The effect of galanin message-associated peptide in spinal sensory processing

The effect of Galanin Message-Associated Peptide in spinal sensoryprocessing Galanin message associated peptide (GMAP), the C-terminal flanking peptide inthe precursor protein of galanin, has been studied to established whether this peptidehas its own biological action. With some exceptions, GMAP is generally colocalizedwith galanin in the central nervous system as well as the peripheral nervous system.This study was focused on the effect of GMAP in spinal sensory processing and identificationof endogenously occurring fragments of GMAP. Nerve injury is one incident which regulatesthe expression of the precursor protein of galanin/GMAP. Two weeks after axotomyof the sciatic nerve in rat the effect of intrathecal GMAP on the flexor reflex becomesaltered in comparison to animals with intact sciatic nerves. The effect of GMAP onbaseline flexor reflex was not changed, but the effect on the facilitation inducedby conditioning stimuli (CS) was strongly decreased and GMAP could only weakly antagonisethe facilitation. This was incontrast to the dose dependent manner GMAP antagonisedthe effect of CS in animals with intact sciatic nerves. Interactions with substanceP (SP) and vasoactive intestinal peptide (VIP) effects in the flexor reflex werealso changed after axotomy. SP-induced excitation of the flexor reflex was not inhibitedby GMAP following axotomy as it was in normal rats. In contrast, the effect of VIPwas antagonised in axotomized animals by GMAP. Modulation by putative synthetic fragmentsof GMAP of the flexor reflex were investigated. At least two of the fragments exertsignificant pharmacological activity. In degradation studies of GMAP in vitro, fivedegradation products were isolated with high performance liquid chromatography. Theiramino acids composition were analysed. The pharmacological effects of the fragmentswere studied in the flexor reflex and were shown to partially mimick the effectsof the whole GMAP sequence. GMAP mediated effect on adenylate cyclase and guanylatecyclase were examined to evaluate the coupling to G-protein connected receptors.GMAP had poor affinity to the galanin receptor with a ICso value on 104 M. GMAP wassynthesized by solid phase method in the beginning of this project, which createda lot of problem with very low yield of the peptide. Recently we successfully expressedrecombinant GMAP with the QIAGEN expression system which will open possibilitiesto further studies of GMAP in the future. Key words: galanin, galanin message-associated peptide, spinal cord, flexor reflex,nociception ISBN 91-628-2656-

Consumer Perceptions and Preferences on Solid Wood, Wood-Based Panels, and Composites: A Repertory Grid Study

Knowledge about consumer perception and preferences on solid wood, wood-based panels, and wood-based composites is important for product development and marketing. The aim of this study was to identify attributes and associations that people use to describe different types of wood materials and to explore how they relate to preferences. The study involved nine samples that were evaluated with the Kelly's repertory grid technique and content analysis. Based on respondents' answers, 19 core categories reflecting sample attributes were extracted. General preferences for each sample were also recorded. Principal component analysis generated two factors describing 1) naturalness, wood-likeness, softness, unprocessed origin, living, pleasant, and high value; and 2) solid and homogeneous impression. A third, preliminary factor included categories describing irregular pattern, sleekness, and smoothness. The wood samples were most liked, whereas composites and panels were not appreciated. Preferred core categories were naturalness, wood-likeness, smoothness, living impression, and value. The least liked core categories were processed, hard, and high weight. The implications of the results for product development and marketing are discussed

Starch Microstructure and Starch Hydrolysis in Barley and Oat Tempe During In Vitro Digestion.

Various botanical and structural characteristics of starchy foods are considered to modify the rate of starch digestion and the glycaemic responses in humans. The main objective of the study was to examine the impact of fermented barley and oat microstructure on the rate of in vitro starch hydrolysis. A dynamic gastrointestinal model was used to estimate the degree of starch hydrolysis during in vitro digestion of fermented whole grain cereal meals. Light microscopy and confocal laser scanning microscopy were used to study the microstructural changes. In parallel to the in vitro studies, the impact of fermented barley and oats on postprandial plasma glucose responses was evaluated in a human study. Micrographs were taken during in vitro digestion experiments with fermented whole grains and compared with micrographs of boiled barley (undigested). Images showed that most of the oat starch granules were degraded after 120 min of digestion, whereas barley starch granules were less degraded, even after 180 min of digestion. The findings were confirmed by faster starch hydrolysis from the fermented oat meal, measured as maltose generated during in vitro digestion. The area under the curve (AUC) was calculated from the plotted maltose curves of the meals. AUC for barley tempe (266 \ub1 33) was 40 % of the AUC for oat tempe (663 \ub1 8) and significantly different (

Starch microstructure and starch hydrolysis in barley and oat tempe during in vitro digestion

Various botanical and structural characteristics of starchy foods are considered to modify the rate of starch digestion and the glycaemic responses in humans. The main objective of the study was to examine the impact of fermented barley and oat microstructure on the rate of in vitro starch hydrolysis. A dynamic gastrointestinal model was used to estimate the degree of starch hydrolysis during in vitro digestion of fermented whole grain cereal meals. Light microscopy and confocal laser scanning microscopy were used to study the microstructural changes. In parallel to the in vitro studies, the impact of fermented barley and oats on postprandial plasma glucose responses was evaluated in a human study. Micrographs were taken during in vitro digestion experiments with fermented whole grains and compared with micrographs of boiled barley (undigested). Images showed that most of the oat starch granules were degraded after 120 min of digestion, whereas barley starch granules were less degraded, even after 180 min of digestion. The findings were confirmed by faster starch hydrolysis from the fermented oat meal, measured as maltose generated during in vitro digestion. The area under the curve (AUC) was calculated from the plotted maltose curves of the meals. AUC for barley tempe (266 \ub1 33) was 40 % of the AUC for oat tempe (663 \ub1 8) and significantly different (

Association between sports participation, factor VIII levels and bleeding in hemophilia A

Background Little is known on how sports participation affects bleeding risk in hemophilia. This study aimed to examine associations between sports participation, factor VIII (FVIII) levels and bleeding in persons with hemophilia A. Methods In this observational, prospective, single-center study, persons with hemophilia A who regularly participated in sports were followed for 12 months. The associations of patient characteristics, FVIII levels, and type/frequency of sports participation with bleeding were analyzed by repeated time-to-event modelling. Results One hundred and twelve persons (median age: 24 years [interquartile range:16 34], 49% severe, 49% on prophylaxis) were included. During follow-up, 70 bleeds of which 20 sports-induced were observed. FVIII levels were inversely correlated with the bleeding hazard; a 50% reduction of the baseline bleeding hazard was observed at FVIII levels of 3.1 and a 90% reduction at 28.0 IU/dL. The bleeding hazard did not correlate with sports participation. In addition, severe hemophilia, prestudy annual bleeding rate, and presence of arthropathy showed a positive association with the bleeding hazard. Conclusion This analysis showed that FVIII levels were an important determinant of the bleeding hazard, but sports participation was not. This observation most likely reflects the presence of adequate FVIII levels during sports participation in our study. Persons with severe hemophilia A exhibited a higher bleeding hazard at a similar FVIII levels than nonsevere, suggesting that the time spent at lower FVIII levels impacts overall bleeding hazard. These data may be used to counsel persons with hemophilia regarding sports participation and the necessity of adequate prophylaxis

Antibiotics should not be used for back/leg pain

Antibiotics have been suggested as treatment for selected patients with chronic back pain, with or without leg pain, and in association with Modic changes type 1 (MC1) on MRI (Modic et al. 1988, Albert et al. 2013a). The hypothesis is that various bacteria, but above all the common skin bacterium Cutibacterium acnes (formerly Propionibacterium acnes), would spread hematogenously to degenerated discs, where a “low-grade subclinical infection” would trigger an inflammatory reaction and cause MC1 (Albert et al. 2013a), irritate nociceptive nerve endings, and induce pain. Other studies have not found this connection, or have been cautious in their conclusions (Birkenmaier 2013, Urquhart et al. 2015) but have not had the same public impact. Since back/leg pain is common, and Modic changes occur in people with or without back/leg pain (Wang et al. 2012), and as antibiotic resistance is a major health threat (Carlsson et al. 2019), the suggestion of treating chronic back/leg pain with antibiotics must be thoroughly investigated. Research groups in Sweden, Denmark, and Norway have independently conducted studies from 3 different perspectives, but with a focus on the same basic questions: is there a causative link between Modic changes, back pain, and bacteria. The studies, all published during 2019, conclude that antibiotics should not be used for back/leg pain, unless there is a clinically relevant infection in the disc/vertebra (discitis/spondylitis)

Bacteria: back pain, leg pain and Modic sign-a surgical multicentre comparative study

Purpose To compare bacterial findings in pain-generating degenerated discs in adults operated on for lumbar disc herniation (LDH), and mostly also suffering from low back pain (LBP), with findings in adolescent patients with non-degenerated non-pain-generating discs operated on for scoliosis, and to evaluate associations with Modic signs on magnetic resonance imaging (MRI). Cutibacterium acnes (Propionibacterium acnes) has been found in painful degenerated discs, why it has been suggested treating patients with LDH/LBP with antibiotics. As multidrug-resistant bacteria are a worldwide concern, new indications for using antibiotics should be based on solid scientific evidence. Methods Between 2015 and 2017, 40 adults with LDH/LBP (median age 43, IQR 33-49) and 20 control patients with scoliosis (median age 17, IQR 15-20) underwent surgery at seven Swedish hospitals. Samples were cultured from skin, surgical wound, discs and vertebrae. Genetic relatedness of C. acnes isolates was investigated using single-nucleotide polymorphism analysis. DNA samples collected from discs/vertebrae were analysed using 16S rRNA-based PCR sequencing. MRI findings were assessed for Modic changes. Results No bacterial growth was found in 6/40 (15%) LDH patients, compared with 3/20 (15%) scoliosis patients. Most positive samples in both groups were isolated from the skin and then from subcutis or deep within the wound. Of the four disc and vertebral samples from each of the 60 patients, 235/240 (98%) were DNA negative by bacterial PCR. A single species, C. acnes, was found exclusively in the disc/vertebra from one patient in each group. In the LDH group, 29/40 (72%) patients had at least one sample with growth of C. acnes, compared to 14/20 (70%) in the scoliosis group. Bacterial findings and Modic changes were not associated. Conclusions Cutibacterium acnes found in discs and vertebrae during surgery for disc herniation in adults with degenerated discs may be caused by contamination, as findings in this group were similar to findings in a control group of young patients with scoliosis and non-degenerated discs. Furthermore, such findings were almost always combined with bacterial findings on the skin and/or in the wound. There was no association between preoperative Modic changes and bacterial findings. Antibiotic treatment of lumbar disc herniation with sciatica and/or low back pain, without signs of clinical discitis/spondylitis, should be seriously questioned.Funding Agencies|FORSS, a Swedish regional research foundation</p

The back-step method—Method for obtaining unbiased population parameter estimates for ordered categorical data

A significant bias in parameters, estimated with the proportional odds model using the software NONMEM, has been reported. Typically, this bias occurs with ordered categorical data, when most of the observations are found at one extreme of the possible outcomes. The aim of this study was to assess, through simulations, the performance of the Back-Step Method (BSM), a novel approach for obtaining unbiased estimates when the standard approach provides biased estimates. BSM is an iterative method involving sequential simulation-estimation steps. BSM was compared with the standard approach in the analysis of a 4-category ordered variable using the Laplacian method in NONMEM. The bias in parameter estimates and the accuracy of model predictions were determined for the 2 methods on 3 conditions: (1) a nonskewed distribution of the response with low interindividual variability (IIV), (2) a skewed distribution with low IIV, and (3) a skewed distribution with high IIV. An increase in bias with increasing skewness and IIV was shown in parameters estimated using the standard approach in NON-MEM. BSM performed without appreciable bias in the estimates under the 3 conditions, and the model predictions were in good agreement with the original data. Each BSM estimation represents a random sample of the population; hence, repeating the BSM estimation reduces the imprecision of the parameter estimates. The BSM is an accurate estimation method when the standard modeling approach in NONMEM gives biased estimates