Medicine and Health Sciences Commons^™

Progressive Acceleration Of Insulin Exposure Over 7 Days Of Infusion Set Wear, Jasmin R. Kastner, Timothy S. Bailey, Poul Strange, Leon Shi, Keith A. Oberg, Paul J. Strasma, Jeffrey I. Joseph, Douglas B. Muchmore

Department of Anesthesiology Faculty Papers

Insulin exposure varies over 3 days of insulin infusion set (IIS) wear making day-to-day insulin dosing challenging for people with diabetes (PWD). Here we report insulin pharmacodynamic (PD) and pharmacokinetic (PK) data extending these observations to 7 days of IIS wear. PWD (A1C ≤8.5%, C-peptide tmax (P < 0.001), Cmax (P < 0.05), and mean residence time (P < 0.0001). Area under the insulin concentration curve (AUC0–300) declined by ∼24% from days 0 to 7 (P < 0.05). These results confirm/extend previous observations showing progressive acceleration of insulin exposure over IIS wear time. This may have implications for PWD and designers of closed-loop algorithms, although larger studies are necessary to confirm this. The study was registered in clinicaltrials.gov (NCT04398030).

How To Manage The Initiation Of Apomorphine Therapy Without Antiemetic Pretreatment: A Review Of The Literature, Stuart H. Isaacson, Richard B. Dewey, Rajesh Pahwa, Daniel E. Kremens

Department of Neurology Faculty Papers

Introduction

Pretreatment with the antiemetic trimethobenzamide has been recommended practice in the United States (US) to address the risk of nausea and vomiting during initiation of apomorphine treatment. However, trimethobenzamide is no longer being manufactured in the US, and despite the recent update to the US prescribing information, there may be uncertainty regarding how to initiate apomorphine.

Methods

To better understand why antiemetic pretreatment was recommended and if it is necessary when initiating apomorphine therapy, we performed a literature review of subcutaneous apomorphine therapy initiation with and without antiemetic pretreatment in patients with PD.

Results

Three studies were identified as …

Delta Oscillation Coupled Propagating Fast Ripples Precede Epileptiform Discharges In Patients With Focal Epilepsy, Shennan A. Weiss, Laurent Sheybani, Nitish Seenarine, Itzhak Fried, Chengyuan Wu, Ashwini Sharan, Jerome Engel Jr., Michael R. Sperling, Yuval Nir, Richard J. Staba

Department of Neurology Faculty Papers

Epileptiform spikes are used to localize epileptogenic brain tissue. The mechanisms that spontaneously trigger epileptiform discharges are not yet elucidated. Pathological fast ripple (FR, 200–600 Hz) are biomarkers of epileptogenic brain, and we postulated that FR network interactions are involved in generating epileptiform spikes. Using macroelectrode stereo intracranial EEG (iEEG) recordings from a cohort of 46 patients we found that, in the seizure onset zone (SOZ), propagating FR were more often followed by an epileptiform spike, as compared with non-propagating FR (p < 0.05). Propagating FR had a distinct frequency and larger power (p < 1e-10) and were more strongly phase coupled to the peak of iEEG delta oscillation, which likely correspond with the DOWN states during non-REM sleep (p < 1e-8), than non-propagating FR. While FR propagation was rare, all FR occurred with the highest probability within +/− 400 msec of epileptiform spikes with superimposed high-frequency oscillations (p < 0.05). Thus, a sub-population of epileptiform spikes in the SOZ, are preceded by propagating FR that are coordinated by the DOWN state during non-REM sleep.

Individualised Prediction Of Drug Resistance And Seizure Recurrence After Medication Withdrawal In People With Juvenile Myoclonic Epilepsy: A Systematic Review And Individual Participant Data Meta-Analysis, Remi Stevelink, Dania Al-Toma, Floor E. Jansen, Herm J. Lamberink, Ali A. Asadi-Pooya, Mohsen Farazdaghi, Gonçalo Cação, Sita Jayalakshmi, Anuja Patil, Çiğdem Özkara, Şenay Aydın, Joanna Gesche, Christoph P. Beier, Linda J. Stephen, Martin J. Brodie, Gopeekrishnan Unnithan, Ashalatha Radhakrishnan, Julia Höfler, Eugen Trinka, Roland Krause, Emanuele Cerulli Irelli, Carlo Di Bonaventura, Jerzy P. Szaflarski, Laura E. Hernández-Vanegas, Monica L. Moya-Alfaro, Yingying Zhang, Dong Zhou, Nicola Pietrafusa, Nicola Specchio, Giorgi Japaridze, Sándor Beniczky, Mubeen Janmohamed, Patrick Kwan, Marte Syvertsen, Kaja K. Selmer, Bernd J. Vorderwülbecke, Martin Holtkamp, Lakshminarayanapuram G. Viswanathan, Sanjib Sinha, Betül Baykan, Ebru Altindag, Felix Von Podewils, Juliane Schulz, Udaya Seneviratne, Alejandro Viloria-Alebesque, Ioannis Karakis, Wendyl J. D'Souza, Josemir W. Sander, Bobby P. C. Koeleman, Willem M. Otte, Kees P. J. Braun

Department of Neurology Faculty Papers

BACKGROUND: A third of people with juvenile myoclonic epilepsy (JME) are drug-resistant. Three-quarters have a seizure relapse when attempting to withdraw anti-seizure medication (ASM) after achieving seizure-freedom. It is currently impossible to predict who is likely to become drug-resistant and safely withdraw treatment. We aimed to identify predictors of drug resistance and seizure recurrence to allow for individualised prediction of treatment outcomes in people with JME.

METHODS: We performed an individual participant data (IPD) meta-analysis based on a systematic search in EMBASE and PubMed - last updated on March 11, 2021 - including prospective and retrospective observational studies reporting on …

The Enigma Of Primary Hypertension In Childhood, Bonita Falkner

Department of Medicine Faculty Papers

Beginning in the 1970s, hypertension in children and adolescents has been defined as systolic and/or diastolic blood pressure (BP) that is equal to or greater than the 95th percentile of the normal BP distribution in healthy children. The definition of hypertension in adults is based on longitudinal data that links a BP level with an increased risk for subsequent adverse outcomes related to hypertension including heart failure, kidney failure, stroke, or death. The statistical definition of hypertension continues to be used in childhood because there have been no data that link a BP level in childhood with a heightened risk …

Intrinsic Disorder In Bap1 And Its Association With Uveal Melanoma., Mak B Djulbegovic, David J Taylor, Vladimir N Uversky, Anat Galor, Carol L Shields, Carol L Karp

Wills Eye Hospital Papers

BACKGROUND: Specific subvariants of uveal melanoma (UM) are associated with increased rates of metastasis compared to other subvariants. BRCA1 (BReast CAncer gene 1)-associated protein-1 (BAP1) is encoded by a gene that has been linked to aggressive behavior in UM.

METHODS: We evaluated BAP1 for the presence of intrinsically disordered protein regions (IDPRs) and its protein-protein interactions (PPI). We evaluated specific sequence-based features of the BAP1 protein using a set of bioinformatic databases, predictors, and algorithms.

RESULTS: We show that BAP1's structure contains extensive IDPRs as it is highly enriched in proline residues (the most disordered amino acid; p-value < 0.05), the average percent of predicted disordered residues (PPDR) was 57.34%, and contains 9 disorder-based binding sites (ie. molecular recognition features (MoRFs)). BAP1's intrinsic disorder allows it to engage in a complex PPI network with at least 49 partners (p …