Low QRS Voltage in Limb Leads Indicates Accompanying Precordial Voltage Attenuation Resulting in Underestimation of Left Ventricular Hypertrophy.
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ABSTRACT:
SUBMITTER: Gwag HB
PROVIDER: S-EPMC8700898 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Despite smaller primary tumor burdens, Pten-/-Dicer-/+ mice develop seminal vesicle obstruction at high penetrance by 32 weeks, which is in sharp contrast to that observed in Pten-/- mice. This phenomenon implies that tumors in Pten-/-Dicer-/+ mice are more locally invasive. To corroborate this invasive phenotype, we examined global changes in gene expression using Agilent 44k whole genome expression microarrays. A total of 544 genes were statistically significantly altered by at least 1.4 fold in either Pten-/-Dicer-/+ or Pten-/-Dicer-/- mice, or both mice, as compared with Pten-/- mice. Approximately 22% genes were altered in the same trend in both Pten-/-Dicer-/+ and Pten-/-Dicer-/- mice, while 70% genes were only significantly affected in Pten-/-Dicer-/- mice. Very few genes were differentially regulated between Pten-/-Dicer-/+ and Pten-/-Dicer-/- mice or were only altered in Pten-/-Dicer-/+ mice. Data analysis identified that a list of genes associated with epithelial-mesenchymal transition, cell adhesion, migration, and extracellular matrix deposition are statistically significantly altered in favor of tumor metastasis in the Pten-/-Dicer-/+ mice. QRT-PCR confirmed the changes in expression of some genes including growth factors (Tgfb1 and Ctgf), transcription factors (Snail, Twist2, and Foxc1), protease (MMPs etc.), and extracellular matrix components (Collagens). This finding corroborates the phenotypic invasiveness of the tumors in Pten-/-Dicer-/+ mice at a molecular level. Cancerous urogenital tissues from Pten-/- (Dicer WT), Pten-/-Dicer-/+ (Dicer HET), and Pten-/-Dicer-/- (Dicer KO) mice were profiled for gene expression, using Agilent microarrays. multiple group comparison
2013-07-17 | E-GEOD-42820 | biostudies-arrayexpress
Project description:Despite smaller primary tumor burdens, Pten-/-Dicer-/+ mice develop seminal vesicle obstruction at high penetrance by 32 weeks, which is in sharp contrast to that observed in Pten-/- mice. This phenomenon implies that tumors in Pten-/-Dicer-/+ mice are more locally invasive. To corroborate this invasive phenotype, we examined global changes in gene expression using Agilent 44k whole genome expression microarrays. A total of 544 genes were statistically significantly altered by at least 1.4 fold in either Pten-/-Dicer-/+ or Pten-/-Dicer-/- mice, or both mice, as compared with Pten-/- mice. Approximately 22% genes were altered in the same trend in both Pten-/-Dicer-/+ and Pten-/-Dicer-/- mice, while 70% genes were only significantly affected in Pten-/-Dicer-/- mice. Very few genes were differentially regulated between Pten-/-Dicer-/+ and Pten-/-Dicer-/- mice or were only altered in Pten-/-Dicer-/+ mice. Data analysis identified that a list of genes associated with epithelial-mesenchymal transition, cell adhesion, migration, and extracellular matrix deposition are statistically significantly altered in favor of tumor metastasis in the Pten-/-Dicer-/+ mice. QRT-PCR confirmed the changes in expression of some genes including growth factors (Tgfb1 and Ctgf), transcription factors (Snail, Twist2, and Foxc1), protease (MMPs etc.), and extracellular matrix components (Collagens). This finding corroborates the phenotypic invasiveness of the tumors in Pten-/-Dicer-/+ mice at a molecular level.
2013-07-17 | GSE42820 | GEO
Project description:Mitochondrial dysfunction has been implicated as a central mechanism in the metabolic myopathy accompanying critical limb ischemia (CLI). However, whether mitochondrial dysfunction is directly related to lower extremity ischemia and the structural and molecular mechanisms underpinning mitochondrial dysfunction in CLI patients is not understood. Here, we aimed to study whether mitochondrial dysfunction is a distinctive characteristic of CLI myopathy by assessing mitochondrial respiration in gastrocnemius muscle from 14 CLI patients (65.3 ± 7.8 y) and 15 matched control patients (CON) with a similar comorbidity risk profile and medication regimen but without peripheral ischemia (67.4 ± 7.4 y). Furthermore, we studied potential structural and molecular mechanisms of mitochondrial dysfunction by measuring total, sub-population, and fiber-type-specific mitochondrial volumetric content and cristae density with transmission electron microscopy and by assessing mitophagy and fission/fusion-related protein expression. Finally, we asked whether commonly used biomarkers of mitochondrial content are valid in patients with cardiovascular disease. CLI patients exhibited inferior mitochondrial respiration compared to CON. This respiratory deficit was not related to lower whole-muscle mitochondrial content or cristae density. However, stratification for fiber types revealed ultrastructural mitochondrial alterations in CLI patients compared to CON. CLI patients exhibited an altered expression of mitophagy-related proteins but not fission/fusion-related proteins compared to CON. Citrate synthase, cytochrome c oxidase subunit IV (COXIV), and 3-hydroxyacyl-CoA dehydrogenase (β-HAD) could not predict mitochondrial content. Mitochondrial dysfunction is a distinctive characteristic of CLI myopathy and is not related to altered organelle content or cristae density. Our results link this intrinsic mitochondrial deficit to dysregulation of the mitochondrial quality control system, which has implications for the development of therapeutic strategies.
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Project description:BACKGROUND:Apnea of Prematurity (AOP) is common, affecting the majority of infants born at <34 weeks gestational age. Apnea and periodic breathing are accompanied by intermittent hypoxia (IH). Animal and human studies demonstrate that IH exposure contributes to multiple pathologies, including retinopathy of prematurity (ROP), injury to sympathetic ganglia regulating cardiovascular action, impaired pancreatic islet cell and bone development, cerebellar injury, and neurodevelopmental disabilities. Current standard of care for AOP/IH includes prone positioning, positive pressure ventilation, and methylxanthine therapy; these interventions are inadequate, and not optimal for early development. OBJECTIVE:The objective is to support breathing in premature infants by using a simple, non-invasive vibratory device placed over limb proprioceptor fibers, an intervention using the principle that limb movements trigger reflexive facilitation of breathing. METHODS:Premature infants (23-34 wks gestational age), with clinical evidence of AOP/IH episodes were enrolled 1 week after birth. Caffeine treatment was not a reason for exclusion. Small vibration devices were placed on one hand and one foot and activated in 6 hour ON/OFF sequences for a total of 24 hours. Heart rate, respiratory rate, oxygen saturation (SpO2), and breathing pauses were continuously collected. RESULTS:Fewer respiratory pauses occurred during vibration periods, relative to baseline (p<0.005). Significantly fewer SpO2 declines occurred with vibration (p<0.05), relative to control periods. Significantly fewer bradycardic events occurred during vibration periods, relative to no vibration periods (p<0.05). CONCLUSIONS:In premature neonates, limb proprioceptive stimulation, simulating limb movement, reduces breathing pauses and IH episodes, and lowers the number of bradycardic events that accompany aberrant breathing episodes. This low-cost neuromodulatory procedure has the potential to provide a non-invasive intervention to reduce apnea, bradycardia and intermittent hypoxia in premature neonates. TRIAL REGISTRATION:ClinicalTrials.gov NCT02641249.
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Project description:AimsIncreased left ventricular mass index (LVMI) disproportionate to electrocardiographic QRS voltage has been reported to be associated with cardiac fibrosis and amyloid infiltration to myocardium. This study aimed to assess whether the LVMI-to-QRS-voltage ratio predicts clinical outcomes in heart failure with preserved ejection fraction (HFpEF).Methods and resultsThe Japanese Heart Failure Syndrome with Preserved Ejection Fraction (JASPER) registry is a nationwide, observational, and prospective registration of Japanese patients hospitalized with HFpEF (EF ≥ 50%). LVMI was assessed by echocardiography using the cube formula. QRS voltage was assessed by Sokolow-Lyon voltage criteria. We divided 290 patients in the registry who met inclusion criteria into five groups according to the quintile values of their LVMI-to-QRS-voltage ratio. In the highest quintile group (≥71.8 g/m2 /mV), approximately 50% of the patients had concentric hypertrophy and 30% had eccentric hypertrophy. These patients had the highest proportion of atrial fibrillation (61.4%) and history of pacemaker implantation (12.1%) among the five groups (P < 0.05). During the mean follow-up of 587 ± 300 days, 31.4% of all patients met the composite endpoint of all-cause death or rehospitalization for HF. Even after adjustment for demographic and baseline variables, the highest quintile group had a significantly higher incidence of the composite endpoints than the lowest quintile group (<30.7 g/m2 /mV) (hazard ratio: 2.205, 95% confidence interval: 1.106-4.395, P < 0.05).ConclusionsA high LVMI-to-QRS-voltage ratio is independently associated with poor outcomes in patients with HFpEF.
| S-EPMC8934982 | biostudies-literature
Project description:BackgroundThe most primitive ornithischian dinosaurs were small bipeds, but quadrupedality evolved three times independently in the clade. The transition to quadrupedality from bipedal ancestors is rare in the history of terrestrial vertebrate evolution, and extant analogues do not exist. Constraints imposed on quadrupedal ornithischians by their ancestral bipedal bauplan remain unexplored, and consequently, debate continues about their stance and gait. For example, it has been proposed that some ornithischians could run, while others consider that none were cursorial.Methodology/principal findingsDrawing on biomechanical concepts of limb bone scaling and locomotor theory developed for extant taxa, we use the largest dataset of ornithischian postcranial measurements so far compiled to examine stance and gait in quadrupedal ornithischians. Differences in femoral midshaft eccentricity in hadrosaurs and ceratopsids may indicate that hadrosaurs placed their feet on the midline during locomotion, while ceratopsids placed their feet more laterally, under the hips. More robust humeri in the largest ceratopsids relative to smaller taxa may be due to positive allometry in skull size with body mass in ceratopsids, while slender humeri in the largest stegosaurs may be the result of differences in dermal armor distribution within the clade. Hadrosaurs are found to display the most cursorial morphologies of the quadrupedal ornithischian cades, indicating higher locomotor performance than in ceratopsids and thyreophorans.Conclusions/significanceLimb bone scaling indicates that a previously unrealised diversity of stances and gaits were employed by quadrupedal ornithischians despite apparent convergence in limb morphology. Grouping quadrupedal ornithischians together as a single functional group hides this disparity. Differences in limb proportions and scaling are likely due to the possession of display structures such as horns, frills and dermal armor that may have affected the center of mass of the animal, and differences in locomotor behaviour such as migration, predator escape or home range size.
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Project description:INTRODUCTION:We investigated improvement of electrocardiographic LVH detection by adding measures of adiposity and/or novel electrocardiographic measures. Left ventricular hypertrophy (LVH) is an important risk factor for adverse cardiovascular outcomes. Improvement of electrocardiographic criteria for LVH is desirable, since electrocardiography is widely used. METHODS:We included 1091 participants of the Netherlands Epidemiology of Obesity Study (NEO) who underwent cardiac magnetic resonance imaging (MRI). Performance of Sokolow-Lyon and Cornell voltage and product criteria was assessed. Stepwise regression analysis was performed with each conventional electrocardiographic criterion and age, sex, body mass index (BMI), waist circumference, and waist:hip ratio (p-entry < 0.05, p-removal > 0.10). T-wave abnormalities or the spatial QRS-T angle (SA) were added to the improved models. RESULTS:The study population had a mean (SD) age of 56 (6) years, BMI of 26.1 (4.0) kg/m2 and 46% were men. MRI-LVH was present in 10% of participants. The c-statistic for Sokolow-Lyon voltage was 0.58, R2 was 0.02 and sensitivity at 90% specificity was 16%, for Sokolow-Lyon product this was 0.62, 0.02, and 21%, for Cornell voltage 0.65, 0.04, and 28% and for Cornell product 0.67, 0.04, and 25%. Best performing models were obtained by addition of both BMI and SA (Sokolow-Lyon voltage: c-statistic 0.74, R2 0.11, sensitivity of 41% at 90% specificity; Sokolow-Lyon product: 0.75, 0.12, 42%; Cornell voltage: c-statistic 0.70, R2 0.08, sensitivity of 38% at 90% specificity; Cornell product: c-statistic 0.72, R2 0.08, sensitivity of 44% at 90% specificity). CONCLUSIONS:Electrocardiographic detection of LVH improved by adding BMI and SA to a model with conventional electrocardiographic criteria. This approach would require little extra effort and application in clinical practice is feasible. However, results should first be replicated in high-risk populations.
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Project description:ObjectiveThe US Preventive Services Task Force (USPSTF) requires the estimation of lifetime pack-years to determine lung cancer screening eligibility. Leading electronic health record (EHR) vendors calculate pack-years using only the most recently recorded smoking data. The objective was to characterize EHR smoking data issues and to propose an approach to addressing these issues using longitudinal smoking data.Materials and methodsIn this cross-sectional study, we evaluated 16 874 current or former smokers who met USPSTF age criteria for screening (50-80 years old), had no prior lung cancer diagnosis, and were seen in 2020 at an academic health system using the Epic® EHR. We described and quantified issues in the smoking data. We then estimated how many additional potentially eligible patients could be identified using longitudinal data. The approach was verified through manual review of records from 100 subjects.ResultsOver 80% of evaluated records had inaccuracies, including missing packs-per-day or years-smoked (42.7%), outdated data (25.1%), missing years-quit (17.4%), and a recent change in packs-per-day resulting in inaccurate lifetime pack-years estimation (16.9%). Addressing these issues by using longitudinal data enabled the identification of 49.4% more patients potentially eligible for lung cancer screening (P < .001).DiscussionMissing, outdated, and inaccurate smoking data in the EHR are important barriers to effective lung cancer screening. Data collection and analysis strategies that reflect changes in smoking habits over time could improve the identification of patients eligible for screening.ConclusionThe use of longitudinal EHR smoking data could improve lung cancer screening.
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