The native architecture of a photosynthetic membrane

In photosynthesis, the harvesting of solar energy and its subsequent conversion into a stable charge separation are dependent upon an interconnected macromolecular network of membrane-associated chlorophyll–protein complexes. Although the detailed structure of each complex has been determined, the size and organization of this network are unknown. Here we show the use of atomic force microscopy to directly reveal a native bacterial photosynthetic membrane. This first view of any multi-component membrane shows the relative positions and associations of the photosynthetic complexes and reveals crucial new features of the organization of the network: we found that the membrane is divided into specialized domains each with a different network organization and in which one type of complex predominates. Two types of organization were found for the peripheral light-harvesting LH2 complex. In the first, groups of 10–20 molecules of LH2 form light-capture domains that interconnect linear arrays of dimers of core reaction centre (RC)–light-harvesting 1 (RC–LH1–PufX) complexes; in the second they were found outside these arrays in larger clusters. The LH1 complex is ideally positioned to function as an energy collection hub, temporarily storing it before transfer to the RC where photochemistry occurs: the elegant economy of the photosynthetic membrane is demonstrated by the close packing of these linear arrays, which are often only separated by narrow 'energy conduits' of LH2 just two or three complexes wide

The effect of prior statin use on 30-day mortality for patients hospitalized with community-acquired pneumonia

BACKGROUND: Recent studies suggest that HMG-CoA reductase inhibitors ("statins") may have beneficial effects for patients at risk for some types of infections. We examined the effect of prior outpatient use of statins on mortality for patients hospitalized with community-acquired pneumonia. METHODS: A retrospective cohort study conducted at two tertiary teaching hospitals. Eligible subjects were admitted with a diagnosis of, had a chest x-ray consistent with, and had a discharge ICD-9 diagnosis of pneumonia. Subjects were excluded if they were "comfort measures only" or transferred from another acute care hospital. Subjects were considered to be on a medication if they were taking it at the time of presentation. RESULTS: Data was abstracted on 787 subjects at the two hospitals. Mortality was 9.2% at 30-days and 13.6% at 90-days. At presentation 52% of subjects were low risk, 34% were moderate risk, and 14% were high risk based on the pneumonia severity index. In the multivariable regression analysis, after adjusting for potential confounders including a propensity score, the use of statins at presentation (odds ratio 0.36, 95% confidence interval 0.14–0.92) was associated with decreased 30-day mortality. DISCUSSION: Prior outpatient statin use was associated with decreased mortality in patients hospitalized with community-acquired pneumonia despite their use being associated with comorbid illnesses likely to contribute to increased mortality. Confirmatory studies are needed, as well as research to determine the mechanism(s) of this protective effect

Hyponatremia and hospital outcomes among patients with pneumonia: a retrospective cohort study

<p>Abstract</p> <p>Background</p> <p>Community-acquired (CAP) and nosocomial pneumonias contribute substantially to morbidity and hospital resource utilization. Hyponatremia, occurring in >1/4 of patients with CAP, is associated with greater disease severity and worsened outcomes.</p> <p>Methods</p> <p>To explore how hyponatremia is associated with outcomes in hospitalized patients with pneumonia, we analyzed a large administrative database with laboratory component from January 2004 to December 2005. Hyponatremia was defined as at least two [Na⁺] < 135 mEq/L within 24 hours of admission value.</p> <p>Results</p> <p>Of 7,965 patients with pneumonia, 649 (8.1%) with hyponatremia were older (72.4 ± 15.7 vs. 68.0 ± 22.0, p < 0.01), had a higher mean Deyo-Charlson Comorbidity Index Score (1.7 ± 1.7 vs. 1.6 ± 1.6, p = 0.02), and higher rates of ICU (10.0% vs. 6.3%, p < 0.001) and MV (3.9% vs. 2.3%, p = 0.01) in the first 48 hours of hospitalization than patients with normal sodium. Hyponatremia was associated with an increased ICU (6.3 ± 5.6 vs. 5.3 ± 5.1 days, p = 0.07) and hospital lengths of stay (LOS, 7.6 ± 5.3 vs. 7.0 ± 5.2 days, p < 0.001) and a trend toward increased hospital mortality (5.4% vs. 4.0%, p = 0.1). After adjusting for confounders, hyponatremia was associated with an increased risk of ICU (OR 1.58, 95% CI 1.20–2.08), MV (OR 1.75 95% CI 1.13–2.69), and hospital death (OR 1.3, 95% CI 0.90–1.87) and with increases of 0.8 day to ICU and 0.3 day to hospital LOS, and over $1,300 to total hospital costs.</p> <p>Conclusion</p> <p>Hyponatremia is common among hospitalized patients with pneumonia and is associated with worsened clinical and economic outcomes. Studies in this large population are needed to explore whether prompt correction of [Na⁺] may impact these outcomes.</p

The impact of prior outpatient ACE inhibitor use on 30-day mortality for patients hospitalized with community-acquired pneumonia

BACKGROUND: Recent studies suggest that angiotensin-converting enzyme (ACE) inhibitors may have beneficial effects for patients at risk for some types of infections. We examined the effect of prior outpatient use of ACE inhibitors on mortality for patients hospitalized with community-acquired pneumonia. METHODS: A retrospective cohort study conducted at two tertiary teaching hospitals. Eligible subjects were admitted with a diagnosis of, had a chest x-ray consistent with, and had a discharge ICD-9 diagnosis of pneumonia. Subjects were excluded if they were "comfort measures only" or transferred from another acute care hospital. Subjects were considered to be on a medication if they were taking it at the time of presentation. RESULTS: Data was abstracted on 787 subjects at the two hospitals. Mortality was 9.2% at 30-days and 13.6% at 90-days. At presentation 52% of subjects were low risk, 34% were moderate risk, and 14% were high risk. In the multivariable conditional logistic regression analysis, after adjusting for potential confounders, the use of ACE inhibitors at presentation (odds ratio 0.44, 95% confidence interval 0.22–0.89) was significantly associated with 30-day mortality. CONCLUSION: Prior outpatient use of an ACE inhibitor was associated with decreased mortality in patients hospitalized with community-acquired pneumonia despite their use being associated with comorbid illnesses likely to contribute to increased mortality. Confirmatory studies are needed, as well as research to determine the mechanism(s) of this protective effect

Combination antibiotic therapy for community-acquired pneumonia

Community-acquired pneumonia (CAP) is a common and potentially serious illness that is associated with morbidity and mortality. Although medical care has improved during the past decades, it is still potentially lethal. Streptococcus pneumoniae is the most frequent microorganism isolated. Treatment includes mandatory antibiotic therapy and organ support as needed. There are several antibiotic therapy regimens that include β-lactams or macrolides or fluoroquinolones alone or in combination. Combination antibiotic therapy achieves a better outcome compared with monotherapy and it should be given in the following subset of patients with CAP: outpatients with comorbidities and previous antibiotic therapy, nursing home patients with CAP, hospitalized patients with severe CAP, bacteremic pneumococcal CAP, presence of shock, and necessity of mechanical ventilation. Better outcome is associated with combination therapy that includes a macrolide for wide coverage of atypical pneumonia, polymicrobial pneumonia, or resistant Streptococcus pneumoniae. Macrolides have shown different properties other than antimicrobial activity, such as anti-inflammatory properties. Although this evidence comes from observational, most of them retrospective and nonblinded studies, the findings are consistent. Ideally, a prospective, multicenter, randomized trial should be performed to confirm these findings

Improved outcomes in patients with chronic obstructive pulmonary disease treated with salmeterol compared with placebo/usual therapy: results of a meta-analysis

BACKGROUND: Several studies have demonstrated that long-acting β(2)-agonists such as salmeterol are beneficial in chronic obstructive pulmonary disease (COPD). A meta-analysis was therefore conducted to review studies in COPD to provide pooled estimates of the effect of salmeterol 50 mcg taken twice daily in addition to usual therapy on several clinically relevant endpoints, when compared with placebo/usual therapy. METHODS: An extensive search of literature and clinical trial databases was conducted using the terms salmeterol, COPD, chronic, obstructive, bronchitis and emphysema. Nine randomized, double-blind, parallel-group, placebo-controlled trials of ≥12 week duration with salmeterol 50 mcg bid treatment in COPD were included (>3500 patients), with a further 14 trials excluded due to study design or reporting timelines. All patients were included, and a sub-group of subjects (84%) with poorly reversible COPD were considered separately. Statistical testing was carried out at the 5% level, except for interaction testing which was carried out at the 10% level. RESULTS: Patients treated with salmeterol over 12 months were less likely to withdraw early from the studies (19% patients compared with 25% on their current usual therapy, p < 0.001), less likely to suffer a moderate/severe exacerbation (34% compared with 39%, p < 0.0001) and had a greater increase in average FEV(1 )(73 mL difference vs placebo/usual therapy, p < 0.0001). Similar differences were found at 3 and 6 months. At all time points, more patients experienced an improvement in health status and also a greater change with salmeterol than with placebo/usual therapy (p < 0.002). There was no evidence of tachyphylaxis to salmeterol over 12 months. CONCLUSION: The meta-analysis confirmed clinically and statistically significant, sustained and consistent superiority of salmeterol 50 mcg bid over placebo/usual therapy on a broad range of outcome measures

Environmental and genetic risk factors and gene-environment interactions in the pathogenesis of chronic obstructive lung disease.

Current understanding of the pathogenesis of chronic obstructive pulmonary disease (COPD), a source of substantial morbidity and mortality in the United States, suggests that chronic inflammation leads to the airways obstruction and parenchymal destruction that characterize this condition. Environmental factors, especially tobacco smoke exposure, are known to accelerate longitudinal decline of lung function, and there is substantial evidence that upregulation of inflammatory pathways plays a vital role in this process. Genetic regulation of both inflammatory responses and anti-inflammatory protective mechanisms likely underlies the heritability of COPD observed in family studies. In alpha-1 protease inhibitor deficiency, the only genetic disorder known to cause COPD, lack of inhibition of elastase activity, results in the parenchymal destruction of emphysema. Other genetic polymorphisms have been hypothesized to alter the risk of COPD but have not been established as causes of this condition. It is likely that multiple genetic factors interacting with each other and with a number of environmental agents will be found to result in the development of COPD

Sicily statement on classification and development of evidence-based practice learning assessment tools

<p>Abstract</p> <p>Background</p> <p>Teaching the steps of evidence-based practice (EBP) has become standard curriculum for health professions at both student and professional levels. Determining the best methods for evaluating EBP learning is hampered by a dearth of valid and practical assessment tools and by the absence of guidelines for classifying the purpose of those that exist. Conceived and developed by delegates of the Fifth International Conference of Evidence-Based Health Care Teachers and Developers, the aim of this statement is to provide guidance for purposeful classification and development of tools to assess EBP learning.</p> <p>Discussion</p> <p>This paper identifies key principles for designing EBP learning assessment tools, recommends a common taxonomy for new and existing tools, and presents the Classification Rubric for EBP Assessment Tools in Education (CREATE) framework for classifying such tools. Recommendations are provided for developers of EBP learning assessments and priorities are suggested for the types of assessments that are needed. Examples place existing EBP assessments into the CREATE framework to demonstrate how a common taxonomy might facilitate purposeful development and use of EBP learning assessment tools.</p> <p>Summary</p> <p><it>The widespread adoption of EBP into professional education requires valid and reliable measures of learning. Limited tools exist with established psychometrics. This international consensus statement strives to provide direction for developers of new EBP learning assessment tools and a framework for classifying the purposes of such tools</it>.</p