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Find video protocols related to scientific articles indexed in Pubmed.
Microsurgical treatment of arteriovenous malformations in pediatric patients: the Boston Children's Hospital experience.
J Neurosurg Pediatr
PUBLISHED: 11-01-2014
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OBJECT Outcomes of microsurgical treatment of arteriovenous malformations (AVMs) in children are infrequently reported across large cohorts. METHODS The authors undertook a retrospective review of departmental and hospital databases to obtain the medical data of all patients up to 18 years of age who were diagnosed with cerebral AVMs. Demographic and AVM angioarchitectural characteristics were analyzed, and for the patients who underwent surgery, the authors also analyzed the estimated intraoperative blood loss, postoperative angiographically confirmed obliteration rates, and neurological complications and outcomes classified according to the modified Rankin Scale (mRS). RESULTS Of 117 children with cerebral AVMs, 94 underwent microsurgical resection (80%). Twenty (21%) of these 94 patients underwent adjunctive preoperative embolization. The overall postoperative angiographically confirmed obliteration rate was 94%. As part of a new protocol, the last 50 patients in this series underwent immediate perioperative angiography, improving the subsequent obliteration rate from 86% to 100% (p = 0.01). No other factors, such as a hemorrhagic AVM, size of the AVM, location, drainage, or Spetzler-Martin grade, had a statistically significant impact on the obliteration rate. Perioperative neurological deficits occurred in 17% of the patients, but the vast majority of these (77%) were predictable visual field cuts. Arteriovenous malformations that were hemorrhagic or located in noneloquent regions were each associated with lower rates of postoperative neurological complications (p = 0.05 and 0.002, respectively). In total, 94% of the children had good functional outcomes (mRS Scores 0-2), and these outcomes were significantly influenced by the mRS score on presentation before surgery (p = 0.01). A review of 1- and 5-year follow-up data indicated an overall annual hemorrhage rate of 0.3% and a recurrence rate of 0.9%. CONCLUSIONS Microsurgical resection of AVMs in children is associated with high rates of angiographically confirmed obliteration and low rates of significant neurological complications. Implementation of a protocol using perioperative angiography in this series led to complete radiographically confirmed obliteration of all AVMs, with low annual repeat hemorrhage and recurrence rates.
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Endochondral Ossification for Enhancing Bone Regeneration: Converging Native ECM Biomaterials and Developmental Engineering in vivo.
Tissue Eng Part B Rev
PUBLISHED: 10-23-2014
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Autologous bone grafting (ABG) remains entrenched as the gold standard of treatment in bone regenerative surgery. Consequently, many marginally successful bone tissue engineering strategies have focused on mimicking portions of ABG's 'ideal' osteoconductive, osteoinductive, and osteogenic composition resembling the late reparative stage extracellular matrix (ECM) in bone fracture repair, also known as the 'hard' or 'bony' callus. An alternative, less common approach that has emerged in the last decade harnesses endochondral (EC) ossification through developmental engineering principles, which acknowledges that the molecular and cellular mechanisms involved in developmental skeletogenesis, specifically EC ossification, are closely paralleled during native bone healing. EC ossification naturally occurs during the majority of bone fractures1-9 and thus can potentially be utilized to enhance bone regeneration for nearly any orthopedic indication, especially in avascular critical-sized defects where hypoxic conditions favor initial chondrogenesis instead of direct intramembranous (IM) ossification. The body's native EC ossification response, however, is not capable of regenerating critical-sized defects without intervention. We propose that an underexplored potential exists to regenerate bone through the native EC ossification response by utilizing strategies that mimic the initial inflammatory or fibrocartilaginous ECM (i.e., 'pro-' or 'soft' callus) observed in the early reparative stage of bone fracture repair. To date, the majority of strategies utilizing this approach rely on clinically burdensome in vitro cell expansion protocols. This review will focus on the confluence of two evolving areas, (i) native ECM biomaterials and (ii) developmental engineering, which will attempt to overcome the technical, business and regulatory challenges that persist in the area of bone regeneration. Significant attention will be given to native 'raw' materials and ECM-based designs that provide necessary osteo- and chondro- conductive and inductive features for enhancing EC ossification. Additionally, critical perspectives on existing stem cell based therapeutic (SCBT) strategies will be discussed with a focus on their use as an extension of the acellular ECM based designs for specific clinical indications. Within this framework, a novel realm of unexplored design strategies for bone tissue engineering will be introduced into the collective consciousness of the regenerative medicine field.
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Simvastatin treatment preserves synaptic plasticity in A?PPswe/PS1dE9 mice.
J. Alzheimers Dis.
PUBLISHED: 10-22-2014
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Epidemiological evidence suggests that chronic treatment with simvastatin may protect against the development of Alzheimer's disease (AD), but as yet it is unclear how this effect is mediated. Extensive data also indicates that the amyloid ?-protein (A?) plays a central role in the disease process, and it has been suggested that the protective effects of simvastatin may be mediated by reducing A? production or by counteracting the toxic effects of A?. Accordingly, using the A?PPswe/PS1dE9 mouse model of AD, we investigated the effects of simvastatin on long-term potentiation (LTP), amyloid biology, and two key kinases involved in A?-mediated toxicity. Since burgeoning data indicate that both fibrillar and non-fibrillar forms of A? play a prominent role in AD pathogenesis, we were careful to investigate the effects of simvastatin on three biochemically distinct pools of A?. In untreated A?PPswe/PS1dE9 mice, there was a dramatic and significant increase in the levels of water-soluble A? between 6 and 8 months, but this remained constant between 8 and 18 months. In contrast, the concentrations of detergent-soluble and formic acid (FA)-soluble A? species increased across all ages examined, thus demonstrating that while amyloid deposition continued, the levels of water-soluble A? remained relatively constant. LTP was normal at 6 months, but was significantly impaired at 8 and 18 months. Importantly, a diet supplemented with 0.04% simvastatin for one month (at 7 months) positively affected synaptic plasticity in A?PPswe/PS1dE9 mice and did not significantly alter levels of water-soluble, detergent-soluble, or FA-soluble A?, but did increase phosphorylation of both Akt and GSK-3, while tau and tau phosphorylation were unaltered. These results indicate that the protective effects of simvastatin may be mediated by maintaining signaling pathways that help to protect and rescue LTP.
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Radiation Therapy at End-of-Life in Children.
J Palliat Med
PUBLISHED: 09-13-2014
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Abstract Objective: Few data exist on evaluating utilization patterns of radiotherapy (RT) at the end of life (EOL) in children. Metastatic disease in pediatric patients is not pathognomonic for palliative treatment intent; further complicating the issue are complexities surrounding the very select population of children receiving proton therapy (PrT). We compared data for RT and PrT in terms of death rate within 30 days. Methods: We performed chart reviews for patients receiving radiation therapy at age ?21 years treated at Indiana University Health Proton Therapy Center (IUHPTC) between June 2008 and June 2013 and University of Miami Radiation Oncology Department (UM) between June 2000 and June 2013. Included were patients not completing prescribed courses of RT, and those dying within 30 days of therapy. Comparison was made of differences between practice data for PrT and conventional RT. Results: At IUHPTC, 2 children of 272 did not complete their courses and died within 30 days (0.7%). At UM, data are available for 425 children; 9 did not complete their courses and 7 died within 30 days (1.6%). Neither the number of patients who did not complete treatment nor the 30-day death rates (P=.21) for PrT and RT were significantly different. Conclusions: Delivery of RT for children at EOL is complex. Frequency of RT at EOL in children occurs in is <2% of cases, and is not significantly less frequent in the proton milieu. This appears to be about an order of magnitude less than in adults.
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Advanced phase change composite by thermally annealed defect-free graphene for thermal energy storage.
ACS Appl Mater Interfaces
PUBLISHED: 08-20-2014
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Organic phase change materials (PCMs) have been utilized as latent heat energy storage and release media for effective thermal management. A major challenge exists for organic PCMs in which their low thermal conductivity leads to a slow transient temperature response and reduced heat transfer efficiency. In this work, 2D thermally annealed defect-free graphene sheets (GSs) can be obtained upon high temperature annealing in removing defects and oxygen functional groups. As a result of greatly reduced phonon scattering centers for thermal transport, the incorporation of ultralight weight and defect free graphene applied as nanoscale additives into a phase change composite (PCC) drastically improve thermal conductivity and meanwhile minimize the reduction of heat of fusion. A high thermal conductivity of the defect-free graphene-PCC can be achieved up to 3.55 W/(m K) at a 10 wt % graphene loading. This represents an enhancement of over 600% as compared to pristine graphene-PCC without annealing at a comparable loading, and a 16-fold enhancement than the pure PCM (1-octadecanol). The defect-free graphene-PCC displays rapid temperature response and superior heat transfer capability as compared to the pristine graphene-PCC or pure PCM, enabling transformational thermal energy storage and management.
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Recurrence after gross-total resection of low-grade pediatric brain tumors: the frequency and timing of postoperative imaging.
J Neurosurg Pediatr
PUBLISHED: 07-25-2014
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Low-grade glial and glioneuronal brain tumors are frequently encountered in the pediatric population and can be effectively treated by resection. The authors aimed to use imaging to evaluate how often tumors recurred and to determine if recurrences were associated with any clinical symptoms, along with the financial costs of imaging, in patients with radiographically proven gross-total resection (GTR) at Boston Children's Hospital. These data were assessed to propose guidelines regarding postoperative surveillance.
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Thoracic Epidural analgesia versus Rectus Sheath Catheters for open midline incisions in major abdominal surgery within an enhanced recovery programme (TERSC): study protocol for a randomised controlled trial.
Trials
PUBLISHED: 06-09-2014
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Thoracic epidural analgesia (TEA) is recommended for post-operative pain relief in patients undergoing major abdominal surgery via a midline incision. However, the effectiveness of TEA is variable with high failure rates reported post-operatively. Common side effects such as low blood pressure and motor block can reduce mobility and hinder recovery, and a number of rare but serious complications can also occur following their use.Rectus sheath catheters (RSC) may provide a novel alternative approach to somatic analgesia without the associated adverse effects of TEA. The aim of this study is to compare the efficacy of both techniques in terms of pain relief, patient experience, post-operative functional recovery, safety and cost-effectiveness.
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Analysis of comments in a petition defending electronic cigarettes.
Nicotine Tob. Res.
PUBLISHED: 05-13-2014
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A 2009 petition opposing a Food and Drug Administration (FDA) ban on electronic cigarettes (e-cigs) garnered international attention from e-cig users (vapers). Petitioners' comments described the perceived benefits of vaping.
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Neuronal GLP1R mediates liraglutide's anorectic but not glucose-lowering effect.
J. Clin. Invest.
PUBLISHED: 04-24-2014
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Glucose control and weight loss are cornerstones of type 2 diabetes treatment. Currently, only glucagon-like peptide-1 (GLP1) analogs are able to achieve both weight loss and glucose tolerance. Both glucose and body weight are regulated by the brain, which contains GLP1 receptors (GLP1R). Even though the brain is poised to mediate the effects of GLP1 analogs, it remains unclear whether the glucose- and body weight-lowering effects of long-acting GLP1R agonists are via direct action on CNS GLP1R or the result of downstream activation of afferent neuronal GLP1R. We generated mice with either neuronal or visceral nerve-specific deletion of Glp1r and then administered liraglutide, a long-acting GLP1R agonist. We found that neither reduction of GLP1R in the CNS nor in the visceral nerves resulted in alterations in body weight or food intake in animals fed normal chow or a high-fat diet. Liraglutide treatment provided beneficial glucose-lowering effects in both chow- and high-fat-fed mice lacking GLP1R in the CNS or visceral nerves; however, liraglutide was ineffective at altering food intake, body weight, or causing a conditioned taste aversion in mice lacking neuronal GLP1R. These data indicate that neuronal GLP1Rs mediate body weight and anorectic effects of liraglutide, but are not required for glucose-lowering effects.
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Dihydromyricetin prevents fetal alcohol exposure-induced behavioral and physiological deficits: the roles of GABAA receptors in adolescence.
Neurochem. Res.
PUBLISHED: 03-20-2014
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Fetal alcohol exposure (FAE) can lead to a variety of behavioral and physiological disturbances later in life. Understanding how alcohol (ethanol, EtOH) affects fetal brain development is essential to guide the development of better therapeutics for FAE. One of EtOH's many pharmacological targets is the ?-aminobutyric acid type A receptor (GABAAR), which plays a prominent role in early brain development. Acute EtOH potentiates inhibitory currents carried by certain GABAAR subtypes, whereas chronic EtOH leads to persistent alterations in GABAAR subunit composition, localization and function. We recently introduced a flavonoid compound, dihydromyricetin (DHM), which selectively antagonizes EtOH's intoxicating effects in vivo and in vitro at enhancing GABAAR function as a candidate for alcohol abuse pharmacotherapy. Here, we studied the effect of FAE on physiology, behavior and GABAAR function of early adolescent rats and tested the utility of DHM as a preventative treatment for FAE-induced disturbances. Gavage administration of EtOH (1.5, 2.5, or 5.0 g/kg) to rat dams on day 5, 8, 10, 12, and 15 of pregnancy dose-dependently reduced female/male offspring ratios (largely through decreased numbers of female offspring) and offspring body weights. FAE (2.5 g/kg) rats tested on postnatal days (P) 25-32 also exhibited increased anxiety and reduced pentylenetetrazol (PTZ)-induced seizure threshold. Patch-clamp recordings from dentate gyrus granule cells (DGCs) in hippocampal slices from FAE (2.5 g/kg) rats at P25-35 revealed reduced sensitivity of GABAergic miniature inhibitory postsynaptic currents (mIPSCs) and tonic current (Itonic) to potentiation by zolpidem (0.3 ?M). Interestingly, potentiation of mIPSCs by gaboxadol increased, while potentiation of Itonic decreased in DGCs from FAE rats. Co-administration of EtOH (1.5 or 2.5 g/kg) with DHM (1.0 mg/kg) in pregnant dams prevented all of the behavioral, physiological, and pharmacological alterations observed in FAE offspring. DHM administration alone in pregnant rats had no adverse effect on litter size, progeny weight, anxiety level, PTZ seizure threshold, or DGC GABAAR function. Our results indicate that FAE induces long-lasting alterations in physiology, behavior, and hippocampal GABAAR function and that these deficits are prevented by DHM co-treatment of EtOH-exposed dams. The absence of adverse side effects and the ability of DHM to prevent FAE consequences suggest that DHM is an attractive candidate for development as a treatment for prevention of fetal alcohol spectrum disorders.
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Dissemination of go sun smart in outdoor recreation: effect of program exposure on sun protection of guests at high-altitude ski areas.
J Health Commun
PUBLISHED: 03-11-2014
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Go Sun Smart is a theory-based health communication program designed to influence sun-protection behaviors of employees and guests at high-altitude ski areas to reduce skin cancer risk. The effects of Go Sun Smart, in a Phase IV dissemination randomized posttest-only trial, on sun-protection behaviors of ski area guests are reported. Program use was assessed by on-site observation and guest message exposure, and sun protection was measured in intercept surveys at ski areas. Dissemination strategy-enhanced versus basic-was not significantly related to sun safety practices. Additional analyses examined the relation between message exposure and guests' sun safety practices. Ski areas displaying at least 6 Go Sun Smart materials in guest-only areas and 9 Go Sun Smart materials throughout the area increased guests' message exposure. Higher message exposure within the high-use ski areas was associated with improved sun protection by guests but not within the low-use ski areas. The authors underscore the importance of program implementation and message exposure on the success of evidence-based health communication efforts applied industrywide.
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Xbp1s in Pomc neurons connects ER stress with energy balance and glucose homeostasis.
Cell Metab.
PUBLISHED: 03-06-2014
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The molecular mechanisms underlying neuronal leptin and insulin resistance in obesity and diabetes remain unclear. Here we show that induction of the unfolded protein response transcription factor spliced X-box binding protein 1 (Xbp1s) in pro-opiomelanocortin (Pomc) neurons alone is sufficient to protect against diet-induced obesity as well as improve leptin and insulin sensitivity, even in the presence of strong activators of ER stress. We also demonstrate that constitutive expression of Xbp1s in Pomc neurons contributes to improved hepatic insulin sensitivity and suppression of endogenous glucose production. Notably, elevated Xbp1s levels in Pomc neurons also resulted in activation of the Xbp1s axis in the liver via a cell-nonautonomous mechanism. Together our results identify critical molecular mechanisms linking ER stress in arcuate Pomc neurons to acute leptin and insulin resistance as well as liver metabolism in diet-induced obesity and diabetes.
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Preparative regimen dosing for hematopoietic stem cell transplantation in patients with chronic kidney disease: analysis of the literature and recommendations.
Biol. Blood Marrow Transplant.
PUBLISHED: 02-17-2014
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Hematopoietic stem cell transplantation (HSCT) is a potentially life-saving therapy that has traditionally been associated with high treatment-related mortality due to direct regimen toxicity and a high incidence of graft-versus-host disease. Historically, pre-existing renal insufficiency has been considered an exclusion criterion for transplantation. The advent of nonmyeloablative conditioning regimens as a less toxic modality for treatment has made HSCT more accessible to elderly patients and patients with comorbidities, such as renal impairment. However, there is no clear standard for how to dose preparative regimens for patients with chronic renal impairment who undergo HSCT. This article serves as a review of the current literature to provide dosing recommendations for commonly used preparative agents in the setting of chronic kidney disease, with the aim of providing optimal dosing for this patient population.
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Pial synangiosis in patients with moyamoya younger than 2 years of age.
J Neurosurg Pediatr
PUBLISHED: 02-14-2014
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Object Patients with moyamoya who are younger than 2 years of age represent a therapeutic challenge because of their frequent neurological instability and concomitant anesthetic risks. The authors report their experience with pial synangiosis revascularization in this population. Methods The authors reviewed the clinical and radiographic records of all patients with moyamoya in a consecutive series of patients under 2 years of age, who underwent cerebral revascularization surgery using pial synangiosis at a single institution. Results During a 12-year period (1994-2005), 34 procedures (bilateral in 15 patients, unilateral in 4) were performed in 19 patients younger than 2 years (out of a total of 456 procedures in 240 patients). Eighteen of these patients presented with either stroke or transient ischemic attack. The average age of the 19 patients at first surgery was 1.4 years (range 6 months-1.9 years). Unanticipated staged operations occurred in 3 patients, due to persistent electroencephalographic changes during the initial surgery in 2 cases and due to brain swelling during the procedure requiring ventriculostomy in the other. There were 2 perioperative strokes; both patients had postoperative seizures but made clinical recoveries. The average follow-up was 7 years (range 1-14 years). Long term, at follow-up, 13 patients (68%) were clinically independent for their age, with 8 (42%) having no significant deficit. Late complications included subdural hygroma evacuation (1), additional revascularization procedures performed years later for frontal lobe ischemia (2), late infarction (1), and asymptomatic ischemic change on routine follow-up MRI studies (1). All patients who had both pre- and postoperative angiography demonstrated progression of disease. Conclusions Despite the challenges inherent to this population, the majority of children with moyamoya under the age of 2 years have a good long-term prognosis. The data from this study support the use of pial synangiosis as a safe, effective, and durable method for treatment of moyamoya for most children in this potentially high-risk population.
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Pharmacological rescue of Ras signaling, GluA1-dependent synaptic plasticity, and learning deficits in a fragile X model.
Genes Dev.
PUBLISHED: 02-05-2014
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Fragile X syndrome, caused by the loss of Fmr1 gene function, is the most common form of inherited mental retardation, with no effective treatment. Using a tractable animal model, we investigated mechanisms of action of a few FDA-approved psychoactive drugs that modestly benefit the cognitive performance in fragile X patients. Here we report that compounds activating serotonin (5HT) subtype 2B receptors (5HT2B-Rs) or dopamine (DA) subtype 1-like receptors (D1-Rs) and/or those inhibiting 5HT2A-Rs or D2-Rs moderately enhance Ras-PI3K/PKB signaling input, GluA1-dependent synaptic plasticity, and learning in Fmr1 knockout mice. Unexpectedly, combinations of these 5HT and DA compounds at low doses synergistically stimulate Ras-PI3K/PKB signal transduction and GluA1-dependent synaptic plasticity and remarkably restore normal learning in Fmr1 knockout mice without causing anxiety-related side effects. These findings suggest that properly dosed and combined FDA-approved psychoactive drugs may effectively treat the cognitive impairment associated with fragile X syndrome.
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Immune activation alters cellular and humoral responses to yellow fever 17D vaccine.
J. Clin. Invest.
PUBLISHED: 01-28-2014
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Defining the parameters that modulate vaccine responses in African populations will be imperative to design effective vaccines for protection against HIV, malaria, tuberculosis, and dengue virus infections. This study aimed to evaluate the contribution of the patient-specific immune microenvironment to the response to the licensed yellow fever vaccine 17D (YF-17D) in an African cohort.
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Preparative regimen dosing for hematopoietic stem cell transplantation in patients with chronic hepatic impairment: analysis of the literature and recommendations.
Biol. Blood Marrow Transplant.
PUBLISHED: 01-28-2014
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Hematopoietic stem cell transplantation (HSCT) is a potentially life-saving therapy for patients with malignant and nonmalignant disease states. Transplant has been associated with high treatment-related morbidity and mortality, therefore limiting its usefulness in patients with baseline liver dysfunction. In the event that a patient with hepatic insufficiency is selected for HSCT, dosage adjustments may be considered; however, no reliable endogenous biomarkers can serve as a guide for adjustments. There is no clear standard or guideline for how to approach these patients, and most adjustments are made empirically on the basis of expert opinion. This article offers practical advice and outlines our personal approaches to provide dosing recommendations for commonly-used preparative agents in the setting of hepatic impairment with the aim to optimize dosing for this patient population.
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Reproductive toxicity in rats with crystal nephropathy following high doses of oral melamine or cyanuric acid.
Food Chem. Toxicol.
PUBLISHED: 01-24-2014
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The industrial chemical melamine was used in 2007 and 2008 to raise the apparent protein content in pet feed and watered down milk, respectively. Because humans may be exposed to melamine via several different routes into the human diet as well as deliberate contamination, this study was designed to characterize the effect of high dose melamine or cyanuric acid oral exposure on the pregnant animal and developing fetus, including placental transfer. Clear rectangular crystals formed following a single triazine exposure which is a different morphology from the golden spherulites caused by combined exposure or the calculi formed when melamine combines with endogenous uric acid. Crystal nephropathy, regardless of cause, induces renal failure which in turn has reproductive sequelae. Specifically, melamine alone-treated dams had increased numbers of early and late fetal deaths compared to controls or cyanuric acid-treated dams. As melamine was found in the amniotic fluid, this study confirms transfer of melamine from mammalian mother to fetus and our study provides evidence that cyanuric acid also appears in the amniotic fluid if mothers are exposed to high doses.
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Exome sequencing identifies BRAF mutations in papillary craniopharyngiomas.
Nat. Genet.
PUBLISHED: 01-12-2014
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Craniopharyngiomas are epithelial tumors that typically arise in the suprasellar region of the brain. Patients experience substantial clinical sequelae from both extension of the tumors and therapeutic interventions that damage the optic chiasm, the pituitary stalk and the hypothalamic area. Using whole-exome sequencing, we identified mutations in CTNNB1 (?-catenin) in nearly all adamantinomatous craniopharyngiomas examined (11/12, 92%) and recurrent mutations in BRAF (resulting in p.Val600Glu) in all papillary craniopharyngiomas (3/3, 100%). Targeted genotyping revealed BRAF p.Val600Glu in 95% of papillary craniopharyngiomas (36 of 39 tumors) and mutation of CTNNB1 in 96% of adamantinomatous craniopharyngiomas (51 of 53 tumors). The CTNNB1 and BRAF mutations were clonal in each tumor subtype, and we detected no other recurrent mutations or genomic aberrations in either subtype. Adamantinomatous and papillary craniopharyngiomas harbor mutations that are mutually exclusive and clonal. These findings have important implications for the diagnosis and treatment of these neoplasms.
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Treatment of Moyamoya disease in the adult population with pial synangiosis.
J. Neurosurg.
PUBLISHED: 01-03-2014
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Surgical treatment of moyamoya disease in the adult population commonly uses direct revascularization, the superficial temporal artery (STA) to middle cerebral artery (MCA) bypass (STA-MCA). Pial synangiosis, a method of indirect revascularization, has been used in adult patients with moyamoya when STA-MCA bypass was not technically feasible. Although the effectiveness of pial synangiosis has been well described in children, only limited reports have examined its role in adult patients with moyamoya disease. In this study the authors report on their experience with pial synangiosis revascularization for this population.
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The extracellular domain of myelin oligodendrocyte glycoprotein elicits atypical experimental autoimmune encephalomyelitis in rat and macaque species.
PLoS ONE
PUBLISHED: 01-01-2014
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Atypical models of experimental autoimmune encephalomyelitis (EAE) are advantageous in that the heterogeneity of clinical signs appears more reflective of those in multiple sclerosis (MS). Conversely, models of classical EAE feature stereotypic progression of an ascending flaccid paralysis that is not a characteristic of MS. The study of atypical EAE however has been limited due to the relative lack of suitable models that feature reliable disease incidence and severity, excepting mice deficient in gamma-interferon signaling pathways. In this study, atypical EAE was induced in Lewis rats, and a related approach was effective for induction of an unusual neurologic syndrome in a cynomolgus macaque. Lewis rats were immunized with the rat immunoglobulin variable (IgV)-related extracellular domain of myelin oligodendrocyte glycoprotein (IgV-MOG) in complete Freund's adjuvant (CFA) followed by one or more injections of rat IgV-MOG in incomplete Freund's adjuvant (IFA). The resulting disease was marked by torticollis, unilateral rigid paralysis, forelimb weakness, and high titers of anti-MOG antibody against conformational epitopes of MOG, as well as other signs of atypical EAE. A similar strategy elicited a distinct atypical form of EAE in a cynomolgus macaque. By day 36 in the monkey, titers of IgG against conformational epitopes of extracellular MOG were evident, and on day 201, the macaque had an abrupt onset of an unusual form of EAE that included a pronounced arousal-dependent, transient myotonia. The disease persisted for 6-7 weeks and was marked by a gradual, consistent improvement and an eventual full recovery without recurrence. These data indicate that one or more boosters of IgV-MOG in IFA represent a key variable for induction of atypical or unusual forms of EAE in rat and Macaca species. These studies also reveal a close correlation between humoral immunity against conformational epitopes of MOG, extended confluent demyelinating plaques in spinal cord and brainstem, and atypical disease induction.
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Flammer syndrome.
EPMA J
PUBLISHED: 01-01-2014
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The new term Flammer syndrome describes a phenotype characterized by the presence of primary vascular dysregulation together with a cluster of symptoms and signs that may occur in healthy people as well as people with disease. Typically, the blood vessels of the subjects with Flammer syndrome react differently to a number of stimuli, such as cold and physical or emotional stress. Nearly all organs, particularly the eye, can be involved. Although the syndrome has some advantages, such as protection against the development of atherosclerosis, Flammer syndrome also contributes to certain diseases, such as normal tension glaucoma. The syndrome occurs more often in women than in men, in slender people than in obese subjects, in people with indoor rather than outdoor jobs, and in academics than in blue collar workers. Affected subjects tend to have cold extremities, low blood pressure, prolonged sleep onset time, shifted circadian rhythm, reduced feeling of thirst, altered drug sensitivity, and increased general sensitivity, including pain sensitivity. The plasma level of endothelin-1 is slightly increased, and the gene expression in lymphocytes is changed. In the eye, the retinal vessels are stiffer and their spatial variability larger; the autoregulation of ocular blood flow is decreased. Glaucoma patients with Flammer syndrome have an increased frequency of the following: optic disc hemorrhages, activated retinal astrocytes, elevated retinal venous pressure, optic nerve compartmentalization, fluctuating diffuse visual field defects, and elevated oxidative stress. Further research should lead to a more concise definition, a precise diagnosis, and tools for recognizing people at risk. This may ultimately lead to more efficient and more personalized treatment.
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Characterization of excitatory and inhibitory neuron activation in the mouse medial prefrontal cortex following palatable food ingestion and food driven exploratory behavior.
Front Neuroanat
PUBLISHED: 01-01-2014
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The medial prefrontal cortex (mPFC) is implicated in aspects of executive function, that include the modulation of attentional and memory processes involved in goal selection. Food-seeking behavior has been shown to involve activation of the mPFC, both during the execution of strategies designed to obtain food and during the consumption of food itself. As these behaviors likely require differential engagement of the prefrontal cortex, we hypothesized that the pattern of neuronal activation would also be behavior dependent. In this study we describe, for the first time, the expression of Fos in different layers and cell types of the infralimbic/dorsal peduncular and prelimbic/anterior cingulate subdivisions of mouse mPFC following both the consumption of palatable food and following exploratory activity of the animal directed at obtaining food reward. While both manipulations led to increases of Fos expression in principal excitatory neurons relative to control, food-directed exploratory activity produced a significantly greater increase in Fos expression than observed in the food intake condition. Consequently, we hypothesized that mPFC interneuron activation would also be differentially engaged by these manipulations. Interestingly, Fos expression patterns differed substantially between treatments and interneuron subtype, illustrating how the differential engagement of subsets of mPFC interneurons depends on the behavioral state. In our experiments, both vasoactive intestinal peptide- and parvalbumin-expressing neurons showed enhanced Fos expression only during the food-dependent exploratory task and not during food intake. Conversely, elevations in arcuate and paraventricular hypothalamic fos expression were only observed following food intake and not following food driven exploration. Our data suggest that select activation of these cell types may be required to support high cognitive demand states such as observed during exploration while being dispensable during the ingestion of freely available food.
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Castlemans disease and primary effusion lymphoma in a HIV-positive patient.
Int J STD AIDS
PUBLISHED: 11-28-2013
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We present a case of Primary Effusion Lymphoma (PEL) occurring simultaneously with Castlemans disease in the same patient. Castlemans disease is distinct from PEL, although both are associated with HHV-8. Other cases have debated whether the coexistence of PEL and Castlemans disease is a recurrence of original PEL tumor in an extracavitary site, or a secondary HHV-8-associated lymphoma distinct from primary PEL. Our case, along with those described previously, show that co-occurrence of PEL and Castlemans disease is possible and plausible. PEL needs to be included in the differential diagnosis in any HIV-positive patient who presents with a pleural effusion, and diagnosis requires only a simple thoracentesis and appropriate immunohistochemistry.
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A modified method for measuring antibiotic use in healthcare settings: implications for antibiotic stewardship and benchmarking.
J. Antimicrob. Chemother.
PUBLISHED: 11-11-2013
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To determine whether adjusting the denominator of the common hospital antibiotic use measurement unit (defined daily doses/100 bed-days) by including age-adjusted comorbidity score (100 bed-days/age-adjusted comorbidity score) would result in more accurate and meaningful assessment of hospital antibiotic use.
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Skunk musk causes methemoglobin and Heinz body formation in vitro.
Vet Clin Pathol
PUBLISHED: 09-17-2013
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A captive Red Panda developed a regenerative anemia with Heinz bodies after being sprayed by a skunk. A definite cause-and-effect relationship between skunk musk and oxidative erythrocyte damage has not been reported, but it was suspected in one reported case of a dog with Heinz body hemolytic anemia.
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Resection of supratentorial lobar cavernous malformations in children: clinical article..
J Neurosurg Pediatr
PUBLISHED: 08-23-2013
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The authors present a series of children with supratentorial lobar cavernous malformations (CMs). Current imaging and operative techniques along with long-term follow-up were incorporated to characterize the response to surgical treatment in this pediatric population.
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Relationship between 24-hour mean ocular perfusion pressure fluctuation and rate of paracentral visual field progression in normal-tension glaucoma.
Invest. Ophthalmol. Vis. Sci.
PUBLISHED: 08-22-2013
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To investigate the relationship between unstable mean ocular perfusion pressure (MOPP) and the rate of paracentral visual field (PVF) progression in patients with medically treated normal-tension glaucoma (NTG).
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Imaging after direct and indirect extracranial-intracranial bypass surgery.
AJR Am J Roentgenol
PUBLISHED: 06-25-2013
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The purpose of this article is to describe the imaging features of different types of surgical cerebral revascularization techniques.
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Low-Tilt Monophasic and Biphasic Waveforms Compared with Standard Biphasic Waveforms in the Transvenous Defibrillation of Ventricular Fibrillation.
Pacing Clin Electrophysiol
PUBLISHED: 06-21-2013
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Commercially available implantable defibrillators utilize a high-tilt waveform. Studies in atrial fibrillation and transthoracic defibrillation of ventricular fibrillation (VF) have shown improved defibrillation efficacy using low-tilt (LT) waveforms. We investigated the feasibility, efficacy, and safety of a LT waveform in the transvenous defibrillation of VF and hypothesized that it would be more efficacious than standard tilted biphasic (STB) waveforms.
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Cavernous malformations of the basal ganglia in children.
J Neurosurg Pediatr
PUBLISHED: 06-21-2013
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Cavernous malformations (CMs) of the basal ganglia are relatively rare lesions that can lead to considerable neurological impairment because of their eloquent location. The authors reviewed the clinical course and surgical outcome of a series of children with basal ganglia CMs.
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Maximizing exosome colloidal stability following electroporation.
Anal. Biochem.
PUBLISHED: 06-10-2013
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Development of exosome-based semisynthetic nanovesicles for diagnostic and therapeutic purposes requires novel approaches to load exosomes with cargo. Electroporation has previously been used to load exosomes with RNA. However, investigations into exosome colloidal stability following electroporation have not been considered. Herein, we report the development of a unique trehalose pulse media (TPM) that minimizes exosome aggregation following electroporation. Dynamic light scattering (DLS) and RNA absorbance were employed to determine the extent of exosome aggregation and electroextraction post electroporation in TPM compared to common PBS pulse media or sucrose pulse media (SPM). Use of TPM to disaggregate melanoma exosomes post electroporation was dependent on both exosome concentration and electric field strength. TPM maximized exosome dispersal post electroporation for both homogenous B16 melanoma and heterogeneous human serum-derived populations of exosomes. Moreover, TPM enabled heavy cargo loading of melanoma exosomes with 5nm superparamagnetic iron oxide nanoparticles (SPION5) while maintaining original exosome size and minimizing exosome aggregation as evidenced by transmission electron microscopy. Loading exosomes with SPION5 increased exosome density on sucrose gradients. This provides a simple, label-free means of enriching exogenously modified exosomes and introduces the potential for MRI-driven theranostic exosome investigations in vivo.
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Effects of a curricular revision on learner outcomes in veterinary clinical pathology.
J Vet Med Educ
PUBLISHED: 05-24-2013
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A mixed-methods evaluation was conducted to study learner attitudes and knowledge about clinical pathology across a curricular change that instituted a stand-alone clinical pathology course in place of content within a previously integrated pathology course structure. Groups of pre- and post-change students were assessed three times across the two semesters leading up to graduation. At each time, rank-ordered and open-ended response items probed attitudes, and multiple-choice items assessed knowledge. Data about student clinical pathology performance were also collected from clinical pathology instructors and supervising clinicians. Student rank-ordered items were evaluated by factor analysis; resulting factor-scale scores, multiple-choice scores, and rank responses from study cohorts were statistically assessed between groups and within each group over time. Intraclass correlations were calculated for the coding of student open-ended responses, and all coded responses were compared among groups. Analysis revealed that students in the revised curriculum had greater satisfaction with their training and greater confidence in data interpretation compared to students without exposure to an independent clinical pathology course. Although differences in knowledge of clinical pathology were not detected, it was also apparent that the independent clinical pathology course filled a student-perceived curricular need without raising criticisms related to diminished integration with anatomic pathology. Secondary study outcomes included formative feedback for course improvement, evidence of clerkship efficacy, and baseline data for further studies.
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Radiation therapy for angiosarcoma: the 35-year University of Florida experience.
Am. J. Clin. Oncol.
PUBLISHED: 05-11-2013
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We sought to identify prognostic factors and successful therapeutic approaches when treating angiosarcoma with radiotherapy.
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Intrasacral meningocele in the pediatric population.
J Neurosurg Pediatr
PUBLISHED: 04-19-2013
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Intrasacral meningoceles are rare cystic lesions that can cause focal compression within the bony sacral canal. Their mechanisms are poorly understood, but most intrasacral meningoceles appear to be intrasacral extradural cysts caused by arachnoid herniating through a small dural defect in the caudal end of the thecal sac. As opposed to perineural cysts, they are not associated with an exiting nerve root. When symptomatic, they can cause sacral pain or sacral nerve root dysfunction due to local compression.
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Vascular collateralization along ventriculoperitoneal shunt catheters in moyamoya disease.
J Neurosurg Pediatr
PUBLISHED: 04-12-2013
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Surgically created openings such as bur holes can serve as avenues for the development of collateral blood supply to the brain in patients with moyamoya disease. When such collateralization occurs through preexisting shunt catheter sites, the potential exists for perioperative stroke if these vessels are damaged during revision of a ventricular catheter for shunt malfunction. In this paper the authors report on a series of patients with a history of ventriculoperitoneal (VP) shunts who later developed moyamoya disease and were found to have spontaneous transdural collateral vessels at ventricular catheter sites readily visualized on diagnostic angiography. A consecutive surgical series of 412 patients with moyamoya disease treated at Boston Childrens Hospital from 1990 to 2010 were reviewed to identify patients with concomitant moyamoya and a VP shunt. The clinical records and angiograms of these patients were reviewed to determine the extent of bur hole collaterals through the shunt site. Three patients were identified who had VP shunts placed for hydrocephalus and subsequently developed moyamoya disease. All 3 patients demonstrated spontaneous transdural collaterals at the ventricular catheter bur hole, as confirmed by angiography during the workup for moyamoya disease. No patients required subsequent revision of their ventricular catheters following the diagnosis of moyamoya. All patients have remained stroke free and clinically stable following pial synangiosis. Although the association of moyamoya and shunted hydrocephalus is rare, it may present a significant potential problem for the neurosurgeon treating a shunt malfunction in this patient population, because shunt bur holes may become entry sites for the ingrowth of significant cortical transdural collateral blood supply to the underlying brain. Shunt revision might therefore be associated with an increased risk of postoperative stroke or operative-site hemorrhage in this population if this vascularization is interrupted when shunt catheters are removed and replaced. A knowledge of the existence of shunt-related collaterals in patients with moyamoya may aid the surgeon in planning shunt revisions and considering, for example, a new entry point for a ventricular catheter, rather than replacing an existing one, to minimize the risk of jeopardizing existing collaterals.
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Effects of acute psychosocial stress in a nonhuman primate model of allergic asthma.
J. Am. Assoc. Lab. Anim. Sci.
PUBLISHED: 04-09-2013
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Current husbandry and care guidelines for laboratory animals recommend social housing for nonhuman primates and all other social species. However, not all individuals of a social species are compatible, which can lead to psychosocial stress on certain members. Because stress affects immune responses, we undertook the present study to determine whether psychosocial stress associated with changes in the group housing of nonhuman primates affected allergic responses in a nonhuman primate model of allergic asthma. Historic records from 35 cynomolgus macaques (Macaca fascicularis) sensitive to house dust mites (HDM) and enrolled in asthma studies from 2007 to 2011 were reviewed for variations in response to aerosolized HDM that could not be explained by clinical or experimental interventions. We then compared these variations with husbandry and clinical records to determine whether the unexplained variations in responses were associated with events known to induce psychosocial stress in this species, including restructuring of social groups, temporary isolation of group members, and changes in cage or room configurations. Adult macaques in stable social groups exhibited little variation in responses to aerosolized antigen. Changes in group membership (conspecifics), cage configurations, and temporary isolation of a group member were associated with decreased responses to HDM. This attenuation lasted 2 to 3 mo on average, although some macaques showed prolonged responses. No evidence for a stress-induced increase in allergic responses was noted. These results demonstrate that acute stress in HDM-sensitive cynomolgus macaques diminishes the physiologic response to inhaled allergen.
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MRI findings and sleep apnea in children with Chiari I malformation.
Pediatr. Neurol.
PUBLISHED: 03-19-2013
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Chiari I malformation is characterized by downward herniation of the cerebellar tonsils through the foramen magnum. Scant data are available on the clinical course, relationship to the extent of herniation on magnetic resonance imaging in Chiari I malformation and the presence of sleep-disordered breathing on polysomnography. Retrospective analysis was performed looking at polysomnographic findings of children diagnosed with Chiari I malformation. Details on how Chiari I malformation was diagnosed, brainstem magnetic resonance imaging findings, and indications for obtaining the polysomnogram in these patients were reviewed. We also reviewed available data on children who had decompression surgery followed by postoperative polysomnography findings. Twenty-two children were identified in our study (11 males, median age 10 years, range 1 to 18). Three had central sleep apnea, five had obstructive sleep apnea, and one had both obstructive and central sleep apnea. Children with sleep-disordered breathing had excessive crowding of the brainstem structures at the foramen magnum and were more likely to have a greater length of herniation compared with those children without sleep-disordered breathing (P = 0.046). Patients with central sleep apneas received surgical decompression, and their conditions were significantly improved on follow-up polysomnography. These data suggest that imaging parameters may correlate with the presence of sleep-disordered breathing in children with Chiari I malformation.
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The role of high-throughput technologies in clinical cancer genomics.
Expert Rev. Mol. Diagn.
PUBLISHED: 03-13-2013
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Cancer is a genetic disease driven by both heritable and somatic alterations in DNA, which underpin not only oncogenesis but also progression and eventual metastasis. The major impetus for elucidating the nature and function of somatic mutations in cancer genomes is the potential for the development of effective targeted anticancer therapies. Over the last decade, high-throughput technologies have allowed us unprecedented access to a host of cancer genomes, leading to an influx of new information about their pathobiology. The challenge now is to integrate such emerging information into clinical practice to achieve tangible benefits for cancer patients. This review examines the roles array-based comparative genomic hybridization and next-generation sequencing are playing in furthering our understanding of both hematological and solid-organ tumors. Furthermore, the authors discuss the current challenges in translating the role of these technologies from bench to bedside.
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Predictors of neoplastic disease in children with isolated pituitary stalk thickening.
Pediatr Blood Cancer
PUBLISHED: 03-12-2013
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The significance of pituitary stalk thickening (PST) on magnetic resonance imaging (MRI) is often unclear. We evaluated presenting symptoms, MRI findings, clinical course, and outcome predictors of patients with PST.
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From cytoplasm to environment: the inorganic ingredients for the origin of life.
Astrobiology
PUBLISHED: 02-13-2013
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Early in its history, Earths surface developed from an uninhabitable magma ocean to a place where life could emerge. The first organisms, lacking ion transporters, fixed the composition of their cradle environment in their intracellular fluid. Later, though life adapted and spread, it preserved some qualities of its initial environment within. Modern prokaryotes could thus provide insights into the conditions of early Earth and the requirements for the emergence of life. In this work, we constrain Earths life-forming environment through detailed analysis of prokaryotic intracellular fluid. Rigorous assessment of the constraints placed on the early Earth environment by intracellular liquid will provide insight into the conditions of abiogenesis, with implications not only for our understanding of early Earth but also the formation of life elsewhere in the Universe.
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Moyamoya syndrome associated with neurofibromatosis Type 1: perioperative and long-term outcome after surgical revascularization.
J Neurosurg Pediatr
PUBLISHED: 02-01-2013
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Children with neurofibromatosis Type 1 (NF1) can present with progressive arteriopathy of the branches of the internal carotid artery consistent with moyamoya syndrome. Clinical symptoms, radiographic evidence of ischemia, and the potential for disease progression may necessitate surgical revascularization to minimize the risk of stroke and progressive neurological deficits. This study aims to evaluate the presentation and surgical outcomes of these patients by reviewing clinical, radiographic, and angiographic data.
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Toxicologic assessment of a commercial decolorized whole leaf aloe vera juice, lily of the desert filtered whole leaf juice with aloesorb.
J Toxicol
PUBLISHED: 01-30-2013
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Aloe vera, a common ingredient in cosmetics, is increasingly being consumed as a beverage supplement. Although consumer interest in aloe likely stems from its association with several health benefits, a concern has also been raised by a National Toxicology Program Report that a nondecolorized whole leaf aloe vera extract taken internally by rats was associated with intestinal mucosal hyperplasia and ultimately malignancy. We tested a decolorized whole leaf (DCWL) aloe vera, treated with activated charcoal to remove the latex portion of the plant, for genotoxicity in bacteria, acute/subacute toxicity in B6C3F1 mice, and subchronic toxicity in F344 rats. We found this DCWL aloe vera juice to be nongenotoxic in histidine reversion and DNA repair assays. Following acute administration, mice exhibited no adverse signs at 3- or 14-day evaluation periods. When fed to male and female F344 rats over 13 weeks, DCWL aloe led to no toxicity as assessed by behavior, stools, weight gain, feed consumption, organ weights, and hematologic or clinical chemistry profiles. These rats had intestinal mucosal morphologies-examined grossly and microscopically-that were similar to controls. Our studies show that oral administration of this DCWL aloe juice has a different toxicology profile than that of the untreated aloe juice at exposures up to 13 weeks.
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Interior Least Tern (Sternula antillarum) breeding distribution and ecology: implications for population-level studies and the evaluation of alternative management strategies on large, regulated rivers.
Ecol Evol
PUBLISHED: 01-29-2013
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Interior Least Terns (Sternula antillarum) (ILT) are colonial, fish-eating birds that breed within active channels of large sand bed rivers of the Great Plains and in the Lower Mississippi Valley. Multipurpose dams, irrigation structures, and engineered navigation systems have been present on these rivers for many decades. Despite severe alteration of channels and flow regimes, regulation era floods have remained effective at maintaining bare sandbar nesting habitat on many river segments and ILT populations have been stable or expanding since they were listed as endangered in 1985. We used ILT breeding colony locations from 2002 to 2012 and dispersal information to identify 16 populations and 48 subpopulations. More than 90% of ILT and >83% of river km with suitable nesting habitat occur within the two largest populations. However, replicate populations remain throughout the entire historical, geophysical, and ecological range of ILT. Rapid colonization of anthropogenic habitats in areas that were not historically occupied suggests metapopulation dynamics. The highest likelihood of demographic connectivity among ILT populations occurs across the Southern Plains and the Lower Mississippi River, which may be demographically connected with Least Tern populations on the Gulf Coast. Paired ecological and bird population models are needed to test whether previously articulated threats limit ILT population growth and to determine if management intervention is necessary and where. Given current knowledge, the largest sources of model uncertainty will be: (1) uncertainty in relationships between high flow events and subsequent sandbar characteristics and (2) uncertainty regarding the frequency of dispersal among population subunits. We recommend research strategies to reduce these uncertainties.
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Representation of ecological systems within the protected areas network of the Continental United States.
PLoS ONE
PUBLISHED: 01-23-2013
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If conservation of biodiversity is the goal, then the protected areas network of the continental US may be one of our best conservation tools for safeguarding ecological systems (i.e., vegetation communities). We evaluated representation of ecological systems in the current protected areas network and found insufficient representation at three vegetation community levels within lower elevations and moderate to high productivity soils. We used national-level data for ecological systems and a protected areas database to explore alternative ways we might be able to increase representation of ecological systems within the continental US. By following one or more of these alternatives it may be possible to increase the representation of ecological systems in the protected areas network both quantitatively (from 10% up to 39%) and geographically and come closer to meeting the suggested Convention on Biological Diversity target of 17% for terrestrial areas. We used the Landscape Conservation Cooperative framework for regional analysis and found that increased conservation on some private and public lands may be important to the conservation of ecological systems in Western US, while increased public-private partnerships may be important in the conservation of ecological systems in Eastern US. We have not assessed the pros and cons of following the national or regional alternatives, but rather present them as possibilities that may be considered and evaluated as decisions are made to increase the representation of ecological systems in the protected areas network across their range of ecological, geographical, and geophysical occurrence in the continental US into the future.
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An in vitro and in vivo toxicologic evaluation of a stabilized aloe vera gel supplement drink in mice.
Food Chem. Toxicol.
PUBLISHED: 01-09-2013
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Aloe vera gel is increasingly consumed as a beverage dietary supplement. The purpose of this study was to determine potential toxicity of a stabilized aloe vera gel derived from the inner gel fillet and marketed as a drink. The gel juice was assessed through assays of genotoxicity in vivo and acute and subchronic toxicity in B6C3F1 mice. Aloe vera did not increase the SOS DNA repair response in Escherichia coli and at 1× and 0.25× it did not increase mutagenesis of Salmonella TA100 resulting in histidine biosynthesis. At 3 and 14days following acute exposure, male and female mice gavaged with the stabilized aloe gel had daily appearances, total body weight gain, selected organ weights, necropsy and hematology tests similar to control mice gavaged with water. After a 13-week aloe gel feed study, male and female mice evaluated by the same criteria as the acute study plus feed consumption and serum chemistry tests were found to be equivalent to control groups. These data indicate that a commercial stabilized aloe gel consumed as a beverage was not genotoxic or toxic in vivo. These results contrast with those obtained using preparations containing aloe latex phenolic compounds such as anthraquinones.
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Chorea in the clinical presentation of moyamoya disease: results of surgical revascularization and a proposed clinicopathological correlation.
J Neurosurg Pediatr
PUBLISHED: 01-04-2013
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Chorea is a movement disorder characterized by brief, irregular, involuntary contractions that appear to flow from 1 muscle to another. There are a limited number of reports in the literature that have linked moyamoya disease and chorea. The authors describe their experience in treating moyamoya disease in patients in whom chorea developed as part of the clinical presentation.
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Neural Adaptation and Behavioral Measures of Temporal Processing and Speech Perception in Cochlear Implant Recipients.
PLoS ONE
PUBLISHED: 01-01-2013
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The objective was to determine if one of the neural temporal features, neural adaptation, can account for the across-subject variability in behavioral measures of temporal processing and speech perception performance in cochlear implant (CI) recipients. Neural adaptation is the phenomenon in which neural responses are the strongest at the beginning of the stimulus and decline following stimulus repetition (e.g., stimulus trains). It is unclear how this temporal property of neural responses relates to psychophysical measures of temporal processing (e.g., gap detection) or speech perception. The adaptation of the electrical compound action potential (ECAP) was obtained using 1000 pulses per second (pps) biphasic pulse trains presented directly to the electrode. The adaptation of the late auditory evoked potential (LAEP) was obtained using a sequence of 1-kHz tone bursts presented acoustically, through the cochlear implant. Behavioral temporal processing was measured using the Random Gap Detection Test at the most comfortable listening level. Consonant nucleus consonant (CNC) word and AzBio sentences were also tested. The results showed that both ECAP and LAEP display adaptive patterns, with a substantial across-subject variability in the amount of adaptation. No correlations between the amount of neural adaptation and gap detection thresholds (GDTs) or speech perception scores were found. The correlations between the degree of neural adaptation and demographic factors showed that CI users having more LAEP adaptation were likely to be those implanted at a younger age than CI users with less LAEP adaptation. The results suggested that neural adaptation, at least this feature alone, cannot account for the across-subject variability in temporal processing ability in the CI users. However, the finding that the LAEP adaptive pattern was less prominent in the CI group compared to the normal hearing group may suggest the important role of normal adaptation pattern at the cortical level in speech perception.
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Differentiation of prostate cancer cells using flexible fluorescent polymers.
Anal. Chem.
PUBLISHED: 12-14-2011
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Using water-soluble, fluorescent, flexible polymers, we have devised a novel methodology for identification and differentiation of prostate cancer cells. Using a stepwise linear discriminant analysis, we demonstrate that the differential modulations of the polymer emission intensities in the presence of conditioned cell culture media can be used to distinguish between prostate cancer subtypes and between cancerous and noncancer cells. The differences in the compositions of the conditioned cell culture media are likely contributing to different fluorescence spectral patterns of the polymers. This in vitro approach may provide a novel platform for the development of an alternative prostate cancer diagnostic and subtyping technique.
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Flow cytometric assessment of canine erythrocytes and platelets for dog erythrocyte antigen 1.1.
Vet Clin Pathol
PUBLISHED: 12-06-2011
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In human medicine, transfusion of ABO-mismatched platelets has been associated with shortened platelet survival and refractoriness to platelet transfusion because of expression of certain blood group antigens on platelets. It remains unknown if canine platelets express dog erythrocyte antigens (DEAs).
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Discovery of asymptomatic moyamoya arteriopathy in pediatric syndromic populations: radiographic and clinical progression.
Neurosurg Focus
PUBLISHED: 12-03-2011
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Limited data exist to guide management of incidentally discovered pediatric moyamoya. Best exemplified in the setting of unilateral moyamoya, in which the unaffected side is monitored, this phenomenon also occurs in populations undergoing routine surveillance of the cerebral vasculature for other conditions, such as sickle cell disease (SCD) or neurofibromatosis Type 1 (NF1). The authors present their experience with specific syndromic moyamoya populations to better characterize the natural history of radiographic and clinical progression in patients with asymptomatic moyamoya.
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Sustainability of the dissemination of an occupational sun protection program in a randomized trial.
Health Educ Behav
PUBLISHED: 11-18-2011
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Sustainability of an occupational sun safety program, Go Sun Smart (GSS), was explored in a randomized trial, testing dissemination strategies at 68 U.S. and Canadian ski areas in 2004-2007. All ski areas received GSS from the National Ski Areas Association through a Basic Dissemination Strategy (BDS) using conference presentations and free materials. Half of the ski areas were randomly assigned to a theory-based Enhanced Dissemination Strategy (EDS) with personal contact supporting GSS use. GSS use was assessed at immediate and long-term follow-up posttests by on-site observation. Use of GSS declined from immediate (M = 6.24) to long-term follow-up (M = 4.72), F(1, 62) = 6.95, p = .01, but EDS ski areas (M = 6.53) continued to use GSS more than BDS ski areas (M = 4.49), F(1, 62) = 5.75, p = .02, regardless of timing of posttest, strategy × observation F(1, 60) = 0.05, p = .83. Despite declines over time, a group of ski areas had sustained high program use and active dissemination methods had sustained positive effects on implementation.
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Comparison of tools for the assessment of inappropriate prescribing in hospitalized older people.
J Eval Clin Pract
PUBLISHED: 08-24-2011
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RATIONAL, AIMS AND OBJECTIVE: The aim of the present study was to compare the ease of use and the capability of four approaches [Medication Appropriateness Index (MAI), the Beers criteria 2003, the Improved Prescribing in the Elderly Tool (IPET) and Health Plan Employer Data and Information Set (HEDIS)] in assessing changes in medication appropriateness in elderly patients over a period of hospitalization.
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Structure of the B4 liquid crystal phase near a glass surface.
Chemphyschem
PUBLISHED: 07-29-2011
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The B4 liquid crystal phase of bent-core molecules, a smectic phase of helical nanofilaments, is one of the most complex hierarchical self-assemblies in soft materials. We describe the layer topology of the B4 phase of mesogens in the P-n-OPIMB homologous series near the liquid crystal/glass interface. Freeze-fracture transmission electron microscopy reveals that the twisted layer structure of the bulk is suppressed, the layers instead forming a structure with periodic layer undulations, with the topography depending on the distance from the glass. The surface layer structure is modeled as parabolic focal conic arrays generated by equidistant parabolas whose foci are defect lines along the glass surface. Nucleation and growth of toric focal conics near the glass substrate is also observed. Although the growth of twisted nanofilaments, the usual manifestation of structural chirality in the B4 phase, is suppressed near the surface, the smectic layers are intrinsically chiral, and the helical filaments that form on top of them grow with specific handedness.
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The proteome of mouse brain microvessel membranes and basal lamina.
J. Cereb. Blood Flow Metab.
PUBLISHED: 07-27-2011
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The blood-brain barrier (BBB) is a multicellular vascular structure separating blood from the brain parenchyma that is composed of endothelial cells with tight intercellular junctions, surrounded by a basal lamina, astrocytes, and pericytes. Previous studies have generated detailed databases of the microvessel transcriptome; however, less information is available on the BBB at the protein level. In this study, we specifically focused on characterization of the membrane fraction of cells within the BBB to generate a more complete understanding of membrane transporters, tight junction proteins, and associated extracellular matrix proteins that are functional hallmarks of the BBB. We used Multidimensional Protein Identification Technology to identify a total of 1,143 proteins in mouse brain microvessels, of which 53% were determined to be membrane associated. Analyses of specific classes of BBB-associated proteins in the context of recent transcriptome reports provide a unique database to assess the relative contribution of genes at the level of both RNA and protein in the maintenance of normal BBB integrity.
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Nutrition knowledge in athletes: a systematic review.
Int J Sport Nutr Exerc Metab
PUBLISHED: 07-02-2011
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Nutrition education aims to enhance knowledge and improve dietary intake in athletes. Understanding athletes nutrition knowledge and its influence on dietary intake will inform nutrition-education programs in this population.
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Alzheimers disease brain-derived amyloid-?-mediated inhibition of LTP in vivo is prevented by immunotargeting cellular prion protein.
J. Neurosci.
PUBLISHED: 05-20-2011
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Synthetic amyloid-? protein (A?) oligomers bind with high affinity to cellular prion protein (PrP(C)), but the role of this interaction in mediating the disruption of synaptic plasticity by such soluble A? in vitro is controversial. Here we report that intracerebroventricular injection of A?-containing aqueous extracts of Alzheimers disease (AD) brain robustly inhibits long-term potentiation (LTP) without significantly affecting baseline excitatory synaptic transmission in the rat hippocampus in vivo. Moreover, the disruption of LTP was abrogated by immunodepletion of A?. Importantly, intracerebroventricular administration of antigen-binding antibody fragment D13, directed to a putative A?-binding site on PrP(C), prevented the inhibition of LTP by AD brain-derived A?. In contrast, R1, a Fab directed to the C terminus of PrP(C), a region not implicated in binding of A?, did not significantly affect the A?-mediated inhibition of LTP. These data support the pathophysiological significance of SDS-stable A? dimer and the role of PrP(C) in mediating synaptic plasticity disruption by soluble A?.
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Integrated medicines management - can routine implementation improve quality?
J Eval Clin Pract
PUBLISHED: 04-19-2011
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Previous service development work in the area of integrated medicines management (IMM) has demonstrated clear quality improvements in a targeted group of patients within a hospital in Northern Ireland. In order to determine whether this programme could be transferable to routine practice and thereby assess its generalizability, research has been carried out to quantify the health care benefits of incorporating the concept of IMM as routine clinical practice.
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Multihospital outbreak of Clostridium difficile ribotype 027 infection: epidemiology and analysis of control measures.
Infect Control Hosp Epidemiol
PUBLISHED: 04-05-2011
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To report a large outbreak of Clostridium difficile infection (CDI; ribotype 027) between June 2007 and August 2008, describe infection control measures, and evaluate the impact of restricting the use of fluoroquinolones in controlling the outbreak.
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Cognitive stimulation and cognitive and functional decline in Alzheimers disease: the cache county dementia progression study.
J Gerontol B Psychol Sci Soc Sci
PUBLISHED: 03-25-2011
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To examine the association of engagement in cognitively stimulating activities with cognitive and functional decline in a population-based sample of incident Alzheimers disease (AD).
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Quantifying the evolution of vascular barrier disruption in advanced atherosclerosis with semipermeant nanoparticle contrast agents.
PLoS ONE
PUBLISHED: 03-24-2011
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Acute atherothrombotic occlusion in heart attack and stroke implies disruption of the vascular endothelial barrier that exposes a highly procoagulant intimal milieu. However, the evolution, severity, and pathophysiological consequences of vascular barrier damage in atherosclerotic plaque remain unknown, in part because quantifiable methods and experimental models are lacking for its in vivo assessment.
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Leptin receptor expression in hindbrain Glp-1 neurons regulates food intake and energy balance in mice.
J. Clin. Invest.
PUBLISHED: 03-09-2011
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Leptin is an adipose-derived hormone that signals to inform the brain of nutrient status; loss of leptin signaling results in marked hyperphagia and obesity. Recent work has identified several groups of neurons that contribute to the effects of leptin to regulate energy balance, but leptin receptors are distributed throughout the brain, and the function of leptin signaling in discrete neuronal populations outside of the hypothalamus has not been defined. In the current study, we produced mice in which the long form of the leptin receptor (Lepr) was selectively ablated using Cre-recombinase selectively expressed in the hindbrain under control of the paired-like homeobox 2b (Phox2b) promoter (Phox2b Cre Lepr(flox/flox) mice). In these mice, Lepr was deleted from glucagon-like 1 peptide-expressing neurons resident in the nucleus of the solitary tract. Phox2b Cre Lepr(flox/flox) mice were hyperphagic, displayed increased food intake after fasting, and gained weight at a faster rate than wild-type controls. Paradoxically, Phox2b Cre Lepr(flox/flox) mice also exhibited an increased metabolic rate independent of a change in locomotor activity that was dependent on food intake, and glucose homeostasis was normal. Together, these data support a physiologically important role of direct leptin action in the hindbrain.
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Education in sleep disorders in US dental schools DDS programs.
Sleep Breath
PUBLISHED: 03-08-2011
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Medical school surveys of pre-doctoral curriculum hours in the somnology, the study of sleep, and its application in sleep medicine/sleep disorders (SM) show slow progress. Limited information is available regarding dentist training. This study assessed current pre-doctoral dental education in the field of somnology with the hypothesis that increased curriculum hours are being devoted to SM but that competencies are still lacking.
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The mesenchymal stem cells in multiple sclerosis (MSCIMS) trial protocol and baseline cohort characteristics: an open-label pre-test: post-test study with blinded outcome assessments.
Trials
PUBLISHED: 03-02-2011
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No treatments are currently available that slow, stop, or reverse disease progression in established multiple sclerosis (MS). The Mesenchymal Stem Cells in Multiple Sclerosis (MSCIMS) trial tests the safety and feasibility of treatment with a candidate cell-based therapy, and will inform the wider challenge of designing early phase clinical trials to evaluate putative neuroprotective therapies in progressive MS. Illustrated by the MSCIMS trial protocol, we describe a novel methodology based on detailed assessment of the anterior visual pathway as a model of wider disease processes--the "sentinel lesion approach".
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Melanocortin-4 receptors expressed by cholinergic neurons regulate energy balance and glucose homeostasis.
Cell Metab.
PUBLISHED: 02-03-2011
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Melanocortin-4 receptor (MC4R) mutations cause dysregulation of energy balance and hyperinsulinemia. We have used mouse models to study the physiological roles of extrahypothalamic MC4Rs. Re-expression of MC4Rs in cholinergic neurons (ChAT-Cre, loxTB MC4R mice) modestly reduced body weight gain without altering food intake and was sufficient to normalize energy expenditure and attenuate hyperglycemia and hyperinsulinemia. In contrast, restoration of MC4R expression in brainstem neurons including those in the dorsal motor nucleus of the vagus (Phox2b-Cre, loxTB MC4R mice) was sufficient to attenuate hyperinsulinemia, while the hyperglycemia and energy balance were not normalized. Additionally, hepatic insulin action and insulin-mediated suppression of hepatic glucose production were improved in ChAT-Cre, loxTB MC4R mice. These findings suggest that MC4Rs expressed by cholinergic neurons regulate energy expenditure and hepatic glucose production. Our results also provide further evidence of the dissociation in pathways mediating the effects of melanocortins on energy balance and glucose homeostasis.
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Detection of early locomotor abnormalities in a Drosophila model of Alzheimers disease.
J. Neurosci. Methods
PUBLISHED: 01-21-2011
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Behavioural assays represent sensitive methods for detecting neuronal dysfunction in model organisms. A number of manual methods have been established for Drosophila, however these are time-consuming and generate parameter-poor phenotype descriptors. Here, we have developed an automated computer vision system to monitor accurately the three-dimensional locomotor trajectories of flies. This approach allows the quantitative description of fly trajectories, using small fly cohorts and short acquisition times. The application of this approach to a Drosophila model of Alzheimers disease enables the early detection of progressive locomotor deficits and the quantitative assessment of phenotype severity. The approach can be widely applied to different disease models in a number of model organisms.
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A point prevalence survey of antibiotic prescriptions: benchmarking and patterns of use.
Br J Clin Pharmacol
PUBLISHED: 01-12-2011
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The aim of the study was to assess current patterns of antibiotic prescribing and the impact of a hospital antibiotic policy on these practices.
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Hcrtr1 and 2 signaling differentially regulates depression-like behaviors.
Behav. Brain Res.
PUBLISHED: 01-11-2011
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The orexin/hypocretin system has the potential to significantly modulate affect, based on both the neuroanatomical projection patterns of these neurons and on the sites of orexin receptor expression. However, there is little data supporting the role of specific orexin receptors in the modulation of depression-like behavior. Here we report behavioral profiling of mice after genetic or pharmacologic inhibition of hcrtr1 and 2 receptor signaling. Hcrtr1 null mice displayed a significant reduction in behavioral despair in the forced swim test and tail suspension test. Wild-type mice treated with the hcrtr1 antagonist SB-334867 also displayed a similar reduction in behavioral despair. No difference in anxiety-like behavior was noted following hcrtr1 deletion. In contrast, hcrtr2-null mice displayed an increase in behavioral despair with no effect on measures of anxiety. These studies suggest that the balance of orexin action at either the hcrtr1 or the hcrtr2 receptor produces an anti-depressant or pro-depressant like effect, depending on the receptor subtype activated.
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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.