The innate immune response is a complex process involving multiple pathogen-recognition receptors, including toll-like receptors (TLRs) and nucleotide-binding oligomerization domain (NOD)-like ...receptors. Complement is also a critical component of innate immunity. While complement is known to interact with TLR-mediated signals, the interactions between NOD-like receptors and complement are not well understood. Here we report a synergistic interaction between C5a and Nod2 signaling in RAW 264.7 macrophages. Long-term treatment with muramyl dipeptide (MDP), a NOD2 ligand, enhanced C5a-mediated expression of chemokine mRNAs in RAW 264.7 cells. This response was dependent on NOD2 expression and was associated with a decrease in expression of C5L2, a receptor for C5a which acts as a negative modulator of C5a receptor (C5aR) activity. MDP amplified C5a-mediated phosphorylation of p38 MAPK. Treatment of RAW264.7 cells with an inhibitor of p38 attenuated the synergistic effects of C5a on MDP-primed cells on MIP-2, but not MCP-1, mRNA. In contrast, inhibition of AKT prevented C5a stimulation of MCP-1, but not MIP-2, mRNA, in MDP-primed cells. Taken together, these data demonstrated a synergistic interaction between C5a and NOD2 in the regulation of chemokine expression in macrophages, associated with a down-regulation of C5L2, a negative regulator of C5a receptor activity.
Background Child undernutrition affects millions of children globally. We investigated associations between suboptimal growth and mortality by pooling large studies. Methods Pooled analysis involving ...children 1 week to 59 months old in 10 prospective studies in Africa, Asia and South America. Utilizing most recent measurements, we calculated weight-for-age, height/length-for-age and weight-for-height/length Z scores, applying 2006 WHO Standards and the 1977 NCHS/WHO Reference. We estimated all-cause and cause-specific mortality hazard ratios (HR) using proportional hazards models comparing children with mild (-2 less than or equal to Z<-1), moderate (-3 less than or equal to Z<-2), or severe (Z<-3) anthropometric deficits with the reference category (Z greater than or equal to -1). Results 53 809 children were eligible for this re-analysis and contributed a total of 55 359 person-years, during which 1315 deaths were observed. All degrees of underweight, stunting and wasting were associated with significantly higher mortality. The strength of association increased monotonically as Z scores decreased. Pooled mortality HR was 1.52 (95% Confidence Interval 1.28, 1.81) for mild underweight; 2.63 (2.20, 3.14) for moderate underweight; and 9.40 (8.02, 11.03) for severe underweight. Wasting was a stronger determinant of mortality than stunting or underweight. Mortality HR for severe wasting was 11.63 (9.84, 13.76) compared with 5.48 (4.62, 6.50) for severe stunting. Using older NCHS standards resulted in larger HRs compared with WHO standards. In cause-specific analyses, all degrees of anthropometric deficits increased the hazards of dying from respiratory tract infections and diarrheal diseases. The study had insufficient power to precisely estimate effects of undernutrition on malaria mortality. Conclusions All degrees of anthropometric deficits are associated with increased risk of under-five mortality using the 2006 WHO Standards. Even mild deficits substantially increase mortality, especially from infectious diseases.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Chronic obstructive pulmonary disease is a common, burdensome and underdiagnosed condition in Australia. Spirometry is the basis of diagnosis and assessing severity in individual patients. Smoking ...cessation is the keystone for slowing the rate of decline in lung function. Pulmonary rehabilitation reduces breathlessness, anxiety and depression, and improves exercise capacity and quality of life. Multidisciplinary care plans and individual self-management plans may help to prevent or manage crises. Inhaled bronchodilators provide symptom relief and may increase exercise capacity. Systemic steroids reduce the severity and shorten recovery from acute exacerbations. Patients with chronic obstructive pulmonary disease should receive influenza and pneumococcal vaccination.
BACKGROUND: Of all the major diseases, chronic obstructive pulmonary disease (COPD) is the one for which the burden is increasing the fastest. OBJECTIVE: This article discusses the diagnoses and ...assessment of COPD, and provides management guidelines including smoking cessation, bronchodilator therapy, the use of inhaled corticosteroids, combination therapies, oxygen therapy, and rehabilitation. DISCUSSION: Diagnosis is by clinical suspicion in patients with an appropriate clinical history and airflow obstruction is confirmed using spirometry. Although smoking cessation and oxygen in selected individuals are the only interventions known to alter the natural history of COPD, many other treatments can significantly lessen breathlessness, reduce exacerbations, and improve exercise and quality of life. (author abstract)
It is unclear whether short-term benefits from supplemental oxygen translate into improved quality of life in patients with severe COPD. In a 12 wk double-blind randomized crossover study, we ...assessed the effects of supplemental air and oxygen on exercise performance (step tests and 6 min walking distance 6MWD) initially and after two 6 wk periods at home using exertional cylinder air or oxygen. We measured quality of life at baseline and after the two 6 wk domiciliary periods. The 26 patients (24 males) had a mean age of 73 +/- 6 yr; mean FEV1, 0.9 +/- 0.4 L; mean DLCO, 10.6 +/- 2.4 ml/min/mm Hg; mean resting PO2, 69 +/- 8.5 (range 58 to 82) mm Hg; mean PCO2, 41 +/- 3.3 mm Hg; and mean resting SaO2, 94 +/- 2.1 (mean +/- SD). Laboratory tests were performed breathing intranasal air or oxygen at 4 L/min, and measurements were made of SaO2 and Borg dysnea scores. Supplemental oxygen increased 6MWD and steps by small, statistically significant increments acutely at baseline and after 6 and 12 wk, without corresponding falls in Borg score. Degree of desaturation at baseline did not correlate with increase in 6MWD or steps achieved at baseline or at 6 or 12 wk, nor with the domiciliary gas used. There was no difference in 6MWD or steps achieved while breathing supplemental oxygen after 6 wk of domiciliary oxygen compared with domiciliary air. Small improvements in quality of life indices were found after domiciliary oxygen, and mastery also improved after domiciliary air. There were no differences in quality of life, however, when domiciliary oxygen was compared with domiciliary air. Although oxygen supplementation induced small acute increments in laboratory exercise performance, such improvements had little impact on the patients' daily lives.
Nine patients with tumour stage mycosis fungoides (MF) have been entered into a pilot study of T‐cell depletion and autologous stem cell transplantation (SCT). Eight patients had detectable ...rearrangements of the T‐cell receptor (TCR) γ‐gene demonstrated by polymerase chain reaction (PCR)/single‐stranded conformation polymorphism (SSCP) in the peripheral blood. The median age was 47 years and the median duration of disease before SCT was 61 months; Peripheral blood progenitor cells were mobilized using high‐dose etoposide (1·6 g/m2) and granulocyte colony‐stimulating factor (G‐CSF). The apheresis products underwent rigorous T‐cell depletion with immunomagnetic methods. Double CD34‐positive and CD4/CD8‐negative selection achieved a median reduction of 3·89 log of T cells. All nine patients have been transplanted. Conditioning included carmustine (BCNU), etoposide and melphalan (BEM) in seven patients and total body irradiation plus etoposide or melphalan in two. Eight patients engrafted promptly and one patient died of septicaemia. All survivors entered complete remission. Seven patients have relapsed at a median of 7 months (2–14) post SCT. However, most patients have relapsed into a less aggressive stage, which has responded to conventional therapy. Four out of seven evaluable patients had detectable TCR rearrangements in the T‐cell depleted graft. A T‐cell clone was also detected in the peripheral blood before relapse in four cases. Autologous SCT is feasible, safe and can result in complete remission in a significant proportion of patients with tumour stage mycosis fungoides. Despite a short relapse‐free survival, most patients achieved good disease control at the time of relapse.
The implementation of the Australian Curriculum: Science across the compulsory years of schooling (F-10) in most Australian states this year requires science teachers to address the teaching of ...scientific argumentation in their classrooms. To attend to this challenge, the authors conducted an argumentation professional development program with practising secondary science teachers, who possessed a range of teaching experience. Examples of the pedagogical activities implemented in the program are outlined in this paper, in addition to a discussion of five teachers' experiences of the program sourced from pre and post-intervention interviews. Shifts in participants' views of argumentation, participants' perceived implementation of argumentation, and barriers to the successful implementation of argumentation are also discussed. Author abstract
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
BACKGROUND Children's hospitals should advocate for children's health by modeling optimum health environments. OBJECTIVES To determine whether children's hospitals provide optimum health environments ...and to identify associated factors. DESIGN Telephone survey. SETTING Canadian and US hospitals with accredited pediatric residency programs. PARTICIPANTS Food services directors or administrative dietitians. MAIN OUTCOME MEASURES Health environment grades as determined for 4 domains quantifying (1) the amount of less nutritious food sold at cafeterias (cafeteria grade), (2) the presence of fast food outlets (outlet grade), (3) the amount of nutritious food alternatives available (healthful alternative grade), and (4) the presence of patient obesity or employee exercise programs (program grade). RESULTS The overall response rate was 87%. Compared with Canadian hospitals, US hospitals had more food outlets (89% vs 50%) and more snack/beverage vending machines (median, 16 vs 12) (P = .001 for both), despite equivalent consumer numbers. External companies managed more outlets at US vs Canadian hospitals (65% vs 14%; P = .01), and, generally, US hospitals recuperated more revenue from their outlets. Worst cafeteria grade was associated with US hospital location (odds ratio OR, 8.9; 95% confidence interval CI, 1.6-50; P = .01) and lower healthful alternative grade (OR, 0.016; 95% CI, 0.002-0.15; P<.001). Lower grade in any domain was related to whether hospitals received more revenue from noncafeteria food outlets (OR, 1.7; 95% CI, 1.06-2.72; P = .03) and the presence of more internally operated cafeterias (OR, 2.3 per cafeteria; 95% CI, 1.53-3.36; P<.001). CONCLUSIONS Children's hospitals provide suboptimal health environments. Reliance on revenue may be an important motivating factor encouraging the adoption of outlets that serve less nutritious food.-->
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