Coordinatively unsaturated ruthenium complexes as efficient alkyne-azide cycloaddition catalysts

The performance of 16-electron ruthenium complexes with the general formula Cp*Ru(L)X (in which L = phosphine or N-heterocyclic carbene ligand; X = Cl or OCH2CF3) was explored in azide−alkyne cycloaddition reactions that afford the 1,2,3- triazole products. The scope of the Cp*Ru(PiPr3)Cl precatalyst was investigated for terminal alkynes leading to new 1,5-disubstituted 1,2,3-triazoles in high yields. Mechanistic studies were conducted and revealed a number of proposed intermediates. Cp*Ru- (PiPr3)(η2-HCCPh)Cl was observed and characterized by 1H, 13C, and 31P NMR at temperatures between 273 and 213 K. A rare example of N,N-κ2-phosphazide complex, Cp*Ru(κ2-iPr3PN3Bn)Cl, was fully characterized, and a single-crystal X-ray diffraction structure was obtained. DFT calculations describe a complete map of the catalytic reactivity with phenylacetylene and/or benzylazide.Publisher PDFPeer reviewe

Self-reported pain and disability outcomes from an endogenous model of muscular back pain

<p>Abstract</p> <p>Background</p> <p>Our purpose was to develop an induced musculoskeletal pain model of acute low back pain and examine the relationship among pain, disability and fear in this model.</p> <p>Methods</p> <p>Delayed onset muscle soreness was induced in 52 healthy volunteers (23 women, 17 men; average age 22.4 years; average BMI 24.3) using fatiguing trunk extension exercise. Measures of pain intensity, unpleasantness, and location, and disability, were tracked for one week after exercise.</p> <p>Results</p> <p>Pain intensity ranged from 0 to 68 with 57.5% of participants reporting peak pain at 24 hours and 32.5% reporting this at 48 hours. The majority of participants reported pain in the low back with 33% also reporting pain in the legs. The ratio of unpleasantness to intensity indicated that the sensation was considered more unpleasant than intense. Statistical differences were noted in levels of reported disability between participants with and without leg pain.</p> <p>Pain intensity at 24 hours was correlated with pain unpleasantness, pain area and disability. Also, fear of pain was associated with pain intensity and unpleasantness. Disability was predicted by sex, presence of leg pain, and pain intensity; however, the largest amount of variance was explained by pain intensity (27% of a total 40%). The second model, predicting pain intensity only included fear of pain and explained less than 10% of the variance in pain intensity.</p> <p>Conclusions</p> <p>Our results demonstrate a significant association between pain and disability in this model in young adults. However, the model is most applicable to patients with lower levels of pain and disability. Future work should include older adults to improve the external validity of this model.</p

Manipulation of pain catastrophizing: An experimental study of healthy participants

Pain catastrophizing is associated with the pain experience; however, causation has not been established. Studies which specifically manipulate catastrophizing are necessary to establish causation. The present study enrolled 100 healthy individuals. Participants were randomly assigned to repeat a positive, neutral, or one of three catastrophizing statements during a cold pressor task (CPT). Outcome measures of pain tolerance and pain intensity were recorded. No change was noted in catastrophizing immediately following the CPT (F(1,84) = 0.10, p = 0.75, partial η2 < 0.01) independent of group assignment (F(4,84) = 0.78, p = 0.54, partial η2 = 0.04). Pain tolerance (F(4) = 0.67, p = 0.62, partial η2 = 0.03) and pain intensity (F(4) = 0.73, p = 0.58, partial η2 = 0.03) did not differ by group. This study suggests catastrophizing may be difficult to manipulate through experimental pain procedures and repetition of specific catastrophizing statements was not sufficient to change levels of catastrophizing. Additionally, pain tolerance and pain intensity did not differ by group assignment. This study has implications for future studies attempting to experimentally manipulate pain catastrophizing

Preserving neuromuscular synapses in ALS by stimulating MuSK with a therapeutic agonist antibody

In amyotrophic lateral sclerosis (ALS) and animal models of ALS, including SOD1-G93A mice, disassembly of the neuromuscular synapse precedes motor neuron loss and is sufficient to cause a decline in motor function that culminates in lethal respiratory paralysis. We treated SOD1-G93A mice with an agonist antibody to MuSK, a receptor tyrosine kinase essential for maintaining neuromuscular synapses, to determine whether increasing muscle retrograde signaling would slow nerve terminal detachment from muscle. The agonist antibody, delivered after disease onset, slowed muscle denervation, promoting motor neuron survival, improving motor system output, and extending the lifespan of SOD1-G93A mice. These findings suggest a novel therapeutic strategy for ALS, using an antibody format with clinical precedence, which targets a pathway essential for maintaining attachment of nerve terminals to muscle

Stability of behavioral estimates of activity-dependent modulation of pain

Temporal sensory summation of pain (TSSP) is a proxy measure of windup in humans and results in increased ratings of pain caused by a repetitive, low-frequency noxious stimulus. Aftersensations (ASs) are pain sensations that remain after TSSP has been induced. We examined the within-session and across-session variability in TSSP and AS estimation in healthy participants and in participants with exercise-induced muscle pain in order to determine whether the presence of pain affected the stability of TSSP and ASs. TSSP was estimated by application of 10 repetitive, low-frequency (<0.33 Hz) thermal pulses and measured by the simple slope of pain ratings between the first and fifth pulses. ASs were measured by the presence of any remaining pain sensations up to 1 minute after TSSP was induced. TSSP estimation remained moderately stable in pain-free participants and in participants with pain within a single testing session but demonstrated low stability across sessions in pain-free participants. AS estimation was stable for all groups. Estimation of TSSP and ASs using these protocols appears to be a reliable single-session outcome measure in studies of interventions for acute muscle pain and in experimental studies with healthy participants. This article evaluates the reliability of a commonly used method of estimating TSSP and ASs in both healthy participants and in a clinically relevant model of acute pain. These protocols have the potential to be used as single-session outcome measures for interventional studies and in experimental studies