the longer CMC.

  11. Motor-evoked potential gain is a helpful test for the detection of corticospinal tract dysfunction in amyotrophic lateral sclerosis.

    Science.gov (United States)

    Duclos, Y; Grapperon, A M; Jouve, E; Truillet, R; Zemmour, C; Verschueren, A; Pouget, J; Attarian, S

    2017-02-01

    The detection of upper motor neuron (UMN) dysfunction is necessary for the diagnosis of amyotrophic lateral sclerosis (ALS). However, signs of UMN dysfunction may be difficult to establish. This study aimed to determine whether motor-evoked potential (MEP) gain (MEP area/background electromyographic activity) represents an efficient alternative to assess UMN dysfunction. MEP area, MEP/compound muscle action potential (CMAP) area ratio, and MEP gain were tested at different force levels in healthy control subjects and ALS patients. Receiver operating characteristic (ROC) curve analyses was used to determine the diagnostic utility of MEP gain and compare it to alternative techniques, namely, diffusion tensor imaging (DTI) and the triple stimulation technique (TST). MEP gain revealed a significant difference between the patients and healthy control subjects in contrast to MEP area and MEP/CMAP area ratio. The diagnostic utility of MEP gain was comparable with that of TST and superior to that of DTI. MEP gain can distinguish ALS patients from control subjects and may be helpful for the diagnosis of ALS. MEP gain appears to be a useful adjunct test and noninvasive method for the assessment of corticospinal dysfunction. Copyright © 2016 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.

  12. Executive dysfunction and motor symptoms in Parkinson's disease Disfunções executivas e sintomas motores na doença de Parkinson

    Directory of Open Access Journals (Sweden)

    Indira Silveira Campos-Sousa

    2010-04-01

    Full Text Available The aim of this study is to analyze executive function and motor symptoms in patients with idiopathic Parkinson's disease (PD. The sample consisted of 44 subjects with PD between the ages of 45 to 75, who were examined consecutively. The subjects were divided into two groups according to the duration of the disease. The control group was composed of spouses, family and accompanying members. Patients included were submitted to motor dysfunction evaluation using the UPDRS. The executive functions modalities analyzed included: operational memory, inhibitory control, planning, cognitive flexibility and inductive reasoning. Significant differences between the experimental and control groups were found in all the executive domains studied. Evidence of tremor, rigidity and bradykinesia correlation with executive dysfunction were not observed. Patients with PD, even in the initial phase of the disease, presented executive dysfunction. The cardinal motor signs of the disease were not correlated with the cognitive dysfunction found.O objetivo do estudo é avaliar as funções executivas e sintomas motores em pacientes portadores de doença de Parkinson. A amostra se constituiu de 44 portadores de doença de Parkinson com idade entre 45 e 75 anos, examinados consecutivamente, os quais foram divididos em dois grupos de acordo com o tempo de duração da doença. O grupo controle foi composto de acompanhantes ou cônjuges. Os sujeitos selecionados foram submetidos à avaliação motora utilizando-se a escala UPDRS e à avaliação das funções executivas nas modalidades: raciocínio indutivo, memória operacional, controle inibitório, planejamento e flexibilidade cognitiva. Os resultados apontaram diferenças significantes entre os grupos experimentais e controle nas modalidades analisadas. Não encontramos evidência de associação entre tremor, rigidez e bradicinesia com as funções executivas. Conclui-se que os pacientes com doença de Parkinson

  13. Heterozygous Polg mutation causes motor dysfunction due to mtDNA deletions

    Science.gov (United States)

    Fuke, Satoshi; Kametani, Mizue; Yamada, Kazuyuki; Kasahara, Takaoki; Kubota-Sakashita, Mie; Kujoth, Gregory C; Prolla, Tomas A; Hitoshi, Seiji; Kato, Tadafumi

    2014-01-01

    Objective Mutations in nuclear-encoded mitochondrial DNA (mtDNA) polymerase (POLG) are known to cause autosomal dominant chronic progressive external ophthalmoplegia (adCPEO) with accumulation of multiple mtDNA deletions in muscles. However, no animal model with a heterozygous Polg mutation representing mtDNA impairment and symptoms of CPEO has been established. To understand the pathogenic mechanism of CPEO, it is important to determine the age dependency and tissue specificity of mtDNA impairment resulting from a heterozygous mutation in the Polg gene in an animal model. Methods We assessed behavioral phenotypes, tissue-specific accumulation of mtDNA deletions, and its age dependency in heterozygous PolgD257A knock-in mice carrying a proofreading-deficient mutation in the Polg. Results Heterozygous PolgD257A knock-in mice exhibited motor dysfunction in a rotarod test. Polg+/D257A mice had significant accumulation of multiple mtDNA deletions, but did not show significant accumulation of point mutations or mtDNA depletion in the brain. While mtDNA deletions increased in an age-dependent manner regardless of the tissue even in Polg+/+ mice, the age-dependent accumulation of mtDNA deletions was enhanced in muscles and in the brain of Polg+/D257A mice. Interpretation Heterozygous PolgD257A knock-in mice showed tissue-specific, age-dependent accumulation of multiple mtDNA deletions in muscles and the brain which was likely to result in neuromuscular symptoms. Polg+/D257A mice may be used as an animal model of adCPEO associated with impaired mtDNA maintenance. PMID:25540805

  14. Functional MRI evidence for fine motor praxis dysfunction in children with persistent speech disorders

    Science.gov (United States)

    Redle, Erin; Vannest, Jennifer; Maloney, Thomas; Tsevat, Rebecca K.; Eikenberry, Sarah; Lewis, Barbara; Shriberg, Lawrence D.; Tkach, Jean; Holland, Scott K.

    2014-01-01

    Children with persistent speech disorders (PSD) often present with overt or subtle motor deficits; the possibility that speech disorders and motor deficits could arise from a shared neurological base is currently unknown. Functional MRI (fMRI) was used to examine the brain networks supporting fine motor praxis in children with PSD and without clinically identified fine motor deficits. Methods This case-control study included 12 children with PSD (mean age 7.42 years, 4 female) and 12 controls (mean age 7.44 years, 4 female). Children completed behavioral evaluations using standardized motor assessments and parent reported functional measures. During fMRI scanning, participants completed a cued finger tapping task contrasted passive listening. A general linear model approach identified brain regions associated with finger tapping in each group and regions that differed between groups. The relationship between regional fMRI activation and fine motor skill was assessed using a regression analysis. Results Children with PSD had significantly poorer results for rapid speech production and fine motor praxis skills, but did not differ on classroom functional skills. Functional MRI results showed that children with PSD had significantly more activation in the cerebellum during finger tapping. Positive correlations between performance on a fine motor praxis test and activation multiple cortical regions were noted for children with PSD but not for controls. Conclusions Over-activation in the cerebellum during a motor task may reflect a subtle abnormality in the non-speech motor neural circuitry in children with PSD. PMID:25481413

  15. Pathophysiology of Motor Dysfunction in Parkinson's Disease as the Rationale for Drug Treatment and Rehabilitation

    OpenAIRE

    Francesca Magrinelli; Alessandro Picelli; Pierluigi Tocco; Angela Federico; Laura Roncari; Nicola Smania; Giampietro Zanette; Stefano Tamburin

    2016-01-01

    Cardinal motor features of Parkinson’s disease (PD) include bradykinesia, rest tremor, and rigidity, which appear in the early stages of the disease and largely depend on dopaminergic nigrostriatal denervation. Intermediate and advanced PD stages are characterized by motor fluctuations and dyskinesia, which depend on complex mechanisms secondary to severe nigrostriatal loss and to the problems related to oral levodopa absorption, and motor and nonmotor symptoms and signs that are secondary to...

  16. Motor dysfunction in NF1: Mediated by attention deficit or inherent to the disorder?

    Science.gov (United States)

    Haas-Lude, Karin; Heimgärtner, Magdalena; Winter, Sarah; Mautner, Victor-Felix; Krägeloh-Mann, Ingeborg; Lidzba, Karen

    2018-01-01

    Attention deficit and compromised motor skills are both prevalent in Neurofibromatosis type 1 (NF1), but the relationship is unclear. We investigated motor function in children with NF1 and in children with Attention Deficit/Hyperactivity Disorder (ADHD), and explored if, in patients with NF1, attention deficit influences motor performance. Motor performance was measured using the Movement Assessment Battery for Children (M-ABC) in 71 children (26 with NF1 plus ADHD, 14 with NF1 without ADHD, and 31 with ADHD without NF1) aged 6-12 years. There was a significant effect of group on motor performance. Both NF1 groups scored below children with ADHD without NF1. Attention performance mediated motor performance in children with ADHD without NF1, but not in children with NF1. Motor function is not mediated by attention performance in children with NF1. While in ADHD, attention deficit influences motor performance, motor problems in NF1 seem to be independent from attention deficit. This argues for different pathomechanisms in these two groups of developmental disorders. Copyright © 2017 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

  17. Prevalence of non-motor dysfunction among Parkinson's disease patients from a tertiary referral center in Mexico City.

    Science.gov (United States)

    Rodríguez-Violante, Mayela; Cervantes-Arriaga, Amin; Villar-Velarde, Alejandra; Corona, Teresa

    2010-12-01

    Data on the frequency of non-motor symptoms among patients with Parkinson's disease (PD) in Mexico has not been reported. To study the prevalence of these symptoms in a sample of Mexican PD patients attending a referral neurologic center using the Non Motor Symptoms Questionnaire (NMSQuest) and the Non Motor Symtpoms Scale (NMSS). One-hundred consecutive PD patients, of all ages and disease severity were included in a cross-sectional design study. The NMSQuest and NMSS were applied during the "on" state. Sample had a mean age of 64.5±10.9 years and disease duration of 6.6±4.8 years. Total NMSQuest median score was 10 and the mean NMSS score was 69.3±56.7. Positive answers classified by domain were as follows: gastrointestinal symptoms 30%, urinary symptoms 60%, memory/attention/apathy 39%, hallucinations/delusions 16%, depression/anxiety 55%, sexual dysfunction 30%, cardiovascular symptoms 35%, sleep disorders 40% and miscellany 27%. The prevalence of non-motor symptoms among mexican patients with PD is similar to other countries. Mood, cognitive and perceptual symptoms seems to be more severe in our population. Copyright © 2010 Elsevier B.V. All rights reserved.

  18. Decreased tonic inhibition in cerebellar granule cells causes motor dysfunction in a mouse model of Angelman syndrome.

    Science.gov (United States)

    Egawa, Kiyoshi; Kitagawa, Kyoko; Inoue, Koichi; Takayama, Masakazu; Takayama, Chitoshi; Saitoh, Shinji; Kishino, Tatsuya; Kitagawa, Masatoshi; Fukuda, Atsuo

    2012-12-05

    Angelman syndrome is a neurodevelopmental disorder caused by loss of function of the UBE3A gene encoding a ubiquitin E3 ligase. Motor dysfunction is a characteristic feature of Angelman syndrome, but neither the mechanisms of action nor effective therapeutic strategies have yet been elucidated. We report that tonic inhibition is specifically decreased in cerebellar granule cells of Ube3a-deficient mice, a model of Angelman syndrome. As a mechanism underlying this decrease in tonic inhibition, we show that Ube3a controls degradation of γ-aminobutyric acid (GABA) transporter 1 (GAT1) and that deficiency of Ube3a induces a surplus of GAT1 that results in a decrease in GABA concentrations in the extrasynaptic space. Administering low doses of 4,5,6,7-tetrahydroisothiazolo-[5,4-c]pyridin-3-ol (THIP), a selective extrasynaptic GABA(A) receptor agonist, improves the abnormal firing properties of a population of Purkinje cells in cerebellar brain slices and reduces cerebellar ataxia in Ube3a-deficient mice in vivo. These results suggest that pharmacologically increasing tonic inhibition may be a useful strategy for alleviating motor dysfunction in Angelman syndrome.

  19. Lutein protects dopaminergic neurons against MPTP-induced apoptotic death and motor dysfunction by ameliorating mitochondrial disruption and oxidative stress.

    Science.gov (United States)

    Nataraj, Jagatheesan; Manivasagam, Thamilarasan; Thenmozhi, Arokiasamy Justin; Essa, Musthafa Mohammed

    2016-07-01

    Mitochondrial dysfunction and oxidative stress-mediated apoptosis plays an important role in various neurodegenerative diseases including Huntington's disease, Parkinson's disease (PD) and Alzheimer's disease (AD). 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), the most widely used neurotoxin mimics the symptoms of PD by inhibiting mitochondrial complex I that stimulates excessive intracellular reactive oxygen species (ROS) and finally leads to mitochondrial-dependent apoptosis. Lutein, a carotenoid of xanthophyll family, is found abundantly in leafy green vegetables such as spinach, kale and in egg yolk, animal fat and human eye retinal macula. Increasing evidence indicates that lutein has offers benefits against neuronal damages during diabetic retinopathy, ischemia and AD by virtue of its mitochondrial protective, antioxidant and anti-apoptotic properties. Male C57BL/6 mice (23-26 g) were randomized and grouped in to Control, MPTP, and Lutein treated groups. Lutein significantly reversed the loss of nigral dopaminergic neurons by increasing the striatal dopamine level in mice. Moreover, lutein-ameliorated MPTP induced mitochondrial dysfunction, oxidative stress and motor abnormalities. In addition, lutein repressed the MPTP-induced neuronal damage/apoptosis by inhibiting the activation of pro-apoptotic markers (Bax, caspases-3, 8 and 9) and enhancing anti-apoptotic marker (Bcl-2) expressions. Our current results revealed that lutein possessed protection on dopaminergic neurons by enhancing antioxidant defense and diminishing mitochondrial dysfunction and apoptotic death, suggesting the potential benefits of lutein for PD treatment.

  20. [Phantom limb pain originates from dysfunction of the primary motor cortex].

    Science.gov (United States)

    Sumitani, Masahiko; Miyauchi, Satoru; Uematsu, Hironobu; Yozu, Arito; Otake, Yuko; Yamada, Yoshitsugu

    2010-11-01

    Accumulated knowledge indicates that phantom limb pain is a phenomenon of the central nervous system that is related to plastic changes at several levels of the nervous systems. Especially, reports using patients with neuropathic pain clearly indicate the sensorimotor cortex as underlying mechanisms of phantom limb and its pain. Here, we focus the notion that limb amputation or deafferentation results in plasticity of connections between the brain and the body, and that the cortical motor representation of the missing or deafferented limb seemingly disappears. Meanwhile, the sensory representation of the limb does not disappear and thereby patients feel phantom limbs. We propose that dissociation between motor and sensory representations in the primary motor cortex induces pathologic pain and reconcile of sensorimotor integration of the limb would alleviate pain, on the basis of our neurorehabilitation approaches and artificial neuromodulation strategies.

  1. Can music-based movement therapy improve motor dysfunction in patients with Parkinson's disease? Systematic review and meta-analysis.

    Science.gov (United States)

    Zhang, Shuai; Liu, Dong; Ye, Dan; Li, Haiyu; Chen, Feng

    2017-06-21

    This study aimed to quantify whether there is association between music-based movement therapy and motor dysfunction in patients with Parkinson's disease, and, if so, whether music-based movement therapy can be used as first-line non-pharmacological treatment. To conduct a systematic review and meta-analysis of clinical trials that examined the effect of music-based movement therapy on patient-relevant and disease-specific outcomes. Comprehensive literature was searched of PubMed, EMbase, and the Cochrane Library from inception to November 2016. Randomized controlled trial of patients with Parkinson's disease was searched to identify trials comparing music-based movement therapy with no music care. A total of 8 studies (11 analyses, 241 subjects) were included; all of them had acceptable quality by PEDro scale score. Studies based on any type of Parkinson's disease patients were combined and subgroup analyzed. Compared with the control group, the SMD of Berg Balance Scale score was 0.85(0.46 to 1.25), -0.60 (-0.98 to -0.22) in Parkinson Disease Questionnaire-39 summary index, -0.90s (-1.56 to -0.23) in Time Up and Go text, and -0.43 (-1.11 to 0.25) in Unified Parkinson's Disease Rating Scale Motor Subscale 3 as instrument methods for motor function. Secondary outcomes included cognitive function and quality of life. There was positive evidence to support the use of music-based movement therapy on treatment of motor function; there was neutral evidence to support the use of music for the treatment of cognitive function quality of life.

  2. High-Definition and Non-Invasive Brain Modulation of Pain and Motor Dysfunction in Chronic TMD

    Science.gov (United States)

    Donnell, Adam; Nascimento, Thiago; Lawrence, Mara; Gupta, Vikas; Zieba, Tina; Truong, Dennis Q.; Bikson, Marom; Datta, Abhi; Bellile, Emily; DaSilva, Alexandre F.

    2015-01-01

    Background Temporomandibular disorders (TMD) have a relatively high prevalence and in many patients pain and masticatory dysfunction persist despite a range of treatments. Non-invasive brain neuromodulatory methods, namely transcranial direct current stimulation (tDCS), can provide relatively long-lasting pain relief in chronic pain patients. Objective To define the neuromodulatory effect of five daily 2×2 motor cortex high-definition tDCS (HD-tDCS) sessions on clinical pain and motor measures in chronic TMD patients. It is predicted that M1 HD-tDCS will selectively modulate clinical measures, by showing greater analgesic after-effects compared to placebo, and active treatment will increase pain free jaw movement more than placebo. Methods Twenty-four females with chronic myofascial TMD pain underwent five daily, 20-minute sessions of active or sham 2 milliamps (mA) HD-tDCS. Measurable outcomes included pain-free mouth opening, visual analog scale (VAS), sectional sensory-discriminative pain measures tracked by a mobile application, short form of the McGill Pain Questionnaire, and the Positive and Negative Affect Schedule. Follow-up occurred at one-week and four-weeks post treatment. Results There were significant improvements for clinical pain and motor measurements in the active HD-tDCS group compared to the placebo group for: responders with pain relief above 50% in the VAS at four-week follow-up (p=0.04); pain-free mouth opening at one-week follow-up (ppain area, intensity and their sum measures contralateral to putative M1 stimulation during the treatment week (ppain and motor measures during stimulation, and up to four weeks post-treatment in chronic myofascial TMD pain patients. PMID:26226938

  3. Neural correlates of motor dysfunction in children with traumatic brain injury: exploration of compensatory recruitment patterns.

    NARCIS (Netherlands)

    Caeyenberghs, K.; Wenderoth, N.; Smits-Engelsman, B.C.M.; Sunaert, S.; Swinnen, S.P.

    2009-01-01

    Traumatic brain injury (TBI) is a common form of disability in children. Persistent deficits in motor control have been documented following TBI but there has been less emphasis on changes in functional cerebral activity. In the present study, children with moderate to severe TBI (n = 9) and

  4. Towards Engaging Upper Extremity Motor Dysfunction Assessment Using Augmented Reality Games

    NARCIS (Netherlands)

    Cidota, M.A.; Lukosch, S.G.; Bank, Paulina J.M.; Ouwehand, P.W.

    2017-01-01

    Advances in technology offer new opportunities for a better understanding of how different disorders affect motor function. Our aim is to explore the potential of augmented reality (AR) using free hand and body tracking to develop engaging games for a uniform, cost-effective and objective evaluation

  5. Mindfulness for Motor and Nonmotor Dysfunctions in Parkinson’s Disease

    Directory of Open Access Journals (Sweden)

    Nadeeka N. W. Dissanayaka

    2016-01-01

    Full Text Available Background. Motor and nonmotor symptoms negatively influence Parkinson’s disease (PD patients’ quality of life. Mindfulness interventions have been a recent focus in PD. The present study explores effectiveness of a manualized group mindfulness intervention tailored for PD in improving both motor and neuropsychiatric deficits in PD. Methods. Fourteen PD patients completed an 8-week mindfulness intervention that included 6 sessions. The Five Facet Mindfulness Questionnaire (FFMQ, Geriatric Anxiety Inventory, Hamilton Depression Rating Scale, PD Cognitive Rating Scale, Unified PD Rating Scale, PD Quality of Life Questionnaire, and Outcome Questionnaire (OQ-45 were administered before and after the intervention. Participants also completed the FFMQ-15 at each session. Gains at postassessment and at 6-month follow-up were compared to baseline using paired t-tests and Wilcoxon nonparametric tests. Results. A significant increase in FFMQ-Observe subscale, a reduction in anxiety, depression, and OQ-45 symptom distress, an increase in PDCRS-Subcortical scores, and an improvement in postural instability, gait, and rigidity motor symptoms were observed at postassessment. Gains for the PDCRS were sustained at follow-up. Conclusion. The mindfulness intervention tailored for PD is associated with reduced anxiety and depression and improved cognitive and motor functioning. A randomised controlled trial using a large sample of PD patients is warranted.

  6. Risk Factors for Gross Motor Dysfunction in Infants with Congenital Heart Disease

    Science.gov (United States)

    Long, Suzanne H.; Eldridge, Bev J.; Galea, Mary P.; Harris, Susan R.

    2011-01-01

    Infants with congenital heart disease (CHD) that is severe enough to require early surgery are at risk for cognitive and motor delays, as well as musculoskeletal impairments, and are best managed by an interdisciplinary team during their hospital stay and after discharge. The purpose of this article is to review some of the risk factors associated…

  7. The role of language areas in motor control dysfunction in Parkinson's disease

    NARCIS (Netherlands)

    Albani, G; Kunig, G; Soelch, CM; Mauro, A; Priano, L; Martignoni, E; Leenders, K.L.

    We evaluated the differences in motor control organization between parkinsonian patients with (seven cases) and without(ten cases) gait disorder. We used positron emission tomography (O-15-H2O-PET) to measure regional cerebral blood flow as a correlate for local neuronal activation. This has been

  8. Cognitive dysfunction in hereditary spastic paraplegias and other motor neuron disorders

    Directory of Open Access Journals (Sweden)

    Ingrid Faber

    Full Text Available ABSTRACT Hereditary spastic paraplegia (HSP is a diverse group of single-gene disorders that share the predominant clinical feature of progressive lower limb spasticity and weakness. More than 70 different genetic subtypes have been described and all modes of inheritance are possible. Intellectual dysfunction in HSP is frequent in recessive forms but rare in dominant families. It may manifest by either mental retardation and/or cognitive decline. The latter may be subtle, restricted to executive dysfunction or may evolve to severe dementia. The cognitive profile is thought to depend largely on the genetic subtype of HSP, although wide phenotypic variability within the same genetic subtype and also within the same family can be found.

  9. Urinary dysfunction with detrusor hyperactivity in women with Parkinson's disease cannot be blamed as a factor of worsening motor performance

    Directory of Open Access Journals (Sweden)

    Raimundo Nonato Campos-Sousa

    2013-09-01

    Full Text Available Introduction Detrusor hyperactivity is the leading cause of urinary dysfunction in Parkinson's disease (PD. There are few studies correlating PD clinical aspects with this autonomic feature. Methods A cohort of 63 women with PD were prospectively examined for assessment of clinical aspects and disease severity using unified Parkinson's disease rating scale and Hoehn-Yahr scale, respectively. The urologic function was evaluated by the urodynamic study. Two groups were categorized at this time - groups with and without detrusor hyperactivity. After seven years, the same parameters were re-evaluated. Results Progression of the disease on mental scores was found in the group with detrusor hyperactivity. On follow-up, clinical symptoms and severity did not show significant worsening between the groups. Conclusion Detrusor hyperactivity is a frequent urodynamic finding in PD, and even though it is associated with dopaminergic dysfunction, it cannot be blamed as a factor of worsening motor performance, but is probably associated with poor cognitive and mental prognosis.

  10. Age-related motor dysfunction: Manual slowing in Gorilla gorilla gorilla.

    Science.gov (United States)

    Mahovetz, Lindsay M; Stoinski, Tara S

    2015-12-01

    Aging in humans and rhesus monkeys is commonly associated with motor function decrements including dexterity, speed, and strength. Despite their longevity and phylogenetic relatedness to humans, the effects of aging on motor function in non-human apes have been minimally studied. We conducted two experiments with western lowland gorillas (11-54 years of age) to determine whether aged gorillas exhibit motor deficits similar to those seen in other species. In experiment one, gorillas extracted up to 12 food rewards lodged in holes of a Lexan board. Extraction rates were calculated for eight test sessions. A repeated measures ANOVA revealed no main effects of session or sex on extraction rate, but a significant main effect of age. Comparisons between the first and last sessions showed that experience significantly improved extraction rates in young but not aged gorillas. In experiment two, gorillas retrieved a hex nut from three differently shaped rods with each hand for a reward. Latencies of retrieval were calculated for 16 test sessions. A repeated measures ANOVA revealed significant main effects of age class, sex, and session. There were significant interactions between session and sex, session and age, and session, sex, and age. These findings held when analyzing each rod shape separately. Post hoc comparisons revealed that young gorillas were significantly faster at the task than aged gorillas, and females were faster than males. This finding held only for the question mark shaped rod when analyzing each rod shape separately. Comparisons between the first and last sessions showed that experience did not significantly improve latencies in either age or sex class. The direction of these results are congruent with previous findings in humans and monkeys and suggest that aged gorillas experience deficits in bimanual coordination compared to younger gorillas and that age and sex influence fine motor ability in gorillas. © 2015 Wiley Periodicals, Inc.

  11. Cognitive-motor dysfunction after severe traumatic brain injury: A cerebral interhemispheric disconnection syndrome.

    Science.gov (United States)

    Falchook, Adam D; Porges, Eric C; Nadeau, Stephen E; Leon, Susan A; Williamson, John B; Heilman, Kenneth M

    2015-01-01

    In most right-handed people, the left hemisphere is dominant for programming the temporal and spatial "how" (praxis) aspects of purposeful skilled movements, and the right hemisphere is dominant for control of the intentional "when" aspects of actions that mediate initiation, persistence, termination, and inhibition. Since the interhemispheric axons of the corpus callosum are especially susceptible to shearing from torsional forces during traumatic brain injury (TBI), the goal of this study was to learn whether participants with a history of severe traumatic brain injury demonstrate three types of cognitive-motor impairments that may result from callosal injury: ideomotor apraxia of the left hand, limb kinetic apraxia of the left hand, and hypokinesia of the right hand in response to left hemispatial stimuli. Nine participants with severe TBI and nine healthy control participants were studied for the presence of ideomotor apraxia, limb kinetic apraxia, and hypokinesia. When compared to the control participants, the participants with TBI revealed ideomotor apraxia and limb kinetic apraxia of the left hand and hypokinesia in response to left-sided visual stimuli when tested with the right hand. TBI appears to cause unilateral disorders of cognitive-motor functions. Future research is needed to understand how these cognitive-motor disorders are related to interhemispheric disconnection most likely induced by injury to the corpus callosum.

  12. Progression of motor axon dysfunction and ectopic Na(v)1.8 expression in a mouse model of Charcot-Marie-Tooth disease 1B

    DEFF Research Database (Denmark)

    Rosberg, Mette R.; Alvarez Herrero, Susana; Klein, Dennis

    2016-01-01

    Mice heterozygously deficient for the myelin protein P0 gene (P0+/-) develop a slowly progressing neuropathy modeling demyelinating Charcot-Marie-Tooth disease (CMT1B). The aim of the study was to investigate the long-term progression of motor dysfunction in P0+/- mice at 3, 7, 12 and 20months...

  13. High-Definition and Non-invasive Brain Modulation of Pain and Motor Dysfunction in Chronic TMD.

    Science.gov (United States)

    Donnell, Adam; D Nascimento, Thiago; Lawrence, Mara; Gupta, Vikas; Zieba, Tina; Truong, Dennis Q; Bikson, Marom; Datta, Abhi; Bellile, Emily; DaSilva, Alexandre F

    2015-01-01

    Temporomandibular disorders (TMD) have a high prevalence and in many patients pain and masticatory dysfunction persist despite a range of treatments. Non-invasive brain neuromodulatory methods, namely transcranial direct current stimulation (tDCS), can provide relatively long-lasting pain relief in chronic pain patients. To define the neuromodulatory effect of five daily 2x2 motor cortex high-definition tDCS (HD-tDCS) sessions on clinical pain and motor measures in chronic TMD patients. It is predicted that M1 HD-tDCS will selectively modulate clinical measures, by showing greater analgesic after-effects compared to placebo, and active treatment will increase pain free jaw movement more than placebo. Twenty-four females with chronic myofascial TMD pain underwent five daily, 20-min sessions of active or sham 2 milliamps (mA) HD-tDCS. Measurable outcomes included pain-free mouth opening, visual analog scale (VAS), sectional sensory-discriminative pain measures tracked by a mobile application, short form of the McGill Pain Questionnaire, and the Positive and Negative Affect Schedule. Follow-up occurred at one-week and four-weeks post-treatment. There were significant improvements for clinical pain and motor measurements in the active HD-tDCS group compared to the placebo group for: responders with pain relief above 50% in the VAS at four-week follow-up (P = 0.04); pain-free mouth opening at one-week follow-up (P treatment week (P treatment in chronic myofascial TMD pain patients. Copyright © 2015 Elsevier Inc. All rights reserved.

  14. A mouse model of non-motor symptoms in Parkinson’s disease: focus on pharmacological interventions targeting affective dysfunctions

    Directory of Open Access Journals (Sweden)

    Alessandra eBonito Oliva

    2014-08-01

    Full Text Available Non-motor symptoms, including psychiatric disorders, are increasingly recognized as a major challenge in the treatment of Parkinson’s disease (PD. These ailments, which often appear in the early stage of the disease, affect a large number of patients and are only partly resolved by conventional antiparkinsonian medications, such as L-DOPA. Here, we investigated non-motor symptoms of PD in a mouse model based on bilateral injection of the toxin 6-hydroxydopamine (6-OHDA in the dorsal striatum. This model presented only subtle gait modifications, which did not affect horizontal motor activity in the open-field test. Bilateral 6-OHDA lesion also impaired olfactory discrimination, in line with the anosmia typically observed in early stage parkinsonism. The effect of 6-OHDA was then examined for mood-related dysfunctions. Lesioned mice showed increased immobility in the forced swim test and tail suspension test, two behavioral paradigms of depression. Moreover, the lesion exerted anxiogenic effects, as shown by reduced time spent in the open arms, in the elevated plus maze test, and by increased thigmotaxis in the open-field test. L-DOPA did not modify depressive- and anxiety-like behaviors, which were instead counteracted by the dopamine D2/D3 receptor agonist, pramipexole. Reboxetine, a noradrenaline reuptake inhibitor, was also able to prevent the depressive and anxiogenic effects produced by the lesion with 6-OHDA. Interestingly, pre-treatment with desipramine prior to injection of 6-OHDA, which is commonly used to preserve noradrenaline neurons, did not modify the effect of the lesion on depressive- and anxiety-like behaviors. Thus, in the present model, mood-related conditions are independent of the reduction of noradrenaline caused by 6-OHDA. Based on these findings we propose that the anti-depressive and anxiolytic action of reboxetine is mediated by promoting dopamine transmission through blockade of dopamine uptake from residual

  15. Usability and Acceptability of ASSESS MS: Assessment of Motor Dysfunction in Multiple Sclerosis Using Depth-Sensing Computer Vision.

    Science.gov (United States)

    Morrison, Cecily; D'Souza, Marcus; Huckvale, Kit; Dorn, Jonas F; Burggraaff, Jessica; Kamm, Christian Philipp; Steinheimer, Saskia Marie; Kontschieder, Peter; Criminisi, Antonio; Uitdehaag, Bernard; Dahlke, Frank; Kappos, Ludwig; Sellen, Abigail

    2015-06-24

    Sensor-based recordings of human movements are becoming increasingly important for the assessment of motor symptoms in neurological disorders beyond rehabilitative purposes. ASSESS MS is a movement recording and analysis system being developed to automate the classification of motor dysfunction in patients with multiple sclerosis (MS) using depth-sensing computer vision. It aims to provide a more consistent and finer-grained measurement of motor dysfunction than currently possible. To test the usability and acceptability of ASSESS MS with health professionals and patients with MS. A prospective, mixed-methods study was carried out at 3 centers. After a 1-hour training session, a convenience sample of 12 health professionals (6 neurologists and 6 nurses) used ASSESS MS to capture recordings of standardized movements performed by 51 volunteer patients. Metrics for effectiveness, efficiency, and acceptability were defined and used to analyze data captured by ASSESS MS, video recordings of each examination, feedback questionnaires, and follow-up interviews. All health professionals were able to complete recordings using ASSESS MS, achieving high levels of standardization on 3 of 4 metrics (movement performance, lateral positioning, and clear camera view but not distance positioning). Results were unaffected by patients' level of physical or cognitive disability. ASSESS MS was perceived as easy to use by both patients and health professionals with high scores on the Likert-scale questions and positive interview commentary. ASSESS MS was highly acceptable to patients on all dimensions considered, including attitudes to future use, interaction (with health professionals), and overall perceptions of ASSESS MS. Health professionals also accepted ASSESS MS, but with greater ambivalence arising from the need to alter patient interaction styles. There was little variation in results across participating centers, and no differences between neurologists and nurses. In typical

  16. The influence of a vestibular dysfunction on the motor development of hearing-impaired children.

    Science.gov (United States)

    De Kegel, Alexandra; Maes, Leen; Baetens, Tina; Dhooge, Ingeborg; Van Waelvelde, Hilde

    2012-12-01

    To identify the predictive ability of vestibular function test results on motor performance among hearing-impaired children. Cross-sectional study. Fifty-one typically developing children and 48 children with a unilateral (n = 9) or bilateral hearing impairment (n = 39) of more than 40 dB HL between 3 and 12 years were tested by the Movement Assessment Battery for Children-Second Edition (M ABC-2), clinical balance tests, posturography, rotatory chair testing, and vestibular evoked myogenic potential (VEMP). From the group of hearing-impaired children, 23 had cochlear implants. Balance performance on M ABC-2, clinical balance tests, as well as the sway velocity assessed by posturography in bipedal stance on a cushion with eyes closed and in unilateral stance differed significantly between both groups. Presence of a VEMP response is an important clinical parameter because comparison of the motor performance among hearing-impaired children between those with present and absent VEMPs showed significant differences in balance performance. The three most important predictor variables on motor performance by bivariate regression analyses are the vestibular-ocular reflex (VOR) gain value of the rotatory chair test at 0.01 and 0.05 Hz frequency, as well as the VEMP asymmetry ratio. Multivariate regression analyses suggest that the VOR asymmetry value of the rotatory chair test at 0.05 Hz and the etiology of the hearing loss seem to have additional predictive value. Hearing-impaired children are at risk for balance deficits. A combination of rotatory chair testing and VEMP testing can predict the balance performance. Copyright © 2012 The American Laryngological, Rhinological, and Otological Society, Inc.

  17. Motor dysfunction in cerebellar Purkinje cell-specific vesicular GABA transporter knockout mice

    Directory of Open Access Journals (Sweden)

    Mikiko eKayakabe

    2014-01-01

    Full Text Available γ-Aminobutyric acid (GABA is a major inhibitory neurotransmitter in the adult mammalian central nervous system and plays modulatory roles in neural development. The vesicular GABA transporter (VGAT is an essential molecule for GABAergic neurotransmission due to its role in vesicular GABA release. Cerebellar Purkinje cells (PCs are GABAergic projection neurons that are indispensable for cerebellar function. To elucidate the significance of VGAT in cerebellar PCs, we generated and characterized PC-specific VGAT knockout (L7-VGAT mice. VGAT mRNAs and proteins were specifically absent in the 40-week-old L7-VGAT PCs. The morphological charactereistics, such as lamination and foliation of the cerebellar cortex, of the L7-VGAT mice were similar to those of the control littermate mice. Moreover, the protein expression levels and patterns of pre- (calbindin and parvalbumin and postsynaptic (GABA-A receptor α1 subunit (GABAARα1 and gephyrin molecules between the L7-VGAT and control mice were similar in the deep cerebellar nuclei that receive PC projections. However, the L7-VGAT mice performed poorly in the accelerating rotarod test and displayed ataxic gait in the footprint test. The L7-VGAT mice also exhibited severer ataxia as VGAT deficits progressed. These results suggest that VGAT in cerebellar Purkinje cells is not essential for the rough maintenance of cerebellar structure, but does play an important role in motor coordination. The L7-VGAT mice are a novel model of ataxia without PC degeneration, and would also be useful for studying the role of Purkinje cells in cognition and emotion.

  18. Effects of different frequencies of repetitive transcranial magnetic stimulation on the recovery of upper limb motor dysfunction in patients with subacute cerebral infarction.

    Science.gov (United States)

    Li, Jiang; Meng, Xiang-Min; Li, Ru-Yi; Zhang, Ru; Zhang, Zheng; Du, Yi-Feng

    2016-10-01

    Studies have confirmed that low-frequency repetitive transcranial magnetic stimulation can decrease the activity of cortical neurons, and high-frequency repetitive transcranial magnetic stimulation can increase the excitability of cortical neurons. However, there are few studies concerning the use of different frequencies of repetitive transcranial magnetic stimulation on the recovery of upper-limb motor function after cerebral infarction. We hypothesized that different frequencies of repetitive transcranial magnetic stimulation in patients with cerebral infarction would produce different effects on the recovery of upper-limb motor function. This study enrolled 127 patients with upper-limb dysfunction during the subacute phase of cerebral infarction. These patients were randomly assigned to three groups. The low-frequency group comprised 42 patients who were treated with 1 Hz repetitive transcranial magnetic stimulation on the contralateral hemisphere primary motor cortex (M1). The high-frequency group comprised 43 patients who were treated with 10 Hz repetitive transcranial magnetic stimulation on ipsilateral M1. Finally, the sham group comprised 42 patients who were treated with 10 Hz of false stimulation on ipsilateral M1. A total of 135 seconds of stimulation was applied in the sham group and high-frequency group. At 2 weeks after treatment, cortical latency of motor-evoked potentials and central motor conduction time were significantly lower compared with before treatment. Moreover, motor function scores were significantly improved. The above indices for the low- and high-frequency groups were significantly different compared with the sham group. However, there was no significant difference between the low- and high-frequency groups. The results show that low- and high-frequency repetitive transcranial magnetic stimulation can similarly improve upper-limb motor function in patients with cerebral infarction.

  19. Delayed detection of motor pathway dysfunction after selective reduction of thoracic spinal cord blood flow in pigs

    NARCIS (Netherlands)

    Lips, Jeroen; de Haan, Peter; Bouma, Gerrit J.; Jacobs, Michael J.; Kalkman, Cor J.

    2002-01-01

    Objective: Clinical monitoring of myogenic motor evoked potentials to transcranial stimulation provides rapid evaluation of motor-pathway function during surgical procedures in which spinal cord ischemia can occur. However, a severe reduction of spinal cord blood flow that remains confined to the

  20. Evaluating the Influence of Motor Control on Selective Attention through a Stochastic Model: The Paradigm of Motor Control Dysfunction in Cerebellar Patient

    Directory of Open Access Journals (Sweden)

    Giacomo Veneri

    2014-01-01

    Full Text Available Attention allows us to selectively process the vast amount of information with which we are confronted, prioritizing some aspects of information and ignoring others by focusing on a certain location or aspect of the visual scene. Selective attention is guided by two cognitive mechanisms: saliency of the image (bottom up and endogenous mechanisms (top down. These two mechanisms interact to direct attention and plan eye movements; then, the movement profile is sent to the motor system, which must constantly update the command needed to produce the desired eye movement. A new approach is described here to study how the eye motor control could influence this selection mechanism in clinical behavior: two groups of patients (SCA2 and late onset cerebellar ataxia LOCA with well-known problems of motor control were studied; patients performed a cognitively demanding task; the results were compared to a stochastic model based on Monte Carlo simulations and a group of healthy subjects. The analytical procedure evaluated some energy functions for understanding the process. The implemented model suggested that patients performed an optimal visual search, reducing intrinsic noise sources. Our findings theorize a strict correlation between the “optimal motor system” and the “optimal stimulus encoders.”

  1. Treadmill Exercise Improves Motor Dysfunction and Hyperactivity of the Corticostriatal Glutamatergic Pathway in Rats with 6-OHDA-Induced Parkinson’s Disease

    Directory of Open Access Journals (Sweden)

    Wei Chen

    2017-01-01

    Full Text Available Hyperactivity in the corticostriatal glutamatergic pathway (CGP induces basal ganglia dysfunction, contributing to parkinsonian syndrome (PS. Physical exercise can improve PS. However, the effect of exercise on the CGP, and whether this pathway is involved in the improvement of PS, remains unclear. Parkinson’s disease (PD was induced in rats by 6-hydroxydopamine injection into the right medial forebrain bundle. Motor function was assessed using the cylinder test. Striatal neuron (SN spontaneous and evoked firing activity was recorded, and the expression levels of Cav1.3 and CaMKII in the striatum were measured after 4 weeks of treadmill exercise. The motor function in PD rats was improved by treadmill exercise. SN showed significantly enhanced excitability, and treadmill exercise reduced SN excitability in PD rats. In addition, firing activity was evoked in SNs by stimulation of the primary motor cortex, and SNs exhibited significantly decreased stimulus threshold, increased firing rates, and reduced latency. The expression of Cav1.3 and p-CaMKII (Thr286 in the striatum were enhanced in PD rats. However, these effects were reversed by treadmill exercise. These findings suggest that treadmill exercise inhibits CGP hyperactivity in PD rats, which may be related to improvement of PS.

  2. Prevention of COPD exacerbations

    DEFF Research Database (Denmark)

    Vestbo, Jørgen; Lange, Peter

    2015-01-01

    Exacerbations have significant impact on the morbidity and mortality of patients with chronic obstructive pulmonary disease. Most guidelines emphasise prevention of exacerbations by treatment with long-acting bronchodilators and/or anti-inflammatory drugs. Whereas most of this treatment is eviden...

  3. Motor neuron dysfunction in a mouse model of ALS: gender-dependent effect of P2X7 antagonism.

    Science.gov (United States)

    Cervetto, Chiara; Frattaroli, Daniela; Maura, Guido; Marcoli, Manuela

    2013-09-06

    Amyotrophic lateral sclerosis (ALS) is a neurodegenerative progressive currently untreatable disease, characterized by selective motor neuron degeneration; the incidence and prevalence of ALS are greater in men than in women. Although some important mechanisms that might contribute to the death of motor neurons have been identified, the mechanisms underlying disease pathophysiology are still uncertain. In particular, the mechanisms underlying the role of gender in ALS and whether treatments should take into account sexual dimorphism remain only partially understood. Recently, the P2X7 receptor for ATP was reported to display neurotoxic potential in motor neuron disorders, and antagonism of the receptor has been suggested to be helpful in these disorders. Studying transgenic mice with superoxide dismutase 1 gene mutations, widely used as model for ALS, may provide a better understanding of pathogenic mechanisms and of toxicity towards motor neurons, also possibly helping to understand whether treatments for ALS should take into account sexual dimorphism. The aim of the work was (1) investigating on gender-dependence of disease progression in the standard model for ALS - the transgenic mouse bearing superoxide dismutase 1 gene mutations - and (2) assessing if a P2X7 receptor antagonist treatment should take into account sexual dimorphism. We evaluated if gender affect the disease course, the motor performance, the weight loss and the lifespan in mice overexpressing mutant superoxide dismutase 1. We measured motor impairment, motor strength and coordination by rotarod and grip strength testing. Further, we assessed if a treatment with the P2X7 receptor antagonist Brilliant Blue G - a dye that can cross the blood-brain barrier, has low toxicity, and has exhibited therapeutic effects in animal models of neurodegenerative diseases - impact on the disease progression, in male and female ALS mice. We found that (1) the onset and the disease progression, and the survival

  4. Role of Ocimum basilicum L. in prevention of ischemia and reperfusion-induced cerebral damage, and motor dysfunctions in mice brain.

    Science.gov (United States)

    Bora, Kundan Singh; Arora, Shruti; Shri, Richa

    2011-10-11

    The genus Ocimum (Lamiaceae) has a long history of use as culinary and medicinal herbs. Many species are used for their antioxidant and neuroprotective activity in various parts of the world. Ocimum basilicum Linn. has been used traditionally for the treatment of anxiety, diabetes, cardiovascular diseases, headaches, nerve pain, as anticonvulsant and anti-inflammatory, and used in a variety of neurodegenerative disorders. The present study is designed to investigate the effect of ethyl acetate extract of Ocimum basilicum leaves on ischemia and reperfusion-induced cerebral damage, and motor dysfunctions in mice. Global cerebral ischemia was induced by bilateral carotid artery occlusion for 15 min followed by reperfusion for 24h. Cerebral infarct size was measured using triphenyltetrazolium chloride staining. The concentration of thiobarbituric acid reactive substances (TBARS) and reduced glutathione (GSH) content was determined by colorimetric assay. Short-term memory was evaluated using elevated plus-maze. Inclined beam walking was employed to assess motor coordination. Bilateral carotid artery occlusion followed by reperfusion produced significant increase in cerebral infarct size and lipid peroxidation (TBARS), and reduced GSH content, and impaired short-term memory and motor coordination. Pre-treatment with standardized ethyl acetate extract of Ocimum basilicum (100 and 200mg/kg, p.o.) markedly reduced cerebral infarct size and lipid peroxidation, restored GSH content, and attenuated impairment in short-term memory and motor coordination. The results of the study suggest that Ocimum basilicum could be useful clinically in the prevention of stroke. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  5. Altered microstructural connectivity of the superior and middle cerebellar peduncles are related to motor dysfunction in children with diffuse periventricular leucomalacia born preterm: A DTI tractography study

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Shanshan, E-mail: jelly_66@126.com; Fan, Guo Guang, E-mail: cjr.fanguoguang@vip.163.com; Xu, Ke, E-mail: cjr.xuke@vip.163.com; Wang, Ci, E-mail: xiangxuehai19850224@yahoo.cn

    2014-06-15

    Purpose: To investigate the microstructural integrity of superior cerebellar peduncles (SCP) and middle cerebellar peduncles (MCP) by using DTI tractography method, and further to detect whether the microstructural integrity of these major cerebellar pathways is related to motor function in children with diffuse periventricular leucomalacia (PVL) born preterm. Materials and methods: 46 children with diffuse PVL (30 males and 16 females; age range 3–48 months; mean age 22.4 ± 6.7 months; mean gestational age 30.5 ± 2.2 weeks) and 40 healthy controls (27 males and 13 females; age range 3.5–48 months; mean age 22.1 ± 5.8 months) were enrolled in this study. DTI outcome measurements, fractional anisotropy (FA), for the SCP, MCP and cortical spinal tract (CST) were calculated. The gross motor function classification system (GMFCS) was used for assessing motor functions. Results: Compared to the controls, patients with diffuse PVL had a significantly lower FA in bilateral SCP, MCP and CST. There was a significant negative correlation between GMFCS levels and FA in bilateral SCP, MCP and CST in the patients group. In addition, significant inverse correlation of FA value was found between not only the contralateral but also the ipsilateral CST and SCP/MCP. Conclusions: These findings suggest that the injury of SCP and MCP may contribute to the motor dysfunction of diffuse PVL. Moreover, the correlations we found between supratentorial and subtentorial injured white matter extend our knowledge about the cerebro-cerebellar white matter interaction in children with diffuse PVL.

  6. Altered microstructural connectivity of the superior and middle cerebellar peduncles are related to motor dysfunction in children with diffuse periventricular leucomalacia born preterm: a DTI tractography study.

    Science.gov (United States)

    Wang, Shanshan; Fan, Guo Guang; Xu, Ke; Wang, Ci

    2014-06-01

    To investigate the microstructural integrity of superior cerebellar peduncles (SCP) and middle cerebellar peduncles (MCP) by using DTI tractography method, and further to detect whether the microstructural integrity of these major cerebellar pathways is related to motor function in children with diffuse periventricular leucomalacia (PVL) born preterm. 46 children with diffuse PVL (30 males and 16 females; age range 3-48 months; mean age 22.4 ± 6.7 months; mean gestational age 30.5 ± 2.2 weeks) and 40 healthy controls (27 males and 13 females; age range 3.5-48 months; mean age 22.1 ± 5.8 months) were enrolled in this study. DTI outcome measurements, fractional anisotropy (FA), for the SCP, MCP and cortical spinal tract (CST) were calculated. The gross motor function classification system (GMFCS) was used for assessing motor functions. Compared to the controls, patients with diffuse PVL had a significantly lower FA in bilateral SCP, MCP and CST. There was a significant negative correlation between GMFCS levels and FA in bilateral SCP, MCP and CST in the patients group. In addition, significant inverse correlation of FA value was found between not only the contralateral but also the ipsilateral CST and SCP/MCP. These findings suggest that the injury of SCP and MCP may contribute to the motor dysfunction of diffuse PVL. Moreover, the correlations we found between supratentorial and subtentorial injured white matter extend our knowledge about the cerebro-cerebellar white matter interaction in children with diffuse PVL. Copyright © 2014. Published by Elsevier Ireland Ltd.

  7. Serious Gaming in Augmented Reality using HMDs for Assessment of Upper Extremity Motor Dysfunctions : User Studies for Engagement and Usability

    NARCIS (Netherlands)

    Cidota, M.A.; Lukosch, S.G.; Dezentje, P; Bank, PJM; Lukosch, H.K.; Clifford, RMS

    For a better understanding of how different disorders affect motor function, a uniform, standardized and objective evaluation is a desirable goal for the clinical community. We explore the potential of Augmented Reality (AR) combined with serious gaming and free hand tracking to facilitate

  8. Resting-state functional MRI reveals altered brain connectivity and its correlation with motor dysfunction in a mouse model of Huntington's disease.

    Science.gov (United States)

    Li, Qiang; Li, Gang; Wu, Dan; Lu, Hanbing; Hou, Zhipeng; Ross, Christopher A; Yang, Yihong; Zhang, Jiangyang; Duan, Wenzhen

    2017-12-01

    Huntington's disease (HD) is an autosomal dominant inherited neurodegenerative disorder, and no cure is available currently. Treatment of HD is likely to be most beneficial in the early, possibly pre-manifestation stage. The challenge is to determine the best time for intervention and evaluate putative efficacy in the absence of clinical symptoms. Resting-state functional MRI may represent a promising tool to develop biomarker reflecting early neuronal dysfunction in HD brain, because it can examine multiple brain networks without confounding effects of cognitive ability, which makes the resting-state fMRI promising as a translational bridge between preclinical study in animal models and clinical findings in HD patients. In this study, we examined brain regional connectivity and its correlation to brain atrophy, as well as motor function in the 18-week-old N171-82Q HD mice. HD mice exhibited significantly altered functional connectivity in multiple networks. Particularly, the weaker intra-striatum connectivity was positively correlated with striatal atrophy, while striatum-retrosplenial cortex connectivity is negatively correlated with striatal atrophy. The resting-state brain regional connectivity had no significant correlation with motor deficits in HD mice. Our results suggest that altered brain connectivity detected by resting-state fMRI might serve as an early disease biomarker in HD.

  9. Etomidate and Ketamine: Residual Motor and Adrenal Dysfunction that Persist beyond Recovery from Loss of Righting Reflex in Rats

    Directory of Open Access Journals (Sweden)

    Daniel Diaz-Gil

    2014-12-01

    Full Text Available We tested the hypothesis that etomidate and ketamine produce residual effects that modify functional mobility (measured by the balance beam test and adrenal function (adrenocorticotropic hormone (ACTH stimulation immediately following recovery from loss of righting reflex in rats. Intravenous etomidate or ketamine was administered in a randomized, crossover fashion (2 or 4 mg/kg and 20 or 40 mg/kg, respectively on eight consecutive days. Following recovery of righting reflex, animals were assessed for residual effects on functional mobility on the balance beam, motor behavior in the open field and adrenal function through ACTH stimulation. We evaluated the consequences of the effects of the anesthetic agent-induced motor behavior on functional mobility. On the balance beam, etomidate-treated rats maintained their grip longer than ketamine-treated rats, indicating greater balance abilities (mean ± SD, 21.5 ± 25.1 s vs. 3.0 ± 4.3 s respectively, p < 0.021. In the open field test, both dosages of etomidate and ketamine had opposite effects on travel behavior, showing ketamine-induced hyperlocomotion and etomidate-induced hypolocomotion. There was a significant interaction between anesthetic agent and motor behavior effects for functional mobility effects (p < 0.001. Corticosterone levels were lower after both 40 mg/kg ketamine and 4 mg/kg etomidate anesthesia compared to placebo, an effect stronger with etomidate than ketamine (p < 0.001. Following recovery from anesthesia, etomidate and ketamine have substantial side effects. Ketamine-induced hyperlocomotion with 20 and 40 mg/kg has stronger effects on functional mobility than etomidate-induced hypolocomotion with 2 and 4 mg/kg. Etomidate (4 mg/kg has stronger adrenal suppression effects than ketamine (40 mg/kg.

  10. Exacerbation of brain pathology after partial restraint in hypertensive rats following SiO₂ nanoparticles exposure at high ambient temperature.

    Science.gov (United States)

    Sharma, Hari S; Muresanu, Dafin F; Patnaik, Ranjana; Sharma, Aruna

    2013-10-01

    This investigation examines the possibility that exposure to silica dust of hypertensive individuals may exacerbate brain pathology and sensory motor dysfunction at high environmental temperature. Hypertension was produced in rats (200-250 g) by two-kidney one clip (2K1C) method, and in these animals, SiO2 nanoparticles (NPs; 50 to 60 nm) were administered at 50 mg/kg, i.p. daily for 1 week. On the 8th day, these rats were subjected to partial restraint in a Perspex box for 4 h either at room temperature (21 °C) or at 33 °C in a biological oxygen demand incubator (wind velocity, 2.6 cm/s; relative humidity, 65 to 67 %). In these animals, behavioral functions, blood-brain barrier (BBB) permeability to Evans blue albumin (EBA) and radioiodine (([131]-)Iodine), brain water content and neuronal injuries were determined. Hypertensive rats subjected to 4 h restraint at room temperature did not exhibit BBB dysfunction, brain edema, neural injury, or alterations in rotarod or inclined plane angle performances. However, when these hypertensive rats were subjected to restraint at 33 °C, breakdown of the cortical BBB (EBA, +38 %; radioiodine, +56 %), brain water (+0.88 %), neuronal damages (+18 %), and behavioral impairment were exacerbated. Interestingly, SiO2 exposure to these rats further exacerbated BBB breakdown (EBA, 280 %; radioiodine, 350 %), brain edema (4 %), and neural injury (30 %) after identical restraint depending on the ambient temperature. SiO2 treatment also induced brain pathology and alteration in behavioral functions in normotensive rats after restraint at high temperature. These observations clearly show that hypertension significantly enhances restraint-induced brain pathology, and behavioral anomalies particularly at high ambient temperature and SiO2 intoxication further exacerbated these brain pathologies and cognitive dysfunctions.

  11. Reverse Engineering Tone-Deafness: Disrupting Pitch-Matching by Creating Temporary Dysfunctions in the Auditory-Motor Network

    Directory of Open Access Journals (Sweden)

    Anja Hohmann

    2018-01-01

    Full Text Available Perceiving and producing vocal sounds are important functions of the auditory-motor system and are fundamental to communication. Prior studies have identified a network of brain regions involved in pitch production, specifically pitch matching. Here we reverse engineer the function of the auditory perception-production network by targeting specific cortical regions (e.g., right and left posterior superior temporal (pSTG and posterior inferior frontal gyri (pIFG with cathodal transcranial direct current stimulation (tDCS—commonly found to decrease excitability in the underlying cortical region—allowing us to causally test the role of particular nodes in this network. Performance on a pitch-matching task was determined before and after 20 min of cathodal stimulation. Acoustic analyses of pitch productions showed impaired accuracy after cathodal stimulation to the left pIFG and the right pSTG in comparison to sham stimulation. Both regions share particular roles in the feedback and feedforward motor control of pitched vocal production with a differential hemispheric dominance.

  12. Manual motor speed dysfunction as a neurocognitive endophenotype in euthymic bipolar disorder patients and their healthy relatives. Evidence from a 5-year follow-up study.

    Science.gov (United States)

    Correa-Ghisays, P; Balanzá-Martínez, V; Selva-Vera, G; Vila-Francés, J; Soria-Olivas, E; Vivas-Lalinde, J; San Martín, C; Borrás, A M; Ayesa-Arriola, R; Sanchez-Moreno, J; Sánchez-Ort, J; Crespo-Facorro, B; Vieta, E; Tabarés-Seisdedos, R

    2017-06-01

    Few studies have examined Manual Motor Speed (MMS) in bipolar disorder (BD). The aim of this longitudinal, family study was to explore whether dysfunctional MMS represents a neurocognitive endophenotype of BD. A sample of 291 subjects, including 131 BD patients, 77 healthy first-degree relatives (BD-Rel), and 83 genetically-unrelated healthy controls (HC), was assessed with the Finger-Tapping Test (FTT) on three occasions over a 5-year period. Dependence of FTT on participants´ age was removed by means of a lineal model of HC samples, while correcting simultaneously the time and learning effect. Differences between groups were evaluated with an ANOVA test. The patients' performance was significantly worse than that of HC over time (p≤0.006), and these deficits remained when non-euthymic BD patients (n=9) were excluded from analysis. Some significant differences between BD patients and BD-Rel (p≤0.037) and between BD-Rel and HC (p≤0.033) were found, but they tended to disappear as time progressed (p≥0.057). Performance of the BD-Rel group was intermediate to that of BD and HC. Most sociodemographic and clinical variables did not affect these results in patients. (p≥0.1). However, treatment with carbamazepine and benzodiazepines may exert a iatrogenic effect on MMS performance (p≤0.006). Only right-handed subjects were included in this study. Substantial attrition over time was detected. There were significant differences between the patients´ MMS performance and that of healthy relatives and controls, regardless of most clinical and sociodemographic variables. Dysfunctional MMS could be considered an endophenotype of BD. Further studies are needed to rule out possible iatrogenic effects of some psychopharmacological treatments. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Comparison of robotics, functional electrical stimulation, and motor learning methods for treatment of persistent upper extremity dysfunction after stroke: a randomized controlled trial.

    Science.gov (United States)

    McCabe, Jessica; Monkiewicz, Michelle; Holcomb, John; Pundik, Svetlana; Daly, Janis J

    2015-06-01

    To compare response to upper-limb treatment using robotics plus motor learning (ML) versus functional electrical stimulation (FES) plus ML versus ML alone, according to a measure of complex functional everyday tasks for chronic, severely impaired stroke survivors. Single-blind, randomized trial. Medical center. Enrolled subjects (N=39) were >1 year postsingle stroke (attrition rate=10%; 35 completed the study). All groups received treatment 5d/wk for 5h/d (60 sessions), with unique treatment as follows: ML alone (n=11) (5h/d partial- and whole-task practice of complex functional tasks), robotics plus ML (n=12) (3.5h/d of ML and 1.5h/d of shoulder/elbow robotics), and FES plus ML (n=12) (3.5h/d of ML and 1.5h/d of FES wrist/hand coordination training). Primary measure: Arm Motor Ability Test (AMAT), with 13 complex functional tasks; secondary measure: upper-limb Fugl-Meyer coordination scale (FM). There was no significant difference found in treatment response across groups (AMAT: P≥.584; FM coordination: P≥.590). All 3 treatment groups demonstrated clinically and statistically significant improvement in response to treatment (AMAT and FM coordination: P≤.009). A group treatment paradigm of 1:3 (therapist/patient) ratio proved feasible for provision of the intensive treatment. No adverse effects. Severely impaired stroke survivors with persistent (>1y) upper-extremity dysfunction can make clinically and statistically significant gains in coordination and functional task performance in response to robotics plus ML, FES plus ML, and ML alone in an intensive and long-duration intervention; no group differences were found. Additional studies are warranted to determine the effectiveness of these methods in the clinical setting. Copyright © 2015 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

  14. Transplantation of human umbilical cord blood-derived mononuclear cells induces recovery of motor dysfunction in a rat model of Parkinson's disease

    Directory of Open Access Journals (Sweden)

    Chen C

    2016-04-01

    Full Text Available Chao Chen,1,* Jing Duan,1,* Aifang Shen,2,* Wei Wang,1 Hao Song,1 Yanming Liu,1 Xianjie Lu,1 Xiaobing Wang,2 Zhiqing You,1 Zhongchao Han,3,4 Fabin Han1 1Center for Stem Cells and Regenerative Medicine, The Liaocheng People's Hospital, Affiliated Liaocheng Hospital, Taishan Medical University, Shandong, People's Republic of China; 2Department of Gynecology and Obstetrics, The Liaocheng People's Hospital, Affiliated Liaocheng Hospital, Taishan Medical University, Shandong, People's Republic of China; 3The State Key Laboratory of Experimental Hematology, Institute of Hematology and Hospital of Blood Diseases, Chinese Academy of Medical Sciences, Peking Union of Medical College, Tianjin, People's Republic of China; 4National Engineering Research Center of Cell Products, AmCellGene Co. Ltd., TEDA, Tianjin, People's Republic of China*These authors contributed equally to this workAbstract: Human umbilical cord blood-derived mononuclear cells (hUCB-MNCs were reported to have neurorestorative capacity for neurological disorders such as stroke and traumatic brain injury. This study was performed to explore if hUCB-MNC transplantation plays any therapeutic effects for Parkinson's disease (PD in a 6-OHDA-lesioned rat model of PD. hUCB-MNCs were isolated from umbilical cord blood and administered to the striatum of the 6-OHDA-lesioned rats. The apomorphine-induced locomotive turning-overs were measured to evaluate the improvement of motor dysfunctions of the rats after administration of hUCB-MNCs. We observed that transplanted hUCB-MNCs significantly improve the motor deficits of the PD rats and that grafted hUCB-MNCs integrated to the host brains and differentiated to neurons and dopamine neurons in vivo after 16 weeks of transplantation. Our study provided evidence that transplanted hUCB-MNCs play therapeutic effects in a rat PD model by differentiating to neurons and dopamine neurons. Keywords: hUCB-MNCs, Parkinson's disease, transplantation

  15. Antagonist of peroxisome proliferator-activated receptor {gamma} induces cerebellar amyloid-{beta} levels and motor dysfunction in APP/PS1 transgenic mice

    Energy Technology Data Exchange (ETDEWEB)

    Du, Jing; Sun, Bing [Protein Science Key Laboratory of the Ministry of Education, Department of Biological Sciences and Biotechnology, School of Medicine, Tsinghua University, Beijing 100084 (China); Chen, Kui [Department of Pharmacology, Anhui Medical University, Hefei, Anhui 230032 (China); Fan, Li [Department of Pharmacology, Anhui Medical University, Hefei, Anhui 230032 (China); Cardiovascular Research, Starr Academic Center, Providence Heart and Vascular Institute, Portland, OR 97225 (United States); Wang, Zhao, E-mail: zwang@tsinghua.edu.cn [Protein Science Key Laboratory of the Ministry of Education, Department of Biological Sciences and Biotechnology, School of Medicine, Tsinghua University, Beijing 100084 (China)

    2009-07-03

    Recent evidences show that peroxisome proliferator-activated receptor {gamma} (PPAR{gamma}) is involved in the modulation of the amyloid-{beta} (A{beta}) cascade causing Alzheimer's disease (AD) and treatment with PPAR{gamma} agonists protects against AD pathology. However, the function of PPAR{gamma} steady-state activity in A{beta} cascade and AD pathology remains unclear. In this study, an antagonist of PPAR{gamma}, GW9662, was injected into the fourth ventricle of APP/PS1 transgenic mice to inhibit PPAR{gamma} activity in cerebellum. The results show that inhibition of PPAR{gamma} significantly induced A{beta} levels in cerebellum and caused cerebellar motor dysfunction in APP/PS1 transgenic mice. Moreover, GW9662 treatment markedly decreased the cerebellar levels of insulin-degrading enzyme (IDE), which is responsible for the cellular degradation of A{beta}. Since cerebellum is spared from significant A{beta} accumulation and neurotoxicity in AD patients and animal models, these findings suggest a crucial role of PPAR{gamma} steady-state activity in protection of cerebellum against AD pathology.

  16. Beneficial effects of a pyrroloquinolinequinone-containing dietary formulation on motor deficiency, cognitive decline and mitochondrial dysfunction in a mouse model of Alzheimer’s disease

    Directory of Open Access Journals (Sweden)

    Darrell Sawmiller

    2017-04-01

    Full Text Available Alzheimer’s disease (AD, a progressive neurodegenerative disorder, is linked to oxidative stress, altered amyloid precursor protein (APP proteolysis, tau hyperphosphorylation and the accumulation of amyloid-β (Aβ plaques and neurofibrillary tangles (NFT. A growing body of evidence suggests that mitochondrial dysfunction can be a key promoter of all of these pathologies and predicts that restoration of mitochondrial function might be a potential therapeutic strategy for AD. Therefore, in the present study, we tested the beneficial effect of a nutraceutical formulation Nutrastem II (Nutra II, containing NT020 (a mitochondrial restorative and antioxidant proprietary formulation and pyrroloquinolinequinone (PQQ, a stimulator of mitochondria biogenesis in 5XFAD transgenic mice. Animals were fed Nutra II for 12 weeks, starting at 3 months of age, after which behavioral and neuropathological endpoints were determined. The data from behavioral test batteries clearly revealed that dietary supplementation of Nutra II effectively ameliorated the motor deficiency and cognitive impairment of 5XFAD mice. In addition, Nutra II also protected mitochondrial function in 5XFAD mice brain, as evidenced by declined ROS levels and membrane hyperpolarization, together with elevated ATP levels and respiratory states. Interestingly, while Nutra II treatment only slightly reduced soluble Aβ42 levels, this formulation significantly impacted tau metabolism, as shown by reduced total and phosphorylated tau levels of 5XFAD mouse brain. Taken together, these preclinical findings confirm that mitochondrial function may be a key treatment target for AD and that Nutra II should be further investigated as a potential candidate for AD therapy.

  17. Sleep Deprivation-Induced Blood-Brain Barrier Breakdown and Brain Dysfunction are Exacerbated by Size-Related Exposure to Ag and Cu Nanoparticles. Neuroprotective Effects of a 5-HT3 Receptor Antagonist Ondansetron.

    Science.gov (United States)

    Sharma, Aruna; Muresanu, Dafin F; Lafuente, José V; Patnaik, Ranjana; Tian, Z Ryan; Buzoianu, Anca D; Sharma, Hari S

    2015-10-01

    Military personnel are often subjected to sleep deprivation (SD) during combat operations. Since SD is a severe stress and alters neurochemical metabolism in the brain, a possibility exists that acute or long-term SD will influence blood-brain barrier (BBB) function and brain pathology. This hypothesis was examined in young adult rats (age 12 to 14 weeks) using an inverted flowerpot model. Rats were placed over an inverted flowerpot platform (6.5 cm diameter) in a water pool where the water levels are just 3 cm below the surface. In this model, animals can go to sleep for brief periods but cannot achieve deep sleep as they would fall into water and thus experience sleep interruption. These animals showed leakage of Evans blue in the cerebellum, hippocampus, caudate nucleus, parietal, temporal, occipital, cingulate cerebral cortices, and brain stem. The ventricular walls of the lateral and fourth ventricles were also stained blue, indicating disruption of the BBB and the blood-cerebrospinal fluid barrier (BCSFB). Breakdown of the BBB or the BCSFB fluid barrier was progressive in nature from 12 to 48 h but no apparent differences in BBB leakage were seen between 48 and 72 h of SD. Interestingly, rats treated with metal nanoparticles, e.g., Cu or Ag, showed profound exacerbation of BBB disruption by 1.5- to 4-fold, depending on the duration of SD. Measurement of plasma and brain serotonin showed a close correlation between BBB disruption and the amine level. Repeated treatment with the serotonin 5-HT3 receptor antagonist ondansetron (1 mg/kg, s.c.) 4 and 8 h after SD markedly reduced BBB disruption and brain pathology after 12 to 24 h SD but not following 48 or 72 h after SD. However, TiO2-nanowired ondansetron (1 mg/kg, s.c) in an identical manner induced neuroprotection in rats following 48 or 72 h SD. However, plasma and serotonin levels were not affected by ondansetron treatment. Taken together, our observations are the first to show that (i) SD could induce BBB

  18. Dark chocolate exacerbates acne.

    Science.gov (United States)

    Vongraviopap, Saivaree; Asawanonda, Pravit

    2016-05-01

    The effects of chocolate on acne exacerbations have recently been reevaluated. For so many years, it was thought that it had no role in worsening acne. To investigate whether 99% dark chocolate, when consumed in regular daily amounts, would cause acne to worsen in acne-prone male subjects, twenty-five acne prone male subjects were asked to consume 25 g of 99% dark chocolate daily for 4 weeks. Assessments which included Leeds revised acne scores as well as lesion counts took place weekly. Food frequency questionnaire was used, and daily activities were recorded. Statistically significant changes of acne scores and numbers of comedones and inflammatory papules were detected as early as 2 weeks into the study. At 4 weeks, the changes remained statistically significant compared to baseline. Dark chocolate when consumed in normal amounts for 4 weeks can exacerbate acne in male subjects with acne-prone skin. © 2015 The International Society of Dermatology.

  19. Aspirin-Exacerbated Asthma

    OpenAIRE

    Varghese, Mathew; Lockey, Richard F

    2008-01-01

    This review focuses on aspirin-exacerbated asthma (AEA). The review includes historical perspective of aspirin, prevalence, pathogenesis, clinical features and treatment of AEA. The pathogenesis of AEA involves the cyclooxygenase and lipooxygenase pathway. Aspirin affects both of these pathways by inhibiting the enzyme cycooxygenase-1 (COX-1). Inhibition of COX-1 leads to a decrease in prostaglandin E2 (PGE2). The decrease in PGE2 results in an increase in cysteinyl leukotrienes by the lipoo...

  20. COPD exacerbation: Lost in translation

    Directory of Open Access Journals (Sweden)

    Bouros Demosthenes

    2009-01-01

    Full Text Available Abstract The introduction and acceptance of a standard definition for exacerbations of COPD can be helpful in prompt diagnosis and management of these events. The latest GOLD executive committee recognised this necessity and it has now included a definition of exacerbation in the guidelines for COPD which is an important step forward in the management of the disease. This definition is pragmatic and compromises the different approaches for exacerbation. However, the inclusion of the "healthcare utilisation" approach (".. may warrant a change in regular medication" in the definition may introduce in the diagnosis of exacerbation factors related to the access to health care services which may not be related to the underlying pathophysiologal process which characterizes exacerbations. It should be also noted that the aetiology of COPD exacerbations has not yet been included in the current definition. In this respect, the definition does not acknowledge the fact that many patients with COPD may suffer from additional conditions (i.e. congestive cardiac failure or pulmonary embolism that can masquerade as exacerbations but they should not be considered as causes of them. The authors therefore suggest that an inclusion of the etiologic factors of COPD exacerbations in the definition. Moreover, COPD exacerbations are characterized by increased airway and systemic inflammation and significant deterioration in lung fuction. These fundamental aspects should be accounted in diagnosis/definition of exacerbations. This could be done by the introduction of a "laboratory" marker in the diagnosis of these acute events. The authors acknowledge that the use of a test or a biomarker in the diagnosis of exacerbations meets certain difficulties related to performing lung function tests or to sampling during exacerbations. However, the introduction of a test that reflects airway or systemic inflammation in the diagnosis of exacerbations might be another step forward

  1. Exacerbations of asthma during pregnancy

    DEFF Research Database (Denmark)

    Ali, Z; Hansen, A V; Ulrik, C S

    2016-01-01

    that asthma exacerbations during pregnancy increase the risk of pre-eclampsia, gestational diabetes, placental abruption and placenta praevia. Furthermore, these women also have higher risk for breech presentation, haemorrhage, pulmonary embolism, caesarean delivery, maternal admission to the intensive care...... to these outcomes. In conclusion, asthma exacerbations during pregnancy are associated with complications of pregnancy, labour and delivery. Prevention of exacerbations is essential to reduce the risk of complications and poor outcome....

  2. Exacerbations of asthma - A descriptive study of 425 severe exacerbations

    NARCIS (Netherlands)

    Tattersfield, AE; Postma, DS; Barnes, PJ; Svensson, K; Bauer, CA; O'Byrne, PM; Lofdahl, CG; Pauwels, RA; Ullman, A

    The identification, prevention, and prompt treatment of exacerbations are major objectives of asthma management. We looked at change in PEF, symptoms, and use of rescue p-agonists during the 425 severe exacerbations that occurred during a 12-mo parallel group study (FACET) in which low and high

  3. Recovery of post stroke proximal arm function, driven by complex neuroplastic bilateral brain activation patterns and predicted by baseline motor dysfunction severity

    Directory of Open Access Journals (Sweden)

    Svetlana ePundik

    2015-07-01

    Full Text Available Objectives: Neuroplastic changes that drive recovery of shoulder/elbow function after stoke have been poorly understood. The purpose of this study was to determine the relationship between neuroplastic brain changes related to shoulder/elbow movement control in response to treatment and recovery of arm motor function in chronic stroke survivors. Methods: Twenty-three chronic stroke survivors were treated with 12 weeks of arm rehabilitation. Outcome measures included functional Magnetic Resonance Imaging (fMRI for the shoulder/elbow components of reach and a skilled motor function test (Arm Motor Abilities Test (AMAT, collected before and after treatment.Results: We observed two patterns of neuroplastic changes that were associated with gains in motor function: decreased or increased task-related brain activation. Those with significantly better motor function at baseline exhibited a decrease in brain activation in response to treatment, evident in the ipsilesional primary motor and contralesional supplementary motor regions; in contrast, those with greater baseline motor impairment, exhibited increased brain activation in response to treatment. There was an linear relationship between greater functional gain (AMAT and increased activation in bilateral primary motor, contralesional primary and secondary sensory regions, and contralesional lateral premotor area, after adjusting for baseline AMAT, age, and time since stroke. Conclusions: Recovery of functional reach involves recruitment of several contralesional and bilateral primary motor regions. In response to intensive therapy, the direction of functional brain change (i.e. increase or decrease in task-related brain recruitment for shoulder/elbow reach components depends on baseline level of motor function and may represent either different phases or different strategies of neuroplasticity that drive functional recovery.

  4. Aspirin-Exacerbated Asthma

    Directory of Open Access Journals (Sweden)

    Varghese Mathew

    2008-06-01

    Full Text Available This review focuses on aspirin-exacerbated asthma (AEA. The review includes historical perspective of aspirin, prevalence, pathogenesis, clinical features and treatment of AEA. The pathogenesis of AEA involves the cyclooxygenase and lipooxygenase pathway. Aspirin affects both of these pathways by inhibiting the enzyme cycooxygenase-1 (COX-1. Inhibition of COX-1 leads to a decrease in prostaglandin E2 (PGE2. The decrease in PGE2 results in an increase in cysteinyl leukotrienes by the lipooxygenase pathway involving the enzyme 5-lipooxygenase (5-LO. Leukotriene C4 (LTC4 synthase is the enzyme responsible for the production of leukotriene C4, the chief cysteinyl leukotriene responsible for AEA. There have been familial occurences of AEA. An allele of the LTC4 synthase gene in AEA is known as allele C. Allele C has a higher frequency in AEA. Clinical presentation includes a history of asthma after ingestion of aspirin, nasal congestion, watery rhinorrhea and nasal polyposis. Treatment includes leukotriene receptor antagonists, leukotriene inhibitors, aspirin desinsitaztion and surgery. AEA is the most well-defined phenotype of asthma. Although AEA affects adults and children with physician-diagnosed asthma, in some cases there is no history of asthma and AEA often goes unrecognized and underdiagnosed.

  5. [Treatment of multiple sclerosis symptoms and exacerbations].

    Science.gov (United States)

    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.

  6. Long-term dietary extra-virgin olive oil rich in polyphenols reverses age-related dysfunctions in motor coordination and contextual memory in mice: role of oxidative stress.

    Science.gov (United States)

    Pitozzi, Vanessa; Jacomelli, Michela; Catelan, Dolores; Servili, Maurizio; Taticchi, Agnese; Biggeri, Annibale; Dolara, Piero; Giovannelli, Lisa

    2012-12-01

    The aim of this study was to evaluate the effects of olive oil phenols on brain aging in mice and to verify whether the antioxidant and antiinflammatory activities of these polyphenols were involved. C57Bl/6J mice were fed from middle age to senescence with extra-virgin olive oil (10% wt/wt dry diet) rich in phenols (total polyphenol dose/day, 6 mg/kg). Behavioral tests were employed to assess cognitive, motor, and emotional behavior after 6 or 12 months of treatment. Parameters of oxidative status and inflammation were measured in different brain areas at the same times and evaluated for correlation with behavioral changes. The treatment with olive oil phenols improved contextual memory in the step-down test to levels similar to young animals and prevented the age-related impairment in motor coordination in the rotarod test. This motor effect was correlated with reduced lipid peroxidation in the cerebellum (pextra-virgin olive oil can improve some age-related dysfunctions by differentially affecting different brain areas. Such a modulation can be obtained with an olive oil intake that is normal in the Mediterranean area, provided that the oil has a sufficiently high content of polyphenols.

  7. Oculo-Visual Dysfunction in Parkinson’s Disease

    Science.gov (United States)

    Armstrong, R.A.

    2015-01-01

    This review describes the oculo-visual problems likely to be encountered in Parkinson’s disease (PD) with special reference to three questions: (1) are there visual symptoms characteristic of the prodromal phase of PD, (2) is PD dementia associated with specific visual changes, and (3) can visual symptoms help in the differential diagnosis of the parkinsonian syndromes, viz. PD, progressive supranuclear palsy (PSP), dementia with Lewy bodies (DLB), multiple system atrophy (MSA), and corticobasal degeneration (CBD)? Oculo-visual dysfunction in PD can involve visual acuity, dynamic contrast sensitivity, colour discrimination, pupil reactivity, eye movement, motion perception, and visual processing speeds. In addition, disturbance of visuo-spatial orientation, facial recognition problems, and chronic visual hallucinations may be present. Prodromal features of PD may include autonomic system dysfunction potentially affecting pupil reactivity, abnormal colour vision, abnormal stereopsis associated with postural instability, defects in smooth pursuit eye movements, and deficits in visuo-motor adaptation, especially when accompanied by idiopathic rapid eye movement (REM) sleep behaviour disorder. PD dementia is associated with the exacerbation of many oculo-visual problems but those involving eye movements, visuo-spatial function, and visual hallucinations are most characteristic. Useful diagnostic features in differentiating the parkinsonian symptoms are the presence of visual hallucinations, visuo-spatial problems, and variation in saccadic eye movement dysfunction. PMID:26599301

  8. Invited commentary on comparison of robotics, functional electrical stimulation, and motor learning methods for treatment of persistent upper extremity dysfunction after stroke: a randomized controlled trial.

    Science.gov (United States)

    Kwakkel, Gert; van Wegen, Erwin E; Meskers, Carel M

    2015-06-01

    In this issue of Archives of Physical Medicine and Rehabilitation, Jessica McCabe and colleagues report findings from their methodologically sound, dose-matched clinical trial in 39 patients beyond 6 months poststroke. In this phase II trial, the effects of 60 treatment sessions, each involving 3.5 hours of intensive practice plus either 1.5 hours of functional electrical stimulation (FES) or a shoulder-arm robotic therapy, were compared with 5 hours of intensive daily practice alone. Although no significant between-group differences were found on the primary outcome measure of Arm Motor Ability Test and the secondary outcome measure of Fugl-Meyer Arm motor score, 10% to 15% within-group therapeutic gains were on the Arm Motor Ability Test and Fugl-Meyer Arm. These gains are clinically meaningful for patients with stroke. However, the underlying mechanisms that drive these improvements remain poorly understood. The approximately $1000 cost reduction per patient calculated for the use of motor learning (ML) methods alone or combined with FES, compared with the combination of ML and shoulder-arm robotics, further emphasizes the need for cost considerations when making clinical decisions about selecting the most appropriate therapy for the upper paretic limb in patients with chronic stroke. Copyright © 2015 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

  9. Acute asthma exacerbations: an overview

    Directory of Open Access Journals (Sweden)

    Domenico Lorenzo Urso

    2014-07-01

    Full Text Available Asthma is a chronic inflammatory disease of the airways. All patient with asthma are at risk of having exacerbations characterized by worsening symptoms, airflow obstruction, and an increased requirement for rescue bronchodilators. Asthma exacerbations can be classified as mild, moderate, severe, or life threatening. The goals of treatment are correction of severe hypoxemia, rapid reversal of airflow obstruction, and reduction of the risk of relapse.http://dx.doi.org/10.7175/rhc.v5i3.932

  10. Subarachnoid Transplant of the Human Neuronal hNT2.19 Serotonergic Cell Line Attenuates Behavioral Hypersensitivity without Affecting Motor Dysfunction after Severe Contusive Spinal Cord Injury

    Directory of Open Access Journals (Sweden)

    Mary J. Eaton

    2011-01-01

    Full Text Available Transplant of cells which make biologic agents that can modulate the sensory and motor responses after spinal cord injury (SCI would be useful to treat pain and paralysis. To address this need for clinically useful human cells, a unique neuronal cell line that synthesizes and secretes/releases the neurotransmitter serotonin (5HT was isolated. Hind paw tactile allodynia and thermal hyperalgesia induced by severe contusive SCI were potently reversed after lumbar subarachnoid transplant of differentiated cells, but had no effect on open field motor scores, stride length, foot rotation, base of support, or gridwalk footfall errors associated with the SCI. The sensory effects appeared 1 week after transplant and did not diminish during the 8-week course of the experiment when grafts were placed 2 weeks after SCI. Many grafted cells were still present and synthesizing 5HT at the end of the study. These data suggest that the human neuronal serotonergic hNT2.19 cells can be used as a biologic minipump for receiving SCI-related neuropathic pain, but likely requires intraspinal grafts for motor recovery.

  11. A high-fat jelly diet restores bioenergetic balance and extends lifespan in the presence of motor dysfunction and lumbar spinal cord motor neuron loss in TDP-43A315T mutant C57BL6/J mice.

    Science.gov (United States)

    Coughlan, Karen S; Halang, Luise; Woods, Ina; Prehn, Jochen H M

    2016-09-01

    Transgenic transactivation response DNA-binding protein 43 (TDP-43) mice expressing the A315T mutation under control of the murine prion promoter progressively develop motor function deficits and are considered a new model for the study of amyotrophic lateral sclerosis (ALS); however, premature sudden death resulting from intestinal obstruction halts disease phenotype progression in 100% of C57BL6/J congenic TDP-43(A315T) mice. Similar to our recent results in SOD1(G93A) mice, TDP-43(A315T) mice fed a standard pellet diet showed increased 5' adenosine monophosphate-activated protein kinase (AMPK) activation at postnatal day (P)80, indicating elevated energetic stress during disease progression. We therefore investigated the effects of a high-fat jelly diet on bioenergetic status and lifespan in TDP-43(A315T) mice. In contrast to standard pellet-fed mice, mice fed high-fat jelly showed no difference in AMPK activation up to P120 and decreased phosphorylation of acetly-CoA carboxylase (ACC) at early-stage time points. Exposure to a high-fat jelly diet prevented sudden death and extended survival, allowing development of a motor neuron disease phenotype with significantly decreased body weight from P80 onward that was characterised by deficits in Rotarod abilities and stride length measurements. Development of this phenotype was associated with a significant motor neuron loss as assessed by Nissl staining in the lumbar spinal cord. Our work suggests that a high-fat jelly diet improves the pre-clinical utility of the TDP-43(A315T) model by extending lifespan and allowing the motor neuron disease phenotype to progress, and indicates the potential benefit of this diet in TDP-43-associated ALS. © 2016. Published by The Company of Biologists Ltd.

  12. A high-fat jelly diet restores bioenergetic balance and extends lifespan in the presence of motor dysfunction and lumbar spinal cord motor neuron loss in TDP-43A315T mutant C57BL6/J mice

    Directory of Open Access Journals (Sweden)

    Karen S. Coughlan

    2016-09-01

    Full Text Available Transgenic transactivation response DNA-binding protein 43 (TDP-43 mice expressing the A315T mutation under control of the murine prion promoter progressively develop motor function deficits and are considered a new model for the study of amyotrophic lateral sclerosis (ALS; however, premature sudden death resulting from intestinal obstruction halts disease phenotype progression in 100% of C57BL6/J congenic TDP-43A315T mice. Similar to our recent results in SOD1G93A mice, TDP-43A315T mice fed a standard pellet diet showed increased 5′ adenosine monophosphate-activated protein kinase (AMPK activation at postnatal day (P80, indicating elevated energetic stress during disease progression. We therefore investigated the effects of a high-fat jelly diet on bioenergetic status and lifespan in TDP-43A315T mice. In contrast to standard pellet-fed mice, mice fed high-fat jelly showed no difference in AMPK activation up to P120 and decreased phosphorylation of acetly-CoA carboxylase (ACC at early-stage time points. Exposure to a high-fat jelly diet prevented sudden death and extended survival, allowing development of a motor neuron disease phenotype with significantly decreased body weight from P80 onward that was characterised by deficits in Rotarod abilities and stride length measurements. Development of this phenotype was associated with a significant motor neuron loss as assessed by Nissl staining in the lumbar spinal cord. Our work suggests that a high-fat jelly diet improves the pre-clinical utility of the TDP-43A315T model by extending lifespan and allowing the motor neuron disease phenotype to progress, and indicates the potential benefit of this diet in TDP-43-associated ALS.

  13. Early detection of motor dysfunction in the SOD1G93A mouse model of Amyotrophic Lateral Sclerosis (ALS) using home cage running wheels.

    Science.gov (United States)

    Bennett, Ellen J; Mead, Richard J; Azzouz, Mimoun; Shaw, Pamela J; Grierson, Andrew J

    2014-01-01

    The SOD1G93A mouse has been used since 1994 for preclinical testing in amyotrophic lateral sclerosis (ALS). Despite recent genetic advances in our understanding of ALS, transgenic mice expressing mutant SOD1 remain the best available, and most widely used, vertebrate model of the disease. We previously described an optimised and rapid approach for preclinical studies in the SOD1G93A mouse. Here we describe improvements to this approach using home cage running wheels to obtain daily measurements of motor function, with minimal intervention. We show that home cage running wheels detect reductions in motor function at a similar time to the rotarod test, and that the data obtained are less variable allowing the use of smaller groups of animals to obtain satisfactory results. This approach refines use of the SOD1G93A model, and reduces the number of animals undergoing procedures of substantial severity, two central principles of the 3Rs (replacement, reduction and refinement of animal use in research). The small group sizes and rapid timescales enable affordable large-scale therapeutic pre-screening in the SOD1G93A mouse, as well as rapid validation of published positive effects in a second laboratory, one of the major stumbling blocks in ALS preclinical therapy development.

  14. Mitochondrial dysfunction in obesity.

    Science.gov (United States)

    de Mello, Aline Haas; Costa, Ana Beatriz; Engel, Jéssica Della Giustina; Rezin, Gislaine Tezza

    2018-01-01

    Obesity leads to various changes in the body. Among them, the existing inflammatory process may lead to an increase in the production of reactive oxygen species (ROS) and cause oxidative stress. Oxidative stress, in turn, can trigger mitochondrial changes, which is called mitochondrial dysfunction. Moreover, excess nutrients supply (as it commonly is the case with obesity) can overwhelm the Krebs cycle and the mitochondrial respiratory chain, causing a mitochondrial dysfunction, and lead to a higher ROS formation. This increase in ROS production by the respiratory chain may also cause oxidative stress, which may exacerbate the inflammatory process in obesity. All these intracellular changes can lead to cellular apoptosis. These processes have been described in obesity as occurring mainly in peripheral tissues. However, some studies have already shown that obesity is also associated with changes in the central nervous system (CNS), with alterations in the blood-brain barrier (BBB) and in cerebral structures such as hypothalamus and hippocampus. In this sense, this review presents a general view about mitochondrial dysfunction in obesity, including related alterations, such as inflammation, oxidative stress, and apoptosis, and focusing on the whole organism, covering alterations in peripheral tissues, BBB, and CNS. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Toward a Consensus Definition for COPD Exacerbations

    National Research Council Canada - National Science Library

    Roberto Rodriguez-Roisin

    2000-01-01

    .... Exacerbations are associated with a significant increase in mortality, hospitalization, and health-care utilization, but there is currently no widely accepted definition of what constitutes an exacerbation of COPD...

  16. Norepinephrine mediates the transcriptional effects of heterotypic chronic stress on colonic motor function.

    Science.gov (United States)

    Choudhury, Barun K; Shi, Xuan-Zheng; Sarna, Sushil K

    2009-06-01

    Chronic stress precipitates or exacerbates the symptoms of functional bowel disorders, including motility dysfunction. The cellular mechanisms of these effects are not understood. We tested the hypothesis that heterotypic chronic stress (HeCS) elevates the release of norepinephrine from the adrenal medulla, which enhances transcription of the gene-regulating expression of Ca(v)1.2 (L-type) channels in colonic circular smooth muscle cells, resulting in enhanced colonic motor function. The experiments were performed in rats using a 9-day heterotypic chronic stress (HeCS) protocol. We found that HeCS, but not acute stress, time dependently enhances the contractile response to ACh in colonic circular smooth muscle strips and in single dissociated smooth muscle cells, the plasma levels of norepinephrine and the mRNA and protein expressions of the alpha(1C) subunit of Ca(v)1.2 channels. These effects result in faster colonic transit and increase in defecation rate. The effects of HeCS are blocked by adrenalectomy but not by depletion of norepinephrine in sympathetic neurons. The inhibition of receptors for glucocortocoids, corticotropin-releasing hormone or nicotine also does not block the effects of heterotypic chronic stress. Norepinephrine acts on alpha- and beta(3)-adrenergic receptors to induce the transcription of alpha(1C) subunit. We conclude that HeCS alters colonic motor function by elevating the plasma levels of norepinephrine. Colonic motor dysfunction is associated with enhanced gene transcription of Ca(v)1.2 channels in circular smooth muscle cells. These findings suggest the potential cellular mechanisms by which heterotypic chronic stress may exacerbate motility dysfunction in patients with irritable bowel syndrome.

  17. Motor Impairments in Angelman Syndrome

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap

    2004-04-01

    Full Text Available Of 33 children and adolescents (median age 6 years investigated for learning disability, epilepsy, and motor dysfunction to detect suspected Angelman syndrome (AS, in a study at Goteborg University, Sweden, 23 fulfilled criteria for AS.

  18. Neural Stem Cells Rescue Cognitive and Motor Dysfunction in a Transgenic Model of Dementia with Lewy Bodies through a BDNF-Dependent Mechanism

    Directory of Open Access Journals (Sweden)

    Natalie R.S. Goldberg

    2015-11-01

    Full Text Available Accumulation of α-synuclein (α-syn into insoluble aggregates occurs in several related disorders collectively referred to as synucleinopathies. To date, studies have used neural stem cells (NSCs to examine questions about α-syn propagation, but have overlooked the therapeutic potential of NSC transplantation to modulate cognition in disorders such as dementia with Lewy bodies or Parkinson’s disease dementia. Here, we show that striatal transplantation of NSCs into aged α-syn transgenic mice significantly improves performance in multiple cognitive and motor domains. This recovery is associated with NSC expression of brain-derived neurotrophic factor (BDNF, which restores depleted levels and modulates dopaminergic and glutamatergic systems. Most importantly, transplantation of BDNF-depleted NSCs fails to improve behavior, whereas AAV-mediated BDNF delivery mimics the benefits of NSC transplantation, supporting a critical role for this neurotrophin in functional improvement. Thus, NSC transplantation could offer a promising approach to treat the understudied yet devastating cognitive components of many synucleinopathies.

  19. Neural Stem Cells Rescue Cognitive and Motor Dysfunction in a Transgenic Model of Dementia with Lewy Bodies through a BDNF-Dependent Mechanism.

    Science.gov (United States)

    Goldberg, Natalie R S; Caesar, Jacqueline; Park, Ashley; Sedgh, Shawn; Finogenov, Gilana; Masliah, Eliezer; Davis, Joy; Blurton-Jones, Mathew

    2015-11-10

    Accumulation of α-synuclein (α-syn) into insoluble aggregates occurs in several related disorders collectively referred to as synucleinopathies. To date, studies have used neural stem cells (NSCs) to examine questions about α-syn propagation, but have overlooked the therapeutic potential of NSC transplantation to modulate cognition in disorders such as dementia with Lewy bodies or Parkinson's disease dementia. Here, we show that striatal transplantation of NSCs into aged α-syn transgenic mice significantly improves performance in multiple cognitive and motor domains. This recovery is associated with NSC expression of brain-derived neurotrophic factor (BDNF), which restores depleted levels and modulates dopaminergic and glutamatergic systems. Most importantly, transplantation of BDNF-depleted NSCs fails to improve behavior, whereas AAV-mediated BDNF delivery mimics the benefits of NSC transplantation, supporting a critical role for this neurotrophin in functional improvement. Thus, NSC transplantation could offer a promising approach to treat the understudied yet devastating cognitive components of many synucleinopathies. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  20. Erectile Dysfunction

    Science.gov (United States)

    ... of things can interfere with sexual feelings and cause or worsen erectile dysfunction. These include: Depression, anxiety or other mental health conditions Stress Relationship problems due to stress, poor communication or other concerns ...

  1. Erectile Dysfunction

    Science.gov (United States)

    ... Diabetes Association. http://www.diabetes.org/living-with-diabetes/treatment-and-care/men/erectile-dysfunction.html. Accessed Nov. ... medicine and a synthesis of the main available therapies. Diabetes & Metabolism. 2012;38:1. Nippoldt TB (expert opinion). ...

  2. Orgasmic dysfunction

    Science.gov (United States)

    ... dysfunction is when a woman either cannot reach orgasm, or has trouble reaching orgasm when she is sexually excited. When sex is ... to 15% of women have never had an orgasm. Surveys suggest that up to one half of ...

  3. Erectile dysfunction

    National Research Council Canada - National Science Library

    Giuliano, F; Droupy, S

    2013-01-01

    Erectile dysfunction (ED) is the most commonly studied sexual disorder. ED is defined by a consistent or recurrent inability to attain and/or maintain penile erection sufficient for sexual activity...

  4. Erectile Dysfunction

    Science.gov (United States)

    ... rigid. Medications The oral medications for erectile dysfunction, sildenafil (Viagra), tadalafil (Cialis), and vardenafil (Levitra), relax the muscles ... to begin working; the erection helping effects of sildenafil and vardenafil last for about 8 hours and ...

  5. Erectile dysfunction

    Science.gov (United States)

    Yafi, Faysal A.; Jenkins, Lawrence; Albersen, Maarten; Corona, Giovanni; Isidori, Andrea M.; Goldfarb, Shari; Maggi, Mario; Nelson, Christian J.; Parish, Sharon; Salonia, Andrea; Tan, Ronny; Mulhall, John P.; Hellstrom, Wayne J. G.

    2016-01-01

    Erectile dysfunction is a multidimensional but common male sexual dysfunction that involves an alteration in any of the components of the erectile response, including organic, relational and psychological. Roles for nonendocrine (neurogenic, vasculogenic and iatrogenic) and endocrine pathways have been proposed. Owing to its strong association with metabolic syndrome and cardiovascular disease, cardiac assessment may be warranted in men with symptoms of erectile dysfunction. Minimally invasive interventions to relieve the symptoms of erectile dysfunction include lifestyle modifications, oral drugs, injected vasodilator agents and vacuum erection devices. Surgical therapies are reserved for the subset of patients who have contraindications to these nonsurgical interventions, those who experience adverse effects from (or are refractory to) medical therapy and those who also have penile fibrosis or penile vascular insufficiency. Erectile dysfunction can have deleterious effects on a man’s quality of life; most patients have symptoms of depression and anxiety related to sexual performance. These symptoms, in turn, affect his partner’s sexual experience and the couple’s quality of life. This Primer highlights numerous aspects of erectile dysfunction, summarizes new treatment targets and ongoing preclinical studies that evaluate new pharmacotherapies, and covers the topic of regenerative medicine, which represents the future of sexual medicine. PMID:27188339

  6. Infective Exacerbation of Pasteurella multocida

    Directory of Open Access Journals (Sweden)

    Mayumi Hamada

    2016-01-01

    Full Text Available An 89-year-old lady presented with a one-day history of shortness of breath as well as a cough productive of brown sputum. Her medical history was significant for chronic obstructive pulmonary disease (COPD. She was in severe type one respiratory failure and blood tests revealed markedly raised inflammatory markers; however her chest X-ray was clear. On examination there was bronchial breathing with widespread crepitations and wheeze. She was treated as per an infective exacerbation of COPD. Subsequent blood cultures grew Pasteurella multocida, a common commensal in the oropharynx of domesticated animals. The patient was then asked about any contact with animals, after which she revealed she had a dog and was bitten on her left hand the day before admission. We should not forget to enquire about recent history of injuries or animal bites when patients present acutely unwell. She made a complete recovery after treatment with penicillin.

  7. Asthma exacerbation prediction: recent insights.

    Science.gov (United States)

    Fleming, Louise

    2018-04-01

    Asthma attacks are frequent in children with asthma and can lead to significant adverse outcomes including time off school, hospital admission and death. Identifying children at risk of an asthma attack affords the opportunity to prevent attacks and improve outcomes. Clinical features, patient behaviours and characteristics, physiological factors, environmental data and biomarkers are all associated with asthma attacks and can be used in asthma exacerbation prediction models. Recent studies have better characterized children at risk of an attack: history of a severe exacerbation in the previous 12 months, poor adherence and current poor control are important features which should alert healthcare professionals to the need for remedial action. There is increasing interest in the use of biomarkers. A number of novel biomarkers, including patterns of volatile organic compounds in exhaled breath, show promise. Biomarkers are likely to be of greatest utility if measured frequently and combined with other measures. To date, most prediction models are based on epidemiological data and population-based risk. The use of digital technology affords the opportunity to collect large amounts of real-time data, including clinical and physiological measurements and combine these with environmental data to develop personal risk scores. These developments need to be matched by changes in clinical guidelines away from a focus on current asthma control and stepwise escalation in drug therapy towards inclusion of personal risk scores and tailored management strategies including nonpharmacological approaches. There have been significant steps towards personalized prediction models of asthma attacks. The utility of such models needs to be tested in the ability not only to predict attacks but also to reduce them.

  8. Laryngeal Dysfunction

    DEFF Research Database (Denmark)

    Hull, James H; Backer, Vibeke; Gibson, Peter G

    2016-01-01

    The larynx is one of the most highly innervated organs in humans and serves a number of vitally important, complex, and highly evolved biological functions. On a day-to-day basis, the larynx functions autonomously, addressing several roles including airway protection, swallowing, and phonation....... In some situations the larynx appears to adopt a functional state that could be considered maladaptive or "dysfunctional." This laryngeal dysfunction can underpin and account for a number of respiratory symptoms that otherwise appear incongruous with a clinical disease state and/or contribute...

  9. [Non-motor symptoms of Parkinson's disease

    NARCIS (Netherlands)

    Weerkamp, N.J.; Nijhof, A.; Tissingh, G.

    2012-01-01

    Parkinson's disease has traditionally been viewed as a disease with only motor features. Nowadays, a wide variety of non-motor symptoms and signs are also recognised as being characteristic of the disease. Non-motor symptoms, most importantly autonomic dysfunction, neuropsychiatric symptoms and

  10. Erectile dysfunction.

    Science.gov (United States)

    Khera, Mohit; Goldstein, Irwin

    2011-06-29

    Erectile dysfunction may affect 30% to 50% of men aged 40 to 70 years, with age, smoking, and obesity being the main risk factors, although 20% of cases have psychological causes. We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of phosphodiesterase inhibitors in men with erectile dysfunction of any cause? What are the effects of phosphodiesterase inhibitors on erectile dysfunction in men with diabetes, with cardiovascular disease, with spinal cord injury, and with prostate cancer or undergoing prostatectomy? What are the effects of drug treatments other than phosphodiesterase inhibitors in men with erectile dysfunction of any cause? What are the effects of devices, psychological/behavioural treatments, and alternative treatments in men with erectile dysfunction of any cause? We searched: Medline, Embase, The Cochrane Library, and other important databases up to August 2009 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). We found 81 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. In this systematic review we present information relating to the effectiveness and safety of the following interventions: alprostadil (intracavernosal, intraurethral, topical), cognitive behavioural therapy, ginseng, papaverine, papaverine plus phentolamine (bimix), papaverine plus phentolamine plus alprostadil (trimix), penile prostheses, phosphodiesterase inhibitors (sildenafil, tadalafil, vardenafil), psychosexual counselling, vacuum devices, and yohimbine.

  11. Cortical activation during finger tapping in thyroid dysfunction: A ...

    Indian Academy of Sciences (India)

    Keywords. fMRI; hypothyroid; hyperthyroid; motor task. Abstract. Thyroid dysfunction is associated with attention deficit and impairment of the motor system (muscle weakness and fatigue). This paper investigates possible motor function deficit in thyroid patients, compared to the controls. Functional MRI studies (fMRI) were ...

  12. Blood Coagulation and Asthma Exacerbation in Children.

    Science.gov (United States)

    Manuyakorn, Wiparat; Mairiang, Dara; Sirachainan, Nongnuch; Kadegasem, Praguywan; Kamchaisatian, Wasu; Benjaponpitak, Suwat; Chuansumrit, Ampaiwan

    2016-01-01

    Recent studies have demonstrated the activation of coagulation pathways in asthmatic airways. This study aimed to determine systemic blood coagulation during asthma exacerbation compared with the stable state in children. Pediatric patients (aged between 5 and 15 years) suffering from asthma exacerbation were enrolled. von Willebrand factor (vWF), plasminogen activator inhibitor type-1 (PAI-1), protein C, D-dimer, prothrombin fragment 1 + 2 (F1 + 2), thrombin-antithrombin complex (TAT), and C-reactive protein (CRP) levels were measured during asthma exacerbation and stable state. A total of 22 patients were enrolled. The median vWF, PAI-1, and CRP during asthma exacerbation were significantly higher than those of the stable state: 147.5% (interquartile range, IQR: 111.05-196.57) versus 94% (IQR: 69.72-109.62, p coagulation in asthma exacerbation. © 2016 S. Karger AG, Basel.

  13. [Treatment and prevention of COPD exacerbation].

    Science.gov (United States)

    Yamaya, Mutsuo; Yasuda, Hiroyasu; Yoshida, Motoki; Nishimura, Hidekazu; Nakayama, Katsutoshi

    2007-04-01

    Airway inflammation, mucosal edema, epithelial hyperpermeability, mucus secretion and airway smooth muscle contraction induced by airway bacterial, virus infection and exposure to air pollution may be associated with COPD exacerbation. Severity of COPD exacerbation is estimated by blood gas analysis, serum CRP values and the chest radiograph. Patients with COPD exacerbations are recommended to be treated with additional inhalations of beta-2 agonists and anti -cholinergic agents, systemic administered glucocorticosteroids, oxygen inhalation, and, in cases with purulent sputum, antibiotics. Glucocorticosteroids, beta-2 agonists and anti-cholinergic agents reduce the frequency of COPD exacerbation. We reported the inhibitory effects of glucocorticosteroids on rhinovirus infection, the major cause of common colds, and the inhibitory effects of L-carbocisteine and erythromycin on COPD exacerbations and rhinovirus infection.

  14. Optimizing antibiotic selection in treating COPD exacerbations

    Directory of Open Access Journals (Sweden)

    Attiya Siddiqi

    2008-03-01

    Full Text Available Attiya Siddiqi, Sanjay SethiDivision of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, Veterans Affairs Western New York Health Care System and University of Buffalo, State University of New York, Buffalo, New York, USAAbstract: Our understanding of the etiology, pathogenesis and consequences of acute exacerbations of chronic obstructive pulmonary disease (COPD has increased substantially in the last decade. Several new lines of evidence demonstrate that bacterial isolation from sputum during acute exacerbation in many instances reflects a cause-effect relationship. Placebo-controlled antibiotic trials in exacerbations of COPD demonstrate significant clinical benefits of antibiotic treatment in moderate and severe episodes. However, in the multitude of antibiotic comparison trials, the choice of antibiotics does not appear to affect the clinical outcome, which can be explained by several methodological limitations of these trials. Recently, comparison trials with nontraditional end-points have shown differences among antibiotics in the treatment of exacerbations of COPD. Observational studies that have examined clinical outcome of exacerbations have repeatedly demonstrated certain clinical characteristics to be associated with treatment failure or early relapse. Optimal antibiotic selection for exacerbations has therefore incorporated quantifying the risk for a poor outcome of the exacerbation and choosing antibiotics differently for low risk and high risk patients, reserving the broader spectrum drugs for the high risk patients. Though improved outcomes in exacerbations with antibiotic choice based on such risk stratification has not yet been demonstrated in prospective controlled trials, this approach takes into account concerns of disease heterogeneity, antibiotic resistance and judicious antibiotic use in exacerbations.Keywords: COPD, exacerbation, bronchitis, antibiotics

  15. Dietary Salt Exacerbates Experimental Colitis.

    Science.gov (United States)

    Tubbs, Alan L; Liu, Bo; Rogers, Troy D; Sartor, R Balfour; Miao, Edward A

    2017-08-01

    The Western diet is characterized by high protein, sugar, fat, and low fiber intake, and is widely believed to contribute to the incidence and pathogenesis of inflammatory bowel disease (IBD). However, high sodium chloride salt content, a defining feature of processed foods, has not been considered as a possible environmental factor that might drive IBD. We set out to bridge this gap. We examined murine models of colitis on either a high salt diet (HSD) or a low salt diet. We demonstrate that an HSD exacerbates inflammatory pathology in the IL-10-deficient murine model of colitis relative to mice fed a low salt diet. This was correlated with enhanced expression of numerous proinflammatory cytokines. Surprisingly, sodium accumulated in the colons of mice on an HSD, suggesting a direct effect of salt within the colon. Similar to the IL-10-deficient model, an HSD also enhanced cytokine expression during infection by Salmonella typhimurium This occurred in the first 3 d of infection, suggesting that an HSD potentiates an innate immune response. Indeed, in cultured dendritic cells we found that high salt media potentiates cytokine expression downstream of TLR4 activation via p38 MAPK and SGK1. A third common colitis model, administration of dextran sodium sulfate, was hopelessly confounded by the high sodium content of the dextran sodium sulfate. Our results raise the possibility that high dietary salt is an environmental factor that drives increased inflammation in IBD. Copyright © 2017 by The American Association of Immunologists, Inc.

  16. Can we predict fall asthma exacerbations? Validation of the seasonal asthma exacerbation index.

    Science.gov (United States)

    Hoch, Heather E; Calatroni, Agustin; West, Joseph B; Liu, Andrew H; Gergen, Peter J; Gruchalla, Rebecca S; Khurana Hershey, Gurjit K; Kercsmar, Carolyn M; Kim, Haejin; Lamm, Carin I; Makhija, Melanie M; Mitchell, Herman E; Teach, Stephen J; Wildfire, Jeremy J; Busse, William W; Szefler, Stanley J

    2017-10-01

    A Seasonal Asthma Exacerbation Predictive Index (saEPI) was previously reported based on 2 prior National Institute of Allergy and Infectious Diseases Inner City Asthma Consortium trials. This study sought to validate the saEPI in a separate trial designed to prevent fall exacerbations with omalizumab therapy. The saEPI and its components were analyzed to characterize those who had an asthma exacerbation during the Preventative Omalizumab or Step-Up Therapy for Fall Exacerbations (PROSE) study. We characterized those inner-city children with and without asthma exacerbations in the fall period treated with guidelines-based therapy (GBT) in the absence and presence of omalizumab. A higher saEPI was associated with an exacerbation in both the GBT alone (P asthma exacerbation in both groups. Copyright © 2017 American Academy of Allergy, Asthma & Immunology. All rights reserved.

  17. Asthma Exacerbation in Children: A Practical Review

    Directory of Open Access Journals (Sweden)

    Lin-Shien Fu

    2014-04-01

    Full Text Available Asthma is the most common chronic lower respiratory tract disease in childhood throughout the world. Despite advances in asthma management, acute exacerbations continue to be a major problem in patients and they result in a considerable burden on direct/indirect health care providers. A severe exacerbation occurring within 1 year is an independent risk factor. Respiratory tract viruses have emerged as the most frequent triggers of exacerbations in children. It is becoming increasingly clear that interactions may exist between viruses and other triggers, increasing the likelihood of an exacerbation. In this study, we provide an overview of current knowledge about asthma exacerbations, including its definition, impact on health care providers, and associated factors. Prevention management in intermittent asthma as well as intermittent wheeze in pre-school children and those with persistent asthma are discussed. Our review findings support the importance of controlling persistent asthma, as indicated in current guidelines. In addition, we found that early episodic intervention appeared to be crucial in preventing severe attacks and future exacerbations. Besides the use of medication, timely education after an exacerbation along with a comprehensive plan in follow up is also vitally important.

  18. Prevention of exacerbations of COPD with pharmacotherapy.

    Science.gov (United States)

    Miravitlles, M

    2010-06-01

    Exacerbations are a frequent event in the evolution of chronic obstructive pulmonary disease (COPD) patients. Individuals with COPD have a mean of 1-3 episodes per year, some of which lead to hospital admission and may even be a cause of death. The importance of COPD exacerbations has become increasingly apparent due to the impact these episodes have on the natural history of disease. It is now known that frequent exacerbations can adversely affect health-related quality of life and short- and long-term pulmonary function. Optimising treatment for stable COPD will help to reduce exacerbations. Long-acting bronchodilators, alone or combined with inhaled corticosteroids, have demonstrated efficacy in reducing the rate of exacerbations in patients with COPD. Other innovative approaches are being investigated, such as the long-term use of macrolides or the use of antibiotics in an effort to suppress bronchial colonisation and consequent exacerbations. Other drugs, such as mucolytics and immunomodulators, have recently provided positive results. Non-pharmacological interventions such as rehabilitation, self-management plans and the maintenance of high levels of physical activity in daily life are also useful strategies to prevent exacerbations in patients with COPD and should be implemented in regular clinical practice.

  19. Prevention of exacerbations of COPD with pharmacotherapy

    Directory of Open Access Journals (Sweden)

    M. Miravitlles

    2010-06-01

    Full Text Available Exacerbations are a frequent event in the evolution of chronic obstructive pulmonary disease (COPD patients. Individuals with COPD have a mean of 1–3 episodes per year, some of which lead to hospital admission and may even be a cause of death. The importance of COPD exacerbations has become increasingly apparent due to the impact these episodes have on the natural history of disease. It is now known that frequent exacerbations can adversely affect health-related quality of life and short- and long-term pulmonary function. Optimising treatment for stable COPD will help to reduce exacerbations. Long-acting bronchodilators, alone or combined with inhaled corticosteroids, have demonstrated efficacy in reducing the rate of exacerbations in patients with COPD. Other innovative approaches are being investigated, such as the long-term use of macrolides or the use of antibiotics in an effort to suppress bronchial colonisation and consequent exacerbations. Other drugs, such as mucolytics and immunomodulators, have recently provided positive results. Non-pharmacological interventions such as rehabilitation, self-management plans and the maintenance of high levels of physical activity in daily life are also useful strategies to prevent exacerbations in patients with COPD and should be implemented in regular clinical practice.

  20. Prevention of exacerbations of COPD with pharmacotherapy

    OpenAIRE

    M. Miravitlles

    2010-01-01

    Exacerbations are a frequent event in the evolution of chronic obstructive pulmonary disease (COPD) patients. Individuals with COPD have a mean of 1–3 episodes per year, some of which lead to hospital admission and may even be a cause of death. The importance of COPD exacerbations has become increasingly apparent due to the impact these episodes have on the natural history of disease. It is now known that frequent exacerbations can adversely affect health-related quality of life and short- an...

  1. Fine particulate matter in acute exacerbation of COPD

    Directory of Open Access Journals (Sweden)

    Lei eNi

    2015-10-01

    Full Text Available Chronic obstructive pulmonary disease (COPD is a common airway disorder. In particular, acute exacerbations of COPD (AECOPD can significantly reduce pulmonary function. The majority of AECOPD episodes are attributed to infections, although environmental stress also plays a role. Increasing urbanization and associated air pollution, especially in developing countries, have been shown to contribute to COPD pathogenesis. Elevated levels of particulate matter (PM in polluted air are strongly correlated with the onset and development of various respiratory diseases. In this review, we have conducted an extensive literature search of recent studies of the role of PM2.5 (fine PM in AECOPD. PM2.5 leads to AECOPD via inflammation, oxidative stress, immune dysfunction, and altered airway epithelial structure and microbiome. Reducing PM2.5 levels is a viable approach to lower AECOPD incidence, attenuate COPD progression and decrease the associated healthcare burden.

  2. Acute High Dose Lithium-Induced Exacerbation of Obsessive Compulsive Symptoms

    OpenAIRE

    Umesh, Shreekantiah; Sinha, Vinod Kumar

    2014-01-01

    Obsessive compulsive disorder (OCD) is a chronic neuropsychiatric disorder whose pathophysiology is linked to serotonergic dysfunction. More recently, the role of glutamate has also been posited. Lithium is used as an adjunctive for the treatment of OCD which is found to enhance serotonergic transmission. We present a case of OCD who was on stable dose of sertraline developed exacerbation of obsessive compulsive symptoms with acute high dose of lithium but improved after dose reduction.

  3. Motor Neurons

    DEFF Research Database (Denmark)

    Hounsgaard, Jorn

    2017-01-01

    Motor neurons translate synaptic input from widely distributed premotor networks into patterns of action potentials that orchestrate motor unit force and motor behavior. Intercalated between the CNS and muscles, motor neurons add to and adjust the final motor command. The identity and functional...

  4. Acute exacerbations of fibrotic interstitial lung disease.

    Science.gov (United States)

    Churg, Andrew; Wright, Joanne L; Tazelaar, Henry D

    2011-03-01

    An acute exacerbation is the development of acute lung injury, usually resulting in acute respiratory distress syndrome, in a patient with a pre-existing fibrosing interstitial pneumonia. By definition, acute exacerbations are not caused by infection, heart failure, aspiration or drug reaction. Most patients with acute exacerbations have underlying usual interstitial pneumonia, either idiopathic or in association with a connective tissue disease, but the same process has been reported in patients with fibrotic non-specific interstitial pneumonia, fibrotic hypersensitivity pneumonitis, desquamative interstitial pneumonia and asbestosis. Occasionally an acute exacerbation is the initial manifestation of underlying interstitial lung disease. On biopsy, acute exacerbations appear as diffuse alveolar damage or bronchiolitis obliterans organizing pneumonia (BOOP) superimposed upon the fibrosing interstitial pneumonia. Biopsies may be extremely confusing, because the acute injury pattern can completely obscure the underlying disease; a useful clue is that diffuse alveolar damage and organizing pneumonia should not be associated with old dense fibrosis and peripheral honeycomb change. Consultation with radiology can also be extremely helpful, because the fibrosing disease may be evident on old or concurrent computed tomography scans. The aetiology of acute exacerbations is unknown, and the prognosis is poor; however, some patients survive with high-dose steroid therapy. © 2010 Blackwell Publishing Limited.

  5. Vitamin D deficiency and adult asthma exacerbations.

    Science.gov (United States)

    Salas, Natalie Mariam; Luo, Li; Harkins, Michelle S

    2014-11-01

    There is growing evidence indicating a connection between vitamin D deficiency and the severity of asthma exacerbations. This study seeks to assess the relationship between vitamin D deficiency and the number and severity of asthma exacerbation in adults. A retrospective analysis was conducted in 92 patients being treated for asthma at the University of New Mexico Adult Asthma Clinic. Serum 25-hydroxyvitamin D3 levels were analyzed in adults with mild to severe persistent asthma. Using multi-variant modeling, the relationship was examined between serum vitamin D levels and the odds of asthma exacerbations ranging in severity from moderate to severe over the span of five years. This study demonstrates that vitamin D sufficiency was significantly associated with a decreased total number of asthma exacerbations (incidence rate ratio [IRR]: 0.61, 95% confidence interval [CI]: 0.44-0.84, p = 0.002), decreased total severe asthma exacerbations (IRR: 0.41, 95% CI: 0.24-0.72, p = 0.002) and decreased emergency room visits (IRR: 0.42, 95% CI: 0.20-0.88, p = 0.023). Vitamin D deficiency may be linked to the risk of severe asthma exacerbations in adults.

  6. Deep brain stimulation exacerbates hypokinetic dysarthria in a rat model of Parkinson's disease.

    Science.gov (United States)

    King, Nathaniel O; Anderson, Collin J; Dorval, Alan D

    2016-02-01

    Motor symptoms of Parkinson's disease (PD) follow the degeneration of dopaminergic neurons in the substantia nigra pars compacta. Deep brain stimulation (DBS) treats some parkinsonian symptoms, such as tremor, rigidity, and bradykinesia, but may worsen certain medial motor symptoms, including hypokinetic dysarthria. The mechanisms by which DBS exacerbates dysarthria while improving other symptoms are unclear and difficult to study in human patients. This study proposes an animal model of DBS-exacerbated dysarthria. We use the unilateral, 6-hydroxydopamine (6-OHDA) rat model of PD to test the hypothesis that DBS exacerbates quantifiable aspects of vocalization. Mating calls were recorded from sexually experienced male rats under healthy and parkinsonian conditions and during DBS of the subthalamic nucleus. Relative to healthy rats, parkinsonian animals made fewer calls with shorter and less complex vocalizations. In the parkinsonian rats, putatively therapeutic DBS further reduced call frequency, duration, and complexity. The individual utterances of parkinsonian rats spanned a greater bandwidth than those of healthy rats, potentially reducing the effectiveness of the vocal signal. This utterance bandwidth was further increased by DBS. We propose that the parkinsonism-associated changes in call frequency, duration, complexity, and dynamic range combine to constitute a rat analog of parkinsonian dysarthria. Because DBS exacerbates the parkinsonism-associated changes in each of these metrics, the subthalamic stimulated 6-OHDA rat is a good model of DBS-induced hypokinetic dysarthria in PD. This model will help researchers examine how DBS alleviates many motor symptoms of PD while exacerbating parkinsonian speech deficits that can greatly diminish patient quality of life. © 2015 Wiley Periodicals, Inc.

  7. Environmental enteric dysfunction and the fecal microbiota in Malawian children

    Science.gov (United States)

    Environmental enteric dysfunction (EED) is often measured with a dual sugar absorption test and implicated as a causative factor in childhood stunting. Disturbances in the gut microbiota are hypothesized to be a mechanism by which EED is exacerbated, although this supposition lacks support. We perfo...

  8. Beta cell dysfunction and insulin resistance

    Directory of Open Access Journals (Sweden)

    Marlon E Cerf

    2013-03-01

    Full Text Available Beta cell dysfunction and insulin resistance are inherently complex with their interrelation for triggering the pathogenesis of diabetes also somewhat undefined. Both pathogenic states induce hyperglycemia and therefore increase insulin demand. Beta cell dysfunction results from inadequate glucose sensing to stimulate insulin secretion therefore elevated glucose concentrations prevail. Persistently elevated glucose concentrations above the physiological range result in the manifestation of hyperglycemia. With systemic insulin resistance, insulin signaling within glucose recipient tissues is defective therefore hyperglycemia perseveres. Beta cell dysfunction supersedes insulin resistance in inducing diabetes. Both pathological states influence each other and presumably synergistically exacerbate diabetes. Preserving beta cell function and insulin signaling in beta cells and insulin signaling in the glucose recipient tissues will maintain glucose homeostasis.

  9. Intended and unintended (sensory-)motor coupling between the affected and unaffected upper limb in Complex Regional Pain Syndrome

    NARCIS (Netherlands)

    Bank, P.J.M.; Peper, C.E.; Marinus, J.; Van Hilten, J.J.; Beek, P.J.

    2015-01-01

    Background Motor dysfunction in complex regional pain syndrome (CRPS) has been associated with bilateral malfunction of sensory and motor circuits, which hints at abnormal coupling between the affected and the contralateral unaffected limb. In addition, clinical observations suggest that motor

  10. Acute bacterial exacerbations in bronchitis and asthma.

    Science.gov (United States)

    Chodosh, S

    1987-04-27

    Symptomatic exacerbations are frequent problems in the management of chronic bronchitis and bronchial asthma. Identification of a bacterial etiology as the cause of specific exacerbations should be based on changes in clinical symptoms and documentation of significant bronchial bacterial flora and a neutrophilic inflammatory response. Most acute bacterial exacerbations in patients with bronchitis or asthma are caused by Hemophilus influenzae, Streptococcus pneumoniae, or Branhamella catarrhalis. Treatment with ampicillins, synthetic tetracyclines, or trimethoprim/sulfamethoxazole is successful in 80 to 90 percent of bacterial exacerbations. Emergence of resistant Hemophilus species and pneumococci motivates development of new orally administered antimicrobial drugs. Appropriate treatment depends on the prompt recognition that bacterial infection is present. Once instituted, antimicrobial therapy should be continued for a minimum of 10 to 14 days, which should increase the duration of the infection-free period until the next bacterial exacerbation. Adequate response should be evaluated by the return of symptoms to pre-infectious levels and by decreased sputum bacterial flora and neutrophilic inflammation.

  11. Acute exacerbation of asthma: a case report

    Directory of Open Access Journals (Sweden)

    Domenico Lorenzo Urso

    2011-09-01

    Full Text Available Asthma is a chronic inflammatory disease of the airways with a worldwide prevalence ranging from 1% to 18%. We report the case of a 43-year-old man with acute asthma exacerbation admitted to Emergency Department. All patients with asthma are at risk of having exacerbations characterised by worsening symptoms, airflow obstruction, and an increased requirement for rescue bronchodilators. Patients should be evaluated and triaged quickly to assess the presence of exacerbations and the need for urgent intervention. The goals of treatment may be summarised as maintenance of adequate oxygen saturation with supplemental oxygen, relief of airway obstruction with repetitive administration of rapid-acting inhaled bronchodilators, and treatment of airway inflammation with systemic corticosteroids.

  12. [Asthmatic exacerbations: specific features in children].

    Science.gov (United States)

    Carsin, A; Pham-Thi, N

    2011-12-01

    Asthma concerns more than 10% of 10-year-old children. Despite the similarities between adult and childhood asthma, the pediatric population presents some specific characteristics, notably in relation to exacerbations. Asthma in the newborn infant is a specific entity, the definition of which has recently been officially recognized. In exacerbations, the most important trigger factors are respiratory virus infections, the strain having prognostic importance. The indoor and outdoor environments are risk factors, particularly high levels of atmospheric pollution. Nutrients seem to play a prognostic role through vitamin D or food allergy. Measurement of exhaled nitric oxide and examination of induced sputum may help in diagnosis and adjustment of treatment but these tools are not yet effective as predictive factors in asthma exacerbations. Prevention, early management and continued education of children and their families remain the best methods to improve asthma control. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

  13. Infant and child motor development.

    Science.gov (United States)

    Edwards, Sara L; Sarwark, John F

    2005-05-01

    Identifying infant and child developmental delay is a skill important for orthopaedic surgeons to master because they often are asked to distinguish between normal and abnormal movement. An emphasis has been placed on early detection and referral for intervention, which has been shown to enhance the lives of the infant or child and his or her family. Appropriate recognition of delay is necessary for referral to early intervention services, which serve to help these children overcome or improve motor dysfunction and to help families grow more confident in caring for children with special needs. We define early intervention, discuss normal and abnormal motor development, and provide useful examination tools to assess motor development.

  14. Acute exacerbation of airspace enlargement with fibrosis

    Directory of Open Access Journals (Sweden)

    Tomoyuki Kakugawa

    2014-01-01

    Full Text Available In 2008, Kawabata et al. described a lesion which they termed “airspace enlargement with fibrosis” that could be included on the spectrum of smoking-related interstitial lung diseases. This group also reported that patients with airspace enlargement with fibrosis but without coexisting interstitial pneumonia of another type had no acute exacerbations and favorable prognoses on clinical follow-up. Here we describe the first case, to our knowledge, of acute exacerbation of airspace enlargement with fibrosis without coexisting interstitial pneumonia of another type. An 82-year-old man was referred to our department for worsening dyspnea and new alveolar opacities on chest radiograph following left pulmonary segmentectomy (S6 for cancer. A diagnosis of acute exacerbation of airspace enlargement with fibrosis without coexisting interstitial pneumonia of other types was made, based on pathological evidence of airspace enlargement with fibrosis and organizing diffuse alveolar damage. Treatment with high-dose methylprednisolone followed by tapered oral prednisolone resulted in gradual improvement of the clinical condition and chest radiographic findings. Clinicians should be aware that patients with airspace enlargement with fibrosis may experience acute exacerbation.

  15. Prevention of Acute Exacerbations of COPD

    Science.gov (United States)

    Bourbeau, Jean; Diekemper, Rebecca L.; Ouellette, Daniel R.; Goodridge, Donna; Hernandez, Paul; Curren, Kristen; Balter, Meyer S.; Bhutani, Mohit; Camp, Pat G.; Celli, Bartolome R.; Dechman, Gail; Dransfield, Mark T.; Fiel, Stanley B.; Foreman, Marilyn G.; Hanania, Nicola A.; Ireland, Belinda K.; Marchetti, Nathaniel; Marciniuk, Darcy D.; Mularski, Richard A.; Ornelas, Joseph; Stickland, Michael K.

    2015-01-01

    BACKGROUND: COPD is a major cause of morbidity and mortality in the United States as well as throughout the rest of the world. An exacerbation of COPD (periodic escalations of symptoms of cough, dyspnea, and sputum production) is a major contributor to worsening lung function, impairment in quality of life, need for urgent care or hospitalization, and cost of care in COPD. Research conducted over the past decade has contributed much to our current understanding of the pathogenesis and treatment of COPD. Additionally, an evolving literature has accumulated about the prevention of acute exacerbations. METHODS: In recognition of the importance of preventing exacerbations in patients with COPD, the American College of Chest Physicians (CHEST) and Canadian Thoracic Society (CTS) joint evidence-based guideline (AECOPD Guideline) was developed to provide a practical, clinically useful document to describe the current state of knowledge regarding the prevention of acute exacerbations according to major categories of prevention therapies. Three key clinical questions developed using the PICO (population, intervention, comparator, and outcome) format addressed the prevention of acute exacerbations of COPD: nonpharmacologic therapies, inhaled therapies, and oral therapies. We used recognized document evaluation tools to assess and choose the most appropriate studies and to extract meaningful data and grade the level of evidence to support the recommendations in each PICO question in a balanced and unbiased fashion. RESULTS: The AECOPD Guideline is unique not only for its topic, the prevention of acute exacerbations of COPD, but also for the first-in-kind partnership between two of the largest thoracic societies in North America. The CHEST Guidelines Oversight Committee in partnership with the CTS COPD Clinical Assembly launched this project with the objective that a systematic review and critical evaluation of the published literature by clinical experts and researchers in

  16. Motor Music

    OpenAIRE

    Richards, John

    2014-01-01

    Motor Music II (2014) for small group and motors What happens when an AC or DC motor is plugged raw into a mixing desk or connected directly to a speaker? Motor Music II explores ‘low level’ instrument design and a reductionist approach. The piece also sets up a proposition concerning electronic music: ‘How can it be done simpler?’ The motor as ‘instrument’ encourages an objection-orientated approach to sound and music making: the motor itself has inherent musical qualities and po...

  17. Motor cortical activity during motor tasks is normal in patients with complex regional pain syndrome.

    Science.gov (United States)

    van Velzen, Gijsbrecht A J; Marinus, Johan; van Dijk, J Gert; van Zwet, Erik W; Schipper, Inger B; van Hilten, Jacobus J

    2015-01-01

    Motor dysfunction in complex regional pain syndrome (CRPS) is often considered a functional movement disorder. Earlier studies in patients with functional movement disorders found evidence of cortical inhibition during explicit but not implicit motor tasks, suggesting active inhibition from other brain areas. In this study, we explored whether active inhibition occurs in CRPS patients. We compared patients with CRPS with 2 control groups: healthy controls matched for age and sex, and patients whose hand was immobilized to treat a scaphoid fracture. We used transcranial magnetic stimulation to measure corticospinal excitability at rest and during motor imagery (explicit motor task) and motor observation (implicit motor task). Motor corticospinal excitation measured at rest and during implicit and explicit motor tasks was similar for CRPS patients and healthy controls. Patients with an immobilized hand showed an absence of motor cortical excitation of the corresponding hemisphere during motor imagery of tasks involving the immobilized hand, but not during motor observation. The normal motor cortical processing during motor imagery and motor observation found in the corresponding hemisphere of CPRS patients suggests that the nature of motor dysfunction in this condition differs from that described in literature for patients with functional paresis or under circumstances of limb immobilization. This study shows that the nature of motor dysfunction in CRPS patients differs from that encountered in patients with functional paresis or under circumstances of limb immobilization. This information is important for patients and pain clinicians and could help prevent implementation of therapeutic strategies based on incorrect assumptions. Copyright © 2015 American Pain Society. Published by Elsevier Inc. All rights reserved.

  18. SMN is required for sensory-motor circuit function in Drosophila

    Science.gov (United States)

    Imlach, Wendy L.; Beck, Erin S.; Choi, Ben Jiwon; Lotti, Francesco; Pellizzoni, Livio; McCabe, Brian D.

    2012-01-01

    Summary Spinal muscular atrophy (SMA) is a lethal human disease characterized by motor neuron dysfunction and muscle deterioration due to depletion of the ubiquitous Survival Motor Neuron (SMN) protein. Drosophila SMN mutants have reduced muscle size and defective locomotion, motor rhythm and motor neuron neurotransmission. Unexpectedly, restoration of SMN in either muscles or motor neurons did not alter these phenotypes. Instead, SMN must be expressed in proprioceptive neurons and interneurons in the motor circuit to non-autonomously correct defects in motor neurons and muscles. SMN depletion disrupts the motor system subsequent to circuit development and can be mimicked by the inhibition of motor network function. Furthermore, increasing motor circuit excitability by genetic or pharmacological inhibition of K+ channels can correct SMN-dependent phenotypes. These results establish sensory-motor circuit dysfunction as the origin of motor system deficits in this SMA model and suggest that enhancement of motor neural network activity could ameliorate the disease. PMID:23063130

  19. Non-motor extranigral signs and symptoms in Parkinson's disease

    NARCIS (Netherlands)

    Wolters, E.C.

    2009-01-01

    Clinical symptoms in Parkinson's disease (PD) comprise both motor and non-motor symptoms. In this disease, synucleinopathic-induced, nigral dopamine deficiency-related dysfunction of the basal ganglia is held responsible for the characteristic levodopa-responsive motor signs and symptoms

  20. 25-hydroxyvitamin D deficiency, exacerbation frequency and human rhinovirus exacerbations in chronic obstructive pulmonary disease

    Directory of Open Access Journals (Sweden)

    Quint Jennifer K

    2012-06-01

    Full Text Available Abstract Background 25-hydroxyvitamin D deficiency is associated with COPD and increased susceptibility to infection in the general population. Methods We investigated whether COPD patients deficient in 25-hydroxyvitamin D were more likely to be frequent exacerbators, had reduced outdoor activity and were more susceptible to human rhinovirus (HRV exacerbations than those with insufficient and normal levels. We also investigated whether the frequency of FokI, BsmI and TaqIα 25-hydroxyvitamin D receptor (VDR polymorphisms differed between frequent and infrequent exacerbators. Results There was no difference in 25-hydroxyvitamin D levels between frequent and infrequent exacerbators in the summer; medians 44.1nmol/L (29.1 – 68.0 and 39.4nmol/L (22.3 – 59.2 or winter; medians 24.9nmol/L (14.3 – 43.1 and 27.1nmol/L (19.9 – 37.6. Patients who spent less time outdoors in the 14 days prior to sampling had lower 25-hydroxyvitamin D levels (p = 0.02. Day length was independently associated with 25-hydroxyvitamin D levels (p = 0.02. There was no difference in 25-hydroxyvitamin D levels between baseline and exacerbation; medians 36.2nmol/L (IQR 22.4-59.4 and 33.3nmol/L (23.0-49.7; p = 0.43. HRV positive exacerbations were not associated with lower 25-hydroxyvitamin D levels at exacerbation than exacerbations that did not test positive for HRV; medians 30.0nmol/L (20.4 – 57.8 and 30.6nmol/L (19.4 – 48.7. There was no relationship between exacerbation frequency and any VDR polymorphisms (all p > 0.05. Conclusions Low 25-hydroxyvitamin D levels in COPD are not associated with frequent exacerbations and do not increase susceptibility to HRV exacerbations. Independent of day length, patients who spend less time outdoors have lower 25-hydroxyvitamin D concentration.

  1. Neonatal iron supplementation potentiates oxidative stress, energetic dysfunction and neurodegeneration in the R6/2 mouse model of Huntington's disease

    Directory of Open Access Journals (Sweden)

    Kiersten L. Berggren

    2015-04-01

    Full Text Available Huntington’s disease (HD is a progressive neurodegenerative disorder caused by a CAG repeat expansion that encodes a polyglutamine tract in huntingtin (htt protein. Dysregulation of brain iron homeostasis, oxidative stress and neurodegeneration are consistent features of the HD phenotype. Therefore, environmental factors that exacerbate oxidative stress and iron dysregulation may potentiate HD. Iron supplementation in the human population is common during infant and adult-life stages. In this study, iron supplementation in neonatal HD mice resulted in deterioration of spontaneous motor running activity, elevated levels of brain lactate and oxidized glutathione consistent with increased energetic dysfunction and oxidative stress, and increased striatal and motor cortical neuronal atrophy, collectively demonstrating potentiation of the disease phenotype. Oxidative stress, energetic, and anatomic markers of degeneration were not affected in wild-type littermate iron-supplemented mice. Further, there was no effect of elevated iron intake on disease outcomes in adult HD mice. We have demonstrated an interaction between the mutant huntingtin gene and iron supplementation in neonatal HD mice. Findings indicate that elevated neonatal iron intake potentiates mouse HD and promotes oxidative stress and energetic dysfunction in brain. Neonatal-infant dietary iron intake level may be an environmental modifier of human HD.

  2. Motor Fuel Excise Taxes

    Energy Technology Data Exchange (ETDEWEB)

    2015-09-01

    A new report from the National Renewable Energy Laboratory (NREL) explores the role of alternative fuels and energy efficient vehicles in motor fuel taxes. Throughout the United States, it is common practice for federal, state, and local governments to tax motor fuels on a per gallon basis to fund construction and maintenance of our transportation infrastructure. In recent years, however, expenses have outpaced revenues creating substantial funding shortfalls that have required supplemental funding sources. While rising infrastructure costs and the decreasing purchasing power of the gas tax are significant factors contributing to the shortfall, the increased use of alternative fuels and more stringent fuel economy standards are also exacerbating revenue shortfalls. The current dynamic places vehicle efficiency and petroleum use reduction polices at direct odds with policies promoting robust transportation infrastructure. Understanding the energy, transportation, and environmental tradeoffs of motor fuel tax policies can be complicated, but recent experiences at the state level are helping policymakers align their energy and environmental priorities with highway funding requirements.

  3. Pneumonic vs nonpneumonic acute exacerbations of COPD.

    Science.gov (United States)

    Lieberman, David; Lieberman, Devora; Gelfer, Yevgenia; Varshavsky, Raiesa; Dvoskin, Bella; Leinonen, Maija; Friedman, Maureen G

    2002-10-01

    To describe and compare the background, clinical manifestations, disease course, and infectious etiologies of pneumonic acute exacerbations (PNAE) vs nonpneumonic acute exacerbations (NPAE) of COPD. A prospective, observational study. A tertiary university medical center in southern Israel. Twenty-three hospitalizations for PNAE and 217 hospitalizations for NPAE were included in the study. Paired sera were obtained for each of the hospitalizations and were tested serologically for 12 pathogens. Only a significant change in antibody titers or levels was considered diagnostic. No significant differences were found between the two groups for any of the parameters related to COPD or comorbidity. The clinical type of the exacerbation was not significantly different between the groups. Compared to NPAE, patients with PNAE had lower PO(2) values at hospital admission (p = 0.004) but higher rates of abrupt onset (p = 0.005), ICU admissions (p = 0.006), invasive mechanical ventilation (p = 0.01), mortality (p = 0.007), and longer hospital stay (p = 0.001). In 22 PNAE hospitalizations (96%) and in 153 NPAE hospitalizations (71%), at least one infectious etiology was identified (p = 0.001). Mixed infection was found in 13 patients with PNAE (59%) and in 59 patients with NPAE (39%; not significant [NS]). Viral etiology was identified in 18 patients with PNAE (78%) compared with 99 patients with NPAE (46%; p = 0.003). Pneumococcal etiology was found in 10 patients with PNAE (43%) and in 38 patients with NPAE (18%; p = 0.006). An atypical etiology was identified in 8 patients with PNAE (35%) and 64 patients with NPAE (30%; NS). Community-acquired pneumonia is common among patients hospitalized for an acute exacerbation of COPD and is generally manifested by more severe clinical and laboratory parameters. In PNAE, compared to NPAE, viral and pneumococcal etiologies are more common, but the rate of atypical pathogens is similar. The therapeutic significance of these findings

  4. Visual dysfunction in Parkinson disease without dementia.

    Science.gov (United States)

    Uc, E Y; Rizzo, M; Anderson, S W; Qian, S; Rodnitzky, R L; Dawson, J D

    2005-12-27

    To determine the profiles of visual dysfunction and their relationship to motor and cognitive dysfunction and to disability in mild to moderate Parkinson disease (PD) without dementia. Seventy-six independently living participants with mild to moderate PD and 161 neurologically normal older adults were studied using a comprehensive battery to assess visual acuity, contrast sensitivity (CS), visual speed of processing and attention, spatial and motion perception, visual and verbal memory, visuoconstructional abilities, executive functions, depression, and motor function. Participants with PD scored significantly worse on all tests of vision and cognition compared with normal elderly persons. Reduced CS contributed to deficits on tests of spatial and motion perception and attention in participants with PD. Impairments in visual attention and spatial perception predicted worse cognitive function. Worse performances on tests of visual speed of processing and attention, spatial and motion perception, visual construction, and executive functions correlated with measures of postural instability and gait difficulty (in the Motor section of the Unified Parkinson's Disease Rating Scale). Impairments in motor function, visual memory, mood, and executive functions predicted worse disability as measured by Schwab-England Activities of Daily Living Scale. Patients with mild to moderate Parkinson disease showed impaired visual perception and cognition compared with elderly control subjects. Visual dysfunction contributes to parkinsonian disability through its influences on cognition and locomotion.

  5. Biomarkers Predictive of Exacerbations in the SPIROMICS and COPDGene Cohorts.

    Science.gov (United States)

    Keene, Jason D; Jacobson, Sean; Kechris, Katerina; Kinney, Gregory L; Foreman, Marilyn G; Doerschuk, Claire M; Make, Barry J; Curtis, Jeffrey L; Rennard, Stephen I; Barr, R Graham; Bleecker, Eugene R; Kanner, Richard E; Kleerup, Eric C; Hansel, Nadia N; Woodruff, Prescott G; Han, MeiLan K; Paine, Robert; Martinez, Fernando J; Bowler, Russell P; O'Neal, Wanda K

    2017-02-15

    Chronic obstructive pulmonary disease exacerbations are associated with disease progression, higher healthcare cost, and increased mortality. Published predictors of future exacerbations include previous exacerbation, airflow obstruction, poor overall health, home oxygen use, and gastroesophageal reflux. To determine the value of adding blood biomarkers to clinical variables to predict exacerbations. Subjects from the SPIROMICS (Subpopulations and Intermediate Outcomes Measures in COPD Study) (n = 1,544) and COPDGene (Genetic Epidemiology of COPD) (n = 602) cohorts had 90 plasma or serum candidate proteins measured on study entry using Myriad-RBM multiplex panels. We defined total exacerbations as subject-reported worsening in respiratory health requiring therapy with corticosteroids and/or antibiotics, and severe exacerbations as those leading to hospitalizations or emergency room visits. We assessed retrospective exacerbations during the 12 months before enrollment and then documented prospective exacerbations in each cohort. Exacerbations were modeled for biomarker associations with negative binomial regression including clinical covariates (age, sex, percent predicted FEV1, self-reported gastroesophageal reflux, St. George's Respiratory Questionnaire score, smoking status). We used the Stouffer-Liptak test to combine P values for metaanalysis. Between the two cohorts, 3,471 total exacerbations (1,044 severe) were reported. We identified biomarkers within each cohort that were significantly associated with a history of exacerbation and with a future exacerbation, but there was minimal replication between the cohorts. Although established clinical features were predictive of exacerbations, of the blood biomarkers only decorin and α2-macroglobulin increased predictive value for future severe exacerbations. Blood biomarkers were significantly associated with the occurrence of exacerbations but were not robust between cohorts and added little to the

  6. Fine particulate pollution and asthma exacerbations.

    Science.gov (United States)

    Bouazza, Naïm; Foissac, Frantz; Urien, Saik; Guedj, Romain; Carbajal, Ricardo; Tréluyer, Jean-Marc; Chappuy, Hélène

    2017-12-19

    As the results from epidemiological studies about the impact of outdoor air pollution on asthma in children are heterogeneous, our objective was to investigate the association between asthma exacerbation in children and exposure to air pollutants. A database of 1 264 585 paediatric visits during the 2010-2015 period to the emergency rooms from 20 emergency departments (EDs) of 'Assistance Publique Hôpitaux de Paris (APHP)', the largest hospital group in Europe, was used. A total of 47 107 visits were classified as asthma exacerbations. Concentration of air pollutants (nitrogen dioxide, ozone, fine particulate matter (PM) with an aerodynamic diameter smaller than 10  µm (PM10) and 2.5 µm (PM2.5)), as well as meteorological data, evolution of respiratory syncytial virus infection and pollen exposition, were collected on an hourly or daily basis for the same period using institutional databases. To assess the association between air pollution and asthma, mixed-effects quasi-Poisson regression modelling was performed. The only compound independently associated with ED visits for asthma was PM2.5 (Peffect, was estimated at 13.5 µg/m3. We found an association between daily asthma exacerbation in paediatric visits to the ED and fine particulate air pollutants. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  7. [Prevention of COPD exacerbation: a fundamental challenge].

    Science.gov (United States)

    Roche, N; Aguilaniu, B; Burgel, P-R; Durand-Zaleski, I; Dusser, D; Escamilla, R; Perez, T; Raherison, C; Similowski, T

    2012-06-01

    Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are a cause of suffering for patients and a burden for healthcare systems and society. Their prevention represents individual and collective challenge. The present article is based on the work of a group of experts who met on 5th and 6th May 2011 and seeks to highlight the importance of AECOPD. In the absence of easily quantifiable criteria, the definition of AECOPD varies in the literature, making identification difficult and affecting interpretation of study results. Exacerbations increase mortality and risk of cardiovascular disease. They also increase the risk of developing further exacerbations, accelerate the decline in lung function and contribute to reduction in muscle mass. By limiting physical activity and affecting mental state (anxiety, depression), AECOPD are disabling and impair quality of life. They increase work absenteeism and are responsible for about 60% of the global cost of COPD. Earlier identification with simple criteria, possibly associated to patient phenotyping, could be helpful in preventing hospitalization. Given their immediate and delayed impact, AECOPD should not be trivialized or neglected. Their prevention is a fundamental issue. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

  8. Myasthenia gravis exacerbation and diarrhea associated with erythromycin treatment

    Directory of Open Access Journals (Sweden)

    Sora Yasr

    2017-02-01

    Full Text Available An important problem in management of the case with myasthenia gravis (MG is the control of exacerbation. There are several possible causes of exacerbation of MG including the use of drug. Here, the authors report a case of MG exacerbation and diarrhea associated with erythromycin treatment.

  9. Adiponectin deficiency exacerbates age-related hearing impairment

    Science.gov (United States)

    Tanigawa, T; Shibata, R; Ouchi, N; Kondo, K; Ishii, M; Katahira, N; Kambara, T; Inoue, Y; Takahashi, R; Ikeda, N; Kihara, S; Ueda, H; Murohara, T

    2014-01-01

    Obesity-related disorders are closely associated with the development of age-related hearing impairment (ARHI). Adiponectin (APN) exerts protective effects against obesity-related conditions including endothelial dysfunction and atherosclerosis. Here, we investigated the impact of APN on ARHI. APN-knockout (APN-KO) mice developed exacerbation of hearing impairment, particularly in the high frequency range, compared with wild-type (WT) mice. Supplementation with APN prevented the hearing impairment in APN-KO mice. At 2 months of age, the cochlear blood flow and capillary density of the stria vascularis (SV) were significantly reduced in APN-KO mice as compared with WT mice. APN-KO mice also showed a significant increase in terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive apoptotic cells in the organ of Corti in the cochlea at 2 months of age. At the age of 6 months, hair cells were lost at the organ of Corti in APN-KO mice. In cultured auditory HEI-OC1 cells, APN reduced apoptotic activity under hypoxic conditions. Clinically, plasma APN levels were significantly lower in humans with ARHI. Multiple logistic regression analysis identified APN as a significant and independent predictor of ARHI. Our observations indicate that APN has an important role in preventing ARHI. PMID:24763046

  10. Acute exacerbation of sleep apnea by hyperoxia impairs cognitive flexibility in Brown-Norway rats.

    Science.gov (United States)

    Topchiy, Irina; Amodeo, Dionisio A; Ragozzino, Michael E; Waxman, Jonathan; Radulovacki, Miodrag; Carley, David W

    2014-11-01

    To determine whether learning deficits occur during acute exacerbation of spontaneous sleep related breathing disorder (SRBD) in rats with high (Brown Norway; BN) and low (Zucker Lean; ZL) apnea propensity. Spatial acquisition (3 days) and reversal learning (3 days) in the Morris water maze (MWM) with polysomnography (12:00-08:00): (1) with acute SRBD exacerbation (by 20-h hyperoxia immediately preceding reversal learning) or (2) without SRBD exacerbation (room air throughout). Randomized, placebo-controlled, repeated-measures design. 14 BN rats; 16 ZL rats. 20-h hyperoxia. Apneas were detected as cessation of respiration ≥ 2 sec. Swim latency in MWM, apnea indices (AI; apneas/hour of sleep) and percentages of recording time for nonrapid eye movement (NREM), rapid eye movement (REM), and total sleep were assessed. Baseline AI in BN rats was more than double that of ZL rats (22.46 ± 2.27 versus 10.7 ± 0.9, P = 0.005). Hyperoxia increased AI in both BN (34.3 ± 7.4 versus 22.46 ± 2.27) and ZL rats (15.4 ± 2.7 versus 10.7 ± 0.9) without changes in sleep stage percentages. Control (room air) BN and ZL rats exhibited equivalent acquisition and reversal learning. Acute exacerbation of AI by hyperoxia produced a reversal learning performance deficit in BN but not ZL rats. In addition, the percentage of REM sleep and REM apnea index in BN rats during hyperoxia negatively correlated with reversal learning performance. Acute exacerbation of sleep related breathing disorder by hyperoxia impairs reversal learning in a rat strain with high apnea propensity, but not a strain with a low apnea propensity. This suggests a non-linear threshold effect may contribute to the relationships between sleep apnea and cognitive dysfunctions, but strain-specific differences also may be important.

  11. Gut dysfunction in Parkinson's disease.

    Science.gov (United States)

    Mukherjee, Adreesh; Biswas, Atanu; Das, Shyamal Kumar

    2016-07-07

    Early involvement of gut is observed in Parkinson's disease (PD) and symptoms such as constipation may precede motor symptoms. α-Synuclein pathology is extensively evident in the gut and appears to follow a rostrocaudal gradient. The gut may act as the starting point of PD pathology with spread toward the central nervous system. This spread of the synuclein pathology raises the possibility of prion-like propagation in PD pathogenesis. Recently, the role of gut microbiota in PD pathogenesis has received attention and some phenotypic correlation has also been shown. The extensive involvement of the gut in PD even in its early stages has led to the evaluation of enteric α-synuclein as a possible biomarker of early PD. The clinical manifestations of gastrointestinal dysfunction in PD include malnutrition, oral and dental disorders, sialorrhea, dysphagia, gastroparesis, constipation, and defecatory dysfunction. These conditions are quite distressing for the patients and require relevant investigations and adequate management. Treatment usually involves both pharmacological and non-pharmacological measures. One important aspect of gut dysfunction is its contribution to the clinical fluctuations in PD. Dysphagia and gastroparesis lead to inadequate absorption of oral anti-PD medications. These lead to response fluctuations, particularly delayed-on and no-on, and there is significant relationship between levodopa pharmacokinetics and gastric emptying in patients with PD. Therefore, in such cases, alternative routes of administration or drug delivery systems may be required.

  12. Posterior Tibial Tendon Dysfunction

    Science.gov (United States)

    .org Posterior Tibial Tendon Dysfunction Page ( 1 ) Posterior tibial tendon dysfunction is one of the most common problems of the foot and ankle. It occurs when the posterior tibial tendon becomes inflamed or torn. As a result, the ...

  13. Female Sexual Dysfunction

    Science.gov (United States)

    ... medically as female sexual dysfunction. Many women experience problems with sexual function at some point. Female sexual dysfunction can occur at any stage of life. It can be lifelong or be acquired later in life. It can ...

  14. Medically treated exacerbations in COPD by GOLD 1-4

    DEFF Research Database (Denmark)

    Ingebrigtsen, Truls S.; Marott, Jacob L.; Lange, Peter

    2015-01-01

    -up. Construct validity of this definition of medically treated exacerbations was assessed by studying baseline determinants as well as by studying the association between GOLD 1 through 4 grades and time to first exacerbation during follow-up. RESULTS: Among individuals with COPD, 964 individuals (7.1%) had...... definition of exacerbations was robust and without major biases. CONCLUSIONS: Compared to individuals with GOLD 1, the risk of exacerbations was 17-fold for GOLD 4, 5-fold for GOLD 3, and 2-fold for GOLD 2. Medically treated exacerbations defined by register linkage seem a valid, robust, and low...

  15. Cannabis exacerbates depressive symptoms in rat model induced by reserpine.

    Science.gov (United States)

    Khadrawy, Yasser A; Sawie, Hussein G; Abdel-Salam, Omar M E; Hosny, Eman N

    2017-05-01

    Cannabis sativa is one of the most widely recreational drugs and its use is more prevalent among depressed patients. Some studies reported that Cannabis has antidepressant effects while others showed increased depressive symptoms in Cannabis users. Therefore, the present study aims to investigate the effect of Cannabis extract on the depressive-like rats. Twenty four rats were divided into: control, rat model of depression induced by reserpine and depressive-like rats treated with Cannabis sativa extract (10mg/kg expressed as Δ9-tetrahydrocannabinol). The depressive-like rats showed a severe decrease in motor activity as assessed by open field test (OFT). This was accompanied by a decrease in monoamine levels and a significant increase in acetylcholinesterase activity in the cortex and hippocampus. Na + ,K + -ATPase activity increased in the cortex and decreased in the hippocampus of rat model. In addition, a state of oxidative stress was evident in the two brain regions. This was indicated from the significant increase in the levels of lipid peroxidation and nitric oxide. No signs of improvement were observed in the behavioral and neurochemical analyses in the depressive-like rats treated with Cannabis extract. Furthermore, Cannabis extract exacerbated the lipid peroxidation in the cortex and hippocampus. According to the present findings, it could be concluded that Cannabis sativa aggravates the motor deficits and neurochemical changes induced in the cortex and hippocampus of rat model of depression. Therefore, the obtained results could explain the reported increase in the depressive symptoms and memory impairment among Cannabis users. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. Stability of the frequent COPD exacerbator in the general population

    DEFF Research Database (Denmark)

    Reilev, Mette; Lykkegaard, Jesper; Halling, Anders

    2017-01-01

    Exacerbation frequency is central in treatment strategies for chronic obstructive pulmonary disease. However, whether chronic obstructive pulmonary disease patients from the general population with frequent exacerbations continue to have frequent exacerbations over an extended period of time...... is currently unknown. In this study, we aimed to investigate the stability of the frequent exacerbator in a population-based setting. To this end, we conducted a nationwide register-based descriptive study with a 10-year follow-up period of chronic obstructive pulmonary disease patients with at least one...... medically treated exacerbation in 2003. Each subsequent year, we divided the population into frequent, infrequent and non-exacerbators and quantified the flow between categories. Further, we estimated the percentage of frequent exacerbators at baseline who stayed in this category each year during a 5-year...

  17. Rhinovirus-Induced Exacerbations of Asthma and COPD

    Science.gov (United States)

    Hershenson, Marc B.

    2013-01-01

    Over the past two decades, increasing evidence has shown that, in patients with chronic airways disease, viral infection is the most common cause of exacerbation. This review will examine the evidence for viral-induced exacerbations of asthma and chronic obstructive lung disease and the potential mechanisms by which viruses cause exacerbations. Attention will be focused on rhinovirus, the most common cause of respiratory exacerbations. Exacerbations due to rhinovirus, which infects relatively few cells in the airway and does not cause the cytotoxicity of other viruses such as influenza or respiratory syncytial virus, are particularly poorly understood. While the innate immune response likely plays a role in rhinovirus-induced exacerbations, its precise role, either adaptive or maladaptive, is debated. Because current treatment strategies are only partially effective, further research examining the cellular and molecular mechanisms underlying viral-induced exacerbations of chronic airways diseases is warranted. PMID:24278777

  18. The electric motor handbook

    Energy Technology Data Exchange (ETDEWEB)

    Hurst, R.W.; Feltham, P. (eds.)

    2004-05-01

    This handbook outlines the important role that electric motors play in modern society. It covers the field of motor applications from various motor types to their use and repair. It also presents practical applications of electric motors and methods on motor efficiency. More than half of all electricity generated, and 75 per cent of all industrial electricity consumption is consumed by electric motors. Electrical personnel must be aware of all factors involved in electric motors in order to choose and apply the appropriate size of electric motor. These factors include efficiency, sizing and proper application. The efficient use and maximum life expectancy of electric motors depends on proper motor protection, control and maintenance. This handbook includes articles from leading experts on electric motors in modern electrical systems. The content includes: design considerations; proper electric motor sizing techniques; optimal electric motor application; electric motor protection technology; electric motor control principles; electric motor maintenance and troubleshooting; induction electric motors; electric motor bearing currents; electric motor bearing lubrication; electromagnetism; electric motor enclosures; electric motor testing; electric motor repair; DC electric motor; electric motor starters; electric motor brushes; industrial electric motors; electric motor diagrams; AC electric motors; electric motor wiring; electric motor service; electric motor rewinding; electric motor winding; diagram of electric motor wiring; electric motor kit; and, troubleshooting electric motors. A directory of motor manufacturers and suppliers was also included. refs., tabs., figs.

  19. UVRAG Deficiency Exacerbates Doxorubicin-Induced Cardiotoxicity

    Science.gov (United States)

    An, Lin; Hu, Xiao-wen; Zhang, Shasha; Hu, Xiaowen; Song, Zongpei; Naz, Amber; Zi, Zhenguo; Wu, Jian; Li, Can; Zou, Yunzeng; He, Lin; Zhu, Hongxin

    2017-01-01

    Doxorubicin (DOX) is an effective chemotherapeutic drug in the treatment of various types of cancers. However, its clinical application has been largely limited by potential development of cardiotoxicity. Previously we have shown that ultra-violet radiation resistance-associated gene (UVRAG), an autophagy-related protein, is essential for the maintenance of autophagic flux in the heart under physiological conditions. Here, we sought to determine the role of UVRAG-mediated autophagy in DOX-induced cardiotoxicity. Mouse models of acute or chronic DOX-induced cardiotoxicity were established. UVRAG deficiency exacerbated DOX-induced mortality and cardiotoxicity manifested by increased cytoplasmic vacuolization, enhanced collagen accumulation, elevated serum activities of lactate dehydrogenase and myocardial muscle creatine kinase, higher ROS levels, aggravated apoptosis and more depressed cardiac function. Autophagic flux was impaired in DOX-induced cardiotoxicity. UVRAG deficiency aggravated impaired autophagic flux in DOX-induced cardiotoxicity. Intermittent fasting restored autophagy and ameliorated pathological alterations of DOX-induced cardiotoxicity. Collectively, our data suggest that UVRAG deficiency exacerbates DOX-induced cardiotoxicity, at least in part, through aggravation of DOX-induced impaired autophagic flux. Intermittent fasting, which restores blunted autophagic flux and ameliorates pathology in the mouse models of DOX-induced cardiotoxicity, may be used as a potential preventive or therapeutic approach for DOX cardiotoxicity. PMID:28225086

  20. Motor teams :

    Indian Academy of Sciences (India)

    . Switch. Welte et al, 1998, Gross et al, 2002. Motion of Lipid droplets in Drosophila embryos. Page 7. • Stochastic transitions between two species of motor yields Bidirectional motion. • Tuning of single-motor parameters. • No need to invoke a ...

  1. Seasonal Risk Factors for Asthma Exacerbations among Inner City Children

    Science.gov (United States)

    Teach, Stephen J.; Gergen, Peter J.; Szefler, Stanley J.; Mitchell, Herman E.; Calatroni, Agustin; Wildfire, Jeremy; Bloomberg, Gordon; Kercsmar, Carolyn; Liu, Andrew H.; Makhija, Melanie; Matsui, Elizabeth; Morgan, Wayne; O'Connor, George; Busse, William W.

    2015-01-01

    Background Exacerbations of asthma remain common even in children and adolescents despite optimal medical management. Identification of host risk factors for exacerbations is incomplete, particularly for seasonal episodes. Objective Define host risk factors for asthma exacerbations unique to their season of occurrence. Methods This is a retrospective analysis of patients aged 6-20 years who comprised the control groups of the Asthma Control Evaluation trial and the Inner City Anti-IgE Therapy for Asthma trial. Univariate and multivariate models were constructed to determine if patient demographic and historical factors, allergic sensitization, fractional exhaled nitric oxide, spirometric measurements, asthma control, and treatment requirements were associated with seasonal exacerbations. Results The analysis included 400 patients (54.5% male; 59.0% African American; median age 13 years). Exacerbations occurred in 37.5% of participants over the periods of observation and were most common in the fall (28.8% of participants). In univariate analysis, impaired pulmonary function was significantly associated with greater odds of exacerbations for all seasons, as was an exacerbation in the previous season for all seasons except spring. In multivariate analysis, exacerbation in the previous season was the strongest predictor in fall and winter while a higher requirement for inhaled corticosteroids was the strongest predictor in spring and summer. The multivariate models had the best predictive power for fall exacerbations (30.5% variance attributed). Conclusions Among a large cohort of inner city children with asthma, patient risk factors for exacerbations vary by season. Thus, individual patient information may be beneficial in strategies to prevent these seasonal events. Clinical Implications Inner city children remain at risk for asthma exacerbations despite appropriate therapy. Because their risk factors vary by season, strategies to prevent them may need to differ as

  2. Molecular motors

    Science.gov (United States)

    Allemand, Jean François Desbiolles, Pierre

    2015-10-01

    How do we move? More precisely, what are the molecular mechanisms that can explain that our muscles, made of very small components can move at a osopic scale? To answer these questions we must introduce molecular motors. Those motors are proteins, or small protein assemblies that, in our cells, transform chemical energy into mechanical work. Then, like we could do for a oscopic motor, used in a car or in a fan, we are going to study the basic behavior of these molecular machines, present what are their energy sources, calculate their power, their yield. If molecular motors are crucial for our oscopic movements, we are going to see that they are also essential to cellular transport and that considering the activity of some enzymes as molecular motors bring some interesting new insights on their activity.

  3. Stiffness-activated GEF-H1 expression exacerbates LPS-induced lung inflammation.

    Directory of Open Access Journals (Sweden)

    Isa Mambetsariev

    Full Text Available Acute lung injury (ALI is accompanied by decreased lung compliance. However, a role of tissue mechanics in modulation of inflammation remains unclear. We hypothesized that bacterial lipopolysacharide (LPS stimulates extracellular matrix (ECM production and vascular stiffening leading to stiffness-dependent exacerbation of endothelial cell (EC inflammatory activation and lung barrier dysfunction. Expression of GEF-H1, ICAM-1, VCAM-1, ECM proteins fibronectin and collagen, lysyl oxidase (LOX activity, interleukin-8 and activation of Rho signaling were analyzed in lung samples and pulmonary EC grown on soft (1.5 or 2.8 kPa and stiff (40 kPa substrates. LPS induced EC inflammatory activation accompanied by expression of ECM proteins, increase in LOX activity, and activation of Rho signaling. These effects were augmented in EC grown on stiff substrate. Stiffness-dependent enhancement of inflammation was associated with increased expression of Rho activator, GEF-H1. Inhibition of ECM crosslinking and stiffening by LOX suppression reduced EC inflammatory activation and GEF-H1 expression in response to LPS. In vivo, LOX inhibition attenuated LPS-induced expression of GEF-H1 and lung dysfunction. These findings present a novel mechanism of stiffness-dependent exacerbation of vascular inflammation and escalation of ALI via stimulation of GEF-H1-Rho pathway. This pathway represents a fundamental mechanism of positive feedback regulation of inflammation.

  4. Swallowing dysfunction in cancer patients.

    Science.gov (United States)

    Raber-Durlacher, Judith E; Brennan, Mike T; Verdonck-de Leeuw, Irma M; Gibson, Rachel J; Eilers, June G; Waltimo, Tuomas; Bots, Casper P; Michelet, Marisol; Sollecito, Thomas P; Rouleau, Tanya S; Sewnaik, Aniel; Bensadoun, Rene-Jean; Fliedner, Monica C; Silverman, Sol; Spijkervet, Fred K L

    2012-03-01

    Dysphagia (swallowing dysfunction) is a debilitating, depressing, and potentially life-threatening complication in cancer patients that is likely underreported. The present paper is aimed to review relevant dysphagia literature between 1990 and 2010 with a focus on assessment tools, prevalence, complications, and impact on quality of life in patients with a variety of different cancers, particularly in those treated with curative chemoradiation for head and neck cancer. The literature search was limited to the English language and included both MEDLINE/PubMed and EMBASE. The search focused on papers reporting dysphagia as a side effect of cancer and cancer therapy. We identified relevant literature through the primary literature search and by articles identified in references. A wide range of assessment tools for dysphagia was identified. Dysphagia is related to a number of factors such as direct impact of the tumor, cancer resection, chemotherapy, and radiotherapy and to newer therapies such as epidermal growth factor receptor inhibitors. Concomitant oral complications such as xerostomia may exacerbate subjective dysphagia. Most literature focuses on head and neck cancer, but dysphagia is also common in other types of cancer. Swallowing impairment is a clinically relevant acute and long-term complication in patients with a wide variety of cancers. More prospective studies on the course of dysphagia and impact on quality of life from baseline to long-term follow-up after various treatment modalities, including targeted therapies, are needed.

  5. Jet Fuel Exacerbated Noise-Induced Hearing Loss: Focus on Prediction of Central Auditory Processing Dysfunction

    Science.gov (United States)

    2017-09-01

    blood, cochlea, fat, kidney, skull, and three brain sections: frontal lobe , brain stem and temporal lobe . Tissue samples (ranging from 15 to 100...content, fresh rat tissues (brain stem, temporal lobe and frontal lobe , skull, cochlea, kidney and fat) were obtained. Data were collected from 10...percent, respectively. The brainstem, temporal lobe , and frontal lobe contained about 70.82 (± 3.43), 79.82 (± 0.49), and 79.25 (± 0.62) percent water

  6. C-C Motif Chemokine Receptor 9 Exacerbates Pressure Overload-Induced Cardiac Hypertrophy and Dysfunction.

    Science.gov (United States)

    Xu, Zhengxi; Mei, Fanghua; Liu, Hanning; Sun, Cheng; Zheng, Zhe

    2016-05-04

    Maladaptive cardiac hypertrophy is a major risk factor for heart failure, which is the leading cause of death worldwide. C-C motif chemokine receptor 9 (CCR9), a subfamily of the G protein-coupled receptor supergene family, has been highlighted as an immunologic regulator in the development and homing of immune cells and in immune-related diseases. Recently, CCR9 was found to be involved in the pathogenesis of other diseases such as cardiovascular diseases; however, the effects that CCR9 exerts in cardiac hypertrophy remain elusive. We observed significantly increased CCR9 protein levels in failing human hearts and in a mouse or cardiomyocyte hypertrophy model. In loss- and gain-of-function experiments, we found that pressure overload-induced hypertrophy was greatly attenuated by CCR9 deficiency in cardiac-specific CCR9 knockout mice, whereas CCR9 overexpression in cardiac-specific transgenic mice strikingly enhanced cardiac hypertrophy. The prohypertrophic effects of CCR9 were also tested in vitro, and a similar phenomenon was observed. Consequently, we identified a causal role for CCR9 in pathological cardiac hypertrophy. Mechanistically, we revealed a lack of difference in the expression levels of mitogen-activated protein kinases between groups, whereas the phosphorylation of AKT/protein kinase B and downstream effectors significantly decreased in CCR9 knockout mice and increased in CCR9 transgenic mice after aortic binding surgery. The prohypertrophic effects of CCR9 were not attributable to the mitogen-activated protein kinase signaling pathway but rather to the AKT-mammalian target of rapamycin-glycogen synthase kinase 3β signaling cascade. © 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

  7. Chronic nitric oxide synthase inhibition exacerbates renal dysfunction in cirrhotic rats

    DEFF Research Database (Denmark)

    Graebe, Martin; Brond, Lone; Christensen, Sten

    2004-01-01

    performed, followed by Western blotting of the electroneutral type 3 sodium/proton exchanger (NHE3) and the Na-K-ATPase present in proximal tubules. Untreated CBL rats showed a decreased proximal reabsorption with a concomitant reduction of NHE3 and Na-K-ATPase levels, indicating that tubular segments...

  8. Does Attention-Deficit-Hyperactivity Disorder Exacerbate Executive Dysfunction in Children with Neurofibromatosis Type 1?

    Science.gov (United States)

    Payne, Jonathan M.; Arnold, Shelley S.; Pride, Natalie A.; North, Kathryn N.

    2012-01-01

    Aim: Although approximately 40% of children with neurofibromatosis type 1 (NF1) meet diagnostic criteria for attention-deficit-hyperactivity disorder (ADHD), the impact of ADHD on the executive functioning of children with NF1 is not understood. We investigated whether spatial working memory and response inhibition are impaired in children with…

  9. Pidotimod activity against chronic bronchitis exacerbations.

    Science.gov (United States)

    Ciaccia, A

    1994-12-01

    The efficacy of pidotimod ((R)-3-[(S)-(5-oxo-2-pyrrolidinyl) carbonyl]-thiazolidine-4-carboxylic acid, PGT/1A, CAS 121808-62-6) in the management of infectious exacerbations of chronic bronchitis was evaluated in a double-blind, placebo-controlled study in parallel groups over 5 months (60 days of treatment and 90 days of follow-up). The study enrolled 580 patients, of whom 514 could be evaluated. The pidotimod group had fewer and shorter infectious episodes, fewer days of antibiotic therapy and fewer days unable to undertake normal activities. The difference vs. placebo was significant during the follow-up period and, in those subjects with a less severe history, during the treatment period also. Pidotimod was well tolerated.

  10. Role of antileukotrienes in acute asthma exacerbations

    Directory of Open Access Journals (Sweden)

    Domenico Lorenzo Urso

    2012-04-01

    Full Text Available Acute asthma exacerbations are one of the most frequent reasons to visit the emergency department or general practitioner. Although current standard treatments for acute asthma – including supplemental oxygen, short-acting β2-agonists, systemic corticosteroids and anticholinergics – are quite effective in most patients, they are inadequate for rapid and sustained improvement in a significant proportion. The antileukotrienes, a relatively new class of drugs, have a role in the treatment of chronic asthma. Their relatively rapid onset of action after endovenous or oral administration and their additive effect to β2-agonists led to the hypothesis that they might be of benefit in acute asthma. This review examines the efficacy of antileukotrienes in the treatment of acute asthma.

  11. Stepper motor

    Science.gov (United States)

    Dekramer, Cornelis

    1994-01-01

    The purpose of this document is to describe the more commonly used permanent magnet stepper motors for spaceflight. It will discuss the mechanical and electrical aspects of the devices, their torque behavior, those parameters which need to be controlled and measured, and test methods to be employed. It will also discuss torque margins, compare these to the existing margin requirements, and determine the applicability of these requirements. Finally it will attempt to generate a set of requirements which will be used in any stepper motor procurement and will fully characterize the stepper motor behavior in a consistent and repeatable fashion.

  12. Exacerbating factors of itch in atopic dermatitis

    Directory of Open Access Journals (Sweden)

    Hiroyuki Murota

    2017-01-01

    Full Text Available Atopic dermatitis (AD displays different clinical symptoms, progress, and response to treatment during early infancy and after childhood. After the childhood period, itch appears first, followed by formation of well-circumscribed plaque or polymorphous dermatoses at the same site. When accompanied with dermatitis and dry skin, treatment of skin lesions should be prioritized. When itch appears first, disease history, such as causes and time of appearance of itch should be obtained by history taking. In many cases, itch increases in the evening when the sympathetic nerve activity decreased. Treatment is provided considering that hypersensitivity to various external stimulations can cause itch. Heat and sweating are thought to especially exacerbate itch. Factors causing itch, such as cytokines and chemical messengers, also induce itch mainly by stimulating the nerve. Scratching further aggravates dermatitis. Skin hypersensibility, where other non-itch senses, such as pain and heat, are felt as itch, sometimes occurs in AD. Abnormal elongation of the sensory nerve into the epidermis, as well as sensitizing of the peripheral/central nerve, are possible causes of hypersensitivity, leading to itch. To control itch induced by environmental factors such as heat, treatment for dermatitis is given priority. In the background of itch exacerbated by sweating, attention should be given to the negative impact of sweat on skin homeostasis due to 1 leaving excess sweat on the skin, and 2 heat retention due to insufficient sweating. Excess sweat on the skin should be properly wiped off, and dermatitis should be controlled so that appropriate amount of sweat can be produced. Not only stimulation from the skin surface, but also visual and auditory stimulation can induce new itch. This “contagious itch” can be notably observed in patients with AD. This article reviews and introduces causes of aggravation of itch and information regarding how to cope with such

  13. Exacerbating factors of itch in atopic dermatitis.

    Science.gov (United States)

    Murota, Hiroyuki; Katayama, Ichiro

    2017-01-01

    Atopic dermatitis (AD) displays different clinical symptoms, progress, and response to treatment during early infancy and after childhood. After the childhood period, itch appears first, followed by formation of well-circumscribed plaque or polymorphous dermatoses at the same site. When accompanied with dermatitis and dry skin, treatment of skin lesions should be prioritized. When itch appears first, disease history, such as causes and time of appearance of itch should be obtained by history taking. In many cases, itch increases in the evening when the sympathetic nerve activity decreased. Treatment is provided considering that hypersensitivity to various external stimulations can cause itch. Heat and sweating are thought to especially exacerbate itch. Factors causing itch, such as cytokines and chemical messengers, also induce itch mainly by stimulating the nerve. Scratching further aggravates dermatitis. Skin hypersensibility, where other non-itch senses, such as pain and heat, are felt as itch, sometimes occurs in AD. Abnormal elongation of the sensory nerve into the epidermis, as well as sensitizing of the peripheral/central nerve, are possible causes of hypersensitivity, leading to itch. To control itch induced by environmental factors such as heat, treatment for dermatitis is given priority. In the background of itch exacerbated by sweating, attention should be given to the negative impact of sweat on skin homeostasis due to 1) leaving excess sweat on the skin, and 2) heat retention due to insufficient sweating. Excess sweat on the skin should be properly wiped off, and dermatitis should be controlled so that appropriate amount of sweat can be produced. Not only stimulation from the skin surface, but also visual and auditory stimulation can induce new itch. This "contagious itch" can be notably observed in patients with AD. This article reviews and introduces causes of aggravation of itch and information regarding how to cope with such causes. Copyright

  14. [Higher Brain Dysfunction].

    Science.gov (United States)

    Kashima, Haruo

    2015-01-01

    The technical term "higher brain dysfunction" is used widely in Japan. However, it is not always clear what "higher" means. The author thinks that the term "higher" is understood as being associated with a meaning. In this article, the differences between higher brain dysfunctions and elementary brain dysfunctions are discussed from the point of view of lesion localization and the consistency of symptoms. The psychiatric approach is indispensable for the assessment of higher brain dysfunction. A simple test for mild Alzheimer-type dementia is also introduced.

  15. Incidence and risk factors for exacerbations of asthma during pregnancy

    Directory of Open Access Journals (Sweden)

    Ali Z

    2013-05-01

    Full Text Available Zarqa Ali, Charlotte Suppli UlrikDepartment of Pulmonary Medicine, Hvidovre Hospital and University of Copenhagen, Copenhagen, DenmarkBackground: Asthma is one of the most common chronic diseases among pregnant women. Acute exacerbations of asthma during pregnancy have an unfavorable impact on pregnancy outcome. This review provides an overview of current knowledge of incidence, mechanisms, and risk factors for acute exacerbations of asthma during pregnancy.Methods: A narrative literature review was carried out using the PubMed database.Results: During pregnancy, up to 6% of women with asthma are hospitalized for an acute exacerbation. The maternal immune system is characterized by a very high T-helper-2:T-helper-1 cytokine ratio during pregnancy and thereby provides an environment essential for fetal survival but one that may aggravate asthma. Cells of the innate immune system such as monocytes and neutrophils are also increased during pregnancy, and this too can exacerbate maternal asthma. Severe or difficult-to-control asthma appears to be the major risk factor for exacerbations during pregnancy, but studies also suggest that nonadherence with controller medication and viral infections are important triggers of exacerbations during pregnancy. So far, inconsistent findings have been reported regarding the effect of fetal sex on exacerbations during pregnancy. Other risk factors for exacerbation during pregnancy include obesity, ethnicity, and reflux, whereas atopy does not appear to be a risk factor.Discussion: The incidence of asthma exacerbations during pregnancy is disturbingly high. Severe asthma – better described as difficult-to-control asthma – nonadherence with controller therapy, viral infections, obesity, and ethnicity are likely to be important risk factors for exacerbations of asthma during pregnancy, whereas inconsistent findings have been reported with regard to the importance of sex of the fetus.Keywords: acute exacerbations

  16. Minor neurological dysfunction and cognition in 9-year-olds born at term

    NARCIS (Netherlands)

    Kikkert, Hedwig K; de Jong, Corina; Hadders-Algra, Mijna

    BACKGROUND: In children with developmental disorders, motor problems often co-occur with cognitive difficulties. Associations between specific cognitive deficits underlying learning problems and minor neurological dysfunction (MND) are still unknown. AIMS: To assess associations between specific

  17. Vocal cord dysfunction in amyotrophic lateral sclerosis: four cases and a review of the literature

    NARCIS (Netherlands)

    van der Graaff, Maaike M.; Grolman, Wilko; Westermann, Erik J.; Boogaardt, Hans C.; Koelman, Hans; van der Kooi, Anneke J.; Tijssen, Marina A.; de Visser, Marianne

    2009-01-01

    We describe 4 patients with amyotrophic lateral sclerosis (ALS) and glottic narrowing due to vocal cord dysfunction, and review the literature found using the following search terms: amyotrophic lateral sclerosis, motor neuron disease, stridor, laryngospasm, vocal cord abductor paresis, and

  18. Saccharomyces boulardii CNCM I-745 supplementation reduces gastrointestinal dysfunction in an animal model of IBS

    National Research Council Canada - National Science Library

    Paola Brun; Melania Scarpa; Chiara Marchiori; Gloria Sarasin; Valentina Caputi; Andrea Porzionato; Maria Cecilia Giron; Giorgio Palù; Ignazio Castagliuolo

    We evaluated the effect of Saccharomyces boulardii CNCM I-745 on intestinal neuromuscular anomalies in an IBS-type mouse model of gastrointestinal motor dysfunctions elicited by Herpes Simplex Virus type 1 (HSV-1...

  19. Saccharomyces boulardii CNCM I-745 supplementation reduces gastrointestinal dysfunction in an animal model of IBS

    National Research Council Canada - National Science Library

    Paola Brun; Melania Scarpa; Chiara Marchiori; Gloria Sarasin; Valentina Caputi; Andrea Porzionato; Maria Cecilia Giron; Giorgio Palù; Ignazio Castagliuolo

    2017-01-01

    Background We evaluated the effect of Saccharomyces boulardii CNCM I-745 on intestinal neuromuscular anomalies in an IBS-type mouse model of gastrointestinal motor dysfunctions elicited by Herpes Simplex Virus type 1 (HSV-1) exposure...

  20. The Effects of Motor Neurone Disease on Language: Further Evidence

    Science.gov (United States)

    Bak, Thomas H.; Hodges, John R.

    2004-01-01

    It might sound surprising that Motor Neurone Disease (MND), regarded still by many as the very example of a neurodegenerative disease affecting selectively the motor system and sparing the sensory functions as well as cognition, can have a significant influence on language. In this article we hope to demonstrate that language dysfunction is not…

  1. Cognition and behaviour in motor neurone disease.

    Science.gov (United States)

    Lillo, Patricia; Hodges, John R

    2010-12-01

    Motor neurone disease has traditionally been considered a pure motor syndrome which spares aspects of cognition and behaviour, although in recent years it has been suggested that up to 50% of patients with motor neurone disease may develop frontal dysfunction which, in some cases, is severe enough to reach criteria for frontotemporal dementia. We review the cognitive and behavioural changes in motor neurone disease emphasizing the recent advances. A major advance in pathology has been the recent discovery of TDP-43 and FUS inclusions as the key components in cases of motor neurone disease, frontotemporal dementia-motor neurone disease and some cases with pure frontotemporal dementia. In addition, mutations in TARDBP and FUS genes have been reported in recent years. Longitudinal studies showed that progression of cognitive impairment over the course of motor neurone disease appears to be mild and occurs only in a proportion of motor neurone disease patients. The presence of cognitive impairment seems to be related to a faster disease and a shorter survival. Motor neurone disease is a multi-system disorder which overlaps with frontotemporal dementia. Behavioural and cognitive changes appear to occur in a subset of patients with motor neurone disease, but the cause of this variability remains unclear.

  2. Determinants of low risk of asthma exacerbation during pregnancy

    DEFF Research Database (Denmark)

    Ali, Zarqa; Nilas, Lisbeth; Ulrik, Charlotte Suppli

    2017-01-01

    BACKGROUND: Assessment of asthma control every 4-6 weeks during pregnancy is recommended to reduce risk of exacerbation, and by that improve outcome. OBJECTIVE: To identify determinants of pregnancies with low risk of asthma exacerbation. METHODS: All pregnant women enrolled into the Management o...... is protected by copyright. All rights reserved....

  3. Inflammatory biomarkers and exacerbations in chronic obstructive pulmonary disease

    DEFF Research Database (Denmark)

    Thomsen, Mette; Ingebrigtsen, Truls Sylvan; Marott, Jacob Louis

    2013-01-01

    Exacerbations of respiratory symptoms in chronic obstructive pulmonary disease (COPD) have profound and long-lasting adverse effects on patients.......Exacerbations of respiratory symptoms in chronic obstructive pulmonary disease (COPD) have profound and long-lasting adverse effects on patients....

  4. Blood Eosinophils and Exacerbations in Chronic Obstructive Pulmonary Disease

    DEFF Research Database (Denmark)

    Vedel-Krogh, Signe; Nielsen, Sune F; Lange, Peter

    2016-01-01

    RATIONALE: Whether high blood eosinophils are associated with COPD exacerbations among individuals with COPD in the general population is largely unknown. OBJECTIVES: To test the hypothesis that high blood eosinophils predict COPD exacerbations. METHODS: Among 81,668 individuals from the Copenhag...

  5. Detection of rhinovirus-associated asthma exacerbations using ...

    African Journals Online (AJOL)

    Ehab

    INTRODUCTION. Acute asthma exacerbation is a cause of strong concern among children and parents and represents a challenge for pediatric healthcare providers1. Studies reported the issue of “virus-induced exacerbation in asthma and chronic obstructive pulmonary disease” and evidence of viral infection is found in ...

  6. Factors associated with change in exacerbation frequency in COPD

    DEFF Research Database (Denmark)

    Donaldson, Gavin C; Müllerova, Hanna; Locantore, Nicholas

    2013-01-01

    Patients with chronic obstructive pulmonary disease (COPD) can be categorized as having frequent (FE) or infrequent (IE) exacerbations depending on whether they respectively experience two or more, or one or zero exacerbations per year. Although most patients do not change category from year...

  7. Prevalence and pattern of asthma exacerbation in children seen at ...

    African Journals Online (AJOL)

    Background: Acute exacerbation is a major cause of morbidity in asthmatic children. It can occur even in well controlled asthma. Aim: To determine the prevalence and pattern of acute exacerbation of asthma in children seen at the emergency room of the University of Nigeria Teaching Hospital (UNTH), Enugu. Materials ...

  8. Incidence and risk factors for exacerbations of asthma during pregnancy

    DEFF Research Database (Denmark)

    Ali, Zarqa; Ulrik, Charlotte Suppli

    2013-01-01

    Asthma is one of the most common chronic diseases among pregnant women. Acute exacerbations of asthma during pregnancy have an unfavorable impact on pregnancy outcome. This review provides an overview of current knowledge of incidence, mechanisms, and risk factors for acute exacerbations of asthma...

  9. Increased neutrophil expression of pattern recognition receptors during COPD exacerbations

    NARCIS (Netherlands)

    Pouwels, Simon D.; Van Geffen, Wouter H.; Jonker, Marnix R.; Kerstjens, Huib A. M.; Nawijn, Martijn C.; Heijink, Irene H.

    Previously, we observed increased serum levels of damage-associated molecular patterns (DAMPs) during COPD exacerbations. Here, gene expression of DAMP receptors was measured in peripheral blood neutrophils of COPD patients during stable disease and severe acute exacerbation. The expression of

  10. Acute exacerbations and pulmonary hypertension in advanced idiopathic pulmonary fibrosis.

    LENUS (Irish Health Repository)

    Judge, Eoin P

    2012-07-01

    The aim of this study was to evaluate the risk factors for and outcomes of acute exacerbations in patients with advanced idiopathic pulmonary fibrosis (IPF), and to examine the relationship between disease severity and neovascularisation in explanted IPF lung tissue. 55 IPF patients assessed for lung transplantation were divided into acute (n=27) and non-acute exacerbation (n=28) groups. Haemodynamic data was collected at baseline, at the time of acute exacerbation and at lung transplantation. Histological analysis and CD31 immunostaining to quantify microvessel density (MVD) was performed on the explanted lung tissue of 13 transplanted patients. Acute exacerbations were associated with increased mortality (p=0.0015). Pulmonary hypertension (PH) at baseline and acute exacerbations were associated with poor survival (p<0.01). PH at baseline was associated with a significant risk of acute exacerbations (HR 2.217, p=0.041). Neovascularisation (MVD) was significantly increased in areas of cellular fibrosis and significantly decreased in areas of honeycombing. There was a significant inverse correlation between mean pulmonary artery pressure and MVD in areas of honeycombing. Acute exacerbations were associated with significantly increased mortality in patients with advanced IPF. PH was associated with the subsequent development of an acute exacerbation and with poor survival. Neovascularisation was significantly decreased in areas of honeycombing, and was significantly inversely correlated with mean pulmonary arterial pressure in areas of honeycombing.

  11. Immune Responses in Rhinovirus-Induced Asthma Exacerbations.

    Science.gov (United States)

    Steinke, John W; Borish, Larry

    2016-11-01

    Acute asthma exacerbations are responsible for urgent care visits and hospitalizations; they interfere with school and work productivity, thereby driving much of the morbidity and mortality associated with asthma. Approximately 80 to 85 % of asthma exacerbations in children, adolescents, and less frequently adults are associated with viral upper respiratory tract viral infections, and rhinovirus (RV) accounts for ∼60-70 % of these virus-associated exacerbations. Evidence suggests that it is not the virus itself but the nature of the immune response to RV that drives this untoward response. In particular, evidence supports the concept that RV acts to exacerbate an ongoing allergic inflammatory response to environmental allergens present at the time of the infection. The interaction of the ongoing IgE- and T cell-mediated response to allergen superimposed on the innate and adaptive immune responses to the virus and how this leads to triggering of an asthma exacerbation is discussed.

  12. Mitochondrial iron accumulation exacerbates hepatic toxicity caused by hepatitis C virus core protein

    Energy Technology Data Exchange (ETDEWEB)

    Sekine, Shuichi; Ito, Konomi; Watanabe, Haruna; Nakano, Takafumi [Laboratory of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8675 (Japan); Moriya, Kyoji; Shintani, Yoshizumi; Fujie, Hajime; Tsutsumi, Takeya; Miyoshi, Hideyuki; Fujinaga, Hidetake; Shinzawa, Seiko; Koike, Kazuhiko [Department of Internal Medicine, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655 (Japan); Horie, Toshiharu, E-mail: t.horie@thu.ac.jp [Laboratory of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8675 (Japan)

    2015-02-01

    Patients with long-lasting hepatitis C virus (HCV) infection are at major risk of hepatocellular carcinoma (HCC). Iron accumulation in the livers of these patients is thought to exacerbate conditions of oxidative stress. Transgenic mice that express the HCV core protein develop HCC after the steatosis stage and produce an excess of hepatic reactive oxygen species (ROS). The overproduction of ROS in the liver is the net result of HCV core protein-induced dysfunction of the mitochondrial respiratory chain. This study examined the impact of ferric nitrilacetic acid (Fe-NTA)-mediated iron overload on mitochondrial damage and ROS production in HCV core protein-expressing HepG2 (human HCC) cells (Hep39b cells). A decrease in mitochondrial membrane potential and ROS production were observed following Fe-NTA treatment. After continuous exposure to Fe-NTA for six days, cell toxicity was observed in Hep39b cells, but not in mock (vector-transfected) HepG2 cells. Moreover, mitochondrial iron ({sup 59}Fe) uptake was increased in the livers of HCV core protein-expressing transgenic mice. This increase in mitochondrial iron uptake was inhibited by Ru360, a mitochondrial Ca{sup 2+} uniporter inhibitor. Furthermore, the Fe-NTA-induced augmentation of mitochondrial dysfunction, ROS production, and cell toxicity were also inhibited by Ru360 in Hep39b cells. Taken together, these results indicate that Ca{sup 2+} uniporter-mediated mitochondrial accumulation of iron exacerbates hepatocyte toxicity caused by the HCV core protein. - Highlights: • Iron accumulation in the livers of patients with hepatitis C virus (HCV) infection is thought to exacerbate oxidative stress. • The impact of iron overload on mitochondrial damage and ROS production in HCV core protein-expressing cells were examined. • Mitochondrial iron uptake was increased in the livers of HCV core protein-expressing transgenic mice. • Ca{sup 2+} uniporter-mediated mitochondrial accumulation of iron exacerbates

  13. Exacerbation of colon carcinogenesis by Blastocystis sp.

    Science.gov (United States)

    Kumar, Suresh

    2017-01-01

    Colorectal cancer (CRC) is one the most commonly diagnosed cancers worldwide and the number is increasing every year. Despite advances in screening programs, CRC remains as the second leading cause of cancer deaths in the United States. Oxidative stress plays an important role in the molecular mechanisms of colorectal cancer (CRC) and has been shown to be associated with Blastocystis sp., a common intestinal microorganism. In the present study, we aimed to identify a role for Blastocystis sp. in exacerbating carcinogenesis using in vivo rat model. Methylene blue staining was used to identify colonic aberrant crypt foci (ACF) and adenomas formation in infected rats whilst elevation of oxidative stress biomarker levels in the urine and serum samples were evaluated using biochemical assays. Histological changes of the intestinal mucosa were observed and a significant number of ACF was found in Blastocystis sp. infected AOM-rats compared to the AOM-controls. High levels of urinary oxidative indices including advanced oxidative protein products (AOPP) and hydrogen peroxide were observed in Blastocystis sp. infected AOM-rats compared to the uninfected AOM-rats. Our study provides evidence that Blastocystis sp. has a significant role in enhancing AOM-induced carcinogenesis by resulting damage to the intestinal epithelium and promoting oxidative damage in Blastocystis sp. infected rats. PMID:28859095

  14. Non-motor and motor features in LRRK2 transgenic mice.

    Directory of Open Access Journals (Sweden)

    Zoë Bichler

    Full Text Available Non-motor symptoms are increasingly recognized as important features of Parkinson's disease (PD. LRRK2 mutations are common causes of familial and sporadic PD. Non-motor features have not been yet comprehensively evaluated in LRRK2 transgenic mouse models.Using a transgenic mouse model overexpressing the R1441G mutation of the human LRRK2 gene, we have investigated the longitudinal correlation between motor and non-motor symptoms and determined if specific non-motor phenotypes precede motor symptoms.We investigated the onset of motor and non-motor phenotypes on the LRRK2(R1441G BAC transgenic mice and their littermate controls from 4 to 21 month-old using a battery of behavioral tests. The transgenic mutant mice displayed mild hypokinesia in the open field from 16 months old, with gastrointestinal dysfunctions beginning at 6 months old. Non-motor features such as depression and anxiety-like behaviors, sensorial functions (pain sensitivity and olfaction, and learning and memory abilities in the passive avoidance test were similar in the transgenic animals compared to littermate controls.LRRK2(R1441G BAC transgenic mice displayed gastrointestinal dysfunction at an early stage but did not have abnormalities in fine behaviors, olfaction, pain sensitivity, mood disorders and learning and memory compared to non-transgenic littermate controls. The observations on olfaction and gastrointestinal dysfunction in this model validate findings in human carriers. These mice did recapitulate mild Parkinsonian motor features at late stages but compensatory mechanisms modulating the progression of PD in these models should be further evaluated.

  15. Multidisciplinary Interventions in Motor Neuron Disease

    Directory of Open Access Journals (Sweden)

    U. E. Williams

    2014-01-01

    Full Text Available Motor neuron disease is a neurodegenerative disease characterized by loss of upper motor neuron in the motor cortex and lower motor neurons in the brain stem and spinal cord. Death occurs 2–4 years after the onset of the disease. A complex interplay of cellular processes such as mitochondrial dysfunction, oxidative stress, excitotoxicity, and impaired axonal transport are proposed pathogenetic processes underlying neuronal cell loss. Currently evidence exists for the use of riluzole as a disease modifying drug; multidisciplinary team care approach to patient management; noninvasive ventilation for respiratory management; botulinum toxin B for sialorrhoea treatment; palliative care throughout the course of the disease; and Modafinil use for fatigue treatment. Further research is needed in management of dysphagia, bronchial secretion, pseudobulbar affect, spasticity, cramps, insomnia, cognitive impairment, and communication in motor neuron disease.

  16. Effect of sildenafil on erectile dysfunction in spinal Cord injured ...

    African Journals Online (AJOL)

    Background: Erectile dysfunction is a preoccupying issue, just like motor and bladder disability, in spinal cord injured (SCI) patients. This is particularly so because of the increasing prevalence of paraplegic and tetraplegic subjects and the fact that these patients are younger, and sexually active. Objective: To determine the ...

  17. Neural Underpinnings of Impaired Predictive Motor Timing in Children with Developmental Coordination Disorder

    Science.gov (United States)

    Debrabant, Julie; Gheysen, Freja; Caeyenberghs, Karen; Van Waelvelde, Hilde; Vingerhoets, Guy

    2013-01-01

    A dysfunction in predictive motor timing is put forward to underlie DCD-related motor problems. Predictive timing allows for the pre-selection of motor programmes (except "program" in computers) in order to decrease processing load and facilitate reactions. Using functional magnetic resonance imaging (fMRI), this study investigated the neural…

  18. Motor learning in animal models of Parkinson's disease: Aberrant synaptic plasticity in the motor cortex.

    Science.gov (United States)

    Xu, Tonghui; Wang, Shaofang; Lalchandani, Rupa R; Ding, Jun B

    2017-04-01

    In Parkinson's disease (PD), dopamine depletion causes major changes in the brain, resulting in the typical cardinal motor features of the disease. PD neuropathology has been restricted to postmortem examinations, which are limited to only a single time of PD progression. Models of PD in which dopamine tone in the brain is chemically or physically disrupted are valuable tools in understanding the mechanisms of the disease. The basal ganglia have been well studied in the context of PD, and circuit changes in response to dopamine loss have been linked to the motor dysfunctions in PD. However, the etiology of the cognitive dysfunctions that are comorbid in PD patients has remained unclear until now. In this article, we review recent studies exploring how dopamine depletion affects the motor cortex at the synaptic level. In particular, we highlight our recent findings on abnormal spine dynamics in the motor cortex of PD mouse models through in vivo time-lapse imaging and motor skill behavior assays. In combination with previous studies, a role of the motor cortex in skill learning and the impairment of this ability with the loss of dopamine are becoming more apparent. Taken together, we conclude with a discussion on the potential role for the motor cortex in PD, with the possibility of targeting the motor cortex for future PD therapeutics. © 2017 International Parkinson and Movement Disorder Society. © 2017 International Parkinson and Movement Disorder Society.

  19. Virus-induced exacerbations in asthma and COPD

    Directory of Open Access Journals (Sweden)

    Daisuke eKurai

    2013-10-01

    Full Text Available Chronic obstructive pulmonary disease (COPD is characterized by chronic airway inflammation and/or airflow limitation due to pulmonary emphysema. Chronic bronchitis, pulmonary emphysema, and bronchial asthma may all be associated with airflow limitation; therefore, exacerbation of asthma may be associated with the pathophysiology of COPD. Furthermore, recent studies have suggested that the exacerbation of asthma, namely virus-induced asthma, may be associated with a wide variety of respiratory viruses.COPD and asthma have different underlying pathophysiological processes and thus require individual therapies. Exacerbation of both COPD and asthma, which are basically defined and diagnosed by clinical symptoms, is associated with a rapid decline in lung function and increased mortality. Similar pathogens, including human rhinovirus, respiratory syncytial virus, influenza virus, parainfluenza virus and coronavirus, are also frequently detected during exacerbation of asthma and/or COPD. Immune response to respiratory viral infections, which may be related to the severity of exacerbation in each disease, varies in patients with both COPD and asthma. In this regard, it is crucial to recognize and understand both the similarities and differences of clinical features in patients with COPD and/or asthma associated with respiratory viral infections, especially in the exacerbative stage.In relation to definition, epidemiology, and pathophysiology, this review aims to summarize current knowledge concerning exacerbation of both COPD and asthma by focusing on the clinical significance of associated respiratory virus infections.

  20. Can meteorological factors forecast asthma exacerbation in a paediatric population?

    Science.gov (United States)

    Hervás, D; Utrera, J F; Hervás-Masip, J; Hervás, J A; García-Marcos, L

    2015-01-01

    Asthma exacerbations attended in emergency departments show a marked seasonality in the paediatric age. This seasonal pattern can change from one population to another and the factors involved are poorly understood. To evaluate the association between meteorological factors and schooling with asthma exacerbations in children attended in the paediatric emergency department of a district hospital. We conducted a retrospective review of the medical records of children 5-14 years of age attended for asthma exacerbations during a 4-year period (2007-2011). Climatic data were obtained from a weather station located very close to the population studied. The number of asthma exacerbations was correlated to temperature, barometric pressure, relative humidity, rainfall, wind speed, wind distance, solar radiation, water vapour pressure and schooling, using regression analyses. During the study period, 371 children were attended for asthma exacerbations; median age was eight years (IQR: 6-11), and 59% were males. Asthma exacerbations showed a bimodal pattern with peaks in spring and summer. Maximum annual peak occurred in week 39, within 15 days from school beginning after the summer holidays. A regression model with mean temperature, water vapour pressure, relative humidity, maximum wind speed and schooling could explain 98.4% (pschooling could predict asthma exacerbations in children attended in a paediatric emergency department. Copyright © 2013 SEICAP. Published by Elsevier Espana. All rights reserved.

  1. Acute kidney injury in stable COPD and at exacerbation

    Directory of Open Access Journals (Sweden)

    Barakat MF

    2015-09-01

    Full Text Available MF Barakat,1 HI McDonald,1 TJ Collier,1 L Smeeth,1 D Nitsch,1 JK Quint1,2 1Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, 2Department of Respiratory Epidemiology, Occupational Medicine and Public Health, National Heart and Lung Institute, Imperial College London, London, UK Background: While acute kidney injury (AKI alone is associated with increased mortality, the incidence of hospital admission with AKI among stable and exacerbating COPD patients and the effect of concurrent AKI at COPD exacerbation on mortality is not known.Methods: A total of 189,561 individuals with COPD were identified from the Clinical Practice Research Datalink. Using Poisson and logistic regressions, we explored which factors predicted admission for AKI (identified in Hospital Episode Statistics in this COPD cohort and concomitant AKI at a hospitalization for COPD exacerbation. Using survival analysis, we investigated the effect of concurrent AKI at exacerbation on mortality (n=36,107 and identified confounding factors.Results: The incidence of AKI in the total COPD cohort was 128/100,000 person-years. The prevalence of concomitant AKI at exacerbation was 1.9%, and the mortality rate in patients with AKI at exacerbation was 521/1,000 person-years. Male sex, older age, and lower glomerular filtration rate predicted higher risk of AKI or death. There was a 1.80 fold (95% confidence interval: 1.61, 2.03 increase in adjusted mortality within the first 6 months post COPD exacerbation in patients suffering from AKI and COPD exacerbation compared to those who were AKI free.Conclusion: In comparison to previous studies on general populations and hospitalizations, the incidence and prevalence of AKI is relatively high in COPD patients. Coexisting AKI at exacerbation is prognostic of poor outcome. Keywords: acute renal failure, mortality, emphysema, chronic bronchitis, prognosis

  2. THE MOTOR

    DEFF Research Database (Denmark)

    Gammelgaard Nielsen, Anders

    2011-01-01

    MOTOR is the first assignment that students at Unit 1a of the School of Architecture are introduced to. The purpose of the assignment is to shake up the students and their preconceptions of what architec- ture is. This is done by introducing them to a working method that al- lows them to develop...

  3. Chronic pelvic floor dysfunction.

    Science.gov (United States)

    Hartmann, Dee; Sarton, Julie

    2014-10-01

    The successful treatment of women with vestibulodynia and its associated chronic pelvic floor dysfunctions requires interventions that address a broad field of possible pain contributors. Pelvic floor muscle hypertonicity was implicated in the mid-1990s as a trigger of major chronic vulvar pain. Painful bladder syndrome, irritable bowel syndrome, fibromyalgia, and temporomandibular jaw disorder are known common comorbidities that can cause a host of associated muscular, visceral, bony, and fascial dysfunctions. It appears that normalizing all of those disorders plays a pivotal role in reducing complaints of chronic vulvar pain and sexual dysfunction. Though the studies have yet to prove a specific protocol, physical therapists trained in pelvic dysfunction are reporting success with restoring tissue normalcy and reducing vulvar and sexual pain. A review of pelvic anatomy and common findings are presented along with suggested physical therapy management. Copyright © 2014 Elsevier Ltd. All rights reserved.

  4. Spinal Cord Dysfunction (SCD)

    Data.gov (United States)

    Department of Veterans Affairs — The Spinal Cord Dysfunction (SCD) module supports the maintenance of local and national registries for the tracking of patients with spinal cord injury and disease...

  5. Diastolic dysfunction in cirrhosis

    DEFF Research Database (Denmark)

    Møller, Søren; Wiese, Signe Skovgaard; Halgreen, Hanne

    2016-01-01

    Development of esophageal varices, ascites, and hepatic nephropathy is among the major complications of cirrhosis. The presence of cirrhotic cardiomyopathy, which includes a left ventricular diastolic dysfunction (DD), seems to deteriorate the course of the disease and the prognosis. Increased...

  6. Spotlight on olfactory dysfunction in Parkinson's disease

    Directory of Open Access Journals (Sweden)

    Rodríguez-Violante M

    2017-06-01

    Full Text Available Mayela Rodríguez-Violante,1,2 Natalia Ospina-García,1,2 Christian Pérez-Lohman,1,2 Amin Cervantes-Arriaga1,2 1Movement Disorders Clinic, National Institute of Neurology and Neurosurgery, Mexico City, Mexico; 2Clinical Neurodegenerative Research Unit, National Institute of Neurology and Neurosurgery, Mexico City, Mexico Abstract: Olfactory dysfunction is frequent in Parkinson’s disease (PD. A correlation between olfactory dysfunction and the pathophysiological process of the disease has been confirmed. On the other hand, olfaction disturbances are also prevalent in other neurodegenerative diseases, and may be related to other factors such as gender, age, smoking, and trauma. Clinically, hyposmia is commonly assessed by smell identification testing. Good diagnostic accuracy has been widely reported, but differences in sensitivity and specificity due to sociocultural factors have also been reported. Since hyposmia may be present before the onset of motor symptoms, it has the potential to serve as a biomarker for the identification of subjects at risk of developing PD. Several studies have been conducted to assess the utility of smell testing as an isolated or combined biomarker for this end. Finally, severe olfactory dysfunction has been associated with faster disease progression and higher risk of cognitive decline in patients with PD. Olfactory dysfunction assessment in PD will continue to be relevant in research and clinical practice. Keywords: Parkinson’s disease, olfaction, smell identification test, biomarker 

  7. Cognitive dysfunction and hepatitis C virus infection.

    Science.gov (United States)

    Solinas, Antonio; Piras, Maria Rita; Deplano, Angelo

    2015-05-08

    Cognitive dysfunction in patients with chronic hepatitis C virus (HCV) infection is a distinct form of minimal hepatic encephalopathy (MHE). In fact, the majority of HCV-positive patients, irrespective of the grading of liver fibrosis, display alterations of verbal learning, attention, executive function, and memory when they are evaluated by suitable neuropsychological tests. Similarities between the cognitive dysfunction of HCV patients and MHE of patients with different etiologies are unclear. It is also unknown how the metabolic alterations of advanced liver diseases interact with the HCV-induced cognitive dysfunction, and whether these alterations are reversed by antiviral therapies. HCV replication in the brain may play a role in the pathogenesis of neuroinflammation. HCV-related brain dysfunction may be associated with white matter neuronal loss, alterations of association tracts and perfusion. It is unclear to what extent, in patients with cirrhosis, HCV triggers an irreversible neurodegenerative brain damage. New insights on this issue will be provided by longitudinal studies using the protocols established by the diagnostic and statistical manual of mental disorders fifth edition for cognitive disorders. The domains to be evaluated are complex attention; executive functions; learning and memory; perceptual motor functions; social cognition. These evaluations should be associated with fluorodeoxyglucose positron emission tomography and magnetic resonance imaging (MRI) protocols for major cognitive disorders including magnetic resonance spectroscopy, diffusion tensor imaging, magnetic resonance perfusion, and functional MRI. Also, the characteristics of portal hypertension, including the extent of liver blood flow and the type of portal shunts, should be evaluated.

  8. Crohn's Disease Exacerbation Induced by Edwardsiella tarda Gastroenteritis.

    Science.gov (United States)

    Arya, Aman V; Rostom, Alaa; Dong, Wei-Feng; Flynn, Andrew N

    2011-09-01

    Exacerbations of Crohn's disease are not infrequently associated with bacterial gastroenteritis. The recognition of synchronous infections in such patients is vital for the initiation of appropriate antimicrobial therapy. Furthermore, the detection of active bacterial infections may lead the clinician to delay starting biological therapy. We report here a man presenting with an exacerbation of his Crohn's disease during a trip to Thailand. Stool cultures were positive for the unusual gut pathogen Edwardsiella tarda. The patient's symptoms resolved with concurrent antibiotic and steroid therapy. This finding demonstrates the value of performing stool culture in all patients presenting with exacerbations of inflammatory bowel diseases.

  9. Crohn’s Disease Exacerbation Induced by Edwardsiella tarda Gastroenteritis

    Directory of Open Access Journals (Sweden)

    Aman V. Arya

    2011-10-01

    Full Text Available Exacerbations of Crohn’s disease are not infrequently associated with bacterial gastroenteritis. The recognition of synchronous infections in such patients is vital for the initiation of appropriate antimicrobial therapy. Furthermore, the detection of active bacterial infections may lead the clinician to delay starting biological therapy. We report here a man presenting with an exacerbation of his Crohn’s disease during a trip to Thailand. Stool cultures were positive for the unusual gut pathogen Edwardsiella tarda. The patient’s symptoms resolved with concurrent antibiotic and steroid therapy. This finding demonstrates the value of performing stool culture in all patients presenting with exacerbations of inflammatory bowel diseases.

  10. Renal dysfunction in cirrhosis.

    Science.gov (United States)

    Urrunaga, Nathalie H; Mindikoglu, Ayse L; Rockey, Don C

    2015-05-01

    Renal dysfunction causes significant morbidity in cirrhotic patients. Diagnosis is challenging because it is based on serum creatinine, which is used to calculate estimated glomerular filtration rate, which itself is not an ideal measure of renal function in patients with cirrhosis. Finding the exact cause of renal injury in patients with cirrhosis remains problematic due to the limitations of the current diagnostic tests. The purpose of this review is to highlight studies used to diagnose renal dysfunction in patients with renal dysfunction and review current treatments. New diagnostic criteria and classification of renal dysfunction, especially for acute kidney injury (AKI), have been proposed in hopes of optimizing treatment and improving outcomes. New biomarkers that help to differentiate structural from functional AKI in cirrhotic patients have been developed, but require further investigation. Vasoconstrictors are the most commonly recommended treatment of hepatorenal syndrome (HRS). Given the high mortality in patients with type 1 HRS, all patients with HRS should be evaluated for liver transplantation. When renal dysfunction is considered irreversible, combined liver-kidney transplantation is advised. Development of new biomarkers to differentiate the different types of AKI in cirrhosis holds promise. Early intervention in cirrhotic patients with renal dysfunction offers the best hope of improving outcomes.

  11. Brain dysfunction in psychosis

    Energy Technology Data Exchange (ETDEWEB)

    Warkentin, S.

    1991-05-24

    The present investigation focused on the questions whether previously reported functional brain abnormalities in schizophrenia could be related to the clinical state of the patient (i.e. the degree of psychosis) at time of study, and whether similar findings in patients with schizophrenia, could be made in patients with cycloid psychosis. To this effect, patients were investigated with regional cerebral blood flow measurements and clinical rating on repeated occasions during their most extreme fluctuations during a psychotic episode, i.e. while they were in an exacerbated state and during clinical remission. A subgroup of schizophrenic patients were investigated before and after neuroleptic treatment and during mental activation with a word fluency test. The schizophrenic group has a normal mean hemispheric blood flow irrespective of clinical state and treatment. During exacerbation a highly significant positive correlation was seen between the frontal-occipital (F/O) ratio and the degree of psychosis, suggesting that the more psychotic the patients was, the higher was the ratio. During remission, the F/O ratio decreased. Schizophrenic patients did not activate their prefrontal cortex during exacerbation, but showed a normal frontal response to the word fluency test during remission. The regional cerebral blood flow of the cycloid patients differed clearly from that of the schizophrenic patients. During exacerbation they had elevated mean hemispheric flow levels, and a decreased F/O ration, while rCBF was normal during remission. The findings suggest that variability in the degree of psychosis can be an important factor underlying the heterogeneity of rCBF findings in schizophrenia. (au).

  12. Evidence of motor-control difficulties in children with attention deficit hyperactivity disorder, explored through a hierarchical motor-systems perspective.

    Science.gov (United States)

    Macoun, Sarah J; Kerns, Kimberly A

    2016-01-01

    Attention deficit hyperactivity disorder (ADHD) may reflect a disorder of neural systems that regulate motor control. The current study investigates motor dysfunction in children with ADHD using a hierarchical motor-systems perspective where frontal-striatal/"medial" brain systems are viewed as regulating parietal/"lateral" brain systems in a top down manner, to inhibit automatic environmentally driven responses in favor of goal-directed behavior. It was hypothesized that due to frontal-striatal hypoactivation, children with ADHD would have difficulty with higher order motor control tasks felt to be dependent on these systems, yet have preserved general motor function. A total of 63 children-ADHD and matched controls-completed experimental motor tasks that required maintenance of internal motor representations and the ability to inhibit visually driven responses. Children also completed a measure of motor inhibition, and a portion of the sample completed general motor function tasks. On motor tasks that required them to maintain internal motor representations and to inhibit automatic motor responses, children with ADHD had significantly greater difficulty than controls, yet on measures of general motor dexterity, their performance was comparable. Children with ADHD displayed significantly greater intraindividual (subject) variability than controls. Intraindividual variability (IIV) contributed to variations in performance across the motor tasks, but did not account for all of the variance on all tasks. These findings suggest that children with ADHD may be more controlled by external stimuli than by internally represented information, possibly due to dysfunction of the medial motor system. However, it is likely that children with ADHD also display general motor-execution problems (as evidenced by IIV findings), suggesting that atypicalities may extend to both medial and lateral motor systems. Findings are interpreted within the context of contemporary theories

  13. Phenytoin induced Stevens-Johnson syndrome exacerbated by cefepime

    OpenAIRE

    Prabhu, Varsha A.; Doddapaneni, Sahiti; Thunga, Girish; Thiyagu, Rajakannan; Prabhu, M. Mukyaprana; Naha, Kushal

    2013-01-01

    Steven Johnson syndrome (SJS) is a rare drug induced mucocutaneous reaction. Here, we present an elaborate report of a 28-year-old female patient who developed Phenytoin induced SJS, which was exacerbated by cefepime.

  14. Phenytoin induced Stevens-Johnson syndrome exacerbated by cefepime.

    Science.gov (United States)

    Prabhu, Varsha A; Doddapaneni, Sahiti; Thunga, Girish; Thiyagu, Rajakannan; Prabhu, M Mukyaprana; Naha, Kushal

    2013-10-01

    Steven Johnson syndrome (SJS) is a rare drug induced mucocutaneous reaction. Here, we present an elaborate report of a 28-year-old female patient who developed Phenytoin induced SJS, which was exacerbated by cefepime.

  15. Susceptibility to exacerbation in chronic obstructive pulmonary disease

    DEFF Research Database (Denmark)

    Hurst, John R; Vestbo, Jørgen; Anzueto, Antonio

    2010-01-01

    BACKGROUND: Although we know that exacerbations are key events in chronic obstructive pulmonary disease (COPD), our understanding of their frequency, determinants, and effects is incomplete. In a large observational cohort, we tested the hypothesis that there is a frequent-exacerbation phenotype...... of follow-up were 0.85 per person for patients with stage 2 COPD (with stage defined in accordance with Global Initiative for Chronic Obstructive Lung Disease [GOLD] stages), 1.34 for patients with stage 3, and 2.00 for patients with stage 4. Overall, 22% of patients with stage 2 disease, 33% with stage 3...... of COPD that is independent of disease severity. METHODS: We analyzed the frequency and associations of exacerbation in 2138 patients enrolled in the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) study. Exacerbations were defined as events that led a care provider...

  16. Childhood obesity in relation to poor asthma control and exacerbations

    NARCIS (Netherlands)

    Ahmadizar, Fariba; Vijverberg, Susanne; Arets, Hubertus; De Boer, Anthonius; Lang, Jason; Kattan, Meyer; Palmer, Colin; Mukhopadhyay, Somnath; Turner, Steve; Van Der Zee, Anke-Hilse Maitland

    2016-01-01

    Background: The relationship between obesity and asthma severity in children is inconsistent across studies. Objectives: To estimate the association between obesity and poor asthma control/ risk of exacerbations in asthmatic children and adolescents, and to assess whether these associations are

  17. Age-Specific Characteristics of Inpatients with Severe Asthma Exacerbation

    Directory of Open Access Journals (Sweden)

    Kiyoshi Sekiya

    2013-01-01

    Conclusions: The characteristics of inpatients with severe asthma vary depending on age. We need to establish countermeasures for asthma exacerbation according to the characteristics of patients depending on age.

  18. Fibrinogen and α1-antitrypsin in COPD exacerbations

    DEFF Research Database (Denmark)

    Ingebrigtsen, Truls S; Marott, Jacob L; Rode, Line

    2015-01-01

    BACKGROUND: We tested the hypotheses that fibrinogen and α1-antitrypsin are observationally and genetically associated with exacerbations in COPD. METHODS: We studied 13,591 individuals with COPD from the Copenhagen General Population Study (2003-2013), of whom 6857 were genotyped for FGB -455 (rs...... in instrumental variable analyses. RESULTS: Elevated fibrinogen and α1-antitrypsin levels were associated with increased risk of exacerbations in COPD, HR=1.14 (1.07 to 1.22, p

  19. Oxygen therapy in acute exacerbations of chronic obstructive pulmonary disease

    DEFF Research Database (Denmark)

    Ringbaek, T.; Lange, P.; Mogensen, T.

    2008-01-01

    Acute exacerbation of COPD is a major cause of hospitalisation in Denmark. Most of the patients require supplemental oxygen in the acute phase and some patients continue oxygen therapy at home after discharge. In this paper we discuss the physiological mechanisms of respiratory failure seen...... in acute exacerbations of COPD. The principles for oxygen therapy in the acute phase are described and recommendations for oxygen therapy are suggested Udgivelsesdato: 2008/5/5...

  20. Beta Blockers for the Prevention of Acute Exacerbations of COPD

    Science.gov (United States)

    2016-10-01

    40%.21 22 ▸ Current therapy with ocular β-blocker medications. ▸ Critical ischaemia related to peripheral arterial disease . ▸ Other diseases that are...exacerbations of chronic obstructive pulmonary disease (βLOCK COPD): a randomised controlled study protocol. Bhatt, SP; Connett, JE; Voelker, H...acute exacerbations of chronic obstructive pulmonary disease (βLOCK COPD): a randomised controlled study protocol Surya P Bhatt,1 John E Connett,2 Helen

  1. [Risk factors for acute exacerbation in patients with bronchiectasis].

    Science.gov (United States)

    Jiao, Rui; Liu, Shuang

    2015-01-27

    To evaluate the risk factors for patients with an acute exacerbation of bronchiectasis. Retrospective analyses were conducted for 228 patients diagnosed with acute exacerbation of bronchiectasis at Affiliated Beijing Anzhen Hospital, Capital Medical University from January 2008 to December 2012. Depending on whether there were recurrences with exacerbation within one year after discharge, they were divided into two groups. Their basic profiles, clinical symptoms and signs, blood tests, sputum culture, dyspnea score (mMRC) and imaging data were analyzed. There were 110 males and 118 females with an average age of (64.5+14.5) years. The incidence of the recurrence of acute exacerbation was 55.7% (127/228) within one year after discharge. Multivariate Logistic regression analysis showed that age ≥ 60 years (OR = 2.583, 95%CI: 1.188-5.613), body mass index (BMI)resolution computed tomography (CT) displayed bronchiectasis involving ≥ 3 lobes (OR = 3.179, 95%CI: 1.449-6.976) and staying in intensive care unit (ICU) (OR = 2.499, 95%CI: 1.301-4.801) were associated with the acute exacerbation of bronchiectasis (all P < 0.05). There are multiple risk factors of acute exacerbation in patients with bronchiectasis. And their proper identification and management shall improve the prognosis of bronchiectasis patients.

  2. The causes and consequences of seasonal variation in COPD exacerbations

    Directory of Open Access Journals (Sweden)

    Donaldson GC

    2014-10-01

    Full Text Available Gavin C Donaldson, Jadwiga A Wedzicha Airways Disease Section, National Heart and Lung Institute, Imperial College London, London, UK Abstract: The time of year when patients experience exacerbations of chronic obstructive pulmonary disease is a much-overlooked feature of the disease. The higher incidence of exacerbations in winter has important consequences for patients in terms of increased morbidity and mortality. The seasonality also imposes a considerable burden on already-overloaded health care services, with both primary care consultations and hospital admissions increasing in number. The seasonality of exacerbations varies with latitude, and is greater in more temperate climates, where there may be less protection from outdoor and indoor cold exposure. The precise causes of the seasonality are unknown, but thought to be partly due to the increased prevalence of respiratory viral infections circulating in cold, damp conditions. Increased susceptibility to viral infection may also be a mechanism mediated through increased airway inflammation or possibly reduced vitamin D levels. The seasonality of exacerbations informs us about the triggers of exacerbations and suggests possible strategies to reduce their number. Keywords: exacerbations of COPD, seasonality, winter mortality, winter morbidity

  3. Antibiotics usefulness and choice in BPCO acute exacerbation

    Directory of Open Access Journals (Sweden)

    Bruno Tartaglino

    2005-10-01

    Full Text Available Although the debate on the role of bacterial infections and antibiotic treatment in AE-COPD remains open, there is evidence that the persistence of bacteria after acute exacerbation (residual bacterial colony influences the frequency and severity of subsequent acute exacerbation and that antibiotic treatment that induces faster and more complete eradication produces better clinical outcomes. New aspects must now be considered, given that COPD is a chronic illness subject to acute exacerbations of varying frequencies and that acute exacerbations correspond to functional respiratory deterioration. One of the parameters that is currently acquiring clinical relevance is the interval free of infection (IFI, the period that elapses between one acute exacerbation and the next, caused by bacterial infection. Another guiding concept in the choice of antibiotic treatment is that not all patients benefit in the same way; those requiring more aggressive treatment are most likely to be those with FEV1 < 50%, frequent exacerbations (> 3/year treated with antibiotics, relevant co-morbidity, under chronic steroid treatment, etc., for these patients it is recommended to administer antibiotics active on the three most common pathogens (in particular H. influenzae, considering the resistance acquired in recent years, and on Pseudomomias aeruginosa.

  4. Voiding dysfunction - A review

    Directory of Open Access Journals (Sweden)

    Sripathi V

    2005-01-01

    Full Text Available In a child who is toilet trained the sudden onset of daytime wetting with frequency or urgency is alarming to the parents. Initially this subject was subdivided into a number of descriptive clinical conditions which led to a lot of confusion in recognition and management. Subsequently, the term elimination dysfunction was coined by Stephen Koff to emphasise the association between recurrent urinary infection, wetting, constipation and bladder overactivity. From a urodynamic point of view, in voiding dysfunction, there is either detrusor overactivity during bladder filling or dyssynergic action between the detrusor and the external sphincter during voiding. Identifying a given condition as a ′filling phase dysfunction′ or ′voiding phase dysfunction′ helps to provide appropriate therapy. Objective clinical criteria should be used to define voiding dysfunction. These include bladder wall thickening, large capacity bladder and infrequent voiding, bladder trabeculation and spinning top deformity of the urethra and a clinically demonstrated Vincent′s curtsy. The recognition and treatment of constipation is central to the adequate treatment of voiding dysfunction. Transcutaneous electric nerve stimuation for the treatment of detrusor overactivity, biofeedback with uroflow EMG to correct dyssynergic voiding, and behavioral therapy all serve to correct voiding dysfunction in its early stages. In established neurogenic bladder disease the use of Botulinum Toxin A injections into the detrusor or the external sphincter may help in restoring continence especially in those refractory to drug therapy. However in those children in whom the upper tracts are threatened, augmentation of the bladder may still be needed.

  5. Management of anxiety and motor symptoms in Parkinson's disease.

    Science.gov (United States)

    Coakeley, Sarah; Martens, Kaylena Ehgoetz; Almeida, Quincy J

    2014-08-01

    Parkinson's disease (PD) is typically known for its cardinal motor symptoms, but a growing body of literature is recognizing a multitude of important nonmotor symptoms as well. Anxiety is one of the most common nonmotor symptoms of PD; unfortunately, neither the management of anxiety nor its influence on motor symptoms is well understood. While recent literature indicates a correlation between motor symptoms and anxiety in PD, it remains uncertain whether one symptom acts as the underlying cause of the other. This review considers the cyclic interaction between anxiety and motor symptoms in PD, each exacerbating the other when they coexist. It may be critically important to disentangle if one symptom serves as an underlying cause of the other, since this might dictate appropriate treatment. Neuroanatomical substrates as well as the treatments for both motor symptoms and anxiety are discussed in detail to consider the evidence-base for the management of PD.

  6. Post-traumatic stress symptoms and exacerbations in COPD patients.

    Science.gov (United States)

    Teixeira, Paulo Josè Zimermann; Porto, Lucia; Kristensen, Christian Haag; Santos, Alvaro Huber; Menna-Barreto, Sergio Saldanha; Do Prado-Lima, Pedro AntÙnio Schmidt

    2015-02-01

    Post-Traumatic Stress Disorder (PTSD) is a common psychological consequence of exposure to traumatic stressful life events. During COPD exacerbations dyspnea can be considered a near-death experience that may induce post-traumatic stress symptoms. The aim of this study was to evaluate the relationship between COPD exacerbations and PTSD- related symptoms. Thirty-three in-patients with COPD exacerbations were screened for the following: PTSS (Screen for Posttraumatic Stress Symptoms), anxiety (Beck Anxiety Inventory) and depression (Beck Depression Inventory). Patients had a median age of 72 years and 72.7% were female. Mean FEV1 and FVC were 0.8 ± 0.3 (37.7 ± 14.9% of predicted) and 1.7 ± 0.6 (60 ± 18.8% of predicted), respectively with a mean exacerbation of 2.9 episodes over the past year. Post-traumatic stress symptoms related to PTSD were found in 11 (33.3%) patients (SPTSS mean score 4.13 ± 2.54); moderate to severe depression in 16 (48.5%) (BDI mean score 21.2 ± 12.1) and moderate to severe anxiety in 23 (69.7%) (BAI mean score 23.5 ± 12.4). In a linear regression model, exacerbations significantly predicted post-traumatic stress symptoms scores: SPTSS scores increased 0.9 points with each exacerbation (p = 0.001). Significant correlations were detected between PTSD-related symptoms and anxiety (rs = 0.57; p = 0.001) and PTSD symptoms and depression (rs = 0.62; p = 0.0001). In a multivariable analysis model, two or more exacerbation episodes led to a near twofold increase in the prevalence ratio of post-traumatic stress symptoms related to PTSD(PR1.71; p = 0.015) specially those requiring hospitalization (PR 1.13; p = 0.030) CONCLUSION: PTSD symptoms increase as the patient's exacerbations increase. Two or more exacerbation episodes lead to a near twofold increase in the prevalence ratio of post-traumatic symptomatology. Overall, these findings suggest that psychological domains should be addressed along with respiratory function and exacerbations in

  7. Determinants of exacerbation risk in patients with COPD in the TIOSPIR study

    Science.gov (United States)

    Calverley, Peter MA; Tetzlaff, Kay; Dusser, Daniel; Wise, Robert A; Mueller, Achim; Metzdorf, Norbert; Anzueto, Antonio

    2017-01-01

    Background Exacerbation history is used to grade the risk of COPD exacerbation, but its reliability and relationship to other risk factors and prior therapy is unclear. To examine these interrelationships, we conducted a post hoc analysis of patients in the TIOSPIR trial with ≥2 years’ follow-up or who died on treatment. Patients and methods Patients were grouped by their annual exacerbation rate on treatment into nonexacerbators, infrequent, and frequent exacerbators (annual exacerbation rates 0, ≤1, and >1, respectively), and baseline characteristics discriminating among the groups were determined. We used univariate and multivariate analyses to explore the effect of baseline characteristics on risk of exacerbation, hospitalization (severe exacerbation), and death (all causes). Results Of 13,591 patients, 6,559 (48.3%) were nonexacerbators, 4,568 (33.6%) were infrequent exacerbators, and 2,464 (18.1%) were frequent exacerbators; 45% of patients without exacerbations in the previous year exacerbated on treatment. Multivariate analysis identified baseline pulmonary maintenance medication as a predictive factor of increased exacerbation risk, with inhaled corticosteroid treatment associated with increased exacerbation risk irrespective of exacerbation history. Conclusion Our data confirm established risk factors for exacerbation, but highlight the limitations of exacerbation history when categorizing patients and the importance of prior treatment when identifying exacerbation risk. PMID:29238184

  8. Biology of Sexual Dysfunction

    Directory of Open Access Journals (Sweden)

    Anil Kumar Mysore Nagaraj

    2009-05-01

    Full Text Available Sexual activity is a multifaceted activity, involving complex interactions between the nervous system, the endocrine system, the vascular system and a variety of structures that are instrumental in sexual excitement, intercourse and satisfaction. Sexual function has three components i.e., desire, arousal and orgasm. Many sexual dysfunctions can be categorized according to the phase of sexual response that is affected. In actual clinical practice however, sexual desire, arousal and orgasmic difficulties more often than not coexist, suggesting an integration of phases. Sexual dysfunction can result from a wide variety of psychological and physiological causes including derangements in the levels of sex hormones and neurotrensmitters. This review deals with the biology of different phases of sexual function as well as implications of hormones and neurotransmitters in sexual dysfunction

  9. Risk factors for swallowing dysfunction in stroke patients

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    Anna Flávia Ferraz Barros Baroni

    2012-06-01

    Full Text Available CONTEXT: Stroke is a frequent cause of dysphagia. OBJECTIVE: To evaluate in a tertiary care hospital the prevalence of swallowing dysfunction in stroke patients, to analyze factors associated with the dysfunction and to relate swallowing dysfunction to mortality 3 months after the stroke. METHODS: Clinical evaluation of deglutition was performed in 212 consecutive patients with a medical and radiologic diagnosis of stroke. The occurrence of death was determined 3 months after the stroke. RESULTS: It was observed that 63% of the patients had swallowing dysfunction. The variables gender and specific location of the lesion were not associated with the presence or absence of swallowing dysfunction. The patients with swallowing dysfunction had more frequently a previous stroke, had a stroke in the left hemisphere, motor and/or sensitivity alterations, difficulty in oral comprehension, alteration of oral expression, alteration of the level of consciousness, complications such as fever and pneumonia, high indexes on the Rankin scale, and low indexes on the Barthel scale. These patients had a higher mortality rate. CONCLUSIONS: Swallowing evaluation should be done in all patients with stroke, since swallowing dysfunction is associated with complications and an increased risk of death.

  10. Gastrointestinal Dysfunctions as a Risk Factor for Sleep Disorders in Children with Idiopathic Autism Spectrum Disorder: A Retrospective Cohort Study

    Science.gov (United States)

    McCue, Lena M.; Flick, Louise H.; Twyman, Kimberly A.; Xian, Hong

    2017-01-01

    Sleep disorders often co-occur with autism spectrum disorder. They further exacerbate autism spectrum disorder symptoms and interfere with children's and parental quality of life. This study examines whether gastrointestinal dysfunctions increase the odds of having sleep disorders in 610 children with idiopathic autism spectrum disorder, aged 2-18…

  11. Mitochondrial NADP+-Dependent Isocitrate Dehydrogenase Deficiency Exacerbates Mitochondrial and Cell Damage after Kidney Ischemia-Reperfusion Injury.

    Science.gov (United States)

    Han, Sang Jun; Jang, Hee-Seong; Noh, Mi Ra; Kim, Jinu; Kong, Min Jung; Kim, Jee In; Park, Jeen-Woo; Park, Kwon Moo

    2017-04-01

    Mitochondrial NADP+-dependent isocitrate dehydrogenase (IDH2) catalyzes the oxidative decarboxylation of isocitrate to α-ketoglutarate, synthesizing NADPH, which is essential for mitochondrial redox balance. Ischemia-reperfusion (I/R) is one of most common causes of AKI. I/R disrupts the mitochondrial redox balance, resulting in oxidative damage to mitochondria and cells. Here, we investigated the role of IDH2 in I/R-induced AKI. I/R injury in mice led to the inactivation of IDH2 in kidney tubule cells. Idh2 gene deletion exacerbated the I/R-induced increase in plasma creatinine and BUN levels and the histologic evidence of tubule injury, and augmented the reduction of NADPH levels and the increase in oxidative stress observed in the kidney after I/R. Furthermore, Idh2 gene deletion exacerbated I/R-induced mitochondrial dysfunction and morphologic fragmentation, resulting in severe apoptosis in kidney tubule cells. In cultured mouse kidney proximal tubule cells, Idh2 gene downregulation enhanced the mitochondrial damage and apoptosis induced by treatment with hydrogen peroxide. This study demonstrates that Idh2 gene deletion exacerbates mitochondrial damage and tubular cell death via increased oxidative stress, suggesting that IDH2 is an important mitochondrial antioxidant enzyme that protects cells from I/R insult. Copyright © 2017 by the American Society of Nephrology.

  12. Side of symptom onset affects motor dysfunction in Parkinson's disease.

    NARCIS (Netherlands)

    Haaxma, C.A.; Helmich, R.C.G.; Borm, G.F.; Kappelle, A.C.; Horstink, M.W.I.M.; Bloem, B.R.

    2010-01-01

    The healthy brain appears to have an asymmetric dopamine distribution, with higher levels of dopamine in the left than in the right striatum. Here, we test the hypothesis that this neurochemical asymmetry renders the right striatum relatively more vulnerable to the effects of dopaminergic

  13. Drooling in cerebral palsy: hypersalivation or dysfunctional oral motor control?

    NARCIS (Netherlands)

    Erasmus, C.E.; Hulst, K. van; Rotteveel, L.J.C.; Jongerius, P.H.; Hoogen, F.J.A. van den; Roeleveld, N.; Rotteveel, J.J.

    2009-01-01

    AIM: To investigate whether drooling in children with cerebral palsy (CP) in general and in CP subtypes is due to hypersalivation. METHOD: Saliva was collected from 61 healthy children (30 males, mean age 9y 5mo [SD 11mo]; 31 females, mean age 9y 6mo [1y 2mo]) and 100 children with CP who drooled

  14. Female sexual dysfunction

    DEFF Research Database (Denmark)

    Giraldi, Annamaria; Wåhlin-Jacobsen, Sarah

    2016-01-01

    Female sexual dysfunction (FSD) is a controversial condition, which has prompted much debate regarding its aetiology, components, and even its existence. Our inability to work together as clinicians, psychologists, patients, and advocates hinders our understanding of FSD, and we will only improve...

  15. Mitochondrial Dysfunction in Gliomas

    Czech Academy of Sciences Publication Activity Database

    Katsetos, C.D.; Anni, H.; Dráber, Pavel

    2013-01-01

    Roč. 20, č. 3 (2013), s. 216-227 ISSN 1071-9091 R&D Projects: GA MŠk LH12050 Institutional support: RVO:68378050 Keywords : gliomas * mitochondrial dysfunction * microtubule proteins Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 1.883, year: 2013

  16. [Significance of biliary dysfunction in the pathogenesis of gallstone disease].

    Science.gov (United States)

    Il'chenko, I A; Deliukina, O V

    2011-01-01

    The paper shows the role of biliary dysfunction in the formation of biliary sludge. Found that among all motor dysfunction themost common is reduction of contractile function of the gallbladder (in 63.3% of cases), which is combined with 73.2% Oddi's sphincter hypertonus. T The combination of ursodeoxycholic acid (UDCA) with mebeverine has a better effect than monotherapy with UDCA, as increases the frequency of relief of biliary dyspepsia symptoms, normalizes the biliary tract functional status and 95% of cases leads to the elimination of biliary sludge.

  17. [Motor system physiotherapy of the masticatory organ].

    Science.gov (United States)

    Jagucka-Metel, Wioletta; Brzeska, Paulina; Sobolewska, Ewa; Machoy-Mokrzyńska, Anna; Baranowska, Agata

    2013-01-01

    The motor system of the masticatory organ is a complex morphological and functional structure. Its dysfunctions are manifested by various symptoms within the masticatory apparatus and in distant organs. The paper presents a discussion on the physiotherapeutic procedure for the treatment of disorders in the motor system of the masticatory organ. Therapeutic methods are presented, including: massage, trigger point therapy, kinesitherapy, biofeedback, manual therapy, postural re-education, kinesiotaping, physical interventions (TENS, hyaluronidase iontophoresis, ultrasound, laser therapy, and magnetoledotherapy). The paper points out the role of a comprehensive approach to the patient in order to eliminate the cause of disorders, going beyond symptomatic treatment.

  18. Linking aβ42-induced hyperexcitability to neurodegeneration, learning and motor deficits, and a shorter lifespan in an Alzheimer's model.

    Directory of Open Access Journals (Sweden)

    Yong Ping

    2015-03-01

    Full Text Available Alzheimer's disease (AD is the most prevalent form of dementia in the elderly. β-amyloid (Aβ accumulation in the brain is thought to be a primary event leading to eventual cognitive and motor dysfunction in AD. Aβ has been shown to promote neuronal hyperactivity, which is consistent with enhanced seizure activity in mouse models and AD patients. Little, however, is known about whether, and how, increased excitability contributes to downstream pathologies of AD. Here, we show that overexpression of human Aβ42 in a Drosophila model indeed induces increased neuronal activity. We found that the underlying mechanism involves the selective degradation of the A-type K+ channel, Kv4. An age-dependent loss of Kv4 leads to an increased probability of AP firing. Interestingly, we find that loss of Kv4 alone results in learning and locomotion defects, as well as a shortened lifespan. To test whether the Aβ42-induced increase in neuronal excitability contributes to, or exacerbates, downstream pathologies, we transgenically over-expressed Kv4 to near wild-type levels in Aβ42-expressing animals. We show that restoration of Kv4 attenuated age-dependent learning and locomotor deficits, slowed the onset of neurodegeneration, and partially rescued premature death seen in Aβ42-expressing animals. We conclude that Aβ42-induced hyperactivity plays a critical role in the age-dependent cognitive and motor decline of this Aβ42-Drosophila model, and possibly in AD.

  19. Uncovering sensory axonal dysfunction in asymptomatic type 2 diabetic neuropathy.

    Directory of Open Access Journals (Sweden)

    Jia-Ying Sung

    Full Text Available This study investigated sensory and motor nerve excitability properties to elucidate the development of diabetic neuropathy. A total of 109 type 2 diabetes patients were recruited, and 106 were analyzed. According to neuropathy severity, patients were categorized into G0, G1, and G2+3 groups using the total neuropathy score-reduced (TNSr. Patients in the G0 group were asymptomatic and had a TNSr score of 0. Sensory and motor nerve excitability data from diabetic patients were compared with data from 33 healthy controls. Clinical assessment, nerve conduction studies, and sensory and motor nerve excitability testing data were analyzed to determine axonal dysfunction in diabetic neuropathy. In the G0 group, sensory excitability testing revealed increased stimulus for the 50% sensory nerve action potential (P<0.05, shortened strength-duration time constant (P<0.01, increased superexcitability (P<0.01, decreased subexcitability (P<0.05, decreased accommodation to depolarizing current (P<0.01, and a trend of decreased accommodation to hyperpolarizing current in threshold electrotonus. All the changes progressed into G1 (TNSr 1-8 and G2+3 (TNSr 9-24 groups. In contrast, motor excitability only had significantly increased stimulus for the 50% compound motor nerve action potential (P<0.01 in the G0 group. This study revealed that the development of axonal dysfunction in sensory axons occurred prior to and in a different fashion from motor axons. Additionally, sensory nerve excitability tests can detect axonal dysfunction even in asymptomatic patients. These insights further our understanding of diabetic neuropathy and enable the early detection of sensory axonal abnormalities, which may provide a basis for neuroprotective therapeutic approaches.

  20. Severe exacerbations and decline in lung function in asthma

    DEFF Research Database (Denmark)

    O'Byrne, Paul M; Pedersen, Søren; Lamm, Carl Johan

    2009-01-01

    are associated with a persistent decline in lung function. METHODS: The START (inhaled steroid treatment as regular therapy in early asthma) study was a 3-year, randomized, double-blind study of 7,165 patients (5-66 yr) with persistent asthma for less than 2 years, to determine whether early intervention...... with low-dose inhaled budesonide prevents severe asthma-related events (exacerbations requiring hospitalization or emergency treatment) and decline in lung function. MEASUREMENTS AND MAIN RESULTS: There were 315 patients who experienced at least one severe asthma exacerbation, of which 305 were analyzable...... difference was seen in both children and in adults, but not in adolescents. In the budesonide group, the change in the post-bronchodilator FEV(1) % predicted in patients who did or did not experience a severe exacerbation was -2.48% and -1.72%, respectively (P = 0.57). The difference in magnitude...

  1. Postpartum airway responsiveness and exacerbation of asthma during pregnancy

    DEFF Research Database (Denmark)

    Ali, Zarqa; Nilas, Lisbeth; Ulrik, Charlotte Suppli

    2017-01-01

    . MATERIALS AND METHODS: In women with asthma who were prescribed controller medication and monitored closely during pregnancy, the risk of exacerbations was analyzed in relation to postpartum measures of fractional exhaled nitric oxide (FENO), skin prick test reactivity, static and dynamic lung volumes......BACKGROUND: Airway responsiveness and inflammation are associated with the clinical manifestations of asthma and the response to pharmacological therapy. OBJECTIVE: To investigate if airway responsiveness and inflammatory characteristics are related to asthma exacerbations during pregnancy......, diffusing capacity for carbon monoxide, bronchial responsiveness to inhaled mannitol, and inflammatory characteristics in induced sputum. Obtained data were analyzed in relation to exacerbation status during pregnancy. The PD15 is defined as the cumulative administered dose causing a 15% decline in forced...

  2. Modulation of airway inflammation to prevent exacerbations of COPD

    Directory of Open Access Journals (Sweden)

    M. Solèr

    2005-12-01

    Full Text Available Exacerbations of chronic obstructive pulmonary disease (COPD are periods in the chronic course of this disease with symptoms of intensified inflammation, induced in part by infections but also by noninfectious irritating mechanisms. Although these exacerbations seem to be linked to accelerated long-term disease progression and impaired quality of life, there are only limited preventive measures available, apart from smoking cessation. This article compares the effectiveness of different pharmacological treatments for the prevention of COPD exacerbations, including the oral bacterial lysate OM-85. Given the differences in the mechanism of action of the treatments discussed, this opens some hope for additive or potentiating effects with combined treatments, which will have to be studied in future controlled trials.

  3. COPD exacerbations in general practice: variability in oral prednisolone courses

    Directory of Open Access Journals (Sweden)

    de Vries Marianne

    2012-01-01

    Full Text Available Abstract Background The use of oral corticosteroids as treatment of COPD exacerbations in primary care is well established and evidence-based. However, the most appropriate dosage regimen has not been determined and remains controversial. Corticosteroid therapy is associated with a number of undesirable side effects, including hyperglycaemias, so differences in prescribing might be relevant. This study examines the differences between GPs in dosage and duration of prednisolone treatment in patients with a COPD exacerbation. It also investigates the number of general practitioners (GPs who adjust their treatment according to the presence of diabetic co-morbidity. Methods Cross-sectional study among 219 GPs and 25 GPs in training, located in the Northern part of the Netherlands. Results The response rate was 69%. Nearly every GP prescribed a continuous dose of prednisolone 30 mg per day. Among GPs there were substantial differences in treatment duration. GPs prescribed courses of five, seven, ten, or fourteen days. A course of seven days was most common. The duration of treatment depended on exacerbation and disease severity. A course of five days was especially prescribed in case of a less severe exacerbation. In a more severe exacerbation duration of seven to fourteen days was more common. Hardly any GP adjusted treatment to the presence of diabetic co-morbidity. Conclusion Under normal conditions GPs prescribe prednisolone quite uniformly, within the range of the current Dutch guidelines. There is insufficient guidance regarding how to adjust corticosteroid treatment to exacerbation severity, disease severity and the presence of diabetic co-morbidity. Under these circumstances, there is a substantial variation in treatment duration.

  4. Can exhaled volatile organic compounds predict asthma exacerbations in children?

    Science.gov (United States)

    van Vliet, Dillys; Smolinska, Agnieszka; Jöbsis, Quirijn; Rosias, Philippe; Muris, Jean; Dallinga, Jan; Dompeling, Edward; van Schooten, Frederik-Jan

    2017-03-01

    Asthma control does not yet meet the goals of asthma management guidelines. Non-invasive monitoring of airway inflammation may help to improve the level of asthma control in children. (1) To identify a set of exhaled volatile organic compounds (VOCs) that is most predictive for an asthma exacerbation in children. (2) To elucidate the chemical identity of predictive biomarkers. In a one-year prospective observational study, 96 asthmatic children participated . During clinical visits at 2 month intervals, asthma control, fractional exhaled nitric oxide, lung function (FEV1, FEV1/VC) and VOCs in exhaled breath were determined by means of gas chromatography time-of-flight mass spectrometry. Random Forrest classification modeling was used to select predictive VOCs, followed by plotting of receiver operating characteristic-curves (ROC-curves). An inverse relationship was found between the predictive power of a set of VOCs and the time between sampling of exhaled breath and the onset of exacerbation. The sensitivity and specificity of the model predicting exacerbations 14 days after sampling were 88% and 75%, respectively. The area under the ROC-curve was 90%. The sensitivity for prediction of asthma exacerbations within 21 days after sampling was 63%. In total, 7 VOCs were selected for the classification model: 3 aldehydes, 1 hydrocarbon, 1 ketone, 1 aromatic compound, and 1 unidentified VOC. VOCs in exhaled breath showed potential for predicting asthma exacerbations in children within 14 days after sampling. Before using this in clinical practice, the validity of predicting asthma exacerbations should be studied in a larger cohort.

  5. Impairment of Procedural Learning and Motor Intracortical Inhibition in Neurofibromatosis Type 1 Patients

    Directory of Open Access Journals (Sweden)

    Máximo Zimerman

    2015-10-01

    Interpretations: Collectively, the present results provide evidence that learning of a motor skill is impaired even in clinically intact NF1 patients based, at least partially, on a GABAergic-cortical dysfunctioning as suggested in previous animal work.

  6. Motor function and respiratory capacity in patients with late-onset pompe disease

    DEFF Research Database (Denmark)

    Illes, Zsolt; Mike, Andrea; Trauninger, Anita

    2014-01-01

    Introduction: The relationship between skeletal muscle strength and respiratory dysfunction in Pompe disease has not been examined by quantitative methods. We investigated correlations among lower extremity proximal muscle strength, respiratory function, and motor performance. Methods: Concentric...

  7. Transcriptomics of aged Drosophila motor neurons reveals a matrix metalloproteinase that impairs motor function.

    Science.gov (United States)

    Azpurua, Jorge; Mahoney, Rebekah E; Eaton, Benjamin A

    2018-02-07

    The neuromuscular junction (NMJ) is responsible for transforming nervous system signals into motor behavior and locomotion. In the fruit fly Drosophila melanogaster, an age-dependent decline in motor function occurs, analogous to the decline experienced in mice, humans, and other mammals. The molecular and cellular underpinnings of this decline are still poorly understood. By specifically profiling the transcriptome of Drosophila motor neurons across age using custom microarrays, we found that the expression of the matrix metalloproteinase 1 (dMMP1) gene reproducibly increased in motor neurons in an age-dependent manner. Modulation of physiological aging also altered the rate of dMMP1 expression, validating dMMP1 expression as a bona fide aging biomarker for motor neurons. Temporally controlled overexpression of dMMP1 specifically in motor neurons was sufficient to induce deficits in climbing behavior and cause a decrease in neurotransmitter release at neuromuscular synapses. These deficits were reversible if the dMMP1 expression was shut off again immediately after the onset of motor dysfunction. Additionally, repression of dMMP1 enzymatic activity via overexpression of a tissue inhibitor of metalloproteinases delayed the onset of age-dependent motor dysfunction. MMPs are required for proper tissue architecture during development. Our results support the idea that matrix metalloproteinase 1 is acting as a downstream effector of antagonistic pleiotropy in motor neurons and is necessary for proper development, but deleterious when reactivated at an advanced age. © 2018 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

  8. Dysfunctions in public psychiatric bureaucracies.

    Science.gov (United States)

    Marcos, L R

    1988-03-01

    The author describes common dysfunctions in public psychiatric organizations according to the model of bureaucracy articulated by Max Weber. Dysfunctions are divided into the categories of goal displacement, outside interference, unclear authority structure and hierarchy, and informal relations in the work place. The author emphasizes the bureaucratic nature of public psychiatry and the need for mental health professionals to understand the dysfunctions of the organizations in which they work, including the impact of these dysfunctions on the provision of quality care.

  9. Can resistive breathing injure the lung? Implications for COPD exacerbations

    Directory of Open Access Journals (Sweden)

    Vassilakopoulos T

    2016-09-01

    Full Text Available Theodoros Vassilakopoulos, Dimitrios Toumpanakis Pulmonary and Critical Care Medicine, Medical School, National and Kapodistrian University of Athens, Greece Abstract: In obstructive lung diseases, airway inflammation leads to bronchospasm and thus resistive breathing, especially during exacerbations. This commentary discusses experimental evidence that resistive breathing per se (the mechanical stimulus in the absence of underlying airway inflammation leads to lung injury and inflammation (mechanotransduction. The potential implications of resistive breathing-induced mechanotrasduction in COPD exacerbations are presented along with the available clinical evidence. Keywords: resistive breathing, COPD, mechanotransduction, bronchoconstriction, inflammation

  10. Acute Exacerbation of Chronic Obstructive Pulmonary Disease: Cardiovascular Links

    Science.gov (United States)

    Laratta, Cheryl R.; van Eeden, Stephan

    2014-01-01

    Chronic obstructive pulmonary disease (COPD) is a chronic, progressive lung disease resulting from exposure to cigarette smoke, noxious gases, particulate matter, and air pollutants. COPD is exacerbated by acute inflammatory insults such as lung infections (viral and bacterial) and air pollutants which further accelerate the steady decline in lung function. The chronic inflammatory process in the lung contributes to the extrapulmonary manifestations of COPD which are predominantly cardiovascular in nature. Here we review the significant burden of cardiovascular disease in COPD and discuss the clinical and pathological links between acute exacerbations of COPD and cardiovascular disease. PMID:24724085

  11. Susceptibility to exacerbation in chronic obstructive pulmonary disease

    DEFF Research Database (Denmark)

    Hurst, John R; Vestbo, Jørgen; Anzueto, Antonio

    2010-01-01

    of COPD that is independent of disease severity. METHODS: We analyzed the frequency and associations of exacerbation in 2138 patients enrolled in the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) study. Exacerbations were defined as events that led a care provider...... of follow-up were 0.85 per person for patients with stage 2 COPD (with stage defined in accordance with Global Initiative for Chronic Obstructive Lung Disease [GOLD] stages), 1.34 for patients with stage 3, and 2.00 for patients with stage 4. Overall, 22% of patients with stage 2 disease, 33% with stage 3...

  12. Chronic obstructive pulmonary disease: Emergency care in acute exacerbation

    Directory of Open Access Journals (Sweden)

    Tedd J. Welniak

    2015-06-01

    The purpose of this paper is to outline the current state of research and international guidelines surrounding the management of acute exacerbation of COPD in the emergency centre. Strict adherence to international guidelines for management of acute exacerbation of COPD may be difficult for many African providers given factors affecting diagnosis, treatment, and access to care for many Africans suffering from COPD. Research looking into the role of the African EM practitioner in providing more cost-effective means of diagnosis and treatment of COPD is limited.

  13. What Is a Dysfunctional School?

    Science.gov (United States)

    Bergman, M. M.

    2013-01-01

    Whether or not a school is dysfunctional depends largely on how dysfunctionality in schools is defined and measured. Dysfunctionality, as any construct, is subject to definition and interpretation, and it is thus always marked by perspectivism. But regardless of the definition games occasionally played by academics, some form of reality takes…

  14. Gross motor control

    Science.gov (United States)

    Gross motor control is the ability to make large, general movements (such as waving an arm or lifting a ... Gross motor control is a milestone in the development of an infant. Infants develop gross motor control before they ...

  15. Congenital and compensated vestibular dysfunction in childhood: an overlooked entity.

    Science.gov (United States)

    Weiss, Avery H; Phillips, James O

    2006-07-01

    We report five children with previously unrecognized vestibular dysfunction detected by clinical examination and confirmed by quantitative vestibular testing. Patient 1 presented with fluctuating visual acuity and intermittent nystagmus. Patient 2 had congenital hearing loss associated with imbalance, delayed motor development, and cyclic vomiting. Patient 3 had neurotrophic keratitis with an intermittent head tilt, imbalance, and motor delays. Patient 4 showed ataxia and eye movement abnormalities following traumatic brain injury and had reading difficulties. Patient 5 had episodic vertigo and eye movement abnormalities from infancy. Clinical vestibular testing emphasized spontaneous nystagmus, rapid head thrust, and assessment of post-rotatory nystagmus. Quantitative vestibular testing included the sinusoidal chair rotation and velocity step tests, measurement of dynamic visual acuity, post-head-shake nystagmus, and computerized platform posturography. Pediatric neurologists encounter children with congenital and compensated vestibular dysfunction, which can be recognized on the basis of relevant history and clinical abnormalities of the ocular-ocular reflex.

  16. Evaluation and treatment of vestibular dysfunction in children.

    Science.gov (United States)

    Rine, Rose Marie; Wiener-Vacher, Sylvette

    2013-01-01

    The effect of vestibular dysfunction since birth is more debilitating than that attained later in life, and unlike adults, children with vestibular dysfunction since or shortly after birth do not recover function without intervention. The purpose of this report is to provide an overview of the etiology of vestibular dysfunction in children as well as the related impairments, and to describe testing methods and evidence based interventions to ameliorate the vestibular related impairments in children. In recent years, investigations have revealed that vestibular dysfunction is more common in children than previously thought, with consequent impairments in motor development, balance and reading abilities. The dysfunction may be due to central or peripheral lesions, each with distinct presentation of symptoms and test results. Common etiologies and clinical presentation of vestibular dysfunction in children are reviewed; appropriate screening and diagnostic techniques and efficacious medical and rehabilitation interventions are presented. Despite advances in clinical and diagnostic testing of vestibular function in children and infants, testing of vestibular function is not typically done. Comprehensive testing of signs and symptoms is critical for diagnosis and implementation of appropriate interventions.

  17. Sexual dysfunction in diabetes.

    Science.gov (United States)

    Tamás, Várkonyi; Kempler, Peter

    2014-01-01

    We aimed to summarize the etiology, clinical characteristics, diagnosis, and possible treatment options of sexual dysfunction in diabetic patients of both sexes. Details of dysfunction in diabetic women are less conclusive than in men due to the lack of standardized evaluation of sexual function in women. Male sexual dysfunction is a common complication of diabetes, including abnormalities of orgasmic/ejaculatory function and desire/libido in addition to penile erection. The prevalence of erectile dysfunction (ED) among diabetic men varies from 35% to 75%. Diabetes-induced ED has a multifactorial etiology including metabolic, neurologic, vascular, hormonal, and psychological components. ED should be regarded as the first sign of cardiovascular disease because it can be present before development of symptomatic coronary artery disease, as larger coronary vessels better tolerate the same amount of plaque compared to smaller penile arteries. The diagnosis of ED is based on validated questionnaires and determination of functional and organic abnormalities. First-, second- and third-line therapy may be applied. Phosphodiesterase-5 (PDE-5) inhibitor treatment from the first-line options leads to smooth muscle relaxation in the corpus cavernosum and enhancement in blood flow, resulting in erection during sexual stimulus. The use of PDE-5 inhibitors in the presence of oral nitrates is strictly contraindicated in diabetic men, as in nondiabetic subjects. All PDE-5 inhibitors have been evaluated for ED in diabetic patients with convincing efficacy data. Second-line therapy includes intracavernosal, trans- or intraurethral administration of vasoactive drugs or application of a vacuum device. Third-line therapies are the implantation of penile prosthesis and penile revascularization.

  18. Older adults with amnestic mild cognitive impairment exhibit exacerbated gait slowing under dual-task challenges.

    Science.gov (United States)

    Tseng, Benjamin Y; Cullum, C Munro; Zhang, Rong

    2014-01-01

    With age, performance of motor tasks becomes more reliant on cognitive resources to compensate for the structural and functional declines in the motor control regions in the brain. We hypothesized that participants with amnestic mild cognitive impairment (aMCI) are more prone to motor dysfunctions than cognitively normal older adults under dual-task conditions where competitive demands challenge cognitive functions while performing a motor task simultaneously. Sixteen aMCI participants (females=9, age=64±5yrs, clinical dementia rating score=0.5) and 10 age- and education-matched cognitively normal adults (females=5, age=62±6yrs) participated. Using a 10-meter-walk test (10MW), gait velocity was recorded at baseline and under 4 different dual-task (DT) conditions designed to challenge working memory, executive function, and episodic memory. Specifically, DT1: verbal fluency; DT2: 5-digit backward span; DT3: serial-7 subtraction; and DT4: 3-item delayed recall. Physical function was measured by Timed Up-and-Go (TUG), simple reaction time (RT) to a free-falling yardstick, and functional reach (FR). No difference was found in physical functions, aerobic fitness, and exercise cardiopulmonary responses between aMCI participants and controls. However, aMCI participants showed more pronounced gait slowing from baseline when compared to the controls (p<0.05; p=0.001; p<0.001; p<0.001, respectively). Our finding supports the theory of shared resource of motor and cognitive control. Participants with aMCI manifested more gait slowing than cognitively-normal older adults under DT conditions, with the largest differences during tests of working and episodic memory. The outcome of dual-task assessment shows promise as a potential marker for detection of aMCI and early Alzheimer disease.

  19. Sexual dysfunction in relapsing-remitting multiple sclerosis: magnetic resonance imaging, clinical, and psychological correlates.

    OpenAIRE

    Barak, Y; Achiron, A.; Elizur, A; Gabbay, U; Noy, S; Sarova-Pinhas, I

    1996-01-01

    The purpose of this study was to examine the sexual complaints and severity of sexual dysfunction in relapsing-remitting multiple sclerosis patients and to correlate them with psychological, neurological, and radiological variables. Frequency and characteristics of sexual disturbances were reported by 41 multiple sclerosis patients (32 females, 9 males; mean age 35.4 +/- 10.2 y). Clinical neurologic variables tested were disease duration, exacerbation rate, and disability; psychological varia...

  20. Motor control for a brushless DC motor

    Science.gov (United States)

    Peterson, William J. (Inventor); Faulkner, Dennis T. (Inventor)

    1985-01-01

    This invention relates to a motor control system for a brushless DC motor having an inverter responsively coupled to the motor control system and in power transmitting relationship to the motor. The motor control system includes a motor rotor speed detecting unit that provides a pulsed waveform signal proportional to rotor speed. This pulsed waveform signal is delivered to the inverter to thereby cause an inverter fundamental current waveform output to the motor to be switched at a rate proportional to said rotor speed. In addition, the fundamental current waveform is also pulse width modulated at a rate proportional to the rotor speed. A fundamental current waveform phase advance circuit is controllingly coupled to the inverter. The phase advance circuit is coupled to receive the pulsed waveform signal from the motor rotor speed detecting unit and phase advance the pulsed waveform signal as a predetermined function of motor speed to thereby cause the fundamental current waveform to be advanced and thereby compensate for fundamental current waveform lag due to motor winding reactance which allows the motor to operate at higher speeds than the motor is rated while providing optimal torque and therefore increased efficiency.

  1. Cognitive Dysfunction in Fibromyalgia

    Directory of Open Access Journals (Sweden)

    Tuba Tulay Koca

    2015-03-01

    Full Text Available The primary symptom of fibromyalgia is widespread pain with muscle tenderness to light palpation. Howeover many patients report a wide range of symptoms including pain, dyscognition, sleep disturbances, fatigue and mood disorders (frequently depression. Such symptoms seem to be related to one another. Besides, a decrease in concentration and memory disorder has recognised as an independent symptom yet; added into literature under the terms and lsquo;dyscognition' and and lsquo;fibrofog'. Recently clinicians interested in investigations about dyscognition in fibromyalgia syndrome. Cognitive symptoms may be exacerbated by the presence of depression, anxiety, sleep dysorders, endocrine disregulations and pain; but the relationship is unclear. Additionally some of recent studies suggest that insulin resistance may represent a risk factor for memory impairment in these patients. There is lack of standardized tests, treatment methods and studies for understanding pathophysiologic pathways of cognitive problems (memory, concentration in fibromyalgia.

  2. Electrophysiological Signs of Supplementary-Motor-Area Deficits in High-Functioning Autism but Not Asperger Syndrome: An Examination of Internally Cued Movement-Related Potentials

    Science.gov (United States)

    Enticott, Peter G.; Bradshaw, John L.; Iansek, Robert; Tonge, Bruce J.; Rinehart, Nicole J.

    2009-01-01

    Aims: Motor dysfunction is common to both autism and Asperger syndrome, but the underlying neurophysiological impairments are unclear. Neurophysiological examinations of motor dysfunction can provide information about likely sites of functional impairment and can contribute to the debate about whether autism and Asperger syndrome are variants of…

  3. Risk Factors Precipitating Exacerbations in Adult Asthma Patients ...

    African Journals Online (AJOL)

    Risk Factors Precipitating Exacerbations in Adult Asthma Patients presenting at Kalafong Hospital, Pretoria. ... South African Family Practice ... The total prevalence of asthma is estimated to lie at 7.2% of the world\\'s population (6% in adults, ...

  4. Accelerated extracellular matrix turnover during exacerbations of COPD

    DEFF Research Database (Denmark)

    Sand, Jannie M B; Knox, Alan J; Lange, Peter

    2015-01-01

    progression. Extracellular matrix (ECM) turnover reflects activity in tissues and consequently assessment of ECM turnover may serve as biomarkers of disease activity. We hypothesized that the turnover of lung ECM proteins were altered during exacerbations of COPD. METHODS: 69 patients with COPD hospitalised...

  5. Risk factors for asthma exacerbation in patients presenting to an ...

    African Journals Online (AJOL)

    Background: Asthma exacerbations are caused by a variety of risk factors. Reducing exposure to these risk factors improves the control of asthma and reduces medication needs. Knowledge of the particular risk factors is essential in formulating controlling and treatment protocols. This study set out to determine the risk ...

  6. Diagnosis and management of acute exacerbations of chronic ...

    African Journals Online (AJOL)

    for at least 2 consecutive days.2,3. However, the severity of exacerbations can be extremely heterogeneous, ranging from a mild increase in symptoms to more serious manifestations and severe respiratory failure. The magnitude of the problem is substantial for the patient, as well as economically. In the USA alone, in 2000, ...

  7. Oxygen therapy in acute exacerbations of chronic obstructive pulmonary disease

    DEFF Research Database (Denmark)

    Ringbaek, T.; Lange, P.; Mogensen, T.

    2008-01-01

    Acute exacerbation of COPD is a major cause of hospitalisation in Denmark. Most of the patients require supplemental oxygen in the acute phase and some patients continue oxygen therapy at home after discharge. In this paper we discuss the physiological mechanisms of respiratory failure seen in ac...

  8. Prevalence and pattern of asthma exacerbation in children seen at ...

    African Journals Online (AJOL)

    2016-01-15

    Jan 15, 2016 ... Exacerbations of asthma symptoms produce significant cost to health care systems and seriously diminish the .... used at home prior to presentation. This included twelve. (46.2%) of the 26 newly ... begin to reverse as the children get older with almost equal rate between 5 and 10 years and more girls be-.

  9. Detection of rhinovirus-associated asthma exacerbations using ...

    African Journals Online (AJOL)

    Background: Acute exacerbations of asthma are the leading cause of emergency department visits in pediatric patients. The development of sensitive diagnostic polymerase chain reaction (PCR) based techniques permitted demonstration of an already clinically suspected association between common viral respiratory ...

  10. COPD exacerbations in general practice : variability in oral prednisolone courses

    NARCIS (Netherlands)

    de Vries, Marianne; Berendsen, Annette J.; Bosveld, Henk E. P.; Kerstjens, Huib A. M.; van der Molen, Thys

    2012-01-01

    Background: The use of oral corticosteroids as treatment of COPD exacerbations in primary care is well established and evidence-based. However, the most appropriate dosage regimen has not been determined and remains controversial. Corticosteroid therapy is associated with a number of undesirable

  11. Effects of N-acetylcysteine on asthma exacerbation.

    Science.gov (United States)

    Aliyali, Masoud; Poorhasan Amiri, Ali; Sharifpoor, Ali; Zalli, Fatemeh

    2010-06-01

    Airway mucus hypersecretion and increased oxidative stress are clinical and pathophysiological features of asthma exacerbation. We studied effects of N-acetylcysteine (NAC) as a mucolytic and antioxidant agent in asthma exacerbation. In this randomized, single-blinded, placebo-controlled study 50 patients ( 17 male, 33 female, mean age 48.94+/-13.68) with asthma exacerbation were randomized to receive either oral 600 mg b.d. N-acetylcysteine or placebo in addition to standard treatment during 5 days hospitalization. Daily measurements of wheezing, dyspnea, cough, sputum, expectoration, night sleep scores and morning PEFR were performed. There was no significant difference in wheezing score between patients assigned NAC and those assigned placebo in day 5(0.84[SD 0.94] VS 0.87[SD 0.79]) and also in cough score (0.72[SD 0.84] VS 0.79[SD 0.97]), dyspnea score (0.84[SD 1.06] VS 0.91[SD 1.01]), sputum score(0.79[SD 0.83] VS 0.62[SD 0.71]), expectoration score(0.79[SD 0.97] VS 0.83[SD 1.09]), night sleep score(1[SD 1.17] VS 0.67[SD 0.98] and morning PEFR (256[SD 96.36] VS 282[SD 98.86]). We concluded that addition of N-acetylcysteine to usual asthma medication has no significant effect in treatment of asthma exacerbation.

  12. How Clinical Diagnosis Might Exacerbate the Stigma of Mental Illness

    Science.gov (United States)

    Corrigan, Patrick W.

    2007-01-01

    Stigma can greatly exacerbate the experience of mental illness. Diagnostic classification frequently used by clinical social workers may intensify this stigma by enhancing the public's sense of "groupness" and "differentness" when perceiving people with mental illness. The homogeneity assumed by stereotypes may lead mental health professionals and…

  13. Obesity-Mediated Autophagy Insufficiency Exacerbates Proteinuria-induced Tubulointerstitial Lesions

    Science.gov (United States)

    Yamahara, Kosuke; Kume, Shinji; Koya, Daisuke; Tanaka, Yuki; Morita, Yoshikata; Chin-Kanasaki, Masami; Araki, Hisazumi; Isshiki, Keiji; Araki, Shin-ichi; Haneda, Masakazu; Matsusaka, Taiji; Kashiwagi, Atsunori; Maegawa, Hiroshi

    2013-01-01

    Obesity is an independent risk factor for renal dysfunction in patients with CKDs, including diabetic nephropathy, but the mechanism underlying this connection remains unclear. Autophagy is an intracellular degradation system that maintains intracellular homeostasis by removing damaged proteins and organelles, and autophagy insufficiency is associated with the pathogenesis of obesity-related diseases. We therefore examined the role of autophagy in obesity-mediated exacerbation of proteinuria-induced proximal tubular epithelial cell damage in mice and in human renal biopsy specimens. In nonobese mice, overt proteinuria, induced by intraperitoneal free fatty acid–albumin overload, led to mild tubular damage and apoptosis, and activated autophagy in proximal tubules reabsorbing urinary albumin. In contrast, diet-induced obesity suppressed proteinuria-induced autophagy and exacerbated proteinuria-induced tubular cell damage. Proximal tubule-specific autophagy-deficient mice, resulting from an Atg5 gene deletion, subjected to intraperitoneal free fatty acid–albumin overload developed severe proteinuria-induced tubular damage, suggesting that proteinuria-induced autophagy is renoprotective. Mammalian target of rapamycin (mTOR), a potent suppressor of autophagy, was activated in proximal tubules of obese mice, and treatment with an mTOR inhibitor ameliorated obesity-mediated autophagy insufficiency. Furthermore, both mTOR hyperactivation and autophagy suppression were observed in tubular cells of specimens obtained from obese patients with proteinuria. Thus, in addition to enhancing the understanding of obesity-related cell vulnerability in the kidneys, these results suggest that restoring the renoprotective action of autophagy in proximal tubules may improve renal outcomes in obese patients. PMID:24092929

  14. Assessment of Aerobic Exercise Adverse Effects during COPD Exacerbation Hospitalization

    Directory of Open Access Journals (Sweden)

    Caroline Knaut

    2017-01-01

    Full Text Available Introduction. Aerobic exercise performed after hospital discharge for exacerbated COPD patients is already recommended to improve respiratory and skeletal muscle strength, increase tolerance to activity, and reduce the sensation of dyspnea. Previous studies have shown that anaerobic activity can clinically benefit patients hospitalized with exacerbated COPD. However, there is little information on the feasibility and safety of aerobic physical activity performed by patients with exacerbated COPD during hospitalization. Objective. To evaluate the effects of aerobic exercise on vital signs in hospitalized patients with exacerbated COPD. Patients and Methods. Eleven COPD patients (63% female, FEV1: 34.2 ± 13.9% and age: 65 ± 11 years agreed to participate. Aerobic exercise was initiated 72 hours after admission on a treadmill; speed was obtained from the distance covered in a 6-minute walk test (6MWT. Vital signs were assessed before and after exercise. Results. During the activity systolic blood pressure increased from 125.2 ± 13.6 to 135.8 ± 15.0 mmHg (p=0.004 and respiratory rate from 20.9 ± 4.4 to 24.2 ± 4.5 rpm (p=0.008 and pulse oximetry (SpO2 decreased from 93.8 ± 2.3 to 88.5 ± 5.7% (p<0.001. Aerobic activity was considered intense, heart rate ranged from 99.2 ± 11.5 to 119.1 ± 11.1 bpm at the end of exercise (p=0.092, and patients reached on average 76% of maximum heart rate. Conclusion. Aerobic exercise conducted after 72 hours of hospitalization in patients with exacerbated COPD appears to be safe.

  15. One-year mortality after severe COPD exacerbation in Bulgaria

    Directory of Open Access Journals (Sweden)

    Evgeni Mekov

    2016-12-01

    Full Text Available Introduction One-year mortality in COPD patients is reported to be between 4% and 43%, depending on the group examined. Aim To examine the one-year mortality in COPD patients after severe exacerbation and the correlation between mortality and patients’ characteristics and comorbidities. Methods A total of 152 COPD patients hospitalized for severe exacerbation were assessed for vitamin D status, diabetes mellitus (DM, arterial hypertension (AH, and metabolic syndrome (MS. Data were gathered about smoking status and number of exacerbations in previous year. CAT and mMRC questionnaires were completed by all patients. Pre- and post-bronchodilatory spirometry was performed. One-year mortality was established from national death register. Results One-year mortality is 7.2%. DM, MS, and VD are not predictors for one-year mortality. However there is a trend for increased mortality in patients with AH (9.5% vs. 2.1%, p = 0.107. There is increased mortality in patients with mMRC > 2 (11.1 vs. 0%, p = 0.013. The presence of severe exacerbation in the previous year is a risk factor for mortality (12.5% vs. 1.4%, p = 0.009. There is a trend for increased mortality in the group with FEV1  80% may be factors for good prognosis. Risk factors for increased mortality are age, FEV1 value, severe exacerbation in previous year and reduced quality of life.

  16. The Burden of Illness Related to Chronic Obstructive Pulmonary Disease Exacerbations in Québec, Canada

    Directory of Open Access Journals (Sweden)

    Tam Dang-Tan

    2017-01-01

    Full Text Available Background. Chronic obstructive pulmonary disease (COPD prevalence in Canada has risen over time. COPD-related exacerbations contribute to the increased health care utilization (HCU in this population. This study investigated the impact of exacerbations on COPD-related HCU. Methods. This retrospective observational cohort study used patient data from the Québec provincial health insurance databases. Eligible patients with a new HCU claim with a diagnostic billing for COPD during 2001–2010 were followed until March 31, 2011. Exacerbation rates and time to first exacerbation were assessed. Unadjusted analyses and multivariable models compared the rate of HCU by exacerbation classification (any [moderate/severe], moderate, or severe. Results. The exacerbation event rate in patients with an exacerbation was 34.3 events/100 patient-years (22.7 for moderate exacerbations and 11.6 for severe exacerbations. Median time to first exacerbation of any classification was 37 months. In unadjusted analyses, COPD-related HCU significantly increased with exacerbation severity. In the multivariable, HCU rates were significantly higher after exacerbation versus before exacerbation (p<0.01 for patients with an exacerbation or moderate exacerbations. For severe exacerbations, general practitioner, respiratory specialist, emergency room, and hospital visits were significantly higher after exacerbation versus before exacerbation (p<0.001. Conclusions. Exacerbations were associated with increased HCU, which was more pronounced for patients with severe exacerbations. Interventions to reduce the risk of exacerbations in patients with COPD may reduce disease burden.

  17. High efficiency motors; Motores de alta eficiencia

    Energy Technology Data Exchange (ETDEWEB)

    Uranga Favela, Ivan Jaime [Energia Controlada de Mexico, S. A. de C. V., Mexico, D. F. (Mexico)

    1992-12-31

    This paper is a technical-financial study of the high efficiency and super-premium motors. As it is widely known, more than 60% of the electrical energy generated in the country is used for the operation of motors, in industry as well as in commerce. Therefore the importance that the motors have in the efficient energy use. [Espanol] El presente trabajo es un estudio tecnico-financiero de los motores de alta eficiencia y los motores super premium. Como es ampliamente conocido, mas del 60% de la energia electrica generada en el pais, es utilizada para accionar motores, dentro de la industria y el comercio. De alli la importancia que los motores tienen en el uso eficiente de la energia.

  18. Motor function deficits in the 12 month-old female 5xFAD mouse model of Alzheimer's disease.

    Science.gov (United States)

    O'Leary, T P; Robertson, A; Chipman, P H; Rafuse, V F; Brown, R E

    2018-01-30

    Motor problems occur early in some patients with Alzheimer's disease (AD) and as the disease progresses many patients develop motor dysfunction. Motor dysfunction has been reported in some mouse models of AD, including the 5xFAD mouse, thus this model may be particularly useful for studying motor dysfunction in AD. In order to determine the extent of motor dysfunction in these mice, we tested 11-13 month old female 5xFAD and wildtype (WT) control mice in a battery of motor behaviour tasks. The 5xFAD mice showed hind limb clasping, weighed less and had slower righting reflexes than WT mice. In the open field, the 5xFAD mice travelled a shorter distance than the WT mice, spent less time moving and had a slower movement speed. The 5xFAD mice fell faster than the WT mice from the balance beam, wire suspension, grid suspension and rotarod tasks, indicating dysfunctions in balance, grip strength, motor co-ordination and motor learning. The 5xFAD mice had a short, shuffling gait with a shorter stride length than WT mice and had a slower swim speed. The 5xFAD mice also failed to show an acoustic startle response, likely due to motor dysfunction and previously reported hearing impairment. The 5xFAD mice did not show deficits in the ability of peripheral motor nerves to drive muscle output, suggesting that motor impairments are not due to dysfunction in peripheral motor nerves. These results indicate that the aged 5xFAD mice are deficient in numerous motor behaviours, and suggest that these mice may prove to be a good model for studying the mechanisms of motor dysfunction in AD, and motor behaviour might prove useful for assessing the efficacy of AD therapeutics. Motor dysfunction in 5xFAD mice must also be considered in behavioural tests of sensory and cognitive function so that performance is not confounded by impaired locomotor or swimming behaviour. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. Astrocyte Activation in Locus Coeruleus Is Involved in Neuropathic Pain Exacerbation Mediated by Maternal Separation and Social Isolation Stress

    Directory of Open Access Journals (Sweden)

    Kazuo Nakamoto

    2017-06-01

    Full Text Available Our previous studies demonstrated that emotional dysfunction associated with early life stress exacerbated nerve injury-induced mechanical allodynia. Sex differences were observed in several anxiety tests, but not in mechanical allodynia. To elucidate the mechanism underlying these findings, we have now investigated the involvement of astrocytes in emotional dysfunction and enhancement of nerve injury-induced mechanical allodynia in mice subjected to maternal separation combined with social isolation (MSSI as an early life stress. We measured expression of glial fibrillary acidic protein (GFAP, an astrocyte maker, in each brain area by immunohistochemistry. GFAP expression in the locus coeruleus (LC of female, but not of male mice, significantly increased after MSSI, corresponding to the behavioral changes at 7 and 12 weeks of age. Lipopolysaccharide (LPS-treated astrocyte-derived supernatant was administered to local brain regions, including LC. Intra-LC injection of conditioned medium from cultured astrocytes treated with LPS increased GFAP expression, anxiety-like behavior and mechanical allodynia in both male and female mice. Furthermore, increases in anxiety-like behavior correlated with increased mechanical allodynia. These findings demonstrate that emotional dysfunction and enhanced nerve injury-induced mechanical allodynia after exposure to MSSI are mediated, at least in part, by astrocyte activation in the LC. Male but not female mice may show resistance to MSSI stress during growth.

  20. Aging and Erectile Dysfunction.

    Science.gov (United States)

    Echeverri Tirado, Laura C; Ferrer, Julio E; Herrera, Ana M

    2016-01-01

    Erectile dysfunction (ED) has been identified as the most common sexual problem that affects mainly men older than 40 years. According to this, there is a strong evidence linking ED with a number of medical conditions and related risk factors that had been described in the literature, yet there is limited information about the specific mechanism involved in the establishment of ED among healthy older men. The purpose of this study is to review the literature and mainly focus on the basic physiologic and vascular alterations and morphologic changes related to aging and its related risk factors, summarizing the main and the latest findings in basic research of tissue remodeling process involved in ED pathophysiology. Data from the pertinent literature were examined to inform our conclusions. This article defines the morphologic and physiologic mechanisms involved in the process of aging, which play a key role in the development of sexual dysfunction. ED has been considered as a nonlife-threatening condition, but the recognition of its multiple comorbid conditions, the importance of aging process over the male sexual performance among them its relation with vascular and nitric oxide content alteration, as well as penile morphologic changes, and the fact that it is a widespread under-reported disease, have established the need of an early diagnosis and treatment of this common sexual problem within the general male population. In this case, morphologic and physiologic mechanisms that are involved in the aging process play a key role in the development of sexual dysfunction in the absence of any other clinical or medical condition. Copyright © 2016 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.

  1. High LRRK2 levels fail to induce or exacerbate neuronal alpha-synucleinopathy in mouse brain.

    Directory of Open Access Journals (Sweden)

    Martin C Herzig

    Full Text Available The G2019S mutation in the multidomain protein leucine-rich repeat kinase 2 (LRRK2 is one of the most frequently identified genetic causes of Parkinson's disease (PD. Clinically, LRRK2(G2019S carriers with PD and idiopathic PD patients have a very similar disease with brainstem and cortical Lewy pathology (α-synucleinopathy as histopathological hallmarks. Some patients have Tau pathology. Enhanced kinase function of the LRRK2(G2019S mutant protein is a prime suspect mechanism for carriers to develop PD but observations in LRRK2 knock-out, G2019S knock-in and kinase-dead mutant mice suggest that LRRK2 steady-state abundance of the protein also plays a determining role. One critical question concerning the molecular pathogenesis in LRRK2(G2019S PD patients is whether α-synuclein (aSN has a contributory role. To this end we generated mice with high expression of either wildtype or G2019S mutant LRRK2 in brainstem and cortical neurons. High levels of these LRRK2 variants left endogenous aSN and Tau levels unaltered and did not exacerbate or otherwise modify α-synucleinopathy in mice that co-expressed high levels of LRRK2 and aSN in brain neurons. On the contrary, in some lines high LRRK2 levels improved motor skills in the presence and absence of aSN-transgene-induced disease. Therefore, in many neurons high LRRK2 levels are well tolerated and not sufficient to drive or exacerbate neuronal α-synucleinopathy.

  2. Clinical and Pulmonary Function Markers of Respiratory Exacerbation Risk in Subjects With Quadriplegic Cerebral Palsy.

    Science.gov (United States)

    Vianello, Andrea; Carraro, Elena; Pipitone, Emanuela; Marchese-Ragona, Rosario; Arcaro, Giovanna; Ferraro, Marco; Paladini, Luciana; Martinuzzi, Andrea

    2015-10-01

    Although respiratory exacerbations are common in patients with quadriplegic cerebral palsy (CP), little is known about the factors that are related to increased exacerbation risk. This study aimed to identify the clinical and pulmonary function variables signaling risk of exacerbation in this type of patient. Thirty-one children and young adults with quadriplegic CP underwent a comprehensive history, physical examination, and pulmonary function test, including arterial blood gas analysis, airway resistance using the interrupter technique, and home overnight SpO2 monitoring. Subjects were divided into 2 groups depending on the number of respiratory exacerbations reported during the year before study entry: frequent exacerbators (ie, ≥ 2 exacerbations) and infrequent exacerbators (ie, < 2 exacerbations). The frequent exacerbators were more likely to require hospitalization due to respiratory disorders compared with the infrequent exacerbators (13/14 vs 9/17, P = .02). Respiratory exacerbation was found to be associated with diagnosis of gastroesophageal reflux (adjusted odds ratio of 23.95 for subjects with confirmed diagnosis, P = .02) and higher PaCO2 levels (adjusted odds ratio of 12.60 for every 5-mm Hg increase in PaCO2 , P = .05). Subjects with PaCO2 ≥ 35 mm Hg showed an exacerbation odds ratio of 15.2 (95% CI 1.5-152.5, P = .01). Gastroesophageal reflux and increased PaCO2 can be considered simple, clinically useful markers of increased exacerbation risk in young subjects with quadriplegic CP. Copyright © 2015 by Daedalus Enterprises.

  3. Motor flexibility problems as a marker for genetic susceptibility to attention-deficit/hyperactivity disorder.

    NARCIS (Netherlands)

    Slaats-Willemse, D.I.; Sonneville, L.; Swaab-Barneveld, H.J.

    2005-01-01

    BACKGROUND: Since many children with attention-deficit/hyperactivity disorder (ADHD) have fine visuomotor problems that are already evident at a young age, motor dysfunctioning is investigated in family-genetic perspective. We hypothesized that if fine motor problems may be a marker for genetic

  4. Uncovering sensory axonal dysfunction in asymptomatic type 2 diabetic neuropathy

    Science.gov (United States)

    Sung, Jia-Ying; Tani, Jowy; Chang, Tsui-San; Lin, Cindy Shin-Yi

    2017-01-01

    This study investigated sensory and motor nerve excitability properties to elucidate the development of diabetic neuropathy. A total of 109 type 2 diabetes patients were recruited, and 106 were analyzed. According to neuropathy severity, patients were categorized into G0, G1, and G2+3 groups using the total neuropathy score-reduced (TNSr). Patients in the G0 group were asymptomatic and had a TNSr score of 0. Sensory and motor nerve excitability data from diabetic patients were compared with data from 33 healthy controls. Clinical assessment, nerve conduction studies, and sensory and motor nerve excitability testing data were analyzed to determine axonal dysfunction in diabetic neuropathy. In the G0 group, sensory excitability testing revealed increased stimulus for the 50% sensory nerve action potential (Pdiabetic neuropathy and enable the early detection of sensory axonal abnormalities, which may provide a basis for neuroprotective therapeutic approaches. PMID:28182728

  5. Managing female sexual dysfunction.

    Science.gov (United States)

    Buster, John E

    2013-10-01

    Female sexual dysfunctions (FSDs) range from short-term aggravations to major emotional disturbances adversely affecting family and workplace. This review highlights diagnosis and management of the four most widely diagnosed FSDs. It initially focuses on hypoactive sexual desire disorder (HSDD) as a driving force at the heart of all other FSDs; nothing happens without sexual desire. Successful resolution of HSDD frequently facilitates resolution of other disorders. Central to understanding HSDD is the impact of aging female sexual endocrinology and its effect on both prevalence and expression patterns of FSD. Advances in this field have enabled introduction of some the most effective treatments yet described for HSDD. Sexual arousal disorder, though commonly affected by the same factors as HSDD, is heavily associated with psychotropic drugs and mood elevators. Orgasmic disorder is frequently the downstream result of other sexual dysfunctions, particularly HSDD, or the result of a major psychosexual trauma. Successful management of the underlying disorder often resolves orgasmic disorder. Sexual pain disorder is frequently the result of a gynecologic disorder, such as endometriosis, that can be substantially managed through successful treatment of that disorder. This article ends with the article's most important note: how to initiate the conversation. Copyright © 2013 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  6. Oral corticosteroids for asthma exacerbations might be associated with adrenal suppression: Are physicians aware of that?

    Directory of Open Access Journals (Sweden)

    Cristina B. Barra

    Full Text Available Summary Introduction: Oral corticosteroids (OCS are a mainstay of treatment for asthma exacerbations, and short-term OCS courses were generally considered to be safe. Nevertheless, frequent short-term OCS courses could lead to hypothalamic-pituitary-adrenal (HPA axis dysfunction. Our study aimed at investigating the integrity of the HPA axis in children with persistent asthma or recurrent wheezing at the beginning of an inhaled corticosteroids (ICS trial. Method: Morning basal cortisol was assessed just before the beginning of ICS, and 30, 60, and 90 days later, using Immulite® Siemens Medical Solutions Diagnostic chemiluminescent enzyme immunoassay (Los Angeles, USA; 2006. Results: In all, 140 children (0.3-15 years old with persistent asthma or recurrent wheezing have been evaluated and 40% of them reported short-term OCS courses for up to 30 days before evaluation. Out of these, 12.5% had biochemical adrenal suppression but showed adrenal recovery during a three-month ICS trial treatment. No significant differences were observed among children with or without adrenal suppression, neither in the number of days free of OCS treatment before cortisol evaluation (p=0.29 nor in the last OCS course duration (p=0.20. The number of short-term OCS courses reported in the year preceding the cortisol evaluation was also not different (p=0.89. Conclusion: Short-term systemic courses of corticosteroids at conventional doses can put children at risk of HPA axis dysfunction. ICS treatment does not impair adrenal recovery from occurring. Health practitioners should be aware of the risk of a blunted cortisol response upon exposure to stress during the follow-up of patients with persistent asthma or recurrent wheezing.

  7. Neural substrates of motor and non-motor symptoms in Parkinson's disease: a resting FMRI study.

    Directory of Open Access Journals (Sweden)

    Kwangsun Yoo

    Full Text Available Recently, non-motor symptoms of Parkinson's disease (PD have been considered crucial factors in determining a patient's quality of life and have been proposed as the predominant features of the premotor phase. Researchers have investigated the relationship between non-motor symptoms and the motor laterality; however, this relationship remains disputed. This study investigated the neural connectivity correlates of non-motor and motor symptoms of PD with respect to motor laterality.Eight-seven patients with PD were recruited and classified into left-more-affected PD (n = 44 and right-more affected PD (n = 37 based on their MDS-UPDRS (Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale motor examination scores. The patients underwent MRI scanning, which included resting fMRI. Brain regions were labeled as ipsilateral and contralateral to the more-affected body side. Correlation analysis between the functional connectivity across brain regions and the scores of various symptoms was performed to identify the neural connectivity correlates of each symptom.The resting functional connectivity centered on the ipsilateral inferior orbito-frontal area was negatively correlated with the severity of non-motor symptoms, and the connectivity of the contralateral inferior parietal area was positively correlated with the severity of motor symptoms (p 0.3.These results suggest that the inferior orbito-frontal area may play a crucial role in non-motor dysfunctions, and that the connectivity information may be utilized as a neuroimaging biomarker for the early diagnosis of PD.

  8. Differences in systemic adaptive immunity contribute to the 'frequent exacerbator' COPD phenotype

    NARCIS (Netherlands)

    Geerdink, J.X.; Simons, S.O.; Pike, R.; Stauss, H.J.; Heijdra, Y.F.; Hurst, J.R.

    2016-01-01

    BACKGROUND: Some COPD patients are more susceptible to exacerbations than others. Mechanisms underlying these differences in susceptibility are not well understood. We hypothesized that altered cell mediated immune responses may underlie a propensity to suffer from frequent exacerbations in COPD.

  9. Vesicoureteral reflux and bladder dysfunction.

    Science.gov (United States)

    Lee, Hyeyoung; Lee, Yong Seung; Im, Young Jae; Han, Sang Won

    2012-09-01

    The relationship between vesicoureteral reflux and bladder dysfunction is inseparable and has long been emphasized. However, the primary concern of all physicians treating patients with vesicoureteral reflux is the prevention of renal scarring and eventual deterioration of renal function. Bladder dysfunction, urinary tract infection and vesicoureteral reflux are the three important factors which are closely related to each other and contribute to the formation of renal scar. Especially, there is ongoing discussion regarding the role of bladder dysfunction in the prognosis of both medically and surgically treated vesicoureteral reflux. The effect of bladder dysfunction on VUR is mostly via inadequate sphincter relaxation during infancy which is closer to immature bladder dyscoordination rather than true dysfunction. But after toilet training, functional obstruction caused by voluntary sphincter constriction during voiding is responsible through elevation in bladder pressure, thus distorting the architecture of bladder and ureterovesical junction. Reports suggest that voiding phase abnormalities in lower urinary tract dysfunction contributes to lower spontaneous resolution rate of VUR. However, filling phase abnormalities such as involuntary detrusor contraction can also cause VUR even in the absence of dysfunctional voiding. With regards to the effect of bladder dysfunction on treatment, meta-analysis reveals that the cure rate of VUR following endoscopic treatment is less in children with bladder bowel dysfunction but there is no difference for open surgery. The pathophysiology of bladder dysfunction associated with UTI can be explained by the 'milk-back' of contaminated urine back into the bladder and significant residual urine resulting from functional outlet obstruction. In addition, involuntary detrusor contraction can decrease perfusion of the bladder mucosa thus decreasing mucosal immunity and creating a condition prone to UTI. In terms of renal scarring

  10. Withdrawal of inhaled glucocorticoids and exacerbations of COPD

    DEFF Research Database (Denmark)

    Magnussen, Helgo; Disse, Bernd; Rodriguez-Roisin, Roberto

    2014-01-01

    BACKGROUND: Treatment with inhaled glucocorticoids in combination with long-acting bronchodilators is recommended in patients with frequent exacerbations of severe chronic obstructive pulmonary disease (COPD). However, the benefit of inhaled glucocorticoids in addition to two long......-acting bronchodilators has not been fully explored. METHODS: In this 12-month, double-blind, parallel-group study, 2485 patients with a history of exacerbation of COPD received triple therapy consisting of tiotropium (at a dose of 18 μg once daily), salmeterol (50 μg twice daily), and the inhaled glucocorticoid...... findings, health status, and dyspnea were also monitored. RESULTS: As compared with continued glucocorticoid use, glucocorticoid withdrawal met the prespecified noninferiority criterion of 1.20 for the upper limit of the 95% confidence interval (CI) with respect to the first moderate or severe COPD...

  11. Gene expression profiles of acute exacerbations of idiopathic pulmonary fibrosis.

    Science.gov (United States)

    Konishi, Kazuhisa; Gibson, Kevin F; Lindell, Kathleen O; Richards, Thomas J; Zhang, Yingze; Dhir, Rajiv; Bisceglia, Michelle; Gilbert, Sebastien; Yousem, Samuel A; Song, Jin Woo; Kim, Dong Soon; Kaminski, Naftali

    2009-07-15

    The molecular mechanisms underlying acute exacerbations of idiopathic pulmonary fibrosis (IPF) are poorly understood. We studied the global gene expression signature of acute exacerbations of IPF. To understand the gene expression patterns of acute exacerbations of IPF. RNA was extracted from 23 stable IPF lungs, 8 IPF lungs with acute exacerbation (IPF-AEx), and 15 control lungs and used for hybridization on Agilent gene expression microarrays. Functional analysis of genes was performed with Spotfire and Genomica. Gene validations for MMP1, MMP7, AGER, DEFA1-3, COL1A2, and CCNA2 were performed by real-time quantitative reverse transcription-polymerase chain reaction. Immunohistochemistry and in situ terminal deoxynucleotidyltransferase dUTP nick end-labeling assays were performed on the same tissues used for the microarray. ELISA for alpha-defensins was performed on plasma from control subjects, patients with stable IPF, and patients with IPF-AEx. Gene expression patterns in IPF-AEx and IPF samples were similar for the genes that distinguish IPF from control lungs. Five hundred and seventy-nine genes were differentially expressed (false discovery rate < 5%) between stable IPF and IPF-AEx. Functional analysis of these genes did not indicate any evidence of an infectious or overwhelming inflammatory etiology. CCNA2 and alpha-defensins were among the most up-regulated genes. CCNA2 and alpha-defensin protein levels were also higher and localized to the epithelium of IPF-AEx, where widespread apoptosis was also detected. alpha-Defensin protein levels were increased in the peripheral blood of patients with IPF-AEx. Our results indicate that IPF-AEx is characterized by enhanced epithelial injury and proliferation, as reflected by increases in CCNA2 and alpha-defensins and apoptosis of epithelium. The concomitant increase in alpha-defensins in the peripheral blood and lungs may suggest their use as biomarkers for this disorder.

  12. Intranasal substituted cathinone "bath salts" psychosis potentially exacerbated by diphenhydramine.

    Science.gov (United States)

    Gunderson, Erik W; Kirkpatrick, Matthew G; Willing, Laura M; Holstege, Christopher P

    2013-01-01

    In this report, we describe a case of intranasal "bath salts"-associated psychosis. Symptoms developed during a 3-week binge and were potentially exacerbated by oral diphenhydramine taken for insomnia. The clinical case conference includes expert discussion from 3 disciplines: emergency medicine toxicology, behavioral pharmacology, and addiction medicine. It is hoped that the discussion will provide insight into the clinical aspects and challenges of addressing acute substituted cathinone toxicity, including acute psychosis, a major adverse effect of bath salts consumption.

  13. Genetic Mechanisms in Aspirin-Exacerbated Respiratory Disease

    OpenAIRE

    Shrestha Palikhe, Nami; Kim, Seung-Hyun; Jin, Hyun Jung; Hwang, Eui-Kyung; Nam, Young Hee; Park, Hae-Sim

    2012-01-01

    Aspirin-exacerbated respiratory disease (AERD) refers to the development of bronchoconstriction in asthmatics following the exposure to aspirin or other nonsteroidal anti-inflammatory drugs. The key pathogenic mechanisms associated with AERD are the overproduction of cysteinyl leukotrienes (CysLTs) and increased CysLTR1 expression in the airway mucosa and decreased lipoxin and PGE2 synthesis. Genetic studies have suggested a role for variability of genes in disease susceptibility and the resp...

  14. Exacerbation of asthma secondary to fentanyl transdermal patch.

    Science.gov (United States)

    Parmar, Malvinder S

    2009-01-01

    Asthma is a common chronic inflammatory disorder of the airways associated with hyperresponsiveness, reversible airflow limitation and respiratory symptoms.1 All patients with asthma are at risk for exacerbations that may range from mild to life threatening. Different triggers cause asthma exacerbation by inducing airway inflammation and/or provoking bronchospasm. Allergen-induced bronchospasm results from IgE-dependent release of mediators including histamine, prostaglandins and leukotrienes.2 Opiates are commonly used to treat chronic pain.3 Although hypersensitivity to opiates or accumulation of opiates can cause respiratory depression, opiates are also used in the management of cough and dyspnoea associated with advanced COPD and heart failure.4(,)5 Here, a report is presented on a patient who developed persistent exacerbation of underlying stable asthma after initiating fentanyl transdermal therapy for chronic low back pain. He underwent extensive investigations and a detailed reassessment of history, especially medication history, led to the possible causative factor; once recognised, removal of the offending agent (fenatnyl) resulted in complete improvement in his symptoms within 72 h.

  15. T cells exacerbate Lyme borreliosis in TLR2-deficient mice

    Directory of Open Access Journals (Sweden)

    Carrie E. Lasky

    2016-11-01

    Full Text Available Infection of humans with the spirochete, Borrelia burgdorferi, causes Lyme borreliosis and can lead to clinical manifestations such as, arthritis, carditis and neurological conditions. Experimental infection of mice recapitulates many of these symptoms and serves as a model system for the investigation of disease pathogenesis and immunity. Innate immunity is known to drive the development of Lyme arthritis and carditis, but the mechanisms driving this response remain unclear. Innate immune cells recognize B. burgdorferi surface lipoproteins primarily via Toll-like receptor (TLR2; however, previous work has demonstrated TLR2-/- mice had exacerbated disease and increased bacterial burden. We demonstrate increased CD4 and CD8 T cell infiltrates in B. burgdorferi-infected joints and hearts of C3H TLR2-/- mice. In vivo depletion of either CD4 or CD8 T cells reduced Borrelia-induced joint swelling and lowered tissue spirochete burden, while depletion of CD8 T cells alone reduced disease severity scores. Exacerbation of Lyme arthritis correlated with increased production of CXCL9 by synoviocytes and this was reduced with CD8 T cell depletion. These results demonstrate T cells can exacerbate Lyme disease pathogenesis and prolong disease resolution possibly through dysregulation of inflammatory responses and inhibition of bacterial clearance.

  16. Factors influencing exacerbation-related self-management in patients with COPD : A qualitative study

    NARCIS (Netherlands)

    Korpershoek, Y. J G; Vervoort, S. C J M; Nijssen, L. I T; Trappenburg, J. C A|info:eu-repo/dai/nl/31144556X; Schuurmans, M. J.

    2016-01-01

    Background: In patients with COPD, self-management skills are important to reduce the impact of exacerbations. However, both detection and adequate response to exacerbations appear to be difficult for some patients. Little is known about the underlying process of exacerbation-related

  17. Low molecular weight heparin and aspirin exacerbate human endometrial endothelial cell responses to antiphospholipid antibodies.

    Science.gov (United States)

    Quao, Zola Chihombori; Tong, Mancy; Bryce, Elena; Guller, Seth; Chamley, Lawrence W; Abrahams, Vikki M

    2018-01-01

    Women with antiphospholipid antibodies (aPL) are at risk for pregnancy complications despite treatment with low molecular weight heparin (LMWH) or aspirin (ASA). aPL recognizing beta2 glycoprotein I can target the uterine endothelium, however, little is known about its response to aPL. This study characterized the effect of aPL on human endometrial endothelial cells (HEECs), and the influence of LMWH and ASA. HEECs were exposed to aPL or control IgG, with or without low-dose LMWH and ASA, alone or in combination. Chemokine and angiogenic factor secretion were measured by ELISA. A tube formation assay was used to measure angiogenesis. aPL increased HEEC secretion of pro-angiogenic VEGF and PlGF; increased anti-angiogenic sFlt-1; inhibited basal secretion of the chemokines MCP-1, G-CSF, and GRO-α; and impaired angiogenesis. LMWH and ASA, alone and in combination, exacerbated the aPL-induced changes in the HEEC angiogenic factor and chemokine profile. There was no reversal of the aPL inhibition of HEEC angiogenesis by either single or combination therapy. By aPL inhibiting HEEC chemokine secretion and promoting sFlt-1 release, the uterine endothelium may contribute to impaired placentation and vascular transformation. LMWH and ASA may further contribute to endothelium dysfunction in women with obstetric APS. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  18. Ablation of serum response factor in dopaminergic neurons exacerbates susceptibility towards MPTP-induced oxidative stress.

    Science.gov (United States)

    Rieker, Claus; Schober, Andreas; Bilbao, Ainhoa; Schütz, Günther; Parkitna, Jan Rodriguez

    2012-03-01

    The high susceptibility of dopaminergic (DA) neurons to cellular stress is regarded as a primary cause of Parkinson's disease. Here we investigate the role of the serum response factor (SRF), an important regulator of anti-apoptotic responses, for the survival of DA neurons in mice. We show that loss of SRF in DA neurons does not affect their viability and does not influence dopamine-dependent behaviors. However, ablation of SRF causes exacerbated sensitivity to 1-methyl 4-phenyl 1,2,3,6-tetrahydropyridine (MPTP), leading to significantly greater loss of DA neurons in the substantia nigra, compared with DA neurons located in the ventral tegmental area. In addition, loss of SRF decreases levels of the anti-apoptotic proteins brain-derived neurotrophic factor (BDNF) and Bcl-2, a plausible underlying cause of increased sensitivity to oxidative stress. These observations support the notion that dysfunction of the SRF-activating mitogen-associated kinase pathway may be part of Parkinson's disease etiology. © 2012 The Authors. European Journal of Neuroscience © 2012 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

  19. Investigation of erectile dysfunction

    Science.gov (United States)

    Patel, D V; Halls, J; Patel, U

    2012-01-01

    Erectile dysfunction (ED) represents a common and debilitating condition with a wide range of organic and non-organic causes. Physical aetiologies can be divided into disorders affecting arterial inflow, the venous occlusion mechanism or the penile structure itself. Various imaging modalities can be utilised to investigate the physical causes of ED, but penile Doppler sonography (PDS) is the most informative technique, indicated in those patients with ED who do not respond to oral pharmacological agents (e.g. phosphodiesterase type 5 inhibitors). This review will examine the anatomical and physiological basis of penile erection, the method for performing PDS and features of specific causes of ED, and will also consider the alternative imaging modalities available. PMID:23118101

  20. Depression and erectile dysfunction.

    Science.gov (United States)

    Seagraves, R T

    2000-05-01

    The association of depression and erectile dysfunction (ED) has been firmly established, but it may be difficult to distinguish between cause and effect--whether ED causes the depression or the depression causes ED--in an individual patient. In most patients who have major depression, successful reversal of the depressive syndrome results in a return of erectile capacity. In other patients--those who suffer from minor depression--restoration of erectile capacity can lead to an improvement in mood. In either case, knowing how to diagnose depression in ED patients is important, not only because depressed patients are more likely to drop out of treatment for ED, but also because untreated depression can be life-threatening.

  1. Progressive posterior cortical dysfunction

    Directory of Open Access Journals (Sweden)

    Fábio Henrique de Gobbi Porto

    Full Text Available Abstract Progressive posterior cortical dysfunction (PPCD is an insidious syndrome characterized by prominent disorders of higher visual processing. It affects both dorsal (occipito-parietal and ventral (occipito-temporal pathways, disturbing visuospatial processing and visual recognition, respectively. We report a case of a 67-year-old woman presenting with progressive impairment of visual functions. Neurologic examination showed agraphia, alexia, hemispatial neglect (left side visual extinction, complete Balint's syndrome and visual agnosia. Magnetic resonance imaging showed circumscribed atrophy involving the bilateral parieto-occipital regions, slightly more predominant to the right . Our aim was to describe a case of this syndrome, to present a video showing the main abnormalities, and to discuss this unusual presentation of dementia. We believe this article can contribute by improving the recognition of PPCD.

  2. Epilepsy and Mitochondrial Dysfunction

    Directory of Open Access Journals (Sweden)

    Russell P. Saneto DO, PhD

    2017-10-01

    Full Text Available Epilepsy is a common manifestation of mitochondrial disease. In a large cohort of children and adolescents with mitochondrial disease (n = 180, over 48% of patients developed seizures. The majority (68% of patients were younger than 3 years and medically intractable (90%. The electroencephalographic pattern of multiregional epileptiform discharges over the left and right hemisphere with background slowing occurred in 62%. The epilepsy syndrome, infantile spasms, was seen in 17%. Polymerase γ mutations were the most common genetic etiology of seizures, representing Alpers-Huttenlocher syndrome (14%. The severity of disease in those patients with epilepsy was significant, as 13% of patients experienced early death. Simply the loss of energy production cannot explain the development of seizures or all patients with mitochondrial dysfunction would have epilepsy. Until the various aspects of mitochondrial physiology that are involved in proper brain development are understood, epilepsy and its treatment will remain unsatisfactory.

  3. Cycling and erectile dysfunction

    Directory of Open Access Journals (Sweden)

    Ina Šibli

    2015-01-01

    Full Text Available Abstract: For many years medical studies have implicated bicycle riding is causing erectile dysfunction (ED in association with higher perineal pressure. This review focuses upon epidemiological studies assesing the impact of cycling on ED, pathogenesis of ED in cyclists  as well as on research considering changes of perineal pressure, hemodynamics, and nerve conduction when cycling. Investigestors were also interested in different saddle sizes, materials and geometry and also in the impact of saddle and riders position on changes to the perineum. Research on female cyclists is very limited but indicates similar genitourinary disorders as in male cyclists. We also review  research on preventative and therapeutic options regarding bicycle riding and ED.

  4. Endothelins & erectile dysfunction.

    Science.gov (United States)

    Ritchie, Robert; Sullivan, Mark

    2011-06-01

    Erectile dysfunction (ED) is common and a significant contributor to poor quality of life and psychosocial morbidity in men. Normal erectile function requires effective co-ordination between a number of complex neural pathways. Penile tumescence occurs in response to rapid arterial inflow to the corpora cavernosa with simultaneous venous outflow restriction due to expansion of the lacunar spaces. This process is under both central and local neuromediation. Endothelins are potent vasoconstrictor peptides that cause strong, slowly developing but sustained contraction of trabecular smooth muscles cells of the corpora cavernosa. Multiple mechanisms of action are proposed, including transmembrane calcium flux, mobilisation of inositol triphosphate sensitive intracellular calcium stores and calcium sensitisation through the Rho-Rho kinase pathway. The exact role of endothelins in the pathogenesis of ED currently remains unclear. Elevated endothelin-1 levels are found in patients with diabetes mellitus and this alone may be sufficient to cause ED. However, this is not borne out in clinical studies. The resultant elevated intracellular calcium may, however, modulate gene expression sufficiently to cause smooth muscle proliferation. Alternatively, alterations in endothelin receptor sensitivity in conditions such as diabetes and hypertension may enhance vasoconstrictor processes. Currently there is contradictory evidence for the role of endothelin receptor antagonists in ED. Animals studies suggest they inhibit corporal vasoconstriction, improve erectile function and protect against diabetes-induced smooth muscle apoptosis. However, the results of clinical studies in ED have been less promising. Uncertainty regarding the exact role of endothelin in penile erection hampers progress in this area. It is possible that the endothelin system may only be relevant to ED in certain conditions where global endothelial dysfunction exists (e.g. diabetes mellitus, systemic sclerosis) and

  5. Electric motor handbook

    CERN Document Server

    Chalmers, B J

    2013-01-01

    Electric Motor Handbook aims to give practical knowledge in a wide range of capacities such as plant design, equipment specification, commissioning, operation and maintenance. The book covers topics such as the modeling of steady-state motor performance; polyphase induction, synchronous, and a.c. commutator motors; ambient conditions, enclosures, cooling and loss dissipation; and electrical supply systems and motor drives. Also covered are topics such as variable-speed drives and motor control; materials and motor components; insulation types, systems, and techniques; and the installation, sit

  6. Damage to the medial motor system in stroke patients with motor neglect

    Directory of Open Access Journals (Sweden)

    Raffaella eMigliaccio

    2014-06-01

    Full Text Available Background and objectives. Motor neglect (MN is a clinically important condition whereby patients with unilateral brain lesions fail to move their contralateral limbs, despite normal muscle strength, reflexes, and sensation. MN has been associated with various lesion sites, including the parietal and frontal cortex, the internal capsule, the lenticulostriate nuclei, and the thalamus. In the present study, we explored the hypothesis that MN depends on a dysfunction of the medial motor system by performing a detailed anatomical analysis in four patients with MN.Methods. Ten patients participated in the study: four with MN, four with left visual neglect but without MN, and three patients with left hemiplegia without MN. We used specific scales for clinical and neuropsychological assessment. We drew the lesion borders directly onto the original brain images of each patient, and plotted the lesions on anatomical atlases for grey and white matter. Results. Lesion locations were highly heterogeneous in our MN patients, and included frontal and parietal sites, basal ganglia and white matter. The only consistently damaged structure across all MN patients was the cingulum bundle, a major pathway of the medial motor system important for motor initiative, and a key connection with limbic structures crucial for motivational aspects of actions. Three MN patients with additional damage to lateral fronto-parietal networks had also signs of contralesional visual neglect. The cingulum bundle was intact in all the control patients with visual neglect or hemiplegia.Conclusions. Cingulum damage may induce MN through unilateral dysfunction of the medial motor system. Additional lateral fronto-parietal dysfunction can result in the association with visual neglect.

  7. Social anxiety and related social impairment are linked to self-efficacy and dysfunctional coping.

    Science.gov (United States)

    Thomasson, Petra; Psouni, Elia

    2010-04-01

    This study investigated relationships between severity of social anxiety as well as related experiences of social impairment and self-efficacy, social control and coping strategies. Social anxiety was regarded as a continuum ranging from mild social discomfort to totally inhibiting anxiety. Participants (N = 113, ages 19-60 years), recruited from a forum for individuals with social phobia and among university students, responded to a self-administered questionnaire. Besides the expected association between a low sense of social control and more severe social anxiety and related social impairment, we found severity of social anxiety and related impairment to be associated with low self-efficacy. This relationship was partly mediated by dysfunctional coping strategies. We suggest that low self-efficacy may increase an individual's tendency to rely on dysfunctional coping strategies for dealing with anxiety experienced in social situations. In turn, using dysfunctional coping strategies appears to exacerbate the experience of impairment from social anxiety.

  8. Bladder Dysfunction and Vesicoureteral Reflux

    Directory of Open Access Journals (Sweden)

    Ulla Sillén

    2008-01-01

    Full Text Available In this overview the influence of functional bladder disturbances and of its treatment on the resolution of vesicoureteral reflux (VUR in children is discussed. Historically both bladder dysfunction entities, the overactive bladder (OAB and the dysfunctional voiding (DV, have been described in conjunction with VUR. Treatment of the dysfunction was also considered to influence spontaneous resolution in a positive way. During the last decades, however, papers have been published which could not support these results. Regarding the OAB, a prospective study with treatment of the bladder overactivity with anticholinergics, did not influence spontaneous resolution rate in children with a dysfunction including also the voiding phase, DV and DES (dysfunctional elimination syndrome, most studies indicate a negative influence on the resolution rate of VUR in children, both before and after the age for bladder control, both with and without treatment. However, a couple of uncontrolled studies indicate that there is a high short-term resolution rate after treatment with flow biofeedback. It should be emphasized that the voiding phase dysfunctions (DV and DES are more severe than the genuine filling phase dysfunction (OAB, with an increased frequency of UTI and renal damage in the former groups. To be able to answer the question if treatment of bladder dysfunction influence the resolution rate of VUR in children, randomized controlled studies must be performed.

  9. Thyroid dysfunction in the elderly

    African Journals Online (AJOL)

    1997-09-09

    Sep 9, 1997 ... hyperthyroidism and 7 of hypothyroidism. Subclinical disease was diagnosed in 40 subjects. The overall prevalence of thyroid dysfunction in this population was. 11.2%. In 22 (3.4%) this had previously been recognised, while in 50 (7.8%) the dysfunction was newly diagnosed by the current survey.

  10. Identification and management of adults with asthma prone to exacerbations: can we do better?

    Directory of Open Access Journals (Sweden)

    Chaudhuri Rekha

    2008-12-01

    Full Text Available Abstract Exacerbations are a major cause of morbidity in asthma and generate high health costs. Identification and management of adults with asthma who are prone to exacerbations is of considerable importance as by this means it should be possible to reduce the number of patients who currently experience inadequately controlled disease. Exacerbations occur most frequently in individuals with severe disease. Other risk factors include a history of a recent exacerbation, co-morbidities such as a raised body mass index and psychological problems as well as current smoking and lower socio-economic status. A low FEV1, particularly if combined with the additional information from questionnaires helps predict exacerbations. Despite the association between these risk factors and exacerbations it remains difficult to accurately predict in an individual patient with asthma whether they will go on to develop an exacerbation in the future. A major aim of international guidelines on the management of asthma is to prevent future risks of exacerbations, but some patients, particularly those with severe disease, respond poorly to current therapies and continue to experience recurrent exacerbations. There is an unmet need for improved management strategies and drugs targeted at preventing asthma exacerbations. Monitoring induced sputum eosinophil cell counts is helpful in preventing exacerbations in some patient with severe asthma. Future developments are likely to include the identification of better biomarkers to predict exacerbations or the cause of exacerbations, augmentation of the immunological response to viruses at the time of the exacerbation, the use of telemonitoring in patients with severe asthma and the development of improved therapies targeted at reducing exacerbations.

  11. Muscle dysfunction in cancer patients

    DEFF Research Database (Denmark)

    Christensen, Jesper Frank; Jones, L W; Andersen, J L

    2014-01-01

    implications of muscle dysfunction in cancer patients. The efficacy of exercise training to prevent and/or mitigate cancer-related muscle dysfunction is also discussed. DESIGN: We identified 194 studies examining muscular outcomes in cancer patients by searching PubMed and EMBASE databases. RESULTS: Muscle...... in oncology practice. Significant progress has been made over the last decade in the field of exercise oncology, indicating that exercise training constitutes a potent modulator of skeletal muscle function in patients with cancer. CONCLUSION: There are clear associations between muscle dysfunction...... dysfunction is evident across all stages of the cancer trajectory. The causes of cancer-related muscle dysfunction are complex, but may involve a wide range of tumor-, therapy- and/or lifestyle-related factors, depending on the clinical setting of the individual patient. The main importance of muscle...

  12. Respiratory dysfunction in Parkinson's disease.

    Science.gov (United States)

    Torsney, K M; Forsyth, D

    2017-03-01

    Respiratory dysfunction has been associated with Parkinson's disease since it was first described in 1817. The respiratory symptoms observed in Parkinson's disease patients vary greatly. Most patients remain asymptomatic, whereas others present with acute shortness of breath and even stridor. In August 2016, an electronic literature search was conducted using PubMed and Google Scholar. Results were screened and studies reporting on respiratory dysfunction associated with Parkinson's disease were included. Respiratory dysfunction is due to a combination of factors including restrictive changes, upper airway obstruction, abnormal ventilatory drive and response to medications. Much debate surrounds the mechanism underlying respiratory dysfunction in Parkinson's disease, its prevalence and the effect of levodopa on respiration. It is clear from this review that larger studies, comparing patients of similar disease duration and severity using the same pulmonary function parameters, are required to provide a better understanding of the pathophysiology underlying respiratory dysfunction in Parkinson's disease.

  13. Overexpression of protein kinase STK25 in mice exacerbates ectopic lipid accumulation, mitochondrial dysfunction and insulin resistance in skeletal muscle

    DEFF Research Database (Denmark)

    Chursa, Urszula; Nuñez-Durán, Esther; Cansby, Emmelie

    2017-01-01

    increases intramyocellular lipid accumulation, impairs skeletal muscle mitochondrial function and sarcomeric ultrastructure, and induces perimysial and endomysial fibrosis, thereby reducing endurance exercise capacity and muscle insulin sensitivity. Furthermore, we observed enhanced lipid accumulation...... and impaired mitochondrial function in rodent myoblasts overexpressing STK25, demonstrating an autonomous action for STK25 within cells. Global phosphoproteomic analysis revealed alterations in the total abundance and phosphorylation status of different target proteins located predominantly to mitochondria...

  14. Overexpression of protein kinase STK25 in mice exacerbates ectopic lipid accumulation, mitochondrial dysfunction and insulin resistance in skeletal muscle

    DEFF Research Database (Denmark)

    Chursa, Urszula; Nuñez-Durán, Esther; Cansby, Emmelie

    2017-01-01

    AIMS/HYPOTHESIS: Understanding the molecular networks controlling ectopic lipid deposition and insulin responsiveness in skeletal muscle is essential for developing new strategies to treat type 2 diabetes. We recently identified serine/threonine protein kinase 25 (STK25) as a critical regulator...... of liver steatosis, hepatic lipid metabolism and whole body glucose and insulin homeostasis. Here, we assessed the role of STK25 in control of ectopic fat storage and insulin responsiveness in skeletal muscle. METHODS: Skeletal muscle morphology was studied by histological examination, exercise performance...... and insulin sensitivity were assessed by treadmill running and euglycaemic-hyperinsulinaemic clamp, respectively, and muscle lipid metabolism was analysed by ex vivo assays in Stk25 transgenic and wild-type mice fed a high-fat diet. Lipid accumulation and mitochondrial function were also studied in rodent...

  15. Predicting an asthma exacerbation in children 2 to 5 years of age

    DEFF Research Database (Denmark)

    Swern, Arlene S; Tozzi, Carol A; Knorr, Barbara

    2008-01-01

    an exacerbation. Caregiver-reported information (daytime cough, breathing difficulties, limitation of activity, nighttime cough or awakening, daytime and nighttime beta2-agonist use) were analyzed using general estimating equations with an exchangeable within-subject log odds ratio regression structure...... to identify predictors of an exacerbation. RESULTS: Average symptom scores and beta2-agonist use increased significantly before exacerbation but at different rates. A combination of daytime cough and wheeze and nighttime beta2-agonist use 1 day before the exacerbation was identified as strongly predictive...... of an exacerbation. These methods predicted 149 (66.8%) of the exacerbations with a very low false-positive rate of 14.2%. CONCLUSIONS: No individual symptom was predictive of an imminent asthma exacerbation, but a combination of increased daytime cough, daytime wheeze, and nighttime beta2-agonist use 1 day before...

  16. Electric Motor Thermal Management

    Energy Technology Data Exchange (ETDEWEB)

    Bennion, Kevin S [National Renewable Energy Laboratory (NREL), Golden, CO (United States)

    2017-09-01

    Thermal management enables more efficient and cost-effective motors. This Annual Merit Review presentation describes the technical accomplishments and progress in electric motor thermal management R&D over the last year. This project supports a broad industry demand for data, analysis methods, and experimental techniques to improve and better understand motor thermal management.

  17. Deficiency of TREK-1 potassium channel exacerbates secondary injury following spinal cord injury in mice.

    Science.gov (United States)

    Fang, Yongkang; Huang, Xiaojiang; Wan, Yue; Tian, Hao; Tian, Yeye; Wang, Wei; Zhu, Suiqiang; Xie, Minjie

    2017-04-01

    Spinal cord injury (SCI) involves complex pathological process which can be complicated by secondary injury. TREK-1 is a member of the two-pore domain potassium (K2P) channel family, which can be modulated by a number of physiological and pathological stimuli. Recent studies suggest that TREK-1 plays an active role in depression, pain and neuroprotection. However, its role in the pathological process after SCI remains unclear. In this study, we tested the expression and function of TREK-1 in spinal cord of mice after traumatic SCI. TREK-1 was widely expressed in mice spinal cord, including astrocytes and neurons. Deficiency of TREK-1 significantly exacerbated focal inflammatory responses as indicated by the increased accumulation of microglia/macrophage as well as pro-inflammatory factor interleukin-1 beta (IL-1β) and tumor necrosis factor alpha expression. Meanwhile, TREK-1 knockout mice showed enhanced reactive astrogliosis, chondroitin sulphate proteoglycans (CSPGs) production and decreased glutamate transporter-1 expression compared to the wide-type mice after SCI. Furthermore, TREK-1 deficiency promoted neurons and oligodendrocytes apoptosis, aggravated demyelination, cavity formation and retarded motor recovery. In summary, our findings provide the first in vivo evidence suggesting that TREK-1 may thereby constitute a promising therapeutic target to treat acute SCI. © 2017 International Society for Neurochemistry.

  18. Predictors of Hospitalized Exacerbations and Mortality in Chronic Obstructive Pulmonary Disease.

    Directory of Open Access Journals (Sweden)

    Miguel Santibáñez

    Full Text Available Exacerbations of chronic obstructive pulmonary disease (COPD carry significant consequences for patients and are responsible for considerable health-care costs-particularly if hospitalization is required. Despite the importance of hospitalized exacerbations, relatively little is known about their determinants. This study aimed to analyze predictors of hospitalized exacerbations and mortality in COPD patients.This was a retrospective population-based cohort study. We selected 900 patients with confirmed COPD aged ≥35 years by simple random sampling among all COPD patients in Cantabria (northern Spain on December 31, 2011. We defined moderate exacerbations as events that led a care provider to prescribe antibiotics or corticosteroids and severe exacerbations as exacerbations requiring hospital admission. We observed exacerbation frequency over the previous year (2011 and following year (2012. We categorized patients according to COPD severity based on forced expiratory volume in 1 second (Global Initiative for Chronic Obstructive Lung Disease [GOLD] grades 1-4. We estimated the odds ratios (ORs by logistic regression, adjusting for age, sex, smoking status, COPD severity, and frequent exacerbator phenotype the previous year.Of the patients, 16.4% had ≥1 severe exacerbations, varying from 9.3% in mild GOLD grade 1 to 44% in very severe COPD patients. A history of at least two prior severe exacerbations was positively associated with new severe exacerbations (adjusted OR, 6.73; 95% confidence interval [CI], 3.53-12.83 and mortality (adjusted OR, 7.63; 95%CI, 3.41-17.05. Older age and several comorbidities, such as heart failure and diabetes, were similarly associated.Hospitalized exacerbations occurred with all grades of airflow limitation. A history of severe exacerbations was associated with new hospitalized exacerbations and mortality.

  19. Disease, dysfunction, and synthetic biology.

    Science.gov (United States)

    Holm, Sune

    2014-08-01

    Theorists analyzing the concept of disease on the basis of the notion of dysfunction consider disease to be dysfunction requiring. More specifically, dysfunction-requiring theories of disease claim that for an individual to be diseased certain biological facts about it must be the case. Disease is not wholly a matter of evaluative attitudes. In this paper, I consider the dysfunction-requiring component of Wakefield's hybrid account of disease in light of the artifactual organisms envisioned by current research in synthetic biology. In particular, I argue that the possibility of artifactual organisms and the case of oncomice and other bred or genetically modified strains of organism constitute a significant objection to Wakefield's etiological account of the dysfunction requirement. I then develop a new alternative understanding of the dysfunction requirement that builds on the organizational theory of function. I conclude that my suggestion is superior to Wakefield's theory because it (a) can accommodate both artifactual and naturally evolved organisms, (b) avoids the possibility of there being a conflict between what an organismic part is supposed to do and the health of the organism, and (c) provides a nonarbitrary and practical way of determining whether dysfunction occurs. © The Author 2014. Published by Oxford University Press, on behalf of the Journal of Medicine and Philosophy Inc. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  20. Incidence and outcomes of patients hospitalized with COPD exacerbation with and without pneumonia

    Directory of Open Access Journals (Sweden)

    Søgaard M

    2016-03-01

    Full Text Available Mette Søgaard,1 Morten Madsen,1 Anders Løkke,2 Ole Hilberg,2 Henrik Toft Sørensen,1 Reimar W Thomsen1 1Department of Clinical Epidemiology, 2Department of Respiratory Medicine, Aarhus University Hospital, Aarhus C, Denmark Background: Pneumonia may be a major contributor to hospitalizations for chronic obstructive pulmonary disease (COPD exacerbation and influence their outcomes.Methods: We examined hospitalization rates, health resource utilization, 30-day mortality, and risk of subsequent hospitalizations for COPD exacerbations with and without pneumonia in Denmark during 2006–2012.Results: We identified 179,759 hospitalizations for COPD exacerbations, including 52,520 first-time hospitalizations (29.2%. Pneumonia was frequent in first-time exacerbations (36.1%, but declined in successive exacerbations to 25.6% by the seventh or greater exacerbation. Pneumonic COPD exacerbations increased 20% from 0.92 per 1,000 population in 2006 to 1.10 per 1,000 population in 2012. Nonpneumonic exacerbations decreased by 6% from 1.74 per 1,000 population to 1.63 per 1,000 population during the same period. A number of markers of health resource utilization were more prevalent in pneumonic exacerbations than in nonpneumonic exacerbations: length of stay (median 7 vs 4 days, intensive care unit admission (7.7% vs 12.5%, and several acute procedures. Thirty-day mortality was 12.1% in first-time pneumonic COPD exacerbations versus 8.3% in first-time nonpneumonic cases (adjusted HR [aHR] 1.20, 95% confidence interval [CI] 1.17–1.24. Pneumonia also predicted increased mortality associated with a second exacerbation (aHR 1.14, 95% CI 1.11–1.18, and up to a seventh or greater exacerbation (aHR 1.10, 95% CI 1.07–1.13. In contrast, the aHR of a subsequent exacerbation was 8%–13% lower for patients with pneumonic exacerbations.Conclusions: Pneumonia is frequent among patients hospitalized for COPD exacerbations and is associated with increased health care

  1. [Thyroid dysfunction during pregnancy].

    Science.gov (United States)

    Díez, Juan J; Iglesias, Pedro; Donnay, Sergio

    2015-10-21

    Recent clinical practice guidelines on thyroid dysfunction and pregnancy have changed health care provided to pregnant women, although their recommendations are under constant revision. Trimester- and area-specific reference ranges for serum thyroid-stimulating hormone are required for proper diagnosis of hypothyroidism and hyperthyroidism. There is no doubt on the need of therapy for overt hypothyroidism, while therapy for subclinical hypothyroidism is controversial. Further research is needed to settle adverse effects of isolated hypothyroxinemia and thyroid autoimmunity. Differentiation between hyperthyroidism due to Graves' disease and the usually self-limited gestational transient thyrotoxicosis is critical. It is also important to recognize risk factors for postpartum thyroiditis. Supplementation with iodine is recommended to maintain adequate iodine nutrition during pregnancy and avoid serious consequences in offspring. Controversy remains about universal screening for thyroid disease during pregnancy or case-finding in high-risk women. Opinions of some scientific societies and recent cost-benefit studies favour universal screening. Randomized controlled studies currently under development should reduce the uncertainties that still remain in this area. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

  2. [Hypothalamic dysfunction in obesity].

    Science.gov (United States)

    van de Sande-Lee, Simone; Velloso, Licio A

    2012-08-01

    Obesity, defined as abnormal or excessive fat accumulation that may impair life quality, is one of the major public health problems worldwide. It results from an imbalance between food intake and energy expenditure. The control of energy balance in animals and humans is performed by the central nervous system (CNS) by means of neuroendocrine connections, in which circulating peripheral hormones, such as leptin and insulin, provide signals to specialized neurons of the hypothalamus reflecting body fat stores, and induce appropriate responses to maintain the stability of these stores. The majority of obesity cases are associated with central resistance to both leptin and insulin actions. In experimental animals, high-fat diets can induce an inflammatory process in the hypothalamus, which impairs leptin and insulin intracellular signaling pathways, and results in hyperphagia, decreased energy expenditure and, ultimately, obesity. Recent evidence obtained from neuroimaging studies and assessment of inflammatory markers in the cerebrospinal fluid of obese subjects suggests that similar alterations may be also present in humans. In this review, we briefly present the mechanisms involved with the loss of homeostatic control of energy balance in animal models of obesity, and the current evidence of hypothalamic dysfunction in obese humans.

  3. Cognitive and autonomic dysfunction in presymptomatic and early Huntington's disease.

    Science.gov (United States)

    Kobal, Jan; Melik, Ziva; Cankar, Ksenija; Strucl, Martin

    2014-06-01

    Huntington's disease is characterized by disorders of movement, cognition and behavior. Individuals with Huntington's disease display aberrant changes in the autonomic nervous system that are detected even before the onset of other symptoms. Subtle cognitive dysfunction may start before other clinical manifestations. The aim of the present study was to investigate the autonomic nervous system response to mental arithmetic and the relationship between the autonomic and cognitive/motor function in presymptomatic and early Huntington's disease. We examined 15 presymptomatic Huntington's disease gene carriers (PHD), 15 early Huntington's disease patients (EHD) and 30 healthy controls. PHD and EHD groups were determined according to Unified Huntington's Disease Rating Scale (UHDRS) motor score. ECG, heart rate, systolic and diastolic blood pressure, and cutaneous laser Doppler flux were measured during rest and during a simple mental arithmetic test. UHDRS cognitive test battery was applied to determine cognitive dysfunction. During mental arithmetic, the heart rate of PHD/EHD increased significantly less than that of controls. Decreased microvascular response to mental arithmetic was found in EHD. Significant correlations for the PHD/EHD group were found between laser Doppler flux response and Symbol Digit Modalities Test score, and between laser Doppler flux response and UHDRS motor score. It seems that central autonomic dysregulation of cardiovascular system in Huntington's disease goes along with the degeneration of other central neuronal systems. This finding is relevant as it could enable simple and noninvasive testing of disease progression.

  4. Motor/generator

    Science.gov (United States)

    Hickam, Christopher Dale [Glasford, IL

    2008-05-13

    A motor/generator is provided for connecting between a transmission input shaft and an output shaft of a prime mover. The motor/generator may include a motor/generator housing, a stator mounted to the motor/generator housing, a rotor mounted at least partially within the motor/generator housing and rotatable about a rotor rotation axis, and a transmission-shaft coupler drivingly coupled to the rotor. The transmission-shaft coupler may include a clamp, which may include a base attached to the rotor and a plurality of adjustable jaws.

  5. Apollo's curse: neurological causes of motor impairments in musicians.

    Science.gov (United States)

    Altenmüller, Eckart; Ioannou, Christos I; Lee, Andre

    2015-01-01

    Performing music at a professional level is probably one of the most complex human accomplishments. Extremely fast and complex, temporo-spatially predefined movement patterns have to be learned, memorized, and retrieved with high reliability in order to meet the expectations of listeners. Performing music requires not only the integration of multimodal sensory and motor information, and its precise monitoring via auditory and kinesthetic feedback, but also emotional communicative skills, which provide a "speaking" rendition of a musical masterpiece. To acquire these specialized auditory-sensory-motor and emotional skills, musicians must undergo extensive training periods over many years, which start in early childhood and continue on through stages of increasing physical and strategic complexities. Performance anxiety, linked to high societal pressures such as the fear of failure and heightened self-demands, frequently accompanies these learning processes. Motor disturbances in musicians are common and include mild forms, such as temporary motor fatigue with short-term reduction of motor skills, painful overuse injuries following prolonged practice, anxiety-related motor failures during performances (choking under pressure), as well as more persistent losses of motor control, here termed "dynamic stereotypes" (DSs). Musician's dystonia (MD), which is characterized by the permanent loss of control of highly skilled movements when playing a musical instrument, is the gravest manifestation of dysfunctional motor programs, frequently linked to a genetic susceptibility to develop such motor disturbances. In this review chapter, we focus on different types of motor failures in musicians. We argue that motor failures in musicians develop along a continuum, starting with subtle transient degradations due to fatigue, overuse, or performance stress, which transform by and by into more permanent, still fluctuating motor degradations, the DSs, until a more irreversible

  6. Automated versus manual oxygen titration in COPD exacerbation: machine or hands, this is the question

    Directory of Open Access Journals (Sweden)

    Karaoren G

    2017-04-01

    Full Text Available Gulsah Karaoren,1 Senay Goksu Tomruk,1 Antonio M Esquinas2 1Department of Anesthesiology and Reanimation, Istanbul Umraniye Research Hospital, Istanbul, Turkey; 2Intensive Care Unit, Hospital Morales Meseguer, Murcia, Spain We have read the article titled “Automated oxygen titration and weaning with FreeO2 in patients with acute exacerbation of COPD: a pilot randomized trial” by Lellouche et al with great interest; however, there are some key aspects to take into account for proper practical implications.1\tFirst, regarding ethical aspects, there seem to be some confusing points about disclosure and researchers. Of the researchers, one is a co-inventor of company that developed the device and two are owners of free oxygen generator. We could not clarify whether any of the authors are medical doctors.\tWith regard to other aspects in the manuscript, the study included COPD patients (aged .40 years with exacerbation and resting saturation ,90% at room environment in whom SpO2 increased to ,92% by 8 L/min oxygen supplementation. It was mentioned that it was impossible to obtain informed consent from patients who stayed in the hospital for .24 h, those with antibiotic-resistant infection, those who underwent intermittent nonintensive ventilation, and those with cognitive dysfunction. Also, the authors did not mention comorbid conditions, body mass index, exercise capacity, duration of COPD, current therapies received, and, most importantly, whether there is comorbid heart failure in the patients.2 The authors performed pulmonary function tests by post-bronchodilator spirometry; however, they did not take COPD grade (mild/moderate/severe into account during standardization.3 In addition, there were no data regarding concurrent therapies given at emergency department and during admission. Did all patients undergo a standard treatment protocol? Moreover, patients of a broad range of age were included in the study. Thus, it is impossible to have no

  7. The effect of virtual reality on visual vertigo symptoms in patients with peripheral vestibular dysfunction: a pilot study

    OpenAIRE

    Pavlou, M.; Kanegaonkar, R. G.; Swapp, D.; Bamiou, D. E.; Slater, Mel; Luxon. L. M.

    2012-01-01

    Individuals with vestibular dysfunction may experience visual vertigo (VV), in which symptoms are provoked or exacerbated by excessive or disorientating visual stimuli (e.g. supermarkets). VV can significantly improve when customized vestibular rehabilitation exercises are combined with exposure to optokinetic stimuli. Virtual reality (VR), which immerses patients in realistic, visually challenging environments, has also been suggested as an adjunct to VR to improve VV symptoms. This pilot st...

  8. Piezoelectric Motors, an Overview

    Directory of Open Access Journals (Sweden)

    Karl Spanner

    2016-02-01

    Full Text Available Piezoelectric motors are used in many industrial and commercial applications. Various piezoelectric motors are available in the market. All of the piezoelectric motors use the inverse piezoelectric effect, where microscopically small oscillatory motions are converted into continuous or stepping rotary or linear motions. Methods of obtaining long moving distance have various drive and functional principles that make these motors categorized into three groups: resonance-drive (piezoelectric ultrasonic motors, inertia-drive, and piezo-walk-drive. In this review, a comprehensive summary of piezoelectric motors, with their classification from initial idea to recent progress, is presented. This review also includes some of the industrial and commercial applications of piezoelectric motors that are presently available in the market as actuators.

  9. Motor degradation prediction methods

    Energy Technology Data Exchange (ETDEWEB)

    Arnold, J.R.; Kelly, J.F.; Delzingaro, M.J.

    1996-12-01

    Motor Operated Valve (MOV) squirrel cage AC motor rotors are susceptible to degradation under certain conditions. Premature failure can result due to high humidity/temperature environments, high running load conditions, extended periods at locked rotor conditions (i.e. > 15 seconds) or exceeding the motor`s duty cycle by frequent starts or multiple valve stroking. Exposure to high heat and moisture due to packing leaks, pressure seal ring leakage or other causes can significantly accelerate the degradation. ComEd and Liberty Technologies have worked together to provide and validate a non-intrusive method using motor power diagnostics to evaluate MOV rotor condition and predict failure. These techniques have provided a quick, low radiation dose method to evaluate inaccessible motors, identify degradation and allow scheduled replacement of motors prior to catastrophic failures.

  10. Neuroplasticity & Motor Learning

    DEFF Research Database (Denmark)

    Jensen, Jesper Lundbye

    Practice of a new motor task is usually associated with an improvement in performance. Indeed, if we stop practicing and return the next day to the same task, we find that our performance has been maintained and may even be better than it was at the start of the first day. This improvement...... is a measure of our ability to form and store a motor memory of the task. However, the initial memory of the task is labile and may be subject to interference. During and following motor learning plastic changes occur within the central nervous system. On one hand these changes are driven by motor practice......, on the other hand the changes underlie the formation of motor memory and the retention of improved motor performance. During motor learning changes may occur at many different levels within the central nervous system dependent on the type of task and training. Here, we demonstrate different studies from our...

  11. Adenosine dysfunction in epilepsy

    Science.gov (United States)

    Boison, Detlev

    2011-01-01

    Extracellular levels of the brain’s endogenous anticonvulsant and neuroprotectant adenosine largely depend on an astrocyte-based adenosine cycle, comprised of ATP release, rapid degradation of ATP into adenosine, and metabolic reuptake of adenosine through equilibrative nucleoside transporters and phosphorylation by adenosine kinase (ADK). Changes in ADK expression and activity therefore rapidly translate into changes of extracellular adenosine, which exerts its potent anticonvulsive and neuroprotective effects by activation of pre- and postsynaptic adenosine A1 receptors. Increases in ADK increase neuronal excitability, whereas decreases in ADK render the brain resistant to seizures and injury. Importantly, ADK was found to be overexpressed and associated with astrogliosis and spontaneous seizures in rodent models of epilepsy, as well as in human specimen resected from patients with hippocampal sclerosis and temporal lobe epilepsy. Several lines of evidence indicate that overexpression of astroglial ADK and adenosine deficiency are pathological hallmarks of the epileptic brain. Consequently, adenosine augmentation therapies constitute a powerful approach for seizure prevention, which is effective in models of epilepsy that are resistant to conventional antiepileptic drugs. The adenosine kinase hypothesis of epileptogenesis suggests that adenosine dysfunction in epilepsy undergoes a biphasic response: An acute surge of adenosine that can be triggered by any type of injury might contribute to the development of astrogliosis via adenosine receptor –dependent and –independent mechanisms. Astrogliosis in turn is associated with overexpression of ADK, which was shown to be sufficient to trigger spontaneous recurrent electrographic seizures. Thus, ADK emerges as a promising target for the prediction and prevention of epilepsy. PMID:22700220

  12. 5-Aminosalicylate intolerance causing exacerbation in pediatric ulcerative colitis.

    Science.gov (United States)

    Shimizu, Hirotaka; Arai, Katsuhiro; Tang, Julian; Hosoi, Kenji; Funayama, Rie

    2017-05-01

    5-Aminosalicylate (5-ASA) is widely used as the first-line drug for ulcerative colitis (UC). 5-ASA is mostly a safe and effective drug, but it can bring about exacerbation due to 5-ASA intolerance. 5-ASA intolerance can be confusing and it can mislead physicians into considering unnecessary treatment escalation, including corticosteroid (CS), biologics, or even surgery. In spite of the clinical importance of 5-ASA intolerance, there have been few studies on its incidence, clinical features, and diagnosis. In order to evaluate the incidence, characteristic symptoms, disease course, and laboratory data of children with 5-ASA intolerance, we retrospectively reviewed the medical records of 80 children with UC. Eleven of 80 children (13.8%) with UC were diagnosed with 5-ASA intolerance. The median time between the initiation of 5-ASA and the onset of 5-ASA intolerance was 10 days (range, 4-20 days) in patients not receiving CS. Drug-induced lymphocyte stimulation test (DLST) was performed in 10 patients, and was positive in eight. C-reactive protein (CRP) increased significantly when exacerbation of colitis symptoms occurred. The incidence of 5-ASA intolerance was relatively high. Besides the challenge test, elevation of CRP and positive DLST appeared to support the diagnosis of 5-ASA intolerance. © 2017 Japan Pediatric Society.

  13. Tic Exacerbation in Adults with Tourette Syndrome: A Case Series

    Directory of Open Access Journals (Sweden)

    Sara M. Schaefer

    2017-03-01

    Full Text Available Background: Tourette syndrome (TS has been described as peaking in adolescence with subsequent regression. We report patients who were diagnosed with TS during childhood who experienced a latent period (significant reduction in or absence of tics followed by tic re-emergence in adulthood.Methods: We performed a retrospective chart review of outpatients over age 21 seen at the Yale neurology clinic between January 2012 and July 2016 who were diagnosed with childhood-onset tics, and who experienced a latent period of greater than 1 year followed by an exacerbation.Results: Sixteen patients were identified. The mean latent period was 16 years. Ten patients (62.5% identified an exacerbation trigger, most commonly changes in substance use (five patients. Seven patients (43.8% reported worsening of tics since childhood. Six patients (37.5% had received pharmacological intervention for tics as children, and 15 patients (93.8% as adults. Six of 15 patients (40.0% had an effective response from those pharmacological intervention(s.Discussion: Our study demonstrates that the decline in symptoms as patients age may represent temporary improvement. The latent period lasted years in our patients, different from the more rapid waxing and waning in children. A change in substance use was an important trigger. Requests for pharmacological intervention were not necessarily correlated with worsening tic severity. 

  14. Sputum Bacterial and Fungal Dynamics during Exacerbations of Severe COPD.

    Directory of Open Access Journals (Sweden)

    Jin Su

    Full Text Available The changes in the microbial community structure during acute exacerbations of severe chronic obstructive pulmonary disease (COPD in hospitalized patients remain largely uncharacterized. Therefore, further studies focused on the temporal dynamics and structure of sputum microbial communities during acute exacerbation of COPD (AECOPD would still be necessary. In our study, the use of molecular microbiological techniques provided insight into both fungal and bacterial diversities in AECOPD patients during hospitalization. In particular, we examined the structure and varieties of lung microbial community in 6 patients with severe AECOPD by amplifying 16S rRNA V4 hyper-variable and internal transcribed spacer (ITS DNA regions using barcoded primers and the Illumina sequencing platform. Sequence analysis showed 261 bacterial genera representing 20 distinct phyla, with an average number of genera per patient of >157, indicating high diversity. Acinetobacter, Prevotella, Neisseria, Rothia, Lactobacillus, Leptotrichia, Streptococcus, Veillonella, and Actinomyces were the most commonly identified genera, and the average total sequencing number per sputum sample was >10000 18S ITS sequences. The fungal population was typically dominated by Candia, Phialosimplex, Aspergillus, Penicillium, Cladosporium and Eutypella. Our findings highlight that COPD patients have personalized structures and varieties in sputum microbial community during hospitalization periods.

  15. Chronic Hepatitis B with Spontaneous Severe Acute Exacerbation

    Directory of Open Access Journals (Sweden)

    Wei-Lun Tsai

    2015-11-01

    Full Text Available Chronic hepatitis B virus (HBV infection is a major global health problem with an estimated 400 million HBV carriers worldwide. In the natural history of chronic hepatitis B (CHB, spontaneous acute exacerbation (AE is not uncommon, with a cumulative incidence of 10%–30% every year. While exacerbations can be mild, some patients may develop hepatic decompensation and even die. The underlying pathogenesis is possibly related to the activation of cytotoxic T lymphocyte-mediated immune response against HBV. An upsurge of serum HBV DNA usually precedes the rise of alanine aminotransferase (ALT and bilirubin. Whether antiviral treatment can benefit CHB with severe AE remains controversial, but early nucleos(tide analogues treatment seemed to be associated with an improved outcome. There has been no randomized study that compared the effects of different nucleos(tide analogues (NA in the setting of CHB with severe AE. However, potent NAs with good resistance profiles are recommended. In this review, we summarized current knowledge regarding the natural history, pathogenetic mechanisms, and therapeutic options of CHB with severe AE.

  16. Acute exacerbation in chronic hepatitis B virus infection

    Directory of Open Access Journals (Sweden)

    Marcio Vieira Santos

    1996-06-01

    Full Text Available A case of an acute exacerbation of liver injury in a chronic HBV infected young male is reported. The correlation between the severe symptomatic hepatitis is done with the histopathologic findings of extense areas of bridging necrosis on the Iwer biopsy. The serological pattern for markers of HBV (HBsAg +, anti HBs g -, HBeAg -, anti HBe +, anti HBcIgG + and IgM - confirm a chronic infection, ana the authors propose that the episode of severe hepatitis relates to the recent spontaneous seroconvertion of HBe Ag to anti HBe. Other causes of hepatitis were excluded, and the control liver biopsy (6 months later showed normalization of hepatic architecture and absence of markers of viral replication in tissue and serum. A review of literature is done in an attempt to elucidate the diagnostic possibilities in this case, with emphasis on new immunoassays useful in differentiating between acute hepatitis B and acute exacerbation of a chronic hepatitis by the same virus.

  17. Cognitive dysfunction after cardiovascular surgery

    DEFF Research Database (Denmark)

    Funder, K S; Steinmetz, J; Rasmussen, L S

    2009-01-01

    This review describes the incidence, risk factors, and long-term consequences of cognitive dysfunction after cardiovascular surgery. Postoperative cognitive dysfunction (POCD) is increasingly being recognized as an important complication, especially in the elderly. A highly sensitive neuropsychol......This review describes the incidence, risk factors, and long-term consequences of cognitive dysfunction after cardiovascular surgery. Postoperative cognitive dysfunction (POCD) is increasingly being recognized as an important complication, especially in the elderly. A highly sensitive...... neuropsychological test battery must be used to detect POCD and a well-matched control group is very useful for the analysis and interpretation of the test RESULTS: Cardiovascular surgery is associated with a high incidence of POCD. Cardiopulmonary bypass was thought to explain this difference, but randomized...

  18. Causes of sexual dysfunction (image)

    Science.gov (United States)

    Female sexual dysfunction describes women who are indifferent or hostile to sexual intercourse, who have no response to sexual advances or stimulation, or who are unable to have an orgasm during sexual intercourse.

  19. Do we know the minimal clinically important difference (MCID) for COPD exacerbations?

    Science.gov (United States)

    Chapman, Kenneth R; Bergeron, Celine; Bhutani, Mohit; Bourbeau, Jean; Grossman, Ronald F; Hernandez, Paul; McIvor, R Andrew; Mayers, Irvin

    2013-04-01

    Frequent exacerbations of COPD are associated with accelerated loss of lung function, declining health status, increased mortality, and increased health care costs. Thus, a key objective in the management of COPD is preventing exacerbations or at least reducing their number and severity. When new interventions are examined, their value is sometimes assessed in reference to the minimal clinically important difference (MCID), a theoretical construct that may be defined and estimated numerically in several different ways. There have been limited attempts to calculate the MCID for COPD exacerbations but a figure of 20% reduction in exacerbation frequency is occasionally cited as the "established" MCID from a single manuscript reviewing six clinical trials. Our review suggests that defining and calculating the MCID for COPD exacerbations is problematic, not only because the methodology around developing endpoints for MCIDs is inconsistent, but because the impact of exacerbation reduction is likely to be influenced dramatically by the definitions of exacerbation severity used and the population's baseline status. Reference to current literature shows that at least one other estimate for exacerbation MCID as low as 4%. MCID is sometimes estimated by expert consensus; a review of articles used to shape COPD guidelines shows frequent reference to articles in which interventions yielded exacerbation differences as low as 11%. We find no evidence of an established MCID but suggest that interventions reducing exacerbations by as little as 11% appear to be regarded widely as clinically important.

  20. Temporomandibular joint dysfunction in Parkinson's Disease: an integrative literature review

    Directory of Open Access Journals (Sweden)

    Taysa Vannoska de Almeida Silva

    Full Text Available ABSTRACT Temporomandibular joint dysfunction is a set of disorders involving the masticatory muscles, temporomandibular joint and associated structures. It is known that the progression of motor symptoms in Parkinson's disease is an indication that these people are more prone to the development of this dysfunction. Thus, this study aims to investigate the signs and symptoms of temporomandibular dysfunction in people with Parkinson's disease. The search was performed in the databases: MEDLINE/ PubMed, LILACs, CINAHL, SCOPUS, Web of Science and PEDro, without timing or language restriction. Specific descriptors were used for each database and keywords, evaluated by the instruments: Critical Appraisal Skill Program and Agency for Health care and Research and Quality. A total of 4,209 articles were found but only 5 were included. After critical analysis of the methodology of the articles, one did not reach the minimum score required by the evaluation instruments, thus, it was excluded. The selected articles addressed, as signs and symptoms of temporomandibular joint dysfunction, the following: myofascial pain, bruxism, limitation of mouth opening, dislocation of the articular disc and asymmetry in the distribution of occlusal contacts. Further studies are needed in order to determine the relationship between cause and effect of the analyzed variables, so as to contribute to more specific and effective therapeutic interventions.

  1. Antibody deficiency in patients with frequent exacerbations of Chronic Obstructive Pulmonary Disease (COPD).

    Science.gov (United States)

    McCullagh, Brian N; Comellas, Alejandro P; Ballas, Zuhair K; Newell, John D; Zimmerman, M Bridget; Azar, Antoine E

    2017-01-01

    Chronic Obstructive Pulmonary Disease is the third leading cause of death in the US, and is associated with periodic exacerbations, which account for the largest proportion of health care utilization, and lead to significant morbidity, mortality, and worsening lung function. A subset of patients with COPD have frequent exacerbations, occurring 2 or more times per year. Despite many interventions to reduce COPD exacerbations, there is a significant lack of knowledge in regards to their mechanisms and predisposing factors. We describe here an important observation that defines antibody deficiency as a potential risk factor for frequent COPD exacerbations. We report a case series of patients who have frequent COPD exacerbations, and who were found to have an underlying primary antibody deficiency syndrome. We also report on the outcome of COPD exacerbations following treatment in a subset with of these patients with antibody deficiency. We identified patients with COPD who had 2 or more moderate to severe exacerbations per year; immune evaluation including serum immunoglobulin levels and pneumococcal IgG titers was performed. Patients diagnosed with an antibody deficiency syndrome were treated with either immunoglobulin replacement therapy or prophylactic antibiotics, and their COPD exacerbations were monitored over time. A total of 42 patients were identified who had 2 or more moderate to severe COPD exacerbations per year. Twenty-nine patients had an underlying antibody deficiency syndrome: common variable immunodeficiency (8), specific antibody deficiency (20), and selective IgA deficiency (1). Twenty-two patients had a follow-up for at least 1 year after treatment of their antibody deficiency, which resulted in a significant reduction of COPD exacerbations, courses of oral corticosteroid use and cumulative annual dose of oral corticosteroid use, rescue antibiotic use, and hospitalizations for COPD exacerbations. This case series identifies antibody deficiency as a

  2. Factors influencing exacerbation-related self-management in patients with COPD: a qualitative study.

    Science.gov (United States)

    Korpershoek, Yjg; Vervoort, Scjm; Nijssen, Lit; Trappenburg, Jca; Schuurmans, M J

    2016-01-01

    In patients with COPD, self-management skills are important to reduce the impact of exacerbations. However, both detection and adequate response to exacerbations appear to be difficult for some patients. Little is known about the underlying process of exacerbation-related self-management. Therefore, the objective of this study was to identify and explain the underlying process of exacerbation-related self-management behavior. A qualitative study using semi-structured in-depth interviews was performed according to the grounded theory approach, following a cyclic process in which data collection and data analysis alternated. Fifteen patients (male n=8; age range 59-88 years) with mild to very severe COPD were recruited from primary and secondary care settings in the Netherlands, in 2015. Several patterns in exacerbation-related self-management behavior were identified, and a conceptual model describing factors influencing exacerbation-related self-management was developed. Acceptance, knowledge, experiences with exacerbations, perceived severity of symptoms and social support were important factors influencing exacerbation-related self-management. Specific factors influencing recognition of exacerbations were heterogeneity of exacerbations and habituation to symptoms. Feelings of fear, perceived influence on exacerbation course, patient beliefs, ambivalence toward treatment, trust in health care providers and self-empowerment were identified as specific factors influencing self-management actions. This study provided insight into factors influencing exacerbation-related self-management behavior in COPD patients. The conceptual model can be used as a framework for health care professionals providing self-management support. In the development of future self-management interventions, factors influencing the process of exacerbation-related self-management should be taken into account.

  3. Antibody deficiency in patients with frequent exacerbations of Chronic Obstructive Pulmonary Disease (COPD)

    Science.gov (United States)

    McCullagh, Brian N.; Comellas, Alejandro P.; Ballas, Zuhair K.; Newell, John D.; Zimmerman, M. Bridget

    2017-01-01

    Chronic Obstructive Pulmonary Disease is the third leading cause of death in the US, and is associated with periodic exacerbations, which account for the largest proportion of health care utilization, and lead to significant morbidity, mortality, and worsening lung function. A subset of patients with COPD have frequent exacerbations, occurring 2 or more times per year. Despite many interventions to reduce COPD exacerbations, there is a significant lack of knowledge in regards to their mechanisms and predisposing factors. We describe here an important observation that defines antibody deficiency as a potential risk factor for frequent COPD exacerbations. We report a case series of patients who have frequent COPD exacerbations, and who were found to have an underlying primary antibody deficiency syndrome. We also report on the outcome of COPD exacerbations following treatment in a subset with of these patients with antibody deficiency. We identified patients with COPD who had 2 or more moderate to severe exacerbations per year; immune evaluation including serum immunoglobulin levels and pneumococcal IgG titers was performed. Patients diagnosed with an antibody deficiency syndrome were treated with either immunoglobulin replacement therapy or prophylactic antibiotics, and their COPD exacerbations were monitored over time. A total of 42 patients were identified who had 2 or more moderate to severe COPD exacerbations per year. Twenty-nine patients had an underlying antibody deficiency syndrome: common variable immunodeficiency (8), specific antibody deficiency (20), and selective IgA deficiency (1). Twenty-two patients had a follow-up for at least 1 year after treatment of their antibody deficiency, which resulted in a significant reduction of COPD exacerbations, courses of oral corticosteroid use and cumulative annual dose of oral corticosteroid use, rescue antibiotic use, and hospitalizations for COPD exacerbations. This case series identifies antibody deficiency as a

  4. Disruption of Axonal Transport in Motor Neuron Diseases

    Directory of Open Access Journals (Sweden)

    Gen Sobue

    2012-01-01

    Full Text Available Motor neurons typically have very long axons, and fine-tuning axonal transport is crucial for their survival. The obstruction of axonal transport is gaining attention as a cause of neuronal dysfunction in a variety of neurodegenerative motor neuron diseases. Depletions in dynein and dynactin-1, motor molecules regulating axonal trafficking, disrupt axonal transport in flies, and mutations in their genes cause motor neuron degeneration in humans and rodents. Axonal transport defects are among the early molecular events leading to neurodegeneration in mouse models of amyotrophic lateral sclerosis (ALS. Gene expression profiles indicate that dynactin-1 mRNA is downregulated in degenerating spinal motor neurons of autopsied patients with sporadic ALS. Dynactin-1 mRNA is also reduced in the affected neurons of a mouse model of spinal and bulbar muscular atrophy, a motor neuron disease caused by triplet CAG repeat expansion in the gene encoding the androgen receptor. Pathogenic androgen receptor proteins also inhibit kinesin-1 microtubule-binding activity and disrupt anterograde axonal transport by activating c-Jun N-terminal kinase. Disruption of axonal transport also underlies the pathogenesis of spinal muscular atrophy and hereditary spastic paraplegias. These observations suggest that the impairment of axonal transport is a key event in the pathological processes of motor neuron degeneration and an important target of therapy development for motor neuron diseases.

  5. Hemispheric Lateralization of Motor Thresholds in Relation to Stuttering

    Science.gov (United States)

    Alm, Per A.; Karlsson, Ragnhild; Sundberg, Madeleine; Axelson, Hans W.

    2013-01-01

    Stuttering is a complex speech disorder. Previous studies indicate a tendency towards elevated motor threshold for the left hemisphere, as measured using transcranial magnetic stimulation (TMS). This may reflect a monohemispheric motor system impairment. The purpose of the study was to investigate the relative side-to-side difference (asymmetry) and the absolute levels of motor threshold for the hand area, using TMS in adults who stutter (n = 15) and in controls (n = 15). In accordance with the hypothesis, the groups differed significantly regarding the relative side-to-side difference of finger motor threshold (p = 0.0026), with the stuttering group showing higher motor threshold of the left hemisphere in relation to the right. Also the absolute level of the finger motor threshold for the left hemisphere differed between the groups (p = 0.049). The obtained results, together with previous investigations, provide support for the hypothesis that stuttering tends to be related to left hemisphere motor impairment, and possibly to a dysfunctional state of bilateral speech motor control. PMID:24146930

  6. Orgasmic Dysfunction after Radical Prostatectomy

    OpenAIRE

    Capogrosso, Paolo; Ventimiglia, Eugenio; Cazzaniga, Walter; Montorsi, Francesco; Salonia, Andrea

    2017-01-01

    In addition to urinary incontinence and erectile dysfunction, several other impairments of sexual function potentially occurring after radical prostatectomy (RP) have been described; as a whole, these less frequently assessed disorders are referred to as neglected side effects. In particular, orgasmic dysfunctions (ODs) have been reported in a non-negligible number of cases, with detrimental impacts on patients' overall sexual life. This review aimed to comprehensively discuss the prevalence ...

  7. Thyroid dysfunction and pregnancy outcomes

    Directory of Open Access Journals (Sweden)

    Sima Nazarpour

    2015-07-01

    Full Text Available Background: Pregnancy has a huge impact on the thyroid function in both healthy women and those that have thyroid dysfunction. The prevalence of thyroid dysfunction in pregnant women is relatively high. Objective: The objective of this review was to increase awareness and to provide a review on adverse effect of thyroid dysfunction including hyperthyroidism, hypothyroidism and thyroid autoimmune positivity on pregnancy outcomes. Materials and Methods: In this review, Medline, Embase and the Cochrane Library were searched with appropriate keywords for relevant English manuscript. We used a variety of studies, including randomized clinical trials, cohort (prospective and retrospective, case-control and case reports. Those studies on thyroid disorders among non-pregnant women and articles without adequate quality were excluded. Results: Overt hyperthyroidism and hypothyroidism has several adverse effects on pregnancy outcomes. Overt hyperthyroidism was associated with miscarriage, stillbirth, preterm delivery, intrauterine growth retardation, low birth weight, preeclampsia and fetal thyroid dysfunction. Overt hypothyroidism was associated with abortion, anemia, pregnancy-induced hypertension, preeclampsia, placental abruption, postpartum hemorrhage, premature birth, low birth weight, intrauterine fetal death, increased neonatal respiratory distress and infant neuro developmental dysfunction. However the adverse effect of subclinical hypothyroidism, and thyroid antibody positivity on pregnancy outcomes was not clear. While some studies demonstrated higher chance of placental abruption, preterm birth, miscarriage, gestational hypertension, fetal distress, severe preeclampsia and neonatal distress and diabetes in pregnant women with subclinical hypothyroidism or thyroid autoimmunity; the other ones have not reported these adverse effects. Conclusion: While the impacts of overt thyroid dysfunction on feto-maternal morbidities have been clearly

  8. Thyroid dysfunction and pregnancy outcomes

    Science.gov (United States)

    Nazarpour, Sima; Ramezani Tehrani, Fahimeh; Simbar, Masoumeh; Azizi, Fereidoun

    2015-01-01

    Background: Pregnancy has a huge impact on the thyroid function in both healthy women and those that have thyroid dysfunction. The prevalence of thyroid dysfunction in pregnant women is relatively high. Objective: The objective of this review was to increase awareness and to provide a review on adverse effect of thyroid dysfunction including hyperthyroidism, hypothyroidism and thyroid autoimmune positivity on pregnancy outcomes. Materials and Methods: In this review, Medline, Embase and the Cochrane Library were searched with appropriate keywords for relevant English manuscript. We used a variety of studies, including randomized clinical trials, cohort (prospective and retrospective), case-control and case reports. Those studies on thyroid disorders among non-pregnant women and articles without adequate quality were excluded. Results: Overt hyperthyroidism and hypothyroidism has several adverse effects on pregnancy outcomes. Overt hyperthyroidism was associated with miscarriage, stillbirth, preterm delivery, intrauterine growth retardation, low birth weight, preeclampsia and fetal thyroid dysfunction. Overt hypothyroidism was associated with abortion, anemia, pregnancy-induced hypertension, preeclampsia, placental abruption, postpartum hemorrhage, premature birth, low birth weight, intrauterine fetal death, increased neonatal respiratory distress and infant neuro developmental dysfunction. However the adverse effect of subclinical hypothyroidism, and thyroid antibody positivity on pregnancy outcomes was not clear. While some studies demonstrated higher chance of placental abruption, preterm birth, miscarriage, gestational hypertension, fetal distress, severe preeclampsia and neonatal distress and diabetes in pregnant women with subclinical hypothyroidism or thyroid autoimmunity; the other ones have not reported these adverse effects. Conclusion: While the impacts of overt thyroid dysfunction on feto-maternal morbidities have been clearly identified and its long

  9. Prostatic Disease and Sexual Dysfunction

    OpenAIRE

    Kim, Sae Woong

    2011-01-01

    Prostatitis and benign prostatic hyperplasia (BPH) are common prostatic diseases. Furthermore, the incidence of prostate cancer has recently shown a rapid increase, even in Korea. Pain caused by prostatitis may induce sexual dysfunction, including erectile dysfunction and ejaculatory disturbance. And BPH itself, or treatments for BPH, may affect sexual function. In addition, with increased detection of localized prostate cancer, surgical treatments and radiation therapy have also increased, a...

  10. Objective acoustic quantification of phonatory dysfunction in Huntington's disease.

    Directory of Open Access Journals (Sweden)

    Jan Rusz

    Full Text Available PURPOSE: Although speech motor changes are reported as a common sign of Huntington's disease (HD, the most prominent signs of voice dysfunction remain unknown. The aim of the current study was to explore specific changes in phonatory function in subjects with HD. METHOD: 34 subjects with HD and 34 age- and sex-matched healthy controls were examined. Participants performed sustained vowel phonation for subsequent analyses of airflow insufficiency, aperiodicity, irregular vibrations of vocal folds, signal perturbations, increased noise, and articulation deficiency. In total, 272 phonations were collected and 12 voice parameters were extracted. Subsequently, a predictive model was built to find the most salient patterns of voice disorders in HD. The results were also correlated with disease severity according to the Unified HD Rating Scale (UHDRS motor score. RESULTS: Subjects with HD showed deterioration in all investigated phonatory functions. Irregular pitch fluctuations, sudden phonation interruption, increased noise, and misplacement of articulators were found to be most significant patterns of phonatory dysfunction in HD (p<0.001. The combination of these four dysphonia aspects contributed to the best classification performance of 94.1% (sensitivity: 95.1%; specificity: 93.2% in the separation of HD patients from healthy participants. Our results further indicated stronger associations between sudden phonation interruption and voluntary components of the UHDRS (r = -0.48, p<0.01 and between misplacement of articulators and involuntary components of the UHDRS (r = 0.52, p<0.01. CONCLUSIONS: Our configuration of phonatory features can detect subtle voice abnormalities in subjects with HD. As impairment of phonatory function in HD was found to parallel increasing motor involvement, a qualitative description of voice dysfunction may be helpful to gain better insight into the pathophysiology of the vocal mechanism.

  11. Peripheral motor axons of SOD1(G127X) mutant mice are susceptible to activity-dependent degeneration

    DEFF Research Database (Denmark)

    Alvarez Herrero, Susana; Calin, A; Graffmo, K S

    2013-01-01

    Motor neuron disorders may be associated with mitochondrial dysfunction, and repetitive electrical impulse conduction during energy restriction has been found to cause neuronal degeneration. The aim of this study was to investigate the vulnerability of motor axons of a presymptomatic late-onset, ...

  12. DIAGNOSIS AND THERAPY OF MOTOR DISTURBANCES IN CHILDREN WITH AUTISM

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    Neli VASILEVA

    2012-09-01

    Full Text Available The paper reveals uncommonly examined aspects concerning the specifics of the motor de­velopment in the children with autistic spectrum disorders and the problems regarding their diagnostics and the­ra­py. An analytical theory of the autistic disorders is des­cribed, connecting autism with disorders in the ba­sic levels of affective behavioral regulation. The re­port in­cludes a classification of the groups of autis­tic children, each of which demonstrates spe­ci­fic motor dysfunctions. Furthermore, the paper ana­ly­zes and recommends methodo­lo­gi­cal approaches to motor therapy which will help improve the de­ve­lop­ment of different motor skills.

  13. Visual pathway neurodegeneration winged by mitochondrial dysfunction.

    Science.gov (United States)

    Petzold, Axel; Nijland, Philip G; Balk, Lisanne J; Amorini, Angela Maria; Lazzarino, Giacomo; Wattjes, Mike P; Gasperini, Claudio; van der Valk, Paul; Tavazzi, Barbara; Lazzarino, Giuseppe; van Horssen, Jack

    2015-02-01

    To test for structural and functional contribution of mitochondrial dysfunction to neurodegeneration in multiple sclerosis (MS). A visual pathway model void of MS lesions was chosen in order to exclude neurodegeneration secondary to lesion related axonotmesis. A single-centre cohort study (230 MS patients, 63 controls). Spectral domain optical coherence tomography of the retina, 3T magnetic resonance imaging of the brain, spectrophotometric assessment of serum lactate levels. Postmortem immunohistochemistry. The visual pathway was void of MS lesions in 31 patients and 31 age-matched controls. Serum lactate was higher in MS compared to controls (P = 0.029). High serum lactate was structurally related to atrophy of the retinal nerve fiber layer at the optic disc (P = 0.041), macula (P = 0.025), and the macular ganglion cell complex (P = 0.041). High serum lactate was functionally related to poor color vision (P < 0.01), Expanded Disability Status Scale score (R = 0.37, P = 0.041), Guy's Neurological disability score (R = 0.38, P = 0.037), MS walking scale (R = 0.50, P = 0.009), upper limb motor function (R = 0.53, P = 0.002). Immunohistochemistry demonstrated increased astrocytic expression of a key lactate generating enzyme in MS lesions as well as profound vascular expression of monocarboxylate transporter-1, which is involved in lactate transport. This study provides structural, functional, and translational evidence for visual pathway neurodegeneration in MS related to mitochondrial dysfunction.

  14. Frequency of exacerbations in patients with chronic obstructive pulmonary disease: an analysis of the SPIROMICS cohort.

    Science.gov (United States)

    Han, MeiLan K; Quibrera, Pedro M; Carretta, Elizabeth E; Barr, R Graham; Bleecker, Eugene R; Bowler, Russell P; Cooper, Christopher B; Comellas, Alejandro; Couper, David J; Curtis, Jeffrey L; Criner, Gerard; Dransfield, Mark T; Hansel, Nadia N; Hoffman, Eric A; Kanner, Richard E; Krishnan, Jerry A; Martinez, Carlos H; Pirozzi, Cheryl B; O'Neal, Wanda K; Rennard, Stephen; Tashkin, Donald P; Wedzicha, Jadwiga A; Woodruff, Prescott; Paine, Robert; Martinez, Fernando J

    2017-08-01

    Present treatment strategies to stratify exacerbation risk in patients with chronic obstructive pulmonary disease (COPD) rely on a history of two or more events in the previous year. We aimed to understand year to year variability in exacerbations and factors associated with consistent exacerbations over time. In this longitudinal, prospective analysis of exacerbations in the Subpopulations and Intermediate Outcome Measures in COPD Study (SPIROMICS) cohort, we analysed patients aged 40-80 years with COPD for whom 3 years of prospective data were available, identified through various means including care at academic and non-academic medical centres, word of mouth, and existing patient registries. Participants were enrolled in the study between Nov 12, 2010, and July 31, 2015. We classified patients according to yearly exacerbation frequency: no exacerbations in any year; one exacerbation in every year during 3 years of follow-up; and those with inconsistent exacerbations (individuals who had both years with exacerbations and years without during the 3 years of follow-up). Participants were characterised by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) spirometric category (1-4) on the basis of post-bronchodilator FEV1. Stepwise logistic regression was used to compare factors associated with one or more acute exacerbations of COPD every year for 3 years versus no exacerbations in the same timeframe. Additionally, a stepwise zero-inflated negative binomial model was used to assess predictors of exacerbation count during follow-up in all patients with available data. Baseline symptom burden was assessed with the COPD assessment test. This trial is registered with ClinicalTrials.gov, number NCT01969344. 2981 patients were enrolled during the study. 1843 patients had COPD, of which 1105 patients had 3 years of complete, prospective follow-up data. 538 (49%) of 1105 patients had at least one acute exacerbation during the 3 years of follow-up, whereas

  15. Decreased activation of inflammatory networks during acute asthma exacerbations is associated with chronic airflow obstruction

    Science.gov (United States)

    Bosco, Anthony; Ehteshami, Samira; Stern, Debra A.; Martinez, Fernando D.

    2010-01-01

    Asthma exacerbations are associated with subsequent deficits in lung function. Here, we tested the hypothesis that a specific pattern of inflammatory responses during acute exacerbations may be associated with chronic airway obstruction. Gene coexpression networks were characterized in induced sputum obtained during an acute exacerbation, from asthmatic children with or without chronic airflow limitation. The data showed that activation of Th1-like/cytotoxic and interferon signalling pathways during acute exacerbations was decreased in asthmatic children with deficits in baseline lung function. These associations were independent of the identification of picornaviruses in nasal secretions or the use of medications at the time of the exacerbation. Th2-related pathways were also detected in the responses, but variations in these pathways were not related to chronic airways obstruction. Our findings demonstrate that decreased activation of Th1-like/cytotoxic and interferon pathways is a hallmark of acute exacerbation responses in asthmatic children with evidence of chronic airways obstruction. PMID:20336062

  16. Bevacizumab Exacerbates Paclitaxel-Induced Neuropathy: A Retrospective Cohort Study.

    Science.gov (United States)

    Matsuoka, Ayumu; Maeda, Osamu; Mizutani, Takefumi; Nakano, Yasuyuki; Tsunoda, Nobuyuki; Kikumori, Toyone; Goto, Hidemi; Ando, Yuichi

    2016-01-01

    Bevacizumab (BEV), a humanized anti-vascular endothelial growth factor (VEGF) monoclonal antibody, enhances the antitumor effectiveness of paclitaxel (PTX)-based chemotherapy in many metastatic cancers. A recent study in mice showed that VEGF receptor inhibitors can interfere with the neuroprotective effects of endogenous VEGF, potentially triggering the exacerbation of PTX-induced neuropathy. In clinical trials, exacerbation of neuropathy in patients who received PTX combined with BEV (PTX+BEV) has generally been explained by increased exposure to PTX owing to the extended duration of chemotherapy. We investigated whether the concurrent use of BEV is associated with the exacerbation of PTX-induced neuropathy. Female patients with breast cancer who had received weekly PTX or PTX+BEV from September 2011 through May 2016 were studied retrospectively. PTX-induced neuropathy was evaluated at the same time points (at the 6th and 12th courses of chemotherapy) in both cohorts. A multivariate Cox proportional-hazards model was used to assess the independent effect of BEV on the time to the onset of neuropathy. A total of 107 patients (median age, 55 years; range, 32-83) were studied. Sixty-one patients received PTX as adjuvant chemotherapy, 23 received PTX for metastatic disease, and 23 received PTX+BEV for metastatic disease. Peripheral sensory neuropathy was worse in patients who received PTX+BEV than in those who received PTX alone: at the 6th course, Grade 0/1/2/3 = 4/13/4/0 vs. 25/42/6/0 (P = 0.095); at the 12th course, 2/3/11/3 vs. 7/30/23/2 (P = 0.016). At the 12th course, the incidence of Grade 2 or higher neuropathy was significantly higher in patients treated with PTX+BEV than in those treated with PTX alone (74% vs. 40%; P = 0.017). In multivariate analysis, BEV was significantly associated with an increased risk of neuropathy (HR 2.32, 95% CI 1.21-4.44, P = 0.012). The concurrent use of BEV could worsen PTX-induced neuropathy in patients with breast cancer.

  17. Exacerbation of diabetic renal alterations in mice lacking vasohibin-1.

    Directory of Open Access Journals (Sweden)

    Norikazu Hinamoto

    Full Text Available Vasohibin-1 (VASH1 is a unique endogenous inhibitor of angiogenesis that is induced in endothelial cells by pro-angiogenic factors. We previously reported renoprotective effect of adenoviral delivery of VASH1 in diabetic nephropathy model, and herein investigated the potential protective role of endogenous VASH1 by using VASH1-deficient mice. Streptozotocin-induced type 1 diabetic VASH1 heterozygous knockout mice (VASH1(+/- or wild-type diabetic mice were sacrificed 16 weeks after inducing diabetes. In the diabetic VASH1(+/- mice, albuminuria were significantly exacerbated compared with the diabetic wild-type littermates, in association with the dysregulated distribution of glomerular slit diaphragm related proteins, nephrin and ZO-1, glomerular basement membrane thickening and reduction of slit diaphragm density. Glomerular monocyte/macrophage infiltration and glomerular nuclear translocation of phosphorylated NF-κB p65 were significantly exacerbated in the diabetic VASH1(+/- mice compared with the diabetic wild-type littermates, accompanied by the augmentation of VEGF-A, M1 macrophage-derived MCP-1 and phosphorylation of IκBα, and the decrease of angiopoietin-1/2 ratio and M2 macrophage-derived Arginase-1. The glomerular CD31(+ endothelial area was also increased in the diabetic VASH1(+/- mice compared with the diabetic-wild type littermates. Furthermore, the renal and glomerular hypertrophy, glomerular accumulation of mesangial matrix and type IV collagen and activation of renal TGF-β1/Smad3 signaling, a key mediator of renal fibrosis, were exacerbated in the diabetic VASH1(+/- mice compared with the diabetic wild-type littermates. In conditionally immortalized mouse podocytes cultured under high glucose condition, transfection of VASH1 small interfering RNA (siRNA resulted in the reduction of nephrin, angiopoietin-1 and ZO-1, and the augmentation of VEGF-A compared with control siRNA. These results suggest that endogenous VASH1 may

  18. Prediction of exacerbation chronic bronchopulmonary diseases in children with influenza

    Directory of Open Access Journals (Sweden)

    O. I. Afanaseva

    2015-01-01

    Full Text Available The objective: To develop a method for predicting exacerbation of chronic illness in children with asthma and cystic fibrosis, patients with influenza, based on the study of the dynamics of cytokines. Materials and methods: Were examined 52 patients with bronchial asthma and 45 children with cystic fibrosis at the age from 1 year to 12 years, located in infectious pulmonary Department at the planned treatment of underlying pathology, in which influenza was in-hospital infection. Control group observations included 40 patients with the flu, without concomitant pulmonary disease. The etiology of viral infection was established by detection of viral RNA in nasopharyngeal swabs by PCR. Among the influenza viruses were identified influenza АH1N1, АH3N2, influenza B, and in 2009–2010 the predominant antigen was the pandemic influenza virus АH1N1pdm09. Determination of the concentration of serum interleukins IL-1β, IL-4, IL-8, IL-10, ТNF-α, IFN-γ was performed in the 1st and 3rd day of hospitalization cytokines by the solid-phase immune-enzyme assay. Analysis of the results performed using statistical package SPSS 17.0 EN for Windows. Results: The flu caused the aggravation associated bronchopulmonary pathology in 2/3 of children, as MV patients, and patients with BA (65,4%-66,7%, respectively. With an increase of the ratio of IL-4 / IFN-γ and IL-10/IFN-γ, at least 5-6 times, influenza can be considered a trigger of exacerbation of chronic bronchopulmonary pathologies that require amplification of the therapy of bronchial asthma and of сystic fibrosis. The growth of prognostic coefficients in 2-3 times allows using for treatment of influenza in these patients only antiviral agents. Conclusion: The study has shown a method for predicting exacerbation of bronchial asthma and cystic fibrosis in children at an early stage of influenza by calculating the ratio of IL-4/IFN-γ and IL-10/IFN-γ in children aged from 1 year to 12 years. 

  19. Modularity for Motor Control and Motor Learning.

    Science.gov (United States)

    d'Avella, Andrea

    2016-01-01

    How the central nervous system (CNS) overcomes the complexity of multi-joint and multi-muscle control and how it acquires or adapts motor skills are fundamental and open questions in neuroscience. A modular architecture may simplify control by embedding features of both the dynamic behavior of the musculoskeletal system and of the task into a small number of modules and by directly mapping task goals into module combination parameters. Several studies of the electromyographic (EMG) activity recorded from many muscles during the performance of different tasks have shown that motor commands are generated by the combination of a small number of muscle synergies, coordinated recruitment of groups of muscles with specific amplitude balances or activation waveforms, thus supporting a modular organization of motor control. Modularity may also help understanding motor learning. In a modular architecture, acquisition of a new motor skill or adaptation of an existing skill after a perturbation may occur at the level of modules or at the level of module combinations. As learning or adapting an existing skill through recombination of modules is likely faster than learning or adapting a skill by acquiring new modules, compatibility with the modules predicts learning difficulty. A recent study in which human subjects used myoelectric control to move a mass in a virtual environment has tested this prediction. By altering the mapping between recorded muscle activity and simulated force applied on the mass, as in a complex surgical rearrangement of the tendons, it has been possible to show that it is easier to adapt to a perturbation that is compatible with the muscle synergies used to generate hand force than to a similar but incompatible perturbation. This result provides direct support for a modular organization of motor control and motor learning.

  20. Administration of nintedanib after discontinuation for acute exacerbation of idiopathic pulmonary fibrosis: a case report

    OpenAIRE

    IKEDA, SATOSHI; Sekine, Akimasa; Baba, Tomohisa; Yamakawa, Hideaki; Morita, Masato; Kitamura, Hideya; Ogura, Takashi

    2016-01-01

    Background Nintedanib is a multi-target receptor tyrosine kinase inhibitor. In two recent randomized phase 3 trials (INPULSIS?-1 and -2), it has been shown to slow the disease progression of idiopathic pulmonary fibrosis (IPF) by reducing the decline in the forced vital capacity (FVC). Although the INPULSIS? trials indicate that nintedanib may serve to prevent acute exacerbations or delay the time to the first acute exacerbation, a certain number of IPF patients develop acute exacerbations wh...

  1. Defining the "Frequent Exacerbator" Phenotype in COPD: A Hypothesis-Free Approach.

    Science.gov (United States)

    Le Rouzic, Olivier; Roche, Nicolas; Cortot, Alexis B; Tillie-Leblond, Isabelle; Masure, Frédéric; Perez, Thierry; Boucot, Isabelle; Hamouti, Latifa; Ostinelli, Juliette; Pribil, Céline; Poutchnine, Christine; Schück, Stéphane; Pouriel, Mathilde; Housset, Bruno

    2017-10-17

    The COPD "frequent exacerbator" phenotype is usually defined by at least two treated exacerbations per year and is associated with a huge impact on patient health. However, existence of this phenotype and corresponding thresholds still need to be formally confirmed by statistical methods analyzing exacerbation profiles with no specific a priori hypothesis. The aim of this study was to confirm the existence of the frequent exacerbator phenotype with an innovative unbiased statistical analysis of prospectively recorded exacerbations. Data from patients with COPD from the French cohort in Exacerbations of COPD Patients (EXACO) were analyzed using the KmL method designed to cluster longitudinal data and receiver operating characteristic (ROC) curve analysis to determine the best threshold to allocate patients to identified clusters. Univariate and multivariate analyses were performed to study characteristics associated with different clusters. Two clusters of patients were identified based on exacerbation frequency over time, with 2.89 exacerbations per year on average in the first cluster (n = 348) and 0.71 on average in the second cluster (n = 116). The best threshold to distinguish these clusters was two moderate to severe exacerbations per year. Frequent exacerbators had more airflow limitation, symptoms, and health-related quality of life impairment. A simple clinical score was derived to help identify patients at risk of exacerbations. These analyses confirmed the existence and clinical relevance of a frequent exacerbator subgroup of patients with COPD and the currently used threshold to define this phenotype. Copyright © 2017 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

  2. Rhinovirus Exacerbates House-Dust-Mite Induced Lung Disease in Adult Mice

    OpenAIRE

    Jennifer A Phan; Anthony Kicic; Luke J. Berry; Fernandes, Lynette B.; Zosky, Graeme R; Sly, Peter D.; Larcombe, Alexander N.

    2014-01-01

    Human rhinovirus is a key viral trigger for asthma exacerbations. To date, murine studies investigating rhinovirus-induced exacerbation of allergic airways disease have employed systemic sensitisation/intranasal challenge with ovalbumin. In this study, we combined human-rhinovirus infection with a clinically relevant mouse model of aero-allergen exposure using house-dust-mite in an attempt to more accurately understand the links between human-rhinovirus infection and exacerbations of asthma. ...

  3. Risk of asthma exacerbation associated with nonsteroidal anti-inflammatory drugs in childhood asthma

    OpenAIRE

    Lo, Pei-Chia; Tsai, Yueh-Ting; Lin,Shun-Ku; Lai, Jung-Nien

    2016-01-01

    Abstract Patients allergic to aspirin or nonsteroidal anti-inflammatory drugs (NSAIDs) who develop respiratory reactions such as bronchospasm or asthma exacerbation have aspirin-induced asthma or NSAIDs-exacerbated respiratory disease. However, large-scale studies have not been conducted to investigate the risk of aspirin/NSAIDs exposure in children with asthma. Therefore, this study evaluated the relationship between aspirin/NSAIDs and the risk of asthma exacerbation in children with asthma....

  4. Prevalence and Risk Factors of Respiratory Viral Infections in Exacerbations of Chronic Obstructive Pulmonary Disease.

    Science.gov (United States)

    Kwak, Hyun Jung; Park, Dong Won; Kim, Jee Eun; Park, Min Kyung; Koo, Gun Woo; Park, Tai Sun; Moon, Ji-Yong; Kim, Tae Hyung; Sohn, Jang Won; Yoon, Ho Joo; Shin, Dong Ho; Kim, Sang-Heon

    2016-10-01

    Exacerbations of chronic obstructive pulmonary disease (COPD) lead to high morbidity and mortality. Respiratory virus infection is considered as one of the important causes of COPD exacerbations. The aim of this study was to assess the prevalence of respiratory virus infection in COPD exacerbations and to find the factors associated with susceptibility to viral infections. Furthermore, we tried to examine if COPD exacerbations caused by viral infections have more severe clinical outcomes in comparison with those with non-viral causes. We enrolled the patients with acute exacerbations of COPD who were hospitalized in a university hospital, over a 2-year period. Nasopharyngeal swabs were taken and viruses were identified by multiplex polymerase chain reaction. A total of 278 episodes of COPD exacerbations were recorded in 213 patients with COPD (number of females = 73). Among the COPD exacerbations, viral infection was detected in 78 episodes (28.1%) from 67 subjects. The most common virus was rhinovirus (38.8%), followed by respiratory syncytial virus, coronavirus, influenza A, parainfluenza, adenovirus and metapneumovirus. In multivariate regression analysis adjusting for sex, age, BMI, lung function and history of exacerbations, female subjects were found to be significantly associated with viral infections in COPD exacerbations (Odds ratio 2.58, 95%CI 1.25-5.31, P = 0.010). The severity of COPD exacerbations were not different between positive and negative viral detections. In conclusion, the prevalence of viral infection was 28.1% in the hospitalized patients with COPD exacerbations. Moreover, female subjects are at significantly higher risk for viral infections in COPD exacerbations.

  5. Leptin Exacerbates Sepsis-Mediated Morbidity and Mortality

    Science.gov (United States)

    Shapiro, Nathan I.; Khankin, Eliyahu V.; Van Meurs, Matijs; Shih, Shou-Ching; Lu, Shulin; Yano, Midori; Castro, Pedro R.; Maratos-Flier, Eleftheria; Parikh, Samir M.; Karumanchi, S. Ananth; Yano, Kiichiro

    2011-01-01

    The adipose-derived hormone leptin is well known for its contribution to energy metabolism and satiety signaling in the hypothalamus. Previous studies suggested that obesity is an independent risk factor for sepsis morbidity and mortality, and it is associated with elevated baseline levels of circulating leptin in normal, nonseptic patients. In mouse endotoxemia and cecal ligation puncture models of sepsis, we observed elevated levels of leptin and soluble leptin receptor (sLR). Exogenously administered leptin increased mortality in endotoxemia and cecal ligation puncture models and was associated with increased expression of adhesion and coagulation molecules, macrophage infiltration into the liver and kidney, and endothelial barrier dysfunction. Conversely, longform leptin receptor-deficient mice were protected from sepsis morbidity and mortality and had less endothelial dysfunction. Furthermore, an in vitro study revealed that leptin-induced endothelial dysfunction is likely mediated, at least in part, by monocytes. Moreover, administration of an sLR conferred a survival benefit. Human septic patients have increased circulating sLR concentrations, which were correlated with disease severity indices. Together, these data support a pathogenic role for leptin signaling during sepsis. PMID:20519646

  6. Aging exacerbates obesity-induced oxidative stress and inflammation in perivascular adipose tissue in mice: a paracrine mechanism contributing to vascular redox dysregulation and inflammation.

    Science.gov (United States)

    Bailey-Downs, Lora C; Tucsek, Zsuzsanna; Toth, Peter; Sosnowska, Danuta; Gautam, Tripti; Sonntag, William E; Csiszar, Anna; Ungvari, Zoltan

    2013-07-01

    Obesity in the elderly individuals is increasing at alarming rates and there is evidence suggesting that elderly individuals are more vulnerable to the deleterious cardiovascular effects of obesity than younger individuals. However, the specific mechanisms through which aging and obesity interact to promote the development of cardiovascular disease remain unclear. The present study was designed to test the hypothesis that aging exacerbates obesity-induced inflammation in perivascular adipose tissue, which contributes to increased vascular oxidative stress and inflammation in a paracrine manner. To test this hypothesis, we assessed changes in the secretome, reactive oxygen species production, and macrophage infiltration in periaortic adipose tissue of young (7 month old) and aged (24 month old) high-fat diet-fed obese C57BL/6 mice. High-fat diet-induced vascular reactive oxygen species generation significantly increased in aged mice, which was associated with exacerbation of endothelial dysfunction and vascular inflammation. In young animals, high-fat diet-induced obesity promoted oxidative stress in the perivascular adipose tissue, which was associated with a marked proinflammatory shift in the profile of secreted cytokines and chemokines. Aging exacerbated obesity-induced oxidative stress and inflammation and significantly increased macrophage infiltration in periaortic adipose tissue. Using cultured arteries isolated from young control mice, we found that inflammatory factors secreted from the perivascular fat tissue of obese aged mice promote significant prooxidative and proinflammatory phenotypic alterations in the vascular wall, mimicking the aging phenotype. Overall, our findings support an important role for localized perivascular adipose tissue inflammation in exacerbation of vascular oxidative stress and inflammation in aging, an effect that likely enhances the risk for development of cardiovascular diseases from obesity in the elderly individuals.

  7. Mitochondrial mislocalization underlies Abeta42-induced neuronal dysfunction in a Drosophila model of Alzheimer's disease.

    Directory of Open Access Journals (Sweden)

    Kanae Iijima-Ando

    2009-12-01

    Full Text Available The amyloid-beta 42 (Abeta42 is thought to play a central role in the pathogenesis of Alzheimer's disease (AD. However, the molecular mechanisms by which Abeta42 induces neuronal dysfunction and degeneration remain elusive. Mitochondrial dysfunctions are implicated in AD brains. Whether mitochondrial dysfunctions are merely a consequence of AD pathology, or are early seminal events in AD pathogenesis remains to be determined. Here, we show that Abeta42 induces mitochondrial mislocalization, which contributes to Abeta42-induced neuronal dysfunction in a transgenic Drosophila model. In the Abeta42 fly brain, mitochondria were reduced in axons and dendrites, and accumulated in the somata without severe mitochondrial damage or neurodegeneration. In contrast, organization of microtubule or global axonal transport was not significantly altered at this stage. Abeta42-induced behavioral defects were exacerbated by genetic reductions in mitochondrial transport, and were modulated by cAMP levels and PKA activity. Levels of putative PKA substrate phosphoproteins were reduced in the Abeta42 fly brains. Importantly, perturbations in mitochondrial transport in neurons were sufficient to disrupt PKA signaling and induce late-onset behavioral deficits, suggesting a mechanism whereby mitochondrial mislocalization contributes to Abeta42-induced neuronal dysfunction. These results demonstrate that mislocalization of mitochondria underlies the pathogenic effects of Abeta42 in vivo.

  8. A case of chronic urticaria exacerbating with menstrual cycles

    Directory of Open Access Journals (Sweden)

    Goknur Kalkan

    2013-09-01

    menstrual cycle, pregnancy, menopause and hormonal contraceptives or hormone replacement therapy. Chronic urticaria is approximately twice more frequent in women than in men. Hypersensitivity reactions to endogenous or exogenous female sex hormones have been implicated in the pathogenesis of urticarial lesions. Progesterone or estrogen-depended urticaria should be suspected in women showing eruption in cyclic interval with each menses or chronic urticarial lesions with periodic variations at different times. Here we would like to present a case of 36-year-old woman that decribes and has urticarial lesions exacerbating in menstrual periods for 12 years and remind this issue which may not take into consideration in daily practice in the pathogenesis of urticaria. Consequently, the influence of fluctuations in the hormonal milieu and altered sex hormone expression on the triggering-off, maintenance or aggravation of urticaria should be taken into account. [J Contemp Med 2013; 3(3.000: 200-202

  9. EXACERBATION OF ANKYLOSING SPONDYLITIS AFTER LOW-DOSE METHOTREXATE THERAPY

    Directory of Open Access Journals (Sweden)

    A. V. Orlov-Morozov

    2014-01-01

    Full Text Available Background: Efficacy of methotrexate in ankylosing spondylitis (AS is disputable. Nevertheless, methotrexate is still used for disease-modifying therapy of AS. Aim: To assess efficacy and safety of methotrexate in AS patients. Materials and methods: It was an open comparative study of efficacy of methotrexate (n=12 versus standard therapy (n=12 in AS patients. Results: Negative results of methotrexate therapy were obtained. In the majority of patients methotrexate therapy was associated with increased joint pain, swelling and morning stiffness as well as elevation of erythrocyte sedimentation rate, fever and visceritis. Worsening of symptoms was regarded as exacerbation of inflammatory process. The study was terminated prematurely. Conclusion: Methotrexate demonstrated no therapeutic effect in AS patients. In AS, methotrexate should be administrated under close physician control in order to ensure treatment safety

  10. Do intercultural factors play a role in exacerbating psychiatric symptoms?

    Science.gov (United States)

    Ong, Yong Lock; Yap, Hwa Ling

    2013-01-01

    We report the case of a 29-year-old mixed-race woman suffering from recurrent major depressive episodes, with suicidal ideation and risk, involving several inpatient admissions. A comorbid diagnosis of borderline personality disorder was also recorded in one of her previous inpatient admissions. During her last inpatient admission, a multidisciplinary case discussion and review of the patient's life highlighted several possible intercultural trigger factors that could have contributed to the exacerbation of her psychiatric illness. We emphasise the need to explore intercultural predisposing and precipitating factors for a more complete psychodynamic understanding of psychiatric illnesses among the multiracial population of Singapore. This also adds to the discussion on the management of such patients with the option of formal in-depth psychotherapy in adjunct to medication. This may prevent recurrent relapses, modify suicide intent and reduce the necessity for inpatient treatment, which will be cost-effective and result in efficacious treatment.

  11. Monitoring asthma in childhood: symptoms, exacerbations and quality of life

    Directory of Open Access Journals (Sweden)

    Paul L.P. Brand

    2015-06-01

    Full Text Available Monitoring asthma in children in clinical practice is primarily performed by reviewing disease activity (daytime and night-time symptoms, use of reliever medication, exacerbations requiring frequent use of reliever medication and urgent visits to the healthcare professional and the impact of the disease on children's daily activities, including sports and play, in a clinical interview. In such an interview, most task force members also discuss adherence to maintenance therapy and the patients' (and parents' views and beliefs on the goals of treatment and the amount of treatment required to achieve those goals. Composite asthma control and quality of life measures, although potentially useful in research, have limited value in clinical practice because they have a short recall window and do not cover the entire spectrum of asthma control. Telemonitoring of children with asthma cannot replace face-to-face follow-up and monitoring because there is no evidence that it is associated with improved health outcomes.

  12. Control motor brushless sensorless

    OpenAIRE

    Solchaga Pérez de Lazárraga, Gonzalo

    2015-01-01

    El proyecto consiste en la creación de un circuito capaz de controlar la velocidad de un motor brushless sensorless. Este tipo de motores eléctricos tienen como característica que no tienen escobillas para cambiar la polaridad del bobinado de su interior y tampoco precisan de un sensor que indique que ha realizado una vuelta. Los motores brushless que son controlados por este tipo de circuitos son específicos para aeronaves no tripuladas y requieren un diseño diferente a un motor brushless pe...

  13. Hybrid vehicle motor alignment

    Science.gov (United States)

    Levin, Michael Benjamin

    2001-07-03

    A rotor of an electric motor for a motor vehicle is aligned to an axis of rotation for a crankshaft of an internal combustion engine having an internal combustion engine and an electric motor. A locator is provided on the crankshaft, a piloting tool is located radially by the first locator to the crankshaft. A stator of the electric motor is aligned to a second locator provided on the piloting tool. The stator is secured to the engine block. The rotor is aligned to the crankshaft and secured thereto.

  14. The Christmas Season as a Risk Factor for Chronic Obstructive Pulmonary Disease Exacerbations

    Directory of Open Access Journals (Sweden)

    Neil W Johnston

    2010-01-01

    Full Text Available BACKGROUND: Epidemics of hospitalization for chronic obstructive pulmonary disease (COPD occur annually during the Christmas holidays, and COPD exacerbations commonly coincide with respiratory viral infections.

  15. Impact and prevention of severe exacerbations of COPD: a review of the evidence

    Science.gov (United States)

    Halpin, David MG; Miravitlles, Marc; Metzdorf, Norbert; Celli, Bartolomé

    2017-01-01

    Severe exacerbations of COPD, ie, those leading to hospitalization, have profound clinical implications for patients and significant economic consequences for society. The prevalence and burden of severe COPD exacerbations remain high, despite recognition of the importance of exacerbation prevention and the availability of new treatment options. Severe COPD exacerbations are associated with high mortality, have negative impact on quality of life, are linked to cardiovascular complications, and are a significant burden on the health-care system. This review identified risk factors that contribute to the development of severe exacerbations, treatment options (bronchodilators, antibiotics, corticosteroids [CSs], oxygen therapy, and ventilator support) to manage severe exacerbations, and strategies to prevent readmission to hospital. Risk factors that are amenable to change have been highlighted. A number of bronchodilators have demonstrated successful reduction in risk of severe exacerbations, including long-acting muscarinic antagonist or long-acting β2-agonist mono- or combination therapies, in addition to vaccination, mucolytic and antibiotic therapy, and nonpharmacological interventions, such as pulmonary rehabilitation. Recognition of the importance of severe exacerbations is an essential step in improving outcomes for patients with COPD. Evidence-based approaches to prevent and manage severe exacerbations should be implemented as part of targeted strategies for disease management. PMID:29062228

  16. Effect of genetic polymorphism of ALOX15 on aspirin-exacerbated respiratory disease

    National Research Council Canada - National Science Library

    Song, Young-Sin; Yang, Eun-Mi; Kim, Seung-Hyun; Jin, Hyun Jung; Park, Hae-Sim

    2012-01-01

    Aspirin-exacerbated respiratory disease (AERD) is a clinical syndrome associated with chronic inflammation in the airways coincident with chronic rhinitis, sinusitis, recurrent polyposis and asthma...

  17. Impact of exacerbations on emphysema progression in chronic obstructive pulmonary disease.

    Science.gov (United States)

    Tanabe, Naoya; Muro, Shigeo; Hirai, Toyohiro; Oguma, Tsuyoshi; Terada, Kunihiko; Marumo, Satoshi; Kinose, Daisuke; Ogawa, Emiko; Hoshino, Yuma; Mishima, Michiaki

    2011-06-15

    Low-attenuation areas assessed by computed tomography reflect the extent of pathological emphysema and correlate with airflow limitation and mortality in patients with chronic obstructive pulmonary disease. The cumulative size distribution of low-attenuation area clusters follows a power law characterized by an exponent, D. The values of D reflect the complexity of the terminal airspace geometry and sensitively detect alveolar structural changes. Exacerbations of chronic obstructive pulmonary disease have a negative impact on lung function and prognosis. However, the impact on emphysema progression remains unclear. We investigated the relationship between exacerbation and emphysema progression assessed by computed tomography in patients with chronic obstructive pulmonary disease. Exacerbations were prospectively recorded for 2 years. Annual changes in computed tomography parameters of emphysema were compared between patients with and without a history of exacerbations. In patients with exacerbations, increases in the percentage of low-attenuation areas and decreases in D were greater than in patients without exacerbations. To interpret these results, we established a novel simulation model and found that not only enlargement of preexisting low-attenuation areas but also coalescence of adjoining low-attenuation areas due to alveolar wall destruction caused emphysema progression in patients with exacerbations. This is the first longitudinal study to demonstrate that exacerbations are involved in emphysema progression in patients with chronic obstructive pulmonary disease. Emphysema progression should be evaluated as part of the outcomes of exacerbations in the management of chronic obstructive pulmonary disease.

  18. Comparison of Canadian versus United States Emergency Department Visits for Chronic Obstructive Pulmonary Disease Exacerbation

    Directory of Open Access Journals (Sweden)

    Brian H Rowe

    2008-01-01

    Full Text Available INTRODUCTION: Despite the frequency of emergency department (ED visits for chronic obstructive pulmonary disease (COPD exacerbation, little is known about practice variation in EDs.

  19. Inflammation and airway microbiota during cystic fibrosis pulmonary exacerbations.

    Directory of Open Access Journals (Sweden)

    Edith T Zemanick

    Full Text Available Pulmonary exacerbations (PEx, frequently associated with airway infection and inflammation, are the leading cause of morbidity in cystic fibrosis (CF. Molecular microbiologic approaches detect complex microbiota from CF airway samples taken during PEx. The relationship between airway microbiota, inflammation, and lung function during CF PEx is not well understood.To determine the relationships between airway microbiota, inflammation, and lung function in CF subjects treated for PEx.Expectorated sputum and blood were collected and lung function testing performed in CF subjects during early (0-3d. and late treatment (>7d. for PEx. Sputum was analyzed by culture, pyrosequencing of 16S rRNA amplicons, and quantitative PCR for total and specific bacteria. Sputum IL-8 and neutrophil elastase (NE; and circulating C-reactive protein (CRP were measured.Thirty-seven sputum samples were collected from 21 CF subjects. At early treatment, lower diversity was associated with high relative abundance (RA of Pseudomonas (r = -0.67, p<0.001, decreased FEV(1% predicted (r = 0.49, p = 0.03 and increased CRP (r = -0.58, p = 0.01. In contrast to Pseudomonas, obligate and facultative anaerobic genera were associated with less inflammation and higher FEV₁. With treatment, Pseudomonas RA and P. aeruginosa by qPCR decreased while anaerobic genera showed marked variability in response. Change in RA of Prevotella was associated with more variability in FEV₁ response to treatment than Pseudomonas or Staphylococcus.Anaerobes identified from sputum by sequencing are associated with less inflammation and higher lung function compared to Pseudomonas at early exacerbation. CF PEx treatment results in variable changes of anaerobic genera suggesting the need for larger studies particularly of patients without traditional CF pathogens.

  20. Exacerbation of Acute Traumatic Brain Injury by Circulating Extracellular Vesicles.

    Science.gov (United States)

    Hazelton, Isla; Yates, Abi; Dale, Ashley; Roodselaar, Jay; Akbar, Naveed; Ruitenberg, Marc J; Anthony, Daniel C; Couch, Yvonne

    2018-02-15

    Inflammatory lesions in the brain activate a systemic acute-phase response (APR), which is dependent on the release of extracellular vesicles (EVs) into the circulation. The resulting APR is responsible for regulating leukocyte mobilization and subsequent recruitment to the brain. Factors that either exacerbate or inhibit the APR will also exacerbate or inhibit central nervous system (CNS) inflammation as a consequence and have the potential to influence ongoing secondary damage. Here, we were interested to discover how the circulating EV population changes after traumatic brain injury (TBI) and how manipulation of the circulating EV pool impacts on the outcome of TBI. We found the number of circulating EVs increased rapidly post-TBI, and this was accompanied by an increase in CNS and hepatic leukocyte recruitment. In an adoptive transfer study, we then evaluated the outcomes of TBI after administering EVs derived from either in vitro macrophage or endothelial cell lines stimulated with lipopolysaccharide (LPS), or from murine plasma from an LPS challenge using the air-pouch model. By manipulating the circulating EV population, we were able to demonstrate that each population of transferred EVs increased the APR. However, the characteristics of the response were dependent on the nature of the EVs; specifically, it was significantly increased when animals were challenged with macrophage-derived EVs, suggesting that the cellular origins of EVs may determine their function. Selectively targeting EVs from macrophage/monocyte populations is likely to be of value in reducing the impact of the systemic inflammatory response on the outcome of traumatic CNS injury.

  1. Exposure to particulate hexavalent chromium exacerbates allergic asthma pathology

    Energy Technology Data Exchange (ETDEWEB)

    Schneider, Brent C. [Department of Microbiology, Immunology and Tropical Medicine, The George Washington University, Washington, DC 20037 (United States); Department of Pharmacology and Physiology, The George Washington University, Washington, DC 20037 (United States); Constant, Stephanie L. [Department of Microbiology, Immunology and Tropical Medicine, The George Washington University, Washington, DC 20037 (United States); Patierno, Steven R. [Department of Pharmacology and Physiology, The George Washington University, Washington, DC 20037 (United States); GW Cancer Institute, The George Washington University, Washington, DC 20037 (United States); Jurjus, Rosalyn A. [Department of Anatomy and Regenerative Biology, The George Washington University, Washington, DC 20037 (United States); Ceryak, Susan M., E-mail: phmsmc@gwumc.edu [Department of Pharmacology and Physiology, The George Washington University, Washington, DC 20037 (United States)

    2012-02-15

    Airborne hexavalent chromate, Cr(VI), has been identified by the Environmental Protection Agency as a possible health threat in urban areas, due to the carcinogenic potential of some of its forms. Particulate chromates are produced in many different industrial settings, with high levels of aerosolized forms historically documented. Along with an increased risk of lung cancer, a high incidence of allergic asthma has been reported in workers exposed to certain inhaled particulate Cr(VI) compounds. However, a direct causal association between Cr(VI) and allergic asthma has not been established. We recently showed that inhaled particulate Cr(VI) induces an innate neutrophilic inflammatory response in BALB/c mice. In the current studies we investigated how the inflammation induced by inhaled particulate Cr(VI) might alter the pathology of an allergic asthmatic response. We used a well-established mouse model of allergic asthma. Groups of ovalbumin protein (OVA)-primed mice were challenged either with OVA alone, or with a combination of OVA and particulate zinc chromate, and various parameters associated with asthmatic responses were measured. Co-exposure to particulate Cr(VI) and OVA mediated a mixed form of asthma in which both eosinophils and neutrophils are present in airways, tissue pathology is markedly exacerbated, and airway hyperresponsiveness is significantly increased. Taken together these findings suggest that inhalation of particulate forms of Cr(VI) may augment the severity of ongoing allergic asthma, as well as alter its phenotype. Such findings may have implications for asthmatics in settings in which airborne particulate Cr(VI) compounds are present at high levels. -- Highlights: ► Allergic asthma correlated with exposure to certain inhaled particulate chromates. ► Direct causal association between Cr(VI) and allergic asthma not established. ► Cr exacerbated pathology and airway hyperresponsiveness in an OVA-challenged mouse. ► Particulate Cr

  2. A novel microbiota stratification system predicts future exacerbations in bronchiectasis.

    Science.gov (United States)

    Rogers, Geraint B; Zain, Nur Masirah M; Bruce, Kenneth D; Burr, Lucy D; Chen, Alice C; Rivett, Damian W; McGuckin, Michael A; Serisier, David J

    2014-05-01

    Although airway microbiota composition correlates with clinical measures in non-cystic fibrosis bronchiectasis, these data are unlikely to provide useful prognostic information at the individual patient level. A system enabling microbiota data to be applied clinically would represent a substantial translational advance. This study aims to determine whether stratification of patients according to the predominant microbiota taxon can provide improved clinical insight compared with standard diagnostics. The presence of bacterial respiratory pathogens was assessed in induced sputum from 107 adult patients by culture, quantitative PCR, and, in 96 samples, by ribosomal gene pyrosequencing. Prospective analysis was performed on samples from 42 of these patients. Microbiological data were correlated with concurrent clinical measures and subsequent outcomes. Microbiota analysis defined three groups: Pseudomonas aeruginosa dominated (n = 26), Haemophilus influenzae dominated (n = 34), and other taxa dominated (n = 36). Patients with P. aeruginosa- and H. influenzae-dominated communities had significantly worse lung function, higher serum levels of C-reactive protein (CRP), and higher sputum levels of IL-8 and IL-1β. Predominance of P. aeruginosa, followed by Veillonella species, was the best predictor of future exacerbation frequency, with H. influenzae-dominated communities having significantly fewer episodes. Detection of P. aeruginosa was associated with poor lung function and exacerbation frequency, irrespective of analytical strategy. Quantitative PCR revealed significant correlations between H. influenzae levels and sputum IL-8, IL-1β, and serum CRP. Genus richness was negatively correlated with 24-hour sputum weight, age, serum CRP, sputum IL-1β, and IL-8. Stratification of patients with non-cystic fibrosis bronchiectasis on the basis of predominant bacterial taxa is more clinically informative than either conventional culture or quantitative PCR-based analysis

  3. Auditory- and Vestibular-Evoked Potentials Correlate with Motor and Non-Motor Features of Parkinson’s Disease

    Science.gov (United States)

    Shalash, Ali Soliman; Hassan, Dalia Mohamed; Elrassas, Hanan Hani; Salama, Mohamed Mosaad; Méndez-Hernández, Edna; Salas-Pacheco, José M.; Arias-Carrión, Oscar

    2017-01-01

    Degeneration of several brainstem nuclei has been long related to motor and non-motor symptoms (NMSs) of Parkinson’s disease (PD). Nevertheless, due to technical issues, there are only a few studies that correlate that association. Brainstem auditory-evoked potential (BAEP) and vestibular-evoked myogenic potential (VEMP) responses represent a valuable tool for brainstem assessment. Here, we investigated the abnormalities of BAEPs, ocular VEMPs (oVEMPs), and cervical VEMPs (cVEMPs) in patients with PD and its correlation to the motor and NMSs. Fifteen patients diagnosed as idiopathic PD were evaluated by Unified Parkinson’s Disease Rating Scale and its subscores, Hoehn and Yahr scale, Schwab and England scale, and Non-Motor Symptoms Scale. PD patients underwent pure-tone, speech audiometry, tympanometry, BAEP, oVEMPs, and cVEMPs, and compared to 15 age-matched control subjects. PD subjects showed abnormal BAEP wave morphology, prolonged absolute latencies of wave V and I–V interpeak latencies. Absent responses were the marked abnormality seen in oVEMP. Prolonged latencies with reduced amplitudes were seen in cVEMP responses. Rigidity and bradykinesia were correlated to the BAEP and cVEMP responses contralateral to the clinically more affected side. Contralateral and ipsilateral cVEMPs were significantly correlated to sleep (p = 0.03 and 0.001), perception (p = 0.03), memory/cognition (p = 0.025), and urinary scores (p = 0.03). The oVEMP responses showed significant correlations to cardiovascular (p = 0.01) and sexual dysfunctions (p = 0.013). PD is associated with BAEP and VEMP abnormalities that are correlated to the motor and some non-motor clinical characteristics. These abnormalities could be considered as potential electrophysiological biomarkers for brainstem dysfunction and its associated motor and non-motor features. PMID:28289399

  4. Body side of motor symptom onset in Parkinson's disease is associated with memory performance.

    Science.gov (United States)

    Amick, M M; Grace, J; Chou, K L

    2006-09-01

    The relation of body side of motor symptom onset in Parkinson's disease (PD) to memory measures associated with hemispheric dominance was examined. Fourteen patients with right body side motor symptom onset (RPD, inferred left hemisphere dysfunction) and 16 patients with left side onset (LPD, right hemisphere dysfunction) were administered measures of verbal (Hopkins Verbal Learning Test-Revised) and visual memory (Brief Visual Memory Test-Revised), that require similar task demands and are associated with left or right hemisphere dominance, respectively. The LPD group demonstrated poorer visual than verbal memory, both within group and in comparison to the RPD group. By contrast, the RPD group showed poorer verbal than visual memory within group. These findings suggest that side of motor symptom onset is associated with asymmetrical memory dysfunction.

  5. Prostatic disease and sexual dysfunction.

    Science.gov (United States)

    Kim, Sae Woong

    2011-06-01

    Prostatitis and benign prostatic hyperplasia (BPH) are common prostatic diseases. Furthermore, the incidence of prostate cancer has recently shown a rapid increase, even in Korea. Pain caused by prostatitis may induce sexual dysfunction, including erectile dysfunction and ejaculatory disturbance. And BPH itself, or treatments for BPH, may affect sexual function. In addition, with increased detection of localized prostate cancer, surgical treatments and radiation therapy have also increased, and the treatments may cause sexual dysfunction. Aging is also an important factor in the deterioration of the quality of life of men. Deterioration of quality of life caused by prostate diseases may be affected not only by the prostate diseases themselves but also by the sexual dysfunction caused by the prostate diseases secondarily. Thus, consideration of these points at the time of treatment of prostate disease is required. Therapies suitable to each condition should be selected with an understanding of the close association of prostate diseases and associated sexual dysfunction with the quality of life of males.

  6. Motor neurone disease: progress and challenges.

    Science.gov (United States)

    Dharmadasa, Thanuja; Henderson, Robert D; Talman, Paul S; Macdonell, Richard Al; Mathers, Susan; Schultz, David W; Needham, Merrillee; Zoing, Margaret; Vucic, Steve; Kiernan, Matthew C

    2017-05-01

    Major progress has been made over the past decade in the understanding of motor neurone disease (MND), changing the landscape of this complex disease. Through identifying positive prognostic factors, new evidence-based standards of care have been established that improve patient survival, reduce burden of disease for patients and their carers, and enhance quality of life. These factors include early management of respiratory dysfunction with non-invasive ventilation, maintenance of weight and nutritional status, as well as instigation of a multidisciplinary team including neurologists, general practitioners and allied health professionals. Advances in technology have enhanced our understanding of the genetic architecture of MND considerably, with implications for patients, their families and clinicians. Recognition of extra-motor involvement, particularly cognitive dysfunction, has identified a spectrum of disease from MND through to frontotemporal dementia. Although riluzole remains the only disease-modifying medication available in clinical practice in Australia, several new therapies are undergoing clinical trials nationally and globally, representing a shift in treatment paradigms. Successful translation of this clinical research through growth in community funding, awareness and national MND research organisations has laid the foundation for closing the research-practice gap on this debilitating disease. In this review, we highlight these recent developments, which have transformed treatment, augmented novel therapeutic platforms, and established a nexus between research and the MND community. This era of change is of significant relevance to both specialists and general practitioners who remain integral to the care of patients with MND.

  7. Anatomy of pelvic floor dysfunction.

    Science.gov (United States)

    Corton, Marlene M

    2009-09-01

    Normal physiologic function of the pelvic organs depends on the anatomic integrity and proper interaction among the pelvic structures, the pelvic floor support components, and the nervous system. Pelvic floor dysfunction includes urinary and anal incontinence; pelvic organ prolapse; and sexual, voiding, and defecatory dysfunction. Understanding the anatomy and proper interaction among the support components is essential to diagnose and treat pelvic floor dysfunction. The primary aim of this article is to provide an updated review of pelvic support anatomy with clinical correlations. In addition, surgical spaces of interest to the gynecologic surgeon and the course of the pelvic ureter are described. Several concepts reviewed in this article are derived and modified from a previous review of pelvic support anatomy.

  8. Mitochondrial Dysfunction in Parkinson's Disease

    Directory of Open Access Journals (Sweden)

    P. C. Keane

    2011-01-01

    Full Text Available Parkinson's disease (PD is a progressive, neurodegenerative condition that has increasingly been linked with mitochondrial dysfunction and inhibition of the electron transport chain. This inhibition leads to the generation of reactive oxygen species and depletion of cellular energy levels, which can consequently cause cellular damage and death mediated by oxidative stress and excitotoxicity. A number of genes that have been shown to have links with inherited forms of PD encode mitochondrial proteins or proteins implicated in mitochondrial dysfunction, supporting the central involvement of mitochondria in PD. This involvement is corroborated by reports that environmental toxins that inhibit the mitochondrial respiratory chain have been shown to be associated with PD. This paper aims to illustrate the considerable body of evidence linking mitochondrial dysfunction with neuronal cell death in the substantia nigra pars compacta (SNpc of PD patients and to highlight the important need for further research in this area.

  9. Sexual dysfunctions in psoriatic patients

    Directory of Open Access Journals (Sweden)

    Maria Isabela Sarbu

    2015-04-01

    Full Text Available Psoriasis is a chronic, immune-mediated disorder with a worldwide occurrence characterized by well-defined infiltrated erythematous papules and plaques, covered by silvery white or yellowish scales. It is a physically, socially and emotionally invalidating disorder that affects 1-2% of the population. Sexual health is an important part of general health and sexual dysfunctions can negatively affect self-esteem, confidence, interpersonal relationships and the quality of life. Dermatology Life Quality Index (DLQI, Psoriasis Disability Index (PDI and the Impact of Psoriasis on Quality of Life (IPSO questionnaire are all questionnaires used to assess the quality of life of patients with psoriasis and each has one question regarding sexual dysfunction. Several scales were also designed to particularly assess sexual satisfaction in men and women. The aim of this paper is to perform an overview of the existing studies on sexual dysfunction in psoriatic patients.

  10. Respiratory diseases and muscle dysfunction.

    Science.gov (United States)

    Gea, Joaquim; Casadevall, Carme; Pascual, Sergi; Orozco-Levi, Mauricio; Barreiro, Esther

    2012-02-01

    Many respiratory diseases lead to impaired function of skeletal muscles, influencing quality of life and patient survival. Dysfunction of both respiratory and limb muscles in chronic obstructive pulmonary disease has been studied in depth, and seems to be caused by the complex interaction of general (inflammation, impaired gas exchange, malnutrition, comorbidity, drugs) and local factors (changes in respiratory mechanics and muscle activity, and molecular events). Some of these factors are also present in cystic fibrosis and asthma. In obstructive sleep apnea syndrome, repeated exposure to hypoxia and the absence of reparative rest are believed to be the main causes of muscle dysfunction. Deconditioning appears to be crucial for the functional impairment observed in scoliosis. Finally, cachexia seems to be the main mechanism of muscle dysfunction in advanced lung cancer. A multidimensional therapeutic approach is recommended, including pulmonary rehabilitation, an adequate level of physical activity, ventilatory support and nutritional interventions.

  11. Attentional focus of feedback and instructions in the treatment of musculoskeletal dysfunction: a systematic review.

    Science.gov (United States)

    Sturmberg, Catrina; Marquez, Jodie; Heneghan, Nicola; Snodgrass, Suzanne; van Vliet, Paulette

    2013-12-01

    An external focus of attention (EFA) during the learning of a motor task improves performance and retention in healthy individuals. People with musculoskeletal dysfunction also learn motor tasks and could potentially benefit from adopting an EFA during practice. To determine whether instructions and feedback provided to individuals with musculoskeletal dysfunction is more effective in improving function and decreasing pain when inducing an external rather than an internal focus of attention (IFA). Systematic review MEDLINE, Embase, CINAHL, AMED, the Cochrane Library and five additional databases were searched. Randomised, quasi-randomised and non-randomised controlled trials, cross over trials and observational studies involving participants with any form of musculoskeletal dysfunction, comparing IFA or EFA with a different attentional focus (AF), control, placebo or no focus condition. Two review authors independently screened titles, abstracts and full texts, then extracted data and appraised the quality of trials using the GRADE system of rating methodological quality. Seven studies were included with a total of 202 participants. Two studies compared an IFA with an EFA, two compared IFA with biofeedback with a different focus condition, and three compared IFA with biofeedback with a no focus condition. Statistically significant improvements in motor performance directly attributable to the focus of attention were only found in the EFA groups. There were no significant improvements in function or pain. There is insufficient evidence to draw conclusions regarding the effects of attentional focus of instructions and feedback on outcomes in musculoskeletal dysfunction. Copyright © 2013 Elsevier Ltd. All rights reserved.

  12. Autonomic Dysfunctions in Parkinsonian Disorders

    Directory of Open Access Journals (Sweden)

    Hyo-Jin Bae

    2009-10-01

    Full Text Available Background and Purpose: Symptoms of autonomic dysfunctions are common in the patients with parkinsonian disorders. Because clinical features of autonomic dysfunctions are diverse, the comprehensive evaluation is essential for the appropriate management. For the appreciation of autonomic dysfunctions and the identification of differences, patients with degenerative parkinsonisms are evaluated using structured questionnaire for autonomic dysfunction (ADQ. Methods: Total 259 patients, including 192 patients with [idiopathic Parkinson’s disease (IPD, age 64.6 ± 9.6 years], 37 with [multiple system atrophy (MSA, 62.8 ± 9.1], 9 with [dementia with Lewy body (DLB, 73.9 ± 4.3], and 21 with [progressive supranuclear palsy (PSP, 69.4 ± 9.6]. The ADQ was structured for evaluation of the presence of symptoms and its severity due to autonomic dysfunction, covering gastrointestinal, urinary, sexual, cardiovascular and thermoregulatory domains. Patients were also evaluated for the orthostatic hypotension. Results: Although dementia with Lewy body (DLB patients were oldest and duration of disease was longest in IPD, total ADQ scores of MSA and PSP (23.9 ± 12.6 and 21.1 ± 7.8 were significantly increased than that of IPD (15.1 ± 10.6. Urinary and cardiovascular symptom scores of MSA and gastrointestinal symptom score of PSP were significantly worse than those of IPD. The ratio of patient with orthostatic hypotension in IPD was 31.2% and not differed between groups (35.1% in MSA, 33.3% in DLB and 33.3% in PSP. But the systolic blood pressure dropped drastically after standing in patients with MSA and DLB than in patients with IPD and PSP. Conclusions: Patients with degenerative parkinsonism showed widespread symptoms of autonomic dysfunctions. The severity of those symptoms in patients with PSP were comparing to that of MSA patients and worse than that of IPD.

  13. Relationships of Behavioral Measures of Frontal Lobe Dysfunction with Underlying Electrophysiology in Cocaine-Dependent Patients

    Science.gov (United States)

    Gjini, Klevest; Qazi, Aisha; Greenwald, Mark K.; Sandhu, Ravinder; Gooding, Diane C.; Boutros, Nash N.

    2013-01-01

    Background and Objectives Despite evidence that frontal lobe functioning is impaired in cocaine-dependent individuals, relationships between behavioral measures of frontal dysfunction and electrophysiological measures of inhibition in cocaine use have not been explored. Methods Using the Frontal System Behavior Scale (FrSBe), frontal dysfunction was assessed in a group of abstinent cocaine-dependent subjects (N=49) and healthy controls (N=32). Using transcranial magnetic stimulation (TMS) and evoked potential (EP)-based electrophysiological measures of inhibition, we assessed associations between these measures and FrSBe estimates of frontal dysfunction. Results Patients had significantly higher FrSBe scores for executive dysfunction, disinhibition and apathy than controls. Lower TMS-based resting motor thresholds (i.e., hyperexcitability) were significantly associated with higher Executive Dysfunction scores in the patients. Conclusions and Scientific Significance Relationships between FrSBe scores and TMS-based measures highlight neurophysiological aberrations underlying frontal lobe dysfunction in cocaine abusers. TMS and EP measures may be useful probes of the intermediary steps between frontal lobe dysfunction and addictive behavior. PMID:24724884

  14. The effect of cold temperature on increased exacerbation of chronic obstructive pulmonary disease: a nationwide study.

    Directory of Open Access Journals (Sweden)

    Ching-Min Tseng

    Full Text Available BACKGROUND: Seasonal variations in the acute exacerbation of chronic obstructive pulmonary disease (COPD have been reported. However, the influence of air temperature and other meteorological factors on COPD exacerbation remains unclear. METHODS: National Health Insurance registry data from January 1, 1999 to December 1, 2009 and meteorological variables from the Taiwan Central Weather Bureau for the same period were analyzed. A case-crossover study design was used to investigate the association between COPD exacerbation and meteorological variables. RESULTS: A total of 16,254 cases who suffered from COPD exacerbation were enrolled. We found that a 1°C decrease in air temperature was associated with a 0.8% increase in the exacerbation rate on event-days (95% confidence interval (CI, 1.015-1.138, p = 0.015. With a 5°C decrease in mean temperature, the cold temperature (28-day average temperature had a long-term effect on the exacerbation of COPD (odds ratio (OR, 1.106, 95% CI 1.063-1.152, p<0.001. In addition, elderly patients and those who did not receive inhaled medication tended to suffer an exacerbation when the mean temperature dropped 5°C. Higher barometric pressure, more hours of sunshine, and lower humidity were associated with an increase in COPD exacerbation. CONCLUSIONS: This study demonstrated the effect of cold temperatures on the COPD exacerbation rate. Elderly patients and those without inhaled medicine before the exacerbation event were affected significantly by lower mean temperatures. A more comprehensive program to prevent cold stress in COPD patients may lead to a reduction in the exacerbations rate of COPD.

  15. The Christmas season as a risk factor for chronic obstructive pulmonary disease exacerbations.

    Science.gov (United States)

    Johnston, Neil W; McIvor, Andrew; Lambert, Kim; Greene, Justina M; Hussack, Pat; Gerhardsson de Verdier, Maria; Higenbottam, Tim; Lewis, Jonathan; Newbold, Paul; Herath, Athula; Jenkins, Martin

    2010-01-01

    Epidemics of hospitalization for chronic obstructive pulmonary disease (COPD) occur annually during the Christmas holidays, and COPD exacerbations commonly coincide with respiratory viral infections. To compare the incidence and determinants of COPD exacerbations occurring between the Christmas holiday period and the remainder of the winter season. Seventy-one subjects with COPD of mixed severity faxed daily symptom diaries to a computer monitoring system from December 1, 2006, to April 30, 2007. Possible exacerbations prompted a home visit for assessment, spirometry and specimen collection for virological testing. Study subjects submitted a total of 95.4% of possible daily symptom diary sheets by fax. Of 114 possible COPD exacerbations detected using the faxed diaries, 110 met the Anthonisen criteria for true exacerbations. A total of 47 exacerbations (mean 6.7/week) occurred during the Christmas holiday period, while 63 exacerbations (mean 4.3/week) occurred during the remainder of winter. Of the Christmas period exacerbations and of those in the balance of winter, 21 (44%) and 20 (32%), respectively, coincided with respiratory viral infections. The incidence of COPD exacerbations during the Christmas period was greater than during the rest of winter in 2006/2007 and peaked immediately before Christmas - in contrast to hospital presentation for COPD, which peaked during the Christmas week. No clear role of respiratory viral infections in the increased rate of exacerbations during the Christmas period was established in the present study. COPD patients were highly compliant with daily symptom reporting using faxed daily diaries, which permitted nearly complete detection of all exacerbations that occurred at incidence.

  16. Physiology of clinical dysfunction of the cerebellum.

    Science.gov (United States)

    Massaquoi, Steve G

    2012-01-01

    Experimental and theoretical research into cerebellar function has begun to converge toward understanding the cerebellum as a "controller" in the engineering sense. The purpose of a controller is to convert high-level intent commands and information describing the current state of a system into low-level control signals suitable for maintaining or changing system behavior. The cerebellar subsystem appears to play this role for parts of the body and other parts of the brain. As with engineering controllers, fundamental functions include stabilization at a fixed posture or state, adjustment of movement or transition amplitude, facilitation of movement/transition speed and crispness of launch and braking, improvement of resistance to disturbances, coordination of control across multiple degrees of freedom, and assistance with estimation and/or prediction of current and future system states. As with adaptive engineering controllers, the cerebellar subsystem also readily tunes itself over time. At a more detailed level, many of the specific actions of cerebellar circuits can be understood in terms of proportional (P), integrator-like (I), and differentiator-like (D) signal processing which are fundamental components of many engineering control systems. This chapter presents an integrated, mechanistic view of ataxia, tremor, and several cerebellar oculomotor signs in terms of PID control and the neural centers that appear to subserve these functions. It also suggests the manner in which impairments in motor learning, perception, and cognition that are associated with cerebellar dysfunction may be viewed from a similar perspective. 2012 Elsevier B.V. All rights reserved.

  17. Cognitive dysfunction in pediatric multiple sclerosis

    Directory of Open Access Journals (Sweden)

    Suppiej A

    2014-07-01

    Full Text Available Agnese Suppiej,1 Elisa Cainelli1,2 1Child Neurology and Clinical Neurophysiology, Pediatric University Hospital, Padua, Italy; 2Lifespan Cognitive Neuroscience Laboratory (LCNL, Department of General Psychology, University of Padua, Italy Abstract: Cognitive and neuropsychological impairments are well documented in adult ­multiple sclerosis (MS. Research has only recently focused on cognitive disabilities in pediatric cases, highlighting some differences between pediatric and adult cases. Impairments in several functions have been reported in children, particularly in relation to attention, processing speed, visual–motor skills, and language. Language seems to be particularly vulnerable in pediatric MS, unlike in adults in whom it is usually preserved. Deficits in executive functions, which are considered MS-specific in adults, have been inconsistently reported in children. In children, as compared to adults, the relationship between cognitive dysfunctions and the two other main symptoms of MS, fatigue and psychiatric disorders, was poorly explored. Furthermore, data on the correlations of cognitive impairments with clinical and neuroimaging features are scarce in children, and the results are often incongruent; interestingly, involvement of corpus callosum and reduced thalamic volume differentiated patients identified as having a cognitive impairment from those without a cognitive impairment. Further studies about pediatric MS are needed in order to better understand the impact of the disease on brain development and the resulting effect on cognitive functions, particularly with respect to different therapeutic strategies. Keywords: central nervous system, child, deficit, IQ, inflammatory demyelination, neuropsychological

  18. "Pure" motor hemiplegia.

    Science.gov (United States)

    Chokroverty, S; Rubino, F A

    1975-01-01

    Attenuation of cerebral evoked responses after stimulation of the median nerve in the hemiplegic limbs suggested that an apparently pure motor hemiplegia in some patients may not have pure involvement of the corticospinal system. Frontoparietal metastasis, infarction in basis pontis and medullary pyramid, and occlusion of internal carotid artery in the neck resulted in pure motor hemiplegia in some individuals. Images PMID:1185228

  19. Artificial molecular motors

    NARCIS (Netherlands)

    Kassem, Salma; van Leeuwen, Thomas; Lubbe, Anouk S.; Wilson, Miriam R.; Feringa, Ben L.; Leigh, David A.

    2017-01-01

    Motor proteins are nature's solution for directing movement at the molecular level. The field of artificial molecular motors takes inspiration from these tiny but powerful machines. Although directional motion on the nanoscale performed by synthetic molecular machines is a relatively new

  20. The Emotional Motor System

    NARCIS (Netherlands)

    Holstege, G.

    1992-01-01

    A large number of new descending motor pathways to caudal brainstem and spinal cord have been recognized recently. Nevertheless all the new pathways seem to belong to one of three motor systems in the central nervous system (CNS). This survey gives an overvieuw of the pathways belonging to the

  1. Modeling Induction Motor Imbalances

    DEFF Research Database (Denmark)

    Armah, Kabenla; Jouffroy, Jerome; Duggen, Lars

    2016-01-01

    This paper gives a study into the development of a generalized model for a three-phase induction motor that offers flexibility of simulating balanced and unbalanced parameter scenarios. By analyzing the interaction of forces within the motor, we achieve our main objective of deriving the system...

  2. Information on stepping motors

    Science.gov (United States)

    Fongarland, G.

    1982-04-01

    The principles of the stepping motors which are often used in servomechanisms are reviewed. Variable reluctance as well as permanent magnet stepping motors are considered. Their operation is explained which includes permanent rotation, starting, stopping, and resonance effects. Several application examples, drawn from problems in automation, are outlined.

  3. GASTROINTESTINAL MANIFESTATIONS OF MITOCHONDRIAL DYSFUNCTION

    Directory of Open Access Journals (Sweden)

    A. A. Ziganshina

    2016-01-01

    Full Text Available Objective: to highlight the current concepts of gastrointestinal manifestations of mitochondrial dysfunction. The data available in Russian and foreign literature on the gastrointestinal manifestations of mitochondrial dysfunction were analyzed. Functional digestive diseases are common in pediatric practice; however, their etiopathogenesis has not been adequately explored today. According to the literature, impaired cellular energy metabolism may underlie gastrointestinal motility disorders in cyclic vomiting syndrome, gastroesophageal reflux, gastric stasis, chronic diarrhea, constipation, intestinal pseudoobstruction, malabsorption syndrome, irritable bowel syndrome, as well as diseases of the liver and pancreas.

  4. Lysosomal dysfunction in neurodegenerative diseases

    Directory of Open Access Journals (Sweden)

    Klaudia Tomala

    2017-05-01

    Full Text Available Recent data advocate for the implication of lysosomes in the development of programmed cell death. Lysosomal dysfunction decreased the efficiency of autophagosome/lysosome fusion that leads to vacuolation of cells. Autophagic vacuoles containing damaged organelles and altered proteins are hallmarks in most neurodegenerative disorders. These aggregates consequently disrupt cellular homeostasis causing neuronal cell death due apoptosis or necrosis. Moreover calpain mediated or mutation inducted lysosomal rupture result in release of lysosomal cathepsins into the cytoplasm and inducing neuronal cell death. In this review we emphasize the pathophysiological mechanism connecting disrupting autophagy – lysosomal pathway and lysosomal dysfunction in neuronal cell death called lysosomal cell death.

  5. Unilateral implicit motor learning deficit in developmental dyslexia.

    Science.gov (United States)

    Yang, Yang; Hong-Yan, Bi

    2011-02-01

    It has been suggested that developmental dyslexia involves various literacy, sensory, motor skill, and processing speed deficits. Some recent studies have shown that individuals with developmental dyslexia exhibit implicit motor learning deficits, which may be related to cerebellar functioning. However, previous studies on implicit motor learning in developmental dyslexics have produced conflicting results. Findings from cerebellar lesion patients have shown that patients' implicit motor learning performance varied when different hands were used to complete tasks. This suggests that dyslexia may have different effects on implicit motor learning between the two hands if cerebellar dysfunction is involved. To specify this question, we used a one-handed version of a serial reaction time task to compare the performance of 27 Chinese children with developmental dyslexics with another 27 age-matched children without reading difficulties. All the subjects were students from two primary schools, Grades 4 to 6. The results showed that children with developmental dyslexic responded more slowly than nondyslexic children, and exhibited no implicit motor learning in the condition of left-hand response. In contrast, there was no significant difference in reaction time between two groups of children when they used the right hand to respond. This finding indicates that children with developmental dyslexia exhibited normal motor skill and implicit motor learning ability provided the right hand was used. Taken together, these results suggested that Chinese children with developmental dyslexia exhibit unilateral deficits in motor skill and implicit motor learning in the left hand. Our findings lend partial support to the cerebellar deficit theory of developmental dyslexia.

  6. Higher Efficiency HVAC Motors

    Energy Technology Data Exchange (ETDEWEB)

    Flynn, Charles Joseph

    2018-02-13

    The objective of this project was to design and build a cost competitive, more efficient heating, ventilation, and air conditioning (HVAC) motor than what is currently available on the market. Though different potential motor architectures among QMP’s primary technology platforms were investigated and evaluated, including through the building of numerous prototypes, the project ultimately focused on scaling up QM Power, Inc.’s (QMP) Q-Sync permanent magnet synchronous motors from available sub-fractional horsepower (HP) sizes for commercial refrigeration fan applications to larger fractional horsepower sizes appropriate for HVAC applications, and to add multi-speed functionality. The more specific goal became the research, design, development, and testing of a prototype 1/2 HP Q-Sync motor that has at least two operating speeds and 87% peak efficiency compared to incumbent electronically commutated motors (EC or ECM, also known as brushless direct current (DC) motors), the heretofore highest efficiency HVACR fan motor solution, at approximately 82% peak efficiency. The resulting motor prototype built achieved these goals, hitting 90% efficiency and .95 power factor at full load and speed, and 80% efficiency and .7 power factor at half speed. Q-Sync, developed in part through a DOE SBIR grant (Award # DE-SC0006311), is a novel, patented motor technology that improves on electronically commutated permanent magnet motors through an advanced electronic circuit technology. It allows a motor to “sync” with the alternating current (AC) power flow. It does so by eliminating the constant, wasteful power conversions from AC to DC and back to AC through the synthetic creation of a new AC wave on the primary circuit board (PCB) by a process called pulse width modulation (PWM; aka electronic commutation) that is incessantly required to sustain motor operation in an EC permanent magnet motor. The Q-Sync circuit improves the power factor of the motor by removing all

  7. Psychological adaptation to life-threatening injury in dyads: the role of dysfunctional disclosure of trauma

    Directory of Open Access Journals (Sweden)

    Laura Pielmaier

    2011-12-01

    Full Text Available Certain modes of trauma disclosure have been found to be associated with more severe symptoms of posttraumatic stress (PTS in different trauma populations: the reluctance to disclose trauma-related thoughts and feelings, a strong urge to talk about it, and physical as well as emotional reactions during disclosure. Although social-contextual influences gain more and more interest in trauma research, no study has yet investigated these “dysfunctional disclosure tendencies” and their association with PTS from an interpersonal perspective.(1 To replicate previous findings on dysfunctional disclosure tendencies in patients with life-threatening injury and their significant others and (2 to study interpersonal associations between dysfunctional disclosure style and PTS at a dyadic level.PTS symptom severity and self-reports on dysfunctional disclosure tendencies were assessed in N=70 dyads comprising one individual with severe traumatic brain injury and a significant other (“proxy” 3 months after injury.Regression analyses predicting PTS symptom severity revealed dysfunctional disclosure tendencies to have incremental validity above and beyond sex, age, and trauma severity within the individual (both patient and proxy, with moderate effect sizes. The interaction between patient's and proxy's disclosure style explained additional portions of the variance in patients’ PTS symptom severity.Findings suggest that dysfunctional disclosure tendencies are related to poorer psychological adaptation to severe traumatic brain injury. This intrapersonal association may be exacerbated by dysfunctional disclosure tendencies on the part of a significant other. Although the results require replication in other trauma samples without brain injury to further generalize the findings beyond the observed population, the study contributes to the expanding literature on the crucial role of interpersonal relationships in trauma recovery.For the abstract or full

  8. To What Extent Can Motor Imagery Replace Motor Execution While Learning a Fine Motor Skill?

    NARCIS (Netherlands)

    Sobierajewicz, Jagna; Szarkiewicz, Sylwia; Prekoracka-Krawczyk, Anna; Jaskowski, Wojciech; van der Lubbe, Robert Henricus Johannes

    2016-01-01

    Motor imagery is generally thought to share common mechanisms with motor execution. In the present study, we examined to what extent learning a fine motor skill by motor imagery may substitute physical practice. Learning effects were assessed by manipulating the proportion of motor execution and

  9. Age exacerbates surgery-induced cognitive impairment and neuroinflammation in Sprague-Dawley rats: the role of IL-4.

    Science.gov (United States)

    Li, Zhe; Liu, Fang; Ma, Hong; White, Paul F; Yumul, Roya; Jiang, Yanhua; Wang, Na; Cao, Xuezhao

    2017-06-15

    Age is the most prominent risk factor for the development of postoperative cognitive dysfunction. This study investigated the potential role of anti-inflammatory interleukin (IL)-4 in age-related differences of surgery-induced cognitive deficits and neuroinflammatory responses. Both adult and aged Sprague-Dawley male rats were subjected to partial hepatectomy or partial hepatectomy with a cisterna magna infusion of IL-4. On postoperative days 1, 3, and 7, the rats were subjected to a reversed Morris water maze test. Hippocampal IL-1β, IL-6, IL-4, and IL-4 receptor (IL-4R) were measured at each time point. Brain derived neurotrophic factor (BDNF), synaptophysin, Ionized calcium-binding adapter molecule 1 (Iba-1), microglial M2 phenotype marker Arg1, and CD200 were also examined in the hippocampus. Age induced an exacerbated cognitive impairment and an amplified neuroinflammatory response triggered by surgical stress on postoperative days 1 and 3. A corresponding decline in the anti-inflammatory cytokine IL-4 and BDNF were also found in the aged rats at the same time point. Treatment with IL-4 downregulated the expression of proinflammatory cytokines (e.g., IL-1β and IL-6), increased the levels of BDNF and synaptophysin in the brain and improved the behavioral performance. An increased Arg1 expression and a high level of CD200 were also observed after a cisterna magna infusion of IL-4. An age-related decrease in IL-4 expression exacerbated surgery-induced cognitive deficits and exaggerated the neuroinflammatory responses. Treatment with IL-4 potentially attenuated these effects by enhancing BDNF and synaptophysin expression, inhibiting microglia activation and decreasing the associated production of proinflammatory cytokines. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Induction motor control

    Science.gov (United States)

    Hansen, Irving G.

    1990-01-01

    Electromechanical actuators developed to date have commonly ultilized permanent magnet (PM) synchronous motors. More recently switched reluctance (SR) motors have been advocated due to their robust characteristics. Implications of work which utilized induction motors and advanced control techniques are discussed. When induction motors are operated from an energy source capable of controlling voltages and frequencies independently, drive characteristics are obtained which are superior to either PM or SR motors. By synthesizing the machine frequency from a high-frequency carrier (nominally 20 kHz), high efficiencies, low distortion, and rapid torque response are available. At this time multiple horsepower machine drives were demonstrated, and work is on-going to develop a 20 hp average, 40 hp peak class of aerospace actuators. This effort is based upon high-frequency power distribution and management techniques developed by NASA for Space Station Freedom.

  11. Induction motor control

    Science.gov (United States)

    Hansen, Irving G.

    Electromechanical actuators developed to date have commonly ultilized permanent magnet (PM) synchronous motors. More recently switched reluctance (SR) motors have been advocated due to their robust characteristics. Implications of work which utilized induction motors and advanced control techniques are discussed. When induction motors are operated from an energy source capable of controlling voltages and frequencies independently, drive characteristics are obtained which are superior to either PM or SR motors. By synthesizing the machine frequency from a high-frequency carrier (nominally 20 kHz), high efficiencies, low distortion, and rapid torque response are available. At this time multiple horsepower machine drives were demonstrated, and work is on-going to develop a 20 hp average, 40 hp peak class of aerospace actuators. This effort is based upon high-frequency power distribution and management techniques developed by NASA for Space Station Freedom.

  12. Evidence for cerebellar dysfunction in Chinese children with developmental dyslexia: an fMRI study.

    Science.gov (United States)

    Yang, Yang; Bi, Hong-Yan; Long, Zhi-Ying; Tao, Sha

    2013-05-01

    Numerous studies reported that developmental dyslexia in alphabetic languages was associated with a wide range of sensorimotor deficits, including balance, motor skill and time estimation, explained by skill automatization deficit hypothesis. Neural correlates of skill automatization deficit point to cerebellar dysfunction. Recently, a behavioral study revealed an implicit motor learning deficit in Chinese children with developmental dyslexia in their left hands, indicating left cerebellar dysfunction. Using functional magnetic resonance imaging (fMRI), our study examined the brain activation during implicit motor learning in 9 Chinese dyslexic and 12 age-matched children. Dyslexic children showed abnormal activations in the left cerebellum, left middle/medial temporal lobe and right thalamus compared with age-matched children during implicit motor learning. These findings provide evidence of cerebellar abnormality in Chinese dyslexic people. Furthermore, dysfunction of the left cerebellum in Chinese dyslexia is inconsistent with the right cerebellum abnormalities that were reported by studies on alphabetic-language dyslexia, suggesting that neurobiological abnormalities of impaired reading are probably language specific.

  13. Neural correlates of the age-related changes in motor sequence learning and motor adaptation in older adults

    Directory of Open Access Journals (Sweden)

    Bradley R King

    2013-04-01

    Full Text Available As the world’s population ages, a deeper understanding of the relationship between aging and motor learning will become increasingly relevant in basic research and applied settings. In this context, this review aims to address the effects of age on motor sequence learning (MSL and motor adaptation (MA with respect to behavioral, neurological and neuroimaging findings. Previous behavioral research investigating the influence of aging on motor learning has consistently reported the following results. First, the initial acquisition of motor sequences is not altered, except under conditions of increased task complexity. Second, older adults demonstrate deficits in motor sequence memory consolidation. And, third, although older adults demonstrate deficits during the exposure phase of MA paradigms, the aftereffects following removal of the sensorimotor perturbation are similar to young adults, suggesting that the adaptive ability of older adults is relatively intact. This paper will review the potential neural underpinnings of these behavioral results, with a particular emphasis on the influence of age-related dysfunctions in the cortico-striatal system on motor learning.

  14. STEPPING MOTOR - HYDRAULIC MOTOR SERVO DRIVES FOR ...

    African Journals Online (AJOL)

    Dr Obe

    machine tool systems wherever the existing production batch sizes and frequency of manufacture justifies it in a developing country. This is so mainly because numerically controlled (NC) ... Because the NC machine is an expensive item of equipment it is ... electric stepping motor is a very precise unit with. 10k ohms.

  15. Respiratory muscle dysfunction: a multicausal entity in the critically ill patient undergoing mechanical ventilation.

    Science.gov (United States)

    Díaz, Magda C; Ospina-Tascón, Gustavo A; Salazar C, Blanca C

    2014-02-01

    Respiratory muscle dysfunction, particularly of the diaphragm, may play a key role in the pathophysiological mechanisms that lead to difficulty in weaning patients from mechanical ventilation. The limited mobility of critically ill patients, and of the diaphragm in particular when prolonged mechanical ventilation support is required, promotes the early onset of respiratory muscle dysfunction, but this can also be caused or exacerbated by other factors that are common in these patients, such as sepsis, malnutrition, advanced age, duration and type of ventilation, and use of certain medications, such as steroids and neuromuscular blocking agents. In this review we will study in depth this multicausal origin, in which a common mechanism is altered protein metabolism, according to the findings reported in various models. The understanding of this multicausality produced by the same pathophysiological mechanism could facilitate the management and monitoring of patients undergoing mechanical ventilation. Copyright © 2012 SEPAR. Published by Elsevier Espana. All rights reserved.

  16. Mood and nonmood components of perceived stress and exacerbation of Crohn's disease.

    Science.gov (United States)

    Cámara, Rafael J A; Schoepfer, Alain M; Pittet, Valérie; Begré, Stefan; von Känel, Roland

    2011-11-01

    Diverse psychological factors are involved in the pathophysiology of stress. In order to devise effective intervention strategies, it is important to elucidate which factors play the most important role in the association between psychological stress and exacerbation of Crohn's disease (CD). We hypothesized that the association between perceived stress and exacerbation of CD would remain after removal of mood and anxiety components, which are largely involved in stress perception. In all, 468 adults with CD were recruited and followed in different hospitals and private practices of Switzerland for 18 months. At inclusion, patients completed the Perceived Stress Questionnaire and anxiety and depression were assessed using the Hospital Anxiety and Depression Scale. During the follow-up, gastroenterologists assessed whether patients presented with a CD exacerbation. By means of binary logistic regression analysis, we estimated the factor by which one standard deviation of perceived stress would increase the odds of exacerbation of CD with and without controlling for anxiety and depression. The odds of exacerbation of CD increased by 1.85 times (95% confidence interval 1.43-2.40, P perceived stress. After removing the anxiety and depression components, the residuals of perceived stress were no longer associated with exacerbation of CD. The association between perceived stress and exacerbation of CD was fully attributable to the mood components, specifically anxiety and depression. Future interventional studies should evaluate the treatment of anxiety and depression as a strategy for potential prevention of CD exacerbations. Copyright © 2011 Crohn's & Colitis Foundation of America, Inc.

  17. Psychological Factors and Pain Exacerbation in Knee Osteoarthritis : A Web Based Case-Crossover Study

    NARCIS (Netherlands)

    Erfani, Tahereh; Keefe, Francis; Bennell, Kim; Chen, J; Makovey, J; Metcalf, B; Williams, A.D.; Zhang, Y; Hunter, David

    2015-01-01

    OBJECTIVES: The pain experienced by osteoarthritis (OA) patients is neither constant nor unchanging and patients experience episodes of pain exacerbations. Using an innovative web based case-crossover design, we evaluated whether psychological factors are risk factors for pain exacerbations in

  18. COPD exacerbation: anthropometric characteristics of patients and the frequency of hospital admissions

    Directory of Open Access Journals (Sweden)

    Gashynova K.Y.

    2014-11-01

    Full Text Available Exceptional importance of exacerbations for COPD course prognosing was reflected in the GOLD, 2011, where the number of exacerbations during the past year has been recognized as one of the main criteria of the future risks for patients. The aim of study was to determine the anthropometric indicators that increase the risk of re-hospitalization due to acute exacerbation of COPD. A retrospective analysis of medical records of inpatients who were hospitalized with COPD exacerbation to therapeutic department of CI "Dnipropetrovs’k sixth municipal clinical hospital" of Dnipropetrovsk regional council" during three years was done. It was established that neither sex, nor height, nor weight affect the rate of hospitalization due to COPD exacerbations. Older age is not a factor that increases the risk of hospitalization due to COPD exacerbation (despite the fact that the majority of hospitalized patients were elderly patients, 37% of them were persons of potentially working age. Severe exacerbation of COPD may occur in any patients with, even one year, experience of the disease. Among anthropometric indices, the most important predictor of re-hospitalization due to exacerbation of COPD is BMI<18.5, so its calculation is advisable in long-term observation of patients.

  19. Low-intensity noninvasive ventilation: Lower pressure, more exacerbations of chronic respiratory failure

    Directory of Open Access Journals (Sweden)

    Toru Kadowaki

    2016-01-01

    Conclusions: Attention should be paid to CRF patients who are initially administered LI-NPPV; they should be carefully observed because they can develop more exacerbations of CRF than patients undergoing C-NPPV. If possible, higher initial PS should be administered to prevent CRF exacerbations.

  20. Definitions of Exacerbations Does It Really Matter in Clinical Trials on COPD?

    NARCIS (Netherlands)

    Effing, Tanja W.; Kerstjens, Huib A. M.; Monninkhof, Evelyn M.; van der Valk, Paul D. L. P. M.; Wouters, Emiel F. M.; Postma, Dirkje S.; Zielhuis, Gerhard A.; van der Palen, Job

    Many definitions of COPD exacerbations are reported. The choice for a definition determines the number of exacerbations observed. However, the effect of different definitions on the effect sizes of randomized controlled trials is unclear. This article provides an overview of the large variation of

  1. Definitions of exacerbations: does it really matter in clinical trials on COPD?

    NARCIS (Netherlands)

    Effing-Tijdhof, T.W.; Kerstjens, H.A.; Monninkhof, E.M.; Valk, P.D.L.P.M. van der; Wouters, E.F.; Postma, D.S.; Zielhuis, G.A.; Palen, J. van der

    2009-01-01

    Many definitions of COPD exacerbations are reported. The choice for a definition determines the number of exacerbations observed. However, the effect of different definitions on the effect sizes of randomized controlled trials is unclear. This article provides an overview of the large variation of

  2. Prospective study on the relationship between infections and multiple sclerosis exacerbations

    NARCIS (Netherlands)

    D. Buljevac (Dragan); H.Z. Flach (Zwenneke); W.C.J. Hop (Wim); D. Hijdra; J.D. Laman (Jon); H.F.J. Savelkoul (Huub); F.G.A. van der Meché (Frans); P.A. van Doorn (Pieter); R.Q. Hintzen (Rogier)

    2002-01-01

    textabstractOne of the characteristics of multiple sclerosis is the unpredictable occurrence of exacerbations and remissions. These fluctuations in disease activity are related to alterations in (auto-)immune activity. Exacerbations lead to short-term morbidity, but may also

  3. The use of cellular and molecular biomarkers to manage COPD exacerbations.

    Science.gov (United States)

    Ho, Terence; Dasgupta, Angira; Hargreave, Frederick E; Nair, Parameswaran

    2017-05-01

    Chronic obstructive pulmonary disease (COPD) exacerbations are a common cause of respiratory morbidity and mortality, and have various etiologies. Multiple cellular and molecular biomarkers have been associated with exacerbations. Quantitative sputum cell counts are able to identify the presence and type of bronchitis, which is an important contributor to exacerbations. Their utility to monitor bronchitis and to help treat exacerbations has been evaluated, yet they are not used in routine clinical practice. Areas covered: This review will provide a brief summary of biomarkers utilized in COPD, with a focus on the application of cellular markers for the management of exacerbations. A case study will demonstrate the application of these methods. With quantitative sputum cell counts, the presence of eosinophilic bronchitis predicts corticosteroid-responsiveness, while neutrophilic bronchitis identifies infection and suggests the need for antibiotics. Gastroesophageal reflux-related aspiration and heart failure can also be identified by examining sputum. Expert commentary: Quantitative sputum cytometry is an essential tool in the management of exacerbations of COPD, particularly those prone to frequent exacerbations. Treatment based on sputum cell counts is superior to current guideline-based recommendations to prevent future exacerbations and hospitalizations in observational and single-centre controlled trials. Large multicentre clinical trials are necessary to confirm this.

  4. Viruses and bacteria in acute asthma exacerbations - A GA2LEN-DARE* systematic review

    NARCIS (Netherlands)

    Papadopoulos, N. G.; Christodoulou, I.; Rohde, G.; Agache, I.; Almqvist, C.; Bruno, A.; Bonini, S.; Bont, L.; Bossios, A.; Bousquet, J.; Braido, F.; Brusselle, G.; Canonica, G. W.; Carlsen, K. H.; Chanez, P.; Fokkens, W. J.; Garcia-Garcia, M.; Gjomarkaj, M.; Haahtela, T.; Holgate, S. T.; Johnston, S. L.; Konstantinou, G.; Kowalski, M.; Lewandowska-Polak, A.; Lodrup-Carlsen, K.; Makela, M.; Malkusova, I.; Mullol, J.; Nieto, A.; Eller, E.; Ozdemir, C.; Panzner, P.; Popov, T.; Psarras, S.; Roumpedaki, E.; Rukhadze, M.; Stipic-Markovic, A.; Bom, A. Todo; Toskala, E.; van Cauwenberge, P.; van Drunen, C.; Watelet, J. B.; Xatzipsalti, M.; Xepapadaki, P.; Zuberbier, T.

    P>A major part of the burden of asthma is caused by acute exacerbations. Exacerbations have been strongly and consistently associated with respiratory infections. Respiratory viruses and bacteria are therefore possible treatment targets. To have a reasonable estimate of the burden of disease induced

  5. Case-fatality of COPD exacerbations: a meta-analysis and statistical modeling approach

    DEFF Research Database (Denmark)

    Hoogendoorn, M; Hoogenveen, R T; Rutten-van Mölken, M P

    2010-01-01

    Objective of the study was to estimate the case-fatality of a severe exacerbation from long-term survival data presented in the literature. A literature search identified studies reporting at least 1.5 year survival after a severe COPD exacerbation resulting in hospitalization. Each study's survi...

  6. Cognitive decline tracks motor progression and not disease duration in Parkinson patients

    Directory of Open Access Journals (Sweden)

    BD Riggeal

    2007-01-01

    Full Text Available BD Riggeal1, GP Crucian1, P Seignourel2, CE Jacobson IV1, MS Okun1, RL Rodriguez1, Hubert H Fernandez11Department of Neurology; 2Department of Community Health and Psychology, University of Florida, Gainesville, FL, USAAbstract: We performed an analysis of prospectively-acquired cross sectional data on 106 Parkinson disease (PD patients who underwent comprehensive neuropsychological testing and the Unified Parkinson Disease Rating Scale (UPDRS motor scale. A significant correlation between the UPDRS motor and neuropsychological tests in all cognitive domains except for general intelligence and visuo-spatial function was seen. In this study, cognitive decline within this PD cohort correlated with motor impairment but not disease duration. Our findings suggest that overall cognitive impairment (except visuospatial dysfunction may track motor progression in PD more than duration of disease. Longitudinal studies are needed to confirm our results.Keywords: Parkinson, dementia, cognition, visual-spatial dysfunction

  7. Effects of oral motor therapy in children with cerebral palsy

    Directory of Open Access Journals (Sweden)

    Seray Nural Sigan

    2013-01-01

    Full Text Available Aim: Oral motor dysfunction is a common issue in children with cerebral palsy (CP. Drooling, difficulties with sucking, swallowing, and chewing are some of the problems often seen. In this study, we aimed to research the effect of oral motor therapy on pediatric CP patients with feeding problems. Materials and Methods: Included in this single centered, randomized, prospective study were 81 children aged 12-42 months who had been diagnosed with CP, had oral motor dysfunction and were observed at the Pediatric Neurology outpatient clinic of the Children′s Health and Diseases Department, Istanbul Medical Faculty, Istanbul University. Patients were randomized into two groups: The training group and the control group. One patient from the training group dropped out of the study because of not participating regularly. Following initial evaluation of all patients by a blinded physiotherapist and pedagogue, patients in the training group participated in 1 h oral motor training sessions with a different physiotherapist once a week for 6 months. All patients kept on routine physiotherapy by their own physiotherapists. Oral motor assessment form, functional feeding assessment (FFA subscale of the multidisciplinary feeding profile (MFP and the Bayley scales of infant development (BSID-II were used to evaluate oral motor function, swallowing, chewing, the gag reflex, the asymmetrical tonic neck reflex, tongue, jaw, and mouth function, severity of drooling, aspiration, choking, independent feeding and tolerated food texture during the initial examination and 6 months later. Results: When the initial and post-therapy FFA and BSID-II scores received by patients in the training and the study group were compared, the training group showed a statistically significant improvement (P < 0.05. Conclusion: Oral motor therapy has a beneficial effect on feeding problems in children with CP.

  8. The Food Contaminant Deoxynivalenol Exacerbates the Genotoxicity of Gut Microbiota.

    Science.gov (United States)

    Payros, Delphine; Dobrindt, Ulrich; Martin, Patricia; Secher, Thomas; Bracarense, Ana Paula F L; Boury, Michèle; Laffitte, Joelle; Pinton, Philippe; Oswald, Eric; Oswald, Isabelle P

    2017-03-14

    An increasing number of human beings from developed countries are colonized by Escherichia coli strains producing colibactin, a genotoxin suspected to be associated with the development of colorectal cancers. Deoxynivalenol (DON) is the most prevalent mycotoxin that contaminates staple food-especially cereal products-in Europe and North America. This study investigates the effect of the food contaminant DON on the genotoxicity of the E. coli strains producing colibactin. In vitro, intestinal epithelial cells were coexposed to DON and E. coli producing colibactin. In vivo, newborn rats colonized at birth with E. coli producing colibactin were fed a DON-contaminated diet. Intestinal DNA damage was estimated by the phosphorylation of histone H2AX. DON exacerbates the genotoxicity of the E. coli producing colibactin in a time- and dose-dependent manner in vitro Although DON had no effect on the composition of the gut microbiota, and especially on the number of E. coli, a significant increase in DNA damage was observed in intestinal epithelial cells of animals colonized by E. coli strains producing colibactin and coexposed to DON compared to animals colonized with E. coli strains unable to produce colibactin or animals exposed only to DON. In conclusion, our data demonstrate that the genotoxicity of E. coli strains producing colibactin, increasingly present in the microbiota of asymptomatic human beings, is modulated by the presence of DON in the diet. This raises questions about the synergism between food contaminants and gut microbiota with regard to intestinal carcinogenesis.IMPORTANCE An increasing number of human beings from developed countries are colonized by Escherichia coli strains producing colibactin, a genotoxin suspected to be associated with the development of colorectal cancers. Deoxynivalenol (DON) is the most prevalent mycotoxin that contaminates staple food-especially cereal products-in Europe and North America. Our in vitro and in vivo results

  9. Factors influencing exacerbation-related self-management in patients with COPD: a qualitative study

    Directory of Open Access Journals (Sweden)

    Korpershoek YJG

    2016-11-01

    Full Text Available YJG Korpershoek,1,2 SCJM Vervoort,3 LIT Nijssen,2 JCA Trappenburg,2 MJ Schuurmans1,2 1Research Group Chronic Illnesses, Faculty of Health Care, University of Applied Sciences Utrecht, 2Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, 3Cancer Center, University Medical Center Utrecht, Utrecht, the Netherlands Background: In patients with COPD, self-management skills are important to reduce the impact of exacerbations. However, both detection and adequate response to exacerbations appear to be difficult for some patients. Little is known about the underlying process of exacerbation-related self-management. Therefore, the objective of this study was to identify and explain the underlying process of exacerbation-related self-management behavior.Methods: A qualitative study using semi-structured in-depth interviews was performed according to the grounded theory approach, following a cyclic process in which data collection and data analysis alternated. Fifteen patients (male n=8; age range 59–88 years with mild to very severe COPD were recruited from primary and secondary care settings in the Netherlands, in 2015.Results: Several patterns in exacerbation-related self-management behavior were identified, and a conceptual model describing factors influencing exacerbation-related self-management was developed. Acceptance, knowledge, experiences with exacerbations, perceived severity of symptoms and social support were important factors influencing exacerbation-related self-management. Specific factors influencing recognition of exacerbations were heterogeneity of exacerbations and habituation to symptoms. Feelings of fear, perceived influence on exacerbation course, patient beliefs, ambivalence toward treatment, trust in health care providers and self-empowerment were identified as specific factors influencing self-management actions.Conclusion: This study provided insight into factors influencing exacerbation

  10. Swallowing dysfunction in cancer patients

    NARCIS (Netherlands)

    Raber-Durlacher, J.E.; Brennan, M.T.; Verdonck- de Leeuw, I.M.; Gibson, R.J.; Eilers, J.G.; Waltimo, T.; Bots, C.P.; Michelet, M.; Sollecito, T.P.; Rouleau, T.S.; Sewnaik, A.; Bensadoun, R.J.; Fliedner, M.C.; Silverman, S.; Spijkervet, F.K.L.

    2012-01-01

    Purpose Dysphagia (swallowing dysfunction) is a debilitating, depressing, and potentially life-threatening complication in cancer patients that is likely underreported. The present paper is aimed to review relevant dysphagia literature between 1990 and 2010 with a focus on assessment tools,

  11. Markers of primary graft dysfunction

    DEFF Research Database (Denmark)

    2012-01-01

    The present invention relates to methods for diagnosing transplant rejection, or a condition associated with transplant rejection, such as, primary graft dysfunction in a subject, to antigen probe arrays for performing such a diagnosis, and to antigen probe sets for generating such arrays....

  12. Photobiomodulation on alcohol induced dysfunction

    Science.gov (United States)

    Yang, Zheng-Ping; Liu, Timon C.; Zhang, Yan; Wang, Yan-Fang

    2007-05-01

    Alcohol, which is ubiquitous today, is a major health concern. Its use was already relatively high among the youngest respondents, peaked among young adults, and declined in older age groups. Alcohol is causally related to more than 60 different medical conditions. Overall, 4% of the global burden of disease is attributable to alcohol, which accounts for about as much death and disability globally as tobacco and hypertension. Alcohol also promotes the generation of reactive oxygen species (ROS) and/or interferes with the body's normal defense mechanisms against these compounds through numerous processes, particularly in the liver. Photobiomodulation (PBM) is a cell-specific effect of low intensity monochromatic light or low intensity laser irradiation (LIL) on biological systems. The cellular effects of both alcohol and LIL are ligand-independent so that PBM might rehabilitate alcohol induced dysfunction. The PBM on alcohol induced human neutrophil dysfunction and rat chronic atrophic gastritis, the laser acupuncture on alcohol addiction, and intravascular PBM on alcoholic coma of patients and rats have been observed. The endonasal PBM (EPBM) mediated by Yangming channel, autonomic nervous systems and blood cells is suggested to treat alcohol induced dysfunction in terms of EPBM phenomena, the mechanism of alcohol induced dysfunction and our biological information model of PBM. In our opinion, the therapeutic effects of PBM might also be achieved on alcoholic myopathy.

  13. Current Concepts in Ejaculatory Dysfunction

    Science.gov (United States)

    Wolters, Jeffrey P; Hellstrom, Wayne J. G

    2006-01-01

    Although erectile dysfunction has recently become the most well-known aspect of male sexual dysfunction, the most prevalent male sexual disorders are ejaculatory dysfunctions. Ejaculatory disorders are divided into 4 categories: premature ejaculation (PE), delayed ejaculation, retrograde ejaculation, and anejaculation/anorgasmia. Pharmacologic treatment for certain ejaculatory disorders exists, for example the off-label use of selective serotonin reuptake inhibitors for PE. Unfortunately, the other ejaculatory disorders are less studied and not as well understood. This review revisits the physiology of the normal ejaculatory response, specifically explores the mechanisms of anejaculation, and presents emerging data. The neurophysiology of the ejaculatory reflex is complex, making classification of the role of individual neurotransmitters extremely difficult. However, recent research has elucidated more about the role of serotonin and dopamine at the central level in the physiology of both arousal and orgasm. Other recent studies that look at differing pharmacokinetic profiles and binding affinities of the α1-antagonists serve as an indication of the centrally mediated role of ejaculation and orgasm. As our understanding of the interaction between central and peripheral modulations and regulation of the process of ejaculation increases, the probability of developing centrally acting pharmaceutical agents for the treatment of sexual dysfunction approaches reality. PMID:17215997

  14. Sweating dysfunction in Parkinson's disease

    NARCIS (Netherlands)

    Swinn, L; Schrag, A; Viswanathan, R; Lees, A; Quinn, N; Bloem, Bastiaan R.

    2003-01-01

    We sought to determine the prevalence and nature of sweating disturbances in patients with Parkinson's disease (PD), and investigated their correlation with other clinical features and with Quality of Life (QoL) measures. A questionnaire on symptoms and consequences of sweating dysfunction was

  15. Swallowing dysfunction in cancer patients

    NARCIS (Netherlands)

    Raber-Durlacher, Judith E.; Brennan, Mike T.; Leeuw, Irma M. Verdonck-de; Gibson, Rachel J.; Eilers, June G.; Waltimo, Tuomas; Bots, Casper P.; Michelet, Marisol; Sollecito, Thomas P.; Rouleau, Tanya S.; Sewnaik, Aniel; Bensadoun, Rene-Jean; Fliedner, Monica C.; Silverman, Sol; Spijkervet, Fred K. L.

    Purpose Dysphagia (swallowing dysfunction) is a debilitating, depressing, and potentially life-threatening complication in cancer patients that is likely underreported. The present paper is aimed to review relevant dysphagia literature between 1990 and 2010 with a focus on assessment tools,

  16. Bronchiectasis exacerbation study on azithromycin and amoxycillin-clavulanate for respiratory exacerbations in children (BEST-2: study protocol for a randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Chang Anne B

    2013-02-01

    Full Text Available Abstract Background Bronchiectasis unrelated to cystic fibrosis (CF is being increasingly recognized in children and adults globally, both in resource-poor and in affluent countries. However, high-quality evidence to inform management is scarce. Oral amoxycillin-clavulanate is often the first antibiotic chosen for non-severe respiratory exacerbations, because of the antibiotic-susceptibility patterns detected in the respiratory pathogens commonly associated with bronchiectasis. Azithromycin has a prolonged half-life, and with its unique anti-bacterial, immunomodulatory, and anti-inflammatory properties, presents an attractive alternative. Our proposed study will test the hypothesis that oral azithromycin is non-inferior (within a 20% margin to amoxycillin-clavulanate at achieving resolution of non-severe respiratory exacerbations by day 21 of treatment in children with non-CF bronchiectasis. Methods This will be a multicenter, randomized, double-blind, double-dummy, placebo-controlled, parallel group trial involving six Australian and New Zealand centers. In total, 170 eligible children will be stratified by site and bronchiectasis etiology, and randomized (allocation concealed to receive: 1 azithromycin (5 mg/kg daily with placebo amoxycillin-clavulanate or 2 amoxycillin-clavulanate (22.5 mg/kg twice daily with placebo azithromycin for 21 days as treatment for non-severe respiratory exacerbations. Clinical data and a parent-proxy cough-specific quality of life (PC-QOL score will be obtained at baseline, at the start and resolution of exacerbations, and on day 21. In most children, blood and deep-nasal swabs will also be collected at the same time points. The primary outcome is the proportion of children whose exacerbations have resolved at day 21. The main secondary outcome is the PC-QOL score. Other outcomes are: time to next exacerbation; requirement for hospitalization; duration of exacerbation, and spirometry data. Descriptive viral and

  17. Exacerbations of asthma during pregnancy: Impact on pregnancy complications and outcome.

    Science.gov (United States)

    Ali, Z; Hansen, A V; Ulrik, C S

    2016-05-01

    Asthma is common among pregnant women, and the incidence of asthma exacerbations during pregnancy is high. This literature review provides an overview of the impact of exacerbations of asthma during pregnancy on pregnancy-related complications. The majority of published retrospective studies reveal that asthma exacerbations during pregnancy increase the risk of pre-eclampsia, gestational diabetes, placental abruption and placenta praevia. Furthermore, these women also have higher risk for breech presentation, haemorrhage, pulmonary embolism, caesarean delivery, maternal admission to the intensive care unit and longer postpartum hospital stay. Asthma has been associated with increased risk of intrauterine growth retardation, small-for-gestational age, low birth weight, infant hypoglycaemia and preterm birth, but more recent prospective studies have not revealed significant associations with regard to these outcomes. In conclusion, asthma exacerbations during pregnancy are associated with complications of pregnancy, labour and delivery. Prevention of exacerbations is essential to reduce the risk of complications and poor outcome.

  18. Viruses and bacteria in acute asthma exacerbations - A GA(2) LEN-DARE* systematic review

    DEFF Research Database (Denmark)

    Papadopoulos, N G; Christodoulou, I; Rohde, G

    2011-01-01

    and bacteria in acute asthma exacerbations - A GA(2) LEN-DARE systematic review. Allergy 2010; DOI: 10.1111/j.1398-9995.2010.02505.x. ABSTRACT: A major part of the burden of asthma is caused by acute exacerbations. Exacerbations have been strongly and consistently associated with respiratory infections...... and sensitive methodologies. This systematic review summarizes current knowledge and developments in infection epidemiology of acute asthma in children and adults, describing the known impact for each individual agent and highlighting knowledge gaps. Among infectious agents, human rhinoviruses are the most...... prevalent in regard to asthma exacerbations. The newly identified type-C rhinoviruses may prove to be particularly relevant. Respiratory syncytial virus and metapneumovirus are important in infants, while influenza viruses seem to induce severe exacerbations mostly in adults. Other agents are relatively...

  19. Predicting an asthma exacerbation in children 2 to 5 years of age

    DEFF Research Database (Denmark)

    Swern, A.S.; Tozzi, C.A.; Knorr, B.

    2008-01-01

    BACKGROUND: Asthma exacerbations in young children are prevalent. Identification of symptoms or other factors that are precursors of asthma exacerbations would be useful for early treatment and prevention. OBJECTIVES: To determine whether diary symptoms and beta2-agonist use before an exacerbation...... could predict an asthma exacerbation in children 2 to 5 years of age. METHODS: Post hoc analyses were conducted on data collected in a study of 689 patients 2 to 5 years of age with asthma symptoms, randomly assigned to montelukast, 4 mg, or placebo daily for 12 weeks. During the study, 196 patients had...... an exacerbation. Caregiver-reported information (daytime cough, breathing difficulties, limitation of activity, nighttime cough or awakening, daytime and nighttime beta2-agonist use) were analyzed using general estimating equations with an exchangeable within-subject log odds ratio regression structure...

  20. Statin use and exacerbations in individuals with chronic obstructive pulmonary disease

    DEFF Research Database (Denmark)

    Ingebrigtsen, Truls S; Marott, Jacob L; Nordestgaard, Børge G

    2015-01-01

    of follow-up we recorded exacerbations with hospital admissions or oral corticosteroid treatment. In a nested case-control design, matching on age, gender, smoking, COPD severity and comorbidity, we estimated the association between statin use and exacerbations. In addition, we examined the association......BACKGROUND: We tested the hypothesis that statin use in individuals with COPD is associated with a reduced risk of exacerbations. METHODS: We identified 5794 individuals with COPD and a measurement of C reactive protein (CRP) in the Copenhagen General Population Study (2003-2008). During 3 years...... between statin use and high CRP (>3 mg/L), and the association between high CRP and exacerbations during follow-up. RESULTS: Statin use was associated with reduced odds of exacerbations in crude analysis, OR=0.68 (95% CI 0.51 to 0.91, p=0.01), as well as in multivariable conditional logistic regression...

  1. Endosomal accumulation of APP in wobbler motor neurons reflects impaired vesicle trafficking: Implications for human motor neuron disease

    OpenAIRE

    Troakes Claire; Shaw Christopher; Heimann Peter; Golfi Panagiota; Palmisano Ralf; Schmitt-John Thomas; Bartsch Jörg W

    2011-01-01

    Abstract Background The cause of sporadic amyotrophic lateral sclerosis (ALS) is largely unknown but hypotheses about disease mechanisms include oxidative stress, defective axonal transport, mitochondrial dysfunction and disrupted RNA processing. Whereas familial ALS is well represented by transgenic mutant SOD1 mouse models, the mouse mutant wobbler (WR) develops progressive motor neuron degeneration due to a point mutation in the Vps54 gene, and provides an animal model for sporadic ALS. VP...

  2. Improve Motor System Efficiency for a Broad Range of Motors with MotorMaster+ International

    Energy Technology Data Exchange (ETDEWEB)

    None

    2005-05-01

    Available at no charge, MotorMaster+ International is designed to support motor systems improvement planning at industrial facilities by identifying the most cost-effective choice when deciding to repair or replace older motor models.

  3. Exendin-4 Protected against Cognitive Dysfunction in Hyperglycemic Mice Receiving an Intrahippocampal Lipopolysaccharide Injection

    Science.gov (United States)

    Liang, Keng-Chen; Jheng, Yu-Syuan; Jhao, Jhih-Jhen; Su, Ming-Tsan; Lee-Chen, Guey-Jen; Hsieh-Li, Hsiu Mei

    2012-01-01

    Background Chronic hyperglycemia-associated inflammation plays critical roles in disease initiation and the progression of diabetic complications, including Alzheimer’s disease (AD). However, the association of chronic hyperglycemia with acute inflammation of the central nervous system in the progression of AD still needs to be elucidated. In addition, recent evidence suggests that Glucagon-like peptide-1 receptor (GLP-1R) protects against neuronal damage in the brain. Therefore, the neuroprotective effects of the GLP-1R agonist exendin-4 (EX-4) against hyperglycemia/lipopolysaccharides (LPS) damage were also evaluated in this study. Methodology/Principal Findings Ten days after streptozotocin (STZ) or vehicle (sodium citrate) treatment in mice, EX-4 treatment (10 µg/kg/day) was applied to the mice before intrahippocampal CA1 injection of LPS or vehicle (saline) and continued for 28 days. This study examined the molecular alterations in these mice after LPS and EX4 application, respectively. The mouse cognitive function was evaluated during the last 6 days of EX-4 treatment. The results showed that the activation of NF-κB-related inflammatory responses induced cognitive dysfunction in both the hyperglycemic mice and the mice that received acute intrahippocampal LPS injection. Furthermore, acute intrahippocampal LPS injection exacerbated the impairment of spatial learning and memory through a strong decrease in monoaminergic neurons and increases in astrocytes activation and apoptosis in the hyperglycemic mice. However, EX-4 treatment protected against the cognitive dysfunction resulting from hyperglycemia or/and intrahippocampal LPS injection. Conclusions/Significance These findings reveal that both hyperglycemia and intrahippocampal LPS injection induced cognitive dysfunction via activation of NF-κB-related inflammatory responses. However, acute intrahippocampal LPS injection exacerbated the progression of cognitive dysfunction in the hyperglycemic mice via a

  4. ISRO's solid rocket motors

    Science.gov (United States)

    Nagappa, R.; Kurup, M. R.; Muthunayagam, A. E.

    1989-08-01

    Solid rocket motors have been the mainstay of ISRO's sounding rockets and the first generation satellite launch vehicles. For the new launch vehicle under development also, the solid rocket motors contribute significantly to the vehicle's total propulsive power. The rocket motors in use and under development have been developed for a variety of applications and range in size from 30 mm dia employing 450 g of solid propellant—employed for providing a spin to the apogee motors—to the giant 2.8 m dia motor employing nearly 130 tonnes of solid propellant. The initial development, undertaken in 1967 was of small calibre motor of 75 mm dia using a double base charge. The development was essentially to understand the technological elements. Extruded aluminium tubes were used as a rocket motor casing. The fore and aft closures were machined from aluminium rods. The grain was a seven-pointed star with an enlargement of the port at the aft end and was charged into the chamber using a polyester resin system. The nozzle was a metallic heat sink type with graphite throat insert. The motor was ignited with a black powder charge and fired for 2.0 s. Subsequent to this, further developmental activities were undertaken using PVC plastisol based propellants. A class of sounding rockets ranging from 125 to 560 mm calibre were realized. These rocket motors employed improved designs and had delivered lsp ranging from 2060 to 2256 Ns/kg. Case bonding could not be adopted due to the higher cure temperatures of the plastisol propellants but improvements were made in the grain charging techniques and in the design of the igniters and the nozzle. Ablative nozzles based on asbestos phenolic and silica phenolic with graphite inserts were used. For the larger calibre rocket motors, the lsp could be improved by metallic additives. In the early 1970s designs were evolved for larger and more efficient motors. A series of 4 motors for the country's first satellite launch vehicle SLV-3 were

  5. Movement does not promote recovery of motor output following acute experimental muscle pain

    DEFF Research Database (Denmark)

    Schabrun, Siobhan M.; Palsson, Thorvaldur Skuli; Thapa, Tribikram

    2018-01-01

    Objective.:  To examine the effect of motor activity on the magnitude and duration of altered corticomotor output following experimental muscle pain. Design. : Experimental, pre-post test. Setting. : University laboratory. Subjects. : Twenty healthy individuals. Methods.:  Participants were rando....... Understanding corticomotor depression in the postpain period and what factors promote recovery has relevance for clinical pain syndromes where ongoing motor dysfunction, in the absence of pain, may predispose to symptom persistence or recurrence....

  6. Motor synergies research in physical therapy: advantages of the uncontrolled manifold approach

    OpenAIRE

    Vaz,Daniela Virgínia

    2017-01-01

    ABSTRACT Movement is central to physical therapy identity and practice. Advances in the science of movement control, motor learning and development are thus inextricably tied to professional development and clinical activity. This paper aims to describe a prominent approach to motor control with potential to greatly advance the understanding of movement dysfunction: the uncontrolled manifold (UCM). An argument is formulated for incorporating this method of data analysis in rehabilitation rese...

  7. Chronic pain/dysfunction in whiplash-associated disorders.

    Science.gov (United States)

    Davis, C

    2001-01-01

    The purposes of this article are (1) to review current knowledge of and recent concepts pertaining to the causes of chronic pain and/or dysfunction following whiplash-type injuries and (2) to acquaint those who treat these types of injuries with possible mechanisms of continued pain and or dysfunction following whiplash. A review of the literature on mechanisms of injury and neurologic considerations was undertaken. A hand search of relevant medical, neuroscience, chiropractic, and online Index Medicus sources and other sources involving mechanisms of nociception, neurotransmitters, and receptors that might evolve from whiplash-type soft tissue injuries was conducted. Pain is a complex phenomenon that has great variability. Chronic pain appears to involve a deficient descending inhibitory process and/or ongoing excitatory input. There is a wide variety of reactions by individuals to any given type of stimulus. Injury may lead to increases in neuronal activity and prolonged changes in the nervous system. Chronic pain may be seen as part of a central disturbance accompanied by disinhibition or sensitization of central pain modulation, mirrored in the immune and endocrine systems. Patients with chronic whiplash syndrome may have a generalized central hyperexcitability from a loss of tonic inhibitory input (disinhibition) and/or ongoing excitatory input contributing to dorsal horn hyperexcitability. Dysfunction of the motor system may also occur, with or without pain. The purpose of treatment should be not only to relieve pain but also to allow for proper proprioception.

  8. Walking, Gross Motor Development, and Brain Functional Connectivity in Infants and Toddlers.

    Science.gov (United States)

    Marrus, Natasha; Eggebrecht, Adam T; Todorov, Alexandre; Elison, Jed T; Wolff, Jason J; Cole, Lyndsey; Gao, Wei; Pandey, Juhi; Shen, Mark D; Swanson, Meghan R; Emerson, Robert W; Klohr, Cheryl L; Adams, Chloe M; Estes, Annette M; Zwaigenbaum, Lonnie; Botteron, Kelly N; McKinstry, Robert C; Constantino, John N; Evans, Alan C; Hazlett, Heather C; Dager, Stephen R; Paterson, Sarah J; Schultz, Robert T; Styner, Martin A; Gerig, Guido; Schlaggar, Bradley L; Piven, Joseph; Pruett, John R

    2018-02-01

    Infant gross motor development is vital to adaptive function and predictive of both cognitive outcomes and neurodevelopmental disorders. However, little is known about neural systems underlying the emergence of walking and general gross motor abilities. Using resting state fcMRI, we identified functional brain networks associated with walking and gross motor scores in a mixed cross-sectional and longitudinal cohort of infants at high and low risk for autism spectrum disorder, who represent a dimensionally distributed range of motor function. At age 12 months, functional connectivity of motor and default mode networks was correlated with walking, whereas dorsal attention and posterior cingulo-opercular networks were implicated at age 24 months. Analyses of general gross motor function also revealed involvement of motor and default mode networks at 12 and 24 months, with dorsal attention, cingulo-opercular, frontoparietal, and subcortical networks additionally implicated at 24 months. These findings suggest that changes in network-level brain-behavior relationships underlie the emergence and consolidation of walking and gross motor abilities in the toddler period. This initial description of network substrates of early gross motor development may inform hypotheses regarding neural systems contributing to typical and atypical motor outcomes, as well as neurodevelopmental disorders associated with motor dysfunction. © The Author 2017. Published by Oxford University Press.

  9. Study design considerations in a large COPD trial comparing effects of tiotropium with salmeterol on exacerbations

    Directory of Open Access Journals (Sweden)

    Kai-Michael Beeh

    2009-02-01

    Full Text Available Kai-Michael Beeh1, Bettina Hederer2, Thomas Glaab2, Achim Müller2, Maureen Rutten-van Moelken3, et al1insaf–Respiratory Research Institute, Wiesbaden, Germany; 2Boehringer Ingelheim, Ingelheim, Germany; 3Institute for Medical Technology Assessment, Erasmus Medical Centre, Rotterdam, The Netherlands, et alAbstract: Currently available long-acting inhaled bronchodilators (tiotropium, salmeterol, formoterol have demonstrated beneficial effects on exacerbations in placebo-controlled trials. However, there have been no direct comparisons of these drugs with exacerbations as the primary outcome and consequently COPD treatment guidelines do not indicate a preference for either bronchodilator. Therefore, an international, randomized, double-blind, double-dummy, parallelgroup clinical trial has been designed to investigate the comparative efficacy of 2 long-acting bronchodilators tiotropium 18 μg daily and salmeterol 50 μg bid on exacerbations. The trial will include at least 6800 randomized patients with diagnosis of COPD, 10 pack-year history of smoking, post-bronchodilator FEV1 ≤ 70% predicted, and a history of exacerbations in the previous year. The primary endpoint is time to first COPD exacerbation. Secondary endpoints include number of exacerbations and time to premature discontinuation of trial medication. The trial has been designed to address several of the challenges in studying exacerbations in a controlled trial by a symptom and event-based definition of exacerbations, frequent follow-up contacts, selection of time to first event as the primary endpoint and using exposure adjusted analysis when examining number of events. Other challenges in designing exacerbation trials such as differential discontinuation and follow-up of discontinued patients are discussed.Keywords: chronic obstructive pulmonary disease, exacerbation, salmeterol, study methodology, tiotropium

  10. Inflammatory Responses, Spirometry, and Quality of Life in Subjects With Bronchiectasis Exacerbations.

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    Guan, Wei-Jie; Gao, Yong-Hua; Xu, Gang; Lin, Zhi-Ya; Tang, Yan; Li, Hui-Min; Lin, Zhi-Min; Jiang, Mei; Zheng, Jin-Ping; Chen, Rong-Chang; Zhong, Nan-Shan

    2015-08-01

    Bronchiectasis exacerbations are critical events characterized by worsened symptoms and signs (ie, cough frequency, sputum volume, malaise). Our goal was to examine variations in airway and systemic inflammation, spirometry, and quality of life during steady state, bronchiectasis exacerbations, and convalescence (1 week following a 2-week antibiotic treatment) to determine whether potentially pathogenic microorganisms, including Pseudomonas aeruginosa, were associated with poorer conditions during bronchiectasis exacerbations. Peripheral blood and sputum were sampled to detect inflammatory mediators and bacterial densities. Spirometry and quality of life (St George Respiratory Questionnaire [SGRQ]) were assessed during the 3 stages. Forty-eight subjects with bronchiectasis (43.2 ± 14.2 y of age) were analyzed. No notable differences in species and density of potentially pathogenic microorganisms were found during bronchiectasis exacerbations. Except for CXCL8 and tumor necrosis factor alpha (TNF-α), serum inflammation was heightened during bronchiectasis exacerbations and recovered during convalescence. Even though sputum TNF-α was markedly higher during bronchiectasis exacerbations and remained heightened during convalescence, the variations in miscellaneous sputum markers were unremarkable. Bronchiectasis exacerbations were associated with notably higher SGRQ symptom and total scores, which recovered during convalescence. FVC, FEV1, and maximum mid-expiratory flow worsened during bronchiectasis exacerbations (median change from baseline of -2.2%, -0.8%, and -1.3%) and recovered during convalescence (median change from baseline of 0.6%, 0.7%, and -0.7%). Compared with no bacterial isolation, potentially pathogenic microorganism or P. aeruginosa isolation at baseline did not result in poorer clinical condition during bronchiectasis exacerbations. Bronchiectasis exacerbations are characterized by heightened inflammatory responses and poorer quality of life and

  11. Relationship between periodontitis-related antibody and frequent exacerbations in chronic obstructive pulmonary disease.

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    Tamaki Takahashi

    Full Text Available BACKGROUND: To identify patients with chronic obstructive pulmonary disease (COPD who are susceptible to frequent exacerbations is important. Although periodontitis aggravated by poor oral hygiene might increase the risk of lower respiratory tract infection, the relationship between periodontitis and COPD exacerbations remains unknown. This prospective cohort study investigates the relationship between periodontitis-related antibody and exacerbation frequency over a one-year period. METHODS: We assessed an IgG antibody titer against Porphyromonas gingivalis, which is a major pathogen of periodontitis, and then prospectively followed up 93 individuals over one year to detect exacerbations. RESULTS: The numbers of exacerbations and the rate of individuals with frequent exacerbations (at least two per year were significantly lower in patients with higher IgG titer than those with normal IgG titer (0.8 vs. 1.2 per year, p= 0.045 and 14.3 vs. 38.6%, p= 0.009, respectively. Multivariate logistic regression analysis showed that being normal-IgG titer for periodontitis-related antibody significantly increased the risk of frequent exacerbations (relative risk, 5.27, 95% confidence interval, 1.30-25.7; p = 0.019 after adjusting for other possible confounders, such as a history of exacerbations in the past year, disease severity, COPD medication and smoking status. CONCLUSIONS: Normal-IgG titer for periodontitis-related antibody can be an independent predictor of frequent exacerbations. Measuring periodontitis-related antibody titers might be useful to identify patients with susceptibility to frequent exacerbations so that an aggressive prevention strategy can be designed.

  12. Association between autonomic dysfunction and fatigue in Parkinson disease.

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    Chou, Kelvin L; Gilman, Sid; Bohnen, Nicolaas I

    2017-06-15

    Fatigue is a disabling non-motor symptom in Parkinson disease (PD). We investigated the relationship between autonomic dysfunction and fatigue in PD while accounting for possible confounding factors. 29 subjects with PD (8F/21M; mean age 61.6±5.9; mean disease duration 4.8±3.0years), underwent clinical assessment and completed several non-motor symptom questionnaires, including a modified version of the Mayo Clinic Composite Autonomic Symptom Score (COMPASS) scale and the Fatigue Severity Scale (FSS). The mean modified COMPASS was 21.6±14.2 (range 1.7-44.2) and the mean FSS score was 3.3±1.6 (range 1.0-6.7). There was a significant bivariate relationship between the modified COMPASS and FSS scores (R=0.69, P<0.0001). Stepwise regression analysis was used to assess the specificity of the association between the modified COMPASS and FSS scores while accounting for possible confounder effects from other variables that were significantly associated with autonomic dysfunction. Results showed that the modified COMPASS (R 2 =0.52, F=28.4, P<0.0001) was highly associated with fatigue, followed by ESS (R 2 =0.13, F=8.4, P=0.008) but no other co-variates. Post-hoc analysis exploring the association between the different modified COMPASS autonomic sub-domain scores and FSS scores found significant regressor effects for the orthostatic intolerance (R 2 =0.45, F=21.2, P<0.0001) and secretomotor sub-domains (R 2 =0.09, F=4.8, P=0.04) but not for other autonomic sub-domains. Autonomic dysfunction, in particular orthostatic intolerance, is highly associated with fatigue in PD. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. RCAN1 overexpression exacerbates calcium overloading-induced neuronal apoptosis.

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    Xiulian Sun

    Full Text Available Down Syndrome (DS patients develop characteristic Alzheimer's Disease (AD neuropathology after their middle age. Prominent neuronal loss has been observed in the cortical regions of AD brains. However, the underlying mechanism leading to this neuronal loss in both DS and AD remains to be elucidated. Calcium overloading and oxidative stress have been implicated in AD pathogenesis. Two major isoforms of regulator of calcineurin 1 (RCAN1, RCAN1.1 and RCAN1.4, are detected in human brains. In this report we defined the transcriptional regulation of RCAN1.1 and RCAN1.4 by two alternative promoters. Calcium overloading upregulated RCAN1.4 expression by activating RCAN1.4 promoter through calcineurin-NFAT signaling pathway, thus forming a negative feedback loop in isoform 4 regulation. Furthermore, RCAN1.4 overexpression exacerbated calcium overloading-induced neuronal apoptosis, which was mediated by caspase-3 apoptotic pathway. Our results suggest that downregulating RCAN1.4 expression in neurons could be beneficial to AD patients.

  14. RCAN1 overexpression exacerbates calcium overloading-induced neuronal apoptosis.

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    Sun, Xiulian; Wu, Yili; Herculano, Bruno; Song, Weihong

    2014-01-01

    Down Syndrome (DS) patients develop characteristic Alzheimer's Disease (AD) neuropathology after their middle age. Prominent neuronal loss has been observed in the cortical regions of AD brains. However, the underlying mechanism leading to this neuronal loss in both DS and AD remains to be elucidated. Calcium overloading and oxidative stress have been implicated in AD pathogenesis. Two major isoforms of regulator of calcineurin 1 (RCAN1), RCAN1.1 and RCAN1.4, are detected in human brains. In this report we defined the transcriptional regulation of RCAN1.1 and RCAN1.4 by two alternative promoters. Calcium overloading upregulated RCAN1.4 expression by activating RCAN1.4 promoter through calcineurin-NFAT signaling pathway, thus forming a negative feedback loop in isoform 4 regulation. Furthermore, RCAN1.4 overexpression exacerbated calcium overloading-induced neuronal apoptosis, which was mediated by caspase-3 apoptotic pathway. Our results suggest that downregulating RCAN1.4 expression in neurons could be beneficial to AD patients.

  15. Asymmetry in acute exacerbation of idiopathic pulmonary fibrosis

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    Akihiko Sokai

    2017-04-01

    Full Text Available Acute exacerbation (AE of idiopathic pulmonary fibrosis (IPF results in poor survival. The objective of the present study was to elucidate the impact of asymmetrical ground-glass opacity (GGO and/or consolidation on outcomes in patients with AE-IPF. The cases of 59 consecutive patients with AE-IPF were retrospectively reviewed. High-resolution computed tomography (HRCT at diagnosis of an AE was assessed to determine the disease extent and asymmetry. Asymmetrical AE was defined as a right-to-left ratio of GGO and consolidation ≥2.0 or ≤0.5. The impacts of HRCT indices and other clinical parameters on 180-day mortality were analysed. The overall 180-day mortality rate was 59.2%, and asymmetrical AE was observed in 13 patients (22.0%. A multivariate analysis revealed that asymmetrical AE was a significant predictor of 180-day mortality (hazard ratio=0.36, p=0.047, long-term oxygen therapy before AE and serum lactate dehydrogenase levels. The 180-day mortality of patients with asymmetrical AE was significantly lower than that of patients with symmetrical AE (asymmetrical AE 30.8% versus symmetrical AE 68.2%, p=0.03. An asymmetrical distribution of GGO and/or consolidation is a predictor of survival in patients with AE-IPF.

  16. Genetic Mechanisms in Aspirin-Exacerbated Respiratory Disease

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    Nami Shrestha Palikhe

    2012-01-01

    Full Text Available Aspirin-exacerbated respiratory disease (AERD refers to the development of bronchoconstriction in asthmatics following the exposure to aspirin or other nonsteroidal anti-inflammatory drugs. The key pathogenic mechanisms associated with AERD are the overproduction of cysteinyl leukotrienes (CysLTs and increased CysLTR1 expression in the airway mucosa and decreased lipoxin and PGE2 synthesis. Genetic studies have suggested a role for variability of genes in disease susceptibility and the response to medication. Potential genetic biomarkers contributing to the AERD phenotype include HLA-DPB1, LTC4S, ALOX5, CYSLT, PGE2, TBXA2R, TBX21, MS4A2, IL10, ACE, IL13, KIF3A, SLC22A2, CEP68, PTGER, and CRTH2 and a four-locus SNP set composed of B2ADR, CCR3, CysLTR1, and FCER1B. Future areas of investigation need to focus on comprehensive approaches to identifying biomarkers for early diagnosis.

  17. COPD Exacerbation Biomarkers Validated Using Multiple Reaction Monitoring Mass Spectrometry.

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    Janice M Leung

    Full Text Available Acute exacerbations of chronic obstructive pulmonary disease (AECOPD result in considerable morbidity and mortality. However, there are no objective biomarkers to diagnose AECOPD.We used multiple reaction monitoring mass spectrometry to quantify 129 distinct proteins in plasma samples from patients with COPD. This analytical approach was first performed in a biomarker cohort of patients hospitalized with AECOPD (Cohort A, n = 72. Proteins differentially expressed between AECOPD and convalescent states were chosen using a false discovery rate 1.2. Protein selection and classifier building were performed using an elastic net logistic regression model. The performance of the biomarker panel was then tested in two independent AECOPD cohorts (Cohort B, n = 37, and Cohort C, n = 109 using leave-pair-out cross-validation methods.Five proteins were identified distinguishing AECOPD and convalescent states in Cohort A. Biomarker scores derived from this model were significantly higher during AECOPD than in the convalescent state in the discovery cohort (p<0.001. The receiver operating characteristic cross-validation area under the curve (CV-AUC statistic was 0.73 in Cohort A, while in the replication cohorts the CV-AUC was 0.77 for Cohort B and 0.79 for Cohort C.A panel of five biomarkers shows promise in distinguishing AECOPD from convalescence and may provide the basis for a clinical blood test to diagnose AECOPD. Further validation in larger cohorts is necessary for future clinical translation.

  18. A novel respiratory symptom scoring system for CF pulmonary exacerbations.

    Science.gov (United States)

    Jarad, N A; Sequeiros, I M

    2012-02-01

    There is currently no simple scoring system to evaluate change in symptoms during a pulmonary exacerbation (PEx) in adult cystic fibrosis (CF) patients. We evaluated 265 episodes in 58 adult CF patients. A simple symptom score was administered at the start and the end of each PEx. The score evaluated four symptoms: cough, sputum, breathlessness and fatigue. Each symptom was scored from one (mild symptoms) to four (severe symptoms). The total symptom score was the summation of all the four symptoms. The total symptom score was compared with CF Respiratory Questionnaire (CFRQ) and with spirometry. There was significant internal correlation between scores for each pair of symptoms. The total symptom score correlated with the functional activity score and the respiratory score domains and with the summary score for CFRQ. The total symptom score correlated with spirometry values. Symptom score improved after 2-week treatment with intravenous (IV) antibiotics in 88.3%, remained unchanged in 7.3% and worsened in 4.4% of all episodes. Changes in symptom score after IV treatment correlated with changes of all main spirometry measurements. This new symptom score is simple and sensitive to change over a short period. It correlates with established quality-of-life questionnaires and with spirometry. The changes of symptom score over a short period correlate with changes in spirometry. This score can be used as an added tool to assess the outcome of CF PExs.

  19. Increasing temperature exacerbated Classic Maya conflict over the long term

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    Carleton, W. Christopher; Campbell, David; Collard, Mark

    2017-05-01

    The impact of climate change on conflict is an important but controversial topic. One issue that needs to be resolved is whether or not climate change exacerbates conflict over the long term. With this in mind, we investigated the relationship between climate change and conflict among Classic Maya polities over a period of several hundred years (363-888 CE). We compiled a list of conflicts recorded on dated monuments, and then located published temperature and rainfall records for the region. Subsequently, we used a recently developed time-series method to investigate the impact of the climatic variables on the frequency of conflict while controlling for trends in monument number. We found that there was a substantial increase in conflict in the approximately 500 years covered by the dataset. This increase could not be explained by change in the amount of rainfall. In contrast, the increase was strongly associated with an increase in summer temperature. These finding have implications not only for Classic Maya history but also for the debate about the likely effects of contemporary climate change.

  20. Cryoprotectants Severely Exacerbate X-ray-Induced Photoreduction.

    Science.gov (United States)

    Nienaber, Kurt H; Pushie, M Jake; Cotelesage, Julien J H; Pickering, Ingrid J; George, Graham N

    2018-01-19

    Approximately 11% of enzymes contain a transition metal ion that is essential for catalytic function. Such metalloenzymes catalyze much of the most chemically challenging and biologically essential chemistry carried out by life. X-ray-based methods, predominantly macromolecular crystallography (MX) and also X-ray absorption spectroscopy (XAS), have proved essential for determining structures of transition metal ion-containing active sites in order to deduce enzyme catalytic mechanisms. However, X-ray irradiation can induce change in both the oxidation state and structure of the metal, which is problematic in structure determination. We present an XAS study of whether cryoprotectants such as polyethylene glycol (PEG) or glycerol, routinely added to MX or XAS samples to improve data quality, affect photoreduction. Our data demonstrate a remarkable 10-fold exacerbation in rate of photoreduction of Cu(II) to Cu(I) when alcohol or ether cryoprotectants are present. Our results suggest that widespread use of cryoprotectants may increase the potential for erroneous structures.

  1. Aspirin exacerbated respiratory disease: Current topics and trends.

    Science.gov (United States)

    Rodríguez-Jiménez, José Carlos; Moreno-Paz, Fernanda Judith; Terán, Luis Manuel; Guaní-Guerra, Eduardo

    2018-02-01

    Aspirin-exacerbated respiratory disease is a chronic and treatment-resistant disease, characterized by the presence of eosinophilic rhinosinusitis, nasal polyposis, bronchial asthma, and nonsteroidal anti-inflammatory drugs hypersensitivity. Alterations in arachidonic acid metabolism may induce an imbalance between pro-inflammatory and anti-inflammatory substances, expressed as an overproduction of cysteinyl leukotrienes and an underproduction of prostaglandin E2. Although eosinophils play a key role, recent studies have shown the importance of other cells and molecules in the development of the disease like mast cells, basophils, lymphocytes, platelets, neutrophils, macrophages, epithelial respiratory cells, IL-33 and thymic stromal lymphopoietin, making each of them promissory diagnostic and treatment targets. In this review, we summarize the most important clinical aspects of the disease, including the current topics about diagnosis and treatment, like provocation challenges and aspirin desensitization. We also discuss recent findings in the pathogenesis of the disease, as well as future trends in diagnosis and treatment, including monoclonal antibodies and a low salicylate diet as a treatment option. Copyright © 2018 Elsevier Ltd. All rights reserved.

  2. Infection with Porphyromonas gingivalis exacerbates endothelial injury in obese mice.

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    Min Ao

    Full Text Available BACKGROUND: A number of studies have revealed a link between chronic periodontitis and cardiovascular disease in obese patients. However, there is little information about the influence of periodontitis-associated bacteria, Porphyromonas gingivalis (Pg, on pathogenesis of atherosclerosis in obesity. METHODS: In vivo experiment: C57BL/6J mice were fed with a high-fat diet (HFD or normal chow diet (CD, as a control. Pg was infected from the pulp chamber. At 6 weeks post-infection, histological and immunohistochemical analysis of aortal tissues was performed. In vitro experiment: hTERT-immortalized human umbilical vein endothelial cells (HuhT1 were used to assess the effect of Pg/Pg-LPS on free fatty acid (FFA induced endothelial cells apoptosis and regulation of cytokine gene expression. RESULTS: Weaker staining of CD31 and increased numbers of TUNEL positive cells in aortal tissue of HFD mice indicated endothelial injury. Pg infection exacerbated the endothelial injury. Immunohistochemically, Pg was detected deep in the smooth muscle of the aorta, and the number of Pg cells in the aortal wall was higher in HFD mice than in CD mice. Moreover, in vitro, FFA treatment induced apoptosis in HuhT1 cells and exposure to Pg-LPS increased this effect. In addition, Pg and Pg-LPS both attenuated cytokine production in HuhT1 cells stimulated by palmitate. CONCLUSIONS: Dental infection of Pg may contribute to pathogenesis of atherosclerosis by accelerating FFA-induced endothelial injury.

  3. The inflammasome pathway in stable COPD and acute exacerbations

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    Rosa Faner

    2016-07-01

    Full Text Available Chronic obstructive pulmonary disease (COPD is characterised by pulmonary and systemic inflammation that bursts during exacerbations of the disease (ECOPD. The NLRP3 inflammasome is a key regulatory molecule of the inflammatory response. Its role in COPD is unclear. We investigated the NLRP3 inflammasome status in: 1 lung tissue samples from 38 patients with stable COPD, 15 smokers with normal spirometry and 14 never-smokers; and 2 sputum and plasma samples from 56 ECOPD patients, of whom 41 could be reassessed at clinical recovery. We observed that: 1 in lung tissue samples of stable COPD patients, NLRP3 and interleukin (IL-1β mRNA were upregulated, but both caspase-1 and ASC were mostly in inactive form, and 2 during infectious ECOPD, caspase-1, oligomeric ASC and associated cytokines (IL-1β, IL-18 were significantly increased in sputum compared with clinical recovery. The NLRP3 inflammasome is primed, but not activated, in the lungs of clinically stable COPD patients. Inflammasome activation occurs during infectious ECOPD. The results of this study suggest that the inflammasome participates in the inflammatory burst of infectious ECOPD.

  4. Influence of Pseudomonas aeruginosa on exacerbation in patients with bronchiectasis

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    Kiran Chawla

    2015-01-01

    Full Text Available Background: A majority of the studies done on the western population have shown that Pseudomonas aeruginosa causes many severe infections in patients with bronchiectasis as compared to other pathogens. There is scarcity of similar data from the Asian population. Materials and Methods: A prospective study was undertaken to identify the various pathogens isolated from the respiratory samples of 117 patients with bronchiectasis from south India and to compare the clinicomicrobiological profile of infections caused by P. aeruginosa and other respiratory pathogens. Results: The respiratory pathogens were isolated from 63 (53.8% patients. P. aeruginosa was the most common isolate (46.0% followed by Klebsiella pneumoniae (14.3% and other pathogenic bacteria. Patients included in the P. aeruginosa group had a higher number of exacerbations (p: 0.008, greater number of hospital admissions (p: 0.007, a prolonged hospital stay (p: 0.03, and poor lung function, compared to the patients infected with the non-Pseudomonas group. Conclusion: It is necessary to investigate the etiology of respiratory tract infections among bronchiectasis patients followed by the prompt management of cases diagnosed with P. aeruginosa infections, so as to lower the morbidity and have a better prognosis.

  5. RIP3-dependent necrosis induced inflammation exacerbates atherosclerosis

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    Meng, Lingjun, E-mail: menglingjun@nibs.ac.cn [College of Biological Sciences, China Agricultural University, Beijing 100094 (China); National Institute of Biological Sciences, Beijing 102206 (China); Jin, Wei [Institute for Immunology, Tsinghua University, Beijing 100084 (China); Wang, Yuhui [Institute of Cardiovascular Sciences, Health Science Center, Peking University, Beijing 100191 (China); Huang, Huanwei; Li, Jia; Zhang, Cai [National Institute of Biological Sciences, Beijing 102206 (China)

    2016-04-29

    Atherothrombotic vascular disease is already the leading cause of mortality worldwide. Atherosclerosis shares features with diseases caused by chronic inflammation. More attention should concentrates on the innate immunity effect atherosclerosis progress. RIP3 (receptor-interacting protein kinase 3) act through the transcription factor named Nr4a3 (Nuclear orphan receptors) to regulate cytokine production. Deletion RIP3 decreases IL-1α production. Injection of anti-IL-1α antibody protects against the progress of atherosclerosis in ApoE −/− mice. RIP3 as a molecular switch in necrosis, controls macrophage necrotic death caused inflammation. Inhibiting necrosis will certainly reduce atherosclerosis through limit inflammation. Necrotic cell death caused systemic inflammation exacerbated cardiovascular disease. Inhibition of necrosis may yield novel therapeutic targets for treatment in years to come. - Highlights: • RIP3 regulate the Nr4a3 to control cytokine production. • Deletion RIP3 decreases IL-1a production. • Injection anti-IL-1a antibody protects against the progress of atherosclerosis. • RIP3 controls macrophage necrotic dead caused inflammation.

  6. Developmental kinesiology: three levels of motor control in the assessment and treatment of the motor system.

    Science.gov (United States)

    Kobesova, Alena; Kolar, Pavel

    2014-01-01

    Three levels of sensorimotor control within the central nervous system (CNS) can be distinguished. During the neonatal stage, general movements and primitive reflexes are controlled at the spinal and brain stem levels. Analysis of the newborn's spontaneous general movements and the assessment of primitive reflexes is crucial in the screening and early recognition of a risk for abnormal development. Following the newborn period, the subcortical level of the CNS motor control emerges and matures mainly during the first year of life. This allows for basic trunk stabilization, a prerequisite for any phasic movement and for the locomotor function of the extremities. At the subcortical level, orofacial muscles and afferent information are automatically integrated within postural-locomotor patterns. Finally, the cortical (the highest) level of motor control increasingly becomes activated. Cortical control is important for the individual qualities and characteristics of movement. It also allows for isolated segmental movement and relaxation. A child with impaired cortical motor control may be diagnosed with developmental dyspraxia or developmental coordination disorder. Human ontogenetic models, i.e., developmental motor patterns, can be used in both the diagnosis and treatment of locomotor system dysfunction. Copyright © 2013 Elsevier Ltd. All rights reserved.

  7. Preventing and managing exacerbations in COPD – critical appraisal of the role of tiotropium

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    Donald P Tashkin

    2010-02-01

    Full Text Available Donald P TashkinDepartment of Medicine, Division of Pulmonary and Critical Care Medicine, David Geffen School of Medicine at UCLA,Los Angeles, CA, USAAbstract: The course of COPD is punctuated by acute exacerbations that are associated with an increase in the morbidity and mortality related to this chronic disease and may contribute to its rate of progression. Therefore, preventing and treating exacerbations are major goals of COPD management. The role of tiotropium in the prevention of exacerbations has been investigated in several placebo-controlled randomized clinical trials varying in duration from 3 months to 4 years in patients with moderate to very severe COPD. In all of these trials, tiotropium has uniformly reduced the proportion of patients experiencing at least one exacerbation and delayed the time to the first exacerbation compared with placebo. In the longer trials (≥6 months’ duration tiotropium has also reduced the exposure-adjusted incidence rate of exacerbations. In trials of at least 1 year in duration, tiotropium either significantly reduced the risk of hospitalization for an exacerbation and/or the proportion of patients with an exacerbation-related hospitalization. In a meta-analysis that included 15 trials of tiotropium vs either placebo (n = 13 and/or a longacting beta-agonist (LABA; n = 4, tiotropium significantly reduced the odds of experiencing an exacerbation compared to placebo as well as a LABA. The potential additive benefits of tiotropium to those of a LABA and/or inhaled corticosteroid in reducing exacerbations require further investigation. The mechanism whereby tiotropium reduces exacerbations is not due to an anti-inflammatory effect but more likely relates to its property of causing a sustained increase in airway patency and reduction in hyperinflation, thereby counteracting the tendency for respiratory insults to worsen airflow obstruction and hyperinflation. For the management of acute exacerbations, an

  8. Colds as predictors of the onset and severity of COPD exacerbations

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    Johnston NW

    2017-03-01

    Full Text Available Neil W Johnston,1 Marita Olsson,2 Staffan Edsbäcker,3 Maria Gerhardsson de Verdier,4 Per Gustafson,5 Christopher McCrae,3 Peter V Coyle,6 R Andrew McIvor11Department of Medicine, Firestone Institute for Respiratory Health, McMaster University, Hamilton, ON, Canada; 2Early Clinical Development Biometrics, 3Respiratory, Inflammation & Autoimmunity Unit, Innovative Medicines & Early Development, 4Medical Evidence and Observational Research Centre, 5Respiratory, Inflammation & Autoimmunity Translational Medicine Unit, Early Clinical Development, Innovative Medicines & Early Development, AstraZeneca Research and Development, Gothenburg, Molndal, Sweden; 6Regional Virology Laboratory, Belfast HS C Trust, Belfast, UKRationale: Common colds are associated with acute respiratory symptom exacerbations in COPD patients.Objective: To determine exacerbation risk and severity in COPD patients with/without coincident self-reported colds.Methods: Global initiative for chronic Obstructive Lung Disease stage I–IV COPD patients electronically transmitted respiratory symptom diaries to research staff daily between December 2006 and April 2009. Respiratory symptom worsening prompted contact by a study nurse and patient assessment to determine if a cold was present or an exacerbation underway. A composite daily symptom score was derived for each subject from diarized symptom data. The exacerbation/cold/virus relation was examined using a Poisson regression model, the relation of colds to respiratory symptom severity using generalized estimating equation models.Results: Daily diary transmission compliance of >97% enabled detection of all possible exacerbations. Among 262 exacerbations meeting Anthonisen criteria, 218 (83% had cold-like symptoms present at their inception, but respiratory viruses were detected in only 106 (40%. Within-subject exacerbation risk was 30 times (95% confidence interval [CI]: 20, 47; P<0.001 greater with colds present. Compared to cold

  9. Serum CCL-18 level is a risk factor for COPD exacerbations requiring hospitalization

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    Dilektasli AG

    2017-01-01

    Full Text Available Asli Gorek Dilektasli,1 Ezgi Demirdogen Cetinoglu,1 Esra Uzaslan,1 Ferah Budak,2 Funda Coskun,1 Ahmet Ursavas,1 Ilker Ercan,3 Ercument Ege1 1Department of Pulmonary Disesaes, 2Department of Immunology, 3Department of Biostatistics, Uludag University Faculty of Medicine, Bursa, Turkey Introduction: Chemokine (C-C motif ligand 18 (CCL-18 has been shown to be elevated in chronic obstructive pulmonary disease (COPD patients. This study primarily aimed to evaluate whether the serum CCL-18 level differentiates the frequent exacerbator COPD phenotype from infrequent exacerbators. The secondary aim was to investigate whether serum CCL-18 level is a risk factor for exacerbations requiring hospitalization. Materials and methods: Clinically stable COPD patients and participants with smoking history but normal spirometry (NSp were recruited for the study. Modified Medical Research Council Dyspnea Scale, COPD Assessment Test, spirometry, and 6-min walking test were performed. Serum CCL-18 levels were measured with a commercial ELISA Kit. Results: Sixty COPD patients and 20 NSp patients were recruited. Serum CCL-18 levels were higher in COPD patients than those in NSp patients (169 vs 94 ng/mL, P<0.0001. CCL-18 level was significantly correlated with the number of exacerbations (r=0.30, P=0.026, although a difference in CCL-18 values between infrequent and frequent exacerbator COPD (168 vs 196 ng/mL subgroups did not achieve statistical significance (P=0.09. Serum CCL-18 levels were significantly higher in COPD patients who had experienced at least one exacerbation during the previous 12 months. Overall, ROC analysis revealed that a serum CCL-18 level of 181.71 ng/mL could differentiate COPD patients with hospitalized exacerbations from those who were not hospitalized with a 88% sensitivity and 88.2% specificity (area under curve: 0.92. Serum CCL-18 level had a strong correlation with the frequency of exacerbations requiring hospitalization (r=0.68, P<0

  10. Motor cortex hyperexcitability to transcranial magnetic stimulation in Alzheimer's disease.

    Science.gov (United States)

    Di Lazzaro, V; Oliviero, A; Pilato, F; Saturno, E; Dileone, M; Marra, C; Daniele, A; Ghirlanda, S; Gainotti, G; Tonali, P A

    2004-04-01

    Recent transcranial magnetic stimulation (TMS) studies demonstrate that motor cortex excitability is increased in Alzheimer's disease (AD) and that intracortical inhibitory phenomena are impaired. The aim of the present study was to determine whether hyperexcitability is due to the impairment of intracortical inhibitory circuits or to an independent abnormality of excitatory circuits. We assessed the excitability of the motor cortex with TMS in 28 patients with AD using several TMS paradigms and compared the data of cortical excitability (evaluated by measuring resting motor threshold) with the amount of motor cortex disinhibition as evaluated using the test for motor cortex cholinergic inhibition (short latency afferent inhibition) and GABAergic inhibition (short latency intracortical inhibition). The data in AD patients were also compared with that from 12 age matched healthy individuals. The mean resting motor threshold was significantly lower in AD patients than in controls. The amount of short latency afferent inhibition was significantly smaller in AD patients than in normal controls. There was also a tendency for AD patients to have less pronounced short latency intracortical inhibition than controls, but this difference was not significant. There was no correlation between resting motor threshold and measures of either short latency afferent or intracortical inhibition (r = -0.19 and 0.18 respectively, NS). In 14 AD patients the electrophysiological study was repeated after a single oral dose of the cholinesterase inhibitor rivastigmine. Resting motor threshold was not significantly modified by the administration of rivastigmine. In contrast, short latency afferent inhibition from the median nerve was significantly increased by the administration of rivastigmine. The change in threshold did not seem to correlate with dysfunction of inhibitory intracortical cholinergic and GABAergic circuits, nor with the central cholinergic activity. We propose that the

  11. Piezoelectric Rotary Tube Motor

    Science.gov (United States)

    Fisher, Charles D.; Badescu, Mircea; Braun, David F.; Culhane, Robert

    2011-01-01

    A custom rotary SQUIGGLE(Registered TradeMark) motor has been developed that sets new benchmarks for small motor size, high position resolution, and high torque without gear reduction. Its capabilities cannot be achieved with conventional electromagnetic motors. It consists of piezoelectric plates mounted on a square flexible tube. The plates are actuated via voltage waveforms 90 out of phase at the resonant frequency of the device to create rotary motion. The motors were incorporated into a two-axis postioner that was designed for fiber-fed spectroscopy for ground-based and space-based projects. The positioner enables large-scale celestial object surveys to take place in a practical amount of time.

  12. Human spinal motor control

    DEFF Research Database (Denmark)

    Nielsen, Jens Bo

    2016-01-01

    interneurons and exert a direct (willful) muscle control with the aid of a context-dependent integration of somatosensory and visual information at cortical level. However, spinal networks also play an important role. Sensory feedback through spinal circuitries is integrated with central motor commands...... and contributes importantly to the muscle activity underlying voluntary movements. Regulation of spinal interneurons is used to switch between motor states such as locomotion (reciprocal innervation) and stance (coactivation pattern). Cortical regulation of presynaptic inhibition of sensory afferents may focus...... the central motor command by opening or closing sensory feedback pathways. In the future, human studies of spinal motor control, in close collaboration with animal studies on the molecular biology of the spinal cord, will continue to document the neural basis for human behavior. Expected final online...

  13. Motor Carrier Crash Data -

    Data.gov (United States)

    Department of Transportation — Contains data on large trucks and buses involved in Federally reportable crashes as per Title 49 U.S.C. Part 390.5 (crashes involving a commercial motor vehicle, and...

  14. Molecular motors: Dynein's gearbox.

    Science.gov (United States)

    Cross, R A

    2004-05-04

    A new optical trapping study shows that the stepsize of cytoplasmic dynein varies according to the applied force, suggesting that this motor can change gear. Complementary biochemical kinetic work on yeast dynein mutants hints at the allosteric mechanisms involved.

  15. Erectile dysfunction among men attending surgical outpatients ...

    African Journals Online (AJOL)

    Background: Erectile dysfunction is becoming a public health issue with high incidences reported in community studies. Objective: To evaluate the characteristics and outcome of treatment in men with erectile dysfunction in a tertiary center in Ibadan southwestern Nigeria. Methods: Data of men with erectile dysfunction was ...

  16. Autonomic Dysfunction in Muscular Dystrophy: A Theoretical Framework for Muscle Reflex Involvement

    Directory of Open Access Journals (Sweden)

    Scott Alan Smith

    2014-02-01

    Full Text Available Muscular dystrophies are a heterogeneous group of genetically inherited disorders whose most prominent clinical feature is progressive degeneration of skeletal muscle. In several forms of the disease, the function of cardiac muscle is likewise affected. The primary defect in this group of diseases is caused by mutations in myocyte proteins important to cellular structure and/or performance. That being stated, a growing body of evidence suggests that the development of autonomic dysfunction may secondarily contribute to the generation of skeletal and cardio-myopathy in muscular dystrophy. Indeed, abnormalities in the regulation of both sympathetic and parasympathetic nerve activity have been reported in a number of muscular dystrophy variants. However, the mechanisms mediating this autonomic dysfunction remain relatively unknown. An autonomic reflex originating in skeletal muscle, the exercise pressor reflex, is known to contribute significantly to the control of sympathetic and parasympathetic activity when stimulated. Given the skeletal myopathy that develops with muscular dystrophy, it is logical to suggest that the function of this reflex might also be abnormal with the pathogenesis of disease. As such, it may contribute to or exacerbate the autonomic dysfunction that manifests. This possibility along with a basic description of exercise pressor reflex function in health and disease are reviewed. A better understanding of the mechanisms that possibly underlie autonomic dysfunction in muscular dystrophy may not only facilitate further research but could also lead to the identification of new therapeutic targets for the treatment of muscular dystrophy.

  17. Clinical management of chronic obstructive pulmonary disease patients with muscle dysfunction

    Science.gov (United States)

    Casadevall, Carme; Pascual, Sergi; Orozco-Levi, Mauricio; Barreiro, Esther

    2016-01-01

    Muscle dysfunction is frequently observed in chronic obstructive pulmonary disease (COPD) patients, contributing to their exercise limitation and a worsening prognosis. The main factor leading to limb muscle dysfunction is deconditioning, whereas respiratory muscle dysfunction is mostly the result of pulmonary hyperinflation. However, both limb and respiratory muscles are also influenced by other negative factors, including smoking, systemic inflammation, nutritional abnormalities, exacerbations and some drugs. Limb muscle weakness is generally diagnosed through voluntary isometric maneuvers such as handgrip or quadriceps muscle contraction (dynamometry); while respiratory muscle loss of strength is usually recognized through a decrease in maximal static pressures measured at the mouth. Both types of measurements have validated reference values. Respiratory muscle strength can also be evaluated determining esophageal, gastric and transdiaphragmatic maximal pressures although there is a lack of widely accepted reference equations. Non-volitional maneuvers, obtained through electrical or magnetic stimulation, can be employed in patients unable to cooperate. Muscle endurance can also be assessed, generally using repeated submaximal maneuvers until exhaustion, but no validated reference values are available yet. The treatment of muscle dysfunction is multidimensional and includes improvement in lifestyle habits (smoking abstinence, healthy diet and a good level of physical activity, preferably outside), nutritional measures (diet supplements and occasionally, anabolic drugs), and different modalities of general and muscle training. PMID:28066619

  18. αSynuclein and Mitochondrial Dysfunction: A Pathogenic Partnership in Parkinson’s Disease?

    Directory of Open Access Journals (Sweden)

    David Protter

    2012-01-01

    Full Text Available Parkinson’s Disease (PD is a complex, chronic, progressive, and debilitating neurodegenerative disorder. Neither a cure nor effective long-term therapy exist and the lack of knowledge of the molecular mechanisms responsible for PD development is a major impediment to therapeutic advances. The protein αSynuclein is a central component in PD pathogenesis yet its cellular targets and mechanism of toxicity remains unknown. Mitochondrial dysfunction is also a common theme in PD patients and this review explores the strong possibility that αSynuclein and mitochondrial dysfunction have an inter-relationship responsible for underlying the disease pathology. Amplifying cycles of mitochondrial dysfunction and αSynuclein toxicity can be envisaged, with either being the disease-initiating factor yet acting together during disease progression. Multiple potential mechanisms exist in which mitochondrial dysfunction and αSynuclein could interact to exacerbate their neurodegenerative properties. Candidates discussed within this review include autophagy, mitophagy, mitochondrial dynamics/fusion/fission, oxidative stress and reactive oxygen species, endoplasmic reticulum stress, calcium, nitrosative stress and αSynuclein Oligomerization.

  19. Subtle bilirubin-induced neurodevelopmental dysfunction (BIND) in the term and late preterm infant : Does it exist?

    NARCIS (Netherlands)

    Lunsing, Roelineke J.

    2014-01-01

    Subtle bilirubin-induced neurological dysfunction (BIND) is defined as disturbances in sensory and sensorimotor integration, central auditory processing, coordination, and muscle tone in the absence of the classical findings of kernicterus. This review is restricted to the (sensori)motor signs of

  20. Mechanical Forces Exacerbate Periodontal Defects in Bsp-null Mice.

    Science.gov (United States)

    Soenjaya, Y; Foster, B L; Nociti, F H; Ao, M; Holdsworth, D W; Hunter, G K; Somerman, M J; Goldberg, H A

    2015-09-01

    Bone sialoprotein (BSP) is an acidic phosphoprotein with collagen-binding, cell attachment, and hydroxyapatite-nucleating properties. BSP expression in mineralized tissues is upregulated at onset of mineralization. Bsp-null (Bsp(-/-)) mice exhibit reductions in bone mineral density, bone turnover, osteoclast activation, and impaired bone healing. Furthermore, Bsp(-/-) mice have marked periodontal tissue breakdown, with a lack of acellular cementum leading to periodontal ligament detachment, extensive alveolar bone and tooth root resorption, and incisor malocclusion. We hypothesized that altered mechanical stress from mastication contributes to periodontal destruction observed in Bsp(-/-) mice. This hypothesis was tested by comparing Bsp(-/-) and wild-type mice fed with standard hard pellet diet or soft powder diet. Dentoalveolar tissues were analyzed using histology and micro-computed tomography. By 8 wk of age, Bsp(-/-) mice exhibited molar and incisor malocclusion regardless of diet. Bsp(-/-) mice with hard pellet diet exhibited high incidence (30%) of severe incisor malocclusion, 10% lower body weight, 3% reduced femur length, and 30% elevated serum alkaline phosphatase activity compared to wild type. Soft powder diet reduced severe incisor malocclusion incidence to 3% in Bsp(-/-) mice, supporting the hypothesis that occlusal loading contributed to the malocclusion phenotype. Furthermore, Bsp(-/-) mice in the soft powder diet group featured normal body weight, long bone length, and serum alkaline phosphatase activity, suggesting that tooth dysfunction and malnutrition contribute to growth and skeletal defects reported in Bsp(-/-) mice. Bsp(-/-) incisors also erupt at a slower rate, which likely leads to the observed thickened dentin and enhanced mineralization of dentin and enamel toward the apical end. We propose that the decrease in eruption rate is due to a lack of acellular cementum and associated defective periodontal attachment. These data demonstrate the