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Find video protocols related to scientific articles indexed in Pubmed.
Blood Flow Vortices along the Main Pulmonary Artery Measured with MR Imaging for Diagnosis of Pulmonary Hypertension.
Radiology
PUBLISHED: 11-06-2014
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Purpose To approximate the functional relationship between invasively measured mean pulmonary arterial pressure ( mPAP mean pulmonary arterial pressure ) and the phase-contrast magnetic resonance (MR) imaging-derived duration of vortical blood flow along the main pulmonary artery and to analyze its applicability for noninvasive diagnosis of pulmonary hypertension ( PH pulmonary hypertension ) and borderline mPAP mean pulmonary arterial pressure . Materials and Methods The local ethics review board approved this prospective study of 145 patients suspected of having PH pulmonary hypertension (69 patients with PH pulmonary hypertension , 19 patients with borderline mPAP mean pulmonary arterial pressure , and 57 patients with normal mPAP mean pulmonary arterial pressure ) who underwent right heart catheterization ( RHC right heart catheterization ) and three-directional phase-contrast MR imaging of the main pulmonary artery. Velocity fields were viewed with dedicated software and evaluated for the duration of vortical blood flow in the main pulmonary artery (tvortex, the percentage of cardiac phases with vortex present). The relationship between mPAP mean pulmonary arterial pressure at RHC right heart catheterization and tvortex was assessed by means of a segmented linear regression model, and by Bland-Altman and receiver operating characteristic curve analyses. Results The relationship between mPAP mean pulmonary arterial pressure and tvortex was described adequately (R(2) = 0.95) as linearly increasing, from tvortex of 0% ( mPAP mean pulmonary arterial pressure ? 16.0 mm Hg) with a slope of 1.59% per millimeter of mercury. The standard deviation between mPAP mean pulmonary arterial pressure values derived from RHC right heart catheterization and those estimated by using tvortex was 3.9 mm Hg. The area under the curve for tvortex-based diagnosis of PH pulmonary hypertension was 0.994 (95% confidence interval [ CI confidence interval ]: 0.982, 0.998), and the calculated PH pulmonary hypertension cut-off value (tvortex ? 14.3%) resulted in sensitivity of 0.97 (95% CI confidence interval : 0.90, 0.99) and specificity of 0.96 (95% CI confidence interval : 0.89, 0.99). Vortical blood flow with tvortex less than 14.3% was specific for borderline mPAP mean pulmonary arterial pressure . Conclusion Duration of vortical blood flow in the main pulmonary artery that is determined by using phase-contrast MR imaging allows accurate estimation of elevated mPAP mean pulmonary arterial pressure and diagnosis of PH pulmonary hypertension . © RSNA, 2014 Clinical trial registration no. NCT00575692.
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Can you ever collect too many oocytes?
Hum. Reprod.
PUBLISHED: 11-02-2014
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Does the chance of pregnancy keep improving with increasing number of oocytes, or can you collect too many?
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[The effect of patient education on glycemic status and self-monitoring activity in type 2 diabetic patients recently switched to basal insulin analogue treatment].
Orv Hetil
PUBLISHED: 10-21-2014
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In addition to medications, patient education is thought to have important beneficial effects in the management of patients with type 2 diabetes mellitus.
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A20--a biomarker of allograft outcome: a showcase in kidney transplantation.
Adv. Exp. Med. Biol.
PUBLISHED: 10-11-2014
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Effective means to identify anti-donor immune activity before the transplant organ is damaged and rejected has been an important goal in transplantation research. Development of sensitive and non-invasive diagnostic methods that probe the immune status of the recipient as well as the resilience of the donor organ should enable personalized application of immunosuppressive drugs. With a non-invasive biomarker for rejection, it should be possible to selectively treat the patients that are rejecting the graft and wean the tolerant patients from immunosuppression. Although A20 is also expressed by activated CD4+ T cells and CD8+ T cells, its expression by mouse tubular cells has been shown to play an important role in protecting allografts from ischemia/reperfusion (I/R) injury and rejection. Using quantitative (real-time) reverse transcriptase polymerase chain reaction (qt-RT-PCR), we showed that expression levels of A20, heme oxygenase (HO)-1, other anti-apoptotic molecules, granzyme-B (GZMB), perforin (PRF1), CD3 and other immune molecules in renal transplant biopsies, urinary cells and peripheral blood cells are predictive of transplantation outcomes. Measuring A20 at mRNA and protein levels has the potentiality to be diagnostic and prognostic of transplantation outcomes and thereby help in timely therapeutic interventions to prolong graft life.
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Chronic stress reduces the number of GABAergic interneurons in the adult rat hippocampus, dorsal-ventral and region-specific differences.
Hippocampus
PUBLISHED: 10-09-2014
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Major depressive disorder is a common and complex mental disorder with unknown etiology. GABAergic dysfunction is likely to contribute to the pathophysiology since disrupted GABAergic systems are well documented in depressed patients. Here we studied structural changes in the hippocampal GABAergic network using the chronic mild stress (CMS) model, as one of the best validated animal models for depression. Rats were subjected to 9 weeks of daily stress and behaviorally characterized using the sucrose consumption test into anhedonic and resilient animals based on their response to stress. Different subtypes of GABAergic interneurons were visualized by immunohistochemistry using antibodies for parvalbumin (PV), calretinin (CR), calbindin (CB), cholecystokinin (CCK), somatostatin (SOM), and neuropeptide Y (NPY). We used an unbiased quantification method to systematically count labeled cells in different subareas of the dorsal and ventral hippocampus. Chronic stress reduced the number of specific interneurons in distinct hippocampal subregions significantly. PV+ and CR+ neurons were reduced in all dorsal subareas, whereas in the ventral part only the CA1 was affected. Stress had the most pronounced effect on the NPY+ and SOM+ cells and reduced their number in almost all dorsal and ventral subareas. Stress had no effect on the CCK+ and CB+ interneurons. In most cases the effect of stress was irrespective to the behavioral phenotype. However, in a few specific areas the number of SOM+, NPY+, and CR+ neurons were significantly reduced in anhedonic animals compared to the resilient group. Overall, these data clearly demonstrate that chronic stress affects the structural integrity of specific GABAergic neuronal subpopulations and this should also affect the functioning of these hippocampal GABAergic networks. © 2014 Wiley Periodicals, Inc.
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Free and total cortisol levels are useful prognostic markers in critically ill patients: a prospective observational study.
Eur. J. Endocrinol.
PUBLISHED: 10-02-2014
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Objective: The role of cortisol in predicting mortality risk in critical illness is controversial in the literature. The aim of this study was to evaluate the prognostic value of cortisol concentrations in a mixed population of critically ill patients with medical emergencies. Design: In this prospective, observational study, total and free cortisol levels were measured in serum samples of 69 critically ill patients (39 males and 30 females, median age of 74 years) at admission (0 hour) and 6, 24, 48 and 96 hours after admission. Methods: Cortisol levels were determined using high performance liquid chromatography coupled high resolution ESI-TOF mass spectrometry. The severity of disease was calculated by prognostic scores. Statistical analyses were performed using the SPSS 22.0 software. Results: The range of total cortisol varied between 49.9 and 8797.8 nmol l-1, free cortisol between 0.4 and 759.9 nmol l-1. Free cortisol at 0, 6, 24, 48 hours and total cortisol at 0, 6 hours were significantly elevated in non-survivors and correlated to the predicted mortality. The prognostic value of these cortisol levels was comparable to the routinely used mortality scores. In predictive models, free cortisol at 6, 24 and 48 hours proved to be independent determinant of mortality. Conclusions: The predictive values of free cortisol in the first 2 days after admission and total cortisol within 6 hours are comparable to the complex, routinely used mortality scores in evaluating the prognosis of critically ill patients. The cortisol response probably reflects the severity of disease.
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Expression of Certain Leukemia/Lymphoma Related microRNAs and its Correlation with Prognosis in Childhood Acute Lymphoblastic Leukemia.
Pathol. Oncol. Res.
PUBLISHED: 09-30-2014
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In spite of the improved efficacy of therapy, it still fails in 15-20 % of childhood acute lymphoblastic leukemia (ALL) patients. Recently, altered expression of certain miRNAs (miRs) have been described in ALL with potential effect on prognosis. Presence of certain miRs (miRNA-16, -21, -24, -29b, -128b, -142-3p, -155, -223) was characterized in human lymphoma and leukemia cells by real-time PCR. Expression of miRs in pediatric ALL patients (n?=?24) was measured before chemotherapy, at conventional response checkpoints and at relapse. Correlation between altered miR expression and response to prednisolone at day 8 of therapy and long term prognosis was statistically analysed. Overexpression of "oncomiR/inflammamiR"-21 - which is characteristic in different tumors-was missing in human ALL cells. However, higher expression of miR-128b and lower expression of miR-223 is generally characteristic for human ALL cell lines and ALL cells isolated from pediatric patients. Correlation was shown between miR-128b expression and prognosis, prednisolone response and survival data in childhood ALL. Expression of miR-128b and miR-223-both are leukemia specific-changed in parallel with percentage of bone marrow blasts in remission and during relapse. Therefore, we suggest that overexpression of miR-128b and downregulation of miR-223 shows a significant correlation with treatment response and prognosis in childhood ALL.
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I716F A?PP Mutation Associates with the Deposition of Oligomeric Pyroglutamate Amyloid-? and ?-Synucleinopathy with Lewy Bodies.
J. Alzheimers Dis.
PUBLISHED: 09-02-2014
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Autosomal dominant familial Alzheimer's disease (AD) is associated with mutations in the A?PP, PSEN1, and PSEN2 genes. The clinical phenotype associated with A?PP mutations is mainly characterized by dementia or by strokes related to cerebral amyloid angiopathy (CAA). We present a comprehensive clinical, neuropathological, genetic, and biochemical study on a patient affected by familial AD associated with the I716F mutation in the A?PP gene. The clinical phenotype was characterized by early age of onset of 47 years, and rapidly progressive cerebellar ataxia, myoclonic jerks, rigidity, and dementia reminiscent of Creutzfeldt-Jakob disease (CJD), followed by a prolonged persistent vegetative state. Neuropathological evaluation of the proband revealed AD-related pathology but also ?-synucleinopathy compatible with dementia with Lewy bodies neocortical stage or Parkinson's disease corresponding to Braak stage 6. Tau-pathology in the form of neurofibrillary degeneration corresponded to stage VI according to the Braak classification. The severe A? pathology included CAA, numerous plaques, and deposition of N-truncated pyroglutamate-modified A? peptides. Remarkably, pyroglutamate A? oligomers were also present intracellularly in Purkinje cells corresponding to the ataxic phenotype. The detection of a CJD-like phenotype expands the spectrum of clinical presentations associated with familial AD. Our study supports the concept that the neuropathology of familial AD expands beyond the classical AD-related pathology as defined by plaques and tangles. Finally, we provide evidence for the first time that oligomeric pyroglutamate A? is present in a specific pattern correlating with the clinical symptoms of a patient with A?PP I716F mutation.
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Detection of disease-associated ?-synuclein in the cerebrospinal fluid: a feasibility study.
Clin. Neuropathol.
PUBLISHED: 08-19-2014
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With the aim to evaluate the significance and reliability of detecting disease-specific ?-synuclein in the cerebrospinal fluid (CSF) we developed an ELISA and bead-assay. We used a commercial antibody (5G4) that does not bind to the physiological monomeric form of ?-synuclein, but is highly specific for the disease-associated forms, including high molecular weight fraction of ?-sheet rich oligomers. We applied both tests in CSF from a series of neuropathologically confirmed ?-synucleinopathy cases, including Parkinson' disease dementia (PDD) and dementia with Lewy bodies (DLB) (n = 7), as well as Alzheimer' disease (n = 6), and control patients without neurodegenerative pathologies (n = 9). Disease-specific ?-synuclein was detectable in the CSF in a subset of patients with ?-synuclein pathology in the brain. When combined with the analysis of total ?-synuclein, the bead-assay for disease-specific ?-synuclein was highly specific for PDD/DLB. Detection of disease-associated ?synuclein combined with the total levels of ?-synuclein is a promising tool for the in-vivo diagnosis of ?-synucleinopathies, including PDD and LBD.
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Oligodendroglial Response in the Spinal Cord in TDP-43 Proteinopathy with Motor Neuron Involvement.
Neurodegener Dis
PUBLISHED: 08-05-2014
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TDP-43 proteinopathies represent a spectrum of neurodegenerative disorders. Variable clinical presentations including frontotemporal dementia, amyotrophic lateral sclerosis (ALS) and mixed forms are associated with the spatial heterogeneity of the TDP-43 pathology. Recent studies have emphasized the role of oligodendrocytes in the pathogenesis of ALS.
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Primary age-related tauopathy (PART): a common pathology associated with human aging.
Acta Neuropathol.
PUBLISHED: 07-24-2014
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We recommend a new term, "primary age-related tauopathy" (PART), to describe a pathology that is commonly observed in the brains of aged individuals. Many autopsy studies have reported brains with neurofibrillary tangles (NFTs) that are indistinguishable from those of Alzheimer's disease (AD), in the absence of amyloid (A?) plaques. For these "NFT+/A?-" brains, for which formal criteria for AD neuropathologic changes are not met, the NFTs are mostly restricted to structures in the medial temporal lobe, basal forebrain, brainstem, and olfactory areas (bulb and cortex). Symptoms in persons with PART usually range from normal to amnestic cognitive changes, with only a minority exhibiting profound impairment. Because cognitive impairment is often mild, existing clinicopathologic designations, such as "tangle-only dementia" and "tangle-predominant senile dementia", are imprecise and not appropriate for most subjects. PART is almost universally detectable at autopsy among elderly individuals, yet this pathological process cannot be specifically identified pre-mortem at the present time. Improved biomarkers and tau imaging may enable diagnosis of PART in clinical settings in the future. Indeed, recent studies have identified a common biomarker profile consisting of temporal lobe atrophy and tauopathy without evidence of A? accumulation. For both researchers and clinicians, a revised nomenclature will raise awareness of this extremely common pathologic change while providing a conceptual foundation for future studies. Prior reports that have elucidated features of the pathologic entity we refer to as PART are discussed, and working neuropathological diagnostic criteria are proposed.
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Patterns of hippocampal tau pathology differentiate neurodegenerative dementias.
Dement Geriatr Cogn Disord
PUBLISHED: 06-26-2014
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Deposits of phosphorylated tau protein and convergence of pathology in the hippocampus are the hallmarks of neurodegenerative tauopathies. Thus we aimed to evaluate whether regional and cellular vulnerability patterns in the hippocampus distinguish tauopathies or are influenced by their concomitant presence.
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Neuropathological assessments of the pathology in frontotemporal lobar degeneration with TDP43-positive inclusions: an inter-laboratory study by the BrainNet Europe consortium.
J Neural Transm
PUBLISHED: 06-24-2014
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The BrainNet Europe consortium assessed the reproducibility in the assignment of the type of frontotemporal lobar degeneration (FTLD) with TAR DNA-binding protein (TDP) 43 following current recommendations. The agreement rates were influenced by the immunohistochemical (IHC) method and by the classification strategy followed. p62-IHC staining yielded good uniform quality of stains, but the most reliable results were obtained implementing specific Abs directed against the hallmark protein TDP43. Both assessment of the type and the extent of lesions were influenced by the Abs and by the quality of stain. Assessment of the extent of the lesions yielded poor results repeatedly; thus, the extent of pathology should not be used in diagnostic consensus criteria. Whilst 31 neuropathologists typed 30 FTLD-TDP cases, inter-rater agreement ranged from 19 to 100 per cent, being highest when applying phosphorylated TDP43/IHC. The agreement was highest when designating Type C or Type A/B. In contrast, there was a poor agreement when attempting to separate Type A or Type B FTLD-TDP. In conclusion, we can expect that neuropathologist, independent of his/her familiarity with FTLD-TDP pathology, can identify a TDP43-positive FTLD case. The goal should be to state a Type (A, B, C, D) or a mixture of Types (A/B, A/C or B/C). Neuropathologists, other clinicians and researchers should be aware of the pitfalls whilst doing so. Agreement can be reached in an inter-laboratory setting regarding Type C cases with thick and long neurites, whereas the differentiation between Types A and B may be more troublesome.
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Distinct differences in gene expression patterns in pulmonary arteries of patients with chronic obstructive pulmonary disease and idiopathic pulmonary fibrosis with pulmonary hypertension.
Am. J. Respir. Crit. Care Med.
PUBLISHED: 06-12-2014
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The development of pulmonary hypertension (PH) in patients with idiopathic pulmonary fibrosis (IPF) or chronic obstructive pulmonary disease (COPD) is associated with increased morbidity.
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mTOR Hyperactivation in down syndrome hippocampus appears early during development.
J. Neuropathol. Exp. Neurol.
PUBLISHED: 06-12-2014
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The mammalian target of rapamycin (mTOR) signaling pathway is a key developmental pathway involved in mechanisms underlying cellular aging and neurodegeneration. We hypothesized that its deregulation may occur during early brain development in patients with Down syndrome (DS). The expression patterns and cellular distribution of components of mTOR signaling (phosphorylated S6, phosphorylated S6 kinase, phosphorylated eukaryotic initiation factor 4E binding protein 1, and phosphorylated mTOR) were investigated in developing hippocampi from controls and patients with DS and from adults with DS and Alzheimer disease-associated pathology using immunocytochemistry. In control hippocampi, only phosphorylated S6 was detected prenatally (19-41 gestational weeks); it became undetectable 2 months postnatally. Increased expression of phosphorylated S6, phosphorylated S6 kinase, phosphorylated eukaryotic initiation factor 4E binding protein 1, and phosphorylated mTOR was observed in DS hippocampus compared with controls. Phosphorylated S6 and phosphorylated S6 kinase were detected prenatally and persisted throughout postnatal development. Prominent expression of mTOR components was observed in pyramidal neurons with granulovacuolar degeneration and in neurons containing neurofibrillary tangles in the hippocampi of DS subjects with Alzheimer disease pathology. These findings suggest that a dysregulated mTOR pathway may contribute to both early hippocampal developmental abnormalities and hippocampal functional impairment developing before neurodegeneration. Moreover, the expression patterns of mTOR components in adult DS hippocampus support its association with Alzheimer disease-related histopathologic changes.
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Multiple sclerosis deep grey matter: the relation between demyelination, neurodegeneration, inflammation and iron.
J. Neurol. Neurosurg. Psychiatr.
PUBLISHED: 06-04-2014
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In multiple sclerosis (MS), diffuse degenerative processes in the deep grey matter have been associated with clinical disabilities. We performed a systematic study in MS deep grey matter with a focus on the incidence and topographical distribution of lesions in relation to white matter and cortex in a total sample of 75 MS autopsy patients and 12 controls. In addition, detailed analyses of inflammation, acute axonal injury, iron deposition and oxidative stress were performed. MS deep grey matter was affected by two different processes: the formation of focal demyelinating lesions and diffuse neurodegeneration. Deep grey matter demyelination was most prominent in the caudate nucleus and hypothalamus and could already be seen in early MS stages. Lesions developed on the background of inflammation. Deep grey matter inflammation was intermediate between low inflammatory cortical lesions and active white matter lesions. Demyelination and neurodegeneration were associated with oxidative injury. Iron was stored primarily within oligodendrocytes and myelin fibres and released upon demyelination. In addition to focal demyelinated plaques, the MS deep grey matter also showed diffuse and global neurodegeneration. This was reflected by a global reduction of neuronal density, the presence of acutely injured axons, and the accumulation of oxidised phospholipids and DNA in neurons, oligodendrocytes and axons. Neurodegeneration was associated with T cell infiltration, expression of inducible nitric oxide synthase in microglia and profound accumulation of iron. Thus, both focal lesions as well as diffuse neurodegeneration in the deep grey matter appeared to contribute to the neurological disabilities of MS patients.
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Reading pulmonary vascular pressure tracings. How to handle the problems of zero leveling and respiratory swings.
Am. J. Respir. Crit. Care Med.
PUBLISHED: 05-30-2014
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The accuracy of pulmonary vascular pressure measurements is of great diagnostic and prognostic relevance. However, there is variability of zero leveling procedures, and the current recommendation of end-expiratory reading may not always be adequate. A review of physiological and anatomical data, supported by recent imaging, leads to the practical recommendation of zero leveling at the cross-section of three transthoracic planes, which are, respectively midchest frontal, transverse through the fourth intercostal space, and midsagittal. As for the inevitable respiratory pressure swings, end-expiratory reading at functional residual capacity allows for minimal influence of elastic lung recoil on pulmonary pressure reading. However, hyperventilation is associated with changes in end-expiratory lung volume and increased intrathoracic pressure, eventually exacerbated by expiratory muscle contraction and dynamic hyperinflation, all increasing pulmonary vascular pressures. This problem is amplified in patients with obstructed airways. With the exception of dynamic hyperinflation states, it is reasonable to assume that negative inspiratory and positive expiratory intrathoracic pressures cancel each other out, so averaging pulmonary vascular pressures over several respiratory cycles is most often preferable. This recommendation may be generalized for the purpose of consistency and makes sense, as pulmonary blood flow measurements are not corrected for phasic inspiratory and expiratory changes in clinical practice.
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Endocannabinoids modulate cortical development by configuring Slit2/Robo1 signalling.
Nat Commun
PUBLISHED: 04-25-2014
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Local environmental cues are indispensable for axonal growth and guidance during brain circuit formation. Here, we combine genetic and pharmacological tools, as well as systems neuroanatomy in human fetuses and mouse models, to study the role of endocannabinoid and Slit/Robo signalling in axonal growth. We show that excess 2-arachidonoylglycerol, an endocannabinoid affecting directional axonal growth, triggers corpus callosum enlargement due to the errant CB1 cannabinoid receptor-containing corticofugal axon spreading. This phenotype mechanistically relies on the premature differentiation and end-feet proliferation of CB2R-expressing oligodendrocytes. We further show the dependence of both axonal Robo1 positioning and oligodendroglial Slit2 production on cell-type-specific cannabinoid receptor activation. Accordingly, Robo1 and/or Slit2 manipulation limits endocannabinoid modulation of axon guidance. We conclude that endocannabinoids can configure focal Slit2/Robo1 signalling to modulate directional axonal growth, which may provide a basis for understanding impaired brain wiring associated with metabolic deficits and prenatal drug exposure.
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[Emergency psychopharmacotherapy in Hungary -- preliminary data].
Neuropsychopharmacol Hung
PUBLISHED: 04-02-2014
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Although the number of patients admitted for psychiatric emergency care is increasing according to data from various countries, there are no large-scale studies assessing clinical emergency practice and in several countries no national guidelines have been published concerning emergency care in psychiatry. The aim of our study was to assess practice related to emergency care of agitated-psychotic patients in Hungary.
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Detection of pulmonary vasculopathy by novel analysis of oxygen uptake in patients with systemic sclerosis: association with pulmonary arterial pressures.
Clin. Exp. Rheumatol.
PUBLISHED: 03-19-2014
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During cardiopulmonary exercise testing (CPET) compromised pulmonary vasculature in patients with systemic sclerosis (SSc) may lead to increases in pulmonary arterial pressures (PAP) and decreased oxygen uptake. We hypothesised that this may lead into a disproportional heart rate (HR) increase with a corresponding V'O2/HR breakpoint and relates to systolic PAP at rest.
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[Flow cytometry in the diagnosis of hemophagocytic lymphohistiocytosis in a case with fatal outcome].
Orv Hetil
PUBLISHED: 03-04-2014
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Hemophagocytic lymphohistiocytosis is a multisystem inflammation, generated by the uncontrolled and excessive activation of cytotoxic T lymphocytes and natural killer cells. Severe immunodeficiency and generalized macrophage activation can often be detected in the background of this life threatening disorder. It is classified as a primary immunodeficiency. Functional abnormalities of the perforin protein or defects in granule secretory mechanisms are caused by gene mutations in most cases. Diagnostic criteria of hemophagocytic lymphohistiocytosis are the following: fever, splenomegaly, cytopenias affecting at least two of the 3 lineages in peripheral blood, hypertriglyceridemia and hyperferritinemia, elevated serum level of soluble interleukin-2 receptor (sCD25), hypofibrinogenemia, hemophagocytosis in bone marrow and decreased cytotoxic T cell and natural killer cell activity. In this case report the authors summarize the utility of functional flow cytometry in the diagnosis of hemophagocytic lymphohistiocytosis. Using flow cytometry, elevated intracellular perforin content, decreased killing activity of cytotoxic T cells and natural killer cells, and impaired cell surface expression of CD107a (LAMP1 protein) from in vitro stimulated blood lymphocytes were detected. Abnormal secretion of perforin was also demonstrated. Genetic testing revealed mutation of the MUNC 13-4 gene, which confirmed the base of the abnormal flow cytometric findings. This case report demonstrates the value of functional flow cytometry in the rapid diagnosis of genetically determined hemophagocytic lymphohistiocytosis, a condition in which early diagnosis is critical for optimal management. The authors emphasize the significance of functional flow cytometry in the differential diagnosis of immunodeficiencies.
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Latent homology and convergent regulatory evolution underlies the repeated emergence of yeasts.
Nat Commun
PUBLISHED: 02-27-2014
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Convergent evolution is common throughout the tree of life, but the molecular mechanisms causing similar phenotypes to appear repeatedly are obscure. Yeasts have arisen in multiple fungal clades, but the genetic causes and consequences of their evolutionary origins are unknown. Here we show that the potential to develop yeast forms arose early in fungal evolution and became dominant independently in multiple clades, most likely via parallel diversification of Zn-cluster transcription factors, a fungal-specific family involved in regulating yeast-filamentous switches. Our results imply that convergent evolution can happen by the repeated deployment of a conserved genetic toolkit for the same function in distinct clades via regulatory evolution. We suggest that this mechanism might be a common source of evolutionary convergence even at large time scales.
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Serum and follicular fluid fetuin-A in women undergoing in vitro fertilization.
Clin. Chem. Lab. Med.
PUBLISHED: 02-26-2014
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This case-control study was designed to assess the possible role of fetuin-A, a multifunctional protein, in reproductive processes of women undergoing in vitro fertilization (IVF).
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Glial and neuronal tau pathology in tauopathies: characterization of disease-specific phenotypes and tau pathology progression.
J. Neuropathol. Exp. Neurol.
PUBLISHED: 02-25-2014
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Tauopathies are degenerative diseases characterized by the accumulation of phosphorylated tau in neurons and glial cells. With some exceptions, tau deposits in neurons are mainly manifested as pretangles and tangles unrelated to the tauopathy. It is thought that abnormal tau deposition in neurons occurs following specific steps, but little is known about the progression of tau pathology in glial cells in tauopathies. We compared tau pathology in different astrocyte phenotypes and oligodendroglial inclusions with that in neurons in a large series of tauopathies, including progressive supranuclear palsy, corticobasal degeneration, argyrophilic grain disease, Pick disease, frontotemporal lobar degenerations (FTLD) associated with mutations in the tau gene, globular glial tauopathy (GGT), and tauopathy in the elderly. Our findings indicate that disease-specific astroglial phenotypes depend on i) the primary amino acid sequence of tau (mutated tau, 3Rtau, and 4Rtau); ii) phospho-specific sites of tau phosphorylation, tau conformation, tau truncation, and ubiquitination in that order (which parallel tau modifications related to pretangle and tangle stages in neurons); and iii) modifications of the astroglial cytoskeleton. In contrast to astrocytes, coiled bodies in oligodendrocytes have similar characteristics whatever the tauopathy, except glial globular inclusions in GGT, and coiled bodies and globular oligodendroglial inclusions in FTLD-tau/K317M. These observations indicate that tau pathology in glial cells largely parallels, but is not identical to, that in neurons in many tauopathies.
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Intracellular processing of disease-associated ?-synuclein in the human brain suggests prion-like cell-to-cell spread.
Neurobiol. Dis.
PUBLISHED: 02-19-2014
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Dementia with Lewy bodies (DLB), Parkinson's disease (PD) and multiple system atrophy are characterized by the deposition of disease-associated ?-synuclein. In the present study we 1) examined the molecular specificity of the novel anti-?-synuclein 5G4 antibody; 2) evaluated immunoreactivity patterns and their correlation in human brain tissue with micro- and astrogliosis in 57 cases with PD or DLB; and 3) performed a systematic immunoelectron microscopical mapping of subcellular localizations. 5G4 strongly binds to the high molecular weight fraction of ?-sheet rich oligomers, while no binding to primarily disordered oligomers or monomers was observed. We show novel localizations of disease-associated ?-synuclein including perivascular macrophages, ependyma and cranial nerves. ?-Synuclein immunoreactive neuropil dots and thin threads associate more with glial reaction than Lewy bodies alone. Astrocytic ?-synuclein is an important component of the pathology. Furthermore, we document ultrastructurally the pathway of processing of disease-associated ?-synuclein within neurons and astroglial cells. Interaction of mitochondria and disease-associated ?-synuclein plays a key role in the molecular-structural cytopathogenesis of disorders with Lewy bodies. We conclude that 1) the 5G4 antibody has strong selectivity for ?-sheet rich ?-synuclein oligomers; 2) Lewy bodies themselves are not the most relevant morphological substrate that evokes tissue lesioning; 3) both neurons and astrocytes internalize disease-associated ?-synuclein in the human brain, suggesting prion-like cell-to-cell spread of ?-synuclein by uptake from surrounding structures, as shown previously in experimental observations.
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[Post-transplantation lymphoproliferative disorder in childhood].
Orv Hetil
PUBLISHED: 02-19-2014
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Among possible complications of transplantation the post-transplant lymphoproliferative disease due to immunosuppressive therapy is of paramount importance. In most cases the direct modulating effect of Epstein-Barr virus on immune cells can be documented.
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Correlation of striatal dopamine transporter imaging with post mortem substantia nigra cell counts.
Mov. Disord.
PUBLISHED: 02-14-2014
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Dopamine transporter imaging is widely used for the differential diagnosis of parkinsonism. Only limited data are available on the relationship between striatal dopamine transporter binding and dopaminergic cell loss in the substantia nigra (SN). We analyzed postmortem SN cell counts in patients who had previously undergone dopamine transporter single-photon emission computed tomography (SPECT). Pathological diagnoses included Parkinson's disease (n?=?1), dementia with Lewy bodies (n?=?2), multiple system atrophy (n?=?1), corticobasal degeneration (n?=?2), atypical parkinsonism with multiple pathological conditions (n?=?1), Alzheimer's disease (n?=?1), and Creutzfeldt-Jakob disease (n?=?1). [(12) (3) I]?-CIT SPECT had been performed in all subjects using a standardized protocol on the same triple-head gamma camera. The density of neuromelanin-containing and tyrosine hydroxylase-positive substantia nigra neurons/mm(2) was evaluated in paraffin-embedded tissue sections by morphometric methods. Mean disease duration at the time of dopamine transporter imaging was 2.3 years, and the mean interval from imaging to death was 29.3 months (range, 4-68 months). Visual analysis of dopamine transporter images showed reduced striatal uptake in all seven patients with neurodegenerative parkinsonism, but not in Alzheimer's and Creutzfeldt-Jakob disease cases. Averaged [(right+left)/2] striatal uptake was highly correlated with averaged SN cell counts (rs ?=?0.98, P?
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Rare mutations in SQSTM1 modify susceptibility to frontotemporal lobar degeneration.
Acta Neuropathol.
PUBLISHED: 02-10-2014
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Mutations in the gene coding for Sequestosome 1 (SQSTM1) have been genetically associated with amyotrophic lateral sclerosis (ALS) and Paget disease of bone. In the present study, we analyzed the SQSTM1 coding sequence for mutations in an extended cohort of 1,808 patients with frontotemporal lobar degeneration (FTLD), ascertained within the European Early-Onset Dementia consortium. As control dataset, we sequenced 1,625 European control individuals and analyzed whole-exome sequence data of 2,274 German individuals (total n = 3,899). Association of rare SQSTM1 mutations was calculated in a meta-analysis of 4,332 FTLD and 10,240 control alleles. We identified 25 coding variants in FTLD patients of which 10 have not been described. Fifteen mutations were absent in the control individuals (carrier frequency <0.00026) whilst the others were rare in both patients and control individuals. When pooling all variants with a minor allele frequency <0.01, an overall frequency of 3.2 % was calculated in patients. Rare variant association analysis between patients and controls showed no difference over the whole protein, but suggested that rare mutations clustering in the UBA domain of SQSTM1 may influence disease susceptibility by doubling the risk for FTLD (RR = 2.18 [95 % CI 1.24-3.85]; corrected p value = 0.042). Detailed histopathology demonstrated that mutations in SQSTM1 associate with widespread neuronal and glial phospho-TDP-43 pathology. With this study, we provide further evidence for a putative role of rare mutations in SQSTM1 in the genetic etiology of FTLD and showed that, comparable to other FTLD/ALS genes, SQSTM1 mutations are associated with TDP-43 pathology.
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Loss of Calbindin immunoreactivity in the dentate gyrus distinguishes Alzheimer's disease from other neurodegenerative dementias.
Neurosci. Lett.
PUBLISHED: 01-27-2014
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Calbindin (Cb) is one of the major Ca(2+) binding proteins exhibiting neuromodulatory functions such as long-term potentiation (LTP), synaptic plasticity, and memory functions. It is expressed in hippocampal interneurons, pyramidal cells and granule cells of the dentate gyrus (DGCs). Cb mRNA levels remain stable during normal ageing, but decrease in Alzheimer's, Huntington, and Parkinson's disease. A recent study suggested a link between A?-induced Alzheimer's disease (AD)-related cognitive deficits and neuronal depletion of Cb. To evaluate whether this is specific for AD, we performed a comparative study of Cb immunoreactivity of DGCs in cases with AD-related neuropathologic change (49), grouped according to the stages of Braak and Braak, BB), Creutzfeldt-Jakob-disease (16), FTLD-tau Pick's disease type (PiD; 5), argyrophilic grain disease (8), and FTLD-TDP types A and B (6). The group of AD cases with BB stages V and VI showed the highest proportion of Cb negative cells in the DGC when compared to all other groups except PiD. The ratio of negative cells correlated significantly with the BB stages. While the total number of DGCs decreased with age in our series, loss of Cb immunoreactivity was shown to be age-dependent only in PiD and FTLD-TDP. We conclude, that late stage AD-neuropathologic change (BB V and VI stages) associates with significantly higher ratios of Cb negative DGCs and this correlates with advanced BB stage. This might suggest an accumulative effect of an epilepsy-like pathway on the Cb expression or the direct influence of local pathological protein deposits on the DGCs.
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Heterogeneous downregulation of angiotensin II AT1-A and AT1-B receptors in arterioles in STZ-induced diabetic rat kidneys.
Biomed Res Int
PUBLISHED: 01-21-2014
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The renin granulation of kidney arterioles is enhanced in diabetes despite the fact that the level of angiotensin II in the diabetic kidney is elevated. Therefore, the number of angiotensin II AT1-A and AT1-B receptors in afferent and efferent arteriole's renin-positive and renin-negative smooth muscle cells (SMC) was estimated.
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The cost-effectiveness of ulipristal acetate tablets in treating patients with moderate to severe symptoms of uterine fibroids.
Eur. J. Obstet. Gynecol. Reprod. Biol.
PUBLISHED: 01-21-2014
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Ulipristal acetate is a selective progesterone receptor modulator that has been demonstrated to be an effective 3-month pre-operative treatment for moderate to severe symptoms of uterine fibroids in adult women of reproductive age. The aim of this analysis was to assess the cost-effectiveness of 5mg ulipristal as an add-on therapy to standard pre-surgical observation and treatment in Hungary.
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Tobacco smoke exposure in pulmonary arterial and thromboembolic pulmonary hypertension.
Respiration
PUBLISHED: 01-20-2014
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Animal studies and data from a single-center study suggest that tobacco smoke exposure may be a risk factor for precapillary pulmonary hypertension (PH).
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A validated method for measurement of serum total, serum free, and salivary cortisol, using high-performance liquid chromatography coupled with high-resolution ESI-TOF mass spectrometry.
Anal Bioanal Chem
PUBLISHED: 01-20-2014
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Blood cortisol level is routinely analysed in laboratory medicine, but the immunoassays in widespread use have the disadvantage of cross-reactivity with some commonly used steroid drugs. Mass spectrometry has become a method of increasing importance for cortisol estimation. However, current methods do not offer the option of accurate mass identification. Our objective was to develop a mass spectrometry method to analyse salivary, serum total, and serum free cortisol via accurate mass identification. The analysis was performed on a Bruker micrOTOF high-resolution mass spectrometer. Sample preparation involved protein precipitation, serum ultrafiltration, and solid-phase extraction. Limit of quantification was 12.5 nmol L(-1) for total cortisol, 440 pmol L(-1) for serum ultrafiltrate, and 600 pmol L(-1) for saliva. Average intra-assay variation was 4.7%, and inter-assay variation was 6.6%. Mass accuracy was <2.5 ppm. Serum total cortisol levels were in the range 35.6-1088 nmol L(-1), and serum free cortisol levels were in the range 0.5-12.4 nmol L(-1). Salivary cortisol levels were in the range 0.7-10.4 nmol L(-1). Mass accuracy was equal to or below 2.5 ppm, resulting in a mass error less than 1 mDa and thus providing high specificity. We did not observe any interference with routinely used steroidal drugs. The method is capable of specific cortisol quantification in different matrices on the basis of accurate mass identification.
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Distinct patterns of sirtuin expression during progression of Alzheimer's disease.
Neuromolecular Med.
PUBLISHED: 01-15-2014
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Aging is one of the major risk factors for Alzheimer's disease (AD). Sirtuins are associated with prolonged life span. To examine whether the expression levels of sirtuins associate with the progression of AD or not, we performed a comparative immunoblotting and immunohistochemical study of SIRT1, 3, and 5 in the entorhinal cortex and hippocampal subregions and white matter in 45 cases grouped according to Braak and Braak stages of neurofibrillary degeneration. In addition, we compared the expression levels with the local load of tau and amyloid-beta deposits, evaluated using morphometry. Our study revealed that (1) the neuronal subcellular redistribution of SIRT1 parallels the decrease in its expression, suggesting stepwise loss of neuroprotection dependent on the neuronal population; (2) in contrast to SIRT1 and 3, expression of SIRT5 increases during the progression of AD; (3) which might be related to its appearance in activated microglial cells. The complex patterns of the expression of sirtuins in relation to tissue damage should be taken into account when searching for therapies interacting with sirtuins.
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?B-crystallin and HSP27 in glial cells in tauopathies.
Neuropathology
PUBLISHED: 01-11-2014
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Tauopathies are neurodegenerative diseases characterized by hyper-phosphorylated tau deposition in neurons and glial cells. Chaperones, such as small heat shock proteins ?B-crystallin and HSP27 highly expressed in normal glial cells, have been postulated as putative molecules preventing abnormal deposition and folding in glial cells in tauopathies. The objective of this work was to assess the expression of ?B-crystallin, phosphorylated ?B-crystallin at Ser59 and HSP27 in glial cells with and without tau deposits in progressive supranuclear palsy, corticobasal degeneration (CBD), argyrophilic grain disease (AGD), Pick's disease (PiD), Alzheimer's disease, frontotemporal lobar degeneration associated with mutations in the tau gene (FTLD-tau), globular glial tauopathy (GGT) and tauopathy in the elderly. Immunohistochemistry, and double-labeling immunofluorescence and confocal microscopy have been used for this purpose. Increased expression of ?B-crystallin and phosphorylated ?B-crystallin at Ser59 occurs in a subpopulation of glial cells with and without hyper-phosphorylated tau deposition in all the analyzed tauopathies, but their expression in neurons is restricted to ballooned neurons in CBD, AGD and PiD. HSP27 barely co-localizes with tau and with phosphorylated ?B-crystallin at Ser59, thus making the formation of active dimers operating as chaperones unlikely. Results suggest a limited function of ?B-crystallin and HSP27 in preventing abnormal tau protein deposition in glial cells and neurons; in addition, the expression of ?B-crystallin phosphorylated at Ser59 may act as a protective factor in glial cells.
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Immunogenicity of a 2009 pandemic influenza virus A H1N1 vaccine, administered simultaneously with the seasonal influenza vaccine, in children receiving chemotherapy.
Pediatr Blood Cancer
PUBLISHED: 01-03-2014
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No examination of simultaneous vaccination against pandemic H1N1 and the seasonal influenza virus strains, in children with cancer receiving chemotherapy, are yet published. We investigated the immunogenicity of a whole-virion, inactivated, adjuvanted pandemic H1N1, and seasonal influenza vaccines administered simultaneously to children with cancer undergoing chemotherapy.
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Finding needles in haystacks: linking scientific names, reference specimens and molecular data for Fungi.
Conrad L Schoch, Barbara Robbertse, Vincent Robert, Duong Vu, Gianluigi Cardinali, László Irinyi, Wieland Meyer, R Henrik Nilsson, Karen Hughes, Andrew N Miller, Paul M Kirk, Kessy Abarenkov, M Catherine Aime, Hiran A Ariyawansa, Martin Bidartondo, Teun Boekhout, Bart Buyck, Qing Cai, Jie Chen, Ana Crespo, Pedro W Crous, Ulrike Damm, Z Wilhelm De Beer, Bryn T M Dentinger, Pradeep K Divakar, Margarita Dueñas, Nicolas Feau, Katerina Fliegerová, Miguel A García, Zai-Wei Ge, Gareth W Griffith, Johannes Z Groenewald, Marizeth Groenewald, Martin Grube, Marieka Gryzenhout, Cécile Gueidan, Liangdong Guo, Sarah Hambleton, Richard Hamelin, Karen Hansen, Valérie Hofstetter, Seung-Beom Hong, Jos Houbraken, Kevin D Hyde, Patrik Inderbitzin, Peter R Johnston, Samantha C Karunarathna, Urmas Kõljalg, Gábor M Kovács, Ekaphan Kraichak, Krisztina Krizsán, Cletus P Kurtzman, Karl-Henrik Larsson, Steven Leavitt, Peter M Letcher, Kare Liimatainen, Jian-Kui Liu, D Jean Lodge, Janet Jennifer Luangsa-ard, H Thorsten Lumbsch, Sajeewa S N Maharachchikumbura, Dimuthu Manamgoda, María P Martín, Andrew M Minnis, Jean-Marc Moncalvo, Giuseppina Mulè, Karen K Nakasone, Tuula Niskanen, Ibai Olariaga, Tamás Papp, Tamás Petkovits, Raquel Pino-Bodas, Martha J Powell, Huzefa A Raja, Dirk Redecker, J M Sarmiento-Ramirez, Keith A Seifert, Bhushan Shrestha, Soili Stenroos, Benjamin Stielow, Sung-Oui Suh, Kazuaki Tanaka, Leho Tedersoo, M Teresa Telleria, Dhanushka Udayanga, Wendy A Untereiner, Javier Diéguez Uribeondo, Krishna V Subbarao, Csaba Vágvölgyi, Cobus Visagie, Kerstin Voigt, Donald M Walker, Bevan S Weir, Michael Weiss, Nalin N Wijayawardene, Michael J Wingfield, J P Xu, Zhu L Yang, Ning Zhang, Wen-Ying Zhuang, Scott Federhen.
Database (Oxford)
PUBLISHED: 01-01-2014
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DNA phylogenetic comparisons have shown that morphology-based species recognition often underestimates fungal diversity. Therefore, the need for accurate DNA sequence data, tied to both correct taxonomic names and clearly annotated specimen data, has never been greater. Furthermore, the growing number of molecular ecology and microbiome projects using high-throughput sequencing require fast and effective methods for en masse species assignments. In this article, we focus on selecting and re-annotating a set of marker reference sequences that represent each currently accepted order of Fungi. The particular focus is on sequences from the internal transcribed spacer region in the nuclear ribosomal cistron, derived from type specimens and/or ex-type cultures. Re-annotated and verified sequences were deposited in a curated public database at the National Center for Biotechnology Information (NCBI), namely the RefSeq Targeted Loci (RTL) database, and will be visible during routine sequence similarity searches with NR_prefixed accession numbers. A set of standards and protocols is proposed to improve the data quality of new sequences, and we suggest how type and other reference sequences can be used to improve identification of Fungi. Database URL: http://www.ncbi.nlm.nih.gov/bioproject/PRJNA177353.
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"Platelet-associated regulatory system (PARS)" with particular reference to female reproduction.
J Ovarian Res
PUBLISHED: 01-01-2014
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Blood platelets play an essential role in hemostasis, thrombosis and coagulation of blood. Beyond these classic functions their involvement in inflammatory, neoplastic and immune processes was also investigated. It is well known, that platelets have an armament of soluble molecules, factors, mediators, chemokines, cytokines and neurotransmitters in their granules, and have multiple adhesion molecules and receptors on their surface.
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Quantification of tortuosity and fractal dimension of the lung vessels in pulmonary hypertension patients.
PLoS ONE
PUBLISHED: 01-01-2014
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Pulmonary hypertension (PH) can result in vascular pruning and increased tortuosity of the blood vessels. In this study we examined whether automatic extraction of lung vessels from contrast-enhanced thoracic computed tomography (CT) scans and calculation of tortuosity as well as 3D fractal dimension of the segmented lung vessels results in measures associated with PH. In this pilot study, 24 patients (18 with and 6 without PH) were examined with thorax CT following their diagnostic or follow-up right-sided heart catheterisation (RHC). Images of the whole thorax were acquired with a 128-slice dual-energy CT scanner. After lung identification, a vessel enhancement filter was used to estimate the lung vessel centerlines. From these, the vascular trees were generated. For each vessel segment the tortuosity was calculated using distance metric. Fractal dimension was computed using 3D box counting. Hemodynamic data from RHC was used for correlation analysis. Distance metric, the readout of vessel tortuosity, correlated with mean pulmonary arterial pressure (Spearman correlation coefficient: ? = 0.60) and other relevant parameters, like pulmonary vascular resistance (? = 0.59), arterio-venous difference in oxygen (? = 0.54), arterial (? = -0.54) and venous oxygen saturation (? = -0.68). Moreover, distance metric increased with increase of WHO functional class. In contrast, 3D fractal dimension was only significantly correlated with arterial oxygen saturation (? = 0.47). Automatic detection of the lung vascular tree can provide clinically relevant measures of blood vessel morphology. Non-invasive quantification of pulmonary vessel tortuosity may provide a tool to evaluate the severity of pulmonary hypertension.
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Massive withdrawal symptoms and affective vulnerability are associated with variants of the CHRNA4 gene in a subgroup of smokers.
PLoS ONE
PUBLISHED: 01-01-2014
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Heterogeneous phenotypes of complex disorders pose a great challenge for genetic association studies and for the development of personalized treatment strategies. Cluster analysis of phenotypic data has been recently proposed as a reliable auxiliary method for such studies. A cohort of 236 treatment-seeking smokers was investigated after overnight nicotine abstinence. Alpha4 nicotinic acetylcholine receptor (nAChR) subunit-related phenotypes were assessed by the Fagerström Test for Nicotine Dependence (FTND), exhaled carbon monoxide (CO) measurements, the Minnesota Nicotine Withdrawal Scale (MNWS) and the Zung Self-Rating Depression Scale (ZSDS). Seven tag SNPs (single-nucleotide polymorphisms) across CHRNA4 (the gene encoding alpha4 subunit of the nicotinic acetylcholine receptor) were genotyped and two-step cluster analysis was used for phenotypic cluster characterization. Haplotype estimation was determined by HapStat module of R 2.0 software. Three different phenotypic clusters were identified and the C3 cluster was characterized by the highest ZSDS and MNWS scores compared to others. Furthermore, lifetime prevalence of major depression was significantly higher in the C3 cluster (p?=?0.019). In genetic association tests, this cluster was also significantly associated with rs3787138 genotypes (p?=?0.004) while haplotype analyses of three SNPs (rs3787138, rs1044396, rs3787140) revealed that the risk for C3 phenotype was almost three times higher in GCC haplotype carriers compared to others (pperm?=?0.013). This is the first report on a significant association between CHRNA4 variants and a subgroup of smokers characterized by massive withdrawal symptoms and affective vulnerability. Identification of such a phenotypic cluster can be a pivotal step for further pharmacogenetic studies on ligands of the alpha4 nAChR subunit. Our results suggest that performing cluster analysis in genetic association studies can be proposed for complex disorders.
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Intensive Chemotherapy for Childhood Acute Lymphoblastic Leukemia: Results of the Randomized Intercontinental Trial ALL IC-BFM 2002.
J. Clin. Oncol.
PUBLISHED: 12-16-2013
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From 2002 to 2007, the International Berlin-Frankfurt-Münster Study Group conducted a prospective randomized clinical trial (ALL IC-BFM 2002) for the management of childhood acute lymphoblastic leukemia (ALL) in 15 countries on three continents. The aim of this trial was to explore the impact of differential delayed intensification (DI) on outcome in all risk groups.
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Changes in the hormone (ACTH, insulin,epinephrine) content of immune cells in children having acute lymphocytic leukemia (all).
Acta Microbiol Immunol Hung
PUBLISHED: 12-03-2013
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Immune cells synthesize, store and secrete hormones, the level of which changes in ALL. In previous experiments the level of histamine, serotonin and triiodothyronine (T3)was studied, while at present that of ACTH, insulin and epinephrine, using flow cytometric analysis for the determination of cell subsets and detection of hor-mone content. The measurements were done in children at the time of diagnosis. ACTH was significantly elevated in each T cell subsets (total T, Th, Tc, activated T), while B and NK cells were not touched. The alterations in the insulin content (decrease in Tc and activated T cells) were uncertain, and NK cells contained significantly less insulin. The disease did not influence the cells epinephrine content. There is not clear explanation for the importance of changes in the cells hormone content, however, it is discussed in the text.
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Oxytocin in learning and addiction: From early discoveries to the present.
Pharmacol. Biochem. Behav.
PUBLISHED: 11-13-2013
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Oxytocin (OXT) has a plethora of effects on brain function. This review provides a historical overview of the development of research on OXT and drug addiction. By focusing on research that has emerged from our laboratories, we describe how early discoveries of the influence of OXT on learning and memory processes and the emerging conceptualization of addiction as pathological learning have contributed to the demonstration that OXT effectively attenuates long-term neuroadaptation related to opiate and psychostimulant addiction. Through integrating earlier evidence with recent discoveries of the social/affiliative role of OXT, we propose that OXT may interfere with reward and addiction by influencing neurobiological processes involved in stress, learning and memory and social/affiliative behavior.
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Changes in Right Ventricular Function Measured by Cardiac Magnetic Resonance Imaging in Patients Receiving Pulmonary Arterial Hypertension-targeted Therapy: The EURO-MR Study.
Circ Cardiovasc Imaging
PUBLISHED: 10-30-2013
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-Most measures that predict survival in pulmonary hypertension (PH) relate directly to, or correlate with, right ventricular (RV) function. Direct assessment of RV function, using non-invasive techniques such as cardiac magnetic resonance imaging (CMRI), may therefore be an appropriate way of determining response to therapy and/or monitoring disease progression in PH.
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Rapidly progressive dementia with thalamic degeneration and peculiar cortical prion protein immunoreactivity, but absence of proteinase K resistant PrP: a new disease entity?
Acta Neuropathol Commun
PUBLISHED: 10-29-2013
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Human prion diseases are a group of rare fatal neurodegenerative conditions with well-developed clinical and neuropathological diagnostic criteria. Recent observations have expanded the spectrum of prion diseases beyond the classically recognized forms.
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Medical and economic burden of influenza in the elderly population in central and eastern European countries.
Hum Vaccin Immunother
PUBLISHED: 10-28-2013
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Influenza affects 5-15% of the population during an epidemic. In Western Europe, vaccination of at-risk groups forms the cornerstone of influenza prevention. However, vaccination coverage of the elderly (> 65 y) is often low in Central and Eastern Europe (CEE); potentially because a paucity of country-specific data limits evidence-based policy making. Therefore the medical and economic burden of influenza were estimated in elderly populations in the Czech Republic, Hungary, Kazakhstan, Poland, Romania, and Ukraine. Data covering national influenza vaccination policies, surveillance and reporting, healthcare costs, populations, and epidemiology were obtained via literature review, open-access websites and databases, and interviews with experts. A simplified model of patient treatment flow incorporating cost, population, and incidence/prevalence data was used to calculate the influenza burden per country. In the elderly, influenza represented a large burden on the assessed healthcare systems, with yearly excess hospitalization rates of ~30/100?000. Burden varied between countries and was likely influenced by population size, surveillance system, healthcare provision, and vaccine coverage. The greatest burden was found in Poland, where direct costs were over EUR 5 million. Substantial differences in data availability and quality were identified, and to fully quantify the burden of influenza in CEE, influenza reporting systems should be standardized. This study most probably underestimates the real burden of influenza, however the public health problem is recognized worldwide, and will further increase with population aging. Extending influenza vaccination of the elderly may be a cost-effective way to reduce the burden of influenza in CEE.
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[Smoking habits in Hungary: analysis based on surveys of the past decade].
Orv Hetil
PUBLISHED: 09-11-2013
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Passing the amendments to the anti-smoking law in Hungary indicates a firm determination of the Department of Health to curb tobacco use. Professional steps were destined to follow policies and control measures. The Methodological Support Center for Smoking Cessation began operation at the National Korányi Institute of Tuberculosis and Pulmonology, Budapest, Hungary in 2012. The objective is to provide methodological assistance for evidence based smoking cessation support. The Center aspires to unite and direct the activities aimed at tobacco control, as well as initiate the drafting of appropriate medical guidelines. The Center works to ensure that information regarding smoking and personalized cessation support reaches wide range of Hungarian smokers through individual group and telephone counseling methods. Analysis of the results of national surveys conducted during the past decade on the adult population reveals that the proportion of daily smokers in Hungary has decreased to 28-29%. The proportion of men smokers (32-34%) indicates a more significant decrease, while the proportion of women smokers (24-25%) levels. Groups that are most affected by increased risk of smoking are people with low level of education, those facing economic hardship, the age groups of 17-34 and 35-64 years and women.
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Intensity of human prion disease surveillance predicts observed disease incidence.
J. Neurol. Neurosurg. Psychiatr.
PUBLISHED: 08-21-2013
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Prospective national screening and surveillance programmes serve a range of public health functions. Objectively determining their adequacy and impact on disease may be problematic for rare disorders. We undertook to assess whether objective measures of disease surveillance intensity could be developed for the rare disorder sporadic Creutzfeldt-Jakob disease (CJD) and whether such measures correlate with disease incidence.
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Metabolic hormones in follicular fluid in women undergoing in vitro fertilization.
J Reprod Med
PUBLISHED: 08-17-2013
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To determine the concentrations of metabolic hormones in follicular fluid (FF) and to find clinical correlates of these biochemical parameters.
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N-truncated Abeta starting with position four: early intraneuronal accumulation and rescue of toxicity using NT4X-167, a novel monoclonal antibody.
Acta Neuropathol Commun
PUBLISHED: 08-08-2013
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The amyloid hypothesis in Alzheimer disease (AD) considers amyloid ? peptide (A?) deposition causative in triggering down-stream events like neurofibrillary tangles, cell loss, vascular damage and memory decline. In the past years N-truncated A? peptides especially N-truncated pyroglutamate A?pE3-42 have been extensively studied. Together with full-length A?1-42 and A?1-40, N-truncated A?pE3-42 and A?4-42 are major variants in AD brain. Although A?4-42 has been known for a much longer time, there is a lack of studies addressing the question whether A?pE3-42 or A?4-42 may precede the other in Alzheimers disease pathology.
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Biomarkers in pulmonary hypertension: what do we know?
Chest
PUBLISHED: 07-25-2013
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Pulmonary hypertension (PH) is a hemodynamic condition that has a poor prognosis and can lead to right-sided heart failure. It may result from common diseases such as left-sided heart or lung disease or may present as the rare entity of idiopathic pulmonary arterial hypertension. Biomarkers that specifically indicate the pathologic mechanism, the severity of the disease, and the treatment response would be ideal tools for the management of PH. In this review, markers related to heart failure, inflammation, hemostasis, remodeling, and endothelial cell-smooth muscle cell interaction are discussed, and their limitations are emphasized. Anemia, hypocarbia, elevated uric acid, and C-reactive protein levels are unspecific markers of disease severity. Brain natriuretic peptide and N-terminal fragment of pro-brain natriuretic peptide have been recommended in current guidelines, whereas other prognostic markers, such as growth differentiation factor-15, osteopontin, and red cell distribution width, are emerging. Chemokines of the CC family and matrix metalloproteases have been linked to the vascular pathologic mechanisms, and new markers such as apelin have been described. Circulating endothelial and progenitor cells have received much attention as markers of disease activity, but with controversial findings. A lack of standards for cell isolation and characterization methods and differences in the pathologic mechanisms of the investigated patients may have contributed to the discrepancies. In conclusion, although several promising markers have been identified over the past few years, the development of more specific markers, standardization, and prospective validation are warranted.
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Value of FDG-PET/CT Examinations in Different Cancers of Children, Focusing on Lymphomas.
Pathol. Oncol. Res.
PUBLISHED: 07-18-2013
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The aim of the study was to assess sensitivity and specificity of FDG-PET/CT in different forms of childhood cancer. We retrospectively evaluated the results dedicated of 162 FDG-PET/CT examinations of 86 children treated with: Hodgkin lymphoma (HL; n?=?31), non-Hodgkin lymphoma (NHL; n?=?30) and other high grade solid tumors (n?=?25). Patients were admitted and treated in two departments of pediatric hematology and oncology in Hungary. FDG-PET/CT was performed for staging (n?=?25) and for posttreatment evaluation (n?=?137). Imaging was performed in three FDG-PET/CT Laboratories, using dedicated PET/CT scanners. False positive results were defined as resolution or absence of disease progression over at least 1 year on FDG-PET/CT scans without any intervention. In some cases histopathological evaluation of suspicious lesions was performed. Fals negative results were defined as negative FDG-PET/CT results in case of active malignancy. Positive predictive values (PPV) and negative predictive values (NPV) were calculated. NPV was 100 %. The highest PPV was observed in high grade solid tumors (81 %), followed by HL (65 %) and NHL (61 %). There was a major difference of PPV in different histological types of HL (50 % in HL of mixed-cellularity subtype, 90 % in nodular sclerosing, and 100 % in lymphocyte-rich and lymphocyte depleted HL). We treated one patient with nodular lymphocyte predominant HL, who had 5 false positive FDG-PET/CT results. PPV of T- and B-lineage NHL were similar (60 % and 62 %, respectively). We observed an interesting difference of PPV in different stages of HL and NHL. In HL PPV was higher in early than in advanced disease forms: 66 % in stage II HL and 60 % in stage III HL, whereas there was an inverse relationship between PPV and disease stages in NHL 0 % in stage I and II patients, 67 % in stage III and 100 % in stage IV patients. PPV was lower in males (54 %) than in females (65 %). PPV were 64 % vs. 58 % in patients under vs. over 10 years of age. Negative FDG-PET/CT results during follow-up reliably predict the absence of malignancy. Positive FDG-PET/CT scan results in general have a low PPV. The relatively high PPV in patients with histologically proven high grade solid tumors, advanced stages of NHL and with nodular sclerosing, lymphocyte-rich and lymphocyte depleted subtypes of HL warrant a confirmation by biopsy, whereas the watch-and-wait approach can be used in other forms of childhood cancer patients with a positive FDG-PET/CT result in course of follow-up examinations.
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Non-invasive determination of pulmonary hypertension with dynamic contrast-enhanced computed tomography: a pilot study.
Eur Radiol
PUBLISHED: 07-05-2013
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In this pilot study we explored whether contrast-material bolus propagation time and speed in the pulmonary arteries (PAs) determined by dynamic contrast-enhanced computed tomography (DCE-CT) can distinguish between patients with and without pulmonary hypertension (PH).
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Asymptomatic hyper-creatine-kinase-emia as sole manifestation of inclusion body myositis.
Neurol Int
PUBLISHED: 06-25-2013
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Sporadic inclusion body myositis (sIBM) usually manifests with painless weakness of the hand, finger and hip flexors. Absence of symptoms or signs, but mild hyper-CK-emia as the sole manifestation of IBM, has not been reported. We report the case of a 73-year-old male who presented with asymptomatic recurrent hyper-CK-emia ranging from 200 to 1324U/L (n<171U/L), since 10 years. Clinical neurologic investigation, nerve conduction studies and EMG were non-informative. Muscle biopsy surprisingly revealed sIBM. sIBM may be asymptomatic and may manifest with hyper-CK-emia exclusively. So, it has to be included in the differential diagnoses of asymptomatic hyper-CK-emia.
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Zero reference level for right heart catheterisation.
Eur. Respir. J.
PUBLISHED: 06-21-2013
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Although in the pulmonary circulation small pressure differences may alter the categorisation of patients, there is no consensus on a standard zero reference level (ZRL). In the supine position, ZRL is mostly set at "5 cm below anterior thorax surface", "1/3 thoracic diameter below anterior thorax surface", "mid-thoracic level" or "10 cm above table level". We retrospectively assessed the distance of these four ZRLs from computed tomography-derived right and left atrial centre levels and from one another in patients undergoing right heart catheterisation and calculated the respective differences in pressure readings. We included 196 consecutive patients. The ZRL at "1/3 thoracic diameter" was most often (98.5%) level with the right atrium, and the ZRL at "mid-thoracic level" was level with the left atrium (97.4%), revealing a median (range) pressure difference of -0.3 (-3.0-1.3) and 0.2 (-2.0-1.3) mmHg from the right and left atrial centre level, respectively. The largest differences (8.0 (2.0-15.4) mmHg) were found between the ZRLs "5 cm below anterior thorax surface" and "10 cm above table level". Accordingly, 59% versus 80% of patients would be classified with pulmonary hypertension and 7% versus 38% with elevated left heart pressures. The choice of ZRL strongly influences pulmonary pressure readings and pulmonary hypertension classification. 1/3 thoracic diameter mostly represents the right atrium while the left atrium is best represented by the mid-thoracic level.
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L-arginine metabolism in early-onset and late-onset pre-eclamptic pregnancies.
Scand. J. Clin. Lab. Invest.
PUBLISHED: 06-18-2013
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The present case-control study was undertaken to investigate l-arginine metabolism in pregnant women with early-onset and late-onset pre-eclampsia. Attempts were made to differentiate these two distinct diseases entities by using measured and derived parameters of l-arginine metabolism.
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Simultaneous specific in planta visualization of root-colonizing fungi using fluorescence in situ hybridization (FISH).
Mycorrhiza
PUBLISHED: 05-29-2013
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In planta detection of mutualistic, endophytic, and pathogenic fungi commonly colonizing roots and other plant organs is not a routine task. We aimed to use fluorescence in situ hybridization (FISH) for simultaneous specific detection of different fungi colonizing the same tissue. We have adapted ribosomal RNA (rRNA) FISH for visualization of common mycorrhizal (arbuscular- and ectomycorrhiza) and endophytic fungi within roots of different plant species. Beside general probes, we designed and used specific ones hybridizing to the large subunit of rRNA with fluorescent dyes chosen to avoid or reduce the interference with the autofluorescence of plant tissues. We report here an optimized efficient protocol of rRNA FISH and the use of both epifluorescence and confocal laser scanning microscopy for simultaneous specific differential detection of those fungi colonizing the same root. The method could be applied for the characterization of other plant-fungal interactions, too. In planta FISH with specific probes labeled with appropriate fluorescent dyes could be used not only in basic research but to detect plant colonizing pathogenic fungi in their latent life-period.
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Non-neuronal cell responses differ between normal and Down syndrome developing brains.
Int. J. Dev. Neurosci.
PUBLISHED: 05-29-2013
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Down syndrome (DS), the most common genetic cause of mental retardation, is characterized by reduced number of neurons and delayed myelination. Though non-neuronal cells in the brain are vital for the development, survival, and function of neurons, there is a paucity of comparative studies of normal development and DS, in particular in the temporal lobe, a region of interest for cognitive decline. We evaluated immunoreactivity for CD68 (macrophage), HLA-DR (microglia), Olig2 and TPPP/p25 (oligodendroglia), and GFAP (astroglia) in the germinal matrix (GM), temporal lobe white matter (TeWM) and hippocampus from 14 weeks of gestations to newborn in 28 DS patients and 30 age-matched controls. The rate of increase of CD68 positive cells in the GM, CA1 hippocampal subregion and subiculum was significantly higher in DS. The density of Olig2 positive cells in the GM was lower in DS brains at early stages, then showed a transient increase contrasting controls. Olig2 expression increased more in the TeWM in DS, suggesting an altered pattern of oligodendrocyte progenitor generation. GFAP-immunoreactivity in DS was significantly lower in the middle pregnancy period in the TeWM and did not increase between early and middle periods in the GM compared to controls, likely reflecting a defect in astrocyte production. The altered expression of non-neuronal cell markers during normal development and DS may play a role in, or reflect, defective neurogenesis, leading to reduced number of neurons and delayed myelination in the developing DS brain. This has implications for the understanding of the mental retardation in DS patients.
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Non-Alzheimer neurodegenerative pathologies and their combinations are more frequent than commonly believed in the elderly brain: a community-based autopsy series.
Acta Neuropathol.
PUBLISHED: 05-02-2013
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Neurodegenerative diseases are characterised by neuronal loss and cerebral deposition of proteins with altered physicochemical properties. The major proteins are amyloid-? (A?), tau, ?-synuclein, and TDP-43. Although neuropathological studies on elderly individuals have emphasised the importance of mixed pathologies, there have been few observations on the full spectrum of proteinopathies in the ageing brain. During a community-based study we performed comprehensive mapping of neurodegeneration-related proteins and vascular pathology in the brains of 233 individuals (age at death 77-87; 73 examined clinically in detail). While all brains (from individuals with and without dementia) showed some degree of neurofibrillary degeneration, A? deposits were observed only in 160 (68.7 %). Further pathologies included ?-synucleinopathies (24.9 %), non-Alzheimer tauopathies (23.2 %; including novel forms), TDP-43 proteinopathy (13.3 %), vascular lesions (48.9 %), and others (15.1 %; inflammation, metabolic encephalopathy, and tumours). TDP-43 proteinopathy correlated with hippocampal sclerosis (p < 0.001) and Alzheimer-related pathology (CERAD score and Braak and Braak stages, p = 0.001). The presence of one specific variable (cerebral amyloid angiopathy, A? parenchymal deposits, TDP-43 proteinopathy, ?-synucleinopathy, vascular lesions, non-Alzheimer type tauopathy) did not increase the probability of the co-occurrence of others (p = 0.24). The number of observed pathologies correlated with AD-neuropathologic change (p < 0.0001). In addition to AD-neuropathologic change, tauopathies associated well with dementia, while TDP-43 pathology and ?-synucleinopathy showed strong effects but lost significance when evaluated together with AD-neuropathologic change. Non-AD neurodegenerative pathologies and their combinations have been underestimated, but are frequent in reality as demonstrated here. This should be considered in diagnostic evaluation of biomarkers, and for better clinical stratification of patients.
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Determination of cardiac output with dynamic contrast-enhanced computed tomography.
Int J Cardiovasc Imaging
PUBLISHED: 04-26-2013
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Cardiac output (CO) is an important diagnostic and prognostic factor in the haemodynamic evaluation of patients. The gold standard for CO measurement, thermodilution, requires an invasive right-heart catheterisation (RHC). In this pilot study we aimed to determine the accuracy of non-invasive CO determination from dynamic contrast-enhanced computed tomography (CT) compared to thermodilution. Patients who underwent diagnostic or follow-up RHC due to suspected or known pulmonary vascular disease at our department and required a thoracic CT between June 2011 and August 2012 were included. CO was determined from CT attenuation-time curves in the pulmonary artery and the ascending aorta using a dynamic contrast-enhanced CT sequence. CO determined in N = 18 patients by dynamic CT in the pulmonary artery was in very good agreement with thermodilution data (r = 0.84). Bland-Altman analysis showed a systematic overestimation of 0.7 ± 0.6 l/min compared to thermodilution. Data from the ascending aorta also showed a good correlation, but with a larger scattering of the values. The average effective dose for the dynamic investigation was 1.2 ± 0.7 mSv. CO determined with dynamic contrast-enhanced CT in the main pulmonary artery reliably predicts the values obtained by thermodilution during RHC. This non-invasive technique might provide an alternative for repeated invasive right-heart catheter investigations in the follow-up of pulmonary arterial hypertension patients.
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[Experiences with a self developed accelerometer].
Ideggyogy Sz
PUBLISHED: 04-24-2013
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In neurology the objective evaluation of improvement of paresis on every-day practice. The aim of this study was to develop and test a small 3-d acceleration measuring device and validate its usefulness.
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Atypical and classical forms of the disease-associated state of the prion protein exhibit distinct neuronal tropism, deposition patterns, and lesion profiles.
Am. J. Pathol.
PUBLISHED: 04-09-2013
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A number of disease-associated PrP forms characterized by abnormally short proteinase K-resistant fragments (atypical PrPres) were recently described in prion diseases. The relationship between atypical PrPres and PrP(Sc), and their role in etiology of prion diseases, remains unknown. We examined the relationship between PrP(Sc) and atypical PrPres, a form characterized by short C-terminal proteinase K-resistant fragments, in a prion strain of synthetic origin. We found that the two forms exhibit distinct neuronal tropism, deposition patterns, and degree of pathological lesions. Immunostaining of brain regions demonstrated a partial overlap in anatomic involvement of the two forms and revealed the sites of their selective deposition. The experiments on amplification in vitro suggested that distinct neuronal tropism is attributed to differences in replication requirements, such as preferences for different cellular cofactors and PrP(C) glycoforms. Remarkably, deposition of atypical PrPres alone was not associated with notable pathological lesions, suggesting that it was not neurotoxic, but yet transmissible. Unlike PrP(Sc), atypical PrPres did not show significant perineuronal, vascular, or perivascular immunoreactivity. However, both forms showed substantial synaptic immunoreactivity. Considering that atypical PrPres is not associated with substantial lesions, this result suggests that not all synaptic disease-related PrP states are neurotoxic. The current work provides important new insight into our understanding of the structure-pathogenicity relationships of transmissible PrP states.
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Globular glial tauopathies (GGT): consensus recommendations.
Acta Neuropathol.
PUBLISHED: 04-08-2013
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Recent studies have highlighted a group of 4-repeat (4R) tauopathies that are characterised neuropathologically by widespread, globular glial inclusions (GGIs). Tau immunohistochemistry reveals 4R immunoreactive globular oligodendroglial and astrocytic inclusions and the latter are predominantly negative for Gallyas silver staining. These cases are associated with a range of clinical presentations, which correlate with the severity and distribution of underlying tau pathology and neurodegeneration. Their heterogeneous clinicopathological features combined with their rarity and under-recognition have led to cases characterised by GGIs being described in the literature using various and redundant terminologies. In this report, a group of neuropathologists form a consensus on the terminology and classification of cases with GGIs. After studying microscopic images from previously reported cases with suspected GGIs (n = 22), this panel of neuropathologists with extensive experience in the diagnosis of neurodegenerative diseases and a documented record of previous experience with at least one case with GGIs, agreed that (1) GGIs were present in all the cases reviewed; (2) the morphology of globular astrocytic inclusions was different to tufted astrocytes and finally that (3) the cases represented a number of different neuropathological subtypes. They also agreed that the different morphological subtypes are likely to be part of a spectrum of a distinct disease entity, for which they recommend that the overarching term globular glial tauopathy (GGT) should be used. Type I cases typically present with frontotemporal dementia, which correlates with the fronto-temporal distribution of pathology. Type II cases are characterised by pyramidal features reflecting motor cortex involvement and corticospinal tract degeneration. Type III cases can present with a combination of frontotemporal dementia and motor neuron disease with fronto-temporal cortex, motor cortex and corticospinal tract being severely affected. Extrapyramidal features can be present in Type II and III cases and significant degeneration of the white matter is a feature of all GGT subtypes. Improved detection and classification will be necessary for the establishment of neuropathological and clinical diagnostic research criteria in the future.
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Developmental patterns of DR6 in normal human hippocampus and in Down syndrome.
J Neurodev Disord
PUBLISHED: 04-04-2013
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Death receptor 6 (DR6) is highly expressed in the human brain: it has been shown to induce axon pruning and neuron death via distinct caspases and to mediate axonal degeneration through binding to N-terminal ? amyloid precursor protein (N-APP).
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Acylcarnitine esters profiling of serum and follicular fluid in patients undergoing in vitro fertilization.
Reprod. Biol. Endocrinol.
PUBLISHED: 03-29-2013
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L-carnitine-mediated beta-oxidation of fatty acids has a well established role in energy supply of oocytes and embryos. Disturbed carnitine metabolism may impair the reproductive potential in IVF and can serve as a biomarker of pregnancy outcome.
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[Examination of late pulmonary toxicity in children treated for malignancies].
Orv Hetil
PUBLISHED: 02-26-2013
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The present investigation was based on a survey in 2005, in which the authors found pulmonary function abnormalities in survivors of childhood cancer, who were treated with anticancer therapy.
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Mammalian target of rapamycin (mTOR) activity dependent phospho-protein expression in childhood acute lymphoblastic leukemia (ALL).
PLoS ONE
PUBLISHED: 02-13-2013
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Modern treatment strategies have improved the prognosis of childhood ALL; however, treatment still fails in 25-30% of patients. Further improvement of treatment may depend on the development of targeted therapies. mTOR kinase, a central mediator of several signaling pathways, has recently attracted remarkable attention as a potential target in pediatric ALL. However, limited data exists about the activity of mTOR. In the present study, the amount of mTOR activity dependent phospho-proteins was characterized by ELISA in human leukemia cell lines and in lymphoblasts from childhood ALL patients (n = 49). Expression was measured before and during chemotherapy and at relapses. Leukemia cell lines exhibited increased mTOR activity, indicated by phospho-S6 ribosomal protein (p-S6) and phosphorylated eukaryotic initiation factor 4E binding protein (p-4EBP1). Elevated p-4EBP1 protein levels were detected in ALL samples at diagnosis; efficacy of chemotherapy was followed by the decrease of mTOR activity dependent protein phosphorylation. Optical density (OD) for p-4EBP1 (ELISA) was significantly higher in patients with poor prognosis at diagnosis, and in the samples of relapsed patients. Our results suggest that measuring mTOR activity related phospho-proteins such as p-4EBP1 by ELISA may help to identify patients with poor prognosis before treatment, and to detect early relapses. Determining mTOR activity in leukemic cells may also be a useful tool for selecting patients who may benefit from future mTOR inhibitor treatments.
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Neuropathology of partial PGC-1? deficiency recapitulates features of mitochondrial encephalopathies but not of neurodegenerative diseases.
Neurodegener Dis
PUBLISHED: 02-13-2013
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Deficient peroxisome proliferator-activated receptor-? coactivator-1? (PGC-1?) function is one component of mitochondrial dysfunction in neurodegenerative diseases. Current molecular classification of such diseases is based on the predominant protein accumulating as intra- or extracellular aggregates. Experimental evidence suggests that mitochondrial dysfunction and impaired protein processing are closely interrelated. In vitro findings further indicate that PGC-1? dysfunction may contribute to protein misfolding in neurodegeneration.
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Comparison of cooling and EMLA to reduce the burning pain during capsaicin 8% patch application: A randomized, double-blind, placebo-controlled study.
Pain
PUBLISHED: 02-08-2013
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Topical capsaicin 8% was developed for the treatment of peripheral neuropathic pain. The pain reduction is associated with a reversible reduction of epidermal nerve fiber density (ENFD). During its application, topical capsaicin 8% provokes distinct pain. In a randomized, double-blind study analyzed with a block factorial analysis of variance, we tested whether cooling the skin would result in reliable prevention of the application pain without inhibiting reduction of ENFD. A capsaicin 8% patch was cut into 4 quarters and 2 each were applied for 1hour on the anterior thighs of 12 healthy volunteers. A randomization scheme provided for 1 of the application sites of each thigh to be pretreated with EMLA and the other with placebo, whereas both application sites of 1 thigh, also randomly selected, were cooled by cool packs, resulting in a site temperature of 20°C during the entire treatment period. The maximum pain level given for the cooled sites (visual analogue scale [VAS] 1.3±1.4) proved to be significantly lower than for the non-cooled sites (VAS 7.5±1.9) (P<.0001). In contrast, there was no significant difference in application pain between the sites pretreated with EMLA or with placebo (VAS 4.1±3.6 vs 4.8±3.5, P=.1084). At all application sites, ENFD was significantly reduced by 8.0±2.8 (ENF/mm±SD, P<.0001), that is, 70%, with no significant differences between the sites with the different experimental conditions. In conclusion, cooling the skin to 20°C reliably prevents the pain from capsaicin 8% patch application, whereas EMLA does not. ENFD reduction is not inhibited by cooling.
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JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.