18 results on '"Chen CV"'
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2. Taiwan.
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Chen, CV and Peng, Josephine
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TAX laws ,TAX administration & procedure ,LIABILITIES (Accounting) ,INSTITUTIONAL investments ,SECURITIES lending ,TREATIES - Abstract
This article explains the application of the beneficial owner principle in Taiwan's tax rulings. The beneficial owner principle is not specifically prescribed under the Income Tax Act, but tax authorities often adopt this principle in assessing tax liabilities. The tax rulings issued by the Ministry of Finance (MOF) on foreign institutional investors (FINI) and securities lending and borrowing transactions indicate the MOF application of this principle in tax assessments. Taiwan has executed tax treaties with 16 jurisdictions, including Australia, Belgium, Denmark, Gambia, Indonesia, Macedonia, Malaysia, the Netherlands, New Zealand, Senegal, Singapore, South Africa, Swaziland, Sweden, Great Britain and Vietnam.
- Published
- 2007
3. Diagnostic Utility of Deeper Level Tissue Sections of Negative Peritoneal Biopsies for Clinically Suspected Endometriosis.
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Chen CV, Orlando MS, Abel MK, Opoku-Anane J, and Rabban JT
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Definitive diagnosis of endometriosis is established by histologic confirmation in tissue from surgically visualized lesions; however, the diagnostic sensitivity of this approach varies widely. We hypothesized that incomplete tissue block sampling may contribute to false-negative diagnosis, particularly if the focus of endometriosis in the tissue section is scant. This study defined the diagnostic value of deeper level tissue sections in cases in which none of the specimen parts contained endometriosis on the initial tissue sections, using the World Health Organization essential criteria for diagnosis of endometriosis (presence of endometrial glands and endometrial stroma). Among 135 patients who underwent surgery for suspected endometriosis by a single surgeon at an academic institution from 2015 to 2019, the initial tissue sections resulted in a diagnosis of endometriosis in 73.3% (99/135), at an average diagnostic yield of 5.9 slides per diagnosis of endometriosis. An additional 9 patients were diagnosed with endometriosis by deeper level tissue sections, increasing the diagnostic rate to 80% (108/135). This 6.7% gain in the diagnostic rate came at an increase in resource utilization, with an overall overage diagnostic yield of 9.8 slides per diagnosis of endometriosis. Overall, 8.3% of patients had a false-negative diagnosis on the initial tissue sections. When extrapolated to a population level, the number of patients potentially affected by this source of false-negative diagnosis and the implications for patients merit consideration of the use of deeper level sections if none of the initial sections of any of the specimens contains endometriosis., Competing Interests: J.T.R. reports that his spouse receives salary and stock options from Merck & Co. The remaining authors declare no conflict of interest., (Copyright © 2024 by the International Society of Gynecological Pathologists.)
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- 2024
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4. Utility and performance of cell blocks in cerebrospinal fluid cytology: Experience at two teaching hospitals.
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Yoon H, Chen CV, Krishnan V, Grochowski J, Iezza G, Vohra P, Balassanian R, and Greenland NY
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- Humans, Retrospective Studies, Female, Male, Middle Aged, Adult, Aged, Cerebrospinal Fluid cytology, Aged, 80 and over, Young Adult, Adolescent, Cytodiagnosis methods, Hospitals, Teaching
- Abstract
Background: Cytology cell blocks (CBs) are not routinely made for cerebrospinal fluid (CSF) specimens. The goal of this study was to identify when CSF CB preparation improves diagnostic performance., Materials and Methods: Under institutional review board approval, a retrospective review of CSF cytology cases was conducted at a tertiary university-based hospital and an affiliated county hospital. Patient history, CSF volume, final diagnosis, use of stains, and whether the CB was contributory was determined from the cytopathology report. CSF nucleated cell count data was obtained from the medical record., Results: A total of 69 CSF specimens with CBs from January 2006 to March 2023 were identified from 61 patients. The median CSF volume was 8 mL (interquartile range, 4-13 mL; range, 1-800 mL), with immunohistochemical stains performed on 29 (42%) cases. Per cytology report, CB was contributory in 23 cases (33%), not contributory in 34 cases (49%), and not discussed in 12 cases (17%). The median volume was 8 mL for cases in which CB was contributory, not contributory, or not discussed. There was no difference in average nucleated cell counts between cases in which CB was contributory versus not contributory (73.9 vs. 40.0, p = .175)., Conclusions: CBs for CSF samples were contributory in a subset (33%) of cases. The authors were unable to identify any specific pre-analytic factors, including specimen volume and average nucleated cell counts, for cases in which CB was contributory. Further evaluation is needed to identify if there are scenarios in which CSF CBs should be routinely prepared., (© 2024 The Authors. Cancer Cytopathology published by Wiley Periodicals LLC on behalf of American Cancer Society.)
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- 2024
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5. A case series of thyroid fine needle aspiration biopsies diagnosed as follicular neoplasm with oncocytic features.
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Chen CV, Krishnan V, and Greenland NY
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- Humans, Adenoma, Oxyphilic pathology, Adenoma, Oxyphilic diagnosis, Biopsy, Fine-Needle, Oxyphil Cells pathology, Thyroid Gland pathology, Adenocarcinoma, Follicular pathology, Adenocarcinoma, Follicular diagnosis, Thyroid Neoplasms pathology, Thyroid Neoplasms diagnosis
- Abstract
Oncocytic lesions of the thyroid are a heterogeneous group encompassing nonneoplastic and neoplastic entities ranging from benign to malignant and have traditionally been classified as separate entities in thyroid pathology. To illustrate the diversity of these thyroid lesions, we describe three cases of fine needle aspiration biopsies (FNAB) diagnosed as Bethesda Category IV: Follicular neoplasm, oncocytic type, under the 2017 Bethesda System for Reporting Thyroid Cytopathology (TBSRTC), with ThyroSeq v3 molecular testing and subsequent surgical excision., (© 2024 The Authors. Diagnostic Cytopathology published by Wiley Periodicals LLC.)
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- 2024
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6. Positive NKX3.1 as a diagnostic pitfall for prostate cancer in extramammary Paget's disease of genitourinary sites.
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Chen CV, Francois RA, Mully TW, Sangoi A, LeBoit PE, Simko JP, and Chan E
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- Male, Humans, Paget Disease, Extramammary diagnosis, Prostatic Neoplasms diagnosis, Genital Neoplasms, Male
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- 2024
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7. Having fun! The role of workplace fun in enhancing employees' creative behaviors in Chinese work settings.
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Yang FR and Chen CV
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Digital platforms and tech giants have led to a rapid shift in values and traditional ways of working. Although "diligence" has long been essential for work success and promotion, employees in modern companies are reluctant to blindly follow this attitude. Many well-known Western companies, such as Facebook and Google, see fun in the workplace as conducive to productivity and creative behavior. We investigated the associations of fun at work with experienced fun, employees' creative behavior, managers' support for fun, and trust in a Chinese context using different scales. Discriminant validity was confirmed by confirmatory factor analysis. A total of 508 workers from Taiwan and mainland China participated in the study and completed questionnaires. A key finding was that fun at work was positively related to employees' creative behavior. In addition, moderators of managerial support for fun and trust between the workplace and experienced fun were confirmed. These results can serve as a reference for Chinese managers who want to encourage creative behaviors and prevent negative behaviors in the workplace. In practice, results suggest that fun should be allowed more in the workplace because it could contribute to positive outcomes. However, managers should create a workplace that is fun, allows for creativity, and at the same time leads to high productivity., Competing Interests: The authors declare no conflict of interest., (© 2023 The Authors. Published by Elsevier Ltd.)
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- 2023
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8. Differential immunohistochemical and molecular profiling of conventional and aggressive components of chromophobe renal cell carcinoma: pitfalls for diagnosis.
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Chen CV, Croom NA, Simko JP, Stohr BA, and Chan E
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- Adult, Aged, Biopsy, Carcinoma, Renal Cell chemistry, Carcinoma, Renal Cell genetics, Carcinoma, Renal Cell secondary, DNA Mutational Analysis, Databases, Factual, Female, Genetic Heterogeneity, High-Throughput Nucleotide Sequencing, Humans, Kidney Neoplasms chemistry, Kidney Neoplasms genetics, Kidney Neoplasms pathology, Male, Middle Aged, Mutation, Predictive Value of Tests, Reproducibility of Results, Retrospective Studies, Biomarkers, Tumor analysis, Biomarkers, Tumor genetics, Carcinoma, Renal Cell diagnosis, Immunohistochemistry, Kidney Neoplasms diagnosis, Molecular Diagnostic Techniques
- Abstract
Chromophobe renal cell carcinoma (ChRCC) is a relatively rare subtype of RCC with a characteristic histologic appearance. Most ChRCCs are slow growing, but sarcomatoid differentiation and metastases can occur, indicative of aggressive behavior and poor prognosis. Herein, we characterize ten ChRCCs with aggressive components, defined as sarcomatoid change and/or metastasis. Immunohistochemistry (IHC) and next-generation sequencing were performed on available formalin-fixed paraffin-embedded tissue, with differential profiling of conventional and aggressive components. All ten cases showed a conventional component of renal tumor morphologically consistent with ChRCC: three had sarcomatoid change, four had metastases, and three had both sarcomatoid change and metastases. In the primary conventional components, a typical ChRCC IHC pattern (CK7+, CD117+, and CAIX-) was observed in 8 of 10 cases; 2 cases had rare CK7 staining. In the aggressive components, CD117 and/or CK7 was lost in 7 of 10 cases; 3 cases showed loss of both. Two of 10 cases showed significant CAIX staining in the aggressive component. All 7 cases that had molecular profiling performed showed characteristic chromosomal losses reported for ChRCC, with the aggressive components generally demonstrating more copy number complexity. Recurrent TP53 mutations (TP53m) were also seen; however, surprisingly, the conventional and aggressive components had no shared TP53m: a TP53m was private to aggressive components in 2 cases and to the conventional component in 1 case, and in 4 cases, components demonstrated different TP53m. Of the 21 pathogenic alterations identified in 7 tumors, only a PTEN splicing alteration was shared between both components in one case. In conclusion, ChRCC can have IHC staining patterns and molecular profile that differ between conventional and aggressive components. Interpretation of stains on metastases or small biopsies to determine histologic subtype can be misleading. The lack of shared pathogenic mutations between the two components supports a model in which aggressive ChRCC can have convergent subclones with different TP53m., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)
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- 2022
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9. Testosterone works through androgen receptors to modulate neuronal response to anxiogenic stimuli.
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Chen CV, Jordan CL, and Breedlove SM
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- Animals, Anxiety genetics, Basolateral Nuclear Complex pathology, Behavior, Animal, Disease Models, Animal, Female, Humans, Loss of Function Mutation, Male, Mice, Mice, Transgenic, Receptors, Androgen genetics, Sex Factors, Suprachiasmatic Nucleus pathology, Anxiety pathology, Basolateral Nuclear Complex metabolism, Receptors, Androgen metabolism, Suprachiasmatic Nucleus metabolism, Testosterone metabolism
- Abstract
Testosterone (T) exerts anxiolytic effects through functional androgen receptors (ARs) in rodents. T treatment of castrated mice reduces anxiety-like behavior in wild-type (WT) males, but not males with a spontaneous mutation that renders AR dysfunctional (testicular feminization mutation, Tfm). Using Cre-LoxP technology we created males carrying induced dysfunctional AR allele (induced TFM; iTfm) to determine the brain regions responsible for T-induced anxiolysis. Adult WT and iTfm mice were castrated and T treated. Castrated WTs given a blank capsule (WT + B) served as additional controls. Mice were later exposed to the anxiogenic light/dark box, sacrificed and their brains processed for immediate early gene cFos immunoreactivity. Analyses revealed that T treatment increased cFos-expressing neurons in the basolateral amygdala (blAMY) of WT males, but not in iTfm males, which did not differ from WT + B mice. In contrast, WT + T males displayed fewer cFos + cells than iTfm + T or WT + B groups in the suprachiasmatic nucleus of the hypothalamus (SCN). No effects of genotype or hormone were seen in cFos expression in the hippocampus, medial prefrontal cortex, paraventricular nucleus of the hypothalamus, oval and anterodorsal bed nucleus of the stria terminalis, or dorsal periaqueductal grey. AR immunohistochemistry indicated that ∼65 % of cells in the blAMY and SCN were AR + in WT males, so AR could act directly within neurons in these regions to modulate the animals' response to anxiogenic stimuli. Because absence of a functional AR did not affect cFos response to mild stress in the other brain regions, they are unlikely to mediate androgen's anxiolytic effects., (Copyright © 2021 Elsevier B.V. All rights reserved.)
- Published
- 2021
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10. Acute ischemic stroke induces magnetic resonance susceptibility signs dominated by endothelial nitric oxide synthase activation.
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Chen CV, Chang C, Lin MF, Huang GS, and Chan WP
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- Animals, Magnetic Resonance Spectroscopy, Nitric Oxide Synthase Type III, Brain Ischemia diagnostic imaging, Ischemic Stroke, Stroke diagnostic imaging
- Abstract
Purpose: Acute ischemic stroke induces deoxyhemoglobin accumulation around the ischemic region while activating endothelial nitric oxide synthase (eNOS) coupling and the subsequent release of nitric oxide (NO). Because deoxyhemoglobin is a natural NO spin trap, its interplay with NO could be prominent during acute stroke. Its interaction with NO has been shown to induce overt paramagnetic signals in vitro; our goal was to investigate whether this interplay can be detected using MRI., Methods: To verify the in vivo image effects using the deoxyhemoglobin-NO interaction during acute stroke, eNOS states were manipulated in an animal model of acute ischemia, and the susceptibility signals, cerebral perfusion, and infarction were assessed noninvasively via MR susceptibility weighted imaging (SWI)., Results: Occlusion of the right middle cerebral artery increased eNOS coupling and susceptibility signals in the ischemic cortex while abolishing regional cerebral blood flow. Pharmacological eNOS blockage led to weakened susceptibility signals in the ischemic cortex as well as worsened tissue survival. Consistently, abolishment of eNOS coupling through genetic editing reduced the regional susceptibility signals in the ischemic cortex, causing large infarcts., Conclusion: Upregulation of eNOS during acute ischemia sustains tissue viability through the interaction between NO and deoxyhemoglobin. This interplay can be traced in vivo using SWI and can be considered a sensitive marker revealing the delicate oxygenation status of the ischemic tissue, therefore, guiding the management of acute stroke in clinical settings., (© 2020 International Society for Magnetic Resonance in Medicine.)
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- 2021
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11. MicroRNA-19b predicts widespread pain and posttraumatic stress symptom risk in a sex-dependent manner following trauma exposure.
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Linnstaedt SD, Rueckeis CA, Riker KD, Pan Y, Wu A, Yu S, Wanstrath B, Gonzalez M, Harmon E, Green P, Chen CV, King T, Lewandowski C, Hendry PL, Pearson C, Kurz MC, Datner E, Velilla MA, Domeier R, Liberzon I, Mogil JS, Levine J, and McLean SA
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- Accidents, Traffic psychology, Adolescent, Adult, Aged, Female, Humans, Male, MicroRNAs genetics, Middle Aged, Pain genetics, Pain psychology, Risk Factors, Sex Factors, Sex Offenses psychology, Stress Disorders, Post-Traumatic genetics, Stress Disorders, Post-Traumatic psychology, Young Adult, MicroRNAs metabolism, Pain metabolism, Stress Disorders, Post-Traumatic metabolism
- Abstract
Posttraumatic widespread pain (PTWP) and posttraumatic stress symptoms (PTSS) are frequent comorbid sequelae of trauma that occur at different rates in women and men. We sought to identify microRNA (miRNA) that may contribute to sex-dependent differences in vulnerability to these outcomes. Monte Carlo simulations (x10,000) identified miRNA in which predicted targeting of PTWP or PTSS genes was most enriched. Expression of the leading candidate miRNA to target PTWP/PTSS-related genes, miR-19b, has been shown to be influenced by estrogen and stress exposure. We evaluated whether peritraumatic miR-19b blood expression levels predicted PTWP and PTSS development in women and men experiencing trauma of motor vehicle collision (n = 179) and in women experiencing sexual assault trauma (n = 74). A sex-dependent relationship was observed between miR-19b expression levels and both PTWP (β = -2.41, P = 0.034) and PTSS (β = -3.01, P = 0.008) development 6 months after motor vehicle collision. The relationship between miR-19b and PTSS (but not PTWP) was validated in sexual assault survivors (β = -0.91, P = 0.013). Sex-dependent expression of miR-19b was also observed in blood and nervous tissue from 2 relevant animal models. Furthermore, in support of increasing evidence indicating a role for the circadian rhythm (CR) in PTWP and PTSS pathogenesis, miR-19b targets were enriched in CR gene transcripts. Human cohort and in vitro analyses assessing miR-19b regulation of key CR transcripts, CLOCK and RORA, supported the potential importance of miR-19b to regulating the CR pathway. Together, these results highlight the potential role that sex-dependent expression of miR-19b might play in PTWP and PTSS development after trauma/stress exposure.
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- 2020
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12. Novel and lethal case of cardiac involvement in DNM1L mitochondrial encephalopathy.
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Vandeleur D, Chen CV, Huang EJ, Connolly AJ, Sanchez H, and Moon-Grady AJ
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- Adult, Alleles, Biopsy, Child, DNA Mutational Analysis, Female, Genetic Association Studies, Genetic Predisposition to Disease, Genotype, Humans, Immunohistochemistry, Male, Dynamins genetics, Heart Diseases diagnosis, Heart Diseases genetics, Mitochondrial Encephalomyopathies diagnosis, Mitochondrial Encephalomyopathies genetics, Mutation, Phenotype
- Abstract
Pathogenic DNM1L mutations cause a mitochondrial disorder with a highly variable clinical phenotype characterized by developmental delay, hypotonia, seizures, microcephaly, poor feeding, ocular abnormalities, and dysarthria. We report the case of an 8-month-old female with autosomal dominant, de novo DNM1L c. 1228G>A (p. E410K) mutation and mitochondrial disorder, septo-optic dysplasia, hypotonia, developmental delay, elevated blood lactate, and severe mitochondrial cardiomyopathy leading to nonischemic congestive heart failure and cardiogenic shock resulting in death. This case suggests that cardiac involvement, previously undescribed, can be a clinically important feature of this syndrome and should be screened for at diagnosis., (© 2019 Wiley Periodicals, Inc.)
- Published
- 2019
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13. Efficacy of topical brinzolamide in children with retinal dystrophies.
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Scruggs BA, Chen CV, Pfeifer W, Wiley JS, Wang K, and Drack AV
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- Child, Child, Preschool, Female, Follow-Up Studies, Humans, Male, Prognosis, Retrospective Studies, Carbonic Anhydrase Inhibitors therapeutic use, Macular Edema drug therapy, Retinal Dystrophies drug therapy, Sulfonamides therapeutic use, Thiazines therapeutic use
- Abstract
Background : Inherited retinal dystrophies are a leading cause of irreversible blindness in children in the United States. Topical carbonic anhydrase inhibitors have improved central vision and cystoid macular edema in patients with retinal dystrophies, but few studies have assessed their efficacy in children. Materials and Methods : A retrospective chart review was performed with Institutional Review Board approval to identify pediatric patients with inherited retinal dystrophies who received topical brinzolamide at a single university center between 2008 and 2015. Serial visual acuity and central macular thicknesses were compared to assess the efficacy of brinzolamide. Results : Seven subjects were identified who met the inclusion criteria. Four had juvenile X-linked retinoschisis, two had retinitis pigmentosa, and one had Leber congenital amaurosis. All were prescribed brinzolamide thrice daily; however, one patient was completely non-compliant. Four of the six treated patients exhibited a mild decrease in central macular thickness in both eyes during the study with all six treated patients having significantly improved vision at the first endpoint, 33.2 ± 8.2 months after treatment initiation. For treated patients, average visual acuity (LogMAR) ± standard error of the mean improved from 0.5 ± 0.04 pre-treatment to 0.3 ± 0.1 at the second endpoint, 50.2 ± 7.3 months after treatment initiation. Conclusions : Mild anatomic improvement of macular cysts was seen in pediatric patients using brinzolamide. Visual acuity improvement occurred even without significant reduction in macular cysts. Further studies are needed to determine whether the beneficial effects of carbonic anhydrase inhibitors are sustained in children with inherited retinal degenerations.
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- 2019
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14. Evaluation of Continuous Lactate Monitoring Systems within a Heparinized In Vivo Porcine Model Intravenously and Subcutaneously.
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Wolf A, Renehan K, Ho KKY, Carr BD, Chen CV, Cornell MS, Ye M, Rojas-Peña A, and Chen H
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- Animals, Biosensing Techniques veterinary, Blood Gas Analysis, Calibration, Central Venous Catheters, Female, Humans, Models, Animal, Monitoring, Physiologic veterinary, Sensitivity and Specificity, Swine, Wireless Technology, Biosensing Techniques instrumentation, Heparin administration & dosage, Lactic Acid analysis, Monitoring, Physiologic instrumentation
- Abstract
We present an animal model used to evaluate the in vivo performance of electrochemical amperometric continuous lactate sensors compared to blood gas instruments. Electrochemical lactate sensors were fabricated, placed into 5 Fr central venous catheters (CVCs), and paired with wireless potentiostat devices. Following in vivo evaluation and calibration, sensors were placed within the jugular and femoral veins of a porcine subject as a preliminary assessment of in vivo measurement accuracy. The mobile electronic circuit potentiostat devices supplied the operational voltage for the sensors, measured the resultant steady-state current, and recorded the sensor response values in internal memory storages. An in vivo time trace of implanted intravenous (IV) sensors demonstrated lactate values that correlated well with the discrete measurements of blood samples on a benchtop point-of-care sensor-based instrument. Currents measured continuously from the implanted lactate sensors over 10 h were converted into lactate concentration values through use of a two-point in vivo calibration. Study shows that intravenously implanted sensors had more accurate readings, faster peak-reaching rates, and shorter peak-detection times compared to subcutaneously placed sensors. IV implanted and subcutaneously placed sensors closer to the upper body (in this case neck) showed faster response rates and more accurate measurements compared to those implanted in the lower portion of the porcine model. This study represents an important milestone not only towards continuous lactate monitoring for early diagnosis and intervention in neonatal patients with congenital heart disease undergoing cardiopulmonary bypass surgeries, but also in the intervention of critical ill patients in the Intensive Care Units or during complex surgical procedures.
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- 2018
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15. Effects of Trauma in Adulthood and Adolescence on Fear Extinction and Extinction Retention: Advancing Animal Models of Posttraumatic Stress Disorder.
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Chen CV, Chaby LE, Nazeer S, and Liberzon I
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Evidence for and against adolescent vulnerability to posttraumatic stress disorder (PTSD) is mounting, but this evidence is largely qualitative, retrospective, or complicated by variation in prior stress exposure and trauma context. Here, we examine the effects of development on trauma vulnerability using adult post-natal (PN) day 61, early adolescent (PN23) and mid adolescence (PN34) rats and two types of trauma: an established animal model of PTSD, single prolonged stress (SPS), and a novel composite model-SPS predation (SPSp) version. We demonstrate that early and mid adolescent rats are capable of fear conditioning and fear extinction, as well as extinction retention. Our results also demonstrate that both types of trauma induced a deficit in the retention of fear extinction in adulthood, a hallmark of PTSD, but not after early or mid adolescence trauma, suggesting that adolescence might convey resilience to SPS and SPSp traumas. Across all three life stages, the effects of SPS exposure and a novel predation trauma model, SPSp, had similar effects on behavior suggesting that trauma type did not affect the likelihood of developing PTSD-like symptoms, and that SPSp is a predation-based trauma model worth exploring.
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- 2018
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16. Down, But Not Out: Partial Elimination of Androgen Receptors in the Male Mouse Brain Does Not Affect Androgenic Regulation of Anxiety or HPA Activity.
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Chen CV, Brummet JL, Jordan CL, and Breedlove SM
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- Amygdala metabolism, Animals, Brain drug effects, Brain metabolism, Hippocampus metabolism, Hypothalamo-Hypophyseal System metabolism, Hypothalamus metabolism, Male, Mice, Mice, Knockout, Periaqueductal Gray metabolism, Pituitary-Adrenal System metabolism, Prefrontal Cortex metabolism, Receptors, Androgen genetics, Receptors, Androgen metabolism, Septal Nuclei metabolism, Androgens pharmacology, Anti-Anxiety Agents pharmacology, Anxiety genetics, Behavior, Animal drug effects, Hypothalamo-Hypophyseal System drug effects, Pituitary-Adrenal System drug effects, Receptors, Androgen drug effects, Testosterone pharmacology
- Abstract
We previously found that androgen receptor (AR) activity mediates two effects of T in adult male mice: reduction of anxiety-like behaviors and dampening of the hypothalamic-pituitary-adrenal response to stress. To determine whether brain ARs mediate these effects, we used the Cre/loxP technology seeking to disable AR throughout the central nervous system (CNS). Female mice carrying the floxed AR allele (ARlox) were crossed with males carrying cre recombinase transgene controlled by the nestin promoter (NesCre), producing cre in developing neurons and glia. Among male offspring, four genotypes resulted: males carrying ARlox and NesCre (NesARko), and three control groups (wild types, NesCre, and ARlox). Reporter mice indicated ubiquitous Cre expression throughout the CNS. Nevertheless, AR immunocytochemistry in NesARko mice revealed efficient knockout (KO) of AR in some brain regions (hippocampus and medial prefrontal cortex [mPFC]), but not others. Substantial AR protein was seen in the amygdala and hypothalamus among other regions, whereas negligible AR remained in others like the bed nucleus of the stria terminalis and dorsal periaqueductal gray. This selective KO allowed for testing the role of AR in hippocampus and mPFC. Males were castrated and implanted with T at postnatal day 60 before testing on postnatal day 90-100. In contrast with males with global KO of AR, T still modulated anxiety-related behavior and hypothalamic-pituitary-adrenal activity in NesARko males. These results leave open the possibility that AR acting in the CNS mediates these effects of T, but demonstrate that AR is not required in the hippocampus or mPFC for T's anxiolytic effects.
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- 2016
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17. New knockout model confirms a role for androgen receptors in regulating anxiety-like behaviors and HPA response in mice.
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Chen CV, Brummet JL, Lonstein JS, Jordan CL, and Breedlove SM
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- Androgen-Insensitivity Syndrome genetics, Androgen-Insensitivity Syndrome physiopathology, Animals, Anxiety physiopathology, Corticosterone blood, Disease Models, Animal, Female, Male, Mice, Mice, Inbred C57BL, Mice, Knockout, Photoperiod, Receptors, Androgen genetics, Receptors, Androgen metabolism, Stress, Psychological metabolism, Stress, Psychological physiopathology, Anxiety metabolism, Behavior, Animal physiology, Hypothalamo-Hypophyseal System metabolism, Models, Animal, Pituitary-Adrenal System metabolism, Receptors, Androgen physiology, Testosterone physiology
- Abstract
Men are less likely than women to suffer from anxiety disorders. Because gonadal hormones play a crucial role in many behavioral sex differences, they may underlie sex differences in human anxiety. In rodents, testosterone (T) exerts anxiolytic effects via the androgen receptor (AR): we found that male mice with a naturally-occurring mutation rendering the AR dysfunctional, referred to as spontaneous testicular feminization mutation (sTfm), showed more anxiety-like behaviors than wildtype (WT) males. Here, we used Cre-lox recombination technology to create another dysfunctional allele for AR. These induced Tfm (iTfm) animals also displayed more anxiety-like behaviors than WTs. We further found that AR-modulation of these behaviors interacts with circadian phase. When tested in the resting phase, iTfms appeared more anxious than WTs in the open field, novel object and elevated plus maze tests, but not the light/dark box. However, when tested during the active phase (lights off), iTfms showed more anxiety-related behavior than WTs in all four tests. Finally, we confirmed a role of T acting via AR in regulating HPA axis activity, as WT males with T showed a lower baseline and overall corticosterone response, and a faster return to baseline following mild stress than did WT males without T or iTfms. These findings demonstrate that this recombined AR allele is a valuable model for studying androgenic modulation of anxiety, that the anxiolytic effects of AR in mice are more prominent in the active phase, and that HPA axis modulation by T is AR dependent., (Copyright © 2014 Elsevier Inc. All rights reserved.)
- Published
- 2014
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18. Highly sensitive flexible pressure sensors with microstructured rubber dielectric layers.
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Mannsfeld SC, Tee BC, Stoltenberg RM, Chen CV, Barman S, Muir BV, Sokolov AN, Reese C, and Bao Z
- Abstract
The development of an electronic skin is critical to the realization of artificial intelligence that comes into direct contact with humans, and to biomedical applications such as prosthetic skin. To mimic the tactile sensing properties of natural skin, large arrays of pixel pressure sensors on a flexible and stretchable substrate are required. We demonstrate flexible, capacitive pressure sensors with unprecedented sensitivity and very short response times that can be inexpensively fabricated over large areas by microstructuring of thin films of the biocompatible elastomer polydimethylsiloxane. The pressure sensitivity of the microstructured films far surpassed that exhibited by unstructured elastomeric films of similar thickness, and is tunable by using different microstructures. The microstructured films were integrated into organic field-effect transistors as the dielectric layer, forming a new type of active sensor device with similarly excellent sensitivity and response times.
- Published
- 2010
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