Mechanisms of quadriceps muscle weakness in knee joint osteoarthritis: the effects of prolonged vibration on torque and muscle activation in osteoarthritic and healthy control subjects

Introduction: A consequence of knee joint osteoarthritis (OA) is an inability to fully activate the quadriceps muscles, a problem termed arthrogenic muscle inhibition (AMI). AMI leads to marked quadriceps weakness that impairs physical function and may hasten disease progression. The purpose of the present study was to determine whether g-loop dysfunction contributes to AMI in people with knee joint OA. Methods: Fifteen subjects with knee joint OA and 15 controls with no history of knee joint pathology participated in this study. Quadriceps and hamstrings peak isometric torque (Nm) and electromyography (EMG) amplitude were collected before and after 20 minutes of 50 Hz vibration applied to the infrapatellar tendon. Between-group differences in pre-vibration torque were analysed using a one-way analysis of covariance, with age, gender and body mass (kg) as the covariates. If the g-loop is intact, vibration should decrease torque and EMG levels in the target muscle; if dysfunctional, then torque and EMG levels should not change following vibration. One-sample t tests were thus undertaken to analyse whether percentage changes in torque and EMG differed from zero after vibration in each group. In addition, analyses of covariance were utilised to analyse between-group differences in the percentage changes in torque and EMG following vibration. Results: Pre-vibration quadriceps torque was significantly lower in the OA group compared with the control group (P = 0.005). Following tendon vibration, quadriceps torque (P < 0.001) and EMG amplitude (P ≤0.001) decreased significantly in the control group but did not change in the OA group (all P > 0.299). Hamstrings torque and EMG amplitude were unchanged in both groups (all P > 0.204). The vibration-induced changes in quadriceps torque and EMG were significantly different between the OA and control groups (all P < 0.011). No between-group differences were observed for the change in hamstrings torque or EMG (all P > 0.554). Conclusions: g-loop dysfunction may contribute to AMI in individuals with knee joint OA, partially explaining the marked quadriceps weakness and atrophy that is often observed in this population

Trading of intensity and interaural coherence in dichotic pitch stimuli

When a signal is added to noise in the NoSπ binaural configuration, a reduction in interaural coherence, ρ, occurs at the signal frequency and increases in tone intensity decrease ρ. Corresponding manipulations of ρ result in the perception of a phantom signal which increases in loudness as ρ decreases [ Culling et al. (2001). J. Acoust. Soc. Am. 110, 1020–1029 ]. In the present study, a narrow sub-band of noise (462–539 Hz) embedded within a broadband (0–3 kHz) diotic noise was manipulated in both intensity and ρ in a 3-interval, odd-one-out task. In the reference intervals, ρ was zero and the spectrum was flat. In the target interval, both ρ and the intensity of the target band were incremented giving opposing effects on loudness. Correct identification of the target interval followed a V-shape as a function of the size of intensity increment. The minimum of this function was often at chance performance, indicating that monaurally and binaurally evoked loudness were fully traded. These results show that reduction in ρ at a given frequency produces increased loudness at that frequency equivalent to up to 6 dB and consistent with an equalization-cancellation mechanism whose binaural output is strongly weighted compared to monaural excitation

The effects of experimental knee pain on lower limb corticospinal and motor cortex excitability

Notable weakness of the quadriceps muscles is typically observed as a consequence of knee joint arthritis, knee surgery and knee injury. This is partly due to ongoing neural inhibition that prevents the central nervous system from fully activating the quadriceps, a process known as arthrogenic muscle inhibition (AMI). To investigate the mechanisms underlying AMI, this study explored the effects of experimental knee pain on lower limb corticospinal and motor cortex excitability

Global monitoring data shows grain size controls turbidity current structure

The first detailed measurements from active turbidity currents have been made in the last few years, at multiple sites worldwide. These data allow us to investigate the factors that control the structure of these flows. By analyzing the temporal evolution of the maximum velocity of turbidity currents at different sites, we aim to understand whether there are distinct types of flow, or if a continuum exists between end-members; and to investigate the physical controls on the different types of observed flow. Our results show that the evolution of the maximum velocity of turbidity currents falls between two end-members. Either the events show a rapid peak in velocity followed by an exponential decay or, flows continue at a plateau-like, near constant velocity. Our analysis suggests that rather than triggers or system input type, flow structure is primarily governed by the grain size of the sediment available for incorporation into the flow

Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease

Background: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. Methods: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P = 0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P = 0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P = 0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P = 0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P = 0.31). Conclusions: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846.