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Find video protocols related to scientific articles indexed in Pubmed.
Dual small fragment plating improves screw-to-screw load sharing for mid-diaphyseal humeral fracture fixation: A finite element study.
Technol Health Care
PUBLISHED: 11-20-2014
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A smaller humerus in some patients makes the use of a large fragment fixation plate difficult. Dual small fragment plate constructs have been suggested as an alternative.
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Peripheral ?-Defensins 1 and 2 are Elevated in Alzheimer's Disease.
J. Alzheimers Dis.
PUBLISHED: 11-20-2014
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Biomarkers enabling the preclinical identification of Alzheimer's disease (AD) remain one of the major unmet challenges in the field. The blood cellular fractions offer a viable alternative to current cerebrospinal fluid and neuroimaging modalities. The current study aimed to replicate our earlier reports of altered binding within the AD-affected blood cellular fraction to copper-loaded immobilized metal affinity capture (IMAC) arrays. IMAC and anti-amyloid-? (A?) antibody arrays coupled with mass spectrometry were used to analyze blood samples collected from 218 participants from within the AIBL Study of Aging. Peripheral A? was fragile and prone to degradation in the AIBL samples, even when stored at -80°C. IMAC analysis of the AIBL samples lead to the isolation and identification of alpha-defensins 1 and 2 at elevated levels in the AD periphery, validating earlier findings. Alpha-defensins 1 and 2 were elevated in AD patients indicating that an inflammatory phenotype is present in the AD periphery; however, peripheral A? levels are required to supplement their prognostic power.
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Capillary electrophoresis for quantitative studies of biomolecular interactions.
Anal. Chem.
PUBLISHED: 11-20-2014
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The development of highly selective and sensitive analytical techniques has been a driving force for unprecedented advances in biotechnology, gene engineering, and drug discovery. Capillary electrophoresis (CE) is becoming a wider accepted analytical method in biology and medicine. CE offers short analysis time, high resolution, and minute consumption of samples and reagents, making it an attractive technique for mass bioassays and drug screening. Since the last Analytical Chemistry's review in this field1 there have been published over ten thousands articles with CE as a topic. Within a variety of studies concerning CE, we have identified the intensively developing area of reversible biomolecular interactions which are defined as highly selective non-covalent binding of ligands with biomolecules. These affinity interactions control cell recognition, signal transduction, immune response, DNA replication, gene expression, and other cellular processes. The knowledge of quantitative parameters of binding reactions (equilibrium and/or rate constants) is essential for understanding the mechanisms of biological processes, which these reactions regulate. The present review covers a three-year period between January 2012 and November 2014. We have attempted to select studies that demonstrate the newest and most impactive developments in the field of biomolecular affinity interactions.
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Virtual experiments in megastudies: a case study of language and emotion.
Q J Exp Psychol (Hove)
PUBLISHED: 11-20-2014
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Abstract A recent dramatic increase in the number and scope of chronometric and norming lexical megastudies offers the ability to conduct virtual experiments, that is, to draw samples of items with properties that vary in critical linguistic dimensions. This paper introduces a bootstrapping approach which enables testing research hypotheses against a range of samples selected in a uniform, principled manner and evaluates how likely a theoretically motivated pattern is in a broad distribution of possible outcome patterns. We apply this approach to conflicting theoretical and empirical accounts of the relationship between the psychological valence (positivity) of a word and its speed of recognition. To this end, we conduct three sets of multiple virtual experiments with a factorial and a regression design, drawing data from two lexical decision megastudies. We discuss the influence that criteria for stimuli selection, statistical power, collinearity and the choice of dataset have on the efficacy and outcomes of the bootstrapping procedure.
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Angiomatoid Fibrous Histiocytoma With Prominent Myxoid Stroma: A Case Report and Review of the Literature.
Am J Dermatopathol
PUBLISHED: 11-20-2014
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: Angiomatoid fibrous histiocytoma is a rare neoplasm of intermediate malignant potential that usually occurs in the dermis or subcutaneous tissues of the extremities in children or young adults. It is characterized by a nodular growth of spindled, histiocytic, or epithelioid cells and blood-filled spaces, surrounded by a fibrous pseudocapsule that contains a lymphocytic cuff. The histological spectrum of this condition has expanded to include cases that contain prominent myxoid stroma. We herein present another instance of myxoid angiomatoid fibrous histiocytoma and review the clinical and histological features, immunohistochemical profile, and molecular genetics of this uncommon variant. We also discuss the diagnostic mimics of this condition, including benign myxoid soft tissue tumors and sarcomas, to illustrate the potential pitfalls in arriving at the diagnosis.
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Plasma exchange to remove HIT antibodies: dissociation between enzyme-immunoassay and platelet activation test reactivities.
Blood
PUBLISHED: 11-20-2014
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Repeated therapeutic plasma exchange (TPE) has been advocated to remove heparin-induced thrombocytopenia (HIT) IgG antibodies prior to cardiac/vascular surgery in patients who have serologically-confirmed acute or subacute HIT; for this situation, a negative platelet activation assay (e.g., platelet serotonin-release assay [SRA]) has been recommended as the target serological endpoint to permit safe surgery. We compared reactivities in the SRA and an anti-PF4/heparin IgG-specific enzyme-immunoassay (EIA), testing serial serum samples in a patient with recent (subacute) HIT who underwent serial TPE pre-cardiac surgery, as well as for 15 other serially-diluted HIT sera. We observed that post-TPE/diluted HIT sera-when first testing SRA-negative-continue to test strongly positive by EIA-IgG. This dissociation between the platelet activation assay and a PF4-dependent immunoassay for HIT antibodies indicates that patients with subacute HIT undergoing repeated TPE prior to heparin re-exposure should be tested by serial platelet activation assays even when their EIAs remain strongly positive.
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The monocarboxylate transporter 4 is required for glycolytic reprogramming and inflammatory response in macrophages.
J. Biol. Chem.
PUBLISHED: 11-20-2014
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There has been fast growing evidence showing that glycolysis plays a critical role in the activation of immune cells. Enhanced glycolysis leads to increased formation of intracellular lactate that is exported to the extracellular environment by monocarboxylate transporter 4 (MCT4). Although the biological activities of extracellular lactate have been well studied, it is less understood how the lactate export is regulated or if lactate export affects glycolysis during inflammatory activation. In this study, we found that MCT4 is upregulated by TLR2 and TLR4, but not TLR3 agonists in a variety of macrophages. The increased expression of MCT4 was mediated by MYD88 in a NF-?B dependent manner. Furthermore, we found that MCT4 is required for macrophage activation upon TLR2 and TLR4 stimulations, as evidenced by attenuated expression of pro-inflammatory mediators in macrophages with MCT4 knockdown. Mechanistically, we found that MCT4 knockdown leads to enhanced intracellular accumulation of lactate and decreased glycolysis in LPS treated macrophages. We found that LPS induced expression of key glycolytic enzymes hexokinase 2 (HK2) and 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3) is diminished in macrophages with MCT4 knockdown. Our data suggest that MCT4 upregulation represents a positive feedback mechanism in macrophages to maintain a high glycolytic rate that is essential to a fully activated inflammatory response.
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Fibrosis: ultimate and proximate causes.
J. Clin. Invest.
PUBLISHED: 11-03-2014
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Fibrotic disorders account for an increasing burden of disease-associated morbidity and mortality worldwide. Although numerous risk factors have been recognized, the etiologies of many of these clinical syndromes have not been identified, and they are often termed idiopathic or cryptogenic. Here, we provide an evolutionary perspective on fibrosis aimed at elucidating its etiopathogenesis. By asking the ultimate question of "why" this process evolved in multicellular organisms, we hope to uncover proximate explanations for "how" it causes disease in humans. We posit that physiological fibrosis-like reactions evolved as an essential process in host defense against pathogens and in normal wound healing. Based on this premise, we reason that pathological fibrosis is related to one or more of the following: unidentified infectious or noninfectious antigens, autoimmunity, impaired regenerative responses, and the antagonistically pleiotropic action of genes involved in wound healing or development. The importance of genetic susceptibility, epigenetics, aging, and the modern-day environment are highlighted. Consideration of both ultimate and proximate causation goes beyond philosophical cogitations, as it will better inform pathobiological mechanisms of disease and aid in the prevention and treatment of fibrotic diseases.
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Plasma amyloid-? levels are significantly associated with a transition toward Alzheimer's disease as measured by cognitive decline and change in neocortical amyloid burden.
J. Alzheimers Dis.
PUBLISHED: 10-31-2014
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We evaluated the utility of longitudinal measures of plasma amyloid-? (A?) as a means to identify pre-symptomatic cognitive decline in Alzheimer's disease (AD) when coupled to neuroimaging and neuropsychological parameters.
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Affective biases in English are bi-dimensional.
Cogn Emot
PUBLISHED: 10-15-2014
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A long-standing observation about the interface between emotion and language is that positive words are used more frequently than negative ones, leading to the Pollyanna hypothesis which alleges a predominantly optimistic outlook in humans. This paper uses the largest available collection of affective ratings as well as insights from linguistics to revisit the Pollyanna hypothesis as it relates to two dimensions of emotion: valence (pleasantness) and arousal (intensity). We identified systematic patterns in the distribution of words over a bi-dimensional affective space, which (1) run counter to and supersede most prior accounts, and (2) differ drastically between word types (unique, distinct words in the lexicon) and word tokens (number of occurrences of available words in the lexicon). We argue for two factors that shape affect in language and society: a pro-social benevolent communication strategy with its emphasis on useful and dangerous phenomena, and the structure of human subjective perception of affect.
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Effect of Supercoiling on the Mechanical and Permeability Properties of Model Collagen IV Networks.
Ann Biomed Eng
PUBLISHED: 10-13-2014
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Collagen IV networks in the glomerular basement membrane (GBM) are essential for the maintenance and regulation of blood filtration in the kidneys. The GBM contains two different types of collagen IV networks: [?1(IV)]2?2(IV) and ?3(IV)?4(IV)?5(IV), the latter of which has a higher number of supercoils (two or more collagens coiling around each other). To investigate the effects of supercoiling on the mechanical and permeability properties of collagen IV networks, we generated model collagen IV networks in the GBM and reconnected them to create different levels of supercoiling. We found that supercoiling greatly increases the stiffness of collagen IV networks but only minimally decreases the permeability. Also, doubling the amount of supercoils in a network had a bigger effect than doubling the stiffness of the supercoils. Our results suggest that the formation of supercoils is a specialized mechanism by the GBM that provides with a network stiff and strong enough to withstand the high hydrostatic pressures of filtration, yet porous enough that filtration is not hindered. Clinically, understanding the effects of supercoiling gives us insight into the mechanisms of GBM failure in some disease states where the normal collagen IV structure is disrupted.
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Differentiating the Frontal Presentation of Alzheimer's Disease with FDG-PET.
J. Alzheimers Dis.
PUBLISHED: 09-28-2014
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Background: Alzheimer's disease (AD) can present with behavioral changes with this syndrome described as frontal variant AD (FvAD). Excess frontal pathology may explain this presentation. Neuroimaging with fluoro-deoxy-glucose positron emission tomography (FDG- PET) can be used to examine the effects of pathology in FvAD. Methods: We administered an assessment scale for frontal behavioral impairment, the Frontal Behavioral Inventory (FBI), to 53 patients with AD. Scores in the top quartile were defined as FvAD. FDG- PET was analyzed in 8 frontal regions. Results: The Z (SD) score for metabolism was significantly higher (indicating greater hypometabolism) in the FvAD group than the remaining AD group for combined left and right orbitofrontal regions (2.64 (SD 0.99) versus 2.11 (1.22), p < 0.03)) and combined left and right medial frontal regions (2.38 (0.63) versus 1.82 (0.88) p < 0.003) but insignificantly different in combined lateral frontal and superior frontal regions. Statistical parametric mapping revealed these frontal regions to be the only brain regions with significantly different metabolism between the FvAD and the remainder of the AD groups. Conclusions: Medial and orbital frontal hypometabolism is greater in AD patients presenting with more frontal/behavioral features, likely reflecting a greater pathological load in these brain regions in FvAD patients. These frontal regions may be more linked to behavioral features than other frontal brain regions.
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Influence of BDNF Val66Met on the relationship between physical activity and brain volume.
Neurology
PUBLISHED: 09-03-2014
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To investigate the association between habitual physical activity levels and brain temporal lobe volumes, and the interaction with the brain-derived neurotrophic factor (BDNF) Val66Met polymorphism.
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Amyloid-? Related Memory Decline is not Associated with Subjective or Informant Rated Cognitive Impairment in Healthy Adults.
J. Alzheimers Dis.
PUBLISHED: 08-11-2014
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Background: The detection of early Alzheimer's disease (AD) can rely on subjective and informant reports of cognitive impairment. However, relationships between subjective cognitive impairment, objectively measured cognitive function, and amyloid-? (A?) biomarkers remain unclear. Objective: To determine the extent to which impairment or decline in subjective and informant rated cognitive impairment was associated with memory in healthy older adults with high A?. Methods: Healthy older adults (n = 289) enrolled in the Australian Imaging, Biomarkers and Lifestyle (AIBL) study were studied at baseline. Pittsburgh Compound B was used to determine A? status at baseline. At baseline and 18 months assessments, subjective memory impairment was assessed using the Memory Complaint Questionnaire and the Short Form of the Informant Questionnaire on Cognitive Decline in the Elderly. Cognition was measured using the Cogstate Brief Battery. Results: At baseline, there were no differences between low and high A? groups in subjective or informant-rated cognitive impairment, depressive and anxiety symptoms, or cognitive function. Longitudinal analyses showed moderate decline in learning and working memory over the 18 months in the high A? group. However there was no change over time in subjective or informant-rated cognitive impairment, depressive and anxiety symptoms, or cognition in either A? group. Conclusions: Although healthy older adults with high A? levels show decline in learning and working memory over 18 months, subjective or informant ratings of cognitive impairment do not change over the same period suggesting subjective cognitive impairment may have limited utility for the very early identification of AD.
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Interaction of the nematophagous fungus Pochonia chlamydosporia and Parascaris equorum eggs in different culture media.
J. Basic Microbiol.
PUBLISHED: 08-05-2014
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Research involving the use of nematophagous fungi in the biological control of parasites of interest to veterinarians has occurred over recent years, with promising results. This article reports the infection of Parascaris equorum eggs by the fungus Pochonia chlamydosporia (isolates VC1 and VC4). Six groups were formed for each isolate, with six different culture media: 2% water-agar (2% WA); agar-chitin (AC); YPSSA (yeast extract, K2HPO4, MgSO4 ·7H2O, soluble starch); AELA extract (starch?+?water?+?agar); 2% corn-meal-agar (2% CMA); and 2% potato dextrose-agar (2% PDA). A total of 1000 eggs of P. equorum were transferred to each plate containing isolates grown for a period of 7 days (treatment group). Also, 1000 eggs were added to each plate without fungus (controlgroup). The plates were kept in an environmental chamber at 25?°C in the dark for 21 days. After, we analyzed the effects on ovicidal activity: effect 1 (accession shell); effect 2 (penetration hyphae); and effect 3 (destruction of the eggs). No differences were observed in the destruction of eggs between the two isolates. The decreasing effectiveness of the different culture media was: PDA (38.9%); CMA (38.3%); WA (36.7%); YPSSA (36.45%); and AC (32.5%). The highest percentage egg destruction was observed when the strains were grown in culture medium AELA (44.9%); this was the best medium.
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Characterization of a new composite PMMA-HA/Brushite bone cement for spinal augmentation.
J Biomater Appl
PUBLISHED: 08-01-2014
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Calcium phosphate fillers have been shown to increase cement osteoconductivity, but have caused drawbacks in cement properties. Hydroxyapatite and Brushite were introduced in an acrylic two-solution cement at varying concentrations. Novel composite bone cements were developed and characterized using rheology, injectability, and mechanical tests. It was hypothesized that the ample swelling time allowed by the premixed two-solution cement would enable thorough dispersion of the additives in the solutions, resulting in no detrimental effects after polymerization. The addition of Hydroxyapatite and Brushite both caused an increase in cement viscosity; however, these cements exhibited high shear-thinning, which facilitated injection. In gel point studies, the composite cements showed no detectable change in gel point time compared to an all-acrylic control cement. Hydroxyapatite and Brushite composite cements were observed to have high mechanical strengths even at high loads of calcium phosphate fillers. These cements showed an average compressive strength of 85?MPa and flexural strength of 65?MPa. A calcium phosphate-containing cement exhibiting a combination of high viscosity, pseudoplasticity and high mechanical strength can provide the essential bioactivity factor for osseointegration without sacrificing load-bearing capability.
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Exposure to cigarette smoke impacts myeloid-derived regulatory cell function and exacerbates airway hyper-responsiveness.
Lab. Invest.
PUBLISHED: 07-10-2014
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Cigarette smoking enhances oxidative stress and airway inflammation in asthma, the mechanisms of which are largely unknown. Myeloid-derived regulatory cells (MDRC) are free radical producing immature myeloid cells with immunoregulatory properties that have recently been demonstrated as critical regulators of allergic airway inflammation. NO (nitric oxide)-producing immunosuppressive MDRC suppress T-cell proliferation and airway-hyper responsiveness (AHR), while the O2(•-) (superoxide)-producing MDRC are proinflammatory. We hypothesized that cigarette smoke (CS) exposure may impact MDRC function and contribute to exacerbations in asthma. Exposure of bone marrow (BM)-derived NO-producing MDRC to CS reduced the production of NO and its metabolites and inhibited their potential to suppress T-cell proliferation. Production of immunoregulatory cytokine IL-10 was significantly inhibited, while proinflammatory cytokines IL-6, IL-1?, TNF-? and IL-33 were enhanced in CS-exposed BM-MDRC. Additionally, CS exposure increased NF-?B activation and induced BM-MDRC-mediated production of O2(•-), via NF-?B-dependent pathway. Intratracheal transfer of smoke-exposed MDRC-producing proinflammatory cytokines increased NF-?B activation, reactive oxygen species and mucin production in vivo and exacerbated AHR in C57BL/6 mice, mice deficient in Type I IFNR and MyD88, both with reduced numbers of endogenous MDRC. Thus CS exposure modulates MDRC function and contributes to asthma exacerbation and identifies MDRC as potential targets for asthma therapy.Laboratory Investigation advance online publication, 3 November 2014; doi:10.1038/labinvest.2014.126.
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Role of 18F-FDG-PET/CT in the management of marginal zone B cell lymphoma.
Hematol Oncol
PUBLISHED: 07-01-2014
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The use of PET in patients with marginal zone B cell lymphoma (MZL) is controversial because of variability of fluorodeoxyglucose (FDG) avidity. We analyzed 40 PET/CT in 25 consecutive patients to compare its performance with CT at staging and as a first-line response assessment. Sensitivity of PET/CT and CT was 96 and 76%. Mean standard uptake value was 6.1, 6.9 and 3.4 (p?=?0.3) in nodal, extranodal and splenic subtypes, respectively. Of 17 patients (extranodal: n?=?9; nodal: n?=?6; splenic subtype: n?=?2) with both imaging tests available at diagnosis, 8 (47%) had more involved areas with PET/CT than with CT, 75% of which were extranodal lesions. PET/CT resulted in upstaging of five patients although treatment of only two of them was changed. Responses of 15 patients with post-treatment PET/CT were the following: 9 negative and 6 positive of which 3 were isolated residual lesions. Progression was documented in two of these three patients. Response was also assessed by CT in 11 patients. Discrepancies were found in three: Two were in complete remission by CT while PET/CT detected localized residual disease; another patient was in partial remission by CT, whereas PET/CT showed only one positive lesion. Two of these three patients relapsed. Patients with negative post-treatment PET/CT did not relapse. With a median follow-up of 50?months (10-152?months), 3-year overall survival was 100 and 80% for patients with negative and positive post-treatment PET/CT (p?=?0.2). Three-year disease-free survival was 86%; the negative predictive value (NPV) was 100%, and the positive predictive value (PPV) was 83.3%. Although a larger number of patients will be required to further confirm these data, we can conclude that PET/CT is a useful imaging tool for both staging and response assessment in patients with nodal and extranodal MZL as a result of its high sensitivity, NPV and PPV. Copyright © 2014 John Wiley & Sons, Ltd.
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Effect of the fungus Pochonia chlamydosporia on Echinostoma paraensei (Trematoda: Echinostomatidae).
Acta Trop.
PUBLISHED: 06-30-2014
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Echinostoma paraensei is a trematode of the genus Echinostoma that causes echinostomiasis in humans. The objectives of this study were to: evaluate the ovicidal activity of the nematophagous fungus Pochonia chlamydosporia (VC1 and VC4) on a solid medium 2% water-agar (2% WA) against E. paraensei eggs (assay A); evaluate ovicidal effect (destruction of eggs) of the isolate VC4 in supplemented culture media (assay B); and evaluate the ovicidal ability of the crude extract (VC4) on E. paraensei eggs (assay C). Eggs of E. paraensei (assay A) were placed in Petri dishes containing 2% WA with an isolate of the fungus P. chlamydosporia (VC1 and VC4) grown for 10 days, and without fungus as a control and evaluated regarding their destruction. In assay B, eggs of E. paraensei were placed in Petri dishes with different supplemented culture media and with VC4 isolate and the destruction of eggs was examined at the end of 25 days of interaction. In assay C, effects of the crude extract of P. chlamydosporia (VC4) on eggs were evaluated at the end of 7 days. In assay A, there was no difference (p>0.05) in ovicidal activity among the tested isolates (VC1 and VC4); however, the highest percentage for ovicidal activity (type 3 effect) was demonstrated by the isolate VC4. In assay B, the culture medium starch-agar showed the best results for the destruction of the eggs, with a percentage of 46.6% at the end of the assay. In assay C, the crude extract of VC4 was effective in the destruction of E. paraensei eggs, with a percentage reduction of 53%. The results of this study demonstrate that a rich culture medium with a greater availability of carbon and nitrogen may interfere directly in the predatory characteristics of ovicidal fungi.
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A? imaging with 18F-florbetaben in prodromal Alzheimer's disease: a prospective outcome study.
J. Neurol. Neurosurg. Psychiatr.
PUBLISHED: 06-28-2014
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We assessed the clinical utility of ?-amyloid (A?) imaging with (18)F-florbetaben (FBB) in mild cognitive impairment (MCI) by evaluating its prognostic accuracy for progression to Alzheimer's disease (AD), comparing semiquantitative with visual scan assessment, and exploring the relationships among A?, hippocampal volume (HV) and memory over time.
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Autobiographical narratives relate to Alzheimer's disease biomarkers in older adults.
Int Psychogeriatr
PUBLISHED: 06-27-2014
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Autobiographical memory (ABM), personal semantic memory (PSM), and autonoetic consciousness are affected in individuals with mild cognitive impairment (MCI) but their relationship with Alzheimer's disease (AD) biomarkers are unclear.
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In vivo tau imaging: obstacles and progress.
Alzheimers Dement
PUBLISHED: 06-14-2014
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The military conflicts of the last decade have highlighted the growing problem of traumatic brain injury in combatants returning from the battlefield. The considerable evidence pointing at the accumulation of tau aggregates and its recognition as a risk factor in neurodegenerative conditions such as Alzheimer's disease have led to a major effort to develop selective tau ligands that would allow research into the physiopathologic underpinnings of traumatic brain injury and chronic traumatic encephalopathy in military personnel and the civilian population. These tracers will allow new insights into tau pathology in the human brain, facilitating research into causes, diagnosis, and treatment of traumatic encephalopathy and major neurodegenerative dementias, such as Alzheimer's disease and some variants of frontotemporal lobar degeneration, in which tau plays a role. The field of selective tau imaging has to overcome several obstacles, some of them associated with the idiosyncrasies of tau aggregation and others related to radiotracer design. A worldwide effort has focused on the development of imaging agents that will allow selective tau imaging in vivo. Recent progress in the development of these tracers is enabling the noninvasive assessment of the extent of tau pathology in the brain, eventually allowing the quantification of changes in tau pathology over time and its relation to cognitive performance, brain volumetrics, and other biomarkers, as well as assessment of efficacy and patient recruitment for antitau therapeutic trials.
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An increased neutrophil-lymphocyte ratio in Alzheimer's disease is a function of age and is weakly correlated with neocortical amyloid accumulation.
J. Neuroimmunol.
PUBLISHED: 05-03-2014
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Inflammation is a hallmark of Alzheimer's disease (AD). Whether directly involved in the pathogenesis, or a downstream consequence of neuronal death, the blood neutrophil-lymphocyte ratio (NLR) is reported to be a putative, non-invasive peripheral biomarker for AD. The aim of this study was to re-evaluate the diagnostic utility of longitudinal measures of the NLR. The NLR was stable across all time-points and weakly correlated with neocortical amyloid burden (R=0.21 at baseline, 0.27 at 18 months, 0.20 at 36 months and 0.10 at 54 months). Cross-sectionally, the NLR was significantly elevated in AD participants as compared to HC participants at baseline (p<0.0001), 18 months (p<0.0001), 36 months (p=0.002) and at 54 months (p=0.007), however only prior to adjustment for age, sex and APOE?4 allele status (p>0.05 at all time-points except for 18 months; p<0.0001). Longitudinally, the NLR was not significantly different between HC and AD participants (p>0.05) adjusted for age, sex and APOE?4 allele status. Comparing the NLR between cognitive transition groups over time (transition towards an AD type dementia), there was no significant difference in the NLR levels between those participants, who did not transition and those participants who did transition, or those in the stable AD group after adjusting for age, sex and APOE?4 allele status (p>0.05). Despite inflammation being a hallmark in AD and previous reports showing that the NLR can discriminate HC from AD patients, our results suggest that the sensitivity of the NLR itself is not robust enough for diagnostic utility. We identified significant relationships cross sectionally (p<0.05 at baseline, 18 months and 36 months) between the NLR and neocortical amyloid burden, but this relationship was lost after longitudinal analyses (p>0.5). The NLR also had limited association with cognitive decline, although in our cohort, the number of participants transitioning was relatively small. In conclusion, the NLR may reflect AD-related inflammatory processes in the periphery, but age and sex are dominant covariates which need to be controlled for in population-based screening.
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Proteolytic activity of the nematophagous fungus Arthrobotrys sinensis on Angiostrongylus vasorum larvae.
BMC Res Notes
PUBLISHED: 04-22-2014
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The predatory nematophagous fungus Arthrobotrys sinensis (SF53) produces three proteases with nematicidal activity when grown on solid media culture. However, the proteolytic profile produced by this fungus, when grown in liquid culture medium remains unknown.
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Identification of the source of PFOS and PFOA contamination at a military air base site.
Environ Monit Assess
PUBLISHED: 04-21-2014
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Although the use of perfluorooctane sulfonic acid (PFOS)/perfluorooctanoic acid (PFOA)-based aqueous fire-fighting foams (AFFF) has been banned due to their persistence, bioaccumulation and toxicity to biota, PFOS and PFOA are still present at significant levels in the environment due to their past usage. This study investigated the reasons for detection of PFOS and PFOA in an evaporation pond used to collect the wastewater arising from fire-fighting exercises at a military air base despite the replacement of PFOS/PFOA-based foam with no PFOS/PFOA-foam about 6 years ago. Concentrations in the wastewater stored in this pond ranged from 3.6 to 9.7 mg/L for PFOS and between 0.6 and 1.7 mg/L for PFOA. The hypothesis tested in a laboratory study was that PFOS and PFOA have accumulated in the sediments of the pond and can be released into the main body of the water. Concentrations detected in the sediments were 38 and 0.3 mg/g for PFOS and PFOA, respectively. These values exceed the recently reported average global values for sediments (0.2-3.8 ng/g for PFOS and from 0.1 to 0.6 ng/g for PFOA) by a factor of several thousands. PFOS and PFOA distribution coefficients were derived for the organic content of the pond sediment (1.6 %). Identification of the source of contamination and knowledge of the partition between soil and aqueous phases are vital first steps in developing a sustainable remediation technology to remove the source from the site. This study clearly suggests that unless the sediment is cleaned of PFOS/PFOA, these chemicals will continue to be detected for a long period in the pond water, with potential adverse impacts on the ecosystem.
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Photophysical properties and singlet oxygen generation efficiencies of water-soluble fullerene nanoparticles.
Photochem. Photobiol.
PUBLISHED: 04-15-2014
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As various fullerene derivatives have been developed, it is necessary to explore their photophysical properties for potential use in photoelectronics and medicine. Here, we address the photophysical properties of newly synthesized water-soluble fullerene-based nanoparticles and polyhydroxylated fullerene as a representative water-soluble fullerene derivative. They show broad emission band arising from a wide-range of excitation energies. It is attributed to the optical transitions from disorder-induced states, which decay in the nanosecond time range. We determine the kinetic properties of the singlet oxygen ((1)O2) luminescence generated by the fullerene nanoparticles and polyhydroxylated fullerene to consider the potential as photodynamic agents. Triplet state decay of the nanoparticles was longer than (1)O2 lifetime in water. Singlet oxygen quantum yield of a series of the fullerene nanoparticles is comparably higher ranging from 0.15 to 0.2 than that of polyhydroxylated fullerene, which is about 0.06.
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Combining displacement field and grip force information to determine mechanical properties of planar tissue with complicated geometry.
J Biomech Eng
PUBLISHED: 04-04-2014
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Performing planar biaxial testing and using nominal stress-strain curves for soft-tissue characterization is most suitable when (1) the test produces homogeneous strain fields, (2) fibers are aligned with the coordinate axes, and (3) strains are measured far from boundaries. Some tissue types [such as lamellae of the annulus fibrosus (AF)] may not allow for these conditions to be met due to their natural geometry and constitution. The objective of this work was to develop and test a method utilizing a surface displacement field, grip force-stretch data, and finite-element (FE) modeling to facilitate analysis of such complex samples. We evaluated the method by regressing a simple structural model to simulated and experimental data. Three different tissues with different characteristics were used: Superficial pectoralis major (SPM) (anisotropic, aligned with axes), facet capsular ligament (FCL) (anisotropic, aligned with axes, bone attached), and a lamella from the AF (anisotropic, aligned off-axis, bone attached). We found that the surface displacement field or the grip force-stretch data information alone is insufficient to determine a unique parameter set. Utilizing both data types provided tight confidence regions (CRs) of the regressed parameters and low parameter sensitivity to initial guess. This combined fitting approach provided robust characterization of tissues with varying fiber orientations and boundaries and is applicable to tissues that are poorly suited to standard biaxial testing. The structural model, a set of C++ finite-element routines, and a Matlab routine to do the fitting based on a set of force/displacement data is provided in the on-line supplementary material.
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Non-invasive assessment of Alzheimer's disease neurofibrillary pathology using 18F-THK5105 PET.
Brain
PUBLISHED: 03-27-2014
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Non-invasive imaging of tau pathology in the living brain would be useful for accurately diagnosing Alzheimer's disease, tracking disease progression, and evaluating the treatment efficacy of disease-specific therapeutics. In this study, we evaluated the clinical usefulness of a novel tau-imaging positron emission tomography tracer 18F-THK5105 in 16 human subjects including eight patients with Alzheimer's disease (three male and five females, 66-82 years) and eight healthy elderly controls (three male and five females, 63-76 years). All participants underwent neuropsychological examination and 3D magnetic resonance imaging, as well as both 18F-THK5105 and 11C-Pittsburgh compound B positron emission tomography scans. Standard uptake value ratios at 90-100 min and 40-70 min post-injection were calculated for 18F-THK5105 and 11C-Pittsburgh compound B, respectively, using the cerebellar cortex as the reference region. As a result, significantly higher 18F-THK5105 retention was observed in the temporal, parietal, posterior cingulate, frontal and mesial temporal cortices of patients with Alzheimer's disease compared with healthy control subjects. In patients with Alzheimer's disease, the inferior temporal cortex, which is an area known to contain high densities of neurofibrillary tangles in the Alzheimer's disease brain, showed prominent 18F-THK5105 retention. Compared with high frequency (100%) of 18F-THK5105 retention in the temporal cortex of patients with Alzheimer's disease, frontal 18F-THK5105 retention was less frequent (37.5%) and was only observed in cases with moderate-to-severe Alzheimer's disease. In contrast, 11C-Pittsburgh compound B retention was highest in the posterior cingulate cortex, followed by the ventrolateral prefrontal, anterior cingulate, and superior temporal cortices, and did not correlate with 18F-THK5105 retention in the neocortex. In healthy control subjects, 18F-THK5105 retention was ?10% higher in the mesial temporal cortex than in the neocortex. Notably, unlike 11C-Pittsburgh compound B, 18F-THK5105 retention was significantly correlated with cognitive parameters, hippocampal and whole brain grey matter volumes, which was consistent with findings from previous post-mortem studies showing significant correlations of neurofibrillary tangle density with dementia severity or neuronal loss. From these results, 18F-THK5105 positron emission tomography is considered to be useful for the non-invasive assessment of tau pathology in the living brain. This technique would be applicable to the longitudinal evaluation of tau deposition and allow a better understanding of the pathophysiology of Alzheimer's disease.
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Do current therapeutic anti-A? antibodies for Alzheimer's disease engage the target?
Acta Neuropathol.
PUBLISHED: 03-12-2014
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Reducing amyloid-? peptide (A?) burden at the pre-symptomatic stages of Alzheimer's disease (AD) is currently the advocated clinical strategy for treating this disease. The most developed method for targeting A? is the use of monoclonal antibodies including bapineuzumab, solanezumab and crenezumab. We have synthesized these antibodies and used surface plasmon resonance (SPR) and mass spectrometry to characterize and compare the ability of these antibodies to target A? in transgenic mouse tissue as well as human AD tissue. SPR analysis showed that the antibodies were able to bind A? with high affinity. All of the antibodies were able to bind A? in mouse tissue. However, significant differences were observed in human brain tissue. While bapineuzumab was able to capture a variety of N-terminally truncated A? species, the A? detected using solanezumab was barely above detection limits while crenezumab did not detect any A?. None of the antibodies were able to detect any A? species in human blood. Immunoprecipitation experiments using plasma from AD subjects showed that both solanezumab and crenezumab have extensive cross-reactivity with non-A? related proteins. Bapineuzumab demonstrated target engagement with brain A?, consistent with published clinical data. Solanezumab and crenezumab did not, most likely as a result of a lack of specificity due to cross-reactivity with other proteins containing epitope overlap. This lack of target engagement raises questions as to whether solanezumab and crenezumab are suitable drug candidates for the preventative clinical trials for AD.
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Incidence of cerebral microbleeds in preclinical Alzheimer disease.
Neurology
PUBLISHED: 03-12-2014
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We sought to determine the incidence and associations of lobar microbleeds (LMBs) in a longitudinal cohort with (11)C-Pittsburgh compound B (PiB) PET imaging.
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A? and cognitive change: Examining the preclinical and prodromal stages of Alzheimer's disease.
Alzheimers Dement
PUBLISHED: 03-05-2014
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High ?-amyloid (A?) is associated with faster memory decline in healthy individuals and adults with mild cognitive impairment (MCI). However, longer prospective studies are required to determine if A?-related memory decline continues and whether it is associated with increased rate of disease progression.
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Comparison of MR-less PiB SUVR quantification methods.
Neurobiol. Aging
PUBLISHED: 02-19-2014
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(11)C-Pittsburgh compound B (PiB) is a positron emission tomography (PET) tracer designed to bind to amyloid-? (A?) plaques, one of the hallmarks of Alzheimer's disease (AD). The potential of PiB as an early marker of AD led to the increasing use of PiB in clinical research studies and development of several F-18-labeled A? radiotracers. Automatic quantification of PiB images requires an accurate parcellation of the brain's gray matter (GM). Typically, this relies on a coregistered magnetic resonance imaging (MRI) to extract the cerebellar GM, compute the standardized uptake value ratio (SUVR), and provide parcellation and segmentation for quantification of regional and global SUVR. However, not all subjects can undergo MRI, in which case, an MR-less method is desirable. In this study, we assess 3 PET-only quantification methods: a mean atlas, an adaptive atlas, and a multi-atlas approaches on a database of 237 subjects having been imaged with both PiB PET and MRI. The PET-only methods were compared against MR-based SUVR quantification and evaluated in terms of correlation, average error, and performance in classifying subjects with low and high A? deposition. The mean atlas method suffered from a significant bias between the estimated neocortical SUVR and the PiB status, resulting in an overall error of 5.6% (R(2) = 0.98), compared with the adaptive and multi-atlas approaches that had errors of 3.06% and 2.74%, respectively (R(2) = 0.98), and no significant bias. In classifying PiB-negative from PiB-positive subjects, the mean atlas had 10 misclassified subjects compared with 0 for the adaptive and 1 for the multi-atlas approach. Overall, the adaptive and the multi-atlas approaches performed similarly well against the MR-based quantification and would be a suitable replacements for PiB quantification when no MRI is available.
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Anxiety symptoms, cerebral amyloid burden and memory decline in healthy older adults without dementia: 3-year prospective cohort study.
Br J Psychiatry
PUBLISHED: 02-13-2014
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Although beta-amyloid, anxiety and depression have linked cross-sectionally to reduced memory function in healthy older adults without dementia, prospective data evaluating these associations are lacking. Using data an observational cohort study of 178 healthy older adults without dementia followed for 3 years, we found that anxiety symptoms significantly moderated the relationship between beta-amyloid level and decline in verbal (Cohen's d = 0.65) and episodic (Cohen's d = 0.38) memory. Anxiety symptoms were additionally linked to greater decline in executive function, irrespective of beta-amyloid and other risk factors. These findings suggest that interventions to mitigate anxiety symptoms may help delay memory decline in otherwise healthy older adults with elevated beta-amyloid.
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In vivo evaluation of a novel tau imaging tracer for Alzheimer's disease.
Eur. J. Nucl. Med. Mol. Imaging
PUBLISHED: 02-11-2014
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Diagnosis of tauopathies such as Alzheimer's disease (AD) still relies on post-mortem examination of the human brain. A non-invasive method of determining brain tau burden in vivo would allow a better understanding of the pathophysiology of tauopathies. The purpose of the study was to evaluate (18)F-THK523 as a potential tau imaging tracer.
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Emotion and language: valence and arousal affect word recognition.
J Exp Psychol Gen
PUBLISHED: 02-03-2014
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Emotion influences most aspects of cognition and behavior, but emotional factors are conspicuously absent from current models of word recognition. The influence of emotion on word recognition has mostly been reported in prior studies on the automatic vigilance for negative stimuli, but the precise nature of this relationship is unclear. Various models of automatic vigilance have claimed that the effect of valence on response times is categorical, an inverted U, or interactive with arousal. In the present study, we used a sample of 12,658 words and included many lexical and semantic control factors to determine the precise nature of the effects of arousal and valence on word recognition. Converging empirical patterns observed in word-level and trial-level data from lexical decision and naming indicate that valence and arousal exert independent monotonic effects: Negative words are recognized more slowly than positive words, and arousing words are recognized more slowly than calming words. Valence explained about 2% of the variance in word recognition latencies, whereas the effect of arousal was smaller. Valence and arousal do not interact, but both interact with word frequency, such that valence and arousal exert larger effects among low-frequency words than among high-frequency words. These results necessitate a new model of affective word processing whereby the degree of negativity monotonically and independently predicts the speed of responding. This research also demonstrates that incorporating emotional factors, especially valence, improves the performance of models of word recognition.
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Quantification of continuous in vivo flexion-extension kinematics and intervertebral strains.
Eur Spine J
PUBLISHED: 01-10-2014
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Healthy subjects performed lumbar flexion and were assessed by video fluoroscopy to measure the in vivo kinematics of the lower lumbar motion segments.
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Prefailure and failure mechanics of the porcine ascending thoracic aorta: experiments and a multiscale model.
J Biomech Eng
PUBLISHED: 01-08-2014
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Ascending thoracic aortic aneurysms (ATAA) have a high propensity for dissection, which occurs when the hemodynamic load exceeds the mechanical strength of the aortic media. Despite our recognition of this essential fact, the complex architecture of the media has made a predictive model of medial failure-even in the relatively simple case of the healthy vessel-difficult to achieve. As a first step towards a general model of ATAA failure, we characterized the mechanical behavior of healthy ascending thoracic aorta (ATA) media using uniaxial stretch-to-failure in both circumferential (n?=?11) and axial (n?=?11) orientations and equibiaxial extensions (n?=?9). Both experiments demonstrated anisotropy, with higher tensile strength in the circumferential direction (2510?±?439.3?kPa) compared to the axial direction (750?±?102.6?kPa) for the uniaxial tests, and a ratio of 1.44 between the peak circumferential and axial loads in equibiaxial extension. Uniaxial tests for both orientations showed macroscopic tissue failure at a stretch of 1.9. A multiscale computational model, consisting of a realistically aligned interconnected fiber network in parallel with a neo-Hookean solid, was used to describe the data; failure was modeled at the fiber level, with an individual fiber failing when stretched beyond a critical threshold. The best-fit model results were within the 95% confidence intervals for uniaxial and biaxial experiments, including both prefailure and failure, and were consistent with properties of the components of the ATA media.
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Can there be a place for intraoperative salvaged blood in spine tumor surgery?
Ann. Surg. Oncol.
PUBLISHED: 01-06-2014
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Intraoperative cell salvage (IOCS) has been used in musculoskeletal surgery extensively. However, it has never found its place in musculoskeletal oncologic surgery. We have conducted the first-ever study to evaluate the feasibility of IOCS in combination with a leucocyte-depletion filter (LDF) in metastatic spine tumor surgery. This was to pave the path for use of IOCS-LDF in musculoskeletal oncologic surgery.
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Cerebral microbleeds: a review of clinical, genetic, and neuroimaging associations.
Front Neurol
PUBLISHED: 01-06-2014
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Cerebral microbleeds (microbleeds) are small, punctuate hypointense lesions seen in T2* Gradient-Recall Echo (GRE) and Susceptibility-Weighted (SWI) Magnetic Resonance Imaging (MRI) sequences, corresponding to areas of hemosiderin breakdown products from prior microscopic hemorrhages. They occur in the setting of impaired small vessel integrity, commonly due to either hypertensive vasculopathy or cerebral amyloid angiopathy. Microbleeds are more prevalent in individuals with Alzheimer's disease (AD) dementia and in those with both ischemic and hemorrhagic stroke. However they are also found in asymptomatic individuals, with increasing prevalence with age, particularly in carriers of the Apolipoprotein (APOE) ?4 allele. Other neuroimaging findings that have been linked with microbleeds include lacunar infarcts and white matter hyperintensities on MRI, and increased cerebral ?-amyloid burden using (11)C-PiB Positron Emission Tomography. The presence of microbleeds has been suggested to confer increased risk of incident intracerebral hemorrhage - particularly in the setting of anticoagulation - and of complications of immunotherapy for AD. Prospective data regarding the natural history and sequelae of microbleeds are currently limited, however there is a growing evidence base that will serve to inform clinical decision-making in the future.
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Assessing THK523 selectivity for tau deposits in Alzheimer's disease and non-Alzheimer's disease tauopathies.
Alzheimers Res Ther
PUBLISHED: 01-01-2014
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The introduction of tau imaging agents such as (18)F-THK523 offers new hope for the in vivo assessment of tau deposition in tauopathies such as Alzheimer's disease (AD), where preliminary (18)F-THK523-PET studies have demonstrated significantly higher cortical retention of (18)F-THK523 in AD compared to age-matched healthy individuals. In addition to AD, tau imaging with PET may also be of value in assessing non-AD tauopathies, such as corticobasal degeneration (CBD), progressive supranuclear palsy (PSP) and Pick's disease (PiD).
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Effect of BDNF Val66Met on memory decline and hippocampal atrophy in prodromal Alzheimer's disease: a preliminary study.
PLoS ONE
PUBLISHED: 01-01-2014
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Cross-sectional genetic association studies have reported equivocal results on the relationship between the brain-derived neurotrophic factor (BDNF) Val66Met and risk of Alzheimer's disease (AD). As AD is a neurodegenerative disease, genetic influences may become clearer from prospective study. We aimed to determine whether BDNF Val66Met polymorphism influences changes in memory performance, hippocampal volume, and A? accumulation in adults with amnestic mild cognitive impairment (aMCI) and high A?.
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MR-less surface-based amyloid assessment based on 11C PiB PET.
PLoS ONE
PUBLISHED: 01-01-2014
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?-amyloid (A?) plaques in brain's grey matter (GM) are one of the pathological hallmarks of Alzheimer's disease (AD), and can be imaged in vivo using Positron Emission Tomography (PET) with (11)C or (18)F radiotracers. Estimating A? burden in cortical GM has been shown to improve diagnosis and monitoring of AD. However, lacking structural information in PET images requires such assessments to be performed with anatomical MRI scans, which may not be available at different clinical settings or being contraindicated for particular reasons. This study aimed to develop an MR-less A? imaging quantification method that requires only PET images for reliable A? burden estimations.
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Wilms tumor 1 (Wt1) regulates pleural mesothelial cell plasticity and transition into myofibroblasts in idiopathic pulmonary fibrosis.
FASEB J.
PUBLISHED: 11-21-2013
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Pleural mesothelial cells (PMCs), which are derived from the mesoderm, exhibit an extraordinary capacity to undergo phenotypic changes during development and disease. PMC transformation and trafficking has a newly defined role in idiopathic pulmonary fibrosis (IPF); however, the contribution of Wilms tumor 1 (Wt1)-positive PMCs to the generation of pathognomonic myofibroblasts remains unclear. PMCs were obtained from IPF lung explants and healthy donor lungs that were not used for transplantation. Short hairpin Wt1-knockdown PMCs (sh Wt1) were generated with Wt1 shRNA, and morphologic and functional assays were performed in vitro. Loss of Wt1 abrogated the PMC phenotype and showed evidence of mesothelial-to-mesenchymal transition (MMT), with a reduced expression of E-cadherin and an increase in the profibrotic markers ?-smooth muscle actin (?-SMA) and fibronectin, along with increased migration and contractility, compared with that of the control. Migration of PMCs in response to active transforming growth factor (TGF)-?1 was assessed by live-cell imaging with 2-photon microscopy and 3D imaging, of Wt1-EGFP transgenic mice. Lineage-tracing experiments to map the fate of Wt1(+) PMCs in mouse lung in response to TGF-?1 were also performed by using a Cre-loxP system. Our results, for the first time, demonstrate that Wt1 is necessary for the morphologic integrity of pleural membrane and that loss of Wt1 contributes to IPF via MMT of PMCs into a myofibroblast phenotype.-Karki, S., Surolia, R., Hock, T. D., Guroji, P., Duggal, R., Ye, T., Thannickal, V., J., Antony, V. B. Wilms tumor 1 (Wt1) regulates pleural mesothelial cell plasticity and transition into myofibroblasts in idiopathic pulmonary fibrosis.
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Rates of diagnostic transition and cognitive change at 18-month follow-up among 1,112 participants in the Australian Imaging, Biomarkers and Lifestyle Flagship Study of Ageing (AIBL).
Int Psychogeriatr
PUBLISHED: 11-20-2013
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ABSTRACT Background: The Australian Imaging, Biomarkers and Lifestyle (AIBL) Flagship Study of Ageing is a prospective study of 1,112 individuals (211 with Alzheimers disease (AD), 133 with mild cognitive impairment (MCI), and 768 healthy controls (HCs)). Here we report diagnostic and cognitive findings at the first (18-month) follow-up of the cohort. The first aim was to compute rates of transition from HC to MCI, and MCI to AD. The second aim was to characterize the cognitive profiles of individuals who transitioned to a more severe disease stage compared with those who did not. Methods: Eighteen months after baseline, participants underwent comprehensive cognitive testing and diagnostic review, provided an 80 ml blood sample, and completed health and lifestyle questionnaires. A subgroup also underwent amyloid PET and MRI neuroimaging. Results: The diagnostic status of 89.9% of the cohorts was determined (972 were reassessed, 28 had died, and 112 did not return for reassessment). The 18-month cohort comprised 692 HCs, 82 MCI cases, 197 AD patients, and one Parkinsons disease dementia case. The transition rate from HC to MCI was 2.5%, and cognitive decline in HCs who transitioned to MCI was greatest in memory and naming domains compared to HCs who remained stable. The transition rate from MCI to AD was 30.5%. Conclusion: There was a high retention rate after 18 months. Rates of transition from healthy aging to MCI, and MCI to AD, were consistent with established estimates. Follow-up of this cohort over longer periods will elucidate robust predictors of future cognitive decline.
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Regional variability of imaging biomarkers in autosomal dominant Alzheimers disease.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 11-05-2013
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Major imaging biomarkers of Alzheimers disease include amyloid deposition [imaged with [(11)C]Pittsburgh compound B (PiB) PET], altered glucose metabolism (imaged with [(18)F]fluro-deoxyglucose PET), and structural atrophy (imaged by MRI). Recently we published the initial subset of imaging findings for specific regions in a cohort of individuals with autosomal dominant Alzheimers disease. We now extend this work to include a larger cohort, whole-brain analyses integrating all three imaging modalities, and longitudinal data to examine regional differences in imaging biomarker dynamics. The anatomical distribution of imaging biomarkers is described in relation to estimated years from symptom onset. Autosomal dominant Alzheimers disease mutation carrier individuals have elevated PiB levels in nearly every cortical region 15 y before the estimated age of onset. Reduced cortical glucose metabolism and cortical thinning in the medial and lateral parietal lobe appeared 10 and 5 y, respectively, before estimated age of onset. Importantly, however, a divergent pattern was observed subcortically. All subcortical gray-matter regions exhibited elevated PiB uptake, but despite this, only the hippocampus showed reduced glucose metabolism. Similarly, atrophy was not observed in the caudate and pallidum despite marked amyloid accumulation. Finally, before hypometabolism, a hypermetabolic phase was identified for some cortical regions, including the precuneus and posterior cingulate. Additional analyses of individuals in which longitudinal data were available suggested that an accelerated appearance of volumetric declines approximately coincides with the onset of the symptomatic phase of the disease.
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Effect of amyloid on memory and non-memory decline from preclinical to clinical Alzheimers disease.
Brain
PUBLISHED: 10-30-2013
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High amyloid has been associated with substantial episodic memory decline over 18 and 36 months in healthy older adults and individuals with mild cognitive impairment. However, the nature and magnitude of amyloid-related memory and non-memory change from the preclinical to the clinical stages of Alzheimers disease has not been evaluated over the same time interval. Healthy older adults (n = 320), individuals with mild cognitive impairment (n = 57) and individuals with Alzheimers disease (n = 36) enrolled in the Australian Imaging, Biomarkers and Lifestyle study underwent at least one positron emission tomography neuroimaging scan for amyloid. Cognitive assessments were conducted at baseline, and 18- and 36-month follow-up assessments. Compared with amyloid-negative healthy older adults, amyloid-positive healthy older adults, and amyloid-positive individuals with mild cognitive impairment and Alzheimers disease showed moderate and equivalent decline in verbal and visual episodic memory over 36 months (ds = 0.47-0.51). Relative to amyloid-negative healthy older adults, amyloid-positive healthy older adults showed no decline in non-memory functions, but amyloid-positive individuals with mild cognitive impairment showed additional moderate decline in language, attention and visuospatial function (ds = 0.47-1.12), and amyloid-positive individuals with Alzheimers disease showed large decline in all aspects of memory and non-memory function (ds = 0.73-2.28). Amyloid negative individuals with mild cognitive impairment did not show any cognitive decline over 36 months. When non-demented individuals (i.e. healthy older adults and adults with mild cognitive impairment) were further dichotomized, high amyloid-positive non-demented individuals showed a greater rate of decline in episodic memory and language when compared with low amyloid positive non-demented individuals. Memory decline does not plateau with increasing disease severity, and decline in non-memory functions increases in amyloid-positive individuals with mild cognitive impairment and Alzheimers disease. The combined detection of amyloid positivity and objectively-defined decline in memory are reliable indicators of early Alzheimers disease, and the detection of decline in non-memory functions in amyloid-positive individuals with mild cognitive impairment may assist in determining the level of disease severity in these individuals. Further, these results suggest that grouping amyloid data into at least two categories of abnormality may be useful in determining the disease risk level in non-demented individuals.
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Diagnostic Imaging Agents for Alzheimers Disease: Copper Radiopharmaceuticals that Target A? Plaques.
J. Am. Chem. Soc.
PUBLISHED: 10-16-2013
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One of the pathological hallmarks of Alzheimers disease is the presence of amyloid-? plaques in the brain and the major constituent of these plaques is aggregated amyloid-? peptide. New thiosemicarbazone-pyridylhydrazine based ligands that incorporate functional groups designed to bind amyloid-? plaques have been synthesized. The new ligands form stable four coordinate complexes with a positron-emitting radioactive isotope of copper, (64)Cu. Two of the new Cu(II) complexes include a functionalized styrylpyridine group and these complexes bind to amyloid-? plaques in samples of post-mortem human brain tissue. Strategies to increase brain uptake by functional group manipulation have led to a (64)Cu complex that effectively crosses the blood-brain barrier in wild-type mice. The new complexes described in this manuscript provide insight into strategies to deliver metal complexes to amyloid-? plaques.
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Nematophagous fungi for biological control of gastrointestinal nematodes in domestic animals.
Appl. Microbiol. Biotechnol.
PUBLISHED: 08-05-2013
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Several studies have been conducted using fungi in the biological control of domestic animals and humans. In this respect, a large amount of research has been undertaken to understand the particularities of each fungus used. These fungi have been demonstrated to act on all classes of helminthes. Therefore, they should not only be called nematophagous but also helmintophagous. Evidence of enzymatic action has also revealed their mechanism of action, as well as potential metabolites that could be synthesized as bioactive molecules. Cultural barriers to the use of fungi should be broken down, since the impact on the environment is minimal. In this context, much is already known about the mechanism of interaction of these organisms with their targets. Recent research has pointed to the search for substances derived from nematophagous fungi that have demonstrated their ovicidal and/or larvicidal activity, thus being a global premise to be studied further. Crude extracts derived from nematophagous fungi of predator and ovicidal groups reduce the amount of larvae of gastrointestinal nematodes and prevent the hatching of their eggs, since they have been demonstrated to act with extracellular proteases and other enzymes. Furthermore, the activity of these enzymes has begun to be explored regarding their possible interaction with the exoskeleton of arthropods, which could emerge as an alternative method of tick control. Finally, it should be clear that nematophagous fungi in general are old friends that are ready to the fight with our old enemies, the gastrointestinal helminth parasites harmful to human and animal health.
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Vascular biomechanical properties in mice with smooth muscle specific deletion of Ndst1.
Mol. Cell. Biochem.
PUBLISHED: 07-26-2013
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Heparan sulfate proteoglycans act as co-receptors for many chemokines and growth factors. The sulfation pattern of the heparan sulfate chains is a critical regulatory step affecting the binding of chemokines and growth factors. N-deacetylase-N-sulfotransferase1 (Ndst1) is one of the first enzymes to catalyze sulfation. Previously published work has shown that HSPGs alter tangent moduli and stiffness of tissues and cells. We hypothesized that loss of Ndst1 in smooth muscle would lead to significant changes in heparan sulfate modification and the elastic properties of arteries. In line with this hypothesis, the axial tangent modulus was significantly decreased in aorta from mice lacking Ndst1 in smooth muscle (SM22?cre(+)Ndst1(-/-), p < 0.05, n = 5). The decrease in axial tangent modulus was associated with a significant switch in myosin and actin types and isoforms expressed in aorta and isolated aortic vascular smooth muscle cells. In contrast, no changes were found in the compliance of smaller thoracodorsal arteries of SM22?cre(+)Ndst1(-/-) mice. In summary, the major findings of this study were that targeted ablation of Ndst1 in smooth muscle cells results in altered biomechanical properties of aorta and differential expression of myosin and actin types and isoforms.
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The association of A? amyloid and composite cognitive measures in healthy older adults and MCI.
Int Psychogeriatr
PUBLISHED: 07-18-2013
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To date evidence of the relationship between cognition and A? amyloid during the early stages of Alzheimers Disease (AD) has been inconsistent. This study aimed to describe the nature and magnitude of the relationship between A? amyloid and cognitive performance of individuals without dementia.
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Novel 18F-labeled arylquinoline derivatives for noninvasive imaging of tau pathology in Alzheimer disease.
J. Nucl. Med.
PUBLISHED: 07-15-2013
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Neurofibrillary tangles in Alzheimer disease (AD) brains are composed of the microtubule-associated protein tau. Noninvasive monitoring of tau protein aggregates in the living brain will provide useful information regarding tau pathophysiology in AD. However, no PET probes are currently available for selective detection of tau pathology in AD. We have previously reported (18)F-labeled THK-523 ((18)F-6-(2-fluoroethoxy)-2-(4-aminophenyl)quinoline) as a tau imaging radiotracer candidate for PET. After compound optimization, we developed novel (18)F-labeled arylquinoline derivatives, (18)F-THK-5105 and (18)F-THK-5117, for use as tau imaging PET tracers.
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Dual Plating of Humeral Shaft Fractures: Orthogonal Plates Biomechanically Outperform Side-by-Side Plates.
Clin. Orthop. Relat. Res.
PUBLISHED: 06-26-2013
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Single large-fragment plate constructs currently are the norm for internal fixation of middiaphyseal humerus fractures. In cases where humeral size is limited, however, dual small-fragment locking plate constructs may serve as an alternative. The mechanical effects of different possible plate configurations around the humeral diaphysis may be important, but to our knowledge, have yet to be investigated.
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Implementation and validation of an adaptive template registration method for 18F-flutemetamol imaging data.
J. Nucl. Med.
PUBLISHED: 06-05-2013
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The spatial normalization of PET amyloid imaging data is challenging because different white and gray matter patterns of negative (A?-) and positive (A?+) uptake could lead to systematic bias if a standard method is used. In this study, we propose the use of an adaptive template registration method to overcome this problem.
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Cross-sectional and longitudinal analysis of the relationship between A? deposition, cortical thickness, and memory in cognitively unimpaired individuals and in Alzheimer disease.
JAMA Neurol
PUBLISHED: 05-29-2013
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?-amyloid (A?) deposition is one of the hallmarks of Alzheimer disease. A? deposition accelerates gray matter atrophy at early stages of the disease even before objective cognitive impairment is manifested. Identification of at-risk individuals at the presymptomatic stage has become a major research interest because it will allow early therapeutic interventions before irreversible synaptic and neuronal loss occur. We aimed to further characterize the cross-sectional and longitudinal relationship between A? deposition, gray matter atrophy, and cognitive impairment.
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Quantitative assessment of global hepatic glycolysis in patients with cirrhosis and normal controls using (18)F-FDG-PET/CT: a pilot study.
Ann Nucl Med
PUBLISHED: 05-24-2013
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To compare differences in global measures of hepatic metabolism between control subjects and subjects with cirrhosis.
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Cognitive consequences of high A? amyloid in mild cognitive impairment and healthy older adults: implications for early detection of Alzheimers disease.
Neuropsychology
PUBLISHED: 05-22-2013
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It has been proposed that only mild cognitive impairment (MCI) with high A? amyloid is indicative of incipient Alzheimers disease (AD), yet MCI with low A? amyloid may reflect other neurodegenerative processes. We aimed to determine the extent to which high A? amyloid influenced cognitive function in healthy older adults and adults with MCI.
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Amyloid imaging with PET in early Alzheimer disease diagnosis.
Med. Clin. North Am.
PUBLISHED: 05-07-2013
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In vivo imaging of amyloid-? (A?) with positron emission tomography has moved from the research arena into clinical practice. Clinicians working with cognitive decline and dementia must become familiar with its benefits and limitations. Amyloid imaging allows earlier diagnosis of Alzheimer disease and better differential diagnosis of dementia and provides prognostic information for mild cognitive impairment. It also has an increasingly important role in therapeutic trial recruitment and for evaluation of anti-A? treatments. Longitudinal observations are required to elucidate the role of A? deposition in the course of Alzheimer disease and provide information needed to fully use the prognostic power of this investigation.
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Mechanical response of wild-type and Alport murine lens capsules during osmotic swelling.
Exp. Eye Res.
PUBLISHED: 05-06-2013
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The mechanical support of basement membranes, such as the lens capsule, is believed to arise from one of their main constituents - collagen IV. The basement membranes of the lens, kidney, and ear normally contain two different types of collagen IV networks, referred to as the major and minor chain networks. In Alport syndrome, a mutation in one of the minor chain COL4 genes leads to the absence of the minor chain network, causing life-threatening disturbances. We hypothesized that the absence of the minor chain network increases basement membrane distensibility, as measured in wild-type (n = 25) and Alport syndrome (n = 21) mice using the lens capsule as a model. Osmotic swelling experiments revealed direction-dependent changes. As a reflection of lens capsule properties, Alport lenses strained significantly more than wild-type lenses in the anterior-posterior direction, i.e. along their thickness, but not in the equatorial direction (p = 0.03 and p = 0.08, respectively). This is consistent with clinical data: Alport patients develop conical protrusions on the anterior and posterior lenticular poles. There was no evidence of significant change in total amount of collagen between Alport and wild-type lenses (p = 0.6). The observed differences in distensibility could indicate that the major chain network alone cannot fully compensate for the absence of the more highly cross-linked minor chain network, which is believed to be stronger, more stable, and resistant to deformation. The addition of mechanical information on Alport syndrome to the currently available biological data provides a fuller picture into the progression of the disease.
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Head-to-head comparison of 11C-PiB and 18F-AZD4694 (NAV4694) for ?-amyloid imaging in aging and dementia.
J. Nucl. Med.
PUBLISHED: 04-10-2013
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(11)C-Pittsburgh compound-B ((11)C-PiB) is the benchmark radiotracer for imaging of ?-amyloid (A?) plaque in Alzheimer disease (AD). (18)F-labeled A? tracers subsequently developed for clinical use show higher nonspecific white matter binding and, in some cases, lower cortical binding in AD that could lead to less accurate interpretation of scans. We compared the cortical and white matter binding of a new (18)F-labeled A? tracer, (18)F-AZD4694 (recently renamed NAV4694), with (11)C-PiB in the same subjects.
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First report of the activity of predatory fungi on Angiostrongylus cantonensis (Nematoda: Angiostrongylidae) first-stage larvae.
Acta Trop.
PUBLISHED: 04-08-2013
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The nematode Angiostrongylus cantonensis causes eosinophilic meningoencephalitis in humans and thus alternative methods of control should be studied. The objective of this work was to evaluate the predatory capacity of eight fungal isolates of the species Duddingtonia flagrans (AC001, CG768 and CG722), Monacrosporium thaumasium (NF34), M. sinense (SF53) and Arthrobotrys robusta (I31), A. cladodes (CG719) and A. conoides (I40) on first-stage larvae (L?) of A. cantonensis under laboratory conditions. The treated groups contained 1000 conidia of the fungal isolates and 1000 A. cantonensis L? in Petri dishes containing 2% water-agar medium (2% WA). The control group (without fungi) contained only 1000 A. cantonensis L? in 2% WA. Evidence of predation was observed at the end of 7 days. Percentage reductions in L? were: AC001, 82.8%; CG768, 71.0%; CG722, 72.8%; NF34, 86.7%; SF53, 89.7%; I40, 48.3%; CG719, 84.7%; and I31, 80.4%. No significant difference was observed (p>0.01) between the actions of the isolates used; however, a difference was noted (p<0.01) in relation to the control group. The results of the present work, confirm previous reports of the effectiveness of the fungi D. flagrans, M. thaumasium, M. sinense and A. robusta in controlling larvae of potentially zoonotic nematodes, this being the first report on A. cantonensis L?.
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Mycelial mass production of fungi Duddingtonia flagrans and Monacrosporium thaumasium under different culture conditions.
BMC Res Notes
PUBLISHED: 04-04-2013
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Duddingtonia flagrans and Monacrosporium thaumasium are promising fungus species in veterinary biological control of gastrointestinal nematodes because of their production capacity of fungal structures (conidia and/or chlamydospores), growth efficiency in laboratory solid media and especially their predatory capacity. However, their large-scale production remains a challenge. This work aimed at evaluating the mycelial mass production of D. flagrans (AC001 and CG722) and M. thaumasium (NF34A) nematophagous fungi under different culture conditions.
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Three-month stability of the CogState brief battery in healthy older adults, mild cognitive impairment, and Alzheimers disease: results from the Australian Imaging, Biomarkers, and Lifestyle-rate of change substudy (AIBL-ROCS).
Arch Clin Neuropsychol
PUBLISHED: 04-03-2013
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Large prospective studies of Alzheimers disease (AD) have sought to understand the pathological evolution of AD and factors that may influence the rate of disease progression. Estimates of rates of cognitive change are available for 12 or 24 months, but not for shorter time frames (e.g., 3 or 6 months). Most clinical drug trials seeking to reduce or modify AD symptoms have been conducted over 12- or 24-week periods. As such, we aimed to characterize the performance of a group of healthy older adults, adults with amnestic mild cognitive impairment (aMCI), and adults with AD on the CogState battery of tests over short test-retest intervals. This study recruited 105 healthy older adults, 48 adults with aMCI, and 42 adults with AD from the Australian Imaging, Biomarkers, and Lifestyle study and administered the CogState battery monthly over 3 months. The CogState battery of tests showed high test-retest reliability and stability in all clinical groups when participants were assessed over 3 months. When considered at baseline, the CogState battery of tests was able to detect AD-related cognitive impairment. The data provide important estimates of the reliability, stability, and variability of each cognitive test in healthy older adults, adults with aMCI, and adults with AD. This may potentially be used to inform future estimates of cognitive change in clinical trials.
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BDNF Val66Met, A? amyloid, and cognitive decline in preclinical Alzheimers disease.
Neurobiol. Aging
PUBLISHED: 03-18-2013
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Brain-derived neurotrophic factor (BDNF) Val66Met polymorphism has previously been implicated in Alzheimers disease (AD)-related cognitive impairment. We aimed to determine the relationship between BDNF Val66Met and beta-amyloid (A?) on cognitive decline, hippocampal atrophy, and A? accumulation over 36 months in 165 healthy adults enrolled in the Australian Imaging, Biomarkers and Lifestyle study. In healthy adults with high A?, Met carriers showed significant and moderate-to-large declines in episodic memory, executive function, and language, and greater hippocampal atrophy over 36 months, compared with Val/Val homozygotes. BDNF Val66Met was not found to be related to rates of change in cognition or hippocampal volume in healthy adults with low A?. BDNF Val66Met did not relate to the amount of A? or to the rate of A? accumulation in either group. High A? levels coupled with Met carriage may be useful prognostic markers of accelerated cognitive decline and hippocampal degeneration in individuals in the preclinical stage of AD.
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Contribution of different anatomical and physiologic factors to iris contour and anterior chamber angle changes during pupil dilation: theoretical analysis.
Invest. Ophthalmol. Vis. Sci.
PUBLISHED: 03-14-2013
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To investigate the contribution of three anatomical and physiologic factors (dilator thickness, dynamic pupillary block, and iris compressibility) to changes in iris configuration and anterior chamber angle during pupil dilation.
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Amyloid ? deposition, neurodegeneration, and cognitive decline in sporadic Alzheimers disease: a prospective cohort study.
Lancet Neurol
PUBLISHED: 03-08-2013
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Similar to most chronic diseases, Alzheimers disease (AD) develops slowly from a preclinical phase into a fully expressed clinical syndrome. We aimed to use longitudinal data to calculate the rates of amyloid ? (A?) deposition, cerebral atrophy, and cognitive decline.
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Clinical profile of PiB-positive corticobasal syndrome.
PLoS ONE
PUBLISHED: 03-05-2013
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Corticobasal syndrome (CBS) is a multifaceted neurodegenerative disorder characterized by a combination of motor and cognitive deficits. Several different pathological entities, including Alzheimers pathology, have been described in association with CBS. The present study aimed to establish clinical, neuropsychological, and neuroimaging features that could be useful in the distinction of CBS due to AD pathology from other CBS cases in life based on [(11)C] Pittsburgh Compound B positron emission tomography (PiB-PET) status.
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Microscale fiber network alignment affects macroscale failure behavior in simulated collagen tissue analogs.
J Biomech Eng
PUBLISHED: 03-01-2013
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A tissues microstructure determines its failure properties at larger length scales, however, the specific relationship between microstructure and macroscopic failure in native and engineered soft tissues (such as capsular ligaments, aortic aneurysms, or vascular grafts) has proven elusive. In this study, variations in the microscale fiber alignment in collagen gel tissue analogs were modeled in order to understand their effects on macroscale damage and failure outcomes. The study employed a multiscale finite-element (FE) model for damage and failure in collagen-based materials. The model relied on microstructural representative volume elements (RVEs) that consisted of stochastically-generated networks of discrete type-I collagen fibers. Fiber alignment was varied within RVEs and between layers of RVEs in a macroscopic FE model of a notched dogbone geometry. The macroscale stretch and the microscale response of fibers for each of the differently aligned cases were compared as the dogbone was uniaxially extended to failure. Networks with greater fiber alignment parallel to the direction of extension failed at smaller strains (with a 6-22% reduction in the Green strain at failure), however, at greater grip forces (a 28-60% increase) than networks with fibers aligned perpendicular to the extension. Alternating layers of crisscrossed network alignments (aligned ±45 deg to the direction of extension) failed at smaller strains but at greater grip forces than those created using one fiber alignment type. In summary, variations in microscale structure via fiber alignment produced different macroscale failure trends. To conclude, these findings may be significant in the realm of tissue engineering and in soft tissue biomechanics.
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What is Visualize?

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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We use abstracts found on PubMed and match them to JoVE videos to create a list of 10 to 30 related methods videos.

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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.