Association of patient-reported outcomes and heart rate trends in heart failure. a report from the chiron project

Patient-reported outcomes (PROs) have been previously considered “soft” end-points because of the lack of association of the reported outcome to measurable biological parameters. The present study aimed to assess whether electrocardiographic measures are associated to PROs changes. We evaluated the association between heart rate (HR), QRS and QT/QTc durations and PROs, classified as “good” or “bad” according to the patients’ overall feeling of health, in patients from the Chiron project. Twenty-four chronic heart failure (HF) patients were enrolled in the study (71% male, mean age 62.9 ± 9.4 years, 42% ischemic etiology, 15 NYHA class II and 9 class III) providing 1086 days of usable physiological recordings (4 hours/day). The mean HR was significantly higher in the “bad” than in the “good” PROs class (74.0 ± 6.4 bpm vs 68.0 ± 7.2 bpm; p < 0.001). Conversely, the ratio between movement and rest activities showed significantly higher values in “good” compared to “bad” PROs. We also found significantly longer QTc and QRS durations in patients with “bad” PROs compared to patients with “good” PROs. That in patients with mild to moderate HF, higher HR, wider QRS and longer QTc, as well as a reduced HR ratio between movement and rest, were associated with “bad” PROs is clinically noteworthy because the association of worse PROs with measurable variations of biological parameters may help physicians in evaluating PROs reliability itself and in their clinical decisions. Whether a timely intervention on these biological parameters may prevent adverse outcomes is important and deserves to be investigated in further studies

Clinical and humoral determinants of congestion in heart failure. potential role of adiponectin

Background: Some patients with heart failure (HF) are more prone to systemic congestion than others. The goal of this study was to identify clinical and humoral factors linked to congestion and its prognostic impact in HF patients. Methods: A total of 371 advanced HF patients underwent physical examination, echocardiography, right heart catheterization, blood samplings, and Minnesota Living with HF Questionnaire. Subjects were followed-up for adverse events (death, urgent transplantation, or assist device implantation without heart transplantation). Results: Thirty-one percent of patients were classified as prone to congestion. During a median follow-up of 1,093 days, 159 (43%) patients had an adverse event. In the Cox analysis, the congestion-prone (CP) status was associated with a 43% higher event risk. The CP status was strongly (p ? 0.001) associated with body weight loss, right ventricular dysfunction (RVD), dilated inferior vena cava (IVC), diuretics, and beta-blockers prescription and the majority of tested hormones in the univariate analysis. In the multivariate analysis, the only independent variables associated with the CP status were adiponectin, albumin, IVC diameter, and RVD. Adiponectin by itself was predictive of adverse events. In a multivariate model, CP status was no longer predictive of adverse events, in contrast to adiponectin. Conclusions: CP patients experienced more severe symptoms and had shorter survival. Potential role of adiponectin, a new independent predictor of CP status, should be further examined

Adult Human Brain Neural Progenitor Cells (NPCs) and Fibroblast-Like Cells Have Similar Properties In Vitro but Only NPCs Differentiate into Neurons

The ability to culture neural progenitor cells from the adult human brain has provided an exciting opportunity to develop and test potential therapies on adult human brain cells. To achieve a reliable and reproducible adult human neural progenitor cell (AhNPC) culture system for this purpose, this study fully characterized the cellular composition of the AhNPC cultures, as well as the possible changes to this in vitro system over prolonged culture periods. We isolated cells from the neurogenic subventricular zone/hippocampus (SVZ/HP) of the adult human brain and found a heterogeneous culture population comprised of several types of post-mitotic brain cells (neurons, astrocytes, and microglia), and more importantly, two distinct mitotic cell populations; the AhNPCs, and the fibroblast-like cells (FbCs). These two populations can easily be mistaken for a single population of AhNPCs, as they both proliferate under AhNPC culture conditions, form spheres and express neural progenitor cell and early neuronal markers, all of which are characteristics of AhNPCs in vitro. However, despite these similarities under proliferating conditions, under neuronal differentiation conditions, only the AhNPCs differentiated into functional neurons and glia. Furthermore, AhNPCs showed limited proliferative capacity that resulted in their depletion from culture by 5–6 passages, while the FbCs, which appear to be from a neurovascular origin, displayed a greater proliferative capacity and dominated the long-term cultures. This gradual change in cellular composition resulted in a progressive decline in neurogenic potential without the apparent loss of self-renewal in our cultures. These results demonstrate that while AhNPCs and FbCs behave similarly under proliferative conditions, they are two different cell populations. This information is vital for the interpretation and reproducibility of AhNPC experiments and suggests an ideal time frame for conducting AhNPC-based experiments

A Dual Role for KRT81: A miR-SNP Associated with Recurrence in Non-Small-Cell Lung Cancer and a Novel Marker of Squamous Cell Lung Carcinoma

MicroRNAs (miRNAs) play an important role in carcinogenesis through the regulation of their target genes. miRNA-related single nucleotide polymorphisms (miR-SNPs) can affect miRNA biogenesis and target sites and can alter microRNA expression and functions. We examined 11 miR-SNPs, including 5 in microRNA genes, 3 in microRNA binding sites and 3 in microRNA-processing machinery components, and evaluated time to recurrence (TTR) according to miR-SNP genotypes in 175 surgically resected non-small-cell lung cancer (NSCLC) patients. Significant differences in TTR were found according to KRT81 rs3660 (median TTR: 20.3 months for the CC genotype versus 86.8 months for the CG or GG genotype; P = 0.003) and XPO5 rs11077 (median TTR: 24.7 months for the AA genotype versus 73.1 months for the AC or CC genotypes; P = 0.029). Moreover, when patients were divided according to stage, these differences were maintained for stage I patients (P = 0.002 for KRT81 rs3660; P<0.001 for XPO5 rs11077). When patients were divided into sub-groups according to histology, the effect of the KRT81 rs3660 genotype on TTR was significant in patients with squamous cell carcinoma (P = 0.004) but not in those with adenocarcinoma. In the multivariate analyses, the KRT81 rs3660 CC genotype (OR = 1.8; P = 0.023) and the XPO5 rs11077 AA genotype (OR = 1.77; P = 0.026) emerged as independent variables influencing TTR. Immunohistochemical analyses in 80 lung specimens showed that 95% of squamous cell carcinomas were positive for KRT81, compared to only 19% of adenocarcinomas (P<0.0001). In conclusion, miR-SNPs are a novel class of SNPs that can add useful prognostic information on the clinical outcome of resected NSCLC patients and may be a potential key tool for selecting high-risk stage I patients. Moreover, KRT81 has emerged as a promising immunohistochemical marker for the identification of squamous cell lung carcinoma

Dysregulation of epicardial adipose tissue in cachexia due to heart failure. the role of natriuretic peptides and cardiolipin

Background: Cachexia worsens long-term prognosis of patients with heart failure (HF). Effective treatment of cachexia is missing. We seek to characterize mechanisms of cachexia in adipose tissue, which could serve as novel targets for the treatment. Methods: The study was conducted in advanced HF patients (n&nbsp;=&nbsp;52; 83% male patients) undergoing heart transplantation. Patients with ≥7.5% non-intentional body weight (BW) loss during the last 6&nbsp;months were rated cachectic. Clinical characteristics and circulating markers were compared between cachectic (n&nbsp;=&nbsp;17) and the remaining, BW-stable patients. In epicardial adipose tissue (EAT), expression of selected genes was evaluated, and a combined metabolomic/lipidomic analysis was performed to assess (i) the role of adipose tissue metabolism in the development of cachexia and (ii) potential impact of cachexia-associated changes on EAT-myocardium environment. Results: Cachectic vs. BW-stable patients had higher plasma levels of natriuretic peptide B (BNP; 2007&nbsp;±&nbsp;1229 vs. 1411&nbsp;±&nbsp;1272&nbsp;pg/mL; P&nbsp;=&nbsp;0.010) and lower EAT thickness (2.1&nbsp;±&nbsp;0.8 vs. 2.9&nbsp;±&nbsp;1.4&nbsp;mm; P&nbsp;=&nbsp;0.010), and they were treated with ~2.5-fold lower dose of both β-blockers and angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (ACE/ARB-inhibitors). The overall pattern of EAT gene expression suggested simultaneous activation of lipolysis and lipogenesis in cachexia. Lower ratio between expression levels of natriuretic peptide receptors C and A was observed in cachectic vs. BW-stable patients (0.47 vs. 1.30), supporting activation of EAT lipolysis by natriuretic peptides. Fundamental differences in metabolome/lipidome between BW-stable and cachectic patients were found. Mitochondrial phospholipid cardiolipin (CL), specifically the least abundant CL 70:6 species (containing C16:1, C18:1, and C18:2 acyls), was the most discriminating analyte (partial least squares discriminant analysis; variable importance in projection score&nbsp;=&nbsp;4). Its EAT levels were higher in cachectic as compared with BW-stable patients and correlated with the degree of BW loss during the last 6&nbsp;months (r&nbsp;=&nbsp;−0.94; P&nbsp;=&nbsp;0.036). Conclusions: Our results suggest that (i) BNP signalling contributes to changes in EAT metabolism in cardiac cachexia and (ii) maintenance of stable BW and ‘healthy’ EAT-myocardium microenvironment depends on the ability to tolerate higher doses of both ACE/ARB inhibitors and β-adrenergic blockers. In line with preclinical studies, we show for the first time in humans the association of cachexia with increased adipose tissue levels of CL. Specifically, CL 70:6 could precipitate wasting of adipose tissue, and thus, it could represent a therapeutic target to ameliorate cachexia

Influencia de un aditivo no comercial sobre la calidad de los yesos en construcción

At the present paper, it shows how has been studied the influence over the quality of a special sort of gypsum, when it has been added as "additive" 0,96% of potasium chlorurus (Kcl), it has been observed the variation on the mechanical proprieties and also over the time of the beginning and end of the set. Also with the use ot a scanner Electronic Microscopic (M.E.B.), it has been observed the results obtained using such additive and it has been made a comparison with the finded values for the standard specimen.En el presente trabajo se ha estudiado la influencia sobre la calidad de un determinado tipo de yeso, al incorporar como "aditivo" 0,96% de cloruro de potasio (KCI), comprobando la variación en el comportamiento mecánico, así como en los tiempos de principio y final de fraguado. También mediante el uso de la Microscopía Electrónica de Barrido (M.E.B.), se han observado los resultados obtenidos al emplear el citado aditivo y se han comparado con los valores encontrados para las probetas patrón

Identification by Real-time PCR of 13 mature microRNAs differentially expressed in colorectal cancer and non-tumoral tissues

PURPOSE: Diffuse large B-cell lymphoma (DLBCL) heterogeneity has prompted investigations for new biomarkers that can accurately predict survival. A previously reported 6-gene model combined with the International Prognostic Index (IPI) could predict patients' outcome. However, even these predictors are not capable of unambiguously identifying outcome, suggesting that additional biomarkers might improve their predictive power. EXPERIMENTAL DESIGN: We studied expression of 11 microRNAs (miRNA) that had previously been reported to have variable expression in DLBCL tumors. We measured the expression of each miRNA by quantitative real-time PCR analyses in 176 samples from uniformly treated DLBCL patients and correlated the results to survival. RESULTS: In a univariate analysis, the expression of miR-18a correlated with overall survival (OS), whereas the expression of miR-181a and miR-222 correlated with progression-free survival (PFS). A multivariate Cox regression analysis including the IPI, the 6-gene model-derived mortality predictor score and expression of the miR-18a, miR-181a, and miR-222, revealed that all variables were independent predictors of survival except the expression of miR-222 for OS and the expression of miR-18a for PFS. CONCLUSION: The expression of specific miRNAs may be useful for DLBCL survival prediction and their role in the pathogenesis of this disease should be examined further

Dietary intake of trans fatty acids in children aged 4–5 in Spain: The INMA cohort study

Trans fatty acid (TFA) intake has been identified as a health hazard in adults, but data on preschool children are scarce. We analyzed the data from the Spanish INMA Project to determine the intake of total, industrial and natural TFA, their main sources and the associated socio-demographic and lifestyle factors in children aged 4–5 (n = 1793). TFA intake was estimated using a validated Food Frequency Questionnaire, and multiple linear regression was used to explore associated factors. The mean daily intakes of total, industrial and natural TFA were 1.36, 0.60, and 0.71 g/day, respectively. Ten percent of the children obtained >1% of their energy intake from TFA. The main sources of industrial TFA were fast food, white bread and processed baked goods. Milk, red and processed meat and processed baked goods were the main sources of natural TFA. Having parents from countries other than Spain was significantly associated with higher natural TFA (in mg/day) intake (β 45.5) and television viewing was significantly associated with higher industrial TFA intake (β 18.3). Higher fruits and vegetables intake was significantly associated with lower intakes of all TFAs, whereas higher sweetened beverages intake was significantly associated with lower total and natural TFA intake. Thus, total and industrial TFA intake was associated with less healthy food patterns and lifestyles in Spanish preschool children

Design and Validation of an FPGA-Based Configurable Transcranial Doppler Neurofeedback System for Chronic Pain Patients

Neurofeedback is a self-regulation technique that can be applied to learn to voluntarily control cerebral activity in specific brain regions. In this work, a Transcranial Doppler-based configurable neurofeedback system is proposed and described. The hardware configuration is based on the Red Pitaya board, which gives great flexibility and processing power to the system. The parameter to be trained can be selected between several temporal, spectral, or complexity features from the cerebral blood flow velocity signal in different vessels. As previous studies have found alterations in these parameters in chronic pain patients, the system could be applied to help them to voluntarily control these parameters. Two protocols based on different temporal lengths of the training periods have been proposed and tested with six healthy subjects that were randomly assigned to one of the protocols at the beginning of the procedure. For the purposes of the testing, the trained parameter was the mean cerebral blood flow velocity in the aggregated data from the two anterior cerebral arteries. Results show that, using the proposed neurofeedback system, the two groups of healthy volunteers can learn to self-regulate a parameter from their brain activity in a reduced number of training sessions.This research was funded by Ministerio de Economía y Competitividad, Spain, grant number PSI2013-48260-C3-2-R. The APC was funded by Ministerio de Economía y Competitividad, Spain, grant number PSI2013-48260-C3-2-R