Search Results (9)

Introduction: Vascular aging is associated with a loss of aortic compliance (C_A), which results in increased left ventricular pressure–volume area (PVA), stroke work (SW) and myocardial oxygen consumption (MVO₂). Myocardial efficiency (MyoEff) is derived from the PVA and MVO₂ construct, which includes potential energy (PE). However, the SW/MVO₂ ratio does not include PE and provides a more accurate physiologic measure. Methods: We used a modified computational model (CM) to assess PVA and SW and calculate MVO₂ using a pressure-work index (e MVO₂), to derive MyoEff–PVA and MyoEff–SW metrics. Phase I evaluated five levels of human C_A from normal (N) to stiff (S) at 80 bpm, and Phase II evaluated two levels of C_A (N and S) at three heart rates (60, 100, and 140 bpm). Results: During Phase I, MyoEff–PVA increased from 20.7 to 31.2%, and MyoEff–SW increased from 14.8 to 18.9%. In Phase II, during the N setting coupled with increases in the heart rate, the MyoEff–PVA decreased from 29.4 to 14.8 to 9.5%; the MyoEff–SW also decreased from 22.5 to 10.3 to 5.9%. As expected, during the S setting, MyoEff–PVA decreased from 45.5 to 22.9 to 14.8; a similar effect occurred with the MyoEff–SW, demonstrating a decrease from 29.9 to 13.9 to 7.9%, respectively. Conclusions: The CM provided insights into a simple and clinically relevant calculation for assessing MyoEff. The agreement on the CM metrics aligns with studies conducted previously in the clinical setting. Full article

Background: Lower socioeconomic status (SES) has been associated with increased mortality from coronary heart disease. This excess risk, relative to affluent patients, may be due to a combination of more adverse cardiovascular-risk factors, inequalities in access to cardiac investigations, longer waiting times for cardiac revascularisation and lower use of secondary prevention drugs. We sought to investigate whether socio-economic status influenced long-term all-cause mortality after PCI in a large metropolitan city (London), which serves a population of 11 million people with a mixed social background over a 10-year period. Methods: We conducted an observational cohort study of 123,780 consecutive PCI procedures from the Pan-London (United Kingdom) PCI registry. This data set is collected prospectively and includes all patients treated between January 2005 and December 2015. The database includes PCI performed for stable angina and ACS (ST-elevation myocardial infarction (STEMI), non-ST elevation myocardial infarction (NSTEMI), and unstable angina). Patient socio-economic status was defined by the English Index of Multiple Deprivation (IMD) score, according to residential postcode. Patients were analysed by quintile of IMD score (Q1, least deprived; Q5, most deprived). Median follow-up was 3.7 (IQR: 2.0–5.1) years and the primary outcome was all-cause mortality. Results: The mean age of the patients was 64.3 ± 12.1 years and 25.2% were female. A total of 22.4% of patients were diabetic and 27.3% had a history of previous myocardial infarction. The rates of long-term all-cause mortality increased progressively across quintiles of IMD score, with patients in Q5 showing significantly higher long-term mortality rates compared with patients in Q1 (p = 0.0044). This persisted following the inclusion of a propensity score in the proportional hazard model as a covariate (HR for Q5 compared to Q1: 1.15 [95% CI: 1.10–1.42]). Conclusions: This study has demonstrated that low SES is an independent predictor of adverse clinical outcomes following PCI in the large, diverse metropolitan city of London. There clearly are inequalities in cardio-vascular risk factors, time to access to medical treatment/PCI, access to complex imaging and devices during PCI, access to secondary prevention after PCI, and even race differences. Hence, attention to reducing the burden of cardiovascular risk factors and improving primary prevention, particularly in patients with lower SES, is required. Full article

The role of magnesium in blood pressure has been studied among hypertensive patients; however, there is a dearth of studies exploring the role of magnesium in hypertensive crises. The primary objective of this study was to evaluate the relationship between serum magnesium and blood pressure in patients with hypertensive crises. This was a single-center, retrospective, chart review, cross-sectional study of patients with hypertensive crises. Patients were included if they were eighteen years of age or older, with an international classification disease ninth revision (ICD-9) code of 401.9 (hypertensive crises: emergency or urgency) and a documented magnesium level on their electronic medical record. The primary outcome of the study was the correlation between serum magnesium and blood pressure (systolic blood pressure and diastolic blood pressure) in patients with hypertensive crises. Two hundred and ninety-three patients were included in the study. The primary outcome result showed that serum magnesium was positively correlated with systolic blood pressure (r = 0.143, p = 0.014), but not diastolic blood pressure. Conclusion: This study found a significant positive association between magnesium and systolic blood pressure, but not diastolic blood pressure, among patients with hypertensive crises. This positive association of serum magnesium with systolic blood pressure was maintained after adjusting for covariates. This study’s findings suggest a potential role of magnesium in blood pressure among patients with hypertensive crises. Full article

Background. Lynch syndrome is the most common genetic predisposition for hereditary cancer. Carriers of pathogenic changes in mismatch repair (MMR) genes have an increased risk of developing colorectal (CRC), endometrial, ovarian, urinary tract, prostate, and other cancers, depending on which gene is malfunctioning. In Lynch syndrome, differences in cancer incidence (penetrance) according to the gene involved have led to the stratification of cancer surveillance. By contrast, any differences in penetrance determined by the type of pathogenic variant remain unknown. Objective. To determine cumulative incidences of cancer in carriers of truncating and missense or aberrant splicing pathogenic variants of the MLH1 and MSH2 genes. Methods. Carriers of pathogenic variants of MLH1 (path_MLH1) and MSH2 (path_MSH2) genes filed in the Prospective Lynch Syndrome Database (PLSD) were categorized as truncating or missense/aberrant splicing according to the InSiGHT criteria for pathogenicity. Results. Among 5199 carriers, 1045 had missense or aberrant splicing variants, and 3930 had truncating variants. Prospective observation years for the two groups were 8205 and 34,141 years, respectively, after which there were no significant differences in incidences for cancer overall or for colorectal cancer or endometrial cancers separately. Conclusion. Truncating and missense or aberrant splicing pathogenic variants were associated with similar average cumulative incidences of cancer in carriers of path MLH1 and path_MSH2. Full article

Cardiac surgery (CSX) can be lifesaving in elderly patients (age ≥ 80 years) but may still be associated with complications and functional decline. Frailty represents a determinant to outcomes in critically ill patients, but little is known about its influence on elderly CSX-patients. This is a secondary exploratory analysis of a multi-center, prospective observational cohort study of 610 elderly patients admitted to the ICU and followed for one year to document long-term outcomes. CSX-ICU-patients (n = 49) were compared to surgical ICU patients (n = 184) with regard to demographics, frailty, and outcomes. Of all surgical patients, 102 (43%) were considered vulnerable or frail. The subdistribution hazard ratio (SHR) of time to discharge home (TTDH) for vulnerable/frail vs. fit/well patients was 0.54 (95% confidence interval (CI), 0.34, 0.86, p = 0.007). The p-value for effect modification between surgery group (CSX vs. surgical ICU patients) and Clinical Frailty Scale (CFS) group was not significant (p = 0.37) suggesting that the observed difference in the CFS effect between the CSX and surgical ICU patients is consistent with random error. A further subgroup analysis shows that among surgical ICU patients, the SHR of time to discharge home (TTDH) for vulnerable/frail vs. fit/well patients was 0.49 (95% CI, 0.29, 0.83) while the corresponding SHR for CSX patients was 0.77 (0.32–1.88). In conclusion, preoperative frailty reduced the rate of discharge to home in both surgical and CSX patients, but a larger sample of CSX patients is needed to adequately address this question in this patient group. Full article

Endometrial cancer (EC) is the commonest gynaecological malignancy. Current prognostic markers are inadequate to accurately predict patient survival, necessitating novel prognostic markers, to improve treatment strategies. Telomerase has a unique role within the endometrium, whilst aberrant telomerase activity is a hallmark of many cancers. The aim of the current in silico study is to investigate the role of telomere and telomerase associated genes and proteins (TTAGPs) in EC to identify potential prognostic markers and therapeutic targets. Analysis of RNA-seq data from The Cancer Genome Atlas identified differentially expressed genes (DEGs) in EC (568 TTAGPs out of 3467) and ascertained DEGs associated with histological subtypes, higher grade endometrioid tumours and late stage EC. Functional analysis demonstrated that DEGs were predominantly involved in cell cycle regulation, while the survival analysis identified 69 DEGs associated with prognosis. The protein-protein interaction network constructed facilitated the identification of hub genes, enriched transcription factor binding sites and drugs that may target the network. Thus, our in silico methods distinguished many critical genes associated with telomere maintenance that were previously unknown to contribute to EC carcinogenesis and prognosis, including NOP56, WFS1, ANAPC4 and TUBB4A. Probing the prognostic and therapeutic utility of these novel TTAGP markers will form an exciting basis for future research. Full article

Background: Virtual reality (VR) is becoming a widespread tool in rehabilitation, especially for postural stability. However, the impact of using VR in a “moving wall paradigm” (visual perturbation), specifically without and with anticipation of the perturbation, is unknown. Methods: Nineteen healthy subjects performed three trials of static balance testing on a force plate under three different conditions: baseline (no perturbation), unexpected VR perturbation, and expected VR perturbation. The statistical analysis consisted of a 1 × 3 repeated-measures ANOVA to test for differences in the center of pressure (COP) displacement, 95% ellipsoid area, and COP sway velocity. Results: The expected perturbation rendered significantly lower (p < 0.05) COP displacements and 95% ellipsoid area compared to the unexpected condition. A significantly higher (p < 0.05) sway velocity was also observed in the expected condition compared to the unexpected condition. Conclusions: Postural stability was lowered during unexpected visual perturbations compared to both during baseline and during expected visual perturbations, suggesting that conflicting visual feedback induced postural instability due to compensatory postural responses. However, during expected visual perturbations, significantly lowered postural sway displacement and area were achieved by increasing the sway velocity, suggesting the occurrence of postural behavior due to anticipatory postural responses. Finally, the study also concluded that VR could be used to induce different postural responses by providing visual perturbations to the postural control system, which can subsequently be used as an effective and low-cost tool for postural stability training and rehabilitation. Full article

This paper introduces GEKKO as an optimization suite for Python. GEKKO specializes in dynamic optimization problems for mixed-integer, nonlinear, and differential algebraic equations (DAE) problems. By blending the approaches of typical algebraic modeling languages (AML) and optimal control packages, GEKKO greatly facilitates the development and application of tools such as nonlinear model predicative control (NMPC), real-time optimization (RTO), moving horizon estimation (MHE), and dynamic simulation. GEKKO is an object-oriented Python library that offers model construction, analysis tools, and visualization of simulation and optimization. In a single package, GEKKO provides model reduction, an object-oriented library for data reconciliation/model predictive control, and integrated problem construction/solution/visualization. This paper introduces the GEKKO Optimization Suite, presents GEKKO’s approach and unique place among AMLs and optimal control packages, and cites several examples of problems that are enabled by the GEKKO library. Full article

Metabolite structure identification remains a significant challenge in nontargeted metabolomics research. One commonly used strategy relies on searching biochemical databases using exact mass. However, this approach fails when the database does not contain the unknown metabolite (i.e., for unknown-unknowns). For these cases, constrained structure generation with combinatorial structure generators provides a potential option. Here we evaluated structure generation constraints based on the specification of: (1) substructures required (i.e., seed structures); (2) substructures not allowed; and (3) filters to remove incorrect structures. Our approach (database assisted structure identification, DASI) used predictive models in MolFind to find candidate structures with chemical and physical properties similar to the unknown. These candidates were then used for seed structure generation using eight different structure generation algorithms. One algorithm was able to generate correct seed structures for 21/39 test compounds. Eleven of these seed structures were large enough to constrain the combinatorial structure generator to fewer than 100,000 structures. In 35/39 cases, at least one algorithm was able to generate a correct seed structure. The DASI method has several limitations and will require further experimental validation and optimization. At present, it seems most useful for identifying the structure of unknown-unknowns with molecular weights <200 Da. Full article