Yoga vs. physical therapy vs. education for chronic low back pain in predominantly minority populations: Study protocol for a randomized controlled trial

Background: Chronic low back pain causes substantial morbidity and cost to society while disproportionately impacting low-income and minority adults. Several randomized controlled trials show yoga is an effective treatment. However, the comparative effectiveness of yoga and physical therapy, a common mainstream treatment for chronic low back pain, is unknown.Methods/Design: This is a randomized controlled trial for 320 predominantly low-income minority adults with chronic low back pain, comparing yoga, physical therapy, and education. Inclusion criteria are adults 18-64 years old with non-specific low back pain lasting ≥12 weeks and a self-reported average pain intensity of ≥4 on a 0-10 scale. Recruitment takes place at Boston Medical Center, an urban academic safety-net hospital and seven federally qualified community health centers located in diverse neighborhoods. The 52-week study has an initial 12-week Treatment Phase where participants are randomized in a 2:2:1 ratio into i) a standardized weekly hatha yoga class supplemented by home practice; ii) a standardized evidence-based exercise therapy protocol adapted from the Treatment Based Classification method, individually delivered by a physical therapist and supplemented by home practice; and iii) education delivered through a self-care book. Co-primary outcome measures are 12-week pain intensity measured on an 11-point numerical rating scale and back-specific function measured using the modified Roland Morris Disability Questionnaire. In the subsequent 40-week Maintenance Phase, yoga participants are re-randomized in a 1:1 ratio to either structured maintenance yoga classes or home practice only. Physical therapy participants are similarly re-randomized to either five booster sessions or home practice only. Education participants continue to follow recommendations of educational materials. We will also assess cost effectiveness from the perspectives of the individual, insurers, and society using claims databases, electronic medical records, self-report cost data, and study records. Qualitative data from interviews will add subjective detail to complement quantitative data.Trial registration: This trial is registered in ClinicalTrials.gov, with the ID number: NCT01343927. © 2014 Saper et al.; licensee BioMed Central Ltd

Asymmetry of 13C labeled 3-pyruvate affords improved site specific labeling of RNA for NMR spectroscopy

Selective isotopic labeling provides an unparalleled window within which to study the structure and dynamics of RNAs by high resolution NMR spectroscopy. Unlike commonly used carbon sources, the asymmetry of 13C-labeled pyruvate provides selective labeling in both the ribose and base moieties of nucleotides using E. coli variants, that until now were not feasible. Here we show that an E. coli mutant strain that lacks succinate and malate dehydrogenases (DL323) and grown on [3-13C]-pyruvate affords ribonucleotides with site specific labeling at C5′ (~95%) and C1′ (~42%) and minimal enrichment elsewhere in the ribose ring. Enrichment is also achieved at purine C2 and C8 (~95%) and pyrimidine C5 (~100%) positions with minimal labeling at pyrimidine C6 and purine C5 positions. These labeling patterns contrast with those obtained with DL323 E. coli grown on [1, 3-13C]-glycerol for which the ribose ring is labeled in all but the C4′ carbon position, leading to multiplet splitting of the C1′, C2′ and C3′ carbon atoms. The usefulness of these labeling patterns is demonstrated with a 27-nt RNA fragment derived from the 30S ribosomal subunit. Removal of the strong magnetic coupling within the ribose and base leads to increased sensitivity, substantial simplification of NMR spectra, and more precise and accurate dynamic parameters derived from NMR relaxation measurements. Thus these new labels offer valuable probes for characterizing the structure and dynamics of RNA that were previously limited by the constraint of uniformly labeled nucleotides

Selective 13C labeling of nucleotides for large RNA NMR spectroscopy using an E. coli strain disabled in the TCA cycle

Escherichia coli (E. coli) is an ideal organism to tailor-make labeled nucleotides for biophysical studies of RNA. Recently, we showed that adding labeled formate enhanced the isotopic enrichment at protonated carbon sites in nucleotides. In this paper, we show that growth of a mutant E. coli strain DL323 (lacking succinate and malate dehydrogenases) on 13C-2-glycerol and 13C-1,3-glycerol enables selective labeling at many useful sites for RNA NMR spectroscopy. For DL323 E. coli grown in 13C-2-glycerol without labeled formate, all the ribose carbon atoms are labeled except the C3′ and C5′ carbon positions. Consequently the C1′, C2′ and C4′ positions remain singlet. In addition, only the pyrimidine base C6 atoms are substantially labeled to ~96% whereas the C2 and C8 atoms of purine are labeled to ~5%. Supplementing the growth media with 13C-formate increases the labeling at C8 to ~88%, but not C2. Not unexpectedly, addition of exogenous formate is unnecessary for attaining the high enrichment levels of ~88% for the C2 and C8 purine positions in a 13C-1,3-glycerol based growth. Furthermore, the ribose ring is labeled in all but the C4′ carbon position, such that the C2′ and C3′ positions suffer from multiplet splitting but the C5′ position remains singlet and the C1′ position shows a small amount of residual C1′–C2′ coupling. As expected, all the protonated base atoms, except C6, are labeled to ~90%. In addition, labeling with 13C-1,3-glycerol affords an isolated methylene ribose with high enrichment at the C5′ position (~90%) that makes it particularly attractive for NMR applications involving CH2-TROSY modules without the need for decoupling the C4′ carbon. To simulate the tumbling of large RNA molecules, perdeuterated glycerol was added to a mixture of the four nucleotides, and the methylene TROSY experiment recorded at various temperatures. Even under conditions of slow tumbling, all the expected carbon correlations were observed, which indicates this approach of using nucleotides obtained from DL323 E. coli will be applicable to high molecular weight RNA systems

Structure of the LpxC deacetylase with a bound substrate-analog inhibitor

The zinc-dependent UDP-3-O-acyl-N-acetylglucosamine deacetylase (LpxC) catalyzes the first committed step in the biosynthesis of lipid A, the hydrophobic anchor of lipopolysaccharide (LPS) that constitutes the outermost monolayer of Gram-negative bacteria. As LpxC is crucial for the survival of Gram-negative organisms and has no sequence homology to known mammalian deacetylases or amidases, it is an excellent target for the design of new antibiotics. The solution structure of LpxC from Aquifex aeolicus in complex with a substrate-analog inhibitor, TU-514, reveals a novel α/β fold, a unique zinc-binding motif and a hydrophobic passage that captures the acyl chain of the inhibitor. On the basis of biochemical and structural studies, we propose a catalytic mechanism for LpxC, suggest a model for substrate binding and provide evidence that mobility and dynamics in structural motifs close to the active site have key roles in the capture of the substrate.link_to_subscribed_fulltex

The effect of timing of administration of oestradiol benzoate on characteristics of oestrus, timing of ovulation and fertility in Bos indicus heifers synchronised with a progesterone releasing intravaginal insert

Objective To compare the timing of onset of oestrus and ovulation, characteristics of oestrus, and fertility in Bos indicus heifers synchronised with a progesterone releasing intra-vaginal insert (IVP4) and administration of oestradiol benzoate (ODB) either at the time of removal of the insert or 24 h later.\ud \ud Design Cohort study.\ud \ud Procedure Bos indicus and Bos indicus cross heifers were treated on two farms (Farm A, n = 273; Farm B, n = 47) with an IVP4 for 8 days with 1.0 mg of ODB administered at the time of device insertion and 250 mg of cloprostenol at the time of device removal. Heifers in the ODB-0 group were administered 0.75 mg of ODB at the time of device removal while heifers in the ODB-24 group were administered the same dose of ODB 24 h after device removal. Heifers were inseminated once daily after detection of oestrus. Heifers not detected in oestrus by 72 h after removal of inserts were inseminated at that time. Oestrus was detected in heifers on Farm A using heatmount detectors while on Farm B oestrus in heifers was monitored using radiotelemetry of mounting pressure. Ovarian follicular development was monitored daily in 30 heifers on Farm B from the time of administration of inserts until ovulation to a maximum of 96 h after removal of inserts, and again 11 days after removal of inserts (Day 19). A blood sample was collected from all heifers on Farm B on Day 19 and analysed for plasma concentration of progesterone. Pregnancy was diagnosed 6 to 8 weeks after insemination.\ud \ud Results Administration of ODB at the time of removal of inserts shortened the time interval to oestrus and ovulation (P < 0.001), increased the number of mounts recorded during oestrus (P = 0.04) and reduced the odds of pregnancy (P = 0.03). The proportion of heifers ovulating on Farm B was 67% and was not affected by treatment group (P = 0.61). The mean diameter of the largest follicle measured in ovaries was greater at the time of removal of inserts (9.1 ± 0.6 vs 10.7 ± 0.4; P = 0.03) and at the expected time of the LH surge (8.1 ± 0.4 vs 11.5 ± 0.3 mm; P < 0.001) in heifers that ovulated compared to heifers that failed to ovulate, respectively. Emergence of a new follicular wave was not detected during the synchronisation treatment in heifers that failed to ovulate. Concentrations of progesterone in plasma on Day 19 were less in non-pregnant heifers (P = 0.05) compared to heifers subsequently diagnosed as pregnant to insemination and were affected by the diameter of the ovulatory follicle (P = 0.01).\ud \ud Conclusion Administration of ODB at the time of removal of inserts can shorten the time interval to oestrus and ovulation and can reduce fertility when insemination is carried out once daily. Further work is needed to determine if prolonged suppression of follicular development, anovulatory oestrus and premature ovulation occuring in some heifers is associated with administration of ODB