Spatial and temporal tracking of multi-layered cells sheet using reporter gene imaging with human sodium iodide symporter: a preclinical study using a rat model of myocardial infarction.

PURPOSE: This study aimed to evaluate a novel technique for cell tracking by visualising the activity of the human sodium/iodide symporter (hNIS) after transplantation of hNIS-expressing multilayered cell sheets in a rat model of chronic myocardial infarction. METHODS: Triple-layered cell sheets were generated from mouse embryonic fibroblasts (MEFs) derived from mice overexpressing hNIS (hNIS-Tg). Myocardial infarction was induced by permanent ligation of the left anterior descending coronary artery in F344 athymic rats, and a triple-layered MEFs sheets were transplanted to the infarcted area two weeks after surgery. To validate the temporal tracking and kinetic analysis of the transplanted MEFs sheets, sequential cardiac single-photon emission computed tomography (SPECT) examinations with a 99mTcO4- injection were performed. The cell sheets generated using MEFs of wild-type mice (WT) served as controls. RESULTS: A significantly higher amount of 99mTcO4- was taken into the hNIS-Tg MEFs than into WT MEFs (146.1 ± 30.9-fold). The obvious accumulation of 99mTcO4- was observed in agreement with the region where hNIS-Tg MEFs were transplanted, and these radioactivities peaked 40-60 min after 99mTcO4- administration. The volume of distribution of the hNIS-Tg MEF sheets declined gradually after transplantation, implying cellular malfunction and a loss in the number of transplanted cells. CONCLUSION: The reporter gene imaging with hNIS enables the serial tracking and quantitative kinetic analysis of cell sheets transplanted to infarcted hearts.

Greater cervical kyphosis during flexion increases the risk of kyphotic deformity after laminoplasty in patients with cervical spondylotic myelopathy.

Kyphotic deformity following the loss of cervical lordosis can lead to unfavourable neurological recovery after cervical laminoplasty (CLP); therefore, it is essential to identify its risk factors. Recent studies have demonstrated that the dynamic parameters of the cervical spine, based on baseline flexion/extension radiographs, are highly useful to estimate the loss of cervical lordosis after CLP. However, it remains unclear whether such dynamic parameters can predict kyphotic deformity development after CLP. Hence, the present study aimed to investigate whether the dynamic parameters could predict kyphotic deformity in patients with cervical spondylotic myelopathy (CSM) after CLP. This retrospective study included 165 patients, consisting of 10 and 155 patients with and without cervical kyphosis of C2-C7 angle ≤ -10° at the final follow-up period, respectively. Among the static and dynamic parameters of the cervical spine, greater cervical kyphosis during flexion (fC2-C7 angle) demonstrated the best discrimination between these two cohorts, with an optimal cutoff value of -27.5°. Meanwhile, greater gap range of motion (gROM = flexion ROM - extension ROM ) had the highest ability to predict a loss of ≥ 10° in C2-C7 angle after CLP, with an optimal cutoff value of 28.5°. This study suggests that in patients with CSM, fC2-C7 angle ≤ -25° on baseline radiographs is a potential risk for kyphotic deformity after CLP. In clinical practice, the patients with this criterion (fC2-C7 angle ≤ -25°) along with gROM ≥ 30° are at high risk of developing significant kyphotic deformity after CLP.

Long-term safety of desmopressin orally disintegrating tablets in men with nocturia due to nocturnal polyuria: Interim results of a specified drug use-results survey in Japan.

OBJECTIVES: This interim report presents the 12-week results of a post-marketing surveillance evaluating the safety of desmopressin orally disintegrating tablets 25 and 50 µg in Japanese men with nocturia due to nocturnal polyuria. METHODS: Of the planned study population of 1000 Japanese men receiving desmopressin for the first time for nocturia due to nocturnal polyuria, 971 cases were enrolled. In this interim analysis, 9 cases, including 6 registry violations and 3 cases of unconfirmed desmopressin dosing, were excluded from the 354 case report forms collected and fixed by the end of December 2021, and data up to 12 weeks after administration in 345 cases were defined as the safety analysis set. RESULTS: The mean age was 74.5 ± 9.9 years and 88.7% of the survey participants were aged ≥65 years. Desmopressin was started at a dose of 25 µg in 153 cases (44.3%). There were 102 adverse drug reactions (ADRs) reported in 71 cases, including 6 serious ADRs in 3 cases (0.9%). The most common ADR was hyponatremia occurring in 29 cases (8.4%). Eight of the hyponatremic cases were asymptomatic. Symptoms were resolved or slightly improved within 4 weeks of onset in 13 of 29 cases of hyponatremia. In addition, hyponatremia occurred in 11 of 217 cases (5.1%), with a serum sodium level before the administration of desmopressin of ≥140 mmol/L, and in 13 of 87 cases (14.9%), with a level of 135-139 mmol/L, and was not measured in 5 hyponatremia cases. Patient characteristics that showed significant differences in the occurrence of hyponatremia included body weight, body mass index, renal function, and pretreatment serum sodium level. Regular monitoring of serum sodium is necessary for early detection of hyponatremia. CONCLUSIONS: Hyponatremia was the most common ADR when desmopressin orally disintegrating tablets were used to treat nocturia due to nocturnal polyuria over a 12-week period.

The role of metabolism in cardiac development.

Metabolism is the fundamental process that sustains life. The heart, in particular, is an organ of high energy demand, and its energy substrates have been studied for more than a century. In recent years, there has been a growing interest in understanding the role of metabolism in the early differentiation of pluripotent stem cells and in cancer research. Studies have revealed that metabolic intermediates from glycolysis and the tricarboxylic acid cycle act as co-factors for intracellular signal transduction, playing crucial roles in regulating cell behaviors. Mitochondria, as the central hub of metabolism, are also under intensive investigation regarding the regulation of their dynamics. The metabolic environment of the fetus is intricately linked to the maternal metabolic status, and the impact of the mother's nutrition and metabolic health on fetal development is significant. For instance, it is well known that maternal diabetes increases the risk of cardiac and nervous system malformations in the fetus. Another notable example is the decrease in the risk of neural tube defects when pregnant women are supplemented with folic acid. These examples highlight the profound influence of the maternal metabolic environment on the fetal organ development program. Therefore, gaining insights into the metabolic environment within developing fetal organs is critical for deepening our understanding of normal organ development. This review aims to summarize recent findings that build upon the historical recognition of the environmental and metabolic factors involved in the developing embryo.

Clinical outcome of surgical management of mild cervical compressive myelopathy based on minimum clinically important difference.

BACKGROUND CONTEXT: Cervical compressive myelopathy (CCM), caused by cervical spondylosis (cervical spondylotic myelopathy [CSM]) or ossification of the posterior longitudinal ligament (OPLL), is a common neurological disorder in the elderly. For moderate/severe CCM, surgical management has been the first-line therapeutic option. Recently, surgical management is also recommended for mild CCM, and a few studies have reported the surgical outcome for this clinical population. Nonetheless, the present knowledge is insufficient to determine the specific surgical outcome of mild CCM. PURPOSE: To examine the surgical outcomes of mild CCM while considering the minimum clinically important difference (MCID). STUDY DESIGN: Retrospective study. PATIENT SAMPLE: Patients who underwent subaxial cervical surgery for CCM caused by CSM and OPLL between 2013 and 2022 were enrolled. OUTCOME MEASURES: The Japanese Orthopedic Association score (JOA score) was employed as the clinical outcomes. Based on previous reports, the JOA score threshold to determine mild myelopathic symptoms was set at ≥14.5 points, and the MCID of the JOA score for mild CCM was set at 1 point. METHODS: The patients with a JOA score of ≥14.5 points at baseline were stratified into the mild CCM and were examined while considering the MCID. The mild CCM cohort was dichotomized into the improvement group, including the patients with an achieved MCID (JOA score ≥1 point) or with a JOA score of 17 points (full mark) at 1 year postoperatively, and the nonimprovement group, including the others. Demographics, symptomatology, radiographic findings, and surgical procedure were compared between the two groups and studied using the receiver operating characteristic (ROC) curve. RESULTS: Of 335 patients with CCM, 43 were stratified into the mild CCM cohort (mean age, 58.5 years; 62.8% male). Among them, 25 (58.1 %) patients were assigned to the improvement group and 18 (41.9 %) were assigned to the nonimprovement group. The improvement group was significantly younger than the nonimprovement group; however, other variables did not significantly differ. ROC curve analysis showed that the optimal cutoff point of the patient's age to discriminate between the improvement and nonimprovement groups was 58 years with an area under the curve of 0.702 (p=.015). CONCLUSIONS: In the present study, the majority of patients with mild CCM experienced improvement reaching the MCID of JOA score at 1 year postoperatively. The present study suggests that for younger patients with mild CCM, especially those aged below 58 years, subjective neurological recovery is more likely to be obtained. Meanwhile, the surgery takes on a more prophylactic significance to halt disease progression for older patients. The results of this study can help in the decision-making process for this clinical population.

Atlas of fetal metabolism during mid-to-late gestation and diabetic pregnancy.

Mounting evidence suggests metabolism instructs stem cell fate decisions. However, how fetal metabolism changes during development and how altered maternal metabolism shapes fetal metabolism remain unexplored. We present a descriptive atlas of in vivo fetal murine metabolism during mid-to-late gestation in normal and diabetic pregnancy. Using 13C-glucose and liquid chromatography-mass spectrometry (LC-MS), we profiled the metabolism of fetal brains, hearts, livers, and placentas harvested from pregnant dams between embryonic days (E)10.5 and 18.5. Our analysis revealed metabolic features specific to a hyperglycemic environment and signatures that may denote developmental transitions during euglycemic development. We observed sorbitol accumulation in fetal tissues and altered neurotransmitter levels in fetal brains isolated from hyperglycemic dams. Tracing 13C-glucose revealed disparate fetal nutrient sourcing depending on maternal glycemic states. Regardless of glycemic state, histidine-derived metabolites accumulated in late-stage fetal tissues. Our rich dataset presents a comprehensive overview of in vivo fetal tissue metabolism and alterations due to maternal hyperglycemia.

Ultrasonographic Evaluation of Upper Esophageal Sphincter for Dysphagia During the Acute Postoperative Phase of Anterior Cervical Surgery.

STUDY DESIGN: A retrospective study. OBJECTIVE: To verify the pathophysiology of dysphagia during the acute postoperative phase of anterior cervical surgery and to identify its predictive features, using ultrasonographic (US) examination for upper esophageal sphincter (UES). SUMMARY OF BACKGROUND DATA: There are no clinical studies investigating dysphagia after anterior cervical surgery, using US examination for UES. MATERIALS AND METHODS: We enrolled patients who underwent anterior cervical spine surgery between August 2018 and March 2022. Dysphagia was evaluated using the Eating Assessment Tool-10 (EAT-10) questionnaires. The US examination was performed preoperatively and 2 weeks postoperatively. Three US parameters for morphologic measurements (outer diameter, inner diameter, and muscle thickness) and 4 for functional measurements (displacement, time to relax, passing duration, and time to contract) were assessed. To verify the pathophysiology of postoperative dysphagia, we examined the change in the ratios of US parameters (=US parameter 2 weeks postoperatively /US parameter at baseline ) and the existence of significant correlations with change in the EAT-10 score (=EAT-10 2 weeks postoperatively -EAT-10 at baseline ). To identify the predictive features, the baseline US parameters were compared between dysphagia (+) and dysphagia (-) groups. RESULTS: A total of 46 patients (mean age, 61.3 y; 78.3% male) were included for analysis. A greater increase of the EAT-10 score after surgery was positively correlated with change ratios of the muscle thickness and time to contract and negatively with change ratio of the inner diameter. The dysphagia (+) group exhibited significantly greater inner diameter and smaller muscle thickness at baseline than the dysphagia (-) group. CONCLUSION: Dysphagia during the acute postoperative phase of anterior cervical surgery is caused by the physical narrowing of the inner lumen due to muscle thickening of the UES and sphincter contractile dysfunction. In addition, a baseline UES morphology characterized by a greater inner diameter and a thinner muscle layer is predictive of postoperative dysphagia.

Rtf1-dependent transcriptional pausing regulates cardiogenesis.

During heart development, a well-characterized network of transcription factors initiates cardiac gene expression and defines the precise timing and location of cardiac progenitor specification. However, our understanding of the post-initiation transcriptional events that regulate cardiac gene expression is still incomplete. The PAF1C component Rtf1 is a transcription regulatory protein that modulates pausing and elongation of RNA Pol II, as well as cotranscriptional histone modifications. Here we report that Rtf1 is essential for cardiogenesis in fish and mammals, and that in the absence of Rtf1 activity, cardiac progenitors arrest in an immature state. We found that Rtf1's Plus3 domain, which confers interaction with the transcriptional pausing and elongation regulator Spt5, was necessary for cardiac progenitor formation. ChIP-seq analysis further revealed changes in the occupancy of RNA Pol II around the transcription start site (TSS) of cardiac genes in rtf1 morphants reflecting a reduction in transcriptional pausing. Intriguingly, inhibition of pause release in rtf1 morphants and mutants restored the formation of cardiac cells and improved Pol II occupancy at the TSS of key cardiac genes. Our findings highlight the crucial role that transcriptional pausing plays in promoting normal gene expression levels in a cardiac developmental context.

Notch and retinoic acid signals regulate macrophage formation from endocardium downstream of Nkx2-5.

Hematopoietic progenitors are enriched in the endocardial cushion and contribute, in a Nkx2-5-dependent manner, to tissue macrophages required for the remodeling of cardiac valves and septa. However, little is known about the molecular mechanism of endocardial-hematopoietic transition. In the current study, we identified the regulatory network of endocardial hematopoiesis. Signal network analysis from scRNA-seq datasets revealed that genes in Notch and retinoic acid (RA) signaling are significantly downregulated in Nkx2-5-null endocardial cells. In vivo and ex vivo analyses validate that the Nkx2-5-Notch axis is essential for the generation of both hemogenic and cushion endocardial cells, and the suppression of RA signaling via Dhrs3 expression plays important roles in further differentiation into macrophages. Genetic ablation study revealed that these macrophages are essential in cardiac valve remodeling. In summary, the study demonstrates that the Nkx2-5/Notch/RA signaling plays a pivotal role in macrophage differentiation from hematopoietic progenitors.

Changes in macrophage immunometabolism as a marker of skeletal muscle dysfunction across the lifespan.

One of the most pronounced changes in the elderly is loss of strength and mobility due to the decline of skeletal muscle function, resulting in a multifactorial condition termed sarcopenia. Although significant clinical changes begin to manifest at advanced ages, recent studies have shown that changes at the cellular and molecular level precede the symptomatology of sarcopenia. By utilizing a single-cell transcriptomic atlas of mouse skeletal muscle across the lifespan, we identified a clear sign of immune senescence that presents during middle age. More importantly, the change in macrophage phenotype in middle age may explain the changes in extracellular matrix composition, especially collagen synthesis, that contributes to fibrosis and overall muscle weakness with advanced age. Our results show a novel paradigm whereby skeletal muscle dysfunction is driven by alterations in tissue-resident macrophages before the appearance of clinical symptoms in middle-aged mice, providing a new therapeutic approach via regulation of immunometabolism.

Studies in the Falls Efficacy Scale-International for patients with cervical compressive myelopathy: Reliability, validity, and minimum clinically important difference.

CONTEXT: Patients with cervical compressive myelopathy (CCM) often complain of body balance problems, such as fear of falling and bodily unsteadiness. However, no accepted patient-reported outcome measures (PROMs) for this symptomatology exist. The Falls Efficacy Scale-International (FES-I) is one of the most widely used PROMs for evaluating impaired body balance in various clinical fields. OBJECTIVE: To examine reliability, validity, and minimum clinically important difference (MCID) of the FES-I for the evaluation of impaired body balance in patients with CCM. METHODS: Patients who underwent surgery for CCM were retrospectively reviewed. The FES-I was administered preoperatively and at 1 year postoperatively. Further, cJOA-LE score (subscore for lower extremities in the Japanese Orthopaedic Association score for cervical myelopathy) and stabilometric data, obtained at the same time points of the FES-I administration, were analyzed. Reliability was examined through internal consistency with Cronbach's alpha. Convergent validity was studied using correlation analysis. The MCID was estimated using anchor- and distribution-based methods. RESULTS: Overall, 151 patients were included for analysis. Cronbach's alpha coefficient was the acceptable value of 0.97 at both baseline and 1 year postoperatively. As for convergent validity, the FES-I had significant correlations with the cJOA-LE score and stabilometric parameters both at baseline and 1 year postoperatively. The MCID calculated using anchor- and distribution-based methods was 5.5 and 10, respectively. CONCLUSION: FES-I is a reliable and valid PROM to evaluate body balance problems for the CCM population. The established thresholds of MCID can help clinicians recognize the clinical significance of changes in patient status.

NanoSPECT imaging reveals the uptake of 123I-labelled oxidized low-density lipoprotein in the brown adipose tissue of mice via CD36.

AIMS: The liver is the major organ shown to remove oxidized low-density lipoprotein (oxLDL) from the circulation. Given increased evidence that thermogenic adipose tissue has anti-effects, we used 123I-labelled oxLDL as a tracer to reveal oxLDL accumulation in the brown adipose tissue (BAT) of mice. We also explored the mechanisms of oxLDL accumulation in BAT. METHODS AND RESULTS: We used high-resolution nanoSPECT/CT to investigate the tissue distribution of 123I-oxLDL and 123I-LDL (control) following intravenous injection into conscious mice. 123I-oxLDL distribution was discovered in BAT at an intensity equivalent to that in the liver, whereas 123I-LDL was detected mostly in the liver. Consistent with the function of BAT related to sympathetic nerve activity, administering anaesthesia in mice almost completely eliminated the accumulation of 123I-oxLDL in BAT, and this effect was reversed by administering ß3-agonist. Furthermore, exposing mice to cold stress at 4°C enhanced 123I-oxLDL accumulation in BAT. Because in 123I-oxLDL, the protein of oxLDL was labelled, we performed additional experiments with DiI-oxLDL in which the lipid phase of oxLDL was fluorescently labelled and observed similar results, suggesting that the whole oxLDL particle was taken up by BAT. To identify the receptor responsible for oxLDL uptake in BAT, we analysed the expression of known oxLDL receptors (e.g. SR-A, CD36, and LOX-1) in cultured brown adipocyte cell line and primary brown adipocytes and found that CD36 was the major receptor expressed. Treatment of cells with CD36 siRNA or CD36 neutralizing antibody significantly inhibited DiI-oxLDL uptake. Finally, CD36 deletion in mice abolished the accumulation of 123I-oxLDL and DiI-oxLDL in BAT, indicating that CD36 is the major receptor for oxLDL in BAT. CONCLUSION: We show novel evidence for the CD36-mediated accumulation of oxLDL in BAT, suggesting that BAT may exert its anti-atherogenic effects by removing atherogenic LDL from the circulation.

A novel murine model of atrial fibrillation by diphtheria toxin-induced injury.

The treatment of atrial fibrillation (AF) continues to be a significant clinical challenge. While genome-wide association studies (GWAS) are beginning to identify AF susceptibility genes (Gudbjartsson et al., Nature, 2007, 448, 353-357; Choi et al., Circ. Res., 2020, 126, 200-209; van Ouwerkerk et al., Circ. Res., 2022, 127, 229-243), non-genetic risk factors including physical, chemical, and biological environments remain the major contributors to the development of AF. However, little is known regarding how non-genetic risk factors promote the pathogenesis of AF (Weiss et al., Heart Rhythm, 2016, 13, 1868-1877; Chakraborty et al., Heart Rhythm, 2020, 17, 1,398-1,404; Nattel et al., Circ. Res., 2020, 127, 51-72). This is, in part, due to the lack of a robust and reliable animal model induced by non-genetic factors. The currently available models using rapid pacing protocols fail to generate a stable AF phenotype in rodent models, often requiring additional genetic modifications that introduce potential sources of bias (Schüttler et al., Circ. Res., 2020, 127, 91-110). Here, we report a novel murine model of AF using an inducible and tissue-specific activation of diphtheria toxin (DT)-mediated cellular injury system. By the tissue-specific and inducible expression of human HB-EGF in atrial myocytes, we developed a reliable, robust and scalable murine model of AF that is triggered by a non-genetic inducer without the need for AF susceptibility gene mutations.

A Collaborative Study on the Classification of Silicone Oil Droplets and Protein Particles Using Flow Imaging Method.

In this study, we conducted a collaborative study on the classification between silicone oil droplets and protein particles detected using the flow imaging (FI) method toward proposing a standardized classifier/model. We compared four approaches, including a classification filter composed of particle characteristic parameters, principal component analysis, decision tree, and convolutional neural network in the performance of the developed classifier/model. Finally, the points to be considered were summarized for measurement using the FI method, and for establishing the classifier/model using machine learning to differentiate silicone oil droplets and protein particles.

Segmental cervical instability does not drive the loss of cervical lordosis after laminoplasty in patients with cervical spondylotic myelopathy.

BACKGROUND/CONTEXT: Kyphotic deformity after cervical laminoplasty (CLP) often leads to unfavorable neurological recovery due to insufficient indirect decompression of the spinal cord. Existing literature has described that segmental cervical instability is a contraindication for CLP because it is a potential risk factor for kyphotic changes after surgery; however, this has never been confirmed in any clinical studies. PURPOSE: To confirm whether segmental cervical instability was an independent risk factor for postoperative kyphotic change and to examine whether segmental cervical instability led to poor neurological outcomes after CLP for cervical spondylotic myelopathy (CSM). STUDY DESIGN/SETTING: A retrospective study PATIENT SAMPLE: Patients who underwent CLP for CSM between January 2013 and January 2021 with a follow-up period of ≥1 year were enrolled. OUTCOME MEASURES: Cervical radiographic measurements including C2-C7 lordosis (C2-7 angle), cervical sagittal vertical axis, C7 slope, flexion range of motion (fROM) and extension ROM (eROM) were assessed using neutral and flexion-extension views. Segmental cervical instability was classified into anterolisthesis (AL) of ≥2 mm displacement, retrolisthesis (RL) of ≥2 mm displacement, and translational instability (TI) of ≥3 mm translational motion. The amount of C2-7 angle loss at the follow-up period compared to the preoperative measurements was defined as cervical lordosis loss (CLL). Neurological outcomes were assessed using the recovery rate of the Japanese Orthopedic Association score (JOA-RR). METHODS: CLL was compared among patients with and without segmental cervical instability. Further, multiple linear regression model for CLL was built for the evaluation with adjustment of the reported risks, including cervical sagittal vertical axis, C7 slope, fROM, eROM, and patient age together with AL, RL, and TI, as independent variables. The JOA-RR was also compared between patients with and without segmental cervical instability. RESULTS: A total of 138 patients (mean age, 68.7 years; 65.9% male) were included in the analysis. AL, RL, and TI were found in 12 (8.7%), 33 (23.9%), and 16 (11.6%) patients, respectively. Comparisons among the groups showed that AL led to greater CLL; however, RL and TI did not. Multiple linear regression analysis revealed that greater CLL is significantly associated with greater fROM and smaller eROM (regression coefficient [ß]=0.328, 95% confidence interval: 0.178 to 0.478, p<.001; ß=-0.372, 95% confidence interval: -0.591 to -0.153, p=.001, respectively). However, there were no significant statistical associations in the AL, RL, and TI. Whereas, patients with AL tended to exhibit lower JOA-RR than those without AL (37.8% vs. 52.0%, p=.108). CONCLUSIONS: Segmental cervical instability is not the definitive driver for loss of cervical lordosis after CLP in patients with CSM; thus, is not a contraindication in and of itself. However, it is necessary to consider the indications for CLP, according to individual cases of patients with AL on baseline radiograph, which is a sign of poor neurological recovery.

Cardio PyMEA: A user-friendly, open-source Python application for cardiomyocyte microelectrode array analysis.

Open source analytical software for the analysis of electrophysiological cardiomyocyte data offers a variety of new functionalities to complement closed-source, proprietary tools. Here, we present the Cardio PyMEA application, a free, modifiable, and open source program for the analysis of microelectrode array (MEA) data obtained from cardiomyocyte cultures. Major software capabilities include: beat detection; pacemaker origin estimation; beat amplitude and interval; local activation time, upstroke velocity, and conduction velocity; analysis of cardiomyocyte property-distance relationships; and robust power law analysis of pacemaker spatiotemporal instability. Cardio PyMEA was written entirely in Python 3 to provide an accessible, integrated workflow that possesses a user-friendly graphical user interface (GUI) written in PyQt5 to allow for performant, cross-platform utilization. This application makes use of object-oriented programming (OOP) principles to facilitate the relatively straightforward incorporation of custom functionalities, e.g. power law analysis, that suit the needs of the user. Cardio PyMEA is available as an open source application under the terms of the GNU General Public License (GPL). The source code for Cardio PyMEA can be downloaded from Github at the following repository: https://github.com/csdunhamUC/cardio_pymea.

Pacemaker translocations and power laws in 2D stem cell-derived cardiomyocyte cultures.

Power laws are of interest to several scientific disciplines because they can provide important information about the underlying dynamics (e.g. scale invariance and self-similarity) of a given system. Because power laws are of increasing interest to the cardiac sciences as potential indicators of cardiac dysfunction, it is essential that rigorous, standardized analytical methods are employed in the evaluation of power laws. This study compares the methods currently used in the fields of condensed matter physics, geoscience, neuroscience, and cardiology in order to provide a robust analytical framework for evaluating power laws in stem cell-derived cardiomyocyte cultures. One potential power law-obeying phenomenon observed in these cultures is pacemaker translocations, or the spatial and temporal instability of the pacemaker region, in a 2D cell culture. Power law analysis of translocation data was performed using increasingly rigorous methods in order to illustrate how differences in analytical robustness can result in misleading power law interpretations. Non-robust methods concluded that pacemaker translocations adhere to a power law while robust methods convincingly demonstrated that they obey a doubly truncated power law. The results of this study highlight the importance of employing comprehensive methods during power law analysis of cardiomyocyte cultures.

The Effects of Surgery on Postural Instability in Patients With Cervical Compressive Myelopathy: Evaluating Subjective Perceptions and Objective Measurements.

STUDY DESIGN: A retrospective study. OBJECTIVE: To investigate the effects of surgery on the subjective perception of bodily unsteadiness and the objective measurements of postural instability in patients with cervical compressive myelopathy (CCM). SUMMARY OF BACKGROUND DATA: Several studies have demonstrated that CCM patients have impaired postural stability and investigated its surgical outcomes. However, these studies have only objectively measured postural stability by using a stabilometer or three-dimensional motion capture system. There have been no studies examining the subjective perception of postural instability in CCM patients. MATERIALS AND METHODS: We retrospectively reviewed patients who underwent decompressive surgery for CCM. The Fall Efficacy Scale-International (FES-I) and a self-prepared questionnaire were used to evaluate subjective perception of bodily unsteadiness. To objectively assess postural instability, a stabilometric analysis was performed with the following parameters: sway area (SwA, cm2), sway velocity (SwV, cm/s), and sway density (SwD, /cm). The evaluations were performed preoperatively, during the early postoperative period (3-6 mo postoperatively), and at 1-year postoperatively in patients with CCM. The evaluation results were compared with age-matched, sex-matched, and body mass index-matched healthy subjects. RESULTS: We included 70 CCM patients and 36 healthy subjects in this study. In both the FES-I and self-prepared questionnaire, CCM patients reported significantly milder postoperative bodily unsteadiness. The stabilometric parameters were significantly improved during the postoperative period when compared with preoperative values. Nevertheless, neither the self-reported outcome measures nor stabilometric parameters of CCM patients reached the levels of those in healthy controls in the postoperative period. CONCLUSION: This was the first study to examine CCM surgical outcomes in terms of both subjective perception and objective postural instability. While both objective postural stability and subjective perception improved following decompressive surgery, they did not reach the levels seen in healthy participants. LEVEL OF EVIDENCE: Level III.