Increased collagen synthesis rate during wound healing in muscle

Wound healing in muscle involves the deposition of collagen, but it is not known whether this is achieved by changes in the synthesis or the degradation of collagen. We have used a reliable flooding dose method to measure collagen synthesis rate in vivo in rat abdominal muscle following a surgical incision. Collagen synthesis rate was increased by 480% and 860% on days 2 and 7 respectively after surgery in the wounded muscle compared with an undamaged area of the same muscle. Collagen content was increased by approximately 100% at both day 2 and day 7. These results demonstrate that collagen deposition during wound healing in muscle is achieved entirely by an increase in the rate of collagen synthesis

Ultrasound-detectable grey scale synovitis predicts future fulfilment of the 2010 ACR/EULAR RA classification criteria in patients with new-onset undifferentiated arthritis

Objective: To determine the clinical outcomes for patients with new-onset undifferentiated arthritis (UA), not fulfilling the 2010 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) rheumatoid arthritis (RA) classification criteria, and the clinical and imaging predictors of disease progression in these patients. Methods: A prospective observational study was conducted in treatment-naïve UA patients. Baseline ultrasound involved semiquantitative assessment of grey scale (GS) synovitis and power Doppler activity (PD) at 26 joints. Outcomes were fulfilment of 2010 RA criteria (joint involvement determined clinically) and initiation of methotrexate over 12 months. Cox proportional hazards analysis was used to investigate predictors of outcome. Results: Of 60 patients, 13(22%) progressed to RA and 32(53%) ever received methotrexate. Analyses of predictors of outcome were conducted in the subgroup (n=41) of patients with complete baseline data. The presence of GS was associated with progression to RA and methotrexate use: HRs (95% CI) were 1.25(1.07 to 1.45) and 1.16(1.02 to 1.32), respectively, for the number of joints with GS≥ grade 2 after adjustment for swollen joints. PD was not predictive in the low levels at which it was observed. Progression to RA was also associated with fulfilment of the 2010 criteria using ultrasound synovitis for enumerating joint involvement, higher baseline disability and radiographic erosion. Conclusions: This is the first report of ultrasound findings in early UA (defined by presence of clinical synovitis and non-fulfilment of 2010 RA criteria). A significant proportion of patients with UA progressed to RA and/or required methotrexate. GS synovitis was predictive of disease progression

Reduction in stiffness of proximal leg muscles during the first 6 months of glucocorticoid therapy for giant cell arteritis: A pilot study using shear wave elastography.

Aim: To investigate muscle stiffness changes in patients treated for giant cell arteritis (GCA) with high‐dose oral glucocorticoids. Methods: Using ultrasound elastography, shear wave velocity (SWV) was measured in the quadriceps, hamstrings and biceps brachii muscles of 14 patients with GCA (4 male, mean age ± SD, 68.2 ± 4.3 years) within the first 2 weeks of initiating glucocorticoid treatment (baseline) and repeated after 3 and 6 months treatment. Muscle strength and performance tests were performed at each visit. Baseline measures were compared with those from 14 healthy controls. Linear mixed models were used to test for change in patient measures over time. Results: At baseline, muscle SWV in patients was not significantly different from controls. With glucocorticoid treatment, there was a reduction in SWV in the leg but not the arm muscles. SWV decreased by a mean of 14% (range 8.3%‐17.3%; P = .001) after 3 months and 18% (range 10.2%‐25.3%; P < .001) after 6‐months in the quadriceps and hamstrings during the resting position. The baseline, 3 and 6 months mean SWV (±SD) for the vastus lateralis were 1.62 ± 0.16 m/s, 1.40 ± 0.10 m/s and 1.31 ± 0.06 m/s, respectively (P < .001). In the patient group as a whole, there was no significant change in muscle strength. However, there were moderate correlations (r = .54‐.69) between exhibiting weaker muscle strength at follow‐up visits and a greater reduction in SWV. Conclusion: Glucocorticoid therapy in patients with GCA was associated with a significant reduction in proximal leg muscle stiffness during the first 6 months. Future research should study a larger sample of patients for a longer duration to investigate if diminished muscle stiffness precedes signs of glucocorticoid‐induced myopathy

Ultrasound erosions in the feet best predict progression to inflammatory arthritis in anti-CCP positive at-risk individuals without clinical synovitis

Objectives To investigate, in anti-cyclic citrullinated peptide antibody positive (CCP+) at-risk individuals without clinical synovitis, the prevalence and distribution of ultrasound (US) bone erosions (BE), their correlation with subclinical synovitis and their association with the development of inflammatory arthritis (IA). Methods Baseline US scans of 419 CCP+ at-risk individuals were analysed. BE were evaluated in the classical sites for rheumatoid arthritis damage: the second and fifth metacarpophalangeal (MCP2 and MCP5) joints, and the fifth metatarsophalangeal (MTP5) joints. US synovitis was defined as synovial hypertrophy (SH) ≥2 or SH ≥1+power Doppler signal ≥1. Subjects with ≥1 follow-up visit were included in the progression analysis (n=400). Results BE were found in ≥1 joint in 41/419 subjects (9.8%), and in 55/2514 joints (2.2%). The prevalence of BE was significantly higher in the MTP5 joints than in the MCP joints (p1 joint 10.6 (95% CI 1.9 to 60.4, p<0.01) and BE and synovitis in ≥1 MTP5 joint 5.1 (95% CI 1.4 to 18.9, p=0.02). In high titre CCP+ at-risk individuals, with positive rheumatoid factor and BE in ≥1 joint, the OR increased to 16.9 (95% CI 2.1–132.8, p<0.01). Conclusions In CCP+ at-risk individuals, BE in the feet appear to precede the onset of clinical synovitis. BE in >1 joint, and BE in combination with US synovitis in the MTP5 joints, are the most predictive for the development of clinical arthritis

Pragmatic randomised controlled trial of very early etanercept and MTX versus MTX with delayed etanercept in RA: the VEDERA trial

Objectives: We sought to confirm in very early rheumatoid arthritis (ERA) a much greater superiority (30%) of first-line etanercept+methotrexate (ETN+MTX) over treat-to-target MTX (MTX-TT) than previously reported in ERA (14%); and explore whether ETN following initial MTX secures a comparable response to first-line ETN+MTX. Methods: Pragmatic, open-label, randomised controlled trial of treatment-naïve ERA (≤12 months symptom), Disease Activity Score 28 joint (DAS28)-erythrocyte sedimentation rate (ESR) ≥3.2, rheumatoid factor (RF)+/−anticitrullinated peptide antibody (ACPA) positive or ultrasound power Doppler (PD) if RF and ACPA negative. Subjects were randomised 1:1 to ETN+MTX; or MTX-TT, escalated to ETN if week 24 DAS28-ESR ≥2.6 and intramuscular corticosteroid at protocolised time points. Primary endpoint of week 48 DAS28ESR remission with clinical and imaging secondary endpoints. Results: We randomised 120 patients, 60 to each arm (71% female, 73% RF/84% ACPA positive, median (IQR) symptom duration 20.3 (13.1, 30.8) weeks; mean (SD) DAS28 5.1 (1.1)). Remission rates with ETN+MTX and MTX-TT, respectively, were 38% vs 33% at week 24; 52% vs 38% at week 48 (ORs 1.6, 95% CI 0.8 to 3.5, p=0.211). Greater, sustained DAS28-ESR remission observed with ETN+MTX versus MTX-TT (42% and 27%, respectively; p=0.035). PD was fully suppressed by week 48 in over 90% in each arm. Planned exploratory analysis revealed OR 2.84, 95% CI 0.8 to 9.6) of achieving remission after 24 weeks of ETN administered first line compared with administered post-MTX. Conclusions: Compared with remission rates typically reported with first-line tumour necrosis factor inhabitor+MTX versus MTX-TT, we did not demonstrate a larger effect in very ERA. Neither strategy conferred remission in the majority of patients although ultrasound confirmed local inflammation suppression. Poorer ETN response following failure of MTX-TT is also suggested. Trial registration number: NCT0243318

ISO LWS observations of planetary nebula fine-structure lines

We have obtained 43–198 μm far-infrared (IR) spectra for a sample of 51 Galactic planetary nebulae (PN) and protoplanetary nebulae (PPN), using the Long Wavelength Spectrometer (LWS) on board the Infrared Space Observatory (ISO). Spectra were also obtained of the former PN candidate Lo 14. The spectra yield fluxes for the fine-structure lines [N II] 122 μm, [N III] 57 μm and [O III] 52 and 88 μm emitted in the ionized regions and the [O I] 63- and 146-μm and [C II] 158-μm lines from the photodissociation regions (PDRs), which have been used to determine electron densities and ionic abundances for the ionized regions and densities, temperatures and gas masses for the PDRs. The strong [N III] and [O III] emission lines detected in the LWS spectrum taken centred on Lo 14 could be associated with the nearby strong radio and infrared source G 331.5–0.1. We find that the electron densities yielded by the [O III] 88 μm/52 μm doublet ratio are systematically lower than those derived from the optical [Ar IV] λ4740/λ4711 and [Cl III] λ5537/λ5517 doublet ratios, which have much higher critical densities than the 52- and 88-μm lines, suggesting the presence of density inhomogeneities in the nebulae. Ionic abundances, N+/H+,N2+/H+ and O2+/H+, as well as the N2+/O2+ abundance ratio, which provides a good approximation to the N/O elemental abundance ratio, are derived. Although ionic abundances relative to H+ deduced from the far-IR fine-structure lines are sensitive to the adopted electron density and the presence of density inhomogeneities, the strong dependence on the nebular physical conditions is largely cancelled out when N2+/O2+ is calculated from the 57 μm/(52 μm+88 μm) flux ratio, owing to the similarity of the critical densities of the lines involved. The temperatures and densities of the PDRs around 24 PN have been determined from the observed [O I] and [C II] line intensity ratios. Except for a few objects, the deduced temperatures fall between 200 and 500 K, peaking around 250 K. The densities of the PDRs vary from 104–105 cm−3, reaching 3×105 cm−3 in some young compact PN. With a derived temperature of 1600 K and a density of 105 cm−3, the PDR of NGC 7027 is one of the warmest and at the same time one of the densest amongst the nebulae studied. For most of the PN studied, the [C II]-emitting regions contain only modest amounts of material, with gas masses ≲0.1 M⊙. Exceptional large PDR masses are found for a few nebulae, including NGC 7027, the bipolar nebulae M2-9 and NGC 6302, the young dense planetary nebulae BD+30°3639, IC 418 and NGC 5315, and the old, probably recombining, nebulae IC 4406 and NGC 6072

The effect of ageing on shear wave elastography muscle stiffness in adults

Background: Skeletal muscle undergoes structural changes with ageing which may alter its biomechanical properties. Shear wave elastography (SWE) may detect these changes by measuring muscle stiffness. Aims: To investigate muscle stiffness in healthy young, middle-aged and elderly cohorts using SWE and correlate it with muscle strength and mass. Methods: Shear wave velocity (SWV) was measured in the quadriceps, hamstrings and biceps brachii of 26 young (range 20–35 years), 21 middle-aged (40–55) and 30 elderly (77–94) volunteers. The participants performed several muscle tests to evaluate their strength. The One-way ANOVA was used to test the muscle stiffness differences between the groups and the Pearson’s correlation coefficient to evaluate the relationship between SWV and muscle strength. Results: The overall resting muscle SWV gradually decreased with age but was only significantly reduced in the elderly group (p < 0.001); with the exception of the vastus lateralis SWV where a significant difference was noted (p < 0.05) between young (1.77 m/s), middle-aged (1.64 m/s) and elderly (1.48 m/s). The elderly group had on average 16.5% lower muscle stiffness compared to the young. SWV significantly correlated with muscle mass (r = 0.316), walking time (r = − 0.560), number of chair stands (r = 0.522), handgrip strength (r = 0.436) and isokinetic knee strength (r = 0.640). Sex and BMI did not explain any significant variation in SWV. Conclusions: Ageing was associated with a decline in skeletal muscle stiffness which positively correlates with muscle weakness. Further research is needed to evaluate the promising role of SWE as a biomarker for sarcopenia assessment and potential falls risk prediction in elderly individuals

Initial fixation placement in face images is driven by top-down guidance

The eyes are often inspected first and for longer period during face exploration. To examine whether this saliency of the eye region at the early stage of face inspection is attributed to its local structure properties or to the knowledge of its essence in facial communication, in this study we investigated the pattern of eye movements produced by rhesus monkeys (Macaca mulatta) as they free viewed images of monkey faces. Eye positions were recorded accurately using implanted eye coils, while images of original faces, faces with scrambled eyes, and scrambled faces except for the eyes were presented on a computer screen. The eye region in the scrambled faces attracted the same proportion of viewing time and fixations as it did in the original faces, even the scrambled eyes attracted substantial proportion of viewing time and fixations. Furthermore, the monkeys often made the first saccade towards to the location of the eyes regardless of image content. Our results suggest that the initial fixation placement in faces is driven predominantly by ‘top-down’ or internal factors, such as the prior knowledge of the location of “eyes” within the context of a face

The effectiveness of neuromuscular warm-up strategies, that require no additional equipment, for preventing lower limb injuries during sports participation: a systematic review

PMCID: PMC3408383The electronic version of this article is the complete one and can be found online at: http://www.biomedcentral.com/1741-7015/10/75. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited