A large-scale database study for the prescription status of a new voltage-gated Ca2+ channel α2δ ligand, mirogabalin, in Japan

Study Design Retrospective database study. Objective Navigation has been increasingly used to treat degenerative disease, with positive radiographic and clinical outcomes and fewer adverse events and reoperations, despite increased operative time. However, short-term analysis on treating adult spinal deformity (ASD) surgery with navigation is limited, particularly using large nationally represented cohorts. This is the first large-scale database study to compare 30-day readmission, reoperation, morbidity, and value-per-operative time for navigated and conventional ASD surgery. Methods Adults were identified in the National Surgical Quality Improvement Program (NSQIP) database. Multivariate regression was used to compare outcomes between navigated and conventional surgery and to control for predictors and baseline differences. Results 3190 ASD patients were included. Navigated and conventional patients were similar. Navigated cases had greater operative time (405 vs 320 min) and mean RVUs per case (81.3 vs 69.7), and had more supplementary pelvic fixations (26.1 vs 13.4%) and osteotomies (50.3 vs 27.7%) ( P <.001). In univariate analysis, navigation had greater reoperation (9.9 vs 5.2%, P = .011), morbidity (57.8 vs 46.8%, P = .007), and transfusion (52.2 vs 41.8%, P = .010) rates. Readmission was similar (11.9 vs 8.4%). In multivariate analysis, navigation predicted reoperation (OR = 1.792, P = .048), but no longer predicted morbidity or transfusion. Most reoperations were infectious and hardware-related. Conclusions Despite controlling for patient-related and procedural factors, navigation independently predicted a 79% increased odds of reoperation but did not predict morbidity or transfusion. Readmission was similar between groups. This is explained, in part, by greater operative time and transfusion, which are risk factors for infection. Reoperation most frequently occurred for wound- and hardware-related reasons, suggesting navigation carries an increased risk of infectious-related events beyond increased operative time.

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Helicobacter pylori eradication failure may have confounded the recent large-scale health database study that showed proton pump inhibitors increase gastric cancer risk

Gut ◽

10.1136/gutjnl-2017-315698 ◽

2017 ◽

Vol 67 (11) ◽

pp. 2071-2072 ◽

Cited By ~ 7

Author(s):

Hidekazu Suzuki ◽

Juntaro Matsuzaki

Keyword(s):

Gastric Cancer ◽

Helicobacter Pylori ◽

Cancer Risk ◽

Proton Pump Inhibitors ◽

Proton Pump ◽

Large Scale ◽

Gastric Cancer Risk ◽

Helicobacter Pylori Eradication ◽

Database Study ◽

Health Database

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Parallel All-Optical Assay to Study Use-Dependent Functioning of Voltage-Gated Ion Channels in a Miniaturized Format

SLAS DISCOVERY Advancing Life Sciences ◽

10.1177/2472555220976083 ◽

2020 ◽

pp. 247255522097608

Author(s):

Viviana Agus ◽

Tod A. Flak ◽

Paola Picardi ◽

Sara Pizzi ◽

Lucia Rutigliano ◽

...

Keyword(s):

Ion Channels ◽

Drug Screening ◽

Large Scale ◽

Neuromuscular Disorders ◽

Optical Recording ◽

Channel Blockers ◽

Voltage Gated ◽

All Optical ◽

Voltage Gated Ion Channels ◽

Gated Ion Channels

Voltage-gated ion channels produce rapid transmembrane currents responsible for action potential generation and propagation at the neuronal, muscular, and cardiac levels. They represent attractive clinical targets because their altered firing frequency is often the hallmark of pathological signaling leading to several neuromuscular disorders. Therefore, a method to study their functioning upon repeated triggers at different frequencies is desired to develop new drug molecules selectively targeting pathological phenotype. Optogenetics provides powerful tools for millisecond switch of cellular excitability in contactless, physiological, and low-cost settings. Nevertheless, its application to large-scale drug-screening operations is still limited by long processing time (due to sequential well read), rigid flashing pattern, lack of online compound addition, or high consumable costs of existing methods. Here, we developed a method that enables simultaneous analysis of 384-well plates with optical pacing, fluorescence recording, and liquid injection. We used our method to deliver programmable millisecond-switched depolarization through light-activated opsin in concomitance with continuous optical recording by a fluorescent indicator. We obtained 384-well pacing of recombinant voltage-activated sodium or calcium channels, as well as induced pluripotent stem cell (iPSC)-derived cardiomyocytes, in all-optical parallel settings. Furthermore, we demonstrated the use-dependent behavior of known ion channel blockers by optogenetic pacing at normal or pathological firing frequencies, obtaining very good signal reproducibility and accordance with electrophysiology data. Our method provides a novel physiological approach to study frequency-dependent drug behavior using reversible programmable triggers. The all-optical parallel settings combined with contained operational costs make our method particularly suited for large-scale drug-screening campaigns as well as cardiac liability studies.

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Characterization of a gene-trap knockout mouse model of Scn2a encoding voltage-gated sodium channel Nav1.2

10.1101/2020.06.23.150367 ◽

2020 ◽

Author(s):

Muriel Eaton ◽

Jingliang Zhang ◽

Zhixiong Ma ◽

Anthony C. Park ◽

Emma Lietzke ◽

...

Keyword(s):

Mouse Model ◽

Sodium Channel ◽

Knockout Mouse ◽

Large Scale ◽

Autism Spectrum ◽

Gene Trap ◽

Fecal Excretion ◽

Loss Of Function ◽

Voltage Gated Sodium Channel ◽

Voltage Gated

ABSTRACTRecent large-scale genomic studies have revealed SCN2A as one of the most frequently mutated gene in patients with neurodevelopmental disorders including autism spectrum disorder and intellectual disability. SCN2A encodes for voltage-gated sodium channel isoform 1.2 (Nav1.2), which is mainly expressed in the central nervous system and responsible for the propagation of neuronal action potentials. Homozygous knockout (null) of Scn2a is perinatal lethal, whereas heterozygous knockout of Scn2a results in mild behavior abnormalities. To achieve a more substantial, but not complete, reduction of Scn2a expression, we characterized a Scn2a deficient mouse model using a targeted gene trap knockout (gtKO) strategy to recapitulate loss-of-function SCN2A disorders. This model produces viable homozygous mice (Scn2agtKO/gtKO) that can survive to adulthood, with markedly low but detectable Nav1.2 expression. Although Scn2agtKO/gtKO adult mice possess normal olfactory, taste, hearing, and mechanical sensitivity, they have decreased thermal and cold tolerance. Innate behaviors are profoundly impaired including impaired nesting, marble burying, and mating. These mice also have increased food and water intake with subsequent increases in fecal excretion of more but smaller fecal boli. This novel Scn2a gene trap knockout mouse thus provides a unique model to study pathophysiology associated with Scn2a deficiency.

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Voltage-gated proton channels exist in the plasma membrane of human oocytes

Human Reproduction ◽

10.1093/humrep/dez178 ◽

2019 ◽

Vol 34 (10) ◽

pp. 1974-1983 ◽

Cited By ~ 1

Author(s):

R Ya Smith ◽

D Morgan ◽

L Sharma ◽

V V Cherny ◽

N Tidswell ◽

...

Keyword(s):

Large Scale ◽

Human Sperm ◽

Proton Channel ◽

Human Oocytes ◽

Proton Channels ◽

Voltage Gated ◽

Registration Number ◽

Heterologous Expression Systems ◽

Competing Interest ◽

Proton Currents

Abstract STUDY QUESTION Do human oocytes express voltage-gated proton channels? SUMMARY ANSWER Human oocytes exhibit voltage-gated proton currents. WHAT IS KNOWN ALREADY Voltage-gated proton currents have been reported in human sperm, where they contribute to capacitation and motility. No such studies of human oocytes exist. STUDY DESIGN, SIZE, DURATION Voltage-clamp studies were undertaken using entire oocytes and vesicles derived from oocytes and in excised patches of membrane from oocytes. PARTICIPANTS/MATERIALS, SETTING, METHODS Frozen, thawed human metaphase II oocytes were obtained from material donated to the gamete repository at the Rush Center for Advanced Reproductive Care. Prior to patch clamping, oocytes were warmed and equilibrated. Formation of an electrically tight seal requires exposing bare oolemma. Sections of the zona pellucida (ZP) were removed using a laser, followed by repeated pipetting, to further separate the oocyte from the ZP. Patch-clamp studies were performed using the whole-cell configuration on oocytes or vesicles derived from oocytes, and using inside-out patches of membrane, under conditions optimized to detect voltage-gated proton currents. MAIN RESULTS AND THE ROLE OF CHANCE Proton currents are present at significant levels in human oocytes where they exhibit properties similar to those reported in other human cells, as well as those in heterologous expression systems transfected with the HVCN1 gene that codes for the voltage-gated proton channel. LARGE SCALE DATA N/A LIMITATIONS, REASONS FOR CAUTION Human oocytes are large cells, which limits our ability to control the intracellular solution. Subtle effects of cryopreservation by vitrification and subsequent warming on properties of HVCN1, the HVCN1 gene product, cannot be ruled out. WIDER IMPLICATIONS OF THE FINDINGS Possible functions for voltage-gated proton channels in human oocytes may now be contemplated. STUDY FUNDING/COMPETING INTEREST(S) NIH R35GM126902 (TED), Bears Care (DM). No competing interests. TRIAL REGISTRATION NUMBER N/A.

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A large scale preparative gel electrophoresis separation of α1 and α2 subunits of the voltage-gated Ca2+ channel from rabbit skeletal muscle

Electrophoresis ◽

10.1002/elps.11501501178 ◽

1994 ◽

Vol 15 (1) ◽

pp. 1186-1190 ◽

Cited By ~ 3

Author(s):

Okot Nyormoi ◽

Toni Schneider ◽

Robert G. Smith

Keyword(s):

Skeletal Muscle ◽

Gel Electrophoresis ◽

Large Scale ◽

Rabbit Skeletal Muscle ◽

Voltage Gated ◽

Electrophoresis Separation

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Some comments about observations and image processing of comet 29P/Schwassmann-Wachmann 1

International Astronomical Union Colloquium ◽

10.1017/s0252921100031493 ◽

1999 ◽

Vol 173 ◽

pp. 243-248

Author(s):

D. Kubáček ◽

A. Galád ◽

A. Pravda

Keyword(s):

Image Processing ◽

Large Scale ◽

Harvard College ◽

Oak Ridge ◽

Large Scale Structures ◽

Short Period Comet ◽

Short Period ◽

Scale Structures ◽

Harvard College Observatory ◽

Period Comet

AbstractUnusual short-period comet 29P/Schwassmann-Wachmann 1 inspired many observers to explain its unpredictable outbursts. In this paper large scale structures and features from the inner part of the coma in time periods around outbursts are studied. CCD images were taken at Whipple Observatory, Mt. Hopkins, in 1989 and at Astronomical Observatory, Modra, from 1995 to 1998. Photographic plates of the comet were taken at Harvard College Observatory, Oak Ridge, from 1974 to 1982. The latter were digitized at first to apply the same techniques of image processing for optimizing the visibility of features in the coma during outbursts. Outbursts and coma structures show various shapes.

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