Activation of cytokines and NF-kappa B in corneal epithelial cells infected by respiratory syncytial virus: potential relevance in ocular inflammation and respiratory infection

BACKGROUND: Respiratory syncytial virus (RSV) is a major cause of lower respiratory tract infection, claiming millions of lives annually. The virus infects various cells of the respiratory tract as well as resident inflammatory cells such as macrophages. Infection activates a variety of cellular factors such as cytokines and the pro-inflammatory transcription factor, NF-kappa B, all of which are important players in the respiratory disease. However, the exact natural route of RSV infection and its etiology remain relatively unknown. In this paper, we test the hypothesis that human corneal epithelial cells, which constitute the outermost layer of the cornea, can be infected with RSV, and that the infection leads to the activation of proinflammatory macromolecules. RESULTS: Corneal swabs obtained from pediatric patients with acute respiratory disease were found to contain RSV at a high frequency (43 positive out of 72 samples, i.e., 60%). Primary corneal epithelial cells in tissue culture supported robust infection and productive growth of RSV. Infection resulted in the activation of TNF-α, IL-6 and sixteen chemokines as well as NF-κB. Three proinflammatory CXC chemokines (MIG, I-TAC, IP-10) underwent the greatest activation. CONCLUSIONS: The ocular epithelium is readily infected by RSV. The pro-inflammatory cytokines are likely to play critical roles in the etiology of inflammation and conjunctivitis commonly seen in pediatric patients with respiratory infections. RSV-eye interactions have important implications in RSV transmission, immunopathology of RSV disease, and in the management of conjunctivitis

Differential regulation of ENA-78 and GCP-2 gene expression in human corneal keratocytes and epithelial

PURPOSE. To determine whether interleukin (IL)-1␣-and tumor necrosis factor (TNF)-␣-stimulated human corneal epithelial cells (HCECs) and human corneal keratocytes (HCKs) produce the ␣-chemokines epithelial cell-derived neutrophil attractant (ENA)-78 and granulocyte chemotactic protein (GCP)-2. METHODS. Cultures of HCECs and HCKs were stimulated with either human recombinant IL-1␣ or TNF-␣. At selected times after stimulation, culture supernatants were harvested and assayed for ENA-78 and GCP-2 by enzyme-linked immunosorbent assay. RNA was extracted from cell cultures to measure steady state levels of intracellular ENA-78 and GCP-2 pre-mRNA and mRNA by the reverse transcription-polymerase chain reaction. RESULTS. Exposure of HCECs to either IL-1␣ or TNF-␣ stimulated a more than 4.5-fold increase in ENA-78 RNA and protein synthesis without stimulating a significant increase in either GCP-2 RNA synthesis or protein production. Exposure of HCK to IL-1␣ stimulated a 10-fold increase in ENA-78 and GCP-2 RNA synthesis and a more than 300-fold increase in ENA-78 and GCP-2 protein production. In contrast, exposure of keratocytes to TNF-␣ significantly enhanced ENA-78 RNA synthesis, resulting in a more than 68-fold increase in ENA-78 protein synthesis without significantly enhancing either GCP-2 gene expression or protein secretion. CONCLUSIONS. ENA-78 gene expression is significantly enhanced in both HCECs and HCKs in response to either IL-1␣ or TNF-␣ stimulation. In contrast, GCP-2 synthesis is only inducible in IL-1␣-stimulated HCKs. The results suggest that GCP-2 gene expression is more tightly regulated in diseased or injured corneal tissue than is ENA-78 gene expression. (Invest Ophthalmol Vis Sci. 2003;44:3432-3437

Associations between nutritional properties of food and consumer perceptions related to weight management

Consumer perceptions of food (for example, how filling or healthy) influence eating behaviour and appetite control. Therefore approaches to understand the global nutritional attributes of foods that predict the strength of consumer perceptions are of academic and commercial interest. The current research describes the development of a flexible platform for systematically mapping the global nutritional attributes of foods (both objective and perceived) to consumer perceptions of those foods. The platform consists of a database of standardised UK food images (currently n= 300), linked to a catalogue of detailed perceptual, nutritional, sensory, cost, and psychological information ('nutritional attributes'). The platform also incorporates demographic and psychometric questionnaires to examine the importance of nutritional attributes on consumer perceptions within or between relevant target groups. In the current study, the platform was applied to a sample of dieting and non-dieting British men and women (n= 887) to examine the global attributes of a subset of foods (n= 75) and their association with successful weight management (i.e. supportive of weight loss, weight loss maintenance or prevention of weight gain). Generalised linear models identified energy density, cost (£/kcal), perceived energy content and satiating capacity as the main nutritional attributes underlying dieters' and non-dieters' perception of successful weight management food. Additionally, pleasantness, and desire not to (over) eat were uniquely associated with dieters' perception of food as good for weight management; pleasantness was positively associated with weight management and desire to eat was negatively associated with weight management. Therefore, global nutritional attributes of foods can predict and distinguish the extent consumers' perceive a food to be related to successful weight management. This platform will be extended to increase the variety of foods and specificity of nutritional attributes in the database suitable for a range of commercial, academic or clinical research applications

Implementation of the "FASTHUG" concept decreases the incidence of ventilator-associated pneumonia in a surgical intensive care unit

<p>Abstract</p> <p>Background</p> <p>Ventilator-associated pneumonia (VAP) is a leading cause of morbidity and mortality in critically ill patients. The Institute for Healthcare Improvement 100,000 Lives Campaign made VAP a target of prevention and performance improvement. Additionally, the Joint Commission on Accreditation of Health Organizations' 2007 Disease Specific National Patient Safety Goals included the reduction of healthcare-associated infections. We report implementation of a performance improvement project that dramatically reduced our VAP rate that had exceeded the 90^thpercentile nationally.</p> <p>Methods</p> <p>From 1 January 2004 to 31 December 2005 a performance improvement project was undertaken to decrease our critical care unit VAP rate. In year one (2004) procedural interventions were highlighted: aggressive oral care, early extubation, management of soiled or malfunctioning respiratory equipment, hand washing surveillance, and maximal sterile barrier precautions. In year two (2005) an evaluative concept called FASTHUG (daily evaluation of patients' feeding, analgesia, sedation, thromboembolic prophylaxis, elevation of the head of the bed, ulcer prophylaxis, and glucose control) was implemented. To determine the long-term effectiveness of such an intervention a historical control period (2003) and the procedural intervention period of 2004, i.e., the pre-FASTHUG period (months 1–24) were compared with an extended post-FASTHUG period (months 25–54).</p> <p>Results</p> <p>The 2003 surgical intensive care VAP rate of 19.3/1000 ventilator-days served as a historical control. Procedural interventions in 2004 were not effective in reducing VAP, p = 0.62. However, implementation of FASTHUG in 2005, directed by a critical care team, resulted in a rate of 7.3/1000 ventilator-days, p ≤ .01. The median pneumonia rate was lower after implementation of FASTHUG when compared to the historical control year (p = .028) and the first year after the procedural interventions (p = .041) using follow-up pairwise comparisons. The pre-FASTHUG period (2003–2004, months 1–24) when compared with an extended post-FASTHUG period (2005–2007, 25–54 months) also demonstrated a significant decrease in the VAP rate, p = .0004. This reduction in the post-FASTHUG period occurred despite a rising Severity of Illness index in critically ill patients, p = .001.</p> <p>Conclusion</p> <p>Implementation of the FASTHUG concept, in the daily evaluation of mechanically ventilated patients, significantly decreased our surgical intensive care unit VAP rate.</p

Automatic Physiological Waveform Processing for fMRI Noise Correction and Analysis

Functional MRI resting state and connectivity studies of brain focus on neural fluctuations at low frequencies which share power with physiological fluctuations originating from lung and heart. Due to the lack of automated software to process physiological signals collected at high magnetic fields, a gap exists in the processing pathway between the acquisition of physiological data and its use in fMRI software for both physiological noise correction and functional analyses of brain activation and connectivity. To fill this gap, we developed an open source, physiological signal processing program, called PhysioNoise, in the python language. We tested its automated processing algorithms and dynamic signal visualization on resting monkey cardiac and respiratory waveforms. PhysioNoise consistently identifies physiological fluctuations for fMRI noise correction and also generates covariates for subsequent analyses of brain activation and connectivity

Beyond the Bayley: Neurocognitive Assessments of Development During Infancy and Toddlerhood

The use of global, standardized instruments is conventional among clinicians and researchers interested in assessing neurocognitive development. Exclusively relying on these tests for evaluating effects may underestimate or miss specific effects on early cognition. The goal of this review is to identify alternative measures for possible inclusion in future clinical trials and interventions evaluating early neurocognitive development. The domains included for consideration are attention, memory, executive function, language and socio-emotional development. Although domain-based tests are limited, as psychometric properties have not yet been well-established, this review includes tasks and paradigms that have been reliably used across various developmental psychology laboratories

Multiple Sources of Contamination in Samples from Patients Reported to Have XMRV Infection

Xenotropic murine leukemia virus (MLV)-related retrovirus (XMRV) was reported to be associated with prostate cancer by Urisman, et al. in 2006 and chronic fatigue syndrome (CFS) by Lombardi, et al. in 2009. To investigate this association, we independently evaluated plasma samples from 4 patients with CFS reported by Lombardi, et al. to have XMRV infection and from 5 healthy controls reported to be XMRV uninfected. We also analyzed viral sequences obtained from supernatants of cell cultures found to contain XMRV after coculture with 9 clinical samples from 8 patients. A qPCR assay capable of distinguishing XMRV from endogenous MLVs showed that the viral sequences detected in the CFS patient plasma behaved like endogenous MLVs and not XMRV. Single-genome sequences (N = 89) from CFS patient plasma were indistinguishable from endogenous MLVs found in the mouse genome that are distinct from XMRV. By contrast, XMRV sequences were detected by qPCR in 2 of the 5 plasma samples from healthy controls (sequencing of the qPCR product confirmed XMRV not MLV). Single-genome sequences (N = 234) from the 9 culture supernatants reportedly positive for XMRV were indistinguishable from XMRV sequences obtained from 22Rv1 and XMRV-contaminated 293T cell-lines. These results indicate that MLV DNA detected in the plasma samples from CFS patients evaluated in this study was from contaminating mouse genomic DNA and that XMRV detected in plasma samples from healthy controls and in cultures of patient samples was due to cross-contamination with XMRV (virus or nucleic acid)

The forgotten smoker: a qualitative study of attitudes towards smoking, quitting, and tobacco control policies among continuing smokers

Although research suggests that the majority of smokers want to quit smoking, the uptake of Stop Smoking Services, designed to assist smokers with quitting, remains low. Little is known about continuing smokers who do not access these services, and opportunities to influence their motivation and encourage quit attempts through the uptake of services. Using PRIME theory, this study explored differences between continuing smokers who had varying levels of motivation to quit, in terms of their plans to quit, evaluative beliefs about smoking, cigarette dependence, and attitudes towards tobacco control policies and services

Socioeconomic status and non-fatal injuries among Canadian adolescents: variations across SES and injury measures

BACKGROUND: While research to date has consistently demonstrated that socioeconomic status (SES) is inversely associated with injury mortality in both children and adults, findings have been less consistent for non-fatal injuries. The literature addressing SES and injury morbidity among adolescents has been particularly inconclusive. To explore potential explanations for these discrepant research findings, this study uniquely compared the relationship across different measures of SES and different causes of injury (recreation versus non-recreation injuries) within a sample of Canadian adolescents. METHODS: The sample included adolescent participants (aged 12 to 19 years) in the Canadian 1996–1997 cross-sectional National Population Health Survey (n = 6967). Five SES measures (household income, two neighbourhood-level proxy measures, two parental indicators) were examined in relation to three injury outcomes (total, recreation, and non-recreation injuries) using multivariable logistic regression. RESULTS: Among males, a clear relationship with injury was observed only for a parental SES index, which was positively associated with total and recreation injuries (odds ratios for the highest versus lowest SES category of 1.9 for total and 2.5 for recreation injuries). Among females, there was some evidence of a positive relationship between SES and injuries, particularly for a neighbourhood-level education measure with total and recreation injuries (odds ratios of 1.7 for total and 2.0 for recreation injuries). CONCLUSION: The results suggest that differences related to the measures of SES chosen and the causes of injury under study may both contribute to discrepancies in past research on SES and non-fatal injuries among adolescents. To clarify the potential SES-injury relationship among youth, the findings emphasize a need for a greater understanding of the meaning and relevance of different SES measures for adolescents, and for an exploration of the pathways through which SES may be related to injury risk

Localized Fetomaternal Hyperglycemia: Spatial and Kinetic Definition by Positron Emission Tomography

to isolated hyperglycemia in the pregnant rat. mg/dL) localized to the left uterine artery was sustained for at least 48 hours while maternal euglycemia was maintained. fetal effects of isolated hyperglycemia. Broadly, this approach can be extended to study a variety of maternal-sided perturbations suspected to directly affect fetal health