Clinical Characteristics, Treatment, and Short-Term Outcome in Patients with Heart Failure and Cancer.

(1) Our study aimed to look at the clinical characteristics, treatment and short-term outcomes of patients hospitalized due to heart failure with coexisting cancer. (2) Methods: Seventy one cancer (Ca) patients and a randomly selected 70 patients without Ca, hospitalized due to heart failure exacerbation in the same time period constituted the study group (Ca patient group) and controls (non-Ca group), respectively. Data on clinical characteristics were collected retrospectively for both groups. (3) Results: Cancer patients presented with a less advanced NYHA class, had more frequent HFpEF, a higher peak troponin T level, and smaller left atrium size, as compared with controls. The in-hospital deaths of Ca patients were associated with: a higher New York Heart Association (NYHA) class, lower HgB level, worse renal function, higher K and AST levels, presence of diabetes mellitus, and HFpEF. By multivariate logistic regression analysis, impaired renal function was the only independent predictor of in-hospital death in Ca patients (OR-1.15; CI 1.05; 1.27); p = 0.017). The following covariates entered the regression: NYHA class, HgB, GFR, K+, AST, diabetes mellitus t.2, and HFpEF. (4) Conclusions: The clinical picture and the course of heart failure in patients with and without cancer are different

Insanity as a Defense to the Civil Fraud Penalty

Most neurological diseases are associated with chronic inflammation initiated by the activation of microglia, which produce cytotoxic and inflammatory factors. Signal transducers and activators of transcription (STATs) are potent regulators of gene expression but contribution of particular STAT to inflammatory gene expression and STAT-dependent transcriptional networks underlying brain inflammation need to be identified. In the present study, we investigated the genomic distribution of Stat binding sites and the role of Stats in the gene expression in lipopolysaccharide (LPS)-activated primary microglial cultures. Integration of chromatin immunoprecipitation-promoter microarray data and transcriptome data revealed novel Stat-target genes including Jmjd3, Ccl5, Ezr, Ifih1, Irf7, Uba7, and Pim1. While knockdown of individual Stat had little effect on the expression of tested genes, knockdown of both Stat1 and Stat3 inhibited the expression of Jmjd3 and inflammatory genes. Transcriptional regulation of Jmjd3 by Stat1 and Stat3 is a novel mechanism crucial for launching inflammatory responses in microglia. The effects of Jmjd3 on inflammatory gene expression were independent of its H3K27me3 demethylase activity. Forced expression of constitutively activated Stat1 and Stat3 induced the expression of Jmjd3, inflammation-related genes, and the production of proinflammatory cytokines as potently as lipopolysacharide. Gene set enrichment and gene function analysis revealed categories linked to the inflammatory response in LPS and Stat1C + Stat3C groups. We defined upstream pathways that activate STATs in response to LPS and demonstrated contribution of Tlr4 and Il-6 and interferon-. signaling. Our findings define novel direct transcriptional targets of Stat1 and Stat3 and highlight their contribution to inflammatory gene expression

Mild hypothermia provides Treg stability

Regulatory T cells (Tregs) play crucial role in maintenance of peripheral tolerance. Recent clinical trials confirmed safety and efficacy of Treg treatment of deleterious immune responses. However, Tregs lose their characteristic phenotype and suppressive potential during expansion ex vivo. Therefore, multiple research teams have been studding Treg biology in aim to improve their stability in vitro. In the current paper, we demonstrate that mild hypothermia of 33 °C induces robust proliferation of Tregs, preserves expression of FoxP3, CD25 and Helios, and prevents TSDR methylation during culture in vitro. Tregs expanded at 33 °C have stronger immunosuppressive potential and remarkably anti-inflammatory phenotype demonstrated by the whole transcriptome sequencing. These observations shed new light on impact of temperature on regulation of immune response. We show that just a simple change in temperature can preserve Treg stability, function and accelerate their proliferation, responding to unanswered question- how to preserve Treg stability in vitro

Comprehensive genetic and epigenetic analysis of sporadic meningioma for macro-mutations on 22q and micro-mutations within the NF2 locus

BACKGROUND: Meningiomas are the most common intracranial neoplasias, representing a clinically and histopathologically heterogeneous group of tumors. The neurofibromatosis type 2 (NF2) tumor suppressor is the only gene known to be frequently involved in early development of meningiomas. The objective of this study was to identify genetic and/or epigenetic factors contributing to the development of these tumors. A large set of sporadic meningiomas were analyzed for presence of 22q macro-mutations using array-CGH in order to identify tumors carrying gene dosage aberrations not encompassing NF2. The NF2 locus was also comprehensively studied for point mutations within coding and conserved non-coding sequences. Furthermore, CpG methylation within the NF2 promoter region was thoroughly analyzed. RESULTS: Monosomy 22 was the predominant finding, detected in 47% of meningiomas. Thirteen percent of the tumors contained interstitial/terminal deletions and gains, present singly or in combinations. We defined at least two minimal overlapping regions outside the NF2 locus that are small enough (~550 kb and ~250 kb) to allow analysis of a limited number of candidate genes. Bialleinactivationo the NF2 gne was detected in 36% of meningiomas. Among the monosomy 22 cases, no additional NF2 mutations could be identified in 35% (17 out of 49) of tumors. Furthermore, the majority of tumors (9 out of 12) with interstitial/terminal deletions did not have any detectable NF2 mutations. Methylation within the NF2 promoter region was only identified at a single CpG site in one tumor sample. CONCLUSION: We confirmed previous findings of pronounced differences in mutation frequency between different histopathological subtypes. There is a higher frequency of biallelic NF2 inactivation in fibroblastic (52%) compared to meningothelial (18%) tumors. The presence of macro-mutations on 22q also shows marked differences between fibroblastic (86%) and meningothelial (39%) subtypes. Thus, inactivation of NF2, often combined with the presence of macro-mutation on 22q, is likely not as important for the development of the meningothelial subtype, as opposed to the fibroblastic form. Analysis of 40 CpG sites distributed within 750 bp of the promoter region suggests that NF2 promoter methylation does not play a major role in meningioma development

Metabolic syndrome and its components in Polish women of childbearing age : a nationwide study

Abstract Background Abnormal body mass and related metabolic disorders may affect female reproductive health. The purpose of the study was to determine the prevalence of underweight, overweight, obesity, lipid and glucose metabolism disorders, hypertension, and metabolic syndrome, among Polish women of childbearing age. Methods One thousand five hundred eighty-eight non-pregnant Polish women of childbearing age (20–49 years) who participated in the Multi-Centre National Population Health Examination Survey (WOBASZ II study) in 2013–2014, were assigned to 3 age groups: 20–29 years (n = 403), 30–39 years (n = 600) and 40–49 years (n = 585). Measurements of weight, height, waist circumference, blood pressure, blood lipids, and blood glucose were taken. For statistical analysis, the Kruskal-Wallis, Chi-Square, and Cohran-Armitage tests were used. Results Of the participants, 4.3% were determined to be underweight, 25.2% were overweight, 15% were obese, and 53.1% had abdominal obesity. With age, the prevalence of both excessive body mass and abdominal obesity tended to increase, and that of underweight to decrease. Frequency of hypercholesterolemia and hypertriglyceridemia found in the whole group were 50% and 12.6% respectively, and also tended to rise with age. Low serum HDL-cholesterol (high density lipoprotein cholesterol) levels were found in 15.1% of the participants. Prevalence of impaired fasting glucose in the whole group was 8.2% and tended to increase with age. Diabetes was found in 1.2% of the participants and its prevalence also tended to rise with age, at the borderline of significance. Frequency of arterial hypertension and metabolic syndrome in the whole group was 15.7% and 14.1% respectively and both tended to increase with age. Conclusions Overweight and obesity, especially of abdominal type, and the related metabolic abnormalities are common in Polish women of childbearing age. Their prevalence tends to increase with age. Underweight is relatively common in the youngest age group

Tobacco smoking in Poland in the years from 2003 to 2014 : multi-centre National Population Health Examination Survey (WOBASZ)

The reduction of tobacco smoking remains a challenge for public health. The main purpose of this study was to evaluate changes in the prevalence and patterns of tobacco use in the adult population of Poles in the years from 2003 to 2014. Furthermore, changes in the smoking addiction, the declared reasons for smoking, as well as readiness and motivation to stop smoking were assessed. Based on data from the Polish studies WOBASZ and WOBASZ II, the analysis included 14 576 participants from the first study (6906 men and 7670 women) and 5696 participants from the second study (2578 men and 3118 women), aged between 20 and 74 years. According to the WOBASZ II study, 30% of men and 21% of women in Poland smoked, the rates being 9% and 4% lower for men and women, respectively, in comparison with the WOBASZ study (P <0.001). The average number of cigarettes smoked daily per smoker significantly decreased during the follow‑up period among men (from 17.9 to 15.8 cigarettes per day) and women (from 13.7 to 12.1 cigarettes per day). The percentage of men who never smoked increased from 29.8% to 36.1% (P <0.0001), while the proportion of women who never smoked did not change. However, the percentage of those expressing unwillingness to quit smoking nearly doubled in WOBASZ II in comparison with WOBASZ. Although the smoking rates in Poland have declined over the past decade, smoking remains prevalent among men and women. Therefore, it is necessary to optimize tobacco control in Poland, including fiscal policy, counseling and tobacco addiction treatment, as well as promotional and educational activities, with a special emphasis on the female population

Prevalence, awareness, treatment and control of hypertension in the adult Polish population : multi-center National Population Health Examination Surveys : WOBASZ studies

Introduction: Hypertension is one of the main risk factors of cardiovascular diseases. The first aim of the study was to evaluate the prevalence, awareness and treatment of hypertension as well as treatment effectiveness (blood pressure < 140/90 mm Hg) in a representative sample of the Polish population over the age of 19, examined in the WOBASZ II program. The second aim was to assess the changes in these parameters between 2003-2005 (WOBASZ study) and 2013-2014 in adults aged 20-74. Material and methods: Sampling was performed in three stages, stratified according to voivodeship (province), type of commune, and gender. Finally, the study included 6163 persons (3406 women and 2757 men) examined in the years 2013-2014 (aged ≥ 19 years). For comparison the data from 14 755 persons (7783 women and 6452 men aged 20-74 years) examined in the years 2003-2005 were used. Results: In the years 2013-2014, the age-standardized prevalence of hypertension, awareness, treatment and control was 42.7%, 59.3%, 46.1%, and 23% respectively. In the last decade an increase in the prevalence of hypertension (relative ratio (RR) 1.12; 95% confidence interval (CI): 1.07- 1.18), treatment (RR = 1.26; 95% CI: 1.17-1.36) and control (RR = 2.16; 95% CI: 1.91-2.45) was found. In contrast, the awareness decreased nonsignificantly (RR = 0.98; 95% CI: 0.92-1.05). Conclusions: The prevalence of hypertension in Poland is high, and increased by about 12% in 10 years. Although the number of treated patients and blood pressure control improved nearly twofold over the last decade, this is still below expectations. Efforts to improve the diagnosis and effective treatment of hypertension in Poland should still be intensifie