Recent advances in community-acquired pneumonia: inpatient and outpatient

Community-acquired pneumonia (CAP) is a common illness, with the majority of patients treated out of the hospital, yet the greatest burden of the cost of care comes from inpatient management. In the past several years, the management of these patients has advanced, with new information about the natural history and prognosis of illness, the utility of serum markers to guide management, the use of appropriate clinical tools to guide the site-of-care decision, and the finding that guidelines can be developed in a way that improves patient outcome. The challenges to patient management include the emergence of new pathogens and the progression of antibiotic resistance in some of the common pathogens such as Streptococcus pneumoniae. Few new antimicrobial treatment options are available, and the utility of some new therapies has been limited by drug-related toxicity. Ancillary care for severe pneumonia with activated protein C and corticosteroids is being studied, but recently, inpatient care has been most affected by the development of evidence-based "core measures" for management that have been promoted by the Centers for Medicare and Medicaid Services, which form the basis for the public reporting of hospital performance in CAP care.     

Arterial ultrasonography and tonometry as adjuncts to cardiovascular risk stratification

Myocardial infarction and stroke often occur without prior warning in asymptomatic individuals. Identifying individuals at risk is important for cost-effective use of preventive therapies. Algorithms based on risk factors statistically associated with cardiovascular events classify individuals into high-risk, intermediate-risk, or low-risk categories. However, more than one-third of adults in the U.S. are in the intermediate-risk category, and decisions regarding therapy are challenging in this subset. Testing for alterations in arterial function and structure that predate cardiovascular events may help refine cardiovascular risk assessment in the intermediate-risk group and identify candidates for aggressive therapy. Vascular ultrasonography and tonometry are promising test modalities for assessment of arterial function and structure in asymptomatic subjects. Several prospective studies have shown that measures of arterial function and structure provide prognostic information incremental to conventional risk factors. Standardization of methodology and establishment of quality control standards in the performance of these tests could facilitate their integration into clinical practice as adjuncts to existing cardiovascular risk stratification algorithms.     

Identification of a nitric oxide-dependent hypotensive effect of anticoagulation factor II from the venom of Agkistrodon acutus

Anticoagulation factor II (ACF II) isolated from the venom of Agkistrodon acutus is a member of the coagulation factor IX/coagulation factor X-binding protein (IX/X-bp) family. ACF II forms a 1:1 complex with activated coagulation factor X in a Ca²⁺-dependent fashion and thereby blocks the amplification of the coagulation cascade. In the present study, we have investigated the effect of ACF II on the mean arterial blood pressure (MABP) and heart rate (HR) in anaesthetized rats. The results indicate that ACF II induces a dose-dependent response in rats with a short fast drop of MABP followed by an increase and then a longer lasting slight decrease in MABP, but does not obviously affect HR. ACF II-induced hypotension is significantly blocked by the nitric oxide (NO) synthase inhibitor N-omega-l-arginine methyl ester (l-NAME). ACF II produces a concentration-dependent relaxation of rat aortic rings with functional-endothelium. The ACF II-induced vasodilatation is completely inhibited by removal of endothelium and significantly inhibited by pretreatment with l-NAME. These observations demonstrate that ACF II induces hypotension through an endothelium-dependent vasodilation, which is strongly mediated by the release of NO from endothelium. ACF II exhibits high anticoagulation activity in vivo based on activated partial thromboplastin time assay. Therefore, ACF II is so far identified as the first unique bifunctional protein in the IX/X-bp family that has both anticoagulant and hypotensive effects on the blood of rats through different pathways.     

基于BP算法的肝硬化患者中医治疗效果神经网络建模研究

目的:建立基于BP神经网络的治疗结果拟合模型,并在已建立的神经网络模型的基础上,进行中医治疗结果的预测和影响因素的敏感度分析,利用本研究的建模结果,为BP神经网络建模的方法学提供一定的参考依据,并能帮助医务人员做出正确的决策和分析。方法:在SPSS Clementine 12.0中进行建模和预测,预测结果用SPSS13.0进行ROC分析。结果:BP神经网络的拟合度和预测准确度为81.224%,门静脉内径、中医症候积分对患者的治疗结果影响最大。结论:BP神经网络是比较适合于治疗结果数据特征的建模方法。     

Comparative distribution of protein components of the A20 ubiquitin-editing complex in normal human brain

Activation of innate and adaptive immune responses is tightly regulated, as insufficient activation could result in defective clearance of pathogens, while excessive activation might lead to lethal systemic inflammation or autoimmunity. A20 functions as a negative regulator of innate and adaptive immunity by inhibiting NF-κB activation. A20 mediates its inhibitory function in a complex with other proteins including RNF11 and Itch, both E3 ubiquitin ligases and TAX1BP1, an adaptor protein. Since NF-κB has been strongly implicated in various neuronal functions, we predict that its inhibitor, the A20 complex, is also present in the nervous system. In efforts to better understand the role of A20 complex and NF-κB signaling pathway, we determined regional distribution of A20 mRNA as well as protein expression levels and distribution of RNF11, TAX1BP1 and Itch, in different brain regions. The distribution of TRAF6 was also investigated since TRAF6, also an E3 ligase, has an important role in NF-κB signaling pathway. Our investigations, for the first time, describe and demonstrate that the essential components of the A20 ubiquitin-editing complex are present and mainly expressed in neurons. The A20 complex components are also differentially expressed throughout the human brain. This study provides useful information about region specific expression of the A20 complex components that will be invaluable while determining the role of NF-κB signaling pathway in neuronal development and degeneration.     

Glucocorticosteroid-resistant pemphigoid gestationis: successful treatment with adjuvant immunoadsorption

A 40-year old prima para presented with multiple urticaria-like plaques and severe pruritus 2 weeks prior to giving birth by cesarean section. Three days after birth, the disease flared up and tense blisters appeared on hands, lower arms and feet. Based on the clinical presentation, direct immunofluorescence microscopy, complement binding test and detection of high levels of circulating anti-BP180 antibodies, the diagnosis of pemphigoid gestationis was established. Despite treatment with class IV topical corticosteroid and prednisolone p.o. up to 60 mg/day, both skin lesions and severe pruritus progressed accompanied by increasing anti-BP180 antibody serum levels. In order to continue breast feeding, the prednisolone dose could not be further increased and 10 immunoadsorptions over 4 weeks were performed. During this period, skin lesions cleared rapidly, pruritus subsided and BP180-specific serum autoantibodies decreased by 99.5% allowing the reduction of prednisolone to 7.5 mg/day. We conclude that immunoadsorption is an effective and safe adjuvant therapeutic option for severe pemphigoid gestationis.     

Blood pressure trajectories and the mediated effects of body mass index and HIV‐related inflammation in a mixed cohort of people with and without HIV in rural Uganda

We sought to describe changes in blood pressure and estimate the effect of HIV on blood pressure (BP) over 4 years of observation in a cohort of 155 HIV‐infected adults (≥40 years) on antiretroviral therapy (ART) and 154 sex‐ and age‐quartile‐matched, population‐based, HIV‐uninfected controls for four years in rural Uganda, we compared changes in blood pressure (BP) by HIV serostatus and tested whether body mass index and inflammation (high‐sensitivity C‐reactive protein and interleukin‐6) and immune activation (sCD14 and sCD163) mediated the effects of HIV on BP using hierarchical multivariate and two‐stage parametric regression models. Overall HIV‐uninfected participants had higher mean BP than HIV‐infected counterparts (differences in trend P < 0.0001 for diastolic BP and P = 0.164 for systolic BP). After initial declines in BP in both groups between years 1 and 2, BP moderately increased in both groups through year 4, with greater change over time observed in the HIV‐uninfected group. Body mass index mediated 72% (95%CI 57, 97) of the association between HIV and systolic BP. We found a minimal mediating effect of sCD14 on the relationship between HIV and SBP (9%, 95% CI 5%, 21%), but found no association between other HIV‐related biomarkers. Over four years of observation, HIV‐infected people in rural Uganda have lower BP than HIV‐uninfected counterparts despite having higher levels of inflammation. BMI, rather than measures of HIV‐associated inflammation, explained a majority of the difference in BP observed.