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The efficacy of rifalazil and other benzoxazinorifamycins was tested in a mouse model of lung infection against Chlamydia pneumoniae. Rifalazil and six related new chemical entities all showed efficacy after one dose per day for 3 days at either 3 or 1 mg/kg of body weight.  相似文献   
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As the U.S. population ages and chronic illness prevalence increases, new approaches to care are needed. Although large health systems have begun to respond to this challenge, most Americans seek care from practitioners functioning in small office settings. Implementing systematic sustainable changes for quality improvement in this setting remains an unresolved challenge. In this study, trained Nurse Coaches (NCs) were employed to assist practices in adopting a new model of patient care called Virtual Integrated Practice (VIP). The feasibility and treatment fidelity of this approach were assessed through process measures and interviews in three practices. Findings document high acceptance of the NC approach and consistent delivery of the intervention. Enactment of the VIP model took place across practices, although to a variable degree. The study suggests that NCs may be an effective delivery method for quality and organizational improvements in small primary care practices.  相似文献   
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Hepatitis B virus (HBV) infection remains a serious global health problem despite the availability of a highly effective vaccine. Approximately 5% of HBV-infected adults develop chronic hepatitis B, which may result in liver cirrhosis or hepatocellular carcinoma. Variants of interleukin-10 (IL10) have been previously associated with chronic hepatitis B infection and progression to hepatocellular carcinoma. Single nucleotide polymorphisms (SNP; n = 42) from the IL10, IL19 and IL20 gene regions were examined for an association with HBV infection outcome, either chronic or recovered, in a nested case-control study of African Americans and European Americans. Among African Americans, three nominally statistically significant SNP associations in IL10, two in IL20, and one haplotype association were observed with different HBV infection outcomes (P = 0.005-0.04). A SNP (rs1518108) in IL20 deviated significantly from Hardy-Weinberg equilibrium in African Americans, with a large excess of heterozygotes in chronic HBV-infected cases (P = 0.0006), which suggests a strong genetic effect. Among European Americans, a nominally statistically significant SNP association in IL20 and an IL20 haplotype were associated with HBV recovery (P = 0.01-0.04). These results suggest that IL10 and IL20 gene variants influence HBV infection outcome and encourage the pursuit of further studies of these cytokines in HBV pathogenesis.  相似文献   
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The twin-arginine translocation (Tat) pathway is a secretory pathway for translocation of folded proteins with two arginines in their signal peptide across the cytoplasmic membrane. Recently, we showed the presence of the Tat secretion pathway in Legionella pneumophila Philadelphia-1 and its role in intracellular replication and biofilm formation. To analyse the importance of the Tat pathway in protein export and its role in L. pneumophila virulence, a comparative 2-D protein gel electrophoresis analysis was performed on supernatants of the wild type and two Tat secretion mutants in order to identify possible Tat substrates. Twenty proteins were identified as differential proteins, eight of which were present in a lower quantity in the supernatant of the tat mutants. Among these, one protein with a typical twin-arginine motif in its signal peptide was identified as the 3′,5′-cyclic nucleotide phosphodiesterase. Two other proteins that resulted as differential proteins from this study were flagellin and LvrE, which were studied in more detail and their Tat-dependence was further confirmed with specific antibodies. LvrE was shown to play a role in intracellular growth in differentiated U937 cells.  相似文献   
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OBJECTIVE—Poor peripheral nerve function is prevalent in diabetes and older populations, and it has great potential to contribute to poor physical performance.RESEARCH DESIGN AND METHODS—Cross-sectional analyses were done for the Health, Aging, and Body Composition (Health ABC) Study participants (n = 2,364; 48% men; 38% black; aged 73–82 years). Sensory and motor peripheral nerve function in legs/feet was assessed by 10- and 1.4-g monofilament perception, vibration detection, and peroneal motor nerve conduction amplitude and velocity. The Health ABC lower-extremity performance battery was a supplemented version of the Established Populations for the Epidemiologic Studies of the Elderly battery (chair stands, standing balance, and 6-m walk), adding increased stand duration, single foot stand, and narrow walk.RESULTS—Diabetic participants had fewer chair stands (0.34 vs. 0.36 stands/s), shorter standing balance time (0.69 vs. 0.75 ratio), slower usual walking speed (1.11 vs. 1.14 m/s), slower narrow walking speed (0.80 vs. 0.90 m/s), and lower performance battery score (6.43 vs. 6.93) (all P < 0.05). Peripheral nerve function was associated with each physical performance measure independently. After addition of peripheral nerve function in fully adjusted models, diabetes remained significantly related to a lower performance battery score and slower narrow walking speed but not to chair stands, standing balance, or usual walking speed.CONCLUSIONS—Poor peripheral nerve function accounts for a portion of worse physical performance in diabetes and may be directly associated with physical performance in older diabetic and nondiabetic adults. The impact of peripheral nerve function on incident disability should be evaluated in older adults.Diabetes is associated with self-reported and objective physical performance measures of functional limitation in U.S. adults (1). Poor peripheral nerve function may play a role in reduced physical function in older diabetic adults (2,3). The incidence (4) and prevalence of poor peripheral nerve function are higher in older adults, even among those without diabetes (47). In the U.S. for 1999–2000, 28% of adults aged 70–79 years and 35% of adults aged ≥80 years had peripheral neuropathy based on a simple screen for reduced sensation at the foot (7). We previously found that diabetes was associated with subclinical functional limitation and physical performance in our cohort, although peripheral nerve function measures were not completed then (8).To our knowledge, the relationship of combined sensory and motor peripheral nerve function to objective physical performance has not been investigated in ambulatory, community-dwelling older adults. We evaluated the distribution of sensory and motor peripheral nerve function in older diabetic and nondiabetic adults and the relationship of peripheral nerve function to objective physical performance. We hypothesized that sensory and motor peripheral nerve function explained the relationship of poor physical performance in an older community-based population, both with and without diabetes.  相似文献   
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