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Ibrahim M Abbass, Eleanor O Caplan, Daniel B Ng, Rita Kristy, Carol R Schermer, Pamela Bradt, Jenna M Collins, Wai Man Maria Chan, Brandon T Suehs
BACKGROUND: The impact of formulary management strategies on utilization and expenditures in overactive bladder (OAB) treatment has not been extensively investigated. In 2013, step therapy (ST) policies for 2 branded OAB treatments, mirabegron and fesoterodine, were removed from Humana Medicare Advantage Prescription Drug (MAPD) plans and Medicare prescription drug plans (PDP), allowing for an examination of the effect of ST policies on OAB medication use patterns and costs. OBJECTIVE: To assess the impact of removal of formulary restriction policies for mirabegron and fesoterodine on medication utilization patterns and costs associated with OAB treatment in Medicare patients...
January 2017: Journal of Managed Care & Specialty Pharmacy
Susan Elliott, Norman Buroker, Jason J Cournoyer, Anna M Potier, Joseph D Trometer, Carole Elbin, Mack J Schermer, Jaana Kantola, Aaron Boyce, Frantisek Turecek, Michael H Gelb, C Ronald Scott
In this data article we provide a detailed standard operating procedure for performing a tandem mass spectrometry, multiplex assay of 6 lysosomal enzymes for newborn screening of the lysosomal storage diseases Mucopolysaccharidosis-I, Pompe, Fabry, Niemann-Pick-A/B, Gaucher, and Krabbe, (Elliott, et al., 2016) [1]. We also provide the mass spectrometry peak areas for the product and internal standard ions typically observed with a dried blood spot punch from a random newborn, and we provide the daily variation of the daily mean activities for all 6 enzymes...
September 2016: Data in Brief
Markus M Rinschen, Christina B Schroeter, Sybille Koehler, Christina Ising, Bernhard Schermer, Martin Kann, Thomas Benzing, Paul T Brinkkoetter
The renal filtration barrier is maintained by the renal podocyte, an epithelial postmitotic cell. Immortalized mouse podocyte cell lines-both in the differentiated and undifferentiated state-are widely utilized tools to estimate podocyte injury and cytoskeletal rearrangement processes in vitro. Here, we mapped the cultured podocyte proteome at a depth of more than 8,800 proteins and quantified 7,240 proteins. Copy numbers of proteins mutated in forms of hereditary nephrotic syndrome or focal segmental glomerulosclerosis (FSGS) were assessed...
September 1, 2016: American Journal of Physiology. Cell Physiology
Susan Elliott, Norman Buroker, Jason J Cournoyer, Anna M Potier, Joseph D Trometer, Carole Elbin, Mack J Schermer, Jaana Kantola, Aaron Boyce, Frantisek Turecek, Michael H Gelb, C Ronald Scott
BACKGROUND: There is current expansion of newborn screening (NBS) programs to include lysosomal storage disorders because of the availability of treatments that produce an optimal clinical outcome when started early in life. OBJECTIVE: To evaluate the performance of a multiplex-tandem mass spectrometry (MS/MS) enzymatic activity assay of 6 lysosomal enzymes in a NBS laboratory for the identification of newborns at risk for developing Pompe, Mucopolysaccharidosis-I (MPS-I), Fabry, Gaucher, Niemann Pick-A/B, and Krabbe diseases...
August 2016: Molecular Genetics and Metabolism
Rik J B Loymans, Persijn J Honkoop, Evelien H Termeer, Jiska B Snoeck-Stroband, Willem J J Assendelft, Tjard R J Schermer, Kian Fan Chung, Ana R Sousa, Peter J Sterk, Helen K Reddel, Jacob K Sont, Gerben Ter Riet
BACKGROUND: Preventing exacerbations of asthma is a major goal in current guidelines. We aimed to develop a prediction model enabling practitioners to identify patients at risk of severe exacerbations who could potentially benefit from a change in management. METHODS: We used data from a 12-month primary care pragmatic trial; candidate predictors were identified from GINA 2014 and selected with a multivariable bootstrapping procedure. Three models were constructed, based on: (1) history, (2) history+spirometry and (3) history+spirometry+FeNO...
September 2016: Thorax
Markus M Rinschen, Puneet Bharill, Xiongwu Wu, Priyanka Kohli, Matthäus J Reinert, Oliver Kretz, Isabel Saez, Bernhard Schermer, Martin Höhne, Malte P Bartram, Sriram Aravamudhan, Bernard R Brooks, David Vilchez, Tobias B Huber, Roman-Ulrich Müller, Marcus Krüger, Thomas Benzing
The PHB-domain protein podocin maintains the renal filtration barrier and its mutation is an important cause of hereditary nephrotic syndrome. Podocin and its Caenorhabditis elegans orthologue MEC-2 have emerged as key components of mechanosensitive membrane protein signalling complexes. Whereas podocin resides at a specialized cell junction at the podocyte slit diaphragm, MEC-2 is found in neurons required for touch sensitivity. Here, we show that the ubiquitin ligase Ubr4 is a key component of the podocin interactome purified both from cultured podocytes and native glomeruli...
April 1, 2016: Human Molecular Genetics
Malte P Bartram, Sandra Habbig, Caroline Pahmeyer, Martin Höhne, Lutz T Weber, Holger Thiele, Janine Altmüller, Nina Kottoor, Andrea Wenzel, Marcus Krueger, Bernhard Schermer, Thomas Benzing, Markus M Rinschen, Bodo B Beck
Genetic diseases constitute the most important cause for end-stage renal disease in children and adolescents. Mutations in the ACTN4 gene, encoding the actin-binding protein α-actinin-4, are a rare cause of autosomal dominant familial focal segmental glomerulosclerosis (FSGS). Here, we report the identification of a novel, disease-causing ACTN4 mutation (p.G195D, de novo) in a sporadic case of childhood FSGS using next generation sequencing. Proteome analysis by quantitative mass spectrometry (MS) of patient-derived urinary epithelial cells indicated that ACTN4 levels were significantly decreased when compared with healthy controls...
March 15, 2016: Human Molecular Genetics
Sebastian Brähler, Christina Ising, Belén Barrera Aranda, Martin Höhne, Bernhard Schermer, Thomas Benzing, Paul Thomas Brinkkoetter
Maintenance of the glomerular filtration barrier with its fenestrated endothelium, the glomerular basement membrane, and the podocytes as the outer layer, is a major prerequisite for proper renal function. Tight regulation of the balance between plasticity and rigidity of the podocytes' architecture is required to prevent the onset of glomerular disease, mainly proteinuria. The underlying cellular signaling pathways that regulate the organization of the podocytes' cytoskeleton are still a matter of controversial debate...
October 1, 2015: American Journal of Physiology. Renal Physiology
Caitlin A Smith, Robert C Gosselin, Garth H Utter, Joseph M Galante, Jason B Young, Lynette A Scherer, Carol R Schermer
Metabolic acidosis has been implicated in the development of coagulopathy, although the specific mechanisms have not been well characterized. We sought to explore whether resuscitation of injured patients with a balanced crystalloid solution affects coagulation, as measured by endogenous thrombin potential (ETP) and thromboelastography (TEG). We performed an exploratory analysis of a subset of subjects enrolled in a randomized trial comparing the effect of resuscitation with isotonic saline versus Plasma-Lyte A (PLA) on acidosis and electrolyte abnormalities...
April 2015: Blood Coagulation & Fibrinolysis: An International Journal in Haemostasis and Thrombosis
Michael M Mueller, Laia Castells-Roca, Vipin Babu, Maria A Ermolaeva, Roman-Ulrich Müller, Peter Frommolt, Ashley B Williams, Sebastian Greiss, Jennifer I Schneider, Thomas Benzing, Bernhard Schermer, Björn Schumacher
Genome maintenance defects cause complex disease phenotypes characterized by developmental failure, cancer susceptibility and premature ageing. It remains poorly understood how DNA damage responses function during organismal development and maintain tissue functionality when DNA damage accumulates with ageing. Here we show that the FOXO transcription factor DAF-16 is activated in response to DNA damage during development, whereas the DNA damage responsiveness of DAF-16 declines with ageing. We find that in contrast to its established role in mediating starvation arrest, DAF-16 alleviates DNA-damage-induced developmental arrest and even in the absence of DNA repair promotes developmental growth and enhances somatic tissue functionality...
December 2014: Nature Cell Biology
Persijn J Honkoop, Rik J B Loijmans, Evelien H Termeer, Jiska B Snoeck-Stroband, Wilbert B van den Hout, Moira J Bakker, Willem J J Assendelft, Gerben ter Riet, Peter J Sterk, Tjard R J Schermer, Jacob K Sont
BACKGROUND: Aiming at partly controlled asthma (PCa) instead of controlled asthma (Ca) might decrease asthma medication use. Biomarkers, such as the fraction of exhaled nitric oxide (Feno), allow further tailoring of treatment. OBJECTIVE: We sought to assess the cost-effectiveness and clinical effectiveness of pursuing PCa, Ca, or Feno-driven controlled asthma (FCa). METHODS: In a nonblind, pragmatic, cluster-randomized trial in primary care, adults (18-50 years of age) with a doctor's diagnosis of asthma who were prescribed inhaled corticosteroids were allocated to one of 3 treatment strategies: (1) aiming at PCa (Asthma Control Questionnaire [ACQ] score <1...
March 2015: Journal of Allergy and Clinical Immunology
Jeffrey J Talbot, Xuewen Song, Xiaofang Wang, Markus M Rinschen, Nicholas Doerr, Wells B LaRiviere, Bernhard Schermer, York P Pei, Vicente E Torres, Thomas Weimbs
Polycystin-1 (PC1) mutations result in proliferative renal cyst growth and progression to renal failure in autosomal dominant polycystic kidney disease (ADPKD). The transcription factor STAT3 (signal transducer and activator of transcription 3) was shown to be activated in cyst-lining cells in ADPKD and PKD mouse models and may drive renal cyst growth, but the mechanisms leading to persistent STAT3 activation are unknown. A proteolytic fragment of PC1 corresponding to the cytoplasmic tail, PC1-p30, is overexpressed in ADPKD...
August 2014: Journal of the American Society of Nephrology: JASN
Garth H Utter, Jason B Young, Leslie A Theard, David M Cropp, Craig J Mohar, Daniel Eisenberg, Carol R Schermer, Leon J Owens
BACKGROUND: In medical settings, motivational interviewing-based "brief intervention" (BI) counseling reduces alcohol-related risk-taking behavior and harm in high-risk populations. Individuals arrested for driving under the influence of alcohol (DUI) are another at-risk population. We sought to determine whether a BI administered shortly after a first DUI arrest might decrease problematic drinking behavior. METHODS: We conducted a single-center, parallel-group, double-blinded superiority randomized trial (NCT01270217), enrolling first-time DUI arrestees at a county jail from December 2010 through April 2011...
March 2014: Journal of Trauma and Acute Care Surgery
Yifan Yang, Jason B Young, Carol R Schermer, Garth H Utter
BACKGROUND: The effectiveness of the nonsteroidal anti-inflammatory drug ketorolac in reducing pulmonary morbidity after rib fractures remains largely unknown. METHODS: A retrospective cohort study was conducted spanning January 2003 to June 2011 assessing pneumonia within 30 days and potential adverse effects of ketorolac among all patients with rib fractures who received ketorolac <4 days after injury compared with a random sample of those who did not. RESULTS: Among 202 patients who received ketorolac and 417 who did not, ketorolac use was associated with decreased pneumonia (odds ratio, ...
April 2014: American Journal of Surgery
S van Bragt, L van den Bemt, B Thoonen, J Jacobs, P Merkus, T Schermer
PURPOSE: To assess psychometric properties of the Pelican instrument, an online Dutch self-administered Quality of Life instrument for childhood asthma for scientific and clinical use. METHODS: A cohort study was done in two asthma populations and healthy children. One asthma population had assessment at start, 4 and 8 weeks. The other asthma population and healthy children had one assessment. All children were aged 6-12 years. Children completed the Pelican instrument, Paediatric Asthma Quality of Life Questionnaire, feeling thermometer and Childhood Asthma Control Test...
April 2014: Quality of Life Research
Jason B Young, Garth H Utter, Carol R Schermer, Joseph M Galante, Ho H Phan, Yifan Yang, Brock A Anderson, Lynette A Scherer
OBJECTIVE: We sought to compare resuscitation with 0.9% NaCl versus Plasma-Lyte A, a calcium-free balanced crystalloid solution, hypothesizing that Plasma-Lyte A would better correct the base deficit 24 hours after injury. BACKGROUND: Sodium chloride (0.9%) (0.9% NaCl), though often used for resuscitation of trauma patients, may exacerbate the metabolic acidosis that occurs with injury, and this acidosis may have detrimental clinical effects. METHODS: We conducted a randomized, double-blind, parallel-group trial (NCT01270854) of adult trauma patients requiring blood transfusion, intubation, or operation within 60 minutes of arrival at the University of California Davis Medical Center...
February 2014: Annals of Surgery
Persijn J Honkoop, Rik J B Loijmans, Evelien H Termeer, Jiska B Snoeck-Stroband, Gerben Ter Riet, Tjard R J Schermer, Jacob K Sont
BACKGROUND: Online self-management programmes for asthma have recently become available. International guidelines suggest that the Asthma Control Questionnaire (ACQ) can be used in these programmes. In order to assess the current level of control and guide therapy, the same cut-off values are being used as in conventional asthma management. However, results might differ between different types of administration of the ACQ. AIMS: To assess the agreement between an online self-administered version of the ACQ and an interviewer-administered version at a routine visit...
September 2013: Primary Care Respiratory Journal: Journal of the General Practice Airways Group
Cynthia Forlini, Wayne Hall, Bruce Maxwell, Simon M Outram, Peter B Reiner, Dimitris Repantis, Maartje Schermer, Eric Racine
No abstract text is available yet for this article.
February 2013: EMBO Reports
Sebastian Brähler, Christina Ising, Henning Hagmann, Melanie Rasmus, Martin Hoehne, Christine Kurschat, Tuelay Kisner, Heike Goebel, Stuart Shankland, Klaus Addicks, Friedrich Thaiss, Bernhard Schermer, Manolis Pasparakis, Thomas Benzing, Paul Thomas Brinkkoetter
Inflammation conveys the development of glomerular injury and is a major cause of progressive kidney disease. NF-κB signaling is among the most important regulators of proinflammatory signaling. Its role in podocytes, the epithelial cells at the kidney filtration barrier, is poorly understood. Here, we inhibited NF-κB signaling in podocytes by specific ablation of the NF-κB essential modulator (NEMO, IKKγ). Podocyte-specific NEMO-deficient mice (NEMO(pko)) were viable and did not show proteinuria or overt changes in kidney morphology...
November 15, 2012: American Journal of Physiology. Renal Physiology
Katja Höpker, Henning Hagmann, Safiya Khurshid, Shuhua Chen, Pia Hasskamp, Tamina Seeger-Nukpezah, Katharina Schilberg, Lukas Heukamp, Tobias Lamkemeyer, Martin L Sos, Roman K Thomas, Drew Lowery, Frederik Roels, Matthias Fischer, Max C Liebau, Ulrike Resch, Tülay Kisner, Fabian Röther, Malte P Bartram, Roman Ulrich Müller, Francesca Fabretti, Peter Kurschat, Björn Schumacher, Matthias Gaestel, René H Medema, Michael B Yaffe, Bernhard Schermer, H Christian Reinhardt, Thomas Benzing
Following genotoxic stress, cells activate a complex signalling network to arrest the cell cycle and initiate DNA repair or apoptosis. The tumour suppressor p53 lies at the heart of this DNA damage response. However, it remains incompletely understood, which signalling molecules dictate the choice between these different cellular outcomes. Here, we identify the transcriptional regulator apoptosis-antagonizing transcription factor (AATF)/Che-1 as a critical regulator of the cellular outcome of the p53 response...
October 17, 2012: EMBO Journal
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