This study aimed to evaluate whether gait speed and grip strength predicted clinical outcomes among older adults with blood cancers. We prospectively recruited 448 patients aged 75 years and older presenting for initial consultation at the myelodysplastic syndrome/leukemia, myeloma, or lymphoma clinic of a large tertiary hospital, who agreed to assessment of gait and grip. A subset of 314 patients followed for ≥6 months at local institutions was evaluated for unplanned hospital or emergency department (ED) use. We used Cox proportional hazard models calculated hazard ratios (HRs) and 95% confidence intervals (CIs) for survival, and logistic regression to calculate odds ratios (ORs) for hospital or ED use. Mean age was 79.7 (± 4.0 standard deviation) years. After adjustment for age, sex, Charlson comorbidity index, cognition, treatment intensity, and cancer aggressiveness/type, every 0.1-m/s decrease in gait speed was associated with higher mortality (HR, 1.20; 95% CI, 1.12-1.29), odds of unplanned hospitalizations (OR, 1.33; 95% CI, 1.16-1.51), and ED visits (OR, 1.34; 95% CI, 1.17-1.53). Associations held among patients with good Eastern Cooperative Oncology Group performance status (0 or 1). Every 5-kg decrease in grip strength was associated with worse survival (adjusted HR, 1.24; 95% CI, 1.07-1.43) but not hospital or ED use. A model with gait speed and all covariates had comparable predictive power to comprehensive validated frailty indexes (phenotype and cumulative deficit) and all covariates. In summary, gait speed is an easily obtained “vital sign” that accurately identifies frailty and predicts outcomes independent of performance status among older patients with blood cancers.

Bacterial Wzx flippases translocate (flip) short oligosaccharide repeat units (O units) across the inner membrane into the periplasm, which is a critical step in the assembly of many O antigens, capsules and other surface polysaccharides. There is enormous diversity in O antigens and capsules in particular, even within species. Wzx proteins are similarly diverse, but it has been widely accepted that they have significant specificity only for the first sugar of an O unit. In this study, we analysed the Wzx from the Salmonella enterica group C2 O antigen gene cluster, which is a unique and divergent member of a set of gene clusters that produce galactose-initiated O antigens. We demonstrate that this Wzx has a strong preference for the presence of an abequose side-branch, which manifests in a reduction of long-chain O antigen and a major growth defect. This contributes to a growing body of evidence that, contrary to earlier proposals, Wzx flippases commonly exhibit a strong preference for the structure of their native O unit.

No abstract

Translocation of lipid-linked oligosaccharides is a common theme across prokaryotes and eukaryotes. For bacteria, such activity is used in cell wall construction, polysaccharide synthesis, and the relatively recently discovered protein glycosylation. To the best of our knowledge, the Gram-negative inner membrane flippase Wzx was the first protein identified as being involved in oligosaccharide translocation, and yet we still have only a limited understanding of this protein after 3 decades of research. At present, Wzx is known to be a multitransmembrane protein with enormous sequence diversity that flips oligosaccharide substrates with varied degrees of preference. In this review, we provide an overview of the major findings for this protein, with a particular focus on substrate preference.

Introduction Lung function is inversely associated with coronary heart disease (CHD) and cardiovascular disease (CVD). We evaluated the prospective association of reduced lung function by spirometry and CHD or CVD events in older community-dwelling adults. Methods We studied 1,548 participants (mean age 73.6±9.2 years, 42% males) from the Rancho Bernardo Study using age, sex, and risk-factor adjusted Cox regression to assess pulmonary function (FEV1, FVC, and FEV1/FVC ratio) as a predictor of CHD and CVD events followed for up to 22 years. Results Of CVD risk factors, older age, male sex, current/past smoking, physical exercise (<3x a week), and prevalent CVD predicted an increased risk of CHD and CVD. Higher FEV1 and FVC were each associated with a decreased risk of CHD [HR 0.80 (0.73-0.88) for both FEV1 and FVC, per SD, p<.01] and CVD [HR 0.82 (0.74-0.91) for both FEV1 and FVC, per SD, p<.01]. Those in the lowest quartiles of FEV1 and FVC had hazard ratios of 1.68 (1.33-2.13) and 1.55 (1.21-2.00) respectively for CHD and 1.74 (1.34-2.25) and 1.49 (1.13-1.96) respectively for CVD (all p<.01, relative to those in the highest quartile). Similar findings were observed for CHD and CVD mortality. Sex- and age-stratified analyses showed the strongest associations for CHD and CVD events in women and in the oldest participants. Conclusions FEV1 and FVC are inversely associated with risk of future CHD and CVD events in older community-dwelling adults and may add to CVD risk stratification in the elderly.

Introduction:We evaluated complementary and alternative medicine (CAM) use among a medically underserved, predominately Hispanic community at the University of California Irvine Family Health Center, a federally qualified health center.Methods: A cross-sectional, anonymous survey assessed patient use of, interest in, and communication preferences concerning CAM.Results: The 150 respondents primarily self-identified as Hispanic (74%), were born outside the United States (55%), were medically insured (56%), and had a high school education or less (55%). Of these respondents, 63% used at least 1 type of CAM; the most commonly used were: vitamins/supplements (32%), herbal medicine (29%), dietary/nutritional therapy (26%), massage (24%), meditation/ relaxation (15%) and chiropractic (11%). Therapies that patients most desired to see provided at the clinic included massage, healthier cooking, guidance on herbs/supplements, and diet/nutrition. Among respondents, 61% were comfortable disclosing CAM use to physicians, 58% agreed physicians should have basic knowledge of CAM, and 47% desired that physicians ask about CAM use.

The staphylococcal multiresistance plasmids are key contributors to the alarming rise in bacterial multidrug resistance. A conserved replication initiator, RepA, encoded on these plasmids is essential for their propagation. RepA proteins consist of flexibly linked N-terminal (NTD) and C-terminal (CTD) domains. Despite their essential role in replication, the molecular basis for RepA function is unknown. Here we describe a complete structural and functional dissection of RepA proteins. Unexpectedly, both the RepA NTD and CTD show similarity to the corresponding domains of the bacterial primosome protein, DnaD. Although the RepA and DnaD NTD both contain winged helix-turn-helices, the DnaD NTD self-assembles into large scaffolds whereas the tetrameric RepA NTD binds DNA iterons using a newly described DNA binding mode. Strikingly, structural and atomic force microscopy data reveal that the NTD tetramer mediates DNA bridging, suggesting a molecular mechanism for origin handcuffing. Finally, data show that the RepA CTD interacts with the host DnaG primase, which binds the replicative helicase. Thus, these combined data reveal the molecular mechanism by which RepA mediates the specific replicon assembly of staphylococcal multiresistant plasmids.RepA_N | replication initiation | S. aureus | two hybrid

Objectives: To (1) determine the attitudes, perceptions, and use of complementary, alternative, and integrative medicine among undergraduate students; (2) assess whether these students would benefit from more academic exposure to complementary and alternative medicine (CAM) and promotion of integrative medicine (IM); and (3) gauge the need and desire of undergraduates, particularly pre-health learners, to take courses about CAM/IM. Methods: This cross-sectional electronic survey study was conducted on the campus of the University of California (UC) Irvine. Selection criteria included being at least 18 years of age and a current undergraduate at UC Irvine. All survey responses were collected between November 20, 2010, and June 1, 2011. The data were analyzed by using Stata software, version 11-SE (Stata Corp., College Station, TX). Results: Completed surveys were received from 2839 participants (mean age of respondents, 20.2 years). Thirty-five percent had used CAM within the past 12 months, and 92.8% believed CAM to be at least somewhat effective; however, only 31% had prior education on CAM. After adjustment for variables, familiarity and belief in effectiveness were both highly linked to the use of CAM, with ascending odds ratios (ORs; 95% confidence interval [CI]) of 3.9 (3