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Find video protocols related to scientific articles indexed in Pubmed.
The HITECH Act and electronic health records' limitation in coordinating care for children with complex chronic conditions.
J Allied Health
PUBLISHED: 06-14-2014
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While the HITECH Act was implemented to promote the use of electronic health records to improve the quality and coordination of healthcare, the limitations established to the setting of the hospital or physician's office affect the care coordination for those who utilize many health-related services outside these settings, including children with complex and chronic conditions. Incentive-based support or nationally supported electronic health record systems for allied and other healthcare professionals are necessary to see the full impact that electronic health records can have on care coordination for individuals who utilize many skilled healthcare services that are not associated with a hospital or physician's office.
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Overexpression of the steroidogenic enzyme cytochrome P450 side chain cleavage in the ventral tegmental area increases 3?,5?-THP and reduces long-term operant ethanol self-administration.
J. Neurosci.
PUBLISHED: 04-25-2014
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Neuroactive steroids are endogenous neuromodulators capable of altering neuronal activity and behavior. In rodents, systemic administration of endogenous or synthetic neuroactive steroids reduces ethanol self-administration. We hypothesized this effect arises from actions within mesolimbic brain regions that we targeted by viral gene delivery. Cytochrome P450 side chain cleavage (P450scc) converts cholesterol to pregnenolone, the rate-limiting enzymatic reaction in neurosteroidogenesis. Therefore, we constructed a recombinant adeno-associated serotype 2 viral vector (rAAV2), which drives P450scc expression and neuroactive steroid synthesis. The P450scc-expressing vector (rAAV2-P450scc) or control GFP-expressing vector (rAAV2-GFP) were injected bilaterally into the ventral tegmental area (VTA) or nucleus accumbens (NAc) of alcohol preferring (P) rats trained to self-administer ethanol. P450scc overexpression in the VTA significantly reduced ethanol self-administration by 20% over the 3 week test period. P450scc overexpression in the NAc, however, did not alter ethanol self-administration. Locomotor activity was unaltered by vector administration to either region. P450scc overexpression produced a 36% increase in (3?,5?)-3-hydroxypregnan-20-one (3?,5?-THP, allopregnanolone)-positive cells in the VTA, but did not increase 3?,5?-THP immunoreactivity in NAc. These results suggest that P450scc overexpression and the resultant increase of 3?,5?-THP-positive cells in the VTA reduces ethanol reinforcement. 3?,5?-THP is localized to neurons in the VTA, including tyrosine hydroxylase neurons, but not astrocytes. Overall, the results demonstrate that using gene delivery to modulate neuroactive steroids shows promise for examining the neuronal mechanisms of moderate ethanol drinking, which could be extended to other behavioral paradigms and neuropsychiatric pathology.
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Abnormal muscle mechanosignaling triggers cardiomyopathy in mice with Marfan syndrome.
J. Clin. Invest.
PUBLISHED: 02-17-2014
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Patients with Marfan syndrome (MFS), a multisystem disorder caused by mutations in the gene encoding the extracellular matrix (ECM) protein fibrillin 1, are unusually vulnerable to stress-induced cardiac dysfunction. The prevailing view is that MFS-associated cardiac dysfunction is the result of aortic and/or valvular disease. Here, we determined that dilated cardiomyopathy (DCM) in fibrillin 1-deficient mice is a primary manifestation resulting from ECM-induced abnormal mechanosignaling by cardiomyocytes. MFS mice displayed spontaneous emergence of an enlarged and dysfunctional heart, altered physical properties of myocardial tissue, and biochemical evidence of chronic mechanical stress, including increased angiotensin II type I receptor (AT1R) signaling and abated focal adhesion kinase (FAK) activity. Partial fibrillin 1 gene inactivation in cardiomyocytes was sufficient to precipitate DCM in otherwise phenotypically normal mice. Consistent with abnormal mechanosignaling, normal cardiac size and function were restored in MFS mice treated with an AT1R antagonist and in MFS mice lacking AT1R or ?-arrestin 2, but not in MFS mice treated with an angiotensin-converting enzyme inhibitor or lacking angiotensinogen. Conversely, DCM associated with abnormal AT1R and FAK signaling was the sole abnormality in mice that were haploinsufficient for both fibrillin 1 and ?1 integrin. Collectively, these findings implicate fibrillin 1 in the physiological adaptation of cardiac muscle to elevated workload.
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Chronic Intermittent Ethanol Exposure and Withdrawal Alters (3?,5?)-3-Hydroxy-Pregnan-20-One Immunostaining in Cortical and Limbic Brain Regions of C57BL/6J Mice.
Alcohol. Clin. Exp. Res.
PUBLISHED: 02-10-2014
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The GABAergic neuroactive steroid (3?,5?)-3-hydroxy-pregnan-20-one (3?,5?-THP; allopregnanolone) has been studied during withdrawal from ethanol (EtOH) in humans, rats, and mice. Serum 3?,5?-THP levels decreased, and brain levels were not altered following acute EtOH administration (2 g/kg) in male C57BL/6J mice; however, the effects of chronic intermittent ethanol (CIE) exposure on 3?,5?-THP levels have not been examined. Given that CIE exposure changes subsequent voluntary EtOH drinking in a time-dependent fashion following repeated cycles of EtOH exposure, we conducted a time-course analysis of CIE effects on 3?,5?-THP levels in specific brain regions known to influence drinking behavior.
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Reduction of circulating and selective limbic brain levels of (3?,5?)-3-hydroxy-pregnan-20-one (3?,5?-THP) following forced swim stress in C57BL/6J mice.
Psychopharmacology (Berl.)
PUBLISHED: 01-24-2014
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Stress activates the hypothalamic-pituitary-adrenal (HPA) axis, and GABAergic neuroactive steroids contribute to homeostatic regulation of this circuitry. Acute forced swim stress (FSS) increases plasma, cortical, and hypothalamic (3?,5?)-3-hydroxy-pregnan-20-one (3?,5?-THP) levels in rats. However, there have not been systemic investigations of acute stress on changes in plasma and brain levels of 3?,5?-THP in mouse models.
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Clinical, diagnostic, and therapeutic aspects of the Marfan syndrome.
Adv. Exp. Med. Biol.
PUBLISHED: 01-21-2014
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Marfan syndrome (MFS) is a relatively common and often lethal disease of connective tissue. Medical, surgical and basic research advances over the last two decades have had a major positive impact on the clinical management of MFS patients. Life expectancy has increased significantly, more discriminating diagnostic criteria have been developed, a number of new clinical entities have been recognized, and exciting opportunities for drug-based therapy have emerged. Despite such a remarkable progress, MFS diagnosis remains difficult and aortic disease progression is very heterogeneous and clinical outcome is unpredictable. Ongoing research efforts are therefore exploiting animal models of MFS to identify novel diagnostic and prognostic biomarkers, genetic, epigenetic and environmental modifiers and druggable biological targets.
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Ethanol alters local cellular levels of (3?,5?)-3-hydroxypregnan-20-one (3?,5?-THP) independent of the adrenals in subcortical brain regions.
Neuropsychopharmacology
PUBLISHED: 01-14-2014
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The neuroactive steroid (3?,5?)-3-hydroxypregnan-20-one (3?,5?-THP or allopregnanolone) is a positive modulator of GABAA receptors synthesized in the brain, adrenal glands, and gonads. In rats, ethanol activates the hypothalamic-pituitary-adrenal axis and elevates 3?,5?-THP in plasma, cerebral cortex, and hippocampus. In vivo, these effects are dependent on both the pituitary and adrenal glands. In vitro, however, ethanol locally increases 3?,5?-THP in hippocampal slices, in the absence of adrenal influence. Therefore, it is not known whether ethanol can change local brain levels of 3?,5?-THP in vivo, independent of the adrenals. To directly address this controversy, we administered ethanol (2 g/kg) or saline to rats that underwent adrenalectomy (ADX) or received sham surgery and performed immunohistochemistry for 3?,5?-THP. In the medial prefrontal cortex (mPFC), ethanol increased 3?,5?-THP after sham surgery, compared with saline controls, with no ethanol-induced change in 3?,5?-THP following ADX. In subcortical regions, 3?,5?-THP was increased independent of adrenals in the CA1 pyramidal cell layer, dentate gyrus polymorphic layer, bed nucleus of the stria terminalis, and paraventricular nucleus of the hypothalamus. Furthermore, ethanol decreased 3?,5?-THP labeling in the nucleus accumbens shore and central nucleus of the amygdala, independent of the adrenal glands. These data indicate that ethanol dynamically regulates local 3?,5?-THP levels in several subcortical regions; however, the adrenal glands contribute to 3?,5?-THP elevations in the mPFC. Using double immunofluorescent labeling we determined that adrenal dependence of 3?,5?-THP induction by ethanol is not due to a lack of colocalization of 3?,5?-THP with the cholesterol transporters steroidogenic acute regulatory protein (StAR) or translocator protein (TSPO).
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Continuation of long-term care for cervical dystonia at an academic movement disorders clinic.
Toxins (Basel)
PUBLISHED: 03-19-2013
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Patients with cervical dystonia (CD) receive much of their care at university based hospital outpatient clinics. This study aimed to describe the clinical characteristics and treatment experiences of patients who continued care at our university based movement disorders clinic, and to document the reasons for which a subset discontinued care. Seventy patients (77% female) were recruited from all patients at the clinic (n = 323). Most (93%) were treated with botulinum neurotoxin (BoNT) injection, and onabotulinumtoxinA was initially used in 97%. The average dose of onabotulinumtoxinA was 270.4 U (range 50-500) and the median number of injections was 14 (range: 1-39). Twenty one patients later received at least one cycle of rimabotulinumtoxinB (33%); of those, 10 switched back to onabotulinumtoxinA (48%). The initial rimabotulinumtoxinB dose averaged 11,996 units (range: 3000-25,000 over 1-18 injections). Twenty one patients (30%) discontinued care. Reasons cited included suboptimal response to BoNT therapy (62%), excessive cost (24%), excessive travel burden (10%), and side effects of BoNT therapy (10%). Most patients (76%) did not seek further care after leaving the clinic. Patients who terminated care received fewer treatment cycles (5.5 vs. 13.0, p = 0.020). There were no other identifiable differences between groups in gender, age, disease characteristics, toxin dose, or toxin formulation. These results indicate that a significant number of CD patients discontinue care due to addressable barriers to access, including cost and travel burden, and that when leaving specialty care, patients often discontinue treatment altogether. These data highlight the need for new initiatives to reduce out-of-pocket costs, as well as training for community physicians on neurotoxin injection in order to lessen the travel burden patients must accept in order to receive standard-of-care treatments.
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Ethanol Administration Produces Divergent Changes in GABAergic Neuroactive Steroid Immunohistochemistry in the Rat Brain.
Alcohol. Clin. Exp. Res.
PUBLISHED: 02-08-2013
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The 5?-reduced pregnane neuroactive steroid (3?,5?)-3-hydroxypregnan-20-one (3?,5?-THP or allopregnanolone) is a potent positive modulator of GABAA receptors capable of modulating neuronal activity. In rats, systemic ethanol (EtOH) administration increases cerebral cortical and hippocampal levels of 3?,5?-THP, but the effects of EtOH on 3?,5?-THP levels in other brain regions are unknown. There is a large body of evidence suggesting that 3?,5?-THP enhances EtOH sensitivity, contributes to some behavioral effects of EtOH, and modulates EtOH reinforcement and motivation to drink. In this study, we used immunohistochemistry (IHC) to determine EtOH-induced changes in cellular 3?,5?-THP expression in brain regions associated with EtOH actions and responses.
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Quantitative photoacoustic imaging of nanoparticles in cells and tissues.
ACS Nano
PUBLISHED: 01-17-2013
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Quantitative visualization of nanoparticles in cells and tissues, while preserving the spatial information, is very challenging. A photoacoustic imaging technique to depict the presence and quantity of nanoparticles is presented. This technique is based on the dependence of the photoacoustic signal on both the nanoparticle quantity and the laser fluence. Quantitative photoacoustic imaging is a robust technique that does not require knowledge of the local fluence, but a relative change in the fluence. This eliminates the need for sophisticated methods or models to determine the energy distribution of light in turbid media. Quantitative photoacoustic imaging was first applied to nanoparticle-loaded cells, and quantitation was validated by inductively coupled plasma mass spectrometry. Quantitative photoacoustic imaging was then extended to xenograft tumor tissue sections, and excellent agreement with traditional histopathological analysis was demonstrated. Our results suggest that quantitative photoacoustic imaging may be used in many applications including the determination of the efficiency and effectiveness of molecular targeting strategies for cell studies and animal models, the quantitative assessment of photoacoustic contrast agent biodistribution, and the validation of in vivo photoacoustic imaging.
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Genetic architecture of maize kernel composition in the nested association mapping and inbred association panels.
Plant Physiol.
PUBLISHED: 12-01-2011
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The maize (Zea mays) kernel plays a critical role in feeding humans and livestock around the world and in a wide array of industrial applications. An understanding of the regulation of kernel starch, protein, and oil is needed in order to manipulate composition to meet future needs. We conducted joint-linkage quantitative trait locus mapping and genome-wide association studies (GWAS) for kernel starch, protein, and oil in the maize nested association mapping population, composed of 25 recombinant inbred line families derived from diverse inbred lines. Joint-linkage mapping revealed that the genetic architecture of kernel composition traits is controlled by 21-26 quantitative trait loci. Numerous GWAS associations were detected, including several oil and starch associations in acyl-CoA:diacylglycerol acyltransferase1-2, a gene that regulates oil composition and quantity. Results from nested association mapping were verified in a 282 inbred association panel using both GWAS and candidate gene association approaches. We identified many beneficial alleles that will be useful for improving kernel starch, protein, and oil content.
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Inhalation of LPS induces inflammatory airway responses mimicking characteristics of chronic obstructive pulmonary disease.
Clin Physiol Funct Imaging
PUBLISHED: 10-14-2011
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Inhalation of lipopolysaccharide (LPS) produces both systemic and pulmonary inflammatory responses. The aim of this study was to further characterize the response to LPS in order to develop a human model suitable for early testing of drug candidates developed for the treatment for chronic obstructive pulmonary disease (COPD).
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Febrile ulceronecrotic Mucha-Habermann disease: a case with systemic symptoms managed with subcutaneous methotrexate.
Australas. J. Dermatol.
PUBLISHED: 09-20-2011
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Febrile ulceronecrotic Mucha-Habermann disease (FUMHD) is a rare, idiopathic, acquired dermatosis that can affect all ages and ethnic groups. We present a 10-year-old patient with FUMHD associated with arthritis and chronic fatigue, managed with methotrexate. Through our literature review, we also explore treatment protocols for a disease for which internationally standardized management is yet to be formulated.
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Tissue-mimicking phantoms for photoacoustic and ultrasonic imaging.
Biomed Opt Express
PUBLISHED: 09-20-2011
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In both photoacoustic (PA) and ultrasonic (US) imaging, overall image quality is influenced by the optical and acoustical properties of the medium. Consequently, with the increased use of combined PA and US (PAUS) imaging in preclinical and clinical applications, the ability to provide phantoms that are capable of mimicking desired properties of soft tissues is critical. To this end, gelatin-based phantoms were constructed with various additives to provide realistic acoustic and optical properties. Forty-micron, spherical silica particles were used to induce acoustic scattering, Intralipid(®) 20% IV fat emulsion was employed to enhance optical scattering and ultrasonic attenuation, while India Ink, Direct Red 81, and Evans blue dyes were utilized to achieve optical absorption typical of soft tissues. The following parameters were then measured in each phantom formulation: speed of sound, acoustic attenuation (from 6 to 22 MHz), acoustic backscatter coefficient (from 6 to 22 MHz), optical absorption (from 400 nm to 1300 nm), and optical scattering (from 400 nm to 1300 nm). Results from these measurements were then compared to similar measurements, which are offered by the literature, for various soft tissue types. Based on these comparisons, it was shown that a reasonably accurate tissue-mimicking phantom could be constructed using a gelatin base with the aforementioned additives. Thus, it is possible to construct a phantom that mimics specific tissue acoustical and/or optical properties for the purpose of PAUS imaging studies.
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Heating mechanisms in gold nanoparticles at radio frequencies.
Conf Proc IEEE Eng Med Biol Soc
PUBLISHED: 08-29-2011
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Gold nanoparticles are under study as a potentially viable mechanism for hyperthermia tumor treatment in two regimes of the electromagnetic spectrum: laser and radio frequency excitation. Gold nanoparticles, nanorods and nanoshells have been applied with visible laser sources that excite the particles at or near their plasmon resonance frequency, and this mechanism has been well studied. The physical processes that describe the experimentally observed heating at radio frequencies (13.56 MHz) are not as well understood. Differing results have been reported in semi-solid phantom materials and liquid phase suspensions. This numerical modeling study was undertaken to inspect the relative importance of several candidate physical processes.
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Determination of free desmosine and isodesmosine as urinary biomarkers of lung disorder using ultra performance liquid chromatography-ion mobility-mass spectrometry.
J. Chromatogr. B Analyt. Technol. Biomed. Life Sci.
PUBLISHED: 06-01-2011
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The elastin degradation products, desmosine (DES) and isodesmosine (IDES) are highly stable, cross-linking amino-acids that are unique to mature elastin. The excretion of DES/IDES in urine, in the free form and with associated peptide fragments, provides an indicator of lung damage in chronic obstructive pulmonary disease (COPD). A quantitative ion mobility-mass spectrometry (IM-MS) method has been developed for the analysis of free DES/IDES in urine with deuterated IDES as an internal standard. Resolution of DES/IDES isomers was achieved in less than five minutes using ultra performance liquid chromatography (UPLC) combined with ion pairing. The optimized UPLC-IM-MS method provided a linear dynamic range of 10-300 ng/mL and a limit of quantitation of 0.028 ng/mL for IDES and 0.03 ng/mL for DES (0.55 ng and 0.61 ng on column respectively). The method reproducibility (%RSD) was <4% for DES and IDES. The UPLC-IM-MS method was applied to the analysis of urine samples obtained from healthy volunteers and COPD patients. The DES/IDES concentrations in healthy and COPD urine showed an increase in DES (79%) and IDES (74%) in the COPD samples, relative to healthy controls. The incorporation of an IM separation prior to m/z measurement by MS was shown to reduce non-target ion responses from the bio-fluid matrix.
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6th Annual Bioanalysis in Clinical Research conference.
Bioanalysis
PUBLISHED: 05-19-2011
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The 6th Annual Bioanalysis in Clinical Research conference held recently in London, UK, targeted numerous themes of significant current interest within the discipline of bioanalysis. The conference invited a diverse speaker panel and attracted an audience consisting of researchers from the pharmaceutical industry, CROs and academia. The range of topics presented covered LC-MS and ligand-binding assays, small- and large-molecule quantification, regulatory issues and concerns and new technologies. Within the scope of LC-MS bioanalysis, presentation topics included new developments in dried blood spot technologies, the use of direct analysis MS techniques, eliminating matrix effects through direct-electron ionization MS, and the complications of developing and validating LC-MS methods for the quantitative determination of endogenous biomarkers. With respect to ligand binding, the importance of assay validation being a continuous process, extending into study analysis, was a recurrent theme in several presentations along with the hot topic of immunogenicity. Of relevance to both analytical disciplines were the presentations on regulatory topics covering the EMA guidelines on method validation and bioanalysis within bioequivalence clinical studies.
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FEM numerical model study of heating in magnetic nanoparticles.
Proc SPIE
PUBLISHED: 02-22-2011
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Electromagnetic heating of nanoparticles is complicated by the extremely short thermal relaxation time constants and difficulty of coupling sufficient power into the particles to achieve desired temperatures. Magnetic field heating by the hysteresis loop mechanism at frequencies between about 100 and 300 kHz has proven to be an effective mechanism in magnetic nanoparticles. Experiments at 2.45 GHz show that Fe3O4 magnetite nanoparticle dispersions in the range of 10(12) to 10(13) NP/mL also heat substantially at this frequency. An FEM numerical model study was undertaken to estimate the order of magnitude of volume power density, Qgen (W m(-3)) required to achieve significant heating in evenly dispersed and aggregated clusters of nanoparticles. The FEM models were computed using Comsol Multiphysics; consequently the models were confined to continuum formulations and did not include film nano-dimension heat transfer effects at the nanoparticle surface. As an example, the models indicate that for a single 36 nm diameter particle at an equivalent dispersion of 10(13) NP/mL located within one control volume (1.0 × 10(-19) m(3)) of a capillary vessel a power density in the neighborhood of 10(17) (W m(-3)) is required to achieve a steady state particle temperature of 52 °C - the total power coupled to the particle is 2.44 ?W. As a uniformly distributed particle cluster moves farther from the capillary the required power density decreases markedly. Finally, the tendency for particles in vivo to cluster together at separation distances much less than those of the uniform distribution further reduces the required power density.
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Ferrimagnetic nanoparticles enhance microwave heating for tumor hyperthermia therapy.
Conf Proc IEEE Eng Med Biol Soc
PUBLISHED: 11-25-2010
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Localized tumor hyperthermia therapy has been intensively studied for the past three decades. One engineering limitation has been the difficulty of specifically targeting cancerous tissues in the normal tissue surroundings. Recent attention has turned to the deposition of nanoparticles in the tumor to enhance heating relative to its surroundings. The work in magnetic nanoparticles has focused on resonant hysteresis loop heating in the 100 to 300 kHz range, where that mechanism dominates - however extremely high magnetic field strengths are required to realize an advantage, up to 10(5) (A/m). We introduce experimental evidence that substantial advantages in heating can also be obtained at the microwave ISM frequency of 2.45 GHz when ?-hematite (Fe(2)O(3)) is dispersed in media at concentrations on the order of 10(12) particles/mL.
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Differential effects of alendronate and losartan therapy on osteopenia and aortic aneurysm in mice with severe Marfan syndrome.
Hum. Mol. Genet.
PUBLISHED: 09-24-2010
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Reduced bone mineral density (osteopenia) is a poorly characterized manifestation of pediatric and adult patients afflicted with Marfan syndrome (MFS), a multisystem disorder caused by structural or quantitative defects in fibrillin-1 that perturb tissue integrity and TGF? bioavailability. Here we report that mice with progressively severe MFS (Fbn1(mgR/mgR) mice) develop osteopenia associated with normal osteoblast differentiation and bone formation. In vivo and ex vivo experiments, respectively, revealed that adult Fbn1(mgR/mgR) mice respond more strongly to locally induced osteolysis and that Fbn1(mgR/mgR) osteoblasts stimulate pre-osteoclast differentiation more than wild-type cells. Greater osteoclastogenic potential of mutant osteoblasts was largely attributed to Rankl up-regulation secondary to improper TGF? activation and signaling. Losartan treatment, which lowers TGF? signaling and restores aortic wall integrity in mice with mild MFS, did not mitigate bone loss in Fbn1(mgR/mgR) mice even though it ameliorated vascular disease. Conversely, alendronate treatment, which restricts osteoclast activity, improved bone quality but not aneurysm progression in Fbn1(mgR/mgR) mice. Taken together, our findings shed new light on the pathogenesis of osteopenia in MFS, in addition to arguing for a multifaceted treatment strategy in this congenital disorder of the connective tissue.
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Drug-based therapies for vascular disease in Marfan syndrome: from mouse models to human patients.
Mt. Sinai J. Med.
PUBLISHED: 08-06-2010
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Marfan syndrome is a congenital disorder of the connective tissue with a long history of clinical and basic science breakthroughs that have forged our understanding of vascular-disease pathogenesis. The biomedical importance of Marfan syndrome was recently underscored by the discovery that the underlying genetic lesion impairs both tissue integrity and transforming growth factor-beta regulation of cell behavior. This discovery has led to the successful implementation of the first pharmacological intervention in a connective-tissue disorder otherwise incurable by either gene-based or stem cell-based therapeutic strategies. More generally, information gathered from the study of Marfan syndrome pathogenesis has the potential to improve the clinical management of common acquired disorders of connective-tissue degeneration.
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Nicotinic receptor ligands reduce ethanol intake by high alcohol-drinking HAD-2 rats.
Alcohol
PUBLISHED: 05-21-2009
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Neuronal nicotinic acetylcholine receptors (nAChRs) are implicated in the reinforcing effects of many drugs of abuse, including ethanol. The present study examined the efficacy of cytisine, a nAChR partial agonist, and lobeline, a putative nAChR antagonist, on the maintenance of ethanol drinking by HAD-2 rats. Adult male HAD-2 rats were given access to ethanol (15 and 30%, with ad libitum access to water and food) 22 h/day for 12 weeks, beginning at 60 days of age, after which cytisine (0.0, 0.5, and 1.5 mg/kg) was tested for 3 consecutive days. The rats were given an 18-day washout period and were then tested with lobeline (0.0, 1.0, and 5.0 mg/kg) for 3 consecutive days. Ethanol intake was measured at 1, 4, and 22 h postinjection. Rats were injected intraperitoneally just before lights out (1200 h). There was a significant main effect of cytisine treatment on the second test day, with the 1.5 mg/kg dose significantly reducing ethanol intake at the 1- and 4-h time-points, relative to saline, and the 0.5 mg/kg dose inducing a significant reduction at the 4-h time-point. Conversely, lobeline treatment resulted in significant main effects of treatment for all three time-points within each test day, with the 5.0 mg/kg dose significantly reducing ethanol intake, relative to saline, at each time-point within each test day. These findings provide further evidence that activity at the nAChR influences ethanol intake and is a promising target for pharmacotherapy development for the treatment of alcohol dependence and relapse.
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Generation of Fbn1 conditional null mice implicates the extracellular microfibrils in osteoprogenitor recruitment.
Genesis
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Loss-of-function experiments in mice have yielded invaluable mechanistic insights into the pathogenesis of Marfan syndrome (MFS) and implicitly, into the multiple roles fibrillin-1 microfibrils play in the developing and adult organism. Unfortunately, neonatal death from aortic complications of mice lacking fibrillin-1 (Fbn1(-/-) mice) has limited the scope of these studies. Here, we report the creation of a conditional mutant allele (Fbn1(fneo) ) that contains loxP sites bordering exon1 of Fbn1 and an frt-flanked neo expression cassette downstream of it. Fbn1(fneo/+) mice were crossed with FLPeR mice and the resulting Fbn1(Lox/+) progeny were crossed with Fbn1(+/-) ;CMV-Cre mice to generate Fbn1(CMV-/-) mice, which were found to phenocopy the vascular abnormalities of Fbn1(-/-) mice. Furthermore, mating Fbn1(Lox/+) mice with Prx1-Cre or Osx-Cre mice revealed an unappreciated role of fibrillin-1 microfibrils in restricting osteoprogenitor cell recruitment. Fbn1(Lox/+) mice are, therefore, an informative genetic resource to further dissect MFS pathogenesis and the role of extracellular fibrillin-1 assemblies in organ development and homeostasis.
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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.

Video X seems to be unrelated to Abstract Y...

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.