Objective assessment of stiffness in Achilles tendinopathy: a novel approach using the MyotonPRO

Objectives The aim of this study was to establish quantitative values for asymptomatic and symptomatic Achilles tendons. Design Cohort study with a single (cross-sectional) time point of patients diagnosed with unilateral Achilles tendinopathy and an asymptomatic group with comparative homogeneity. Methods A sample of 50 participants: 25 diagnosed with symptomatic unilateral Achilles tendinopathy (AT group) and 25 with asymptomatic Achilles tendons (control group 2). The asymptomatic side of the AT group was used as a control (control group 1). Measurements at 2 cm intervals on the tendon from its insertion at the calcaneum up to the musculotendinous junction were taken non-weight bearing (NWB) and weight bearing (WB) using the MyotonPRO. Results There was a significant (p<0.005) decrease in natural oscillation frequency (F) at points 2, 3 and 4 of the AT group (NWB condition) and points 2 and 3 for the WB condition. There was a significant (p<0.005) increase in logarithmic decrement (D) at points 2 and 3 signifying a decrease in elasticity. Dynamic stiffness (S) was significantly (p<0.005) reduced in the AT group at points 2 and 3 WB and point 3 WB. There was no significant difference in creep (C) observed between the symptomatic and asymptomatic tendons. There was a significant (p<0.005) increase in mechanical stress relaxation time (R) at point 2 NWB. There was a correlation between body weight and gender on tendon mechanics, with the symptomatic tendons. No significant differences were observed between the control group 1 and control group 2. Conclusions The MyotonPRO measured decreased stiffness over a section of the tendon corresponding clinically with Achilles tendinopathy. This may have potential in identifying risk of injury and informing rehabilitation, however further extensive research is required to generate baseline data for specific population groups monitoring variables over time. Age, gender and body mass index appear to have some bearing on the mechanical properties of the tendon but mainly in the tendinopathy group

Adenosine-mono-phosphate-activated protein kinase-independent effects of metformin in T cells

The anti-diabetic drug metformin regulates T-cell responses to immune activation and is proposed to function by regulating the energy-stress-sensing adenosine-monophosphate-activated protein kinase (AMPK). However, the molecular details of how metformin controls T cell immune responses have not been studied nor is there any direct evidence that metformin acts on T cells via AMPK. Here, we report that metformin regulates cell growth and proliferation of antigen-activated T cells by modulating the metabolic reprogramming that is required for effector T cell differentiation. Metformin thus inhibits the mammalian target of rapamycin complex I signalling pathway and prevents the expression of the transcription factors c-Myc and hypoxia-inducible factor 1 alpha. However, the inhibitory effects of metformin on T cells did not depend on the expression of AMPK in T cells. Accordingly, experiments with metformin inform about the importance of metabolic reprogramming for T cell immune responses but do not inform about the importance of AMPK

Transdermal Blood Sampling for C-peptide Is a Minimally Invasive, Reliable Alternative to Venous Sampling in Children and Adults With Type 1 Diabetes

OBJECTIVE:C-peptide and islet autoantibodies are key type 1 diabetes biomarkers, typically requiring venous sampling, which limits their utility. We assessed transdermal capillary blood (TCB) collection as a practical alternative.RESEARCH DESIGN AND METHODS:Ninety-one individuals (71 with type 1 diabetes, 20 controls; individuals with type 1 diabetes: aged median 14.8 years [interquartile range (IQR) 9.1–17.1], diabetes duration 4.0 years [1.5–7.7]; controls: 42.2 years [38.0–52.1]) underwent contemporaneous venous and TCB sampling for measurement of plasma C-peptide. Participants with type 1 diabetes also provided venous serum and plasma, and TCB plasma for measurement of autoantibodies to glutamate decarboxylase, islet antigen-2, and zinc transporter 8. The ability of TCB plasma to detect significant endogenous insulin secretion (venous C-peptide ≥200 pmol/L) was compared along with agreement in levels, using Bland-Altman. Venous serum was compared with venous and TCB plasma for detection of autoantibodies, using established thresholds. Acceptability was assessed by age-appropriate questionnaire.RESULTS:Transdermal sampling took a mean of 2.35 min (SD 1.49). Median sample volume was 50 µL (IQR 40–50) with 3 of 91 (3.3%) failures, and 13 of 88 (14.7%) &lt;35 µL. TCB C-peptide showed good agreement with venous plasma (mean venous ln[C-peptide] – TCB ln[C-peptide] = 0.008, 95% CI [−0.23, 0.29], with 100% [36 of 36] sensitivity/100% [50 of 50] specificity to detect venous C-peptide ≥200 pmol/L). Where venous serum in multiple autoantibody positive TCB plasma agreed in 22 of 32 (sensitivity 69%), comparative specificity was 35 of 36 (97%). TCB was preferred to venous sampling (type 1 diabetes: 63% vs. 7%; 30% undecided).CONCLUSIONS:Transdermal capillary testing for C-peptide is a sensitive, specific, and acceptable alternative to venous sampling; TCB sampling for islet autoantibodies needs further assessment

Re-evaluation and extension of the Marine Isotope Stage 5 tephrostratigraphy of the Faroe Islands region: The cryptotephra record

PMA, SMD, WENA and NJGP are supported by NERC through the SMART project (NE/F020600/1, NE/F02116X/1, NE/F021445/1). The research leading to the results for the MIS 4 and 5a tephra horizons has received funding from the European Research Council under the European Union's Seventh Framework Programme (FP7/2007-2013) / ERC grant agreement n° [259253]. PMA, SMD and NJGP acknowledge the support of the Climate Change Consortium of Wales (C3W). JB is funded by the Research Council of Norway through the INTERACT project (project no. 221999).Abstract Previous studies of marine sequences from the Faroe Islands region have identified a series of coarse-grained tephra horizons deposited during Marine Isotope Stage (MIS) 5. Here we reassess the MIS 5 tephrostratigraphy of the Faroe Islands region and focus on the cryptotephra deposits preserved within the fine-grained fraction of marine core LINK 16. We also extend the record to encompass the late MIS 6 and early MIS 4 periods. A density separation technique, commonly used for tephra investigations in lacustrine settings but rarely applied to marine sediments, is utilised to explore the fine-grained material and EPMA and LA-ICP-MS are employed to determine the major and trace element composition of individual tephra shards. In total, 3 basaltic and 3 rhyolitic Icelandic cryptotephra deposits with homogeneous geochemical compositions are identified — all of which have the potential to act as isochronous tie-lines. Geochemical results highlight that the Grímsvötn volcanic system of Iceland is the predominant source of the basaltic horizons and the Öraefajökull or Torfajökull systems are the likely sources of the rhyolitic deposits. Three of the horizons have been previously recognised in Faroe Islands region marine sequences, with two of these deposits traceable into a Norwegian Sea sequence. An early MIS 4 rhyolitic horizon is the most widespread deposit as it can be traced into the Norwegian Sea and to the south into a record from the Rockall Trough. Basaltic and rhyolitic horizons deposited during late MIS 6 have not been recognised in other sequences and represent new additions to the regional tephrostratigraphy.Publisher PDFPeer reviewe

The prevalence of hyperglycaemia and its relationship with mortality, readmissions and length of stay in an older acute surgical population : a multicentre study

Funding statement This research received no specific grant from any funding agency in the public, commercial or not-for-profit sector.Peer reviewedPostprin

Growth and mass wasting of volcanic centers in the northern South Sandwich arc, South Atlantic, revealed by new multibeam mapping

New multibeam (swath) bathymetric sonar data acquired using an EM120 system on the RRS James Clark Ross, supplemented by sub-bottom profiling, reveals the underwater morphology of a not, vert, similar 12,000 km2 area in the northern part of the mainly submarine South Sandwich volcanic arc. The new data extend between 55° 45′S and 57° 20′S and include Protector Shoal and the areas around Zavodovski, Visokoi and the Candlemas islands groups. Each of these areas is a discrete volcanic center. The entirely submarine Protector Shoal area, close to the northern limit of the arc, forms a 55 km long east–west-trending seamount chain that is at least partly of silicic composition. The seamounts are comparable to small subaerial stratovolcanoes in size, with volumes up to 83 km3, indicating that they are the product of multiple eruptions over extended periods. Zavodovski, Visokoi and the Candlemas island group are the summits of three 3–3.5 km high volcanic edifices. The bathymetric data show evidence for relationships between constructional volcanic features, including migrating volcanic centers, structurally controlled constructional ridges, satellite lava flows and domes, and mass wasting of the edifices. Mass wasting takes place mainly by strong erosion at sea level, and dispersal of this material along chutes, probably as turbidity currents and other mass flows that deposit in extensive sediment wave fields. Large scale mass wasting structures include movement of unconsolidated debris in slides, slumps and debris avalanches. Volcanism is migrating westward relative to the underlying plate and major volcanoes are asymmetrical, being steep with abundant recent volcanism on their western flanks, and gently sloping with extinct, eroded volcanic sequences to their east. This is consistent with the calculated rate of subduction erosion of the fore-arc

Resolving polymorphs and radiation-driven effects in microcrystals using fixed-target serial synchrotron crystallography

The ability to determine high-quality, artefact-free structures is a challenge in micro-crystallography, and the rapid onset of radiation damage and requirement for a high-brilliance X-ray beam mean that a multi-crystal approach is essential. However, the combination of crystal-to-crystal variation and X-ray-induced changes can make the formation of a final complete data set challenging; this is particularly true in the case of metalloproteins, where X-ray-induced changes occur rapidly and at the active site. An approach is described that allows the resolution, separation and structure determination of crystal polymorphs, and the tracking of radiation damage in microcrystals. Within the microcrystal population of copper nitrite reductase, two polymorphs with different unit-cell sizes were successfully separated to determine two independent structures, and an X-ray-driven change between these polymorphs was followed. This was achieved through the determination of multiple serial structures from microcrystals using a high-throughput high-speed fixed-target approach coupled with robust data processing

Deep VLA Observations of the Cluster 1RXS J0603.3+4214 in the Frequency Range of 1–2 GHz

We report L-band VLA observations of 1RXS J0603.3+4214, a cluster that hosts a bright radio relic, known as the Toothbrush, and an elongated giant radio halo. These new observations allow us to study the surface brightness distribution down to one arcsec resolution with very high sensitivity. Our images provide an unprecedented detailed view of the Toothbrush, revealing enigmatic filamentary structures. To study the spectral index distribution, we complement our analysis with published LOFAR and GMRT observations. The bright `brush' of the Toothbrush shows a prominent narrow ridge to its north with a sharp outer edge. The spectral index at the ridge is in the range $-0.70\leq\alpha\leq-0.80$. We suggest that the ridge is caused by projection along the line of sight. With a simple toy model for the smallest region of the ridge, we conclude that the magnetic field is below $5\,\rm\mu G$ and varies significantly across the shock front. Our model indicates that the actual Mach number is higher than that obtained from the injection index and agrees well with the one derived from the overall spectrum, namely ${\cal M}=3.78^{+0.3}_{-0.2}$. The radio halo shows an average spectral index of $\alpha=-1.16\pm0.05$ and a slight gradient from north to south. The southernmost part of the halo is steeper and possibly related to a shock front. Excluding the southernmost part, the halo morphology agrees very well with the X-ray morphology. A power-law correlation is found between the radio and X-ray surface brightnessComment: 23 pages, 21 figures, accepted for publication in Ap

Endothelial Function is Not Changed during Short-Term Withdrawal of Thyroxine in Patients with Differentiated Thyroid Cancer and Low Cardiovascular Risk

PURPOSE: The incidence of differentiated thyroid cancer is increasing in young adults and females in Korea. Some of them experience short-term hypothyroidism in preparation for radioiodine (RAI) therapy, which can have a deleterious effect on the cardiovascular system. However, it is not clear if short-term hypothyroidism induces endothelial dysfunction in patients with low cardiovascular risk. Therefore, the aim of this study was to investigate whether short-term hypothyroidism is associated with endothelial dysfunction in patients with low cardiovascular risk. MATERIALS AND METHODS: To evaluate the effect of short-term hypothyroidism on endothelial function in this group, we recruited fifteen female patients with low cardiovascular risk. We analyzed clinical, biochemical, and cardiovascular parameters at four time points: the last day on levothyroxine (LT4) at their usual thyroid-stimulating hormone (TSH)-suppressive doses (P1), 7 days (P2) and 4 weeks (P3) after withdrawal of LT4, and 8 weeks (P4) after replacement of the previous dose of LT4. A high resolution ultrasound was used to measure brachial artery diameter at rest, after reactive hyperemia, and after sublingual nitroglycerin. RESULTS: During short-term hypothyroidism (P3), serum concentrations of total cholesterol and low-density lipoprotein (LDL)-cholesterol were increased (p < 0.001 for each period). In spite of having worsened lipid states, serum high sensitivity C-reactive protein or flow-mediated vasodilatation, which is one of the surrogate markers of the endothelial function, did not change during short-term hypothyroidism. CONCLUSION: Short-term hypothyroidism induced worsening of metabolic parameters, but not enough to induce the endothelial dysfunction in patients with low cardiovascular riskope