221 research outputs found
Association between the c.*229C>T polymorphism of the topoisomerase IIb binding protein 1 (TopBP1) gene and breast cancer
Topoisomerase IIb binding protein 1 (TopBP1)
is involved in cell survival, DNA replication, DNA damage
repair and cell cycle checkpoint control. The biological
function of TopBP1 and its close relation with BRCA1
prompted us to investigate whether alterations in the
TopBP1 gene can influence the risk of breast cancer.
The aim of this study was to examine the association
between five polymorphisms (rs185903567, rs116645643,
rs115160714, rs116195487, and rs112843513) located in
the 30UTR region of the TopBP1 gene and breast cancer
risk as well as allele-specific gene expression. Five hundred
thirty-four breast cancer patients and 556 population controls
were genotyped for these SNPs. Allele-specific Top-
BP1 mRNA and protein expressions were determined by
using real time PCR and western blotting methods,
respectively. Only one SNP (rs115160714) showed an
association with breast cancer. Compared to homozygous
common allele carriers, heterozygous and homozygous for
the T variant had significantly increased risk of breast
cancer (adjusted odds ratio = 3.81, 95 % confidence
interval: 1.63â8.34, p = 0.001). Mean TopBP1 mRNA and
protein expression were higher in the individuals with the
CT or TT genotype. There was a significant association
between the rs115160714 and tumor grade and stage. Most
carriers of minor allele had a high grade (G3) tumors
classified as T2-T4N1M0. Our study raises a possibility
that a genetic variation of TopBP1 may be implicated in
the etiology of breast cancer
PAHs, PCBs, PBDEs and Pesticides in Cold-Pressed Vegetable Oils
The aim of this study was to investigate levels of polychlorinated biphenyls (marker and dioxin-like congeners), polycyclic aromatic hydrocarbons (EPA 15 + 1), polybrominated diphenyl ethers (14 predominant congeners) and pesticides (74 compounds) in various cold-pressed vegetable oils. Poppy seed oil, rapeseed oil, sesame seed oil, pumpkinseed oil, hempseed oil, linaire oil, borage oil and evening star oil were investigated. Results of this study revealed that concentrations of PCBs, PBDEs and PAHs were low in majority of the investigated samples. However, high concentrations of organophosphorus insecticides were found. Chlorpyrifos methyl and pirimiphos methyl were the pesticide residues most commonly found in the studied oils. Concentration of 15 + 1 EPA PAHs was within the 17.85â37.16 Όg kgâ1 range, concentration of (marker) PCBs varied from 127 to 24,882 pg gâ1, dioxin-like TEQ values were below 0.1 pg TEQ gâ1. Concentration of PBDEs was below LOQ in most cases
Treatment of Older Patients with Mantle-Cell Lymphoma
BACKGROUND: The long-term prognosis for older patients with mantle-cell lymphoma is poor. Chemoimmunotherapy results in low rates of complete remission, and most patients have a relapse. We investigated whether a fludarabine-containing induction regimen improved the complete-remission rate and whether maintenance therapy with rituximab prolonged remission. METHODS: We randomly assigned patients 60 years of age or older with mantle-cell lymphoma, stage II to IV, who were not eligible for high-dose therapy to six cycles of rituximab, fludarabine, and cyclophosphamide (R-FC) every 28 days or to eight cycles of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) every 21 days. Patients who had a response underwent a second randomization to maintenance therapy with rituximab or interferon alfa, each given until progression. RESULTS: Of the 560 patients enrolled, 532 were included in the intention-to-treat analysis for response, and 485 in the primary analysis for response. The median age was 70 years. Although complete-remission rates were similar with R-FC and R-CHOP (40% and 34%, respectively; P=0.10), progressive disease was more frequent with R-FC (14%, vs. 5% with R-CHOP). Overall survival was significantly shorter with R-FC than with R-CHOP (4-year survival rate, 47% vs. 62%; P=0.005), and more patients in the R-FC group died during the first remission (10% vs. 4%). Hematologic toxic effects occurred more frequently in the R-FC group than in the R-CHOP group, but the frequency of grade 3 or 4 infections was balanced (17% and 14%, respectively). In 274 of the 316 patients who were randomly assigned to maintenance therapy, rituximab reduced the risk of progression or death by 45% (in remission after 4 years, 58%, vs. 29% with interferon alfa; hazard ratio for progression or death, 0.55; 95% confidence interval, 0.36 to 0.87; P=0.01). Among patients who had a response to R-CHOP, maintenance therapy with rituximab significantly improved overall survival (4-year survival rate, 87%, vs. 63% with interferon alfa; P=0.005). CONCLUSIONS: R-CHOP induction followed by maintenance therapy with rituximab is effective for older patients with mantle-cell lymphom
Relations between assemblages of carpological remains and modern vegetation in a shallow reservoir in southern Poland
This paper explores relations between assemblages of carpological remains and vegetation in and around a small, shallow reservoir in southern Poland. The study was conducted from 2006 to 2008. Quantity and distribution of species in the reservoir were recorded annually during the growing season. In October 2008, 40 samples of surface sediment (top 2 cm) were collected along transects at 10 m intervals. Samples of 100 cm3 were prepared for analysis of plant macroremains. Assemblages of carpological remains generally reflect local vegetation well. In some cases, however, even analysis of numerous samples failed to fully capture the species composition or reflect plant ratios in the parent phytocenosis. Reasons for this include factors that affect seed production, transport and fossilization, which differ among species. Among the best-represented macroremains were plants of the rush phytocenosis. In analysed samples, macroremains of 68.8 % of extant rushes were identified. Sixty percent of submerged and floating-leaf taxa were found in carpological samples, whereas 26.7 % of the trees and bushes were represented in sediment deposits. Species composition of phytocenoses in the reservoir and in surrounding areas was best reflected by macroremains from the nearby reed bed. Numbers of diaspores of Mentha aquatica, Hippuris vulgaris and Carex reflected well their relative abundance in phytocenoses. Chara sp., Juncus inflexus and Eupatorium cannabinum were overrepresented, whereas Typha latifolia and Sparganium minimum were poorly represented in relation to contemporary plant cover. There were no diaspores of Phragmites australis, which dominates the contemporary reed bed. Besides the shape of a reservoir, the key factor influencing diaspore numbers is distribution of plant cover. In many cases, single diaspores (Potentilla erecta, Myosotis scorpioides, Lythrum salicaria, Scutellaria galericulata), or higher concentrations (Hippuris vulgaris, Mentha aquatica, Eleocharis palustris, Schoenoplectus tabernaemontani, Chara sp.) reflected well the location of parent vegetation. The findings indicate that carpological remains in sediments can be an important source of information about plants in and around lakes. They generally reflect well local vegetation and in some cases may be used to identify taxa that dominated in the past
Algal mats transport diaspores and carpological remains in shallow lakes
Algal mats in lakes and reservoirs can transport diaspores and carpological remains of plants, and thus may influence the creation of taphocoenoses. In 2012, I quantified carpological remains in two types of algal mats from a small reservoir in southern Poland. Mats formed by filamentous algae participate primarily in the original transport of diaspores, and can influence their concentration and facilitate their migration, mainly between the shores of the reservoir. Diatom mats partake primarily in diaspore redeposition, but can also cause their dispersal between the shore zone and the central part of the reservoir. This research demonstrates that mats built by diatoms contain far more remains and are more biologically diverse than filamentous algal mats. Movement of carpological remains observed in both types of algal mats points to their role in the formation of taphocoenoses and suggests that algal mats must be considered when interpreting macrofossil records
Quality control of B-lines analysis in stress Echo 2020
Background
The effectiveness trial âStress echo (SE) 2020â evaluates novel applications of SE in and beyond coronary artery disease. The core protocol also includes 4-site simplified scan of B-lines by lung ultrasound, useful to assess pulmonary congestion.
Purpose
To provide web-based upstream quality control and harmonization of B-lines reading criteria.
Methods
60 readers (all previously accredited for regional wall motion, 53 B-lines naive) from 52 centers of 16 countries of SE 2020 network read a set of 20 lung ultrasound video-clips selected by the Pisa lab serving as reference standard, after taking an obligatory web-based learning 2-h module (
http://se2020.altervista.org
). Each test clip was scored for B-lines from 0 (black lung, A-lines, no B-lines) to 10 (white lung, coalescing B-lines). The diagnostic gold standard was the concordant assessment of two experienced readers of the Pisa lab. The answer of the reader was considered correct if concordant with reference standard reading ±1 (for instance, reference standard reading of 5 B-lines; correct answer 4, 5, or 6). The a priori determined pass threshold was 18/20 (â„ 90%) with R value (intra-class correlation coefficient) between reference standard and recruiting center)â>â0.90. Inter-observer agreement was assessed with intra-class correlation coefficient statistics.
Results
All 60 readers were successfully accredited: 26 (43%) on first, 24 (40%) on second, and 10 (17%) on third attempt. The average diagnostic accuracy of the 60 accredited readers was 95%, with R value of 0.95 compared to reference standard reading. The 53 B-lines naive scored similarly to the 7 B-lines expert on first attempt (90 versus 95%, pâ=âNS). Compared to the step-1 of quality control for regional wall motion abnormalities, the mean reading time per attempt was shorter (17â±â3 vs 29â±â12 min, pâ<â.01), the first attempt success rate was higher (43 vs 28%, pâ<â0.01), and the drop-out of readers smaller (0 vs 28%, pâ<â.01).
Conclusions
Web-based learning is highly effective for teaching and harmonizing B-lines reading. Echocardiographers without previous experience with B-lines learn quickly.info:eu-repo/semantics/publishedVersio
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 (25â80) mg. LD dose was increased in 16%, decreased in 8.3%
and unchanged in 76%. Median (IQR) follow-up was 372 (363â419) days. Diuretic dose increase (vs. no change) was
associated with HF death [hazard ratio (HR) 1.53, 95% confidence interval (CI) 1.12â2.08; P = 0.008] and nominally
with cardiovascular death (HR 1.25, 95% CI 0.96â1.63; P = 0.103). Decrease of diuretic dose (vs. no change) was
associated with nominally lower HF (HR 0.59, 95% CI 0.33â1.07; P = 0.083) and cardiovascular mortality (HR 0.62 95% CI 0.38â1.00; P = 0.052). Among patients who had LD dose decreased, systolic blood pressure [odds ratio
(OR) 1.11 per 10 mmHg increase, 95% CI 1.01â1.22; P = 0.032], and absence of (i) sleep apnoea (OR 0.24, 95% CI
0.09â0.69; P = 0.008), (ii) peripheral congestion (OR 0.48, 95% CI 0.29â0.80; P = 0.005), and (iii) moderate/severe
mitral regurgitation (OR 0.57, 95% CI 0.37â0.87; 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
Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018.
Over the past decade, the Nomenclature Committee on Cell Death (NCCD) has formulated guidelines for the definition and interpretation of cell death from morphological, biochemical, and functional perspectives. Since the field continues to expand and novel mechanisms that orchestrate multiple cell death pathways are unveiled, we propose an updated classification of cell death subroutines focusing on mechanistic and essential (as opposed to correlative and dispensable) aspects of the process. As we provide molecularly oriented definitions of terms including intrinsic apoptosis, extrinsic apoptosis, mitochondrial permeability transition (MPT)-driven necrosis, necroptosis, ferroptosis, pyroptosis, parthanatos, entotic cell death, NETotic cell death, lysosome-dependent cell death, autophagy-dependent cell death, immunogenic cell death, cellular senescence, and mitotic catastrophe, we discuss the utility of neologisms that refer to highly specialized instances of these processes. The mission of the NCCD is to provide a widely accepted nomenclature on cell death in support of the continued development of the field
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