Publications by authors named "Lisa Roth"

25 Publications

  • Page 1 of 1

Blood reelin in the progression of chronic liver disease.

Adv Med Sci 2021 Mar 6;66(1):148-154. Epub 2021 Feb 6.

Department of Medicine II, Medical Center University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany; Berta-Ottenstein-Programme, Faculty of Medicine, University of Freiburg, Freiburg, Germany.

Purpose: Reelin is an extracellular matrix protein originally found to be associated with neuropsychiatric disorders. Recent findings indicate, that reelin may also play an important role in the process of liver fibrosis as well as in the development of hepatocellular carcinoma (HCC). Against this background, the aim of our study was to explore alterations in blood reelin levels in different stages of chronic liver diseases.

Patients And Methods: We analyzed blood samples of patients with chronic liver disease without liver fibrosis (n ​= ​25), with liver fibrosis (n ​= ​36), with liver cirrhosis (n ​= ​74), with HCC (n ​= ​26) as well as of healthy controls (n ​= ​15). Blood reelin concentrations were determined utilizing an enzyme-linked immunosorbent assay.

Results: Blood reelin levels were significantly elevated in patients who had liver fibrosis or cirrhosis compared to patients without liver fibrosis and healthy controls (13.9 (10.2-21.1) ng/ml vs. 11.2 (8.8-16.8) ng/ml, p ​= ​0.032). Importantly, patients with HCC displayed significantly higher reelin concentrations compared to patients with liver cirrhosis alone (27.0 (17.3-35.9) ng/ml vs. 16.6 (11.0-22.7) ng/ml, p ​< ​0.001). Blood reelin was not relevantly linked to liver function, inflammation and etiology of liver disease.

Conclusions: Our results demonstrate, that blood reelin levels are altered in different stages of chronic liver disease, which makes reelin a potential biomarker in this setting. This may be especially relevant with regard to its use as an additional tumor marker of HCC.
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http://dx.doi.org/10.1016/j.advms.2021.01.006DOI Listing
March 2021

Propellant Off-Gassing and Implications for Triage and Rescue.

Aerosp Med Hum Perform 2020 Dec;91(12):956-961

: Hypergolic propellants can be released in large amounts during space launch contingencies. Whether propellant-contaminated suit fabric poses a significant risk to rescue crews, due to off-gassing, has not been explored in detail. In this study, we addressed this issue experimentally, exposing space suit fabric to propellants (dinitrogen tetroxide [N₂O₄] and monomethyl hydrazine [MMH]).: The NASA Space Shuttle Program Advanced Crew Escape System II (ACES II) is similar to the NASA Orion Crew Survival System (OCSS) and was utilized here. Suit fabric was placed and sealed into permeation cells. Fabric exterior surface was exposed to constant concentrated hypergolics, simulating permeation and leakage. Fabric was rinsed, and permeation and off-gassing kinetics were measured. Experimental parameters were selected, simulating suited flight crewmembers during an evacuation transport without cabin air flow.: The fabric allows for immediate permeation of liquid or vaporized MMH and N₂O₄. NO₂ off-gassing never exceeded the AEGL-1 8-h level (acute exposure guideline level). In contrast, MMH off-gassing levels culminated in peak levels, approaching AEGL-2 10-min levels, paralleling the drying process of the fabric layers. : Our findings demonstrate that MMH off-gassing is promoted by the drying of suit material in a delayed fashion, resulting in MMH concentrations having the potential for adverse health effects for flight and rescue crews. This indicates that shorter decontamination times could be implemented, provided that suit material is either kept moist to prevent off-gassing or removed prior to medical evacuation. Additional studies using OCSS or commercial crew suits might be needed in the future.
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http://dx.doi.org/10.3357/AMHP.5637.2020DOI Listing
December 2020

The Role of Frozen Section Examination During Inguinal Exploration in Men with Inconclusive Testicular Tumors: A Systematic Review and Meta-analysis.

Eur Urol Focus 2020 Jul 16. Epub 2020 Jul 16.

Department of Urology, University Hospital Zurich, University of Zurich, Zurich, Switzerland.

For inconclusive testicular tumors with negative tumor markers, frozen section examination (FSE) during inguinal exploration is recommended. However, FSE is time-consuming and therefore often not requested. Furthermore, the exact diagnostic benefit remains poorly defined. We performed a systematic review and meta-analysis summarizing 12 published studies and our own series of FSE in patients with inconclusive testicular tumors, resulting in a cohort of 1052 FSEs. FSE showed sensitivity of 99% and specificity of 96% with a positive predictive value of 98% and a negative predictive value of 97%. Most importantly, one-third of all testicular tumors investigated were correctly identified as being suitable for testis-sparing surgery and orchiectomy could be avoided. For patients with inconclusive testicular tumors, FSE is useful for deciding whether testis-sparing surgery is an option or whether radical orchiectomy should be performed. Thus, these patients should be optimally treated in institutions where FSE is available. PATIENT SUMMARY: We found that intraoperative examination of a frozen section is useful in deciding on whether the entire or only parts of the testicle can be removed. We conclude that frozen section examination should be offered to men with small testicular lesions and negative tumor markers.
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http://dx.doi.org/10.1016/j.euf.2020.06.019DOI Listing
July 2020

Adhesion between P. falciparum infected erythrocytes and human endothelial receptors follows alternative binding dynamics under flow and febrile conditions.

Sci Rep 2020 03 11;10(1):4548. Epub 2020 Mar 11.

Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany.

Characterizing the adhesive dynamics of Plasmodium falciparum infected erythrocytes (IEs) to different endothelial cell receptors (ECRs) in flow is a big challenge considering available methods. This study investigated the adhesive dynamics of IEs to five ECRs (CD36, ICAM-1, P-selectin, CD9, CSA) using simulations of in vivo-like flow and febrile conditions. To characterize the interactions between ECRs and knobby and knobless IEs of two laboratory-adapted P. falciplarum isolates, cytoadhesion analysis over time was performed using a new tracking bioinformatics method. The results revealed that IEs performed rolling adhesion exclusively over CD36, but exhibited stationary binding to the other four ECRs. The absence of knobs affected rolling adhesion both with respect to the distance travelled by IEs and their velocity. Knobs played a critical role at febrile temperatures by stabilizing the binding interaction. Our results clearly underline the complexity of the IE-receptor interaction and the importance of knobs for the survival of the parasite at fever temperatures, and lead us to propose a new hypothesis that could open up new strategies for the treatment of malaria.
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http://dx.doi.org/10.1038/s41598-020-61388-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7066226PMC
March 2020

Stringent Selection of Knobby -Infected Erythrocytes during Cytoadhesion at Febrile Temperature.

Microorganisms 2020 Jan 25;8(2). Epub 2020 Jan 25.

Bernhard Nocht Institute for Tropical Medicine, 20359 Hamburg, Germany.

Changes in the erythrocyte membrane induced by invasion allow cytoadhesion of infected erythrocytes (IEs) to the host endothelium, which can lead to severe complications. Binding to endothelial cell receptors (ECRs) is mainly mediated by members of the erythrocyte membrane protein 1 (EMP1) family, encoded by genes. Malaria infection causes several common symptoms, with fever being the most apparent. In this study, the effects of febrile conditions on cytoadhesion of predominately knobless erythrocytes infected with the laboratory isolate IT4 to chondroitin-4-sulfate A (CSA), intercellular adhesion molecule 1 (ICAM-1), and CD36 were investigated. IEs enriched for binding to CSA at 40 °C exhibited significantly increased binding capacity relative to parasites enriched at 37 °C. This interaction was due to increased expression and trafficking of the corresponding EMP1 to the IE surface as well as to a selection of knobby IEs. Furthermore, the enrichment of IEs to ICAM-1 at 40 °C also led to selection of knobby IEs over knobless IEs, whereas enrichment on CD36 did not lead to a selection. In summary, these findings demonstrate that knobs are crucial for parasitic survival in the host, especially during fever episodes, and thus, that selection pressure on the formation of knobs could be controlled by the host.
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http://dx.doi.org/10.3390/microorganisms8020174DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7074740PMC
January 2020

CXCL12 expression is an adverse predictor for disease recurrence in patients with metastatic non-seminomatous testicular germ cell tumors.

BMC Cancer 2019 Aug 14;19(1):802. Epub 2019 Aug 14.

Department of Urology, University Hospital, University of Zurich, Zurich, Switzerland.

Background: To validate the utility of the chemokine ligand 12 (CXCL12) as prognostic marker in patients with localized and metastatic germ cell tumors (GCT).

Methods: CXCL12 expression was analyzed on a tissue microarray consisting of 750 tissue cores of different histological tumor components, Germ cell neoplasia in situ (GCNIS) and adjacent normal tissue of 263 testicular cancer patients using a semi-quantitative score. The association between CXCL12 expression and recurrence-free survival (RFS) as well as overall survival (OS) was assessed using Kaplan-Meier curves with log-rank tests.

Results: CXCL12 expression was absent in all seminomas but was found in 52 of 99 (52.5%) non-seminomas. Follow-up was available for 260 patients of which 36 (13.8%) recurred. In patients with stage 1 non-seminoma GCT, CXCL12 expression was not associated with higher risk of disease recurrence (p = 0.270). In contrast, post chemotherapy RFS of patients with metastatic non-seminoma and positive CXCL12 expression was significantly shorter compared to CXCL12 negative patients (p = 0.003). OS differences were not statistically different between patients with CXCL12 positive or negative tumors for either localized or metastatic disease.

Conclusions: CXCL12 is almost exclusively expressed in non-seminoma. Pure seminoma, GCNIS and adjacent normal testicular tissue are CXCL12 negative. Our analysis suggests that patients with metastatic disease and a CXCL12-positive non-seminoma are at higher risk for disease recurrence after first-line chemotherapy and might thus be candidates for more intensive treatment and/or closer follow-up.
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http://dx.doi.org/10.1186/s12885-019-5961-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6693197PMC
August 2019

Engaging parent-child dyad and healthcare provider stakeholders in a patient-centered comparative effectiveness study.

J Comp Eff Res 2019 07 10;8(9):721-732. Epub 2019 Jul 10.

University of Iowa, IA 52242, USA.

Describe engagement activities in a comparative effectiveness study evaluating two interventions for promoting psychosocial health among youth ages 10-17 who have recently experienced a nonintentional injury. Institutional, community and patient stakeholders from four children's hospitals were engaged through consultation meetings, individual interviews and a collaborative meeting. 67 engagement activities were conducted across four hospitals. Feedback to improve recruitment, retention and continuous engagement in the study was obtained. Finally, disseminating study interventions to school and healthcare settings, and adding alternative delivery formats were identified as priority next steps. Results highlight diverse methods of engaging patient and professional stakeholders, critical recommendations for improving study engagement and retention, and future directions for this patient-engaged comparative effectiveness research.
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http://dx.doi.org/10.2217/cer-2018-0126DOI Listing
July 2019

Pre-orchiectomy tumor marker levels should not be used for International Germ Cell Consensus Classification (IGCCCG) risk group assignment.

J Cancer Res Clin Oncol 2019 Mar 14;145(3):781-785. Epub 2019 Jan 14.

Department of Urology, University Hospital, University of Zurich, Zurich, Switzerland.

Purpose: To investigate whether the use of pre-orchiectomy instead of pre-chemotherapy tumor marker (TM) levels has an impact on the International Germ Cell Consensus Classification (IGCCCG) risk group assignment in patients with metastatic germ cell tumors (GCT).

Methods: Demographic and clinical information of all patients treated for primary metastatic testicular non-seminomatous GCT in our tertiary care academic center were extracted from medical charts. IGCCCG risk group assignment was correctly performed with pre-chemotherapy marker levels and additionally with pre-orchiectomy marker levels. Agreement between pre-chemotherapy and pre-orchiectomy risk group assignments was assessed using Cohen's kappa.

Results: Our cohort consisted of 83 patients. The use of pre-orchiectomy TMs resulted in an IGCCCG risk group upstaging in 12 patients (16%, 8 patients from good to intermediate risk and 4 patients from intermediate to poor risk) and a downstaging in 1 patient (1.2%, from intermediate- to good-risk). The agreement between pre-orchiectomy and pre-chemotherapy IGCCCG risk groups resulted in a Cohen's kappa of 0.888 (p < 0.001).

Conclusions: Using pre-orchiectomy TMs can result in incorrect IGCCCG risk group assignment, which in turn can impact on the clinical management and follow-up of patients with metastatic GCT. Thus, adherence to the IGCCCG standard using pre-chemotherapy TMs levels is recommended.
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http://dx.doi.org/10.1007/s00432-019-02844-zDOI Listing
March 2019

Systemic inflammatory markers have independent prognostic value in patients with metastatic testicular germ cell tumours undergoing first-line chemotherapy.

Br J Cancer 2018 03 27;118(6):825-830. Epub 2018 Feb 27.

Department of Urology, University Hospital, University of Zurich, Zurich 8091, Switzerland.

Background: The prognostic utility of systemic inflammatory markers has so far not been investigated in patients with metastatic testicular germ cell tumours (GCTs).

Methods: International Germ Cell Cancer Cooperative Group (IGCCCG) risk groups and blood-based systemic inflammatory markers (haemoglobin, leukocytes, platelets (P), neutrophils (N), lymphocytes (L), C-reactive protein (CRP) and albumin) of 146 patients undergoing first-line chemotherapy for GCT were retrieved. In addition, N to L ratio (NLR), P to L ratio and the systemic immune-inflammation index (SII=N × P/L) were calculated. The prognostic ability of these markers for overall survival (OS) were assessed using regression analyses and Kaplan-Meier curves with log-rank tests.

Results: In univariate Cox regression, low haemoglobin and albumin as well as high leukocytes, N, NLR, SII and CRP were associated with a shorter OS. In multivariable Cox regression analyses, high leukocyte (hazard ratio (HR) 1.274 (95% confidence interval (CI) 1.057-1.535); P=0.011) and N count (1.470 (1.092-1.980); P=0.011), higher NLR (84.5 (2.2-3193.4); P=0.017) and SII (12.15 (1.17-126.26); P=0.037) remained independent prognostic predictors for OS besides the IGCCCG risk groups.

Conclusions: Systemic inflammatory markers might have prognostic utility for patients with metastatic GCT. The planned IGCCCG update could be an opportunity to test these markers in a larger data set.
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http://dx.doi.org/10.1038/bjc.2017.467DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5877429PMC
March 2018

Characterisation of Plasmodium falciparum populations selected on the human endothelial receptors P-selectin, E-selectin, CD9 and CD151.

Sci Rep 2017 06 22;7(1):4069. Epub 2017 Jun 22.

Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany.

The ability of the parasite Plasmodium falciparum to evade the immune system and be sequestered within human small blood vessels is responsible for severe forms of malaria. The sequestration depends on the interaction between human endothelial receptors and P. falciparum erythrocyte membrane protein 1 (PfEMP1) exposed on the surface of the infected erythrocytes (IEs). In this study, the transcriptomes of parasite populations enriched for parasites that bind to human P-selectin, E-selectin, CD9 and CD151 receptors were analysed. IT4_var02 and IT4_var07 were specifically expressed in IT4 parasite populations enriched for P-selectin-binding parasites; eight var genes (IT4_var02/07/09/13/17/41/44/64) were specifically expressed in isolate populations enriched for CD9-binding parasites. Interestingly, IT4 parasite populations enriched for E-selectin- and CD151-binding parasites showed identical expression profiles to those of a parasite population exposed to wild-type CHO-745 cells. The same phenomenon was observed for the 3D7 isolate population enriched for binding to P-selectin, E-selectin, CD9 and CD151. This implies that the corresponding ligands for these receptors have either weak binding capacity or do not exist on the IE surface. Conclusively, this work expanded our understanding of P. falciparum adhesive interactions, through the identification of var transcripts that are enriched within the selected parasite populations.
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http://dx.doi.org/10.1038/s41598-017-04241-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5481354PMC
June 2017

CD4-Negative Variant of Cutaneous Blastic Plasmacytoid Dendritic Cell Neoplasm With a Novel PBRM1 Mutation in an 11-Year-Old Girl.

Am J Clin Pathol 2017 May;147(5):453-460

Division of Hematopathology, Department of Pathology and Laboratory Medicine.

Objectives: We report a rare case of CD4- cutaneous blastic plasmacytoid dendritic cell neoplasm (BPDCN) with a novel PBRM1 mutation.

Methods: An 11-year-old girl presented with an enlarged mass on her left arm and underwent an incisional biopsy.

Results: Histopathologic examination and immunohistochemistry studies showed a monotonous proliferation of blasts that were CD4-, CD56+, and CD123+. There was no evidence of leukemic dissemination. Next-generation sequencing detected PBRM1 and CIC gene abnormalities. We confirmed and validated a novel PBRM1 mutation by conventional polymerase chain reaction and Sanger sequencing.

Conclusions: CD4- variant of BPDCN may be mistaken for myeloid sarcoma or extramedullary lymphoblastic leukemia/lymphoma because of their overlapping morphologic and immunophenotypic features; thus, a careful clinicopathologic evaluation is essential to reach the correct diagnosis. PBRM1 mutation seems to be a driver event in this case. Our study underscores the importance of alterations in chromatin remodeling in the pathogenesis of BPDCN.
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http://dx.doi.org/10.1093/ajcp/aqx012DOI Listing
May 2017

A 31-Year-Old Man With a Ring-Enhancing Brain Lesion.

J Neuroophthalmol 2017 06;37(2):172-175

Department of Neurology (CSR), Columbia University Medical Center, New York, New York; Department of Pediatrics (LAR), Children's Hospital of Philadelphia, Philadelphia, Pennsylvania; Department of Neurology and Neurological Sciences (JBS), Stanford University Medical Center, Palo Alto, California; Department of Medicine (JR), Columbia University Medical Center, New York, New York; Department of Anatomic Pathology (LCH), Cleveland Clinic, Cleveland, Ohio; Department of Radiology (AMB), Johns Hopkins University School of Medicine, Baltimore, Maryland; and Department of Ophthalmology (GM), Columbia University Medical Center, New York, New York.

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http://dx.doi.org/10.1097/WNO.0000000000000469DOI Listing
June 2017

Verification and feedback for medical students: an observational study during general practice rotations.

Postgrad Med J 2017 Jan 9;93(1095):3-7. Epub 2016 Jun 9.

Department of General Practice/Family Medicine, Philipps University Marburg, Marburg, Germany.

Purpose Of The Study: A general practice and family medicine rotation is mandatory as part of undergraduate medical education. However, little is known about the student-teacher interaction in this specific setting of ambulatory teaching. In this study we analysed how frequently preceptors verified students' history taking and clinical examination skills and how often they gave feedback. The type of feedback given was also categorised.

Methods: From April to December 2012, 410 individual patient consultations were observed in 12 teaching practices associated with the Philipps University Marburg, Germany. Material was collected using structured field-note forms and videotaping. Descriptive data analysis was performed. Informed, written consent was provided by all participants.

Results: We analysed 410 consultations which lasted 14.8 min on average. In 130 (31.7%) consultations students took the patient's medical history; 124 (95.4%) of these were verified by the general practitioner (GP). Physical examination was performed by students in 202 (49.3%) of consultations; 169 (81.9%) of these were verified by the GP. Feedback occurred in 132 (32.2%) of the 410 patient consultations. Feedback was mostly non-specific and positive (68.9%), and occurred during consultation with the patient present. Specific, negative feedback also occurred relatively frequently (29.5%). Specific, positive and non-specific, negative responses were rarely given.

Conclusions: GPs should give feedback more frequently and when doing so, focus on specific feedback. GPs should be further instructed in different feedback techniques.
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http://dx.doi.org/10.1136/postgradmedj-2015-133420DOI Listing
January 2017

Teaching points-do they occur and what do they contain? An observation study concerning the general practice rotation.

BMC Med Educ 2016 Apr 18;16:113. Epub 2016 Apr 18.

Department of General Practice/Family Medicine, Philipps University Marburg, Marburg, Germany.

Background: A general practice rotation is mandatory in most undergraduate medical education programs. However, little is known about the student-teacher interaction which takes place in this setting. In this study we analyzed occurrence and content of teaching points.

Methods: From April to December 2012, 410 individual patient consultations were observed in twelve teaching practices associated with the Philipps University Marburg, Germany. Material was collected using structured field-note forms and videotaping. Data analysis was descriptive in form. A teaching point is defined here as a general rule or specific, case-related information divulged by the teaching practitioner.

Results: According to the analysis of 410 consultations, teaching points were made in 66.3% of consultations. During these consultations, 74.3% general- and 46.3% case related teaching points occurred; multiple categorizations were possible. Of seven possible topics, therapy was most common, followed, in frequency of occurrence, by patient history, diagnostic procedure, physical examination, disease pathology, differential diagnosis, risk factors and case presentation.

Conclusions: The majority of consultations conducted within student presence contained teaching points, most frequently concerning therapy. General teaching points were more common than specific teaching points. Whilst it is encouraging that most consultations included teaching points, faculty development aimed at raising awareness for teaching and learning techniques is important.
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http://dx.doi.org/10.1186/s12909-016-0636-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4834827PMC
April 2016

Measuring disease progression in giant axonal neuropathy: implications for clinical trial design.

J Child Neurol 2015 May 3;30(6):741-8. Epub 2014 Sep 3.

Division of Pediatric Neurology, Department of Neurology, Columbia University Medical Center, New York, NY, USA.

As part of a natural history study of giant axonal neuropathy, we hypothesized that the Friedreich Ataxia Rating Scale and the Gross Motor Function Measure would show a significant change over 6 months, reflecting subjects' decline in motor function. The Friedreich Ataxia Rating Scale was performed on 11 subjects and the Gross Motor Function Measure was performed on 10 subjects twice with a six-month interval. A paired two-tailed t-test was used to assess the difference in each subject's score. Significant changes were found over six months of 11.7 ± 11.0 (P = 0.006) for the Friedreich Ataxia Rating Scale and -10.0 ± 13.5 (P = 0.043) for the Gross Motor Function Measure, reflecting subjects' decline in motor function on examination and by report. These standardized assessments of clinical function are the first to be validated in giant axonal neuropathy and will be used in an upcoming gene therapy clinical trial.
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http://dx.doi.org/10.1177/0883073814542946DOI Listing
May 2015

Giant axonal neuropathy: An updated perspective on its pathology and pathogenesis.

Muscle Nerve 2014 Oct;50(4):467-76

Project A.L.S./Jenifer Estess Laboratory for Stem Cell Research, Center for Motor Neuron Biology and Disease, Columbia Stem Cell Initiative, Columbia University College of Physicians and Surgeons, New York, New York, USA.

Giant axonal neuropathy (GAN) is a rare pediatric neurodegenerative disease. It is best known for the "giant" axons caused by accumulations of intermediate filaments. The disease is progressive, with onset around age 3 years and death by the third decade of life. GAN results from recessive mutations in the GAN gene encoding gigaxonin, and our analysis of all reported mutations shows that they are distributed throughout the protein structure. Precisely how these mutations cause the disease remains to be determined. In addition to changes in peripheral nerves that are similar to those seen in neuropathies such as Charcot-Marie-Tooth type 2, GAN patients exhibit a wide range of central nervous system signs. These features, corroborated by degeneration of central tracts apparent from postmortem pathology, indicate that GAN is also a progressive neurodegenerative disease. To reflect this phenotype more precisely, we therefore propose that the disease should be more appropriately referred to as "giant axonal neurodegeneration."
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http://dx.doi.org/10.1002/mus.24321DOI Listing
October 2014

The absence of curly hair is associated with a milder phenotype in Giant Axonal Neuropathy.

Neuromuscul Disord 2014 Jan 24;24(1):48-55. Epub 2013 Jul 24.

Division of Pediatric Neurology, Department of Neurology, Columbia University Medical Center, New York, NY, United States.

Giant Axonal Neuropathy is a pediatric neurodegenerative disorder caused by autosomal recessive mutations in the GAN gene on chromosome 16q24.1. Mutations in the GAN gene lead to functional impairment of the cytoskeletal protein gigaxonin and a generalized disorder of intermediate filaments, including neurofilaments in axons. Tightly curled hair is a common but not universal feature of Giant Axonal Neuropathy. The pathogenesis of curly hair is unknown, although disruption of keratin architecture is thought to play a role. As part of a broader natural history study of Giant Axonal Neuropathy, we found that the absence of curly hair is correlated with superior motor function (p=0.013) when controlling for age, as measured by the Gross Motor Function Measure. Theoretically, higher levels of functional gigaxonin protein or compensatory mechanisms could produce fewer abnormalities of neurofilaments and keratin, accounting for this phenotype. We suggest that straight-haired patients with Giant Axonal Neuropathy are potentially underdiagnosed due to their divergence from the classic phenotype of the disease. Due to their non-specific features of an axonal neuropathy, these patients may be misdiagnosed with Charcot-Marie-Tooth Disease type 2. Genetic testing for Giant Axonal Neuropathy should be considered in relevant cases of Charcot-Marie-Tooth Disease type 2.
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http://dx.doi.org/10.1016/j.nmd.2013.06.007DOI Listing
January 2014

Rural roadway safety perceptions among rural teen drivers living in and outside of towns.

J Rural Health 2013 28;29(1):46-54. Epub 2012 Sep 28.

University of Iowa Injury Prevention Research Center, Iowa City, IA, USA.

Purpose: To compare perceptions about rural road and general driving behaviors between teens who live in- and out-of-town from rural communities in Iowa.

Methods: A cross-sectional survey was conducted with 160 teens anticipating their Intermediate License within 3 months upon enrollment into this study. Self-administered surveys were used to collect demographics and driving exposures (eg, frequency of driving, age when first drove unsupervised). Two Likert scales were included to measure agreement with safe driving behaviors on rural roads and general safe driving behaviors (eg, speeding, seat belt use). T-tests were calculated comparing mean composite scores between in- and out-of-town teens, and between mean rural road and general driving safety attitude scores. A linear regression multivariable model was constructed to identify predictors of the rural road score.

Results: While the majority of teens endorsed rural road and general safe driving behaviors, up to 40% did not. Thirty-two percent did not believe the dangers of animals on rural roads, and 40% disagreed that exceeding the speed limit is dangerous. In-town teens were less safety conscious about rural road hazards with a significantly lower mean composite score (4.4) than out-of-town teens (4.6); mean scores for general driving behaviors were similar. Living out-of-town and owning one's own car were significant predictors of increased rural road safety scores.

Conclusion: Rural, in-town teens have poorer safety attitudes about rural roadway hazards compared with out-of-town teens. Interventions that involve education, parental supervision, and practice on rural roads are critical for preventing teen crashes on rural roads.
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http://dx.doi.org/10.1111/j.1748-0361.2012.00435.xDOI Listing
December 2013

Implementation evaluation of steering teens safe: engaging parents to deliver a new parent-based teen driving intervention to their teens.

Health Educ Behav 2013 Aug 4;40(4):426-34. Epub 2012 Oct 4.

University of Iowa, Iowa City, IA 52242, USA.

Parents play a fundamental role in teaching their children safe driving skills to reduce risk of motor vehicle crashes, the leading cause of death for teens. Steering Teens Safe is a new parent-based intervention that equips parents with communication skills to talk about, demonstrate, and practice safe driving behaviors and skills with their teens. This implementation evaluation focuses on a sample of 83 parents who delivered Steering Teens Safe to their teens. One-, 2- and 3-month follow-up assessments were conducted with intervention parents to evaluate the self-reported quantity and quality of talking about, demonstrating, and practicing safe driving goals with teens; perceived success and benefit of the program; and barriers to implementation. Over 3 months of follow-up, parents discussed driving goals with their teens for a median of 101.5 minutes. The most frequently addressed topics were general safety principles, including distracted driving, driving in bad weather, wearing a seat belt, and being a safe passenger. Parents spent a median of 30 minutes practicing safe driving skills such as changing lanes. Sixty-seven percent of parents talked to their children about rural road safety, but just 36% demonstrated and half practiced these skills with their teens. Barriers to implementation include time and opportunity barriers and resistant attitudes of their teens. However, barriers neither affected frequency of engagement nor parents' perceived benefit and comfort in delivering the program. Parents with time/opportunity barriers also had higher practice and demonstration times than parents without these barriers. Findings indicate high acceptability among parent implementers and promise for real-world delivery. Future studies are needed to assess intervention impact.
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http://dx.doi.org/10.1177/1090198112459517DOI Listing
August 2013

After the waters receded: a qualitative study of university officials' disaster experiences during the Great Iowa Flood of 2008.

J Community Health 2011 Apr;36(2):307-15

University of Iowa Injury Prevention Research Center, Department of Occupational and Environmental Health, College of Public Health, University of Iowa, 100 Oakdale Campus, Iowa City, IA 52242-5000, USA.

When the Great Flood of 2008 hit towns across Eastern Iowa, officials from the University of Iowa shut its operations for a week, relocated and evacuated students and community residents, and suffered damage to over a dozen buildings. This study is a qualitative assessment of the experiences and perceptions of twelve university officials involved in the response and management of the disaster. Major themes are presented according to phases of the Disaster Management Cycle. During the preparedness phase, an established all-hazards plan as well as specific annexes for flooding and pandemic influenza proved to enhance community response to the flood. However, training university clientele across a large organization to execute these plans and respond to future disasters is not an easy task. The content and effective means for delivering these trainings are areas for further research. During the response phase of the flood, officials swiftly expedited a business continuity plan to assure that personnel were paid during the university closure. However, enforcing a policy to avoid coming to work during the closure was challenging. Thus, future work must be done to determine and implement effective disaster communications that relay clear messages about roles and responsibilities. Now, in recovery, the university must rebuild its infrastructure and consider potential mental health issues. Lessons learned from the Great Flood of 2008 provide the opportunity to self-assess and prepare universities for disasters in the future.
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http://dx.doi.org/10.1007/s10900-010-9312-zDOI Listing
April 2011

Microglial activation is required for Abeta clearance after intracranial injection of lipopolysaccharide in APP transgenic mice.

J Neuroimmune Pharmacol 2007 Jun 27;2(2):222-31. Epub 2007 Mar 27.

Alzheimer Research Laboratory, Department of Molecular Pharmacology and Physiology, School of Basic Biomedical Sciences, College of Medicine, University of South Florida, Tampa, FL 33612-4799, USA.

Inflammation has been argued to play a fundamental role in the pathogenesis of Alzheimer's disease. Mice transgenic for mutant human amyloid precursor protein (APP) develop progressive amyloid deposition, gliosis, and cognitive impairment. Paradoxically, intracranial administration of lipopolysaccharide (LPS) to promote neuroinflammation results in a reduction in amyloid-beta peptide (Abeta) burden concurrent with the inflammatory response. To determine whether microglia mediate Abeta clearance after LPS, we used dexamethasone to inhibit the microglial response. Amyloid precursor protein mice were injected intrahippocampally with either LPS or saline and were allowed to survive for 7 days with or without dexamethasone cotreatment. Brain tissue was then analyzed by immunohistochemistry. Hippocampal Abeta burden was reduced 7 days after LPS injection, and this was prevented by cotreatment with dexamethasone. Markers of microglial activation [CD45, complement receptor 3 (CR3), and macrosialin (CD68)] were increased by LPS, and these increases were attenuated by dexamethasone. Dexamethasone failed to block LPS-induced increases in all microglial markers, and Fcgamma receptors II/III and scavenger receptor A were increased by LPS but were unaffected by dexamethasone cotreatment. These results indicate a complex response by microglia to acute LPS treatment, with only some responses sensitive to steroidal anti-inflammatory drug treatment. Nonetheless, microglial activation was necessary to remove Abeta in this model of neuroinflammation.
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http://dx.doi.org/10.1007/s11481-007-9069-zDOI Listing
June 2007

Glyburide for the management of gestational diabetes: risk factors predictive of failure and associated pregnancy outcomes.

Am J Obstet Gynecol 2006 Oct;195(4):1090-4

Department of Obstetrics, Gynecology and Reproductive Science, Mount Sinai School of Medicine, New York, NY, USA.

Objective: The purpose of this study was to identify characteristics that may predict failure of glyburide therapy for the management of A2 gestational diabetes, and to evaluate whether those that fail are at increased risk for adverse pregnancy outcomes.

Study Design: This was a retrospective cohort of gestational diabetics requiring medical therapy (A2DM) treated between January 2002 and July 2005.

Results: Of the 235 gestational diabetics identified, 79% of the 101 A2DMs were successfully treated with glyburide as first-line therapy. Those that failed had a higher mean glucose value on glucose challenge test (GCT) (200.5 +/- 57.3 vs 176.6 +/- 33.8 mg/dL, P = .019) and were more likely to have a GCT > or = 200 mg/dL (45 vs 22%, P = .043). Only GCT and GCT > or = 200 mg/dL were predictive of failure. Those successfully managed with glyburide had increased NICU admissions, primarily for hypoglycemia and respiratory distress, which resolved prior to discharge. There was no difference in birth weight, cesarean delivery, macrosomia, or shoulder dystocia.

Conclusion: Predicting glyburide failure is difficult, but failure does not appear to be associated with increased adverse pregnancy outcomes.
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http://dx.doi.org/10.1016/j.ajog.2006.07.029DOI Listing
October 2006

The neurologic content of S. Weir Mitchell's fiction.

Neurology 2006 Feb;66(3):403-7

G.H. Sergievsky Center, College of Physicians and Surgeons, Columbia University, New York, NY, USA.

Background: Silas Weir Mitchell (1829 to 1914), one of the most important neurologists in American Medicine, was known for his seminal work on the phantom limb syndrome, causalgia, and nerve injuries. He was also a prolific writer of novels and short stories. The neurologic content of this fiction has not been studied.

Objective: To assess the extent that references to neurologic topics were present in Mitchell's fiction, whether these neurologic references reflected Mitchell's scientific interests and contributions, and whether his fictional accounts of neurologic topics would precede those in his scientific writings.

Methods: The authors read Silas Weir Mitchell's novels and short stories.

Results: Seventeen (63.0%) of 27 fictional works contained neurologic references. Fifty-five (69.6%) of 79 references were brief (a single word or sentence). In two works, a neurologic theme was central to the plot. Some of the neurologic content was sophisticated (aphasia, brain laterality). Phantom limb syndrome, causalgia, and nerve injuries were not prominent in his fiction. Neurologic consequences of battle injuries were featured in 10 (37.0%) works. With the exception of "The Case of George Dedlow" (i.e., phantom limb syndrome), Mitchell's fictional accounts of neurologic topics followed his presentation of these topics in the scientific literature.

Conclusions: The majority of Mitchell's fictional works contained references to neurologic topics but most contained brief references. The number of references to Mitchell's specific scientific interests (phantom limb syndrome, causalgia) was small, although more generally, references to the neurology of battle injuries occurred more frequently.
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http://dx.doi.org/10.1212/01.wnl.0000196645.96131.b2DOI Listing
February 2006

Diverse microglial responses after intrahippocampal administration of lipopolysaccharide.

Glia 2006 Mar;53(4):382-91

Department of Pharmacology and Therapeutics, Alzheimer Research Laboratory, University of South Florida, Tampa, USA.

Inflammation has been argued to play a primary role in the pathogenesis of Alzheimer's disease by contributing to the development of neuropathology and clinical symptoms. However, the mechanisms underlying these effects remain obscure. Lipopolysaccharide (LPS) activates the innate immune response and triggers gliosis when injected into the central nervous system. In the studies described in the present work, we evaluated the time course of microgliosis after a single intrahippocampal injection of LPS. Mice were injected bilaterally with 4 mug of LPS. Post-injection survival times were 1, 6, and 24 h, as well as 3, 7, 14, and 28 days. Protein and RNA analyses were performed for inflammatory markers. Significant elevations of cluster differentiation marker CD45, glial fibrillary acidic protein (GFAP), scavenger receptor A (SRA), and Fcgamma receptor mRNA were seen after 24 h. Immunohistochemistry revealed a complex pattern of protein expression by microglia, as well as changes in cell morphologies. RNA and protein for Fcgamma receptor and SRA were transiently elevated, peaked at 3 days, and returned to basal levels after 1 week. In contrast, microglia remained significantly activated through the 28-day time point, as determined by CD45 and complement receptor 3 levels. These findings indicate a multivariate response to LPS, and evaluation of microglial phenotypes may lead to a better understanding of neuroinflammatory diseases.
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http://dx.doi.org/10.1002/glia.20272DOI Listing
March 2006

Time-dependent reduction in Abeta levels after intracranial LPS administration in APP transgenic mice.

Exp Neurol 2004 Nov;190(1):245-53

Alzheimer Research Laboratory, Department of Pharmacology and Therapeutics, University of South Florida, Tampa, FL 33612-4799, USA.

Inflammation has been argued to play a primary role in the pathogenesis of Alzheimer's disease (AD). Lipopolysaccharide (LPS) activates the innate immune system, triggering gliosis and inflammation when injected in the central nervous system. In studies described here, APP transgenic mice were injected intrahippocampally with 4 or 10 microg of LPS and evaluated 1, 3, 7, 14, or 28 days later. Abeta load was significantly reduced at 3, 7, and 14 days but surprisingly returned near baseline 28 days after the injection. No effects of LPS on congophilic amyloid deposits could be detected. LPS also activated both microglia and astrocytes in a time-dependent manner. The GFAP astrocyte reaction and the Fcgamma receptor microglial reaction peaked at 7 days after LPS injection, returning to baseline by 2 weeks postinjection. When stained for CD45, microglial activation was detected at all time points, although the morphology of these cells transitioned from an ameboid to a ramified and bushy appearance between 7 and 14 days postinjection. These results indicate that activation of brain glia can rapidly and transiently clear diffuse Abeta deposits but has no effect on compacted fibrillar amyloid.
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http://dx.doi.org/10.1016/j.expneurol.2004.07.007DOI Listing
November 2004
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