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Find video protocols related to scientific articles indexed in Pubmed.
Reproducibility of histological assessments of disease activity in UC.
Gut
PUBLISHED: 11-01-2014
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Histopathology is potentially an important outcome measure in UC. Multiple histological disease activity (HA) indices, including the Geboes score (GS) and modified Riley score (MRS), have been developed; however, the operating properties of these instruments are not clearly defined. We assessed the reproducibility of existing measures of HA.
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Accuracy of MR Imaging-estimated Proton Density Fat Fraction for Classification of Dichotomized Histologic Steatosis Grades in Nonalcoholic Fatty Liver Disease.
Radiology
PUBLISHED: 09-24-2014
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Purpose To evaluate the diagnostic performance of previously proposed high-specificity magnetic resonance (MR) imaging-estimated proton density fat fraction ( PDFF proton density fat fraction ) thresholds for diagnosis of steatosis grade 1 or higher ( PDFF proton density fat fraction threshold of 6.4%), grade 2 or higher ( PDFF proton density fat fraction threshold of 17.4%), and grade 3 ( PDFF proton density fat fraction threshold of 22.1%) by using histologic findings as a reference in an independent cohort of adults known to have or suspected of having nonalcoholic fatty liver disease ( NAFLD nonalcoholic fatty liver disease ). Materials and Methods This prospective, cross-sectional, institutional review board-approved, HIPAA-compliant single-center study was conducted in an independent cohort of 89 adults known to have or suspected of having NAFLD nonalcoholic fatty liver disease who underwent contemporaneous liver biopsy. MR imaging PDFF proton density fat fraction was estimated at 3 T by using magnitude-based low-flip-angle multiecho gradient-recalled-echo imaging with T2* correction and multipeak modeling. Steatosis was graded histologically (grades 0, 1, 2, and 3, according to the Nonalcoholic Steatohepatitis Clinical Research Network scoring system). Sensitivity, specificity, and binomial confidence intervals were calculated for the proposed MR imaging PDFF proton density fat fraction thresholds. Results The proposed MR imaging PDFF proton density fat fraction threshold of 6.4% to diagnose grade 1 or higher steatosis had 86% sensitivity (71 of 83 patients; 95% confidence interval [CI]: 76, 92) and 83% specificity (five of six patients; 95% CI: 36, 100). The threshold of 17.4% to diagnose grade 2 or higher steatosis had 64% sensitivity (28 of 44 patients; 95% CI: 48, 78) and 96% specificity (43 of 45 patients; 95% CI: 85, 100). The threshold of 22.1% to diagnose grade 3 steatosis had 71% sensitivity (10 of 14 patients; 95% CI: 42, 92) and 92% specificity (69 of 75 patients; 95% CI: 83, 97). Conclusion In an independent cohort of adults known to have or suspected of having NAFLD nonalcoholic fatty liver disease , the previously proposed MR imaging PDFF proton density fat fraction thresholds provided moderate to high sensitivity and high specificity for diagnosis of grade 1 or higher, grade 2 or higher, and grade 3 steatosis. Prospective multicenter studies are now needed to further validate these high-specificity thresholds. © RSNA, 2014 Online supplemental material is available for this article.
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Use of an inertial measurement unit to assess the effect of forelimb lameness on three-dimensional hoof orientation in horses at a walk and trot.
Am. J. Vet. Res.
PUBLISHED: 08-27-2014
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To determine intralimb orientation changes with an inertial measurement unit (IMU) in hooves of horses at a walk and trot after induction of weight-bearing single forelimb lameness and to determine whether hoof orientations are similar to baseline values following perineural anesthesia.
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Effects of Landau level mixing on the fractional quantum Hall effect in monolayer graphene.
Phys. Rev. Lett.
PUBLISHED: 08-18-2014
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We report results of exact diagonalization studies of the spin- and valley-polarized fractional quantum Hall effect in the N = 0 and N = 1 Landau levels in graphene. We use an effective model that incorporates Landau level mixing to lowest order in the parameter ? = ((e(2)/??)/(?v(F)/?)) = (e(2)/?v(F)?), which is magnetic field independent and can only be varied through the choice of substrate. We find Landau level mixing effects are negligible in the N = 0 Landau level for ? ? 2. In fact, the lowest Landau level projected Coulomb Hamiltonian is a better approximation to the real Hamiltonian for graphene than it is for semiconductor based quantum wells. Consequently, the principal fractional quantum Hall states are expected in the N = 0 Landau level over this range of ?. In the N = 1 Landau level, fractional quantum Hall states are expected for a smaller range of ? and Landau level mixing strongly breaks particle-hole symmetry, producing qualitatively different results compared to the N = 0 Landau level. At half filling of the N = 1 Landau level, we predict the anti-Pfaffian state will occur for ? ? 0.25-0.75.
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Reduced mediodorsal thalamic volume and prefrontal cortical spindle activity in schizophrenia.
Neuroimage
PUBLISHED: 08-17-2014
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We recently found marked deficits in sleep spindles, non-rapid eye movement (NREM) sleep oscillations that are generated within the thalamus and then amplified and sustained in the cortex, in patients with schizophrenia compared to both healthy and psychiatric controls. Here, we investigated the thalamic and cortical contributions to these sleep spindle deficits.
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Magnetic resonance elastography predicts advanced fibrosis in patients with nonalcoholic fatty liver disease: A prospective study.
Hepatology
PUBLISHED: 08-08-2014
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Retrospective studies have shown that two-dimensional magnetic resonance elastography (2D-MRE), a novel MR method for assessment of liver stiffness, correlates with advanced fibrosis in patients with nonalcoholic fatty liver disease (NAFLD). Prospective data on diagnostic accuracy of 2D-MRE in the detection of advanced fibrosis in NAFLD are needed. The aim of this study is to prospectively assess the diagnostic accuracy of 2D-MRE, a noninvasive imaging biomarker, in predicting advanced fibrosis (stage 3 or 4) in well-characterized patients with biopsy-proven NAFLD. This is a cross-sectional analysis of a prospective study including 117 consecutive patients (56% women) with biopsy-proven NAFLD who underwent a standardized research visit: history, exam, liver biopsy assessment (using the nonalcoholic steatohepatitis Clinical Research Network histological scoring system), and 2D-MRE from 2011 to 2013. The radiologist and pathologist were blinded to clinical and pathology/imaging data, respectively. Receiver operating characteristics (ROCs) were examined to assess the diagnostic test performance of 2D-MRE in predicting advanced fibrosis. The mean (± standard deviation) of age and body mass index was 50.1 (± 13.4) years and 32.4 (± 5.0) kg/m(2) , respectively. The median time interval between biopsy and 2D-MRE was 45 days (interquartile range: 50 days). The number of patients with fibrosis stages 0, 1, 2, 3, and 4 was 43, 39, 13, 12, and 10, respectively. The area under the ROC curve for 2D-MRE discriminating advanced fibrosis (stage 3-4) from stage 0-2 fibrosis was 0.924 (P?3.63 kPa had a sensitivity of 0.86 (95% confidence interval [CI]: 0.65-0.97), specificity of 0.91 (95% CI: 0.83-0.96), positive predictive value of 0.68 (95% CI: 0.48-0.84), and negative predictive value of 0.97 (95% CI: 0.91-0.99). Conclusions: MRE is accurate in predicting advanced fibrosis and may be utilized for noninvasive diagnosis of advanced fibrosis in patients with NAFLD. (Hepatology 2014).
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Impact of an integrated disease management program in reducing exacerbations in patients with severe asthma and COPD.
Respir Med
PUBLISHED: 07-02-2014
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Conflicting data exists on the effectiveness of integrated programs in reducing recurrent exacerbations and hospitalizations in patients with Asthma and chronic obstructive lung disease (COPD). We developed a Pulmonologist-led Chronic Lung Disease Program (CLDP) for patients with severe asthma and COPD and analyzed its impact on healthcare utilization and predictors of its effectiveness.
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Population-based analysis of cholesteryl ester transfer protein identifies association between I405V and cognitive decline: the Cache County Study.
Neurobiol. Aging
PUBLISHED: 06-05-2014
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Cholesterol has been implicated in the pathogenesis of late-onset Alzheimer's disease (LOAD) and the cholesteryl ester transfer protein (CETP) is critical to cholesterol regulation within the cell, making CETP an Alzheimer's disease candidate gene. Several studies have suggested that CETP I405V (rs5882) is associated with cognitive function and LOAD risk, but findings vary and most studies have been conducted using relatively small numbers of samples. To test whether this variant is involved in cognitive function and LOAD progression, we genotyped 4486 subjects with up to 12 years of longitudinal cognitive assessment. Analyses revealed an average 0.6-point decrease per year in the rate of cognitive decline for each additional valine (p < 0.011). We failed to detect the association between CETP I405V and LOAD status (p < 0.28). We conclude that CETP I405V is associated with preserved cognition over time but is not associated with LOAD status.
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Effect of Weight Loss on MRI Estimation of Liver Fat and Volume in Patients With Nonalcoholic Steatohepatitis.
Clin. Gastroenterol. Hepatol.
PUBLISHED: 05-21-2014
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Little is known about how weight loss affects magnetic resonance imaging (MRI) of liver fat and volume or liver histology in patients with non-alcoholic steatohepatitis (NASH). We measured changes in liver fat and liver volume associated with weight loss using an advanced MRI method.
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Associations between histologic features of nonalcoholic fatty liver disease (NAFLD) and quantitative diffusion-weighted MRI measurements in adults.
J Magn Reson Imaging
PUBLISHED: 05-04-2014
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To investigate in adults the associations between histologic features of nonalcoholic fatty liver disease (NAFLD) and quantitative measures derived from diffusion-weighted imaging (DWI).
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Updated Physician's Guide to the Off-label Uses of Oral Isotretinoin.
J Clin Aesthet Dermatol
PUBLISHED: 04-26-2014
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While oral isotretinoin is renowned for its ability to treat acne vulgaris, many of its off-label uses continue to go underappreciated. Since the last review on the unapproved indications of isotretinoin, relevant publications have surfaced with new recommendations. This article attempts to provide physicians with the latest information regarding successful and unsuccessful use of isotretinoin as an effective treatment for dermatological conditions, such as rosacea, psoriasis, pityriasis rubra pilaris, condyloma acuminatum, granuloma annulare, Darier's disease, systemic cutaneous lupus erythematosus, nonmelanoma skin cancer, and hidradenitis suppurativa. Variations in dosage regimens and isotretinoin viability as an alternative to other standard treatments are also discussed in relation to these conditions.
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Call for a California Coccidioidomycosis Consortium to Face the Top Ten Challenges Posed by a Recalcitrant Regional Disease.
Mycopathologia
PUBLISHED: 04-18-2014
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Coccidioidomycosis ('Valley Fever'), caused by the inhalation of the fungus Coccidioides, remains a recalcitrant health problem in large parts of California. The incidence and severity of the disease continues to rise in many parts of the state. In this manuscript, we highlight unanswered questions about the disease. Specifically, the extent of disease burden, genetic determinants of host susceptibility, diagnostic and treatment guidelines, natural reservoirs of the pathogens, antifungal drug resistance, and fungal determinants of mild or severe disease are all areas awaiting in depth investigations. We also recommend establishment of a California Coccidioidomycosis Registry to improve clinical care and translational research.
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Valley fever: danger lurking in a dust cloud.
Microbes Infect.
PUBLISHED: 04-01-2014
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Coccidioides immitis and Coccidioides posadasii contribute to the development of Valley Fever. The ability of these fungal pathogens to evade the host immune system creates difficulty in recognition and treatment of this debilitating infection. In this review, we describe the current knowledge of Valley Fever and approaches to improve prevention, detection, and treatment.
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Ultrasound for routine lumbar puncture.
Acad Emerg Med
PUBLISHED: 03-29-2014
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The objective was to determine if use of ultrasound (US) by emergency physicians (EPs) to localize spinal landmarks improves the performance of lumbar puncture (LP).
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Prevalence of respiratory diseases among veterans of Operation Enduring Freedom and Operation Iraqi Freedom: results from the National Health Study for a New Generation of U.S. Veterans.
Mil Med
PUBLISHED: 03-06-2014
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This study investigated the population prevalence of asthma, bronchitis, and sinusitis among veterans deployed to Afghanistan and Iraq compared to nondeployed veterans. A 2009-2011 population-based health survey of 60,000 veterans (34% response rate) asked about the history of doctor-diagnosed respiratory disease. Analyses included smoking history, deployment status, and year of diagnosis. The prevalence of asthma, bronchitis, and sinusitis among those diagnosed during or after 2001 was 3.3%, 5.9%, and 6.9%, respectively, among the deployed veterans and 3.4%, 5.3%, and 5.6%, respectively, among the nondeployed veterans. Deployed veterans were 29% more likely to have been diagnosed with sinusitis during and after 2001 compared to nondeployed veterans (adjusted odds ratio = 1.30, 95% confidence interval = 1.13, 1.49). Deployed veterans are at increased risk for sinusitis compared to nondeployed. There was no significant difference in asthma or bronchitis risk between deployed and nondeployed veterans.
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Generation of orthotopic patient-derived xenografts from gastrointestinal stromal tumor.
J Transl Med
PUBLISHED: 02-06-2014
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Gastrointestinal stromal tumor (GIST) is the most common sarcoma and its treatment with imatinib has served as the paradigm for developing targeted anti-cancer therapies. Despite this success, imatinib-resistance has emerged as a major problem and therefore, the clinical efficacy of other drugs has been investigated. Unfortunately, most clinical trials have failed to identify efficacious drugs despite promising in vitro data and pathological responses in subcutaneous xenografts. We hypothesized that it was feasible to develop orthotopic patient-derived xenografts (PDXs) from resected GIST that could recapitulate the genetic heterogeneity and biology of the human disease.
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Malignant cell contamination may lead to false-positive findings at endosonographic fine needle aspiration for tumor staging.
Endoscopy
PUBLISHED: 01-10-2014
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Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) of lymph nodes is used for staging of gastrointestinal malignancies. False-positive rates of 5?%?-?7?% are not well understood. Elements of EUS examinations that contribute to false-positive cytological findings were investigated.
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Response of African Elephants (Loxodonta africana) to Seasonal Changes in Rainfall.
PLoS ONE
PUBLISHED: 01-01-2014
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The factors that trigger sudden, seasonal movements of elephants are uncertain. We hypothesized that savannah elephant movements at the end of the dry season may be a response to their detection of distant thunderstorms. Nine elephants carrying Global Positioning System (GPS) receivers were tracked over seven years in the extremely dry and rugged region of northwestern Namibia. The transition date from dry to wet season conditions was determined annually from surface- and satellite-derived rainfall. The distance, location, and timing of rain events relative to the elephants were determined using the Tropical Rainfall Measurement Mission (TRMM) satellite precipitation observations. Behavioral Change Point Analysis (BCPA) was applied to four of these seven years demonstrating a response in movement of these elephants to intra- and inter-seasonal occurrences of rainfall. Statistically significant changes in movement were found prior to or near the time of onset of the wet season and before the occurrence of wet episodes within the dry season, although the characteristics of the movement changes are not consistent between elephants and years. Elephants in overlapping ranges, but following separate tracks, exhibited statistically valid non-random near-simultaneous changes in movements when rainfall was occurring more than 100 km from their location. While the environmental trigger that causes these excursions remains uncertain, rain-system generated infrasound, which can travel such distances and be detected by elephants, is a possible trigger for such changes in movement.
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Genome-wide mutational landscape of mucinous carcinomatosis peritonei of appendiceal origin.
Genome Med
PUBLISHED: 01-01-2014
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Mucinous neoplasms of the appendix (MNA) are rare tumors which may progress from benign to malignant disease with an aggressive biological behavior. MNA is often diagnosed after metastasis to the peritoneal surfaces resulting in mucinous carcinomatosis peritonei (MCP). Genetic alterations in MNA are poorly characterized due to its low incidence, the hypo-cellularity of MCPs, and a lack of relevant pre-clinical models. As such, application of targeted therapies to this disease is limited to those developed for colorectal cancer and not based on molecular rationale.
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Increased prefrontal cortex activity during negative emotion regulation as a predictor of depression symptom severity trajectory over 6 months.
JAMA Psychiatry
PUBLISHED: 11-01-2013
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Emotion regulation is critically disrupted in depression, and the use of paradigms that tap into these processes may uncover essential changes in neurobiology during treatment. In addition, because neuroimaging outcome studies of depression commonly use only baseline and end-point data-which are more prone to week-to-week noise in symptomatology-we sought to use all data points over the course of a 6-month trial.
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Mineralization in calcified plaque is like that of cortical bone--further evidence from ultrashort echo time (UTE) magnetic resonance imaging of carotid plaque calcification and cortical bone.
Med Phys
PUBLISHED: 10-05-2013
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This study aims to investigate carotid plaque calcification (CPC) using two-dimensional (2D) and 3D ultrashort echo time (UTE) magnetic resonance imaging (MRI) sequences and compare T1, T2*, water concentration, and bone mineral density (BMD) of CPC with those of cortical bone.
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The effect of two preparation procedures on an equine arena surface in relation to motion of the hoof and metacarpophalangeal joint.
Vet. J.
PUBLISHED: 09-26-2013
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A link between surface characteristics and injury has been identified in equine disciplines. Maintenance procedures are reported to affect surface characteristics and could influence horse movement. The study investigated limb and hoof movement on a synthetic surface following two different preparations (harrowing and rolling). Nine horses were recorded using infrared cameras and retro-reflective markers at walk, trot and canter on two surface preparations in a cross-over design. Hoof rotation and displacement, metacarpophalangeal joint (MCPJ) extension and third metacarpal (McIII) inclination (roll, pitch and yaw) were analysed using a general linear model. Surface hardness and traction were also measured. No differences in hoof rotations or hoof displacements were found between preparations. However, following harrowing, greater (P<0.05) MCPJ extension at mid-stance and greater (P<0.05) McIII adduction at impact was found when gait was grouped. Hardness and traction were statistically similar for both preparations. Alteration to the surface cushion appears to be sufficient to produce subtle changes in stride characteristics.
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Insulin Resistance Increases MRI-Estimated Pancreatic Fat in Nonalcoholic Fatty Liver Disease and Normal Controls.
Gastroenterol Res Pract
PUBLISHED: 09-04-2013
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Background. Ectopic fat deposition in the pancreas and its relationship with hepatic steatosis and insulin resistance have not been compared between patients with nonalcoholic fatty liver disease (NAFLD) and healthy controls. Aim. Using a novel magnetic resonance imaging (MRI) based biomarker, the proton-density-fat-fraction (MRI-PDFF), we compared pancreatic fat content in patients with biopsy-proven NAFLD to healthy controls and determined whether it is associated with insulin resistance and liver fat content. Methods. This nested case-control study was derived from two prospective studies including 43 patients with biopsy-proven NAFLD and 49 healthy controls who underwent biochemical testing and MRI. Results. Compared to healthy controls, patients with NAFLD had significantly higher pancreatic MRI-PDFF (3.6% versus 8.5%, P value <0.001), and these results remained consistent in multivariable-adjusted models including age, sex, body mass index, and diabetes (P value =0.03). We found a strong correlation between hepatic and pancreatic MRI-PDFF (Spearman correlation, P = 0.57, P value <0.001). Participants with increased insulin resistance determined by homeostatic-model-of-insulin-resistance (HOMA-IR) greater than 2.5 had higher pancreatic (7.3% versus 4.5%, P value =0.015) and liver (13.5% versus 4.0%, P value <0.001) MRI-PDFF. Conclusion. Patients with NAFLD have greater pancreatic fat than normal controls. Insulin resistance is associated with liver and pancreatic fat accumulation.
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Effect of forelimb lameness on hoof kinematics of horses at a walk.
Am. J. Vet. Res.
PUBLISHED: 08-28-2013
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To determine kinematic changes to the hoof of horses at a walk after induction of unilateral, weight-bearing forelimb lameness and to determine whether hoof kinematics return to prelameness (baseline) values after perineural anesthesia.
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Effect of forelimb lameness on hoof kinematics of horses at a trot.
Am. J. Vet. Res.
PUBLISHED: 08-28-2013
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To determine kinematic changes to the hoof of horses at a trot after induction of unilateral, weight-bearing forelimb lameness and to determine whether hoof kinematics return to prelameness values after perineural anesthesia.
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Cholecalciferol.
Top Companion Anim Med
PUBLISHED: 06-26-2013
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The primary source of exposure to cholecalciferol in dogs and cats is ingestion of rodenticide baits with vitamin D3 as the active ingredient. Other sources of this toxin are human medications and rarely, contaminated pet food. Although the reported lethal dose 50% for cholecalciferol is 88 mg/kg, deaths have been seen with an individual exposure of 2 mc g/kg in dogs. Clinical signs are induced by profound hypercalcemia affecting multiple body systems. Clinical presentations may include anorexia, depression, muscle weakness, vomiting, polyuria, polydipsia, dehydration, abdominal pain, hematemesis, melena, and bradycardia. Tissue mineralization may develop if calcium × phosphorous product is greater than 60. Serum testing for hypercalcemia, hyperphosphatemia, and decreased serum parathyroid hormone are confirmatory. Initial treatment relies upon decontamination with emesis induction followed by administration of pulse-dose activated charcoal designed to interfere with the extensive enterohepatic recirculation of toxin. Medical management is designed to decrease serum calcium levels by use of intravenous fluid diuresis with administration of furosemide and prednisolone. Biphosphate pamidronate is used to inhibit calcium release from the bone. Phosphate binders aid in decreasing phosphate availability to interact with calcium. The prognosis is better if treatment is instituted early before development of hypercalcemia and hyperphosphatemia enables tissue mineralization to progress.
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Bromethalin.
Top Companion Anim Med
PUBLISHED: 06-26-2013
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Bromethalin is a potent neurotoxin capable of inducing fatal cerebral edema in companion animals. Bromethalin decreases adenosine triphosphate production resulting in cerebral edema. Toxicosis can be seen in cats and dogs with oral exposures as low as 0.3 and 2.5mg/kg, respectively. High doses produce severe muscle tremors, hyperthermia, seizures, and death within a couple hours postingestion. The usual presentation after moderate to low exposure develops over 12-24 hours with progressive ataxia, paresis, and hindlimb paralysis. Central nervous system depression continues to semicoma or coma. Diagnosis is based upon history of exposure, development of progressive appropriate clinical signs and chemical confirmation in tissues. Treatment relies heavily upon early emesis induction and prolonged decontamination with pulse dosing of activated charcoal. There is no specific antidote; attempts to control cerebral edema with diuretics and corticosteroids have met with limited success. Significant supportive care is usually required, often including seizure management, nutritional support, and defense against decubital ulceration. Prognosis is guarded to poor.
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Xylitol.
Top Companion Anim Med
PUBLISHED: 06-26-2013
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Xylitol is a prevalent sugar substitute found in a wide variety of foods, particularly those labeled as "low carb." It is found in many medicines and dental products both for its antibacterial activity and to increase palatability. Originally, this toxin was recognized as a problem in dogs following sugarless gum ingestions. Xylitol is generally nontoxic to mammals except for dogs. In the dog, xylitol induces marked increases in insulin production and occasionally hepatopathy. The clinical syndrome is manifested with signs consistent with profound hypoglycemia, hypokalemia, hypophosphatemia, and acute hepatic failure. Treatment relies upon administration of intravenous glucose, hepatic support, and general supportive care.
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Electricians chrysotile asbestos exposure from electrical products and risks of mesothelioma and lung cancer.
Regul. Toxicol. Pharmacol.
PUBLISHED: 06-25-2013
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Both mechanistic and epidemiology studies indicate chrysotile asbestos has a threshold below which it does not cause mesothelioma or lung cancer. We conducted a critical review to determine whether electricians are at increased risk for these cancers and, if so, whether their exposure to chrysotile in electrical products could be responsible. We found that most, but not all, epidemiology studies indicate electricians are at increased risk for both cancers. Studies that evaluated electricians exposure to asbestos during normal work tasks have generally reported low concentrations in air; an experimental study showed that grinding or drilling products containing encapsulated chrysotile resulted in exposures to chrysotile fibers far below the OSHA permissible exposure limit and the cancer no observed adverse effect level. Studies of other craftsmen who often work in the vicinity of electricians, such as insulators, reported asbestos (including amphibole) exposures that were relatively high. Overall, the evidence does not indicate that exposure to chrysotile in electrical products causes mesothelioma or lung cancer in electricians. Rather, the most likely cause of lung cancer in electricians is smoking, and the most likely cause of mesothelioma is exposure to amphibole asbestos as a result of renovation/demolition work or working in the proximity of other skilled craftsmen.
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Assessment of TREM2 rs75932628 association with Alzheimers disease in a population-based sample: the Cache County Study.
Neurobiol. Aging
PUBLISHED: 06-07-2013
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Recent studies have identified the rs75932628 (R47H) variant in TREM2 as an Alzheimers disease risk factor with estimated odds ratio ranging from 2.9 to 5.1. The Cache County Memory Study is a large, population-based sample designed for the study of memory and aging. We genotyped R47H in 2974 samples (427 cases and 2540 control subjects) from the Cache County study using a custom TaqMan assay. We observed 7 heterozygous cases and 12 heterozygous control subjects with an odds ratio of 3.5 (95% confidence interval, 1.3-8.8; p = 0.0076). The minor allele frequency and population attributable fraction for R47H were 0.0029 and 0.004, respectively. This study replicates the association between R47H and Alzheimers disease risk in a large, population-based sample, and estimates the population frequency and attributable risk of this rare variant.
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Utility of magnetic resonance imaging versus histology for quantifying changes in liver fat in nonalcoholic fatty liver disease trials.
Hepatology
PUBLISHED: 04-09-2013
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The magnetic resonance imaging-estimated proton density fat fraction (MRI-PDFF) is a novel imaging-based biomarker that allows fat mapping of the entire liver, whereas the magnetic resonance spectroscopy-measured proton density fat fraction (MRS-PDFF) provides a biochemical measure of liver fat in small regions of interest. Cross-sectional studies have shown that MRI-PDFF correlates with MRS-PDFF. The aim of this study was to show the utility of MRI-PDFF in assessing quantitative changes in liver fat through a three-way comparison of MRI-PDFF and MRS-PDFF with the liver histology-determined steatosis grade at two time points in patients with nonalcoholic fatty liver disease (NAFLD). Fifty patients with biopsy-proven NAFLD who participated in a randomized trial underwent a paired evaluation with liver biopsy, MRI-PDFF, and MRS-PDFF at the baseline and 24 weeks. The mean age and body mass index were 47.8?±?11.7 years and 30.7?±?6.5 kg/m(2) , respectively. MRI-PDFF showed a robust correlation with MRS-PDFF both at week 0 and at week 24 (r?=?0.98, P?
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Examination of sources of diagnostic error leading to cervical cone biopsies with no evidence of dysplasia.
Am. J. Clin. Pathol.
PUBLISHED: 03-26-2013
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At our institution, 17% of cervical conization specimens are reported as negative for dysplasia or malignancy. To identify sources of error, we reviewed 53 negative conization specimens and their prior and follow-up cytology, biopsy, and endocervical curettage specimens. Examination of deeper-level sections and p16 immunostaining were performed on all conization specimens and selected biopsy specimens. Dysplasia was detected in 26% (14/53) of conization specimens. Twenty-eight percent (15/53) of cones were truly negative, and the presurgical material had been overcalled as high-grade squamous intraepithelial lesions (HSIL). Forty-five percent (24/53) of cones were truly negative and HSIL was confirmed in the presurgical material. Of these, 11% (6/53) showed subsequent evidence of residual dysplasia and 26% (14/53) were negative on further follow-up. Deeper-level sections, p16 immunostains, and consensus review may help identify squamous dysplasia in conization specimens and may prevent the overdiagnosis of HSIL on cervical biopsies.
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Relationships between changes in sustained fronto-striatal connectivity and positive affect in major depression resulting from antidepressant treatment.
Am J Psychiatry
PUBLISHED: 03-26-2013
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OBJECTIVE Deficits in positive affect and their neural bases have been associated with major depression. However, whether reductions in positive affect result solely from an overall reduction in nucleus accumbens activity and fronto-striatal connectivity or the additional inability to sustain engagement of this network over time is unknown. The authors sought to determine whether treatment-induced changes in the ability to sustain nucleus accumbens activity and fronto-striatal connectivity during the regulation of positive affect are associated with gains in positive affect. METHOD Using fMRI, the authors assessed the ability to sustain activity in reward-related networks when attempting to increase positive emotion during performance of an emotion regulation paradigm in 21 depressed patients before and after 2 months of antidepressant treatment. Over the same interval, 14 healthy comparison subjects underwent scanning as well. RESULTS After 2 months of treatment, self-reported positive affect increased. The patients who demonstrated the largest increases in sustained nucleus accumbens activity over the 2 months were those who demonstrated the largest increases in positive affect. In addition, the patients who demonstrated the largest increases in sustained fronto-striatal connectivity were also those who demonstrated the largest increases in positive affect when controlling for negative affect. None of these associations were observed in healthy comparison subjects. CONCLUSIONS Treatment-induced change in the sustained engagement of fronto-striatal circuitry tracks the experience of positive emotion in daily life. Studies examining reduced positive affect in a variety of psychiatric disorders might benefit from examining the temporal dynamics of brain activity when attempting to understand changes in daily positive affect.
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TAMIS-assisted laparoscopic low anterior resection with total mesorectal excision in a cadaveric series.
Surg Endosc
PUBLISHED: 02-11-2013
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To demonstrate the feasibility of an innovative technique for the surgical management of rectal cancer, we performed transanal minimally invasive surgery assisted low anterior resection with total mesorectal excision (TAMIS-assisted LAR with TME) in a cadaver model. Transanal LAR via natural orifice transluminal endoscopic surgery has been reported in cadaveric series using rigid transanal platforms. This procedure has not been described using a combination of a single incision laparoscopy and TAMIS transanal endoscopic platform. We describe the first cadaveric series of TAMIS-assisted LAR with TME.
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Analysis of the effect of various decalcification agents on the quantity and quality of nucleic acid (DNA and RNA) recovered from bone biopsies.
Ann Diagn Pathol
PUBLISHED: 02-07-2013
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Molecular studies are part of standard care for cancer patients. Bone, a common and sometimes sole site of metastasis, requires decalcification for morphological examination. Many commonly used decalcification agents contain strong acids that degrade nucleic acids. The paradigm shift in oncology, with biomarker targeted therapy and gene expression profiling analysis, requires sufficient nucleic acid recovery from bone biopsy specimens. We systematically studied the effects of a spectrum of decalcification agents on the quantity and quality of RNA and DNA recovered from bone biopsies. Multiple bone biopsies of similar size and cellularity were fixed in 10% neutral-buffered formalin, randomized to various decalcification agents for 2 hours then processed, and embedded. Tissue lysates were obtained from unstained sections and nucleic acid isolated. DNA and RNA were quantified. Assessment of DNA and RNA integrity was accomplished by comparison of the average cycle threshold by polymerase chain reaction of selected housekeeping genes for each agent. Results were then analyzed by 2-sample t test. There was a significant decrease in both DNA and RNA yield and integrity with strong acids (hydrochloric, nitric) vs 14% EDTA and formic acid. DNA yield was (mean nanograms) 6.15 vs 68.68 (P<.001) and RNA was (mean nanograms) 121.53 vs 288.89 (P=.003), respectively. DNA integrity (mean cycle threshold) was 35.79 vs 30.16 (P<.001), and RNA was 33.03 vs 26.5 (P<.001), respectively. Decalcification of bone biopsies with EDTA or formic acid agents was associated with a significant improvement in recovered nucleic acid quantity and quality.
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Prognostic implication of liver histology in patients with nonalcoholic fatty liver disease in diabetes.
J. Diabetes Complicat.
PUBLISHED: 01-09-2013
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Nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM) frequently coexist due to shared risk factors. Their rising prevalence parallels the growing epidemic of obesity and insulin resistance (IR). In patients with T2DM and biopsy-proven NAFLD, a significantly higher prevalence of nonalcoholic steatohepatitis (NASH) (63-87%), any fibrosis (22-60%), and advanced fibrosis (4-9%) is noted. Possible risk factors for more advanced liver disease include concomitant metabolic syndrome with three or more components, visceral obesity, older age, increased duration of diabetes, and family history of diabetes. Liver biopsy is strongly suggested in these patients. Cardiovascular disease (CVD) and malignancy are the leading causes of death in this population, but a growing body of evidence shows liver-related mortality as an important cause of death, including an increased rate of hepatocellular carcinoma (HCC) in diabetes. The presence of NAFLD in T2DM is also associated with increased overall mortality. We aim with this review to summarize the results from studies investigating NAFLD in T2DM and to outline the factors that predict more advanced liver histology as well as the impact of these hepatic changes on CVD, overall and liver-related mortality.
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Noninvasive positive pressure ventilation in subjects with stable COPD: a randomized trial.
Int J Chron Obstruct Pulmon Dis
PUBLISHED: 01-01-2013
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The use of domiciliary noninvasive positive pressure ventilation (NPPV) in stable chronic obstructive pulmonary disease (COPD) with chronic hypercapnic respiratory failure has yielded variable effects on survival, quality of life, and dyspnea. We hypothesized that use of NPPV in stable COPD and partial pressure of carbon dioxide (PaCO2) <52 mmHg might result in improvement in quality of life and dyspnea.
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Didanosine Exposure and Noncirrhotic Portal Hypertension in a HIV Clinic in North America: a Follow-up Study.
Br J Med Med Res
PUBLISHED: 12-02-2011
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AIMS: To describe: 1) our cohort of patients diagnosed with NCPH in a HIV academic clinic in North America, and 2) longitudinal follow-up and outcomes of patients following NCPH diagnosis. STUDY DESIGN: Retrospective case series. PLACE AND DURATION OF STUDY: Owen clinic, University of California, San Diego, United States, between October 1990 and December 2010. METHODOLOGY: We describe a cohort of patients diagnosed with NCPH in a HIV academic clinic with emphasis on their follow-up and outcomes after NCPH diagnosis. RESULTS: During the study period, eight HIV-infected men were diagnosed with NCPH. All patients were exposed to Didanosine (ddI) for a median of 37 months. One patient died soon after NCPH diagnosis due to a condition unrelated to NCPH. The other seven patients have received B-blocker therapy and annual esophago-gastro-duodenectomy screenings with banding of esophageal varices when indicated and remain still alive. Three patients were on ddI at the time of NCPH diagnosis. In one patient ddI was discontinued shortly after NCPH diagnosis. The other two patients continued to use ddI after NCPH diagnosis and developed recurrent upper gastrointestinal bleeding in the subsequent 2 years, requiring revascularization interventions. The four patients that were already off ddI at the time of NCPH diagnosis have been followed for a median of 6 years. These four patients remained minimally symptomatic for up to 16 years of follow-up from NCPH diagnosis. CONCLUSION: When ddI was discontinued before portal hypertension was clinically apparent the progression of NCPH appeared to subside without major clinical complications.
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Inverting papilloma of the temporal bone: case report and meta-analysis of risk factors.
Otol. Neurotol.
PUBLISHED: 08-06-2011
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To review the literature on inverting papilloma of the middle ear and mastoid with a focus on familiarizing clinicians with its presentation and cause and to discuss its epidemiologic, diagnostic, and therapeutic issues.
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Acute kidney injury in patients with acute lung injury: impact of fluid accumulation on classification of acute kidney injury and associated outcomes.
Crit. Care Med.
PUBLISHED: 07-26-2011
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It has been suggested that fluid accumulation may delay recognition of acute kidney injury. We sought to determine the impact of fluid balance on the incidence of nondialysis requiring acute kidney injury in patients with acute lung injury and to describe associated outcomes, including mortality.
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Gastrointestinal neoplasia associated with bowel parasitosis: real or imaginary?
J Trop Med
PUBLISHED: 06-14-2011
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Several parasitic species are well known to have carcinogenic properties, namely; Schistosoma hematobium (squamous cell carcinoma of the bladder) and the liver flukes Opisthorchis and Chlonorchis (cholangiocarcinoma). A large number of parasites are known to colonize the gastrointestinal tract. We sought to review the evidence that implicates these parasites in gastrointestinal neoplasia. Schistosoma japonicum, which is endemic primarily in east Asia, has been shown in multiple studies to convey a mildly increased risk of colorectal adenocarcinoma. The data supporting a causative role for Schistosoma mansoni in colorectal or other neoplastic processes are less convincing, limited primarily to small case-control studies and case series. Reports of possible associations between other gastrointestinal parasites (e.g., E. histolytica and A. lumbricoides) and neoplasia may be found in the literature but are limited to individual cases. We conclude that, other than S. japonicum and to a lesser extent S. mansoni, there is little evidence of an association between gastrointestinal parasites and neoplasia.
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A randomized multicenter trial of Crotalidae polyvalent immune F(ab) antivenom for the treatment of rattlesnake envenomation in dogs.
J Vet Emerg Crit Care (San Antonio)
PUBLISHED: 05-16-2011
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To determine clinical efficacy of the Crotalidae polyvalent immune F(ab) (ovine) antivenom (OPCA) against progressive crotalid envenomation in the dog as reflected in stabilization or improvement of snakebite severity scores (SSS). Additionally, due to the potential decreased half-life of the F(ab) antibodies in dogs we compared SSS between dogs receiving 2 different dosing regimes.
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Schistosomiasis and signet ring cell carcinoma of the rectum.
Ann Diagn Pathol
PUBLISHED: 05-04-2011
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A definitive link between Schistosoma hematobium infection and squamous cell carcinoma of the bladder has been identified. A weaker association between S japonicum infection and colorectal neoplasia has been proposed, although reports are limited to case reports, a case series, and epidemiologic studies. Virtually all cases presented in the literature describe intestinal-type adenocarcinoma occurring in association with S japonicum. We here describe a 40-year-old male Filipino patient with signet ring cell carcinoma of the rectum and evidence of infection by S japonicum.
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Reliability of Her2/neu, estrogen receptor, and progesterone receptor testing by immunohistochemistry on cell block of FNA and serous effusions from patients with primary and metastatic breast carcinoma.
Diagn. Cytopathol.
PUBLISHED: 04-14-2011
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The prognostic and predictive value of Her2/neu and the hormone receptors in patient with primary or metastatic breast cancer is essential for a favorable outcome of treatment. We have been experiencing increasing requests to test cytologic specimens for these markers in patients with metastatic breast carcinoma. A recent study threw some doubts on the validity of such testing using cell blocks. In this study we compared our immunohistochemical Her2/neu, ER and PR testing performed on 42 formalin-fixed, paraffin-embedded cell blocks from 27 fine needle aspirations (FNA) and 15 serous effusions of 42 patients with metastatic (n = 38) and primary (n = 4) breast carcinoma to the test results obtained on tissue sections. In seven cases the Her2/neu immunohistochemistry (IHC) results on cell blocks were also compared with Her2/neu fluorescence in situ hybridization (FISH) on tissue or cell block. The study revealed 100% correlation for positive and negative Her2/neu results. For ER testing the results showed 85.7% sensitivity, 100% specificity, 100% positive predictive value (PPV), and 85.7% negative predictive value (NPV). For PR testing the results showed 80% sensitivity, 100% specificity, 100% PPV, and 88.8% NPV respectively. In conclusion, IHC for Her2/neu, ER and PR performed on formalin-fixed, paraffin-embedded cell blocks prepared from fresh FNA and serous fluid is reliable in predicting the expression of these markers when correlated with IHC and FISH performed on the corresponding tumor tissue.
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Pancreatic rest resection using band ligation snare polypectomy.
Dig. Dis. Sci.
PUBLISHED: 03-08-2011
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Although pancreatic rests have characteristic endoscopic features, confirming a histological diagnosis may be desirable to exclude other significant pathology.
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Transcription factor genes Smad4 and Gata4 cooperatively regulate cardiac valve development. [corrected]
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 02-17-2011
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We report that the dominant human missense mutations G303E and G296S in GATA4, a cardiac-specific transcription factor gene, cause atrioventricular septal defects and valve abnormalities by disrupting a signaling cascade involved in endocardial cushion development. These GATA4 missense mutations, but not a mutation causing secundum atrial septal defects (S52F), demonstrated impaired protein interactions with SMAD4, a transcription factor required for canonical bone morphogenetic protein/transforming growth factor-? (BMP/TGF-?) signaling. Gata4 and Smad4 genetically interact in vivo: atrioventricular septal defects result from endothelial-specific Gata4 and Smad4 compound haploinsufficiency. Endothelial-specific knockout of Smad4 caused an absence of valve-forming activity: Smad4-deficient endocardium was associated with acellular endocardial cushions, absent epithelial-to-mesenchymal transformation, reduced endocardial proliferation, and loss of Id2 expression in valve-forming regions. We show that Gata4 and Smad4 cooperatively activated the Id2 promoter, that human GATA4 mutations abrogated this activity, and that Id2 deficiency in mice could cause atrioventricular septal defects. We suggest that one determinant of the phenotypic spectrum caused by human GATA4 mutations is differential effects on GATA4/SMAD4 interactions required for endocardial cushion development.
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A systematic review of factors predicting door to balloon time in ST-segment elevation myocardial infarction treated with percutaneous intervention.
Int. J. Cardiol.
PUBLISHED: 01-15-2011
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Door to balloon time is important in the outcome of ST-elevation myocardial infarction treated with primary percutaneous intervention. This review summarizes prognostic factors for door to balloon time in STEMI patients presenting to a PCI capable hospital.
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Reduced right ventrolateral prefrontal cortex activity while inhibiting positive affect is associated with improvement in hedonic capacity after 8 weeks of antidepressant treatment in major depressive disorder.
Biol. Psychiatry
PUBLISHED: 01-11-2011
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Anhedonia, a reduced ability to experience pleasure, is a chief symptom of major depressive disorder and is related to reduced frontostriatal connectivity when attempting to upregulate positive emotion. The present study examined another facet of positive emotion regulation associated with anhedonia-namely, the downregulation of positive affect-and its relation to prefrontal cortex (PFC) activity.
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Antidepressant effects of selective slow wave sleep deprivation in major depression: a high-density EEG investigation.
J Psychiatr Res
PUBLISHED: 01-05-2011
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Sleep deprivation can acutely reverse depressive symptoms in some patients with major depression. Because abnormalities in slow wave sleep are one of the most consistent biological markers of depression, it is plausible that the antidepressant effects of sleep deprivation are due to the effects on slow wave homeostasis. This study tested the prediction that selectively reducing slow waves during sleep (slow wave deprivation; SWD), without disrupting total sleep time, will lead to an acute reduction in depressive symptomatology. As part of a multi-night, cross-over design study, participants with major depression (non-medicated; n = 17) underwent baseline, SWD, and recovery sleep sessions, and were recorded with high-density EEG (hdEEG). During SWD, acoustic stimuli were played to suppress subsequent slow waves, without waking up the participant. The effects of SWD on depressive symptoms were assessed with both self-rated and researcher-administered scales. Participants experienced a significant decrease in depressive symptoms according to both self-rated (p = .007) and researcher-administered (p = .010) scales, while vigilance was unaffected. The reduction in depressive symptoms correlated with the overnight dissipation of fronto-central slow wave activity (SWA) on baseline sleep, the rebound in right frontal all-night SWA on recovery sleep, and the amount of REM sleep on the SWD night. In addition to highlighting the benefits of hdEEG in detecting regional changes in brain activity, these findings suggest that SWD may help to better understand the pathophysiology of depression and may be a useful tool for the neuromodulatory reversal of depressive symptomatology.
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Thalamic dysfunction in schizophrenia suggested by whole-night deficits in slow and fast spindles.
Am J Psychiatry
PUBLISHED: 09-15-2010
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Slow waves and sleep spindles are the two main oscillations occurring during non-REM sleep. While slow oscillations are primarily generated and modulated by the cortex, sleep spindles are initiated by the thalamic reticular nucleus and regulated by thalamo-reticular and thalamo-cortical circuits. In a recent high-density EEG study, the authors found that 18 medicated schizophrenia patients had reduced sleep spindles, compared with healthy and depressed subjects, during the first non-REM episode. In the present study, the authors investigated whether spindle deficits were present in a larger sample of schizophrenia patients, were consistent across the night, were related to antipsychotic medications, and were suggestive of impairments in specific neuronal circuits.
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Genome-wide identification of mouse congenital heart disease loci.
Hum. Mol. Genet.
PUBLISHED: 05-28-2010
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Empirical evidence supporting a genetic basis for the etiology of congenital heart disease (CHD) is limited and few disease-causing mutations have been identified. To identify novel CHD genes, we performed a forward genetic screen to identify mutant mouse lines with heritable CHD. Lines with recessive N-ethyl-N-nitrsourea-induced CHD-causing mutations were identified using a three-generation backcross. A hierarchical screening protocol was used to test the hypothesis that the fetal-to-neonatal circulatory transition unmasks the specific structural heart defects observed in CHD. Mice with heart defects were efficiently ascertained by selecting for pups exhibiting perinatal lethality and characterizing their cardiac pathology. A marked increase of perinatal lethality was observed in the mutagen-treated cohort compared with an untreated backcross population. Cardiac pathology on perinatal lethals revealed cardiovascular defects in 79 pups from 47 of 321 mutagenized lines. All identified structural abnormalities were analogous to previously described forms of human CHD. Furthermore, the phenotypic recurrence and variance patterns across all lines were similar to human CHD prevalence and recurrence patterns. We mapped the locus responsible for heritable atrioventricular septal defects in six lines (avc1-6). Our screen demonstrated that sporadic CHD may have major genetic component and established a practical, efficient approach for identifying CHD candidate genes.
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Amphicrine carcinoma of the liver.
Ann Diagn Pathol
PUBLISHED: 04-30-2010
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Amphicrine tumors are defined by evidence of both glandular and neuroendocrine differentiation in the same cell. These are extremely rare tumors, with only scattered case reports in the pancreas and stomach. We here report a case of amphicrine carcinoma occurring in apparent isolation in the liver. The tumor was characterized by signet ring cell morphology, mucicarmine, and periodic acid Schiff with diastase (PASD) positivity, and expression of chromogranin, synaptophysin, villin, and CDX2. No other tumor was identified by radiological or endoscopic examination of the gastrointestinal tract. The patient is disease-free 22 months after the resection. We speculate that this represents the first reported occurrence of primary amphicrine carcinoma of the liver.
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Direct imaging and quantification of carotid plaque calcification.
Magn Reson Med
PUBLISHED: 02-16-2010
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Carotid plaque calcification normally appears as a signal void with clinical MR sequences. Here, we describe the use of an adiabatic inversion recovery prepared two-dimensional ultrashort echo time sequence to image and characterize carotid plaque calcification using a clinical 3-T scanner. T(1), T?2*, and free water content were measured for seven carotid samples, and the results were compared with micro-CT imaging. Conventional gradient echo and fast spin echo images were also acquired for comparison. Correlations between T(1), T?2*, free water concentration, and mineral density were performed. There was a close correspondence between inversion recovery prepared two-dimensional ultrashort echo time morphologic and micro-CT appearances. Carotid plaque calcification varied significantly from sample to sample, with T(1) s ranging from 94 ± 19 to 328 ± 21 msec, T?2*s ranging from 0.31 ± 0.12 to 2.15 ± 0.25 msec, and free water concentration ranging from 5.7 ± 2.3% to 16.8 ± 3.4%. There was a significant positive correlation between T(1)(R = 0.709; P < 0.074), T?2* (R = 0.816; P < 0.025), and free water concentration, a negative correlation between T(1) (R = 0.773; P < 0.042), T?2* (R = 0.948; P < 0.001) and CT measured mineral density, and a negative correlation between free water concentration (R = 0.936; P < 0.002) and mineral density.
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Exploiting phenotypic plasticity for the treatment of hepatopulmonary shunting in Abernethy malformation.
J Vasc Interv Radiol
PUBLISHED: 01-10-2010
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An 11-year-old boy presented with exercise intolerance due to chronic hypoxemia. Work-up revealed a diagnosis of hepatopulmonary syndrome (HPS) secondary to a congenital extrahepatic portal-venous shunt (Abernethy malformation). Plasticity in the developing liver was exploited as a strategy for the treatment of HPS. With use of a staged endovascular approach, the portosystemic vascular circuitry was modified in a manner that facilitated progressive growth and development of the severely hypoplastic and underdeveloped intrahepatic portal venous system. After completion of the final procedure, the patients intrahepatic portal veins were normal in appearance; 2 months later, signs and symptoms of HPS completely resolved. The patient remains free of HPS stigmata after 2 years.
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Reduced capacity to sustain positive emotion in major depression reflects diminished maintenance of fronto-striatal brain activation.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 12-22-2009
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Anhedonia, the loss of pleasure or interest in previously rewarding stimuli, is a core feature of major depression. While theorists have argued that anhedonia reflects a reduced capacity to experience pleasure, evidence is mixed as to whether anhedonia is caused by a reduction in hedonic capacity. An alternative explanation is that anhedonia is due to the inability to sustain positive affect across time. Using positive images, we used an emotion regulation task to test whether individuals with depression are unable to sustain activation in neural circuits underlying positive affect and reward. While up-regulating positive affect, depressed individuals failed to sustain nucleus accumbens activity over time compared with controls. This decreased capacity was related to individual differences in self-reported positive affect. Connectivity analyses further implicated the fronto-striatal network in anhedonia. These findings support the hypothesis that anhedonia in depressed patients reflects the inability to sustain engagement of structures involved in positive affect and reward.
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MR imaging of liver fibrosis: current state of the art.
Radiographics
PUBLISHED: 12-05-2009
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Chronic liver disease is a major public health problem worldwide. Liver fibrosis, a common feature of almost all causes of chronic liver disease, involves the accumulation of collagen, proteoglycans, and other macromolecules within the extracellular matrix. Fibrosis tends to progress, leading to hepatic dysfunction, portal hypertension, and ultimately cirrhosis. Liver biopsy, the standard of reference for diagnosing liver fibrosis, is invasive, costly, and subject to complications and sampling variability. These limitations make it unsuitable for diagnosis and longitudinal monitoring in the general population. Thus, development of a noninvasive, accurate, and reproducible test for diagnosis and monitoring of liver fibrosis would be of great value. Conventional cross-sectional imaging techniques have limited capability to demonstrate liver fibrosis. In clinical practice, imaging studies are usually reserved for evaluation of the presence of portal hypertension or hepatocellular carcinoma in cases that have progressed to cirrhosis. In response to the rising prevalence of chronic liver diseases in Western nations, a number of imaging-based methods including ultrasonography-based transient elastography, computed tomography-based texture analysis, and diverse magnetic resonance (MR) imaging-based techniques have been proposed for noninvasive diagnosis and grading of hepatic fibrosis across its entire spectrum of severity. State-of-the-art MR imaging-based techniques in current practice and in development for noninvasive assessment of liver fibrosis include conventional contrast material-enhanced MR imaging, double contrast-enhanced MR imaging, MR elastography, diffusion-weighted imaging, and MR perfusion imaging.
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Sleep-dependent improvement in visuomotor learning: a causal role for slow waves.
Sleep
PUBLISHED: 10-24-2009
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Sleep after learning often benefits memory consolidation, but the underlying mechanisms remain unclear. In previous studies, we found that learning a visuomotor task is followed by an increase in sleep slow wave activity (SWA, the electroencephalographic [EEG] power density between 0.5 and 4.5 Hz during non-rapid eye movement sleep) over the right parietal cortex. The SWA increase correlates with the postsleep improvement in visuomotor performance, suggesting that SWA may be causally responsible for the consolidation of visuomotor learning. Here, we tested this hypothesis by studying the effects of slow wave deprivation (SWD).
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Associations between betel nut (Areca catechu) and symptoms of schizophrenia among patients in Nepal: A longitudinal study.
Psychiatry Res
PUBLISHED: 09-11-2009
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Betel nut is one of the mostly widely used substances in the world, particularly across Asia. Arecoline, a partial muscarinic agonist, has been hypothesized to have beneficial effects on both positive and negative symptoms of schizophrenia. This study aims to further explore associations between betel use and symptoms of schizophrenia in a 4-month longitudinal study in Nepal. Sixty Nepali patients with schizophrenia were recruited from regional outpatient clinics. The Positive and Negative Syndrome Scale (PANSS) and the Social Adaptation Self-Evaluation Scale were used to assess symptoms and social functioning in regular betel users and non-users. No significant group differences or dose-response relationships were noted on either initial or follow-up assessments. Stratifying by sex also failed to reveal an association between symptoms and betel use, which stands in contrast with previously reported data from Micronesia. There were no differences seen in social functioning other than a significantly higher proportion of betel users holding jobs. It was also noted that significantly fewer betel chewers were taking anti-cholinergic medication, which may tentatively indicate a potentially therapeutic role in the future for partial muscarinic agonists in the treatment of medication-induced movement disorders.
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Using metaphorical techniques in focus groups to uncover mothers feelings about family meals.
Nutr Res Pract
PUBLISHED: 05-29-2009
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Traditional nutrition education has not been shown to consistently produce behavior change. While it has been suggested that using emotion-based messages may be a better way to influence nutrition behavior change, this has not been well tested. Producing emotion-based messages is a multi-step process that begins with exploring subconscious barriers to behavior change rather than the more obvious and typically reported barriers. The purpose of this research was to uncover the emotional reasons, sometimes referred to as emotional pulse points, for mothers choosing or not choosing to have more family meals. This would then serve as the first step to developing emotion-based messages promoting the benefits of family meals. Five focus group interviews were conducted with 51 low-income Black (n=28) and white (n=23) mothers. Metaphorical techniques were used to determine underlying feelings toward family and family meals. Discussions were video-taped, transcribed, and manually analyzed using a content-driven, immersion/crystallization approach to qualitative data analysis. Four themes emerged around the definition of family: acceptance, sharing, chaos, and protective/loyal. Some mothers felt mealtime was merely obligatory, and described it as stressful. Some reported a preference for attending to their own needs instead of sitting down with their children, while others felt that mealtime should be used to interact with and educate children and felt guilty when they were not able to provide family meals. Three themes emerged around feelings towards having or not having family meals: unimportant, important, and guilty. When explored further, mothers indicated that using the feeling of guilt to encourage family meals might be effective. Data obtained are being used to develop innovative, emotion-based messages that will be tested for effectiveness in promoting family meals.
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AIDSVAX immunization induces HIV-specific CD8+ T-cell responses in high-risk, HIV-negative volunteers who subsequently acquire HIV infection.
Vaccine
PUBLISHED: 04-17-2009
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Correlates of immune protection from HIV vaccines remain undefined. The first HIV vaccine efficacy trial in the US and Europe VAX004, was designed to assess whether rgp120 envelope subunits (AIDSVAX B/B, VaxGen) can induce partial or complete protection from HIV-1 infection. No effectiveness in the reduction of either the acquisition of infection or levels of plasma viremia after HIV infection was noted. We found evidence of vaccine-specific CD8+ T cells in volunteers who received the vaccine, regardless of behavioral risk. Surprisingly, the CD8-response is significantly higher in participants who would go on to contract HIV infection. These results suggest that AIDSVAX immunization may boost preexisting immune responses-due to pre-infection exposure, and a vaccine-induced immune profile may serve as a biological marker for HIV susceptibility.
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sonic hedgehog is required in pulmonary endoderm for atrial septation.
Development
PUBLISHED: 04-15-2009
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The genesis of the septal structures of the mammalian heart is central to understanding the ontogeny of congenital heart disease and the evolution of cardiac organogenesis. We found that Hedgehog (Hh) signaling marked a subset of cardiac progenitors specific to the atrial septum and the pulmonary trunk in the mouse. Using genetic inducible fate mapping with Gli1(CreERT2), we marked Hh-receiving progenitors in anterior and posterior second heart field splanchnic mesoderm between E8 and E10. In the inflow tract, Hh-receiving progenitors migrated from the posterior second heart field through the dorsal mesocardium to form the atrial septum, including both the primary atrial septum and dorsal mesenchymal protrusion (DMP). In the outflow tract, Hh-receiving progenitors migrated from the anterior second heart field to populate the pulmonary trunk. Abrogation of Hh signaling during atrial septal progenitor specification resulted in atrial and atrioventricular septal defects and hypoplasia of the developing DMP. Hedgehog signaling appeared necessary and sufficient for atrial septal progenitor fate: Hh-receiving cells rendered unresponsive to the Hh ligand migrated into the atrium in normal numbers but populated the atrial free wall rather than the atrial septum. Conversely, constitutive activation of Hh signaling caused inappropriate enlargement of the atrial septum. The close proximity of posterior second heart field cardiac progenitors to pulmonary endoderm suggested a pulmonary source for the Hh ligand. We found that Shh is required in the pulmonary endoderm for atrial septation. Therefore, Hh signaling from distinct pulmonary and pharyngeal endoderm is required for inflow and outflow septation, respectively. These data suggest a model in which respiratory endoderm patterns the morphogenesis of cardiac structural components required for efficient cardiopulmonary circulation.
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Characterization of carbons derived from cellulose and lignin and their oxidative behavior.
Bioresour. Technol.
PUBLISHED: 03-05-2009
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In this study the oxidative behavior of carbons derived from cellulose and lignin were compared using thermogravimetric analysis (TGA). Specific surface area and chemical composition of the two types of carbon were analyzed using nitrogen adsorption at 77K and infrared spectroscopy respectively. The results demonstrate that cellulose carbon has a higher reaction order and lower activation energy than lignin carbon under identical experimental conditions when they were prepared at temperatures lower than 500 degrees C. However, such differences were considerably reduced for the carbon samples prepared at temperatures greater than 700 degrees C. It was verified that lignin carbon is more stable than cellulose carbon due to its higher content of aromatic structures when they are prepared at lower temperature. The specific surface area and porosity have a more limited contribution to the differential oxidative behaviors of the two types of carbon. This research has significance related to the formation of carbon nanotubes from plant materials during low temperature carbonization.
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A systematic review of outcomes and quality measures in adult patients cared for by hospitalists vs nonhospitalists.
Mayo Clin. Proc.
PUBLISHED: 03-03-2009
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A systematic review of English-language literature was undertaken to answer the question, "Are there differences in cost or quality of inpatient medical care provided to adults by hospitalists vs nonhospitalists?" A computerized search was performed, using hospitalist and either quality, outcome, or cost as search terms. References from relevant articles were searched by hand. A standard data-extraction tool was used, and articles were included on the basis of quality and relevance. The reports that were included (N=33) show general agreement that hospitalist care leads to shorter length of stay and lower cost per stay. Three reports show improvement in outcomes for orthopedic surgery patients who had hospitalist consultation or comanagement, 3 reports show improvement in markers of quality of care for patients with pneumonia, and 2 reports show improvement in aspects of heart failure management. Further research should seek to determine why differences in care exist, whether these improvements might be generalized to other physicians, and whether hospitalists provide demonstrable benefit in other areas of care.
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Spirometry utilization after hospitalization for patients with chronic obstructive pulmonary disease exacerbations.
Am J Med Qual
PUBLISHED: 01-14-2009
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Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality in the US population. An area of improvement hinges on early detection and proper monitoring. Spirometry is an important interventional tool; its underuse among hospitalized patients with COPD could affect quality of care. This study evaluates spirometry use at the Community Medical Center-Sierra in hospitalized patients with COPD. A retrospective medical record review from January 1, 2000, to March 15, 2002, assesses 1507 inpatients with COPD. The effects are analyzed of age, sex, race/ethnicity, diagnosis, insurance status, disposition, and admitting service on spirometry use by physicians are analyzed. A questionnaire is used to evaluate the knowledge, attitudes, and behaviors of residents toward spirometry ordering. Baseline characteristics are similar between study groups. Only 3% of 1476 study patients have spirometry performed within the recommended time frame, and only 12.2% have at least 1 spirometry performed. Patients having a primary diagnosis of COPD have a greater likelihood of having spirometry performed (20.3% vs 11.1%, P < .001), as do patients who are discharged to home (13.4% vs 5.9%, P = .001). No significant effects are noted for sex, race/ethnicity, insurance status, or admitting service. The house staff surveys reveal that most do not know the indications for (72.0%) or how to order (46.0%) spirometry. Spirometry is underused among physicians who treat hospitalized patients with COPD. Future educational efforts aimed at improving physicians ordering and use of spirometry are needed to address this disparity.
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Proton-pump inhibitor utilization associated with the change to nonpreferred formulary status for esomeprazole in the TRICARE formulary.
J Manag Care Pharm
PUBLISHED: 01-08-2009
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inhibitor (PPI) esomeprazole in the third copayment tier on the TRICARE formulary on July 17, 2005. The change to nonpreferred formulary status for esomeprazole included a $13 copayment increase (from $9.00 to $22.00) for either a 30-day supply purchased from a community pharmacy or a 90-day supply purchased from the mail-order pharmacy and a $0 copayment if obtained from a military pharmacy but with a prior authorization (PA) requirement. The change to nonpreferred formulary status was designed to encourage the use of PPIs other than esomeprazole and to increase the use of the mail-order pharmacy for esomeprazole purchases.
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Bedside sublingual video imaging of microcirculation in assessing bacterial infection in cirrhosis.
Dig. Dis. Sci.
PUBLISHED: 01-01-2009
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Bacterial infections are common in cirrhosis and can lead to life-threatening complications. Sidestream dark-field (SDF) imaging has recently emerged as a noninvasive tool for capturing real-time video images of sublingual microcirculation in critically ill patients with sepsis. The objective of this study was to assess the utility of SDF in determining underlying infection in patients with cirrhosis. Sublingual microcirculation was compared among patients with compensated cirrhosis (Group A, n=13), cirrhosis without sepsis (Group B, n=18), cirrhosis with sepsis (Group C, n=14), and sepsis only (Group D, n=10). The blood flow was semi-quantitatively evaluated in four equal quadrants in small (10-25 mm); medium (26-50 mm); and large (51-100 mm) sublingual capillaries. The blood flow was described as no flow (0), intermittent flow (1), sluggish flow (2), and continuous flow (3). The overall flow score or microvascular flow index (MFI) was measured for quantitative assessment of microcirculation and predicting power for concurrent infection in cirrhosis. Marked impairment was observed at all levels of microvasculature in Groups B and C when compared with Group A. This effect was restricted to small vessels only when Group B was compared with Group C. MFI<1.5 was found to have highest sensitivity (100%) and specificity (100%) for infection in decompensated cirrhosis. SDF imaging of sublingual microcirculation can be a useful bedside diagnostic tool to assess bacterial infection in cirrhosis.
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Sex-related differences in sleep slow wave activity in major depressive disorder: a high-density EEG investigation.
BMC Psychiatry
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Sleep disturbance plays an important role in major depressive disorder (MDD). Prior investigations have demonstrated that slow wave activity (SWA) during sleep is altered in MDD; however, results have not been consistent across studies, which may be due in part to sex-related differences in SWA and/or limited spatial resolution of spectral analyses. This study sought to characterize SWA in MDD utilizing high-density electroencephalography (hdEEG) to examine the topography of SWA across the cortex in MDD, as well as sex-related variation in SWA topography in the disorder.
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Radiated noise from commercial ships in the Gulf of Maine: implications for whale/vessel collisions.
J. Acoust. Soc. Am.
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To understand mysticete acoustic-based detection of ships, radiated noise from high-speed craft, cruise ships, catamarans and fishing vessels was recorded June-September 2009. Calibrated acoustic data (<2500 Hz) from a vertical hydrophone array was combined with ship passage information. A cruise ship had the highest broadband source level, while a fishing vessel had the lowest. Ship noise radiated asymmetrically and varied with depth. Bow null-effect acoustic shadow zones were observed for all ship classes and were correlated with ship-length-to-draft-ratios. These shadow zones may reduce ship detection by near-surface mysticetes.
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Pathogenetic and predictive value of biomarkers in patients with ALI and lower severity of illness: results from two clinical trials.
Am. J. Physiol. Lung Cell Mol. Physiol.
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Plasma and bronchoalveolar lavage (BAL) biomarkers related to the pathogenesis of acute lung injury (ALI) have previously been associated with poorer clinical outcomes and increased disease severity among patients with ALI. Whether these biomarkers have predictive value in a less severely ill population that excludes septic patients with high APACHE II scores is currently unknown. We tested the association of plasma and BAL biomarkers with physiological markers of ALI severity or clinically relevant outcomes in a secondary analysis of a clinical trial of activated protein C for the treatment of ALI. Plasma plasminogen activator inhibitor-1 (PAI-1) and mini-BAL protein were both significantly associated with increased oxygenation index (P = 0.02 and 0.01, respectively), whereas there was a trend toward an association between IL-6 and oxygenation index (P = 0.057). High plasma IL-6, thrombomodulin, and mini-BAL protein were all significantly associated with fewer ventilator-free days (VFDs) (P = 0.01, 0.01, and 0.05, respectively); no markers were associated with mortality, but we hypothesized that this was due to the small size of our cohort and the low death rate. To confirm these associations in a larger sample, we identified a restricted cohort of patients from the ARDS Network ALVEOLI study with similar baseline characteristics. We retested the associations of the significant biomarkers with markers of severity and clinical outcomes and studied IL-8 as an additional biomarker given its important predictive value in prior studies. In this restricted cohort, IL-6 was significantly associated with oxygenation index (P = 0.02). Both IL-6 and IL-8 were associated with decreased VFDs and increased 28-day mortality. Future studies should be focused on examining larger numbers of patients with less severe ALI to further test the relative predictive value of plasma and mini-BAL biomarkers for clinically relevant outcomes, including VFDs and mortality, and for their prospective utility in risk stratification for future clinical trials.
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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.

How does it work?

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.