Poor Sleep and Impaired Self-Care: Towards a Comprehensive Model Linking Sleep, Cognition, and Heart Failure Outcomes

Background: Persons with heart failure (HF) have significantly lower sleep quantity and quality than persons without HF. The purpose of this article is to propose a conceptual model describing how poor sleep may contribute to inadequate self-care and untoward outcomes in persons with HF. Aims: Our overarching hypothesis is that sleep affects self-care and outcomes through its effects on cognition. Building on the work of others, we outline a conceptual model that illustrates that even transient sleep disruption prevents sleep-related restorative processes and contributes to cognitive dysfunction—especially in the 25–50% of HF patients with existing cognitive impairment. Poor sleep may be sufficient to impair cognition to a level that interferes with higher order functions involved in effective HF self-care practices. Through these mechanisms, inadequate sleep may contribute to poor outcomes such as low health-related quality of life and greater risk of unplanned hospitalization. Conclusion: The proposed model (1) bridges physical, neuropsychological and behavioral phenomena, (2) suggests a mechanism by which poor sleep affects daytime behavior, and (3) is empirically testable. Exploring factors that interfere with sleep may improve self-care and outcomes in persons with HF

Design of a novel flow-and-shoot microbeam

Presented here is a novel microbeam technology—the Flow-And-ShooT (FAST) microbeam—under development at RARAF. In this system, cells undergo controlled fluidic transport along a microfluidic channel intersecting the microbeam path. They are imaged and tracked in real-time, using a high-speed camera and dynamically targeted, using a magnetic Point and Shoot system. With the proposed FAST system, RARAF expects to reach a throughput of 100 000 cells per hour, which will allow increasing the throughput of experiments by at least one order of magnitude. The implementation of FAST will also allow the irradiation of non-adherent cells (e.g. lymphocytes), which is of great interest to many of the RARAF users. This study presents the design of a FAST microbeam and results of first tests of imaging and tracking as well as a discussion of the achievable throughput

DNA damage response in peripheral mouse blood leukocytes in vivo after variable, low-dose rate exposure.

Environmental contamination and ingestion of the radionuclide Cesium-137 (137Cs) is a large concern in fallout from a nuclear reactor accident or improvised nuclear device, and highlights the need to develop biological assays for low-dose rate, internal emitter radiation. To mimic low-dose rates attributable to fallout, we have developed a VAriable Dose-rate External 137Cs irradiatoR (VADER), which can provide arbitrarily varying and progressive low-dose rate irradiations in the range of 0.1-1.2 Gy/day, while circumventing the complexities of dealing with radioactively contaminated biomaterials. We investigated the kinetics of mouse peripheral leukocytes DNA damage response in vivo after variable, low-dose rate 137Cs exposure. C57BL/6 mice were placed in the VADER over 7 days with total accumulated dose up to 2.7 Gy. Peripheral blood response including the leukocyte depletion, apoptosis as well as its signal protein p53 and DNA repair biomarker γ-H2AX was measured. The results illustrated that blood leukocyte numbers had significantly dropped by day 7. P53 levels peaked at day 2 (total dose = 0.91 Gy) and then declined; whereas, γ-H2AX fluorescence intensity (MFI) and foci number generally increased with accumulated dose and peaked at day 5 (total dose = 2.08 Gy). ROC curve analysis for γ-H2AX provided a good discrimination of accumulated dose < 2 Gy and ≥ 2 Gy, highlighting the potential of γ-H2AX MFI as a biomarker for dosimetry in a protracted, environmental exposure scenario

Clinical characteristics of children with Juvenile Systemic Sclerosis: follow-up of 23 patients in a single tertiary center

© 2007 Russo and Katsicas; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution Licens

Different strategies to achieve Pb-tolerance by the two Trebouxia algae coexisting in the lichen Ramalina farinacea

Lichen thalli are permeable to airborne substances, including heavy metals, which are harmful to cell metabolism. Ramalina farinacea shows a moderate tolerance to Pb. This lichen comprises two Trebouxia phycobionts, provisionally referred to as TR1 and TR9, with distinct physiological responses to acute oxidative stress. Thus, there is a more severe decay in photosynthesis and photosynthetic pigments in TR1 than in TR9. Similarly, under oxidative stress, antioxidant enzymes and HSP70 protein decrease in TR1 but increase in TR9. Since Pb toxicity is associated with increased ROS formation, we hypothesized greater Pb tolerance in this phycobiont. Accordingly, the aim of the present study was to characterize the physiological differences in the responses of TR1 and TR9 to Pb exposure. Liquid cultures of isolated phycobionts were incubated for 7 days in the presence of Pb(NO3)2. Thereafter, extracellular and intracellular Pb accumulation, photosynthetic pigments, and photosynthesis (as modulated chlorophyll fluorescence) were analyzed along with the antioxidant enzymes glutathione reductase (GR), superoxide dismutase (SOD), ascorbate peroxidase (APx), and catalase (CAT), and the stress-related protein HSP70. Pb uptake increased with the amount of supplied Pb in both algae. However, while significantly more metal was immobilized extracellularly by TR9, the amount of intracellular Pb accumulation was three times higher in TR1. In neither of the phycobionts were significant effects on photosynthetic pigments or photosynthetic electron transport observed. While under control conditions GR, SOD, and APx levels were significantly higher in TR1 than in TR9, only in the latter were these enzymes induced by Pb. This resulted in quantitatively similar antioxidant activities in the two algae when exposed to Pb. In conclusion, the phycobionts of R. farinacea make use of two different strategies against stress, in which the integration of distinct anatomical and physiological features affords similar levels of Pb tolerance.This study was supported by the Spanish Ministry of Science and Innovation (CGL2009-13429-C02-01/02) and the Generalitat Valenciana (PROMETEO 174/2008 and GVACOMP2011-205). We are grateful to the Central Support Service in Experimental Research (SCSIE), University of Valencia (Spain), for the TEM studies. We acknowledge Dr. Said Agouram (SCSIE, University of Valencia, Spain) for TEM-EDXS characterizations and for helpful discussions during the TEM investigations. We thank Wendy Ran and Daniel Sheerin for the English revision of the manuscript.Álvarez, R.; Del Hoyo, A.; García Breijo, FJ.; Reig Armiñana, J.; Del Campo, EM.; Guéra, A.; Barreno, E.... (2012). Different strategies to achieve Pb-tolerance by the two Trebouxia algae coexisting in the lichen Ramalina farinacea. Journal of Plant Physiology. 169(18):1797-1806. https://doi.org/10.1016/j.jplph.2012.07.005S179718061691

An ultrasoft X-ray multi-microbeam irradiation system for studies of DNA damage responses by fixed- and live-cell fluorescence microscopy

Localized induction of DNA damage is a valuable tool for studying cellular DNA damage responses. In recent decades, methods have been developed to generate DNA damage using radiation of various types, including photons and charged particles. Here we describe a simple ultrasoft X-ray multi-microbeam system for high dose-rate, localized induction of DNA strand breaks in cells at spatially and geometrically adjustable sites. Our system can be combined with fixed- and live-cell microscopy to study responses of cells to DNA damage

A study protocol to evaluate the relationship between outdoor air pollution and pregnancy outcomes

<p>Abstract</p> <p>Background</p> <p>The present study protocol is designed to assess the relationship between outdoor air pollution and low birth weight and preterm births outcomes performing a semi-ecological analysis. Semi-ecological design studies are widely used to assess effects of air pollution in humans. In this type of analysis, health outcomes and covariates are measured in individuals and exposure assignments are usually based on air quality monitor stations. Therefore, estimating individual exposures are one of the major challenges when investigating these relationships with a semi-ecologic design.</p> <p>Methods/Design</p> <p>Semi-ecologic study consisting of a retrospective cohort study with ecologic assignment of exposure is applied. Health outcomes and covariates are collected at Primary Health Care Center. Data from pregnant registry, clinical record and specific questionnaire administered orally to the mothers of children born in period 2007-2010 in Portuguese Alentejo Litoral region, are collected by the research team. Outdoor air pollution data are collected with a lichen diversity biomonitoring program, and individual pregnancy exposures are assessed with spatial geostatistical simulation, which provides the basis for uncertainty analysis of individual exposures. Awareness of outdoor air pollution uncertainty will improve validity of individual exposures assignments for further statistical analysis with multivariate regression models.</p> <p>Discussion</p> <p>Exposure misclassification is an issue of concern in semi-ecological design. In this study, personal exposures are assigned to each pregnant using geocoded addresses data. A stochastic simulation method is applied to lichen diversity values index measured at biomonitoring survey locations, in order to assess spatial uncertainty of lichen diversity value index at each geocoded address. These methods assume a model for spatial autocorrelation of exposure and provide a distribution of exposures in each study location. We believe that variability of simulated exposure values at geocoded addresses will improve knowledge on variability of exposures, improving therefore validity of individual exposures to input in posterior statistical analysis.</p

Selective predisposition to bacterial infections in IRAK-4–deficient children: IRAK-4–dependent TLRs are otherwise redundant in protective immunity

Human interleukin (IL) 1 receptor–associated kinase 4 (IRAK-4) deficiency is a recently discovered primary immunodeficiency that impairs Toll/IL-1R immunity, except for the Toll-like receptor (TLR) 3– and TLR4–interferon (IFN)-a/b pathways. The clinical and immunological phenotype remains largely unknown. We diagnosed up to 28 patients with IRAK-4 deficiency, tested blood TLR responses for individual leukocyte subsets, and TLR responses for multiple cytokines. The patients' peripheral blood mononuclear cells (PBMCs) did not induce the 11 non-IFN cytokines tested upon activation with TLR agonists other than the nonspecific TLR3 agonist poly(I:C). The patients' individual cell subsets from both myeloid (granulocytes, monocytes, monocyte-derived dendritic cells [MDDCs], myeloid DCs [MDCs], and plasmacytoid DCs) and lymphoid (B, T, and NK cells) lineages did not respond to the TLR agonists that stimulated control cells, with the exception of residual responses to poly(I:C) and lipopolysaccharide in MDCs and MDDCs. Most patients (22 out of 28; 79%) suffered from invasive pneumococcal disease, which was often recurrent (13 out of 22; 59%). Other infections were rare, with the exception of severe staphylococcal disease (9 out of 28; 32%). Almost half of the patients died (12 out of 28; 43%). No death and no invasive infection occurred in patients older than 8 and 14 yr, respectively. The IRAK-4–dependent TLRs and IL-1Rs are therefore vital for childhood immunity to pyogenic bacteria, particularly Streptococcus pneumoniae. Conversely, IRAK-4–dependent human TLRs appear to play a redundant role in protective immunity to most infections, at most limited to childhood immunity to some pyogenic bacteria

Modulation of epithelial sodium channel (ENaC) expression in mouse lung infected with Pseudomonas aeruginosa

BACKGROUND: The intratracheal instillation of Pseudomonas aeruginosa entrapped in agar beads in the mouse lung leads to chronic lung infection in susceptible mouse strains. As the infection generates a strong inflammatory response with some lung edema, we tested if it could modulate the expression of genes involved in lung liquid clearance, such as the α, β and γ subunits of the epithelial sodium channel (ENaC) and the catalytic subunit of Na(+)-K(+)-ATPase. METHODS: Pseudomonas aeruginosa entrapped in agar beads were instilled in the lung of resistant (BalB/c) and susceptible (DBA/2, C57BL/6 and A/J) mouse strains. The mRNA expression of ENaC and Na(+)-K(+)-ATPase subunits was tested in the lung by Northern blot following a 3 hours to 14 days infection. RESULTS: The infection of the different mouse strains evoked regulation of α and β ENaC mRNA. Following Pseudomonas instillation, the expression of αENaC mRNA decreased to a median of 43% on days 3 and 7 after infection and was still decreased to a median of 45% 14 days after infection (p < 0.05). The relative expression of βENaC mRNA was transiently increased to a median of 241%, 24 h post-infection before decreasing to a median of 43% and 54% of control on days 3 and 7 post-infection (p < 0.05). No significant modulation of γENaC mRNA was detected although the general pattern of expression of the subunit was similar to α and β subunits. No modulation of α(1)Na(+)-K(+)-ATPase mRNA, the catalytic subunit of the sodium pump, was recorded. The distinctive expression profiles of the three subunits were not different, between the susceptible and resistant mouse strains. CONCLUSIONS: These results show that Pseudomonas infection, by modulating ENaC subunit expression, could influence edema formation and clearance in infected lungs

Salivary changes and dental caries as potential oral markers of autoimmune salivary gland dysfunction in primary Sjögren's syndrome

BACKGROUND: the classification criteria for primary Sjögren's syndrome (pSS) include a number of oral components. In this study we evaluated if salivary flow and composition as well as dental caries are oral markers of disease severity in pSS. METHODS: in 20 patients fulfilling the American-European Consensus criteria for pSS and 20 age-matched healthy controls whole and parotid saliva flow rates and composition, measures of oral dryness, scores of decayed, missing and filled tooth surfaces (DMFS), periodontal indices, oral hygiene, and dietary habits were examined. RESULTS: in pSS, salivary flow rates, pH, and buffer capacities were lower, and DMFS, salivary sodium and chloride concentrations higher than in the healthy controls. DMFS also correlated inversely to salivary flow rates and positively to oral dryness. Apart from slightly increased gingival index, and more frequent dental visits in pSS, the periodontal condition, oral hygiene or sugar intake did not differ between these two groups. In pSS, findings were correlated to labial salivary gland focus score (FS) and presence of serum-autoantibodies to SSA/SSB (AB). The patients having both presence of AB and the highest FS (>2) also had the highest salivary sodium and chloride concentrations, the lowest salivary phosphate concentrations, lowest salivary flow rates, and highest DMFS compared to those with normal salivary concentrations of sodium and chloride at a given flow rate. CONCLUSION: the salivary changes observed in some pSS patients reflect impaired ductal salt reabsorption, but unaffected acinar transport mechanisms, despite low salivary secretion. Our results suggest that changes in salivary flow and composition as well as dental caries may serve as potential markers of the extent of autoimmune-mediated salivary gland dysfunction in pSS. The study also indicates that the ductal epithelium is functionally affected in some pSS patients, which calls for future pathophysiological studies on the mechanisms underlying this impaired salt reabsorption