Quantitative sensory testing in painful hand osteoarthritis demonstrates features of peripheral sensitisation.

Hand osteoarthritis (HOA) is a prevalent condition for which treatments are based on analgesia and physical therapies. Our primary objective was to evaluate pain perception in participants with HOA by assessing the characteristics of nodal involvement, pain threshold in each hand joint, and radiological severity. We hypothesised that inflammation in hand osteoarthritis joints enhances sensitivity and firing of peripheral nociceptors, thereby causing chronic pain. Participants with proximal and distal interphalangeal (PIP and DIP) joint HOA and non-OA controls were recruited. Clinical parameters of joint involvement were measured including clinical nodes, VAS (visual analogue score) for pain (0-100 mm scale), HAQ (health assessment questionnaire), and Kellgren-Lawrence scores for radiological severity and pain threshold measurement were performed. The mean VAS in HOA participants was 59.3 mm ± 8.19 compared with 4.0 mm ± 1.89 in the control group (P < 0.0001). Quantitative sensory testing (QST) demonstrated lower pain thresholds in DIP/PIP joints and other subgroups in the OA group including the thumb, metacarpophalangeal (MCPs), joints, and wrists (P < 0.008) but not in controls (P = 0.348). Our data demonstrate that HOA subjects are sensitised to pain due to increased firing of peripheral nociceptors. Future work to evaluate mechanisms of peripheral sensitisation warrants further investigation

Microstructural Changes in Wheat Starch Dispersions During Heating and Cooling

Microstructural changes in 8-11% wheat starch dispersions during heating, cooling and cold storage have been evaluated by light microscopy and scanning electron microscopy. Heat treatment of wheat starch dispersions gives rise to two stages of swelling and solubilization. During the first phase of swelling, solubilized amylose was observed ln the centre of the granules and, to some extent, outside the granules. Further swelling deformed the granules and more amylose was released. When the temperature treatment took place under shear, the outer layer of the swo llen granules fra ctured at 94°C and above, and amylopectin fragments were dispersed into the cont inuous amylose phase. Fragmentation of amylopectin was not observed when samples were heated with a minimum of mechanical action. There were also differences in the final gel structure between samples due to the mechanical treatment during preparation. Aggregation of amylose took place on cooling and could be observed as irregularities in the gel structure. When the amount of released amylose was limited during the initial phase of swelling and below the critical concentration for gel formation, cooling resulted in deposition of amylose at the surface of the granules. This was expected to have an impact on the behaviour of the granules on further processing

Tenascin-C fragments are endogenous inducers of cartilage matrix degradation

Cartilage destruction is a hallmark of osteoarthritis (OA) and is characterized by increased protease activity resulting in the degradation of critical extracellular matrix (ECM) proteins essential for maintaining cartilage integrity. Tenascin-C (TN-C) is an ECM glycoprotein, and its expression is upregulated in OA cartilage. We aimed to investigate the presence of TN-C fragments in arthritic cartilage and establish whether they promote cartilage degradation. Expression of TN-C and its fragments was evaluated in cartilage from subjects undergoing joint replacement surgery for OA and RA compared with normal subjects by western blotting. The localization of TN-C in arthritic cartilage was also established by immunohistochemistry. Recombinant TN-C fragments were then tested to evaluate which regions of TN-C are responsible for cartilage-degrading activity in an ex vivo cartilage explant assay measuring glycosaminoglycan (GAG) release, aggrecanase and matrix metalloproteinase (MMP) activity. We found that specific TN-C fragments are highly upregulated in arthritic cartilage. Recombinant TN-C fragments containing the same regions as those identified from OA cartilage mediate cartilage degradation by the induction of aggrecanase activity. TN-C fragments mapping to the EGF-L and FN type III domains 3-8 of TN-C had the highest levels of aggrecan-degrading ability that was not observed either with full-length TN-C or with other domains of TN-C. TN-C fragments represent a novel mechanism for cartilage degradation in arthritis and may present new therapeutic targets for the inhibition of cartilage degradation

Microstructure and Rheological Properties of Composites of Potato Starch Granules and Amylose: A Comparison of Observed and Predicted Structures

Potato starch granules were gelatinised in amylose solution to study the effect of adding amylose to a highswelling granular starch system. The effects of varying the amount of potato starch from 1-10% , added to a solution of 2% amylose, were studied by means of dynamic viscoelastic measurements and light microscopy. The granules gelatinised in amylose solution had a lower degree of swelling than those gelatinised in water. The restricted swelling in amylose was reflected in a decrease in the complex shear modulus (G*) at 75\u27C. GeJatinisation in 2% amylopectin also caused a decrease in G*, but gelatinisation in 2% 0-glucose did not affect the rheological behaviour. Microstructural analysis showed that the added amylose was present outside the granules after swelling, whereas the inherent amylose from the potato starch seemed to have diffused main] y to the inner aqueous centre of the granules. The mixed potato starch/amylose systems showed a fast gelation comparable to that of cereal starch. The results were analysed by a model predicting the shear modulus of aqueous biphasic gels. When the system is regarded as a continuous network of added amylose with dispersed potato starch granules, the results from both microscopy and rheology are in excellent agreement with the model at potato starch concentrations below 6%. As the potato starch concentration was raised, the high swelling potential of the potato starch granules led to partial disruption of the continuous amylose network. The results imply that the inherent amylose from potato starch did not contribute to the gel strength caused by the added solubilised amylose

Total Fatty Acid Analysis of Human Blood Samples in One Minute by High-Resolution Mass Spectrometry

Total fatty acid analysis is a routine method in many areas, including lipotyping of individuals in personalized medicine, analysis of foodstuffs, and optimization of oil production in biotechnology. This analysis is commonly done by converting fatty acyl (FA) chains of intact lipids into FA methyl esters (FAMEs) and monitoring these by gas-chromatography (GC)-based methods, typically requiring at least 15 min of analysis per sample. Here, we describe a novel method that supports fast, precise and accurate absolute quantification of total FA levels in human plasma and serum samples. The method uses acid-catalyzed transesterification with O-18-enriched H2O (i.e., (H2O)-O-18) to convert FA chains into O-18-labeled free fatty acids. The resulting "mass-tagged" FA analytes can be specifically monitored with improved signal-to-background by 1 min of high resolution Fourier transform mass spectrometry (FTMS) on an Orbitrap-based mass spectrometer. By benchmarking to National Institute of Standards and Technology (NIST) certified standard reference materials we show that the performance of our method is comparable, and at times superior, to that of gold-standard GC-based methods. In addition, we demonstrate that the method supports the accurate quantification of FA differences in samples obtained in dietary intervention studies and also affords specific monitoring of ingested stable isotope-labeled fatty acids (C-13(16)-palmitate) in normoinsulinemic and hyperinsulinemic human subjects. Overall, our novel high-throughput method is generic and suitable for many application areas, spanning basic research to personalized medicine, and is particularly useful for laboratories equipped with high resolution mass spectrometers, but lacking access to GC-based instrumentation

Immunohistochemical Techniques Applied to Raw and Mildly Heat Treated Meat Systems

Immunohistology was performed with six commercially available antibodies directed against myosins, actins and collagens. The corresponding antigens, appearing on the surface of cryo-sections from meat and meat products heat treated to different end temperatures, were visualized using these antibodies. The meat and meat products were heated from 20 °C to 80 °C. At 80 °C the meat systems were devoid of thermal transitions as judged from differential scanning calorimetric measurements. Our results showed that although reduced binding was the case for systems heated above 60 °C, the signals from the antibody labelling was still sufficiently strong to provide information about specific antigens in meat systems heated to 70-80 °C. Antibodies with a high initial affinity bound to the their respective antigens after the latter had been heated to a few degrees above their denaturation temperature as detected in a scanning calorimeter. This investigation points to the possibility of fmding sufficiently good commercial antibodies to perform immunohistology on meat products heated to temperatures between 70-80 °C. This is important as many commercial meat products are heated to end temperatures in this range. Several examples of the labelling intensity obtained on heated meat and meat products are given. In addition, an example using double labelling with antibodies to collagen III and an antibody to slow myosin in a food product heated to 75 °C is given. Problems related to non-specific staining and to non-specific effects of heat treatment are also briefly discussed

A turn propensity scale for transmembrane helices.

Using a model protein with a 40 residue hydrophobic transmembrane segment, we have measured the ability of all the 20 naturally occurring amino acids to form a tight turn when placed in the middle of the hydrophobic segment. Turn propensities in a transmembrane helix are found to be markedly different from those of globular proteins, and in most cases correlate closely with the hydrophobicity of the residue. The turn propensity scale may be used to improve current methods for membrane protein topology prediction

Oxygen for breathlessness in patients with chronic obstructive pulmonary disease who do not qualify for home oxygen therapy

© 2016 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. Background: Breathlessness is a cardinal symptom of chronic obstructive pulmonary disease (COPD). Long-term oxygen therapy (LTOT) is given to improve survival time in people with COPD and severe chronic hypoxaemia at rest. The efficacy of oxygen therapy for breathlessness and health-related quality of life (HRQOL) in people with COPD and mild or no hypoxaemia who do not meet the criteria for LTOT has not been established. Objectives: To determine the efficacy of oxygen versus air in mildly hypoxaemic or non-hypoxaemic patients with COPD in terms of (1) breathlessness; (2) HRQOL; (3) patient preference whether to continue therapy; and (4) oxygen-related adverse events. Search methods: We searched the Cochrane Airways Group Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and Embase, to 12 July 2016, for randomised controlled trials (RCTs). We handsearched the reference lists of included articles. Selection criteria: We included RCTs of the effects of non-invasive oxygen versus air on breathlessness, HRQOL or patient preference to continue therapy among people with COPD and mild or no hypoxaemia (partial pressure of oxygen (PaO2) > 7.3 kPa) who were not already receiving LTOT. Two review authors independently assessed articles for inclusion in the review. Data collection and analysis: Two review authors independently collected and analysed data. We assessed risk of bias by using the Cochrane 'Risk of bias tool'. We pooled effects recorded on different scales as standardised mean differences (SMDs) with 95% confidence intervals (CIs) using random-effects models. Lower SMDs indicated decreased breathlessness and reduced HRQOL. We performed subanalyses and sensitivity analyses and assessed the quality of evidence according to the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach. Main results: Compared with the previous review, which was published in 2011, we included 14 additional studies (493 participants), excluded one study and included data for meta-analysis of HRQOL. In total, we included in this review 44 studies including 1195 participants, and we included 33 of these (901 participants)in the meta-analysis. We found that breathlessness during exercise or daily activities was reduced by oxygen compared with air (32 studies; 865 participants; SMD -0.34, 95% CI -0.48 to -0.21; I2 = 37%; low-quality evidence). This translates to a decrease in breathlessness of about 0.7 points on a 0 to 10 numerical rating scale. In contrast, we found no effect of short-burst oxygen given before exercise (four studies; 90 participants; SMD 0.01, 95% CI -0.26 to 0.28; I2 = 0%; low-quality evidence). Oxygen reduced breathlessness measured during exercise tests (25 studies; 442 participants; SMD -0.34, 95% CI -0.46 to -0.22; I2 = 29%; moderate-quality evidence), whereas evidence of an effect on breathlessness measured in daily life was limited (two studies; 274 participants; SMD -0.13, 95% CI, -0.37 to 0.11; I2 = 0%; low-quality evidence). Oxygen did not clearly affect HRQOL (five studies; 267 participants; SMD 0.10, 95% CI -0.06 to 0.26; I2 = 0%; low-quality evidence). Patient preference and adverse events could not be analysed owing to insufficient data. Authors' conclusions: We are moderately confident that oxygen can relieve breathlessness when given during exercise to mildly hypoxaemic and non-hypoxaemic people with chronic obstructive pulmonary disease who would not otherwise qualify for home oxygen therapy. Most evidence pertains to acute effects during exercise tests, and no evidence indicates that oxygen decreases breathlessness in the daily life setting. Findings show that oxygen does not affect health-related quality of life

Comment on "First-principles study of the influence of (110)-oriented strain on the ferroelectric properties of rutile TiO2"

In a recent article, Gr\"{u}nebohm et al. [Phys. Rev. B 84 132105 (2011), arXiv:1106.2820] report that they fail to reproduce the A2u ferroelectric instability of TiO2 in the rutile structure calculated with density functional theory within the PBE-GGA approximation by Montanari et al. [Chem. Phys. Lett 364, 528 (2002)]. We demonstrate that this disagreement arises from an erroneous treatment of Ti 3s and 3p semi-core electrons as core in their calculations. Fortuitously the effect of the frozen semi-core pseudopotential cancels the phonon instability of the PBE exchange-correlation, and the combination yields phonon frequencies similar to the LDA harmonic values. Gr\"{u}nebohm et al. also attempted and failed to reproduce the soft acoustic phonon mode instability under (110) strain reported by Mitev et al. [Phys. Rev. B 81 134303 (2010)]. For this mode the combination of PBE-GGA and frozen semi-core yields a small imaginary frequency of 9.8i. The failure of Gr\"{u}nebohm et al. to find this mode probably arose from numerical limitations of the geometry optimization approach in the presence of a shallow double well potential; the optimization method is not suitable for locating such instabilities.Comment: 5 page