scholarly journals Theoretical Models and Computational Analysis of Action Potential Dispersion for Cardiac Arrhythmia Risk Stratification

2021 ◽  
Vol 8 ◽  
Author(s):  
Uma Mahesh R. Avula ◽  
Lea Melki ◽  
Jared S. Kushner ◽  
Stephanie Liang ◽  
Elaine Y. Wan
Keyword(s):  
Mouse Model ◽  
Risk Stratification ◽  
Action Potential ◽  
Cardiac Arrhythmias ◽  
Computational Analysis ◽  
Treatment Strategies ◽  
Theoretical Models ◽  
Regional Heterogeneity ◽  
Dispersion Patterns ◽  
Arrhythmia Risk Stratification

Reentrant cardiac arrhythmias such as atrial fibrillation (AF) and ventricular fibrillation (VF) are common cardiac arrhythmias that account for substantial morbidity and mortality throughout the world. However, the mechanisms and optimal ablation treatment strategies for such arrhythmias are still unclear. Using 2D optical mapping of a mouse model with AF and VF, we have identified regional heterogeneity of the action potential duration (APD) in the atria and ventricles of the heart as key drivers for the initiation and persistence of reentry. The purpose of this paper is to discuss theoretical patterns of dispersion, demonstrate patterns of dispersion seen in our mouse model and discuss the computational analysis of APD dispersion patterns. These analyses and discussions may lead to better understanding of dispersion patterns in patients with these arrhythmias, as well as help comprehend whether and how reducing dispersion can lead to arrhythmia risk stratification and treatment strategies for arrhythmias.

scholarly journals Mice carrying an analogous heterozygous dynamin 2 K562E mutation that causes neuropathy in humans develop predominant characteristics of a primary myopathy

2020 ◽  
Vol 29 (8) ◽  
pp. 1253-1273
Author(s):  
Jorge A Pereira ◽  
Joanne Gerber ◽  
Monica Ghidinelli ◽  
Daniel Gerber ◽  
Luigi Tortola ◽  
...  
Keyword(s):  
Mouse Model ◽  
Treatment Strategies ◽  
Underlying Disease ◽  
Potential Treatment ◽  
Type B ◽  
Disease Mechanism ◽  
Demyelinating Neuropathy ◽  
Charcot Marie Tooth ◽  
Dynamin 2

Abstract Some mutations affecting dynamin 2 (DNM2) can cause dominantly inherited Charcot–Marie–Tooth (CMT) neuropathy. Here, we describe the analysis of mice carrying the DNM2 K562E mutation which has been associated with dominant-intermediate CMT type B (CMTDIB). Contrary to our expectations, heterozygous DNM2 K562E mutant mice did not develop definitive signs of an axonal or demyelinating neuropathy. Rather, we found a primary myopathy-like phenotype in these mice. A likely interpretation of these results is that the lack of a neuropathy in this mouse model has allowed the unmasking of a primary myopathy due to the DNM2 K562E mutation which might be overshadowed by the neuropathy in humans. Consequently, we hypothesize that a primary myopathy may also contribute to the disease mechanism in some CMTDIB patients. We propose that these findings should be considered in the evaluation of patients, the determination of the underlying disease processes and the development of tailored potential treatment strategies.

scholarly journals Biomarkers for sepsis: past, present and future

2016 ◽  
Vol 10 (4) ◽  
pp. 301 ◽  
Author(s):  
Giuseppe Chesi ◽  
Natale Vazzana ◽  
Claudio Giumelli
Keyword(s):  
Clinical Practice ◽  
Risk Stratification ◽  
Supportive Care ◽  
Early Identification ◽  
Antibiotic Stewardship ◽  
Treatment Strategies ◽  
Severe Infection ◽  
Antibiotic Use ◽  
Evidence Based ◽  
Drug Resistant

Sepsis is a complication of severe infection associated with high mortality and open diagnostic issues. Treatment strategies are currently limited and essentially based on prompt recognition, aggressive supportive care and early antibiotic treatment. In the last years, extensive antibiotic use has led to selection, propagation and maintenance of drug-resistant microorganisms. In this context, several biomarkers have been proposed for early identification, etiological definition, risk stratification and improving antibiotic stewardship in septic patient care. Among these molecules, only a few have been translated into clinical practice. In this review, we provided an updated overview of established and developing biomarkers for sepsis, focusing our attention on their pathophysiological profile, advantages, limitations, and appropriate evidence-based use in the management of septic patients.

scholarly journals Capillary transfer of soft films

2020 ◽  
Vol 117 (10) ◽  
pp. 5210-5216 ◽  
Author(s):  
Yue Zhang ◽  
Mengtian Yin ◽  
Yongmin Baek ◽  
Kyusang Lee ◽  
Giovanni Zangari ◽  
...  
Keyword(s):  
High Speed ◽  
Computational Analysis ◽  
Liquid Surface ◽  
Theoretical Models ◽  
Dynamic Contact ◽  
Surface Wetting ◽  
Motion Direction ◽  
Wetting Properties ◽  
Geometric Patterns ◽  
Solid Substrates

Existing transfer technologies in the construction of film-based electronics and devices are deeply established in the framework of native solid substrates. Here, we report a capillary approach that enables a fast, robust, and reliable transfer of soft films from liquid in a defect-free manner. This capillary transfer is underpinned by the transfer front of dynamic contact among receiver substrate, liquid, and film, and can be well controlled by a selectable motion direction of receiver substrates at a high speed. We demonstrate in extensive experiments, together with theoretical models and computational analysis, the robust capabilities of the capillary transfer using a versatile set of soft films with a broad material diversity of both film and liquid, surface-wetting properties, and complex geometric patterns of soft films onto various solid substrates in a deterministic manner.

scholarly journals Hyperexcitability precedes motoneuron loss in the Smn2B/− mouse model of spinal muscular atrophy

2019 ◽  
Vol 122 (4) ◽  
pp. 1297-1311 ◽  
Author(s):  
K. A. Quinlan ◽  
E. J. Reedich ◽  
W. D. Arnold ◽  
A. C. Puritz ◽  
C. F. Cavarsan ◽  
...  
Keyword(s):  
Cell Death ◽  
Mouse Model ◽  
Action Potential ◽  
Spinal Muscular Atrophy ◽  
Postnatal Development ◽  
Motor Unit ◽  
Muscular Atrophy ◽  
Action Potential Firing ◽  
Motor Unit Number Estimation ◽  
Potential Firing

Spinal motoneuron dysfunction and loss are pathological hallmarks of the neuromuscular disease spinal muscular atrophy (SMA). Changes in motoneuron physiological function precede cell death, but how these alterations vary with disease severity and motoneuron maturational state is unknown. To address this question, we assessed the electrophysiology and morphology of spinal motoneurons of presymptomatic Smn2B/− mice older than 1 wk of age and tracked the timing of motor unit loss in this model using motor unit number estimation (MUNE). In contrast to other commonly used SMA mouse models, Smn2B/− mice exhibit more typical postnatal development until postnatal day (P)11 or 12 and have longer survival (~3 wk of age). We demonstrate that Smn2B/− motoneuron hyperexcitability, marked by hyperpolarization of the threshold voltage for action potential firing, was present at P9–10 and preceded the loss of motor units. Using MUNE studies, we determined that motor unit loss in this mouse model occurred 2 wk after birth. Smn2B/− motoneurons were also larger in size, which may reflect compensatory changes taking place during postnatal development. This work suggests that motoneuron hyperexcitability, marked by a reduced threshold for action potential firing, is a pathological change preceding motoneuron loss that is common to multiple models of severe SMA with different motoneuron maturational states. Our results indicate voltage-gated sodium channel activity may be altered in the disease process. NEW & NOTEWORTHY Changes in spinal motoneuron physiologic function precede cell death in spinal muscular atrophy (SMA), but how they vary with maturational state and disease severity remains unknown. This study characterized motoneuron and neuromuscular electrophysiology from the Smn2B/− model of SMA. Motoneurons were hyperexcitable at postnatal day (P)9–10, and specific electrophysiological changes in Smn2B/− motoneurons preceded functional motor unit loss at P14, as determined by motor unit number estimation studies.

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