IL-6 is an antiinflammatory cytokine required for controlling local or systemic acute inflammatory responses.

IL-6 is induced often together with the proinflammatory cytokines TNFalpha and IL-1 in many alarm conditions, and circulating IL-6 plays an important role in the induction of acute phase reactions. However, whether this endogenous IL-6 plays any additional pro- or antiinflammatory roles in local or systemic responses remains unclear. In this study, the role of IL-6 in acute inflammatory responses was investigated in animal models of endotoxic lung or endotoxemia by using IL-6+/+ and IL-6-/- mice. Aerosol exposure of endotoxin induced increased IL-6 and proinflammatory cytokines TNFalpha and MIP-2 and a neutrophilic response in the lung of IL-6+/+ mice. However, the levels of TNFalpha and MIP-2 and neutrophilia were significantly higher in the lung of IL-6-/- mice. The rate of neutrophil apoptosis in these mice was similar to that in IL-6+/+ mice. A low constitutive level of antiinflammatory cytokine IL-10 was not enhanced by endotoxin and remained similar in the lung in both IL-6+/+ and IL-6-/- mice. Systemically, intraperitoneal delivery of endotoxin resulted in much more pronounced circulating levels of TNFalpha, MIP-2, GM-CSF, and IFNgamma in IL-6-/- mice than in IL-6+/+ mice, and administration of recombinant IL-6 to IL-6-/- mice abolished these differences. In contrast, circulating IL-10 levels were induced to a similar degree in both IL-6+/+ and IL-6-/- mice. Thus, our studies reveal that endogenous IL-6 plays a crucial antiinflammatory role in both local and systemic acute inflammatory responses by controlling the level of proinflammatory, but not antiinflammatory, cytokines, and that these antiinflammatory activities by IL-6 cannot be compensated for by IL-10 or other IL-6 family members.     

Organization of health services and tuberculosis care management

The scope of this study was to analyze the discourse of managers regarding the relationship between the organization of the health services and tuberculosis care management in a city in the metropolitan region of Jo?o Pessoa, State of Pernambuco. Using qualitative research in the analytical field of the French line of Discourse Analysis, 16 health workers who worked as members of the management teams took part in the study. The transcribed testimonials were organized using Atlas.ti version 6.0 software. After detailed reading of the empirical material, an attempt was made to identify the paraphrasic, polyssemic and metaphoric processes in the discourses, which enabled identification of the following discourse formation: Organization of the health services and the relation with TB care management: theory and practice. In the discourse of the managers the fragmentation of the actions of control of tuberculosis, the lack of articulation between the services and sectors, the compliance of the specific activities for TB, as well as the lack of strategic planning for management of care of the disease are clearly revealed. In this respect, for the organization of the health services to be effective, it is necessary that tuberculosis be considered a priority and acknowledged as a social problem in the management agenda.     

Inhibition of glycogen synthase kinase-3 by lithium correlates with reduced tauopathy and degeneration in vivo

Neurofibrillary tangles composed of hyperphosphorylated, aggregated tau are a common pathological feature of tauopathies, including Alzheimer's disease. Abnormal phosphorylation of tau by kinases or phosphatases has been proposed as a pathogenic mechanism in tangle formation. To investigate whether kinase inhibition can reduce tauopathy and the degeneration associated with it in vivo, transgenic mice overexpressing mutant human tau were treated with the glycogen synthase kinase-3 (GSK-3) inhibitor lithium chloride. Treatment resulted in significant inhibition of GSK-3 activity. Lithium administration also resulted in significantly lower levels of phosphorylation at several epitopes of tau known to be hyperphosphorylated in Alzheimer's disease and significantly reduced levels of aggregated, insoluble tau. Administration of a second GSK-3 inhibitor also correlated with reduced insoluble tau levels, supporting the idea that lithium exerts its effect through GSK-3 inhibition. Levels of aggregated tau correlated strongly with degree of axonal degeneration, and lithium-chloride-treated mice showed less degeneration if administration was started during early stages of tangle development. These results support the idea that kinases are involved in tauopathy progression and that kinase inhibitors may be effective therapeutically.     

Solute movement across the alveolar-capillary membrane after intratracheally administered bleomycin in rats

The rate of absorption across the alveolar-capillary membrane of inhaled 99mTc-DTPA and the concentration of albumin in the bronchoalveolar lavage (BAL) fluid were characterized in a rat model of bleomycin-induced pulmonary fibrosis. Adult male Lewis rats were studied from 1 h to 120 days after a single intratracheal instillation of bleomycin (0.5 to 0.6 U/100 g body weight). The retention of 99mTc-DTPA in the lungs, expressed as a percentage of the baseline radioactivity, was determined at 15 min (%R15) after delivery of the tracer. The %R15 was 83.7 +/- 6.0 for normal untreated rats and 84.3 +/- 3.7 for saline-treated animals. The rate of absorption of 99mTc-DTPA began to increase 24 h after bleomycin, reaching a maximum at Day 7, with %R15 = 56.0 +/- 6.5 (p less than 0.0001). Resolution to control values occurred by Day 34 after bleomycin. At Day 45 after bleomycin, the rate of absorption of 99mTc-DTPA was slower than sham (control), with %R15 = 89.2 +/- 1.9 (p less than 0.5). However, from Day 63 onwards, removal was not different from control. The concentration of albumin in the BAL fluid began to increase 48 h after bleomycin, was 10-fold greater than control by Day 7 (150 +/- 38 versus 16 +/- 3 micrograms/ml), and returned to control values by Day 28. The percentage of neutrophils in the BAL increased at 12 h, reached a plateau of 33 +/- 9% between 4 and 7 days, and then returned to control values by Day 14.(ABSTRACT TRUNCATED AT 250 WORDS)     

A retrospective analysis of the utility of an artificial neural network to predict ED volume

Objective

The objectives of this study are to design an artificial neural network (ANN) and to test it retrospectively to determine if it may be used to predict emergency department (ED) volume.

Methods

We conducted a retrospective review of patient registry data from February 4, 2007, to December 31, 2009, from an inner city, tertiary care hospital. We harvested data regarding weather, days of week, air quality, and special events to train the ANN. The ANN belongs to a class of neural networks called multilayer perceptrons. We designed an ANN composed of 37 input neurons, 22 hidden neurons, and 1 output neuron designed to predict the daily number of ED visits. The training method is a supervised backpropagation algorithm that uses mean squared error to minimize the average squared error between the ANN's output and the number of ED visits over all the example pairs.

Results

A linear regression between the predicted and actual ED visits demonstrated an R² of 0.957 with a slope of 0.997. Ninety-five percent of the time, the ANN was within 20 visits.

Conclusion

The results of this study show that a properly designed ANN is an effective tool that may be used to predict ED volume. The scatterplot demonstrates that the ANN is least predictive at the extreme ends of the spectrum suggesting that the ANN may be missing important variables. A properly calibrated ANN may have the potential to allow ED administrators to staff their units more appropriately in an effort to reduce patient wait times, decrease ED physician burnout rates, and increase the ability of caregivers to provide quality patient care. A prospective is needed to validate the utility of the ANN.     

Parental sleep experiences on the pediatric oncology ward

Purpose

Parents of pediatric oncology patients are encouraged to sleep on the ward with their child to provide additional care throughout the night. The purpose of this study was to provide the first prevalence estimates of self-reported sleep quantity and quality among parents accommodated on the pediatric oncology ward, compared to parents of age-matched controls.

Methods

Parents of children receiving in-patient cancer treatment and parents of healthy, age-matched children completed a self-report questionnaire, including validated measures of parental sleep and psychological distress, demographic, and clinical characteristics.

Results

In total, 114 parents participated (52 parents of children with cancer; 62 control parents; over all response rate 70 %). Parents on the pediatric oncology ward reported sleeping 5.7 h (SD?=?1.8) on average, in comparison to control parents who reported sleeping 7.0 h at home (SD?=?1.4; t?=?4.3, p?<?0.001). Parents reported waking an average of 4.6 times (SD?=?0.3) per night on the ward, compared to control parents who reported 2.0 (SD?=?0.2) nighttime awakenings (t?=?7.69, p?<?0.001). Parents of children with cancer were significantly more likely to report that they had slept “badly” (67.3 versus 21.0 %; χ²?=?21.9, p?<?0.001). Significant predictors of sleep duration included anxiety (p?=?0.013) and caffeine consumption (p?=?0.017). Parents who slept on the ward attributed poor sleep to feelings of anxiety, environmental noise, and child-related factors.

Conclusions

Parents who sleep on the pediatric oncology ward experience poor sleep outcomes, including inadequate duration and frequent interruptions. The detrimental effects of sleep deprivation on parents' ability to cope during this challenging time require further investigation and intervention.     

Methodologic considerations in mucociliary clearance and lung epithelial absorption measurements

Measurements of mucociliary clearance and lung epithelial permeability are relatively simple to perform, with minimum discomfort to the subjects. Awareness of the factors influencing the outcome of these procedures will help to avoid errors and yield useful information about these two clearance mechanisms from both a physiological and a pathological point of view.

     

Adenoviral infection inhibits allergic airways inflammation in mice

BACKGROUND: Recent epidemiological studies have suggested that exposure to certain viruses and bacteria influences the development of allergy and allergic diseases, such as asthma. However, there is a paucity of experimental evidence examining the consequences of concurrent exposure to allergen and infectious agents, and the potential mechanisms by which allergic disease might be averted as a result. OBJECTIVE: To model this situation experimentally, we investigated whether a virally induced immune response, elicited by a replication-deficient human type 5 adenovirus (RDA) administered at a site distant from the airways, could inhibit ovalbumin (OVA)-induced airways eosinophilic inflammation. METHODS: C57BL/6 mice were infected intramuscularly with RDA 16h prior to intraperitoneal OVA sensitization. Cellular and cytokine responses in the lung/airways were examined after an OVA aerosol challenge. RESULTS: RDA infection significantly inhibited the inflammatory response in the lung tissue after antigen challenge. In the bronchoalveolar lavage (BAL), total cell number, eosinophils and lymphocytes were decreased by 70, 85 and 65%, respectively, after antigen challenge in RDA-treated, compared with untreated, mice. RDA infection had no effect on IgE synthesis. The levels of IL-5, IL-4 and IFNgamma in the BAL after antigen challenge were significantly lower in RDA-treated mice. In vitro production of cytokines by splenocytes in response to OVA restimulation revealed a shift from IL-4 in sensitized, PBS-treated mice, to IFNgamma in sensitized mice treated with RDA. Flow cytometric analysis revealed that RDA infection increased the proportion of CD8 T cells in the BAL; this change in T-cell subsets was accompanied by an increase in both CD4 and CD8 T cells positive for intracellular IFNgamma. Inhibition of antigen-induced airways inflammation was IFNgamma-dependent but did not require IL-12, as RDA-treatment inhibited airways inflammation in IL-12 but not IFNgamma knock-out mice. CONCLUSION: This study demonstrates that an immune response against a replication-deficient adenovirus during the initial exposure to OVA inhibits the development of airways inflammation after antigen aerosol challenge.