86 results on '"Schwartz ES"'
Search Results
2. Valuing American options by simulation: a simple least-squares approach.
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Longstaff, FA, Longstaff, Francis A., Schwartz, ES, and Schwartz, Eduardo S.
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OPTIONS (Finance) ,DERIVATIVE securities ,SIMULATION methods & models - Abstract
Presents an approach for approximating the value of United States-style options by simulation. Numerical example of the simulation approach; Description of general least square Monte Carlo (LSM) algorithm approach; Applications of the LSM algorithm approach; Numerical and implementation issues associated with the LSM algorithm; Advantages of simulation techniques.
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- 2001
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3. Imaging Stewardship: Triage for Neuroradiology MR During Limited-Resource Hours.
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Lopez-Rippe J, Schwartz ES, Davis JC, Dennis RA, Francavilla ML, Jalloul M, and Kaplan SL
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- Humans, Child, Time Factors, Telephone, Triage
- Abstract
Objectives: To decrease call burden on pediatric neuroradiologists, we developed guidelines for appropriate use of MR overnight. These guidelines were implemented using triage by in-house generalist pediatric radiologists. Process measures and balancing measures were assessed during implementation., Methods: For this improvement project, interdepartmental consensus guidelines were developed using exploratory mixed-methods design. Implementation of triage used plan-do-study-act cycles. Process measures included reduction in the number of telephone calls, frequency of calls, triage decisions, and number and type of examinations ordered. Balancing measures included burden of time and effort to the generalist radiologists. Differences in examination orders between implementation intervals was assessed using Kruskal-Wallis, with significance at P < .05., Results: Consensus defined MR requests as "do," "defer," or "divert" (to CT). Guidelines decreased neuroradiologist calls 74% while adding minimal burden to the generalist radiologists. Most nights had zero or one triage request and the most common triage decision was "do," and the most common examination was routine brain MR. Number of MR ordered and completed overnight did not significantly change with triage., Discussion: Multidisciplinary consensus for use of pediatric neurological MR during limited resource hours overnight is an example of imaging stewardship that decreased the burden of calls and burnout for neuroradiologists while maintaining a comparable level of service to the ordering clinicians., (Copyright © 2023 American College of Radiology. Published by Elsevier Inc. All rights reserved.)
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- 2024
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4. Magnetic resonance imaging protocols in pediatric stroke.
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Sotardi ST, Alves CAPF, Serai SD, Beslow LA, Schwartz ES, Magee R, and Vossough A
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- Child, Humans, Magnetic Resonance Imaging, Neuroimaging methods, Tomography, X-Ray Computed, Infarction, Stroke diagnostic imaging
- Abstract
Neuroimaging protocols play an important role in the timely evaluation and treatment of pediatric stroke and its mimics. MRI protocols for stroke in the pediatric population should be guided by the clinical scenario and neurologic examination, with consideration of age, suspected infarct type and underlying risk factors. Acute stroke diagnosis and causes in pediatric age groups can differ significantly from those in adult populations, and delay in stroke diagnosis among children is a common problem. An awareness of pediatric stroke presentations and risk factors among pediatric emergency physicians, neurologists, pediatricians, subspecialists and radiologists is critical to ensuring timely diagnosis. Given special considerations related to unique pediatric stroke risk factors and the need for sedation in some children, expert consensus guidelines for the imaging of suspected pediatric infarct have been proposed. In this article the authors review standard and rapid MRI protocols for the diagnosis of pediatric stroke, as well as the key differences between pediatric and adult stroke imaging., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
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- 2023
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5. Summary of the 2022 ACR Intersociety Meeting.
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Siewert B, Bruno MA, Fleishon HB, Hublall R, Slanetz PJ, Jankovic SN, Kotsenas AL, Schwartz ES, Pawley B, Mukherji SK, Bourland JD, Artunduaga M, Saif M, Poussaint TY, Scanlon MH, Kirsch J, and Lexa FJ
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- Humans, United States, Radiologists, Radiography, Utah, Radiology, Radiation Oncology
- Abstract
The ACR Intersociety Committee meeting of 2022 (ISC-2022) was convened around the theme of "Recovering From The Great Resignation, Moral Injury and Other Stressors: Rebuilding Radiology for a Robust Future." Representatives from 29 radiology organizations, including all radiology subspecialties, radiation oncology, and medical physics, as well as academic and private practice radiologists, met for 3 days in early August in Park City, Utah, to search for solutions to the most pressing problems facing the specialty of radiology in 2022. Of these, the mismatch between the clinical workload and the available radiologist workforce was foremost-as many other identifiable problems flowed downstream from this, including high job turnover, lack of time for teaching and research, radiologist burnout, and moral injury., (Copyright © 2023 American College of Radiology. Published by Elsevier Inc. All rights reserved.)
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- 2023
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6. Somatosensory and motor representations following bilateral transplants of the hands: A 6-year longitudinal case report on the first pediatric bilateral hand transplant patient.
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Gaetz W, Dockstader C, Furlong PL, Amaral S, Vossough A, Schwartz ES, Roberts TPL, and Scott Levin L
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- Humans, Child, Somatosensory Cortex physiology, Hand physiology, Fingers physiology, Magnetoencephalography, Brain Mapping, Neuronal Plasticity physiology, Hand Transplantation
- Abstract
A vascularized composite tissue allotransplantation (VCA) was performed at the Children's Hospital of Philadelphia (CHOP), on an 8-year-old patient in 2015, six years after bilateral hand and foot amputation. Hand VCA resulted in reafferentation of the medial, ulnar, and radial nerves serving hand somatosensation and motor function. We used magnetoencephalography (MEG) to assess somatosensory cortical plasticity following the post-transplantation recovery of the peripheral sensory nerves of the hands. Our 2-year postoperative MEG showed that somatosensory lip representations, initially observed at "hand areas", reverted to canonical, orthotopic lip locations with recovery of post-transplant hand function. Here, we continue the assessment of motor and somatosensory responses up to 6-years post-transplant. Magnetoencephalographic somatosensory responses were recorded eight times over a six-year period following hand transplantation, using a 275-channel MEG system. Somatosensory tactile stimuli were presented to the right lower lip (all 8 visits) as well as right and left index fingers (visits 3-8) and fifth digits (visits 4-8). In addition, left and right-hand motor responses were also recorded for left index finger and right thumb (visit 8 only).During the acute recovery phase (visits 3 and 4), somatosensory responses of the digits were observed to be significantly larger and more phasic (i.e., smoother) than controls. Subsequent measures showed that digit responses maintain this atypical response profile (evoked-response magnitudes typically exceed 1 picoTesla). Orthotopic somatosensory localization of the lip, D2, and D5 was preserved. Motor beta-band desynchrony was age-typical in localization and response magnitude; however, the motor gamma-band response was significantly larger than that observed in a reference population.These novel findings show that the restoration of somatosensory input of the hands resulted in persistent and atypically large cortical responses to digit stimulation, which remain atypically large at 6 years post-transplant; there is no known perceptual correlate, and no reports of phantom pain. Normal somatosensory organization of the lip, D2, and D5 representation remain stable following post-recovery reorganization of the lip's somatosensory response., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)
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- 2023
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7. Burnt Out: Rate of Burnout in Neuropsychology Survey Respondents During the COVID-19 Pandemic, Brief Communication.
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Marra DEC, Simons MU, Schwartz ES, Marston EA, and Hoelzle JB
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- Humans, Child, Neuropsychology, Pandemics, Neuropsychological Tests, Surveys and Questionnaires, COVID-19 epidemiology, Burnout, Professional epidemiology, Burnout, Professional psychology
- Abstract
Objective: Due to the COVID-19 pandemic, burnout among healthcare workers has significantly increased. This study evaluated rates of burnout in neuropsychologists one year into the COVID-19 pandemic., Method: A survey invitation was sent across five neuropsychology-related listservs in April 2021. Burnout was assessed with the Copenhagen Burnout Inventory (CBI; Kristensen, T. S., Borritz, M., Villadsen, E., & Christensen, K. B. (2005). The Copenhagen Burnout Inventory: A new tool for the assessment of burnout. Work & Stress, 19 (3), 192-207) and differences in Personal, Work, and Client burnout scores were evaluated across patient population and work setting., Results: 57.3% and 51.5% of respondents (N = 130) endorsed moderate-to-high levels of personal and work-related burnout, respectively. In the Personal domain, respondents working with pediatric patients had higher mean scores and a higher proportion of respondents endorsed moderate-to-high levels of burnout., Conclusion: More than half of the survey respondents endorsed elevated levels of personal and work-related burnout. This is concerning as burnout is associated with personal challenges and diminished patient care. Potential organizational interventions are discussed., (© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
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- 2023
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8. Natural history of familial cerebral cavernous malformation syndrome in children: a multicenter cohort study.
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Geraldo AF, Alves CAPF, Luis A, Tortora D, Guimarães J, Abreu D, Reimão S, Pavanello M, de Marco P, Scala M, Capra V, Vaz R, Rossi A, Schwartz ES, Mankad K, and Severino M
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- Child, Female, Humans, Male, Cerebral Hemorrhage etiology, Hemorrhage, Magnetic Resonance Imaging, Prospective Studies, Retrospective Studies, Hemangioma, Cavernous, Central Nervous System diagnostic imaging, Hemangioma, Cavernous, Central Nervous System genetics, Hemangioma, Cavernous, Central Nervous System complications
- Abstract
Purpose: There is limited data concerning neuroimaging findings and longitudinal evaluation of familial cerebral cavernous malformations (FCCM) in children. Our aim was to study the natural history of pediatric FCCM, with an emphasis on symptomatic hemorrhagic events and associated clinical and imaging risk factors., Methods: We retrospectively reviewed all children diagnosed with FCCM in four tertiary pediatric hospitals between January 2010 and March 2022. Subjects with first available brain MRI and [Formula: see text] 3 months of clinical follow-up were included. Neuroimaging studies were reviewed, and clinical data collected. Annual symptomatic hemorrhage risk rates and cumulative risks were calculated using survival analysis and predictors of symptomatic hemorrhagic identified using regression analysis., Results: Forty-one children (53.7% males) were included, of whom 15 (36.3%) presenting with symptomatic hemorrhage. Seven symptomatic hemorrhages occurred during 140.5 person-years of follow-up, yielding a 5-year annual hemorrhage rate of 5.0% per person-year. The 1-, 2-, and 5-year cumulative risks of symptomatic hemorrhage were 7.3%, 14.6%, and 17.1%, respectively. The latter was higher in children with prior symptomatic hemorrhage (33.3%), CCM2 genotype (33.3%), and positive family history (20.7%). Number of brainstem (adjusted hazard ratio [HR] = 1.37, P = 0.005) and posterior fossa (adjusted HR = 1.64, P = 0.004) CCM at first brain MRI were significant independent predictors of prospective symptomatic hemorrhage., Conclusion: The 5-year annual and cumulative symptomatic hemorrhagic risk in our pediatric FCCM cohort equals the overall risk described in children and adults with all types of CCM. Imaging features at first brain MRI may help to predict potential symptomatic hemorrhage at 5-year follow-up., (© 2022. The Author(s).)
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- 2023
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9. Radiologists staunchly support patient safety and autonomy, in opposition to the SCOTUS decision to overturn Roe v Wade.
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Karandikar A, Solberg A, Fung A, Lee AY, Farooq A, Taylor AC, Oliveira A, Narayan A, Senter A, Majid A, Tong A, McGrath AL, Malik A, Brown AL, Roberts A, Fleischer A, Vettiyil B, Zigmund B, Park B, Curran B, Henry C, Jaimes C, Connolly C, Robson C, Meltzer CC, Phillips CH, Dove C, Glastonbury C, Pomeranz C, Kirsch CFE, Burgan CM, Scher C, Tomblinson C, Fuss C, Santillan C, Daye D, Brown DB, Young DJ, Kopans D, Vargas D, Martin D, Thompson D, Jordan DW, Shatzkes D, Sun D, Mastrodicasa D, Smith E, Korngold E, Dibble EH, Arleo EK, Hecht EM, Morris E, Maltin EP, Cooke EA, Schwartz ES, Lehrman E, Sodagari F, Shah F, Doo FX, Rigiroli F, Vilanilam GK, Landinez G, Kim GG, Rahbar H, Choi H, Bandesha H, Ojeda-Fournier H, Ikuta I, Dragojevic I, Schroeder JLT, Ivanidze J, Katzen JT, Chiang J, Nguyen J, Robinson JD, Broder JC, Kemp J, Weaver JS, Conyers JM, Robbins JB, Leschied JR, Wen J, Park J, Mongan J, Perchik J, Barbero JPM, Jacob J, Ledbetter K, Macura KJ, Maturen KE, Frederick-Dyer K, Dodelzon K, Cort K, Kisling K, Babagbemi K, McGill KC, Chang KJ, Feigin K, Winsor KS, Seifert K, Patel K, Porter KK, Foley KM, Patel-Lippmann K, McIntosh LJ, Padilla L, Groner L, Harry LM, Ladd LM, Wang L, Spalluto LB, Mahesh M, Marx MV, Sugi MD, Sammer MBK, Sun M, Barkovich MJ, Miller MJ, Vella M, Davis MA, Englander MJ, Durst M, Oumano M, Wood MJ, McBee MP, Fischbein NJ, Kovalchuk N, Lall N, Eclov N, Madhuripan N, Ariaratnam NS, Vincoff NS, Kothary N, Yahyavi-Firouz-Abadi N, Brook OR, Glenn OA, Woodard PK, Mazaheri P, Rhyner P, Eby PR, Raghu P, Gerson RF, Patel R, Gutierrez RL, Gebhard R, Andreotti RF, Masum R, Woods R, Mandava S, Harrington SG, Parikh S, Chu S, Arora SS, Meyers SM, Prabhu S, Shams S, Pittman S, Patel SN, Payne S, Hetts SW, Hijaz TA, Chapman T, Loehfelm TW, Juang T, Clark TJ, Potigailo V, Shah V, Planz V, Kalia V, DeMartini W, Dillon WP, Gupta Y, Koethe Y, Hartley-Blossom Z, Wang ZJ, McGinty G, Haramati A, Allen LM, and Germaine P
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- Humans, United States, Radiologists, Patient Safety, Dissent and Disputes
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- 2023
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10. Prolonged neurologic deficits with brain MRI changes following ECT in an adolescent with a CACNA1a-related disorder; a case report.
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Vithayathil J, Freeman C, Jacobwitz M, Schwartz ES, and Agarwal S
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- Child, Humans, Adolescent, Calcium Channels genetics, Brain, Electroconvulsive Therapy, Brain Edema, Autism Spectrum Disorder, Channelopathies
- Abstract
Background: Electroconvulsive therapy is used to treat depression and schizophrenia with infrequent use in pediatric patients. We report a case of an adolescent with autism spectrum disorder and acute catatonia that presented with status epilepticus (SE) and prolonged neurologic deficits with unilateral left cerebral edema on imaging following unilateral electroconvulsive therapy (ECT) on the right side, subsequently found to have a CACNA1a pathogenic variant. This case highlights a potential adverse effect of ECT in patients with CACNA1a related disorders., Case: The patient received unilateral ECT to the right side and subsequently had an episode of SE with right-sided hemiplegia for 72 h prior to regaining some function with persistent mild right-hand weakness that persisted for at least 1-2 weeks. A brain MRI 2 days after ECT was unremarkable, but a repeat MRI on day four of admission showed left hemisphere cortical diffusion restriction, increased perfusion and T2 prolongation suggestive of cortical edema. They had whole exome genetic testing sent after discharge that showed a known pathogenic CACNA1a variant (p.I1709T). CACNA1a encodes the P/Q type calcium channels and deleterious variants in this gene result in a channelopathy associated with a spectrum of neurodevelopmental disorders that include autism spectrum disorder, hemiplegic migraine with unilateral cerebral edema, epileptic encephalopathies, or episodic ataxia syndromes., Conclusion: A literature review of ECT and neurologic deficits showed that most neurologic deficits resolve within 30 min of ECT. Case reports of prolonged deficits are rare and there are no prior reports of acute MRI changes related to ECT. Thus, the acute deterioration and MRI findings in this patient are likely related to the underlying CACNA1a channelopathy disorder with ECT as a precipitating event. This case report suggests care should be taken when using ECT in patients with pathogenic variants in CACNA1a. Furthermore, it reinforces the utility and importance of expanded genetic testing in patients with neurodevelopmental disorders as findings can provide valuable information that can guide treatment decisions., (© 2022. The Author(s).)
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- 2022
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11. Radiologists staunchly support patient safety and autonomy, in opposition to the SCOTUS draft.
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Andreotti RF, Arleo EK, Arora SS, Broder JC, Brook O, Cooke EA, Davis MA, Dodelzon K, Englander MJ, Fischbein NJ, Fleischer A, Frederick-Dyer K, Gerson RF, Gruen D, Hecht EM, Katzen JT, Kemp J, Kotsenas AL, Ladd LM, Malik A, McGinty G, Meltzer CC, Oliveira A, Phillips C, Porter KK, Rhyner P, Robson C, Shatzkes D, Spalluto LB, Sun M, Tomblinson C, Vincoff NS, Wood MJ, Zigmund B, Glastonbury C, Ivanidze J, Schwartz ES, and Woodard PK
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- Dissent and Disputes, Humans, Patient Safety, Radiologists
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- 2022
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12. Spinal involvement in pediatric familial cavernous malformation syndrome.
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Geraldo AF, Luis A, Alves CAPF, Tortora D, Guimarães J, Reimão S, Pavanello M, de Marco P, Scala M, Capra V, Rossi A, Schwartz ES, Mankad K, and Severino M
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- Child, Female, Humans, Magnetic Resonance Imaging methods, Male, Retrospective Studies, Spinal Cord pathology, Spine, Syndrome, Hemangioma, Cavernous, Central Nervous System diagnostic imaging, Hemangioma, Cavernous, Central Nervous System genetics, Vascular Malformations
- Abstract
Purpose: The aim of the study was to assess the prevalence and characteristics of spinal cord cavernous malformations (SCCM) and intraosseous spinal vascular malformations (ISVM) in a pediatric familial cerebral cavernous malformation (FCCM) cohort and evaluate clinico-radiological differences between children with (SCCM +) and without (SCCM-) SCCM., Methods: All patients with a pediatric diagnosis of FCCM evaluated at three tertiary pediatric hospitals between January 2010 and August 2021 with [Formula: see text] 1 whole spine MR available were included. Brain and spine MR studies were retrospectively evaluated, and clinical and genetic data collected. Comparisons between SCCM + and SCCM- groups were performed using student-t/Mann-Whitney or Fisher exact tests, as appropriate., Results: Thirty-one children (55% boys) were included. Baseline spine MR was performed (mean age = 9.7 years) following clinical manifestations in one subject (3%) and as a screening strategy in the remainder. Six SCCM were detected in five patients (16%), in the cervico-medullary junction (n = 1), cervical (n = 3), and high thoracic (n = 2) regions, with one appearing during follow-up. A tendency towards an older age at first spine MR (P = 0.14) and [Formula: see text] 1 posterior fossa lesion (P = 0.13) was observed in SCCM + patients, lacking statistical significance. No subject demonstrated ISVM., Conclusion: Although rarely symptomatic, SCCM can be detected in up to 16% of pediatric FCCM patients using diverse spine MR protocols and may appear de novo. ISVM were instead absent in our cohort. Given the relative commonality of asymptomatic SCCM, serial screening spine MR should be considered in FCCM starting in childhood., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
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- 2022
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13. A Pilot Program of Virtual Ergonomics Consults for Radiology Staff Working From Home.
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Miranda-Schaeubinger M, Schwartz ES, Sze RW, and Larsen EP
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- Humans, Pilot Projects, Radiography, Ergonomics, Radiology
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- 2021
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14. The American Society of Neuroradiology: Cultivating a Diverse and Inclusive Culture to Build a Stronger Organization.
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Bunch PM, Loevner LA, Bhala R, Hepp MB, Hirsch JA, Johnson MH, Lyp KL, Quigley EP, Salamon N, Jordan JE, and Schwartz ES
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- Cerebral Angiography, Humans, United States, Quality Assurance, Health Care
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- 2021
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15. Prognostic factors of 90-day mortality in patients hospitalised with COVID-19.
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Brieghel C, Ellekvist P, Lund ML, Søborg C, Walsted ES, Thomsen JJ, Biering-Sørensen T, Mohr T, Knop FK, and Ravn P
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- Adolescent, Adult, Age Factors, Aged, Aged, 80 and over, COVID-19 therapy, Child, Cohort Studies, Critical Care, Denmark, Female, Hospital Mortality, Humans, Male, Middle Aged, Survival Rate, Young Adult, COVID-19 diagnosis, COVID-19 mortality, Hospitalization
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Introduction: Mortality due to COVID-19 is higher among elderly patients with comorbidities. Even so, prognostication in COVID-19 remains limited., Methods: We assessed 90-day mortality stratified by comorbidities, routine biochemical markers and oxygen need in a consecutive single-centre cohort from 2 March to 2 June 2020., Results: We included 263 hospitalised patients with laboratory-confirmed COVID-19. On admission, fitness for intensive care was determined in 254 patients including 98 (39%) with a do-not-resuscitate order. Ninety-day overall mortality was 29%, whereas intensive care unit (ICU) mortality was 35% (14/40). Alcohol abuse, liver disease and elevated urea were strongly associated with mortality in univariable analyses. In a mutually adjusted multivariable analysis, we found an independent incremental increase in 90-day mortality with each increasing age by decade (hazard ratio (HR) = 1.5; 95% confidence interval (CI): 1.2-1.9), Charlson Comorbidity Index (CCI) score (HR = 1.2; 95% CI: 1.0-1.4), number of abnormal blood tests (HR = 1.2; 95% CI: 1.1-1.3) and l/min. of supplemental oxygen (HR = 1.1; 95% CI: 1.1-1.2)., Conclusions: The overall mortality was similar to that of other hospitalised patients, whereas the ICU mortality was lower than expected. On admission, each additional age by decade, CCI score, number of abnormal blood tests and magnitude of supplemental oxygen were independently associated with increased mortality., Funding: none., Trial Registration: not relevant., (Articles published in the DMJ are “open access”. This means that the articles are distributed under the terms of the Creative Commons Attribution Non-commercial License, which permits any non-commercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited.)
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- 2021
16. Let Me Not Be Mad-My Story of Unraveling Minds: Neuropsychiatric Self-portrait in a Convex Mirror.
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Schwartz ES
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- Female, Humans, Male, Physician-Patient Relations, Psychophysiology, Mental Disorders
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- 2020
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17. Evaluation of two portable pupillometers to assess clinical utility.
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McKay RE, Kohn MA, Schwartz ES, and Larson MD
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Background: Pupillometers have been proposed as clinical assessment tools. We compared two pupillometers to assess measurement agreement., Materials & Methods: We enrolled 30 subjects and simultaneously measured the pupil diameter and light reflex amplitude with an iPhone pupillometer and a portable infrared pupillometer. We then enrolled 40 additional subjects and made serial measurements with each device., Results: Failure occurred in 30% of attempts made with the iPhone pupillometer compared with 4% of attempts made with the infrared pupillometer (Fisher's exact p = 0.0001). Method comparison of the two devices used simultaneously showed significant disagreement in dynamic measurements., Conclusion: The iPhone pupillometer had poor repeatability and suggests that it is not a practical tool to support clinical decisions., Competing Interests: Financial & competing interests disclosure Financial support was obtained from the Department of Anesthesiology and Perioperative Care, University of California, San Francisco and from a UCSF Surgical Innovations Grant. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript., (© 2020 Merlin D. Larson.)
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- 2020
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18. Initial changes in neuropsychologists clinical practice during the COVID-19 pandemic: A survey study.
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Marra DE, Hoelzle JB, Davis JJ, and Schwartz ES
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- Adolescent, Adult, COVID-19, Child, Communication, Coronavirus Infections psychology, Employment methods, Employment trends, Female, Humans, Male, Neuropsychological Tests, Neuropsychology methods, Pneumonia, Viral psychology, SARS-CoV-2, Young Adult, Betacoronavirus, Coronavirus Infections epidemiology, Coronavirus Infections therapy, Neuropsychology trends, Pandemics, Pneumonia, Viral epidemiology, Pneumonia, Viral therapy, Surveys and Questionnaires
- Abstract
Objective: In light of the COVID-19 pandemic, a majority of clinicians have had to quickly and dramatically alter their clinical practices. Two surveys were administered on 3/26/2020 and 3/30/2020, respectively, to document immediate changes and challenges in clinical practice. Method: Two surveys were administered between 3/26/2020 and 3/30/2020, via SurveyMonkey and Google Forms, asking clinicians questions pertaining to practice issues during the early stages of the COVID-19 pandemic. Quantitative responses from the second survey were stratified by clinical setting (Medical Hospital vs. Private Practice) prior to analysis. Qualitative, free-response items were coded by the authors to better understand immediate changes in practice and other concerns. Results: 266 neuropsychologists completed Survey 1 and 230 completed Survey 2. Results suggest that practices immediately moved towards remote service provision. A meaningful proportion of clinicians and their staff were immediately affected economically by the pandemic, with clinicians in private practice differentially affected. Furthermore, a small but significant minority of respondents faced ethical dilemmas related to service provision and expressed concerns with initial communication from their employment organizations. Respondents requested clear best-practice guidelines from neuropsychological practice organizations. Conclusions: It is clear that field of neuropsychology has drastically shifted clinical practices in response to COVID-19 and is likely to continue to evolve. While these responses were collected in the early stages of stay-at-home orders, policy changes continue to occur and it is paramount that practice organizations consider the initial challenges expressed by clinicians when formulating practice recommendations and evaluating the clinical utility of telehealth services.
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- 2020
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19. Differential Distribution of Flavonoids and Phenolic Acids in Leaves of Kalanchoe delagoensis Ecklon & Zeyher (Crassulaceae).
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Casanova JM, Dos Santos Nascimento LB, Casanova LM, Leal-Costa MV, Costa SS, and Tavares ES
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- Antioxidants analysis, Antioxidants chemistry, Chromatography, High Pressure Liquid methods, Crassulaceae radiation effects, Flavonoids analysis, Kalanchoe cytology, Kalanchoe radiation effects, Microscopy, Fluorescence, Phenols analysis, Plant Extracts analysis, Plant Leaves chemistry, Plant Leaves cytology, Crassulaceae chemistry, Flavonoids chemistry, Hydroxybenzoates chemistry, Kalanchoe chemistry, Plant Extracts chemistry
- Abstract
Kalanchoe delagoensis is adapted to intense solar irradiation, drought, and heat, partially due to the presence of phenols, important photo-protective compounds and antioxidants. This study aimed to evaluate the distribution of flavonoids and phenolic acid derivatives throughout the erect-tubular leaves of K. delagoensis. Specimens grown under sunny conditions were used for histochemical and high-performance liquid chromatography coupled with diode array detection (liquid HPLC-DAD) analysis. The NP (2-aminoethyl diphenylborinate) test suggested the presence of phenolic acids throughout the leaf blade below the epidermis and in chloroplasts, mainly in the leaf base. Flavonoids were detected specifically in chloroplasts, on the adaxial side of the middle third and at the leaf apex, near the meristematic cells. There was a tendency of flavonoid accumulation from the middle third to the apex, especially surrounding the gem, while phenolic acids were observed mainly in the base. This can be explained by the more exposed leaf apex and to the presence of apical buds (high production and regulation sites of ROS). The HPLC-DAD analysis showed different classes of flavonoids and phenolic acid derivatives in the leaf extracts, agreeing with the NP test results. This is the first time that the substitution of phenolic acids by flavonoids from the leaf base to the apex has been described.
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- 2020
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20. Decreasing radiologist burnout through informatics-based solutions.
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Simon AF, Holmes JH, and Schwartz ES
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- Humans, Burnout, Psychological prevention & control, Burnout, Psychological psychology, Informatics methods, Radiologists psychology
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Increased performance demands have interacted with suboptimal use of technology and contributed to burnout among radiologists. Although the problem of radiologist burnout has been well documented, there is a gap in the literature in terms of how technology can be better utilized to lessen the problem. Informatics-based modifications to existing technology hold the potential to reduce the amount of time radiologists spend on noninterpretive tasks, decrease interruptions, facilitate connections with colleagues, and improve patient care. Examples of successful modifications to technology are presented and discussed in relation to how they contribute to improving workplace engagement among radiologists., (Copyright © 2019 Elsevier Inc. All rights reserved.)
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- 2020
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21. Synthetic aperture magnetometry and excess kurtosis mapping of Magnetoencephalography (MEG) is predictive of epilepsy surgical outcome in a large pediatric cohort.
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Gofshteyn JS, Le T, Kessler S, Kamens R, Carr C, Gaetz W, Bloy L, Roberts TPL, Schwartz ES, and Marsh ED
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- Adolescent, Brain surgery, Child, Child, Preschool, Epilepsy surgery, Female, Humans, Male, Neurosurgical Procedures, Prognosis, Retrospective Studies, Treatment Outcome, Brain diagnostic imaging, Epilepsy diagnostic imaging, Magnetoencephalography methods, Magnetometry methods
- Abstract
Objective: Resective surgery is the most effective treatment option for patients with refractory epilepsy; however identification of patients who will benefit from epilepsy surgery remains challenging. Synthetic aperture magnetometry and excess kurtosis mapping (SAM(g2)) of magnetoencephalography (MEG) is a non-invasive tool that warrants further examination in the pediatric epilepsy population. Here, we examined the utility of MEG with SAM(g2) to determine if MEG epileptiform foci correlates with surgical outcome and to develop a predictive model incorporating MEG information to best assess likelihood of seizure improvement/freedom from resective surgery., Methods: 564 subjects who had MEG at the Children's Hospital of Philadelphia between 2010-2015 were screened. Clinical epilepsy history and prior electrographic records were extracted and reviewed and correlated with MEG findings. MEG assessments were made by both a neurologist and neuroradiologist. Predictive models were developed to assess the utility of MEG in determining Engel class at one year and five years after resective epilepsy surgery., Results: The number of MEG spike foci was highly associated with Engel class outcome at both one year and five years; however, using MEG data in isolation was not significantly predictive of 5 year surgical outcome. When combined with clinical factors; scalp EEG (single ictal onset zone), MRI (lesional or not), age and sex in a logistic regression model MEG foci was significant for Engel class outcome at both 1 year (p = 0.03) and 5 years (0.02). The percent correctly classified for Engel class at one year was 78.43% and the positive predictive value was 71.43., Significance: MEG using SAM(g2) analysis in an important non-invasive tool in the identification of those patients who will benefit most from surgery. Integrating MEG data analysis into pre-surgical evaluation can help to predict epilepsy outcome after resective surgery in the pediatric population if utilized with skilled interpretation., (Copyright © 2019 Elsevier B.V. All rights reserved.)
- Published
- 2019
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22. Arterial spin-labeling magnetic resonance imaging of brain maturation in early childhood: Mathematical model fitting to assess age-dependent change of cerebral blood flow.
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Wong AM, Liu HL, Tsai ML, Schwartz ES, Yeh CH, Wang HS, Wu TW, and Lin CY
- Subjects
- Algorithms, Arteries diagnostic imaging, Brain physiology, Child, Preschool, Female, Gray Matter, Humans, Infant, Infant, Newborn, Male, Models, Theoretical, Perfusion, Regression Analysis, Retrospective Studies, Software, Brain diagnostic imaging, Cerebrovascular Circulation, Image Processing, Computer-Assisted methods, Magnetic Resonance Imaging, Spin Labels
- Abstract
Purpose: To determine the trajectory of age-dependent cerebral blood flow (CBF) change in infants and young children by fitting mathematical models to the imaging data., Methods: In this retrospective study, we reviewed the arterial spin-labeling imaging studies of 49 typically developing infants and young children at postmenstrual age (PMA) ranging from 38 to 194 weeks. All patients had normal structural MR imaging. Coregistration and gray matter segmentation were performed to extract whole-brain CBF values. Regional CBF values were obtained using manual region-of-interest placement. Curve estimation regression procedures with the corrected Akaike information criterion (AICc) were performed to determine the mathematical model best fitting the relationship between the CBF (whole-brain and regional measurements) and PMA of the patients., Results: Whole-brain CBF trajectory was best fitted by a cubic model (AICc = 215.95; R
2 = 0.566; P < .001). Whole-brain CBF at 1, 6, 12, and 24 months was estimated to be 36, 52, 58, and 55 mL/100 g/min, respectively. Regional CBF trajectory was also best fitted by a cubic model in the frontal (AICc = 233.63; R2 = 0.442; P < .001), parietal (AICc = 229.18; R2 = 0.614; P < .001), basal ganglion (AICc = 239.39; R2 = 0.178; P = .043), temporal (AICc = 236.01; R2 = 0.441; P < .001), and occipital (AICc = 236.46; R2 = 0.475; P < .001) regions., Conclusions: In early childhood, the trajectory of CBF change was nonlinear and best fitted by the cubic model for the whole brain and all brain regions., (Copyright © 2019 Elsevier Inc. All rights reserved.)- Published
- 2019
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23. A Neuropsychologist's Odyssey: Lyric Experimentation Breathes Life Into Loss.
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Schwartz ES
- Published
- 2019
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24. A retrospective study of the impact of supraglottic airway devices on the appearance of neck masses in children undergoing serial magnetic resonance imaging.
- Author
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Simpao AF, Obsekov V, Gálvez JA, Isserman RS, Rehman MA, and Schwartz ES
- Subjects
- Adolescent, Anesthesia, General instrumentation, Anesthesia, General methods, Female, Hemangioma diagnostic imaging, Humans, Intubation, Intratracheal instrumentation, Intubation, Intratracheal methods, Magnetic Resonance Imaging instrumentation, Male, Neurofibromatosis 1 diagnostic imaging, Retrospective Studies, Laryngeal Masks, Magnetic Resonance Imaging methods, Neck diagnostic imaging
- Abstract
Background: General anesthesia and sedation are used routinely for magnetic resonance imaging (MRI) studies in children to optimize image quality. Airway devices such as supraglottic airways (SGAs) can alter the appearance of cervical soft tissue regions on an MRI and increase the risk of misdiagnosis. This phenomenon has not been well described in vivo., Aims: We conducted this retrospective study to determine how often SGAs affected the appearance of neck masses in children who received multiple anesthetics for MRIs with and without an SGA., Methods: We retrieved data on children 17 years old and younger who had multiple MRIs between January 2005 and January 2015. Inclusion criteria were patients with neck masses who had a SGA for at least one MRI and either a natural airway or endotracheal tube (ETT) for another MRI. We reviewed MRI images and imaging reports to determine if SGAs affected the appearance of neck masses., Results: Twelve of the 921 patients who received anesthesia for neck MRIs during the study period met the inclusion criteria. SGAs affected the appearance of the neck mass in 11 of the 12 patients., Conclusions: Supraglottic airways can significantly alter the appearance of neck masses in children undergoing MRIs and affect radiologists' ability to assess those masses. Communication with the radiologist prior to the induction of anesthesia is crucial when using supraglottic devices in this patient population. It may be more prudent to use a different airway device and/or anesthetic technique when MRIs of these neck masses are undertaken., (© 2018 John Wiley & Sons Ltd.)
- Published
- 2018
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25. Perspectives on Neuroradiology Medical Expert Testimony: Fact and Fiction.
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Yousem DM, Zoarski GH, Mark AS, and Schwartz ES
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- Humans, Expert Testimony, Malpractice legislation & jurisprudence, Neurology, Radiologists, Radiology
- Abstract
There are numerous misconceptions about serving as a medical malpractice expert witness. By maintaining an objective perspective based in the unbiased interpretation of the images provided (for both sides of the conflict), one can best serve society as a whole. Most cases for which a neuroradiology expert is recruited are the following: 1) not with the radiologist as a defendant, 2) resolved without court testimony, and 3) short-lived if frivolous. One can learn much about medicine, our nonradiology colleagues, and the litigation process by participating as an expert witness., (© 2018 by American Journal of Neuroradiology.)
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- 2018
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26. The Stroop test as a measure of performance validity in adults clinically referred for neuropsychological assessment.
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Erdodi LA, Sagar S, Seke K, Zuccato BG, Schwartz ES, and Roth RM
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- Adult, Executive Function, Female, Humans, Male, Middle Aged, Psychometrics, Reproducibility of Results, Sensitivity and Specificity, Neuropsychological Tests, Stroop Test
- Abstract
This study was designed to develop performance validity indicators embedded within the Delis-Kaplan Executive Function Systems (D-KEFS) version of the Stroop task. Archival data from a mixed clinical sample of 132 patients (50% male; M
Age = 43.4; MEducation = 14.1) clinically referred for neuropsychological assessment were analyzed. Criterion measures included the Warrington Recognition Memory Test-Words and 2 composites based on several independent validity indicators. An age-corrected scaled score ≤6 on any of the 4 trials reliably differentiated psychometrically defined credible and noncredible response sets with high specificity (.87-.94) and variable sensitivity (.34-.71). An inverted Stroop effect was less sensitive (.14-.29), but comparably specific (.85-90) to invalid performance. Aggregating the newly developed D-KEFS Stroop validity indicators further improved classification accuracy. Failing the validity cutoffs was unrelated to self-reported depression or anxiety. However, it was associated with elevated somatic symptom report. In addition to processing speed and executive function, the D-KEFS version of the Stroop task can function as a measure of performance validity. A multivariate approach to performance validity assessment is generally superior to univariate models. (PsycINFO Database Record, ((c) 2018 APA, all rights reserved).)- Published
- 2018
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27. Optimization of Aqueous Extraction from Kalanchoe pinnata Leaves to Obtain the Highest Content of an Anti-inflammatory Flavonoid using a Response Surface Model.
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Dos Santos Nascimento LB, de Aguiar PF, Leal-Costa MV, Coutinho MAS, Borsodi MPG, Rossi-Bergmann B, Tavares ES, and Costa SS
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- Animals, Anti-Inflammatory Agents pharmacology, Cell Survival drug effects, Chromatography, High Pressure Liquid, Flavonoids pharmacology, Macrophages drug effects, Mice, Spectrophotometry, Ultraviolet, Anti-Inflammatory Agents analysis, Flavonoids analysis, Kalanchoe chemistry, Models, Chemical, Plant Leaves chemistry
- Abstract
Introduction: The medicinal plant Kalanchoe pinnata is a phenolic-rich species used worldwide. The reports on its pharmacological uses have increased by 70% in the last 10 years. The leaves of this plant are the main source of an unusual quercetin-diglycosyl flavonoid (QAR, quercetin arabinopyranosyl rhamnopyranoside), which can be easily extracted using water. QAR possess a strong in vivo anti-inflammatory activity., Objective: To optimize the aqueous extraction of QAR from K. pinnata leaves using a three-level full factorial design., Material and Methods: After a previous screening design, time (x
1 ) and temperature (x2 ) were chosen as the two independent variables for optimization. Freeze-dried leaves were extracted with water (20% w/v), at 30°C, 40°C or 50°C for 5, 18 or 30 min. QAR content (determined by HPLC-DAD) and yield of extracts were analyzed. The optimized extracts were also evaluated for cytotoxicity., Results: The optimal heating times for extract yield and QAR content were similar in two-dimensional (2D) surface responses (between 12.8 and 30 min), but their optimal extraction temperatures were ranged between 40°C and 50°C for QAR content and 30°C and 38°C for extract yield. A compromise region for both parameters was at the mean points that were 40°C for the extraction temperature and 18 min for the total time., Conclusion: The optimized process is faster and spends less energy than the previous one (water; 30 min at 55°C); therefore is greener and more attractive for industrial purposes. This is the first report of extraction optimization of this bioactive flavonoid. Copyright © 2018 John Wiley & Sons, Ltd., (Copyright © 2018 John Wiley & Sons, Ltd.)- Published
- 2018
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28. Massive cortical reorganization is reversible following bilateral transplants of the hands: evidence from the first successful bilateral pediatric hand transplant patient.
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Gaetz W, Kessler SK, Roberts TPL, Berman JI, Levy TJ, Hsia M, Humpl D, Schwartz ES, Amaral S, Chang B, and Levin LS
- Abstract
In this repeated measures case study, we show that sensory deafferentation after limb amputation leads to changes in cortical somatotopic maps which are reversible after restoration of sensory input. Using magnetoencephalography (MEG), we observed in a child with bilateral hand transplants large-scale shifts in somatosensory lip cortical representation from anatomic hand area to anatomic face region. After recovery of tactile sensation in the digits, responses to finger stimulation were localized to orthotopic sensory cortex, but with atypical electrophysiologic features (amplitude and frequencies).
- Published
- 2017
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29. Anatomical features of the cervical spinal canal in Chiari I deformity with presyrinx: A case-control study.
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Gadde JA, Shah V, Liebo GB, Ringstad GA, Pomeraniec IJ, Bakke SJ, Fric R, Ksendzovsky A, Jane JA Jr, Schwartz ES, and Haughton V
- Subjects
- Arnold-Chiari Malformation pathology, Case-Control Studies, Cervical Vertebrae abnormalities, Child, Edema diagnostic imaging, Edema pathology, Encephalocele diagnostic imaging, Encephalocele pathology, Female, Humans, Male, Spinal Canal abnormalities, Spinal Canal diagnostic imaging, Spinal Cord abnormalities, Syringomyelia pathology, Arnold-Chiari Malformation diagnostic imaging, Cervical Vertebrae diagnostic imaging, Magnetic Resonance Imaging, Spinal Cord diagnostic imaging, Syringomyelia diagnostic imaging
- Abstract
Purpose The relationship between syringomyelia and presyrinx, characterized by edema in the spinal cord, has not been firmly established. Patients with syringomyelia have abnormal spinal canal tapering that alters cerebrospinal fluid flow dynamics, but taper ratios in presyrinx have never been reported. We tested the hypothesis that presyrinx patients have abnormal spinal canal tapering. Materials and methods At six medical institutions, investigators searched the PACS system for patients with Chiari I and spinal cord edema unassociated with tumor, trauma, or other evident cause. In each case taper ratios were calculated for C1 to C4 and C4 to C7. In two age- and gender-matched control groups, Chiari I patients with no syringomyelia and patients with normal MR scans, the same measurements were made. Differences between groups were tested for statistical significance with t tests. Results The study enrolled 21 presyrinx patients and equal numbers of matched Chiari I and normal controls. C4 to C7 taper ratios were positive and steeper in presyrinx patients than in the normal controls ( p = 0.04). The upper cervical spine, C1 to C4, tapered negatively in cases and controls without significant differences between the groups. The difference in degree of tonsillar herniation was statistically significant between presyrinx patients and Chiari I controls ( p = 0.01). Conclusions Presyrinx patients have greater than normal positive tapering in the lower cervical spine and greater degree of tonsillar herniation than the controls.
- Published
- 2017
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30. 18-month outcomes of heterologous bilateral hand transplantation in a child: a case report.
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Amaral S, Kessler SK, Levy TJ, Gaetz W, McAndrew C, Chang B, Lopez S, Braham E, Humpl D, Hsia M, Ferry KA, Xu X, Elder D, Lefkowitz D, Feudtner C, Thibaudeau S, Lin IC, Kovach SJ, Schwartz ES, Bozentka D, Carrigan R, Steinberg D, Kanchwala S, Zlotolow DA, Kozin S, Jensen FE, Bryant PR, Shaked A, Levine MH, and Levin LS
- Abstract
Background: Although heterologous vascular composite allotransplantation has become a burgeoning treatment option for adult amputees, there have been no successful cases previously reported in children. Here, we describe the surgical, immunological, and neurorehabilitation details with functional outcomes 18 months after heterologous bilateral hand and forearm transplantation in an 8-year-old child with quadrimembral amputations and a previous kidney transplant., Methods: 2 years of extensive preparation by medical and surgical teams preceded the hand-forearm transplantation of this child. The initial immunosuppressive protocol included thymoglobulin, tacrolimus, prednisone, and mycophenolate mofetil. In July, 2015, our vascularised composite allotransplantation team did the first bilateral hand and forearm transplantation in a child, an 8-year-old boy with previous living-related kidney transplantation. The surgery included four teams working simultaneously on the donor and recipient limbs, aided by customised cutting guides that aimed to reduce ischaemia time. Following an extended length of time in hospital, skin biopsies and close monitoring of renal function and drug concentrations occurred weekly for the first 3 months and were slowly tapered to monthly, and then quarterly. Skin biopsies were also done when tissue rejection was suspected. Paediatric-specific rehabilitation techniques were applied to promote patient engagement during rehabilitation. Progress was assessed by monthly sensory and motor function tests during routine clinic visits and with serial functional brain imaging studies, including structural brain MRI, magnetoencephalography and transcranial magnetic stimulation., Findings: The surgery lasted 10 h and 40 min. Vascular revision of the ulnar artery was required a few hours postoperatively. There were no further immediate postsurgical complications. Rejection episodes occurred throughout the first year but were reversed. An increase in serum creatinine led to the addition of sirolimus at 3 months after transplantation with concomitant reduction in tacrolimus targets. Sensibility to light touch was present by 6 months after transplantation. Intrinsic hand muscle innervation was present by 7-10 months after transplantation. At 18 months, the child had exceeded his previous adapted abilities. As of 18 months after transplantation surgery he is able to write and feed, toilet, and dress himself more independently and efficiently than he could do before transplantation. He remains on four immunosuppressive medications and functional neuroimaging studies have shown motor and somatosensory cortical reorganisation., Interpretation: Hand transplantation in a child can be surgically, medically, and functionally successful under carefully considered circumstances. Long-term data on the functional trajectory, neurological recovery, psychological sequelae, and the potential late effect of immunosuppression are still needed to support broader implementation of paediatric vascular composite allotransplantation., Funding: The Children's Hospital of Philadelphia., (Copyright © 2017 Elsevier Ltd. All rights reserved.)
- Published
- 2017
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31. Neuromagnetic responses to tactile stimulation of the fingers: Evidence for reduced cortical inhibition for children with Autism Spectrum Disorder and children with epilepsy.
- Author
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Gaetz W, Jurkiewicz MT, Kessler SK, Blaskey L, Schwartz ES, and Roberts TPL
- Subjects
- Child, Female, Fingers, Humans, Magnetoencephalography, Male, Physical Stimulation, Touch, Touch Perception physiology, Autism Spectrum Disorder physiopathology, Epilepsy physiopathology, Evoked Potentials, Somatosensory physiology, Somatosensory Cortex physiopathology
- Abstract
The purpose of this study was to compare somatosensory responses from a group of children with epilepsy and a group of children with autism spectrum disorder (ASD), with age matched TD controls. We hypothesized that the magnitude of the tactile "P50m" somatosensory response would be reduced in both patient groups, possibly due to reduced GABAergic signaling as has been implicated in a variety of previous animal models and in vivo human MRS studies. We observed significant (~ 25%) decreases in tactile P50m dipole moment values from the source localized tactile P50m response, both for children with epilepsy and for children with ASD. In addition, the latency of the tactile P50m peak was observed to be equivalent between TD and ASD groups but was significantly delayed in children with epilepsy by ~ 6 ms. Our data support the hypothesis of impaired GABAergic signaling in both children with ASD and children with epilepsy. Further work is needed to replicate these findings and directly relate them to both in vivo measures of GABA via e.g. magnetic resonance spectroscopy and psychophysical assessments of somatosensory function, and behavioral indices.
- Published
- 2017
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32. Reduced Radiation in Children Presenting to the ED With Suspected Ventricular Shunt Complication.
- Author
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Marchese RF, Schwartz ES, Heuer GG, Lavelle J, Huh JW, Bell LM, Luan X, and Zorc JJ
- Subjects
- Child, Critical Pathways, Female, Humans, Male, Radiation Dosage, Cerebrospinal Fluid Shunts adverse effects, Emergency Service, Hospital statistics & numerical data, Radiation Exposure prevention & control, Tomography, X-Ray Computed methods
- Abstract
Background: Ventricular shunt complications in children can be severe and life-threatening if not identified and treated in a timely manner. Evaluation for shunt obstruction is not without risk, including lifetime cumulative radiation as patients routinely receive computed tomography (CT) scans of the brain and shunt series (multiple radiographs of the skull, neck, chest, and abdomen)., Methods: A multidisciplinary team collaborated to develop a clinical pathway with the goal of standardizing the evaluation and management of patients with suspected shunt complication. The team implemented a low-dose CT scan, specifically tailored for the detection of hydrocephalus and discouraged routine use of shunt series with single-view radiographs used only when specifically indicated., Results: There was a reduction in the average CT effective dose (millisievert) per emergency department (ED) encounter of 50.6% (confidence interval, 46.0-54.9; P ≤ .001) during the intervention period. There was a significant reduction in the number of shunt surveys obtained per ED encounter, from 62.4% to 5.32% ( P < .01). There was no significant change in the 72-hour ED revisit rate or CT scan utilization rate after hospital admission. There were no reports of inadequate patient evaluations or serious medical events., Conclusions: A new clinical pathway has rapidly reduced radiation exposure, both by reducing the radiation dose of CT scans and eliminating or reducing the number of radiographs obtained in the evaluation of patients with ventricular shunts without compromising clinical care., Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2017 by the American Academy of Pediatrics.)
- Published
- 2017
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33. Brain Tumors in the Neonate.
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Shekdar KV and Schwartz ES
- Subjects
- Brain diagnostic imaging, Humans, Infant, Newborn, Magnetic Resonance Imaging methods, Tomography, X-Ray Computed methods, Brain Neoplasms diagnostic imaging, Neuroimaging methods
- Abstract
Brain tumors can develop in the prenatal and neonatal time periods. Neuroimaging studies are crucial for the early detection of prenatal and neonatal brain tumors. Imaging allows for characterization of morphology, as well as the detection of hydrocephalus, local invasion, and distant spread. The imaging features of the more common neonatal brain tumors, including teratomas, choroid plexus tumors, ATRTs, and neoplasm mimics are described., (Copyright © 2016 Elsevier Inc. All rights reserved.)
- Published
- 2017
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34. CVLT-II Forced Choice Recognition Trial as an Embedded Validity Indicator: A Systematic Review of the Evidence.
- Author
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Schwartz ES, Erdodi L, Rodriguez N, Ghosh JJ, Curtain JR, Flashman LA, and Roth RM
- Subjects
- Humans, Cognitive Dysfunction diagnosis, Malingering diagnosis, Neuropsychological Tests standards, Psychometrics instrumentation, Psychomotor Performance physiology
- Abstract
Objectives: The Forced Choice Recognition (FCR) trial of the California Verbal Learning Test, 2nd edition, was designed as an embedded performance validity test (PVT). To our knowledge, this is the first systematic review of classification accuracy against reference PVTs., Methods: Results from peer-reviewed studies with FCR data published since 2002 encompassing a variety of clinical, research, and forensic samples were summarized, including 37 studies with FCR failure rates (N=7575) and 17 with concordance rates with established PVTs (N=4432)., Results: All healthy controls scored >14 on FCR. On average, 16.9% of the entire sample scored ≤14, while 25.9% failed reference PVTs. Presence or absence of external incentives to appear impaired (as identified by researchers) resulted in different failure rates (13.6% vs. 3.5%), as did failing or passing reference PVTs (49.0% vs. 6.4%). FCR ≤14 produced an overall classification accuracy of 72%, demonstrating higher specificity (.93) than sensitivity (.50) to invalid performance. Failure rates increased with the severity of cognitive impairment., Conclusions: In the absence of serious neurocognitive disorder, FCR ≤14 is highly specific, but only moderately sensitive to invalid responding. Passing FCR does not rule out a non-credible presentation, but failing FCR rules it in with high accuracy. The heterogeneity in sample characteristics and reference PVTs, as well as the quality of the criterion measure across studies, is a major limitation of this review and the basic methodology of PVT research in general. (JINS, 2016, 22, 851-858).
- Published
- 2016
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35. Chronic Prostatitis Induces Bladder Hypersensitivity and Sensitizes Bladder Afferents in the Mouse.
- Author
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Schwartz ES, La JH, Young EE, Feng B, Joyce S, and Gebhart GF
- Subjects
- Animals, Blotting, Western, Chronic Disease, Cytokines biosynthesis, Cytokines genetics, Disease Models, Animal, Ganglia, Spinal pathology, Gene Expression Regulation, Immunohistochemistry, Male, Mice, Mice, Inbred C57BL, Polymerase Chain Reaction, Prostatitis diagnosis, Prostatitis genetics, RNA genetics, Urinary Bladder diagnostic imaging, Urinary Bladder Diseases diagnosis, Urinary Bladder Diseases genetics, Ganglia, Spinal metabolism, Prostatitis complications, Urinary Bladder innervation, Urinary Bladder Diseases etiology
- Abstract
Purpose: Chronic prostatitis/chronic pelvic pain syndrome causes symptoms that include the frequent and urgent need to urinate, pain or burning during urination and pain radiating to the back, abdomen and/or colorectum. These bladder symptoms suggest that chronic prostatitis/chronic pelvic pain syndrome is associated with sensitization of adjacent organs, termed cross-organ sensitization. The objective of this study was to determine the extent of 1) changes in immunomodulatory mediators in the prostate and bladder after inflammation of the prostate and 2) bladder function and bladder afferent sensitization., Materials and Methods: Prostate and bladder histology, immunohistochemistry and expression of immunomodulatory targets were examined weekly after zymosan or vehicle was injected in the dorsal lobe of the mouse prostate. Cystometry, bladder and bladder afferent sensitivity were also assessed weekly., Results: Prostate inflammation induced significant up-regulation in proinflammatory and anti-inflammatory cytokines TNF-α (tumor necrosis factor-α) and IL-10 (interleukin-10), growth factor NGF (nerve growth factor), and T-lymphocyte markers FoxP3, CD4 and CD8 in the prostate and the bladder. Notably, prostatitis significantly increased urinary voiding frequency, induced hypersensitivity to bladder distension and sensitized bladder afferents. We also examined sensory (afferent) co-innervation by injecting retrograde tracers DiI and Fast Blue in the bladder wall and the prostate, respectively. This showed that a significant proportion (approximately 17%) of dorsal root ganglion afferent somata contained tracers from the bladder and the prostate., Conclusions: These observations support an afferent contribution to chronic prostatitis/chronic pelvic pain syndrome and cross-organ sensitization from prostate to bladder., (Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)
- Published
- 2016
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36. Roles of isolectin B4-binding afferents in colorectal mechanical nociception.
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La JH, Feng B, Kaji K, Schwartz ES, and Gebhart GF
- Subjects
- Afferent Pathways injuries, Afferent Pathways physiology, Amidines metabolism, Analysis of Variance, Animals, Biophysical Phenomena, Calcitonin Gene-Related Peptide metabolism, Colon physiology, In Vitro Techniques, Lectins toxicity, Male, Mice, Mice, Inbred C57BL, Neurons drug effects, Phosphopyruvate Hydratase metabolism, Physical Stimulation, Ribosome Inactivating Proteins, Type 1 toxicity, Saporins, TRPV Cation Channels metabolism, Colon innervation, Ganglia, Spinal pathology, Lectins metabolism, Neurons metabolism, Visceral Pain pathology
- Abstract
Isolectin B4-binding (IB4+) dorsal root ganglion (DRG) neurons are distinct from peptidergic DRG neurons in their terminal location in the spinal cord and respective contributions to various classes and modalities of nociception. In DRG neurons innervating the mouse colon (c-DRG neurons), the reported proportion of IB4+ population is inconsistent across studies, and little is known regarding their role in colorectal mechanonociception. To address these issues, in C57BL/6J mice, we quantified IB4+ binding after labeling c-DRG neurons with Fast Blue and examined functional consequences of ablating these neurons by IB4-conjugated saporin. Sixty-one percent of Fast Blue-labeled neurons in the L6 DRG were IB4+, and 95% of these IB4+ c-DRG neurons were peptidergic. Intrathecal administration of IB4-conjugated saporin reduced the proportion of IB4+ c-DRG neurons to 37%, which was due to the loss of c-DRG neurons showing strong to medium IB4+ intensity; c-DRG neurons with weak IB4+ intensity were spared. However, this loss altered neither nociceptive behaviors to colorectal distension nor the relative proportions of stretch-sensitive colorectal afferent classes characterized by single-fiber recordings. These findings demonstrate that more than 1 half of viscerosensory L6 c-DRG neurons in C57BL/6J mouse are IB4+ and suggest, in contrast to the reported roles of IB4+/nonpeptidergic neurons in cutaneous mechanonociception, c-DRG neurons with strong-to-medium IB4+ intensity do not play a significant role in colorectal mechanonociception.
- Published
- 2016
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37. The Spaces Between.
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Schwartz ES
- Subjects
- Humans, Dreams psychology, Memory
- Published
- 2016
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38. Certificate in Reverse Psychology probably not worth it.
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Schwartz ES
- Subjects
- Humans, Certification, Psychology
- Published
- 2015
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39. Induction of wound-periderm-like tissue in Kalanchoe pinnata (Lam.) Pers. (Crassulaceae) leaves as a defence response to high UV-B radiation levels.
- Author
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Nascimento LB, Moreira Ndos S, Leal-Costa MV, Costa SS, and Tavares ES
- Subjects
- Kalanchoe growth & development, Plant Leaves growth & development, Plant Leaves immunology, Kalanchoe immunology, Kalanchoe radiation effects, Plant Immunity, Plant Leaves radiation effects, Ultraviolet Rays
- Abstract
Background and Aims: UV-B radiation can be stressful for plants and cause morphological and biochemical changes. Kalanchoe pinnata is a CAM leaf-succulent species distributed in hot and dry regions, and is rich in flavonoids, which are considered to be protective against UV-B radiation. This study aims to verify if K. pinnata has morphological or anatomical responses as a strategy in response to high UV-B levels., Methods: Kalanchoe pinnata plants of the same age were grown under white light (control) or white light plus supplemental UV-B radiation (5 h d(-1)). The plants were treated with the same photoperiod, photosynthetically active radiation, temperature and daily watering system. Fragments of the middle third of the leaf blade and petiole were dehydrated and then embedded in historesin and sectioned in a rotary microtome. Sections were stained with toluidine blue O and mounted in Entellan®. Microchemical analyses by optical microscopy were performed on fresh material with Sudan III, Sudan IV and phloroglucinol, and analysed using fluorescence microscopy., Key Results: Supplemental UV-B radiation caused leaf curling and the formation of brown areas on the leaves. These brown areas developed into a protective tissue on the adaxial side of the leaf, but only in directly exposed regions. Anatomically, this protective tissue was similar to a wound-periderm, with outer layer cell walls impregnated with suberin and lignin., Conclusions: This is the first report of wound-periderm formation in leaves in response to UV-B radiation. This protective tissue could be important for the survival of the species in desert regions under high UV-B stress conditions., (© The Author 2015. Published by Oxford University Press on behalf of the Annals of Botany Company. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)
- Published
- 2015
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40. Congenital spine anomalies: the closed spinal dysraphisms.
- Author
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Schwartz ES and Rossi A
- Subjects
- Female, Humans, Infant, Newborn, Male, Image Enhancement methods, Magnetic Resonance Imaging methods, Neural Tube Defects pathology, Spinal Dysraphism pathology, Spine abnormalities, Spine pathology
- Abstract
The term congenital spinal anomalies encompasses a wide variety of dysmorphology that occurs during early development. Familiarity with current terminology and a practical, clinico-radiologic classification system allows the radiologist to have a more complete understanding of malformations of the spine and improves accuracy of diagnosis when these entities are encountered in practice.
- Published
- 2015
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41. Metaphors and medically unexplained symptoms.
- Author
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Schwartz ES
- Subjects
- Anxiety etiology, Humans, Psychophysiology, Metaphor, Somatoform Disorders diagnosis
- Published
- 2015
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42. Nociceptive and inflammatory mediator upregulation in a mouse model of chronic prostatitis.
- Author
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Schwartz ES, Xie A, La JH, and Gebhart GF
- Subjects
- Animals, Behavior, Animal, Chronic Disease, Disease Models, Animal, Ganglia, Spinal drug effects, Inflammation chemically induced, Inflammation complications, Inflammation Mediators metabolism, Interleukin-10 metabolism, Male, Mice, Nerve Growth Factor metabolism, Pain etiology, Pain psychology, Potassium Channels, Tandem Pore Domain metabolism, Prostate pathology, Prostatitis chemically induced, Prostatitis complications, Prostatitis physiopathology, Receptors, Purinergic P2X metabolism, Tryptases metabolism, Up-Regulation, Zymosan toxicity, Inflammation immunology, Nociceptors metabolism, Pain metabolism, Prostate immunology, Prostate innervation, Prostatitis immunology
- Abstract
Chronic nonbacterial prostatitis, characterized by genitourinary pain in the pelvic region in the absence of an identifiable cause, is common in adult males. Surprisingly, the sensory innervation of the prostate and mediators that sensitize its innervation have received little attention. We thus characterized a mouse model of chronic prostatitis, focusing on the prostate innervation and how organ inflammation affects gene expression of putative nociceptive markers in prostate afferent somata in dorsal root ganglia (DRG) and mediators in the prostate. Retrograde tracing (fast blue) from the prostate revealed that thoracolumbar and lumbosacral DRG are the principal sources of somata of prostate afferents. Nociceptive markers (eg, transient receptor potential, TREK, and P2X channels) were upregulated in fast blue-labeled thoracolumbar and lumbosacral somata for up to four weeks after inflaming the prostate (intraprostate injection of zymosan). Prostatic inflammation was evident histologically, by monocyte infiltration and a significant increase in mast cell tryptase activity 14, 21, and 28 days after zymosan injection. Interleukin 10 and NGF were also significantly upregulated in the prostate throughout the 4 weeks of inflammation. Open-field pain-related behaviors (eg, rearing) were unchanged in prostate-inflamed mice, suggesting the absence of ongoing nociception, but withdrawal thresholds to lower abdominal pressure were significantly reduced. The increases in IL-10, mast cell tryptase, and NGF in the inflamed prostate were cotemporaneous with reduced thresholds to probing of the abdomen and upregulation of nociceptive markers in DRG somata innervating the prostate. The results provide insight and direction for the study of mechanisms underlying pain in chronic prostatitis., Competing Interests: There were no financial or other relationships that led to a conflict of interest.
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- 2015
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43. Ultraviolet-B radiation effects on phenolic profile and flavonoid content of Kalanchoe pinnata.
- Author
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Nascimento LBDS, Leal-Costa MV, Menezes EA, Lopes VR, Muzitano MF, Costa SS, and Tavares ES
- Subjects
- Antioxidants analysis, Antioxidants chemistry, Chromatography, High Pressure Liquid, Chromatography, Thin Layer, Flavonoids analysis, Kalanchoe chemistry, Kalanchoe metabolism, Phenols analysis, Plant Extracts chemistry, Plant Leaves chemistry, Plant Leaves metabolism, Plant Leaves radiation effects, Flavonoids chemistry, Kalanchoe radiation effects, Phenols chemistry, Ultraviolet Rays
- Abstract
Ultraviolet-B radiation is an important abiotic factor that can stimulate the production of secondary metabolites, including polyphenolic compounds. Kalanchoe pinnata (Crassulaceae) is a medicinal plant popularly used in Brazil for treating wounds and inflammation. This species is rich in phenolic compounds, which could account for some of its biological activities, including antileishmanial, antihypertensive and antibacterial properties. We investigated the effects of supplemental UV-B radiation on the phenolic profile, antioxidant activity and total flavonoid content of leaves of K. pinnata. Plants were grown under white light (W - control) and supplemental UV-B radiation (W+UVB). Supplemental UV-B radiation enhanced the total flavonoid content of the leaf extracts, without affecting the antioxidant activity or yield of extracts. Analysis by TLC and HPLC of W and W+UVB leaf extracts revealed quantitative and qualitative differences in their phenolic profiles. W+UVB extracts contained a higher diversity of phenolic compounds and a larger amount of quercitrin, an important bioactive flavonoid of this species. This is the first report of the use of ImageJ® program to analyze a TLC visualized by spraying with NP-PEG reagent. UV-B radiation is proposed as a supplemental light source in K. pinnata cultivation in order to improve its flavonoid composition., (Copyright © 2015 Elsevier B.V. All rights reserved.)
- Published
- 2015
- Full Text
- View/download PDF
44. Novel method to assess axonal excitability using channelrhodopsin-based photoactivation.
- Author
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Zhu Y, Feng B, Schwartz ES, Gebhart GF, and Prescott SA
- Subjects
- Animals, Cells, Cultured, Channelrhodopsins, Light, Male, Mice, Mice, Inbred C57BL, Mice, Inbred Strains, Action Potentials physiology, Axons physiology, Neural Conduction physiology, Optogenetics methods, Photic Stimulation methods
- Abstract
Measuring the excitability of individual axons is complicated by the prohibitive difficulty in obtaining intracellular recordings. Here, we present an innovative methodology that enables local excitability to be measured anywhere in a channelrhodopsin (ChR2)-expressing neuron. The approach hinges on activating ChR2 in a spatially and temporally precise manner while recording the resulting spike train from a remote site. We validated this approach in primary afferent neurons (PANs). Initial encoding of somatosensory stimuli relies on transduction of the physical stimulus into a receptor potential and transformation of the receptor potential into a spike train; the transformation process depends on the excitability of the most distal PAN endings but, as explained above, is extraordinarily difficult to study in situ using traditional methods. Using ChR2-based photoactivation, we show 1) that excitability differs between the distal endings and more proximal portions of PAN axons, 2) that the transformation process differs between PANs, and 3) that the transformation process is directly affected by inflammation. Beyond presenting an innovative method by which to study axonal excitability, this study has validated its utility in helping to decipher the earliest stages of somatosensory encoding., (Copyright © 2015 the American Physiological Society.)
- Published
- 2015
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45. Utility of CT-compatible EEG electrodes in critically ill children.
- Author
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Abend NS, Dlugos DJ, Zhu X, and Schwartz ES
- Subjects
- Adolescent, Adult, Artifacts, Child, Child, Preschool, Cohort Studies, Critical Illness, Equipment Design, Female, Humans, Infant, Male, Plastics, Reproducibility of Results, Retrospective Studies, Critical Care, Electroencephalography, Tomography, X-Ray Computed
- Abstract
Background: Electroencephalographic monitoring is being used with increasing frequency in critically ill children who may require frequent and sometimes urgent brain CT scans. Standard metallic disk EEG electrodes commonly produce substantial imaging artifact, and they must be removed and later reapplied when CT scans are indicated., Objective: To determine whether conductive plastic electrodes caused artifact that limited CT interpretation., Material and Methods: We describe a retrospective cohort of 13 consecutive critically ill children who underwent 17 CT scans with conductive plastic electrodes during 1 year. CT images were evaluated by a pediatric neuroradiologist for artifact presence, type and severity., Results: All CT scans had excellent quality images without artifact that impaired CT interpretation except for one scan in which improper wire placement resulted in artifact., Conclusion: Conductive plastic electrodes do not cause artifact limiting CT scan interpretation and may be used in critically ill children to permit concurrent electroencephalographic monitoring and CT imaging.
- Published
- 2015
- Full Text
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46. A patient advocacy program established through an interprofessional student-run free clinic.
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Schwartz ES, Baugh JJ, Honsky J, and Luebbers E
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- Humans, Ohio, Ambulatory Care Facilities, Interprofessional Relations, Medically Underserved Area, Patient Advocacy, Program Development, Students, Health Occupations
- Abstract
This report describes a student-run free clinic model that exposes medical, nursing, and social work students to interprofessional care of the underserved early in their training. As a result of a new partnership with social work students, a patient advocacy program was established, which helped patients apply for an expanded Medicaid program.
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- 2015
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47. Diagnostic features of myelomeningocele: the role of ultrafast fetal MRI.
- Author
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Mirsky DM, Schwartz ES, and Zarnow DM
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- Female, Fetal Therapies, Humans, Pregnancy, Magnetic Resonance Imaging methods, Neural Tube Defects diagnosis, Prenatal Diagnosis methods
- Abstract
Fetal magnetic resonance imaging (MRI) is a useful adjunct to ultrasound in the evaluation of neural tube defects. The development of ultrafast imaging techniques has contributed to the increasing clinical use of fetal MRI. This review summarizes the utility, safety and technical aspects of fetal MRI and the role it plays in the evaluation of myelomeningocele. Emphasis is placed on the benefit of fetal MRI as it pertains to presurgical planning and perinatal management., (© 2014 S. Karger AG, Basel.)
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- 2015
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48. TRPA1 mediates bladder hyperalgesia in a mouse model of cystitis.
- Author
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DeBerry JJ, Schwartz ES, and Davis BM
- Subjects
- Animals, Cyclophosphamide poisoning, Cystitis, Interstitial chemically induced, Disease Models, Animal, Mice, TRPA1 Cation Channel, Cystitis, Interstitial metabolism, Hyperalgesia metabolism, TRPV Cation Channels metabolism, Transient Receptor Potential Channels metabolism, Urinary Bladder metabolism
- Abstract
Urinary bladder pain is a primary symptom associated with interstitial cystitis/painful bladder syndrome. We used systemic injections of cyclophosphamide (CYP), an alkylating antineoplastic agent, to induce cystitis and examine the roles of 2 channels previously demonstrated to be required for inflammatory visceral hyperalgesia: transient receptor potential vanilloid-1 (TRPV1) and ankyrin-1 (TRPA1). Injection of CYP (100 mg/kg, i.p.) every other day for 5 days was accompanied by bladder edema and urothelial ulceration, but without significant plasma extravasation or infiltration of neutrophils. Toluidine blue staining showed a significant increase in the number of degranulated bladder mast cells after CYP treatment. Despite this mild pathology, CYP-treated mice exhibited bladder hyperalgesia 1 day after the final injection that persisted 7 days later. Although many previous studies of visceral hyperalgesia have reported changes in dorsal root ganglion neuron TRPV1 expression and/or function, we found no change in bladder afferent TRPV1 expression or sensitivity on the basis of the percentage of bladder afferents responsive to capsaicin, including at submaximal concentrations. In contrast, the percentage of bladder afferents expressing functional TRPA1 protein (i.e., those responsive to mustard oil) increased ∼2.5-fold 1 day after CYP treatment, and remained significantly elevated 7 days later. Moreover, bladder hyperalgesia was reversed by acute treatment with the TRPA1 antagonist HC-030031 (300 mg/kg, i.p.). Our results indicate that CYP-induced bladder hyperalgesia can be induced without robust inflammation or changes in primary afferent TRPV1. However, significant changes were observed in TRPA1 expression, and blockade of TRPA1 alleviated CYP-induced bladder hyperalgesia., (Copyright © 2014 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.)
- Published
- 2014
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49. Correlation of prenatal and postnatal MRI findings in schizencephaly.
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Nabavizadeh SA, Zarnow D, Bilaniuk LT, Schwartz ES, Zimmerman RA, and Vossough A
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- Female, Humans, Infant, Newborn, Male, Reproducibility of Results, Sensitivity and Specificity, Magnetic Resonance Imaging methods, Prenatal Diagnosis methods, Schizencephaly embryology, Schizencephaly pathology
- Abstract
Background and Purpose: Schizencephaly is a rare malformation of the brain characterized by a gray matter-lined defect extending from the pial surface to the lateral ventricles. The purpose of this study was to correlate imaging findings of schizencephaly and associated anomalies on fetal and postnatal MR imaging and assess possible changes that may occur from the prenatal-to-postnatal state., Materials and Methods: A retrospective review of subjects with schizencephaly who had both pre- and postnatal MR imaging was performed. Subject age, cleft type, number, location, and features of the defects and associated anomalies were recorded. Normalized dimensions of the defect and ipsilateral ventricle were measured and correlated to changes in the clefts between pre- and postnatal imaging., Results: Ten subjects with 18 clefts (8 bilateral) were included. Most defects (83%) were open on prenatal MR imaging, but 47% of those were found to have subsequently closed on postnatal imaging. Evidence of prior hemorrhage was seen in 83%. Prenatal MR imaging detected all cases of an absent septum pellucidum but detected a fraction of gross polymicrogyria and missed all cases of optic nerve hypoplasia. The normalized ipsilateral ventricular and inner and middle width dimensions of the defects were significantly decreased at postnatal imaging (P < .05). The widths of the defects, ventricular width, and presence of hemorrhage were not predictors of closure of prenatally diagnosed open defects (P > .05)., Conclusions: In our series, nearly half of prenatally open schizencephaly defects had closed on postnatal imaging. Prenatal MR imaging was only able to demonstrate some of the associated anomalies., (© 2014 by American Journal of Neuroradiology.)
- Published
- 2014
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50. Artemin growth factor increases nicotinic cholinergic receptor subunit expression and activity in nociceptive sensory neurons.
- Author
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Albers KM, Zhang XL, Diges CM, Schwartz ES, Yang CI, Davis BM, and Gold MS
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- Animals, Female, Ganglia, Spinal cytology, Glial Cell Line-Derived Neurotrophic Factor Receptors metabolism, Hexamethonium therapeutic use, Hyperalgesia drug therapy, Hyperalgesia physiopathology, Male, Mecamylamine therapeutic use, Membrane Potentials drug effects, Membrane Potentials genetics, Mice, Mice, Inbred C57BL, Mice, Transgenic, Nerve Tissue Proteins genetics, Nerve Tissue Proteins toxicity, Nicotinic Antagonists therapeutic use, Nociceptors drug effects, Protein Subunits genetics, Protein Subunits metabolism, Receptors, Nicotinic genetics, Skin innervation, Skin pathology, Gene Expression Regulation drug effects, Gene Expression Regulation genetics, Nerve Tissue Proteins pharmacology, Nociceptors physiology, Receptors, Nicotinic metabolism, Trigeminal Ganglion pathology
- Abstract
Background: Artemin (Artn), a member of the glial cell line-derived growth factor (GDNF) family, supports the development and function of a subpopulation of peptidergic, TRPV1-positive sensory neurons. Artn (enovin, neublastin) is elevated in inflamed tissue and its injection in skin causes transient thermal hyperalgesia. A genome wide expression analysis of trigeminal ganglia of mice that overexpress Artn in the skin (ART-OE mice) showed elevation in nicotinic acetylcholine receptor (nAChR) subunits, suggesting these ion channels contribute to Artn-induced sensitivity. Here we have used gene expression, immunolabeling, patch clamp electrophysiology and behavioral testing assays to investigate the link between Artn, nicotinic subunit expression and thermal hypersensitivity., Results: Reverse transcriptase-PCR validation showed increased levels of mRNAs encoding the nAChR subunits α3 (13.3-fold), β3 (4-fold) and β4 (7.7-fold) in trigeminal ganglia and α3 (4-fold) and β4 (2.8-fold) in dorsal root ganglia (DRG) of ART-OE mice. Sensory ganglia of ART-OE mice had increased immunoreactivity for nAChRα3 and exhibited increased overlap in labeling with GFRα3-positive neurons. Patch clamp analysis of back-labeled cutaneous afferents showed that while the majority of nicotine-evoked currents in DRG neurons had biophysical and pharmacological properties of α7-subunit containing nAChRs, the Artn-induced increase in α3 and β4 subunits resulted in functional channels. Behavioral analysis of ART-OE and wildtype mice showed that Artn-induced thermal hyperalgesia can be blocked by mecamylamine or hexamethonium. Complete Freund's adjuvant (CFA) inflammation of paw skin, which causes an increase in Artn in the skin, also increased the level of nAChR mRNAs in DRG. Finally, the increase in nAChRs transcription was not dependent on the Artn-induced increase in TRPV1 or TRPA1 in ART-OE mice since nAChRs were elevated in ganglia of TRPV1/TRPA1 double knockout mice., Conclusions: These findings suggest that Artn regulates the expression and composition of nAChRs in GFRα3 nociceptors and that these changes contribute to the thermal hypersensitivity that develops in response to Artn injection and perhaps to inflammation.
- Published
- 2014
- Full Text
- View/download PDF
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