Publications

The SecA2 proteins are a special class of transport-associated ATPases that are related to the SecA component of the general Sec system, and are found in an increasingly large number of Gram-positive bacterial species. The SecA2 substrates are typically linked to the cell wall, but may be lipid-linked, peptidoglycan-linked, or non-covalently associated S-layer proteins. These substrates can have a significant impact on virulence of pathogenic organisms, but may also aid colonization by commensals. The SecA2 orthologues range from being highly similar to their SecA paralogues, to being distinctly different in apparent structure and function. Two broad classes of SecA2 are evident. One transports multiple substrates, and may interact with the general Sec system, or with an as yet unidentified transmembrane channel. The second type transports a single substrate, and is a component of the accessory Sec system, which includes the SecY paralogue SecY2 along with the accessory Sec proteins Asp1-3. Recent studies indicate that the latter three proteins may have a unique role in coordinating post-translational modification of the substrate with transport by SecA2. Comparative functional and phylogenetic analyses suggest that each SecA2 may be uniquely adapted for a specific type of substrate. This article is part of a Special Issue entitled: Protein trafficking and secretion in bacteria. Guest Editors: Anastassios Economou and Ross Dalbey.

BACKGROUND AND STUDY AIMS

Surveillance intervals after colonoscopic resection of serrated polyps are partially predicated on the histology of the polyp(s) removed during the index exam. Histologic discrimination between sessile serrated adenomas/polyps (SSA/P) and hyperplastic polyps is challenging. We devised and tested a simple tool--an envelope--that gastroenterologists can integrate into routine colonoscopy practice to address this problem.

METHODS

In the "modified protocol," immediately after polypectomy each serrated polyp was flattened and enclosed in a paper envelope before being placed in formalin. In the pathology laboratory, each polyp was sectioned after processing. A two-site, prospective, randomized, single-blinded trial was performed to compare this modified protocol with the conventional protocol. Serrated polyps located proximal to the splenic flexure and 5-20 mm in diameter were included. A novel orientation score that measured the number of well-oriented crypts per unit area of polyp (higher orientation score = better orientation) was validated. Orientation score, SSA/P diagnosis rate, and inter-pathologist agreement were measured.

RESULTS

A total of 375 polyps were enrolled, of which 264 were identified for analysis. The mean orientation scores in the modified and conventional protocol groups were 3.11 and 1.13, respectively (P < 0.0001). SSA/Ps were diagnosed in 103/135 cases (76.3%) in the modified protocol group vs. 54/129 (41.9%) in the conventional protocol group (P < 0.0001). Inter-pathologist agreement was higher with the modified than the conventional protocol (77.0% vs. 62.8%; P = 0.015).

CONCLUSION

Standard polyp handling techniques may be sub-optimal for interpretation of serrated polyps resected at colonoscopy, and may lead to inadvertent histologic "under-grading" of many lesions. Our intervention improved histopathologic interpretation and increased the SSA/P diagnosis rate.

BACKGROUND

The National Kidney Foundation (NKF) Kidney Disease Outcomes Quality Initiative (KDOQI) developed guidelines to care for patients with chronic kidney disease (CKD). While these are disseminated through the NKF's website and publications, the guidelines' usage remains suboptimal. The KDOQI Educational Committee was formed to identify barriers to guideline implementation, determine provider and patient educational needs and develop tools to improve care of patients with CKD.

METHODS

An online survey was conducted from May to September 2010 to evaluate renal providers' familiarity, current use of and attitudes toward the guidelines and tools to implement the guidelines.

RESULTS

Most responders reported using the guidelines often and felt that they could be easily implemented into clinical practice; however, approximately one-half identified at least one barrier. Physicians and physician extenders most commonly cited the lack of evidence supporting KDOQI guidelines while allied health professionals most commonly listed patient non-adherence, unrealistic guideline goals and provider time-constraints. Providers thought that the guidelines included too much detail and identified the lack of a quick resource as a barrier to clinical implementation. Most were unaware of the Clinical Action Plans.

CONCLUSIONS

Perceived barriers differed between renal clinicians and allied health professionals; educational and implementation tools tailored for different providers are needed.

OBJECTIVE

Rifampin monoresistant tuberculosis (RMR-TB) is increasingly identified because of scale-up of rapid molecular tests. The longitudinal association of RMR-TB, multidrug-resistant TB (MDR-TB), and HIV/AIDS is incompletely described.

METHODS

We examined clinical characteristics and treatment outcomes of patients with RMR-TB, isoniazid monoresistant TB (IMR-TB), MDR-TB, and drug-susceptible TB during a 16-year period (1993-2008) in California. TB cases were cross-matched with the state HIV/AIDS registry, and HIV prevalence denominators modeled using nonparametric backcalculation.

RESULTS

Of 42,582 TB cases, 178 (0.4%), 3469 (8.1%), and 635 (1.5%) were RMR-TB, IMR-TB, and MDR-TB, respectively. From the pre-HAART (1993-1996) to HAART (2005-2008) era, RMR-TB rates declined rapidly (12.0 vs. 0.5 per 100,000) among patients with HIV infection. The proportion of patients for whom rifampin resistance indicated RMR-TB (rather than MDR-TB) decreased from 31% [95% confidence interval (CI) 26-38%] to 11% (95% CI 5-19%). In multivariate analysis controlling for HIV coinfection and other covariates, patients with RMR-TB were twice as likely to die as patients with drug-sensitive TB (relative risk 1.94, 95% CI 1.40-2.69).

CONCLUSION

RMR-TB/HIV rates declined substantially over time in association with improved TB control and HIV control in California. Mortality among patients with RMR-TB was high, even after adjusting for HIV status.