Cell Cycle- and Cancer-Associated Gene Networks Activated by Dsg2: Evidence of Cystatin A Deregulation and a Potential Role in Cell-Cell Adhesion

This work was supported by grants from the National Institutes of Health (Mahoney, R01AR056067; Riobo, RO1 GM088256). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Sex- and age-related differences in the management and outcomes of chronic heart failure: an analysis of patients from the ESC HFA EORP Heart Failure Long-Term Registry

Aims: This study aimed to assess age- and sex-related differences in management and 1-year risk for all-cause mortality and hospitalization in chronic heart failure (HF) patients. Methods and results: Of 16 354 patients included in the European Society of Cardiology Heart Failure Long-Term Registry, 9428 chronic HF patients were analysed [median age: 66 years; 28.5% women; mean left ventricular ejection fraction (LVEF) 37%]. Rates of use of guideline-directed medical therapy (GDMT) were high (angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, beta-blockers and mineralocorticoid receptor antagonists: 85.7%, 88.7% and 58.8%, respectively). Crude GDMT utilization rates were lower in women than in men (all differences: P\ua0 64 0.001), and GDMT use became lower with ageing in both sexes, at baseline and at 1-year follow-up. Sex was not an independent predictor of GDMT prescription; however, age >75 years was a significant predictor of GDMT underutilization. Rates of all-cause mortality were lower in women than in men (7.1% vs. 8.7%; P\ua0=\ua00.015), as were rates of all-cause hospitalization (21.9% vs. 27.3%; P\ua075 years. Conclusions: There was a decline in GDMT use with advanced age in both sexes. Sex was not an independent predictor of GDMT or adverse outcomes. However, age >75 years independently predicted lower GDMT use and higher all-cause mortality in patients with LVEF 6445%

Association between loop diuretic dose changes and outcomes in chronic heart failure: observations from the ESC-EORP Heart Failure Long-Term Registry

[Abstract] Aims. Guidelines recommend down-titration of loop diuretics (LD) once euvolaemia is achieved. In outpatients with heart failure (HF), we investigated LD dose changes in daily cardiology practice, agreement with guideline recommendations, predictors of successful LD down-titration and association between dose changes and outcomes. Methods and results. We included 8130 HF patients from the ESC-EORP Heart Failure Long-Term Registry. Among patients who had dose decreased, successful decrease was defined as the decrease not followed by death, HF hospitalization, New York Heart Association class deterioration, or subsequent increase in LD dose. Mean age was 66±13 years, 71% men, 62% HF with reduced ejection fraction, 19% HF with mid-range ejection fraction, 19% HF with preserved ejection fraction. Median [interquartile range (IQR)] LD dose was 40 (25–80) mg. LD dose was increased in 16%, decreased in 8.3% and unchanged in 76%. Median (IQR) follow-up was 372 (363–419) days. Diuretic dose increase (vs. no change) was associated with HF death [hazard ratio (HR) 1.53, 95% confidence interval (CI) 1.12–2.08; P = 0.008] and nominally with cardiovascular death (HR 1.25, 95% CI 0.96–1.63; P = 0.103). Decrease of diuretic dose (vs. no change) was associated with nominally lower HF (HR 0.59, 95% CI 0.33–1.07; P = 0.083) and cardiovascular mortality (HR 0.62 95% CI 0.38–1.00; P = 0.052). Among patients who had LD dose decreased, systolic blood pressure [odds ratio (OR) 1.11 per 10 mmHg increase, 95% CI 1.01–1.22; P = 0.032], and absence of (i) sleep apnoea (OR 0.24, 95% CI 0.09–0.69; P = 0.008), (ii) peripheral congestion (OR 0.48, 95% CI 0.29–0.80; P = 0.005), and (iii) moderate/severe mitral regurgitation (OR 0.57, 95% CI 0.37–0.87; P = 0.008) were independently associated with successful decrease. Conclusion. Diuretic dose was unchanged in 76% and decreased in 8.3% of outpatients with chronic HF. LD dose increase was associated with worse outcomes, while the LD dose decrease group showed a trend for better outcomes compared with the no-change group. Higher systolic blood pressure, and absence of (i) sleep apnoea, (ii) peripheral congestion, and (iii) moderate/severe mitral regurgitation were independently associated with successful dose decrease

Energy Consumption Estimation for Embedded Applications

Energy consumption, indeed, represents one of the essential properties of embedded applications, especially for those devices whose autonomy depends on battery life. The lack of accurate and suitable methodology for energy consumption estimation for embedded applications based on ultra-low power heterogeneous multicore DSP platforms inspired a solution that will be presented in this paper. The solution has been developed as a plugin for the Eclipse based MIDE (Multicore Integrated Development Environment), in order to facilitate production of energy efficient firmware solutions. Evaluation of energy loss has been calculated using instruction-level power analysis, virtual platform, debug information, and diverse input loads. The primary goal was to obtain a precise model of energy consumption that will establish a direct link between program solutions and the amount of energy required for their execution, whilst processing different input loads. Estimation has been validated against empirical data, measured on a real DSP platform.Results show that very high accuracy has been reached

Mapping population change index in Southern Serbia (1961-2027) as a function of environmental factors

Niche analysis methods developed within the biogeography community are routinely used for species distribution modeling of wildlife and endangered species. So far, such techniques have not been used to explain distribution of people in an area, nor to assess spatio-temporal dynamics of human populations. In this paper, the MaxEnt approach to species distribution modeling and publicly available gridded predictors were used to analyze the population dynamics in Southern Serbia (South Pomoravlje Region) for the period 1961-2027. Population values from the census administrative units were first downscaled to 200 m grid using a detailed map of populated places and dasymetric interpolation. In the second step, a point pattern representing the whole population (468,500 inhabitants in 2002) was simulated using the R package spatstat. MaxEnt was then used to derive habitat suitability index (HSI) as a function of gridded predictors: distance to roads, elevation, slope, topographic wetness index, enhanced vegetation index and land cover classes. HSI and environmental predictors were further used to explain spatial patterns in the population change index (PCI) through regression modeling. The results show that inhabiting preference for year 1961 is mainly a function of topography (TWI, elevation). The HSI for year 2027 shows that large portions of remote areas are becoming less preferred for inhabiting. The results of cross-validation in MaxEnt show that distribution of population is distinctly controlled by environmental factors (AUC > 0.84). Population decrease is particularly significant in areas >25 km distant from the main road network. The results of regression analysis show that 40% of variability in the PCI values can be explained with these environmental maps, distance to roads and urban areas being the main drivers of migration process. This approach allows precise mapping of demographic patterns that otherwise would not be visible from the census data alone

The telomere profile distinguishes two classes of genetically distinct cutaneous squamous cell carcinomas

The incidence of skin cancer is increasing worldwide and cutaneous squamous cell carcinomas (SCCs) are associated with considerable morbidity and mortality, particularly in immunosuppressed individuals ('carcinomatous catastrophy'). Yet, molecular mechanisms are still insufficiently understood. Besides ultraviolet (UV)-indicative mutations, chromosomal aberrations are prominent. As telomeres are essential in preserving chromosome integrity, and telomere erosion as well as aberrant spatial telomere distribution contribute to genomic instability, we first established telomere length profiles across the whole tissue and identified normal skin (10/30) harboring discrete epidermal sites (stem cell territories) of evenly short telomeres. Precancerous actinic keratoses (AKs) (17) and SCCs (27) expressed two telomere phenotypes: (i) tissue-wide evenly short to intermediate and (ii) longer and tissue-wide heterogeneous telomere lengths, suggesting two modes of initiation, with one likely to originate in the epidermal stem cells. Although tumor histotype, location, patient gender or age failed to distinguish the two SCC telomere phenotypes, as did telomerase activity, we found a trend for a higher degree of aberrant p53 and cyclin D1 expression with long/heterogeneous telomeres. In addition, we established an association for the short/homogeneous telomeres with a simpler and the heterogeneous telomeres with a more complex karyotype correlating also with distinct chromosomal changes. SCCs (13) from renal transplant recipients displayed the same telomere dichotomy, suggesting that both telomere subtypes contribute to 'carcinomatous catastrophy' under immunosuppression by selecting for a common set (3, 9p and 17q) and subtype-specific aberrations (e.g., 6p gain, 13q loss). As a second mechanism of telomere-dependent genomic instability, we investigated changes in telomere distribution with its most severe form of telomeric aggregates (TAs). We identified a telomere length-independent but progression-dependent increase in cells with small telomere associations in AKs (17/17) and additional TAs in SCCs (24/32), basal cell carcinomas (30/31) and malignant melanomas (15/15), and provide evidence for a reactive oxygen species-dependent mechanism in this UV-induced telomere organization-dependent genomic instability

4308Lung ultrasound guided dry-weight probing reduces left and right atrial dimensions and left ventricular filling pressures in hemodialysis patients with hypertension

Abstract Introduction and purpose Left ventricular hypertrophy and dysfunction is tightly associated with adverse outcome in hemodialysis. Hypertension and increased preload due to hypervolemia are major factors for these cardiac anomalies in hemodialysis. This study examined the effect of lung-ultrasound-guided dry-weight reduction on echocardiographic indices of left and right cardiac size, systolic and diastolic function in hypertensive hemodialysis patients. Methods This pilot, single-blind trial randomised 71 clinically euvolemic hypertensive hemodialysis patients in an active group (n=35), following a strategy for dry-weight reduction guided by the total number of US-B lines (US-B lines score) prior to a mid-week dialysis session, and a control group (n=36), following standard-of-care treatment. Among others, patients underwent two-dimensional and tissue-Doppler echocardiographic (TDI) at baseline and after 8-weeks. Results Overall, 19 (54.3%) patients in the active and 5 (13.9%) in the control group had UF intensification (p&lt;0.001) during follow-up (US-B lines 5.3±12.5 vs +2.2±7.6, p&lt;0.001, dry-weight: −0.71±1.39 vs +0.51±0.98 kg, p&lt;0.001). Inferior vena cava diameter was reduced to a greater extend in the active compared to control group (−0.43±4.00 vs 0.71±4.82, p=0.033) at study-end. Reductions in LA and RA sizing parameters were greater in the active group (LA Surface: −1.09±4.61 vs 0.93±3.06 cm2, p=0.034; RA surface: −1.56±6.17 vs 0.47±2.31, p=0.024; LAVi: −2.43±13.14 vs 2.95±9.42 ml/m2, p=0.052). Reductions in LV end-diastolic diameter and volume were marginally greater in the active group. LV filling pressures significantly decreased in the active compared to the control group (E/e' LV: −0.38±3.14 vs 1.36±3.54, p=0.034; DT: 35.43±85.25 vs −18.44±50.69, p=0.002). Systolic function indices were unchanged in both groups. In multivariate analysis, US-B lines reduction was a powerful predictor (OR: 4.542, 95% CI: 1.266–16.292, p=0.020) of E/e' LV ratio decrease, among various factors examined. Conclusions A lung-ultrasound-guided strategy for dry-weight reduction can effectively reduce cardiac chambers dimensions and LV filling pressures without changing systolic performance during an 8-week follow-up in hypertensive hemodialysis patients. </jats:sec

Estrogenic and serotonergic butenolides from the leaves of Piper hispidum Swingle (Piperaceae)

Publisher copyright policies & self-archiving: Author's Pre-print: author can archive pre-print (ie pre-refereeing). Author's Post-print: author can archive post-print (ie final draft post-refereeing). Publisher's Version/PDF: author cannot archive publisher's version/PDF. Documento privadoEthnopharmacological relevance: Our previous work has demonstrated that several plants in the Piperaceae family are commonly used by the Q’eqchi Maya of Livingston, Guatemala to treat amenorrhea, dysmenorrhea, and pain. Extracts of Piper hispidum Swingle (Piperaceae), bound to the estrogen (ER) and serotonin (5-HT7) receptors. Aim of the study: To investigate the estrogenic and serotonergic activities of Piper hispidum extracts in functionalized assays, identify the active chemical constituents in the leaf extract, and test these compounds as agonists or antagonists of ER and 5-HT7. Materials and methods: The effects of the Piper hispidum leaf extracts were investigated in estrogen reporter gene and endogenous gene assays in MCF-7 cells to determine if the extracts acted as an estrogen agonist or antagonist. In addition, the active compounds were isolated using ER- and 5-HT7 receptor bioassay-guided fractionation. The structures of the purified compounds were identified using highresolution LC–MS and NMR spectroscopic methods. The ER- and 5-HT7-agonist effects of the purified chemical constituents were tested in a 2ERE-reporter gene assay in MCF-7 cells and in serotonin binding and functionalized assays. Results: Three butenolides including one new compound (1) were isolated from the leaves of Piper hispidum, and their structures were determined. Compound 1 bound to the serotonin receptor 5-HT7 with IC50 values of 16.1 and 8.3 ␮M, respectively, and using GTP shift assays, Compound 1 was found to be a partial agonist of the 5-HT7 receptor. The Piper hispidum leaf extracts, as well as Compounds 2 and 3 enhanced the expression of estrogen responsive reporter and endogenous genes in MCF-7 cells, demonstrating estrogen agonist effects. Conclusions: Extracts of Piper hispidum act as agonists of the ER and 5-HT7 receptors. Compound 1, a new natural product, identified as 9,10-methylenedioxy-5,6-Z-fadyenolide, was isolated as the 5-HT7 agonist. Compounds 2 and 3 are reported for the first time in Piper hispidum, and identified as the estrogen agonists. No inhibition of CYP450 was observed for any of these compounds in concentrations up to 1 ␮M. These activities are consistent with the Q’eqchi traditional use of the plant for the treatment of disorders associated with the female reproductive cycle.Community Health Sciences Division, School of Public Health, University of Illinois at Chicago, Chicago, IL 60612, USA. Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, University of Illinois at Chicago, IL 60612, USA. Department of Chemistry, Yunnan Normal University, Kunming 650092, People’s Republic of China. Department of Pharmacy Practice, University of Illinois at Chicago, Chicago, IL 60612, USA. School of Biology, Faculty of Chemical Science and Pharmacy, Universidad de San Carlos, Guatemala City, Guatemala. School of Biological Chemistry, Faculty of Pharmacy, Universidad de San Carlos, Guatemala. Centro de Investigaciones en Productos Naturales (CIPRONA), Universidad de Costa Rica, San José, Costa Rica.UCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias Básicas::Centro de Investigaciones en Productos Naturales (CIPRONA

Characterization of 2009 Pandemic Influenza A (H1N1) Virus Specimens with a Positive Hemagglutinin 1 Signal in the Luminex xTAG Respiratory Viral Panel Assay▿

This retrospective review analyzed Luminex xTAG respiratory viral panel (RVP) results for 2009 pandemic influenza A (H1N1) virus specimens. Comparing median fluorescence intensity (MFI) signals for the influenza A virus and hemagglutinin 1 (H1) reactions for specimens with very low positive (MFI < 1,000) or “no-call” H1 results reliably distinguished 2009 H1N1 from seasonal virus