Investigation of fiber/matrix adhesion: test speed and specimen shape effects in the cylinder test

The cylinder test, developed from the microdroplet test, was adapted to assess the interfacial adhesion strength between fiber and matrix. The sensitivity of cylinder test to pull-out speed and specimen geometry was measured. It was established that the effect of test speed can be described as a superposition of two opposite, simultaneous effects which have been modeled mathematically by fitting two parameter Weibull curves on the measured datas. Effects of the cylinder size and its geometrical relation on the measured strength values have been analyzed by finite element method. It was concluded that the geometry has a direct influence on the stress formation. Based on the results achieved, recommendations were given on how to perform the novel single fiber cylinder test

Interleukin 2-regulated in vitro antibody production following a single spinal manipulative treatment in normal subjects

<p>Abstract</p> <p>Background</p> <p>Our recent investigations have demonstrated that cell cultures from subjects, who received a single spinal manipulative treatment in the upper thoracic spine, show increased capacity for the production of the key immunoregulatory cytokine, interleukin-2. However, it has not been determined if such changes influence the response of the immune effector cells. Thus, the purpose of the present study was to determine whether, in the same subjects, spinal manipulation-related augmentation of the <it>in vitro </it>interleukin-2 synthesis is associated with the modulation of interleukin 2-dependent and/or interleukin-2-induced humoral immune response (antibody synthesis).</p> <p>Methods</p> <p>A total of seventy-four age and sex-matched healthy asymptomatic subjects were studied. The subjects were assigned randomly to: venipuncture control (n = 22), spinal manipulative treatment without cavitation (n = 25) or spinal manipulative treatment associated with cavitation (n = 27) groups. Heparinized blood samples were obtained from the subjects before (baseline) and then at 20 minutes and 2 hours post-treatment. Immunoglobulin (antibody) synthesis was induced in cultures of peripheral blood mononuclear cells by stimulation with conventional pokeweed mitogen or by application of human recombinant interleukin-2. Determinations of the levels of immunoglobulin G and immunoglobulin M production in culture supernatants were performed by specific immunoassays.</p> <p>Results</p> <p>The baseline levels of immunoglobulin synthesis induced by pokeweed mitogen or human recombinant interleukin-2 stimulation were comparable in all groups. No significant changes in the production of pokeweed mitogen-induced immunoglobulins were observed during the post-treatment period in any of the study groups. In contrast, the production of interleukin-2 -induced immunoglobulin G and immunoglobulin M was significantly increased in cultures from subjects treated with spinal manipulation. At 20 min post-manipulation, immunoglobulin G synthesis was significantly elevated in subjects who received manipulation with cavitation, relative to that in cultures from subjects who received manipulation without cavitation and venipuncture alone. At 2 hr post-treatment, immunoglobulin M synthesis was significantly elevated in subjects who received manipulation with cavitation relative to the venipuncture group. There were no quantitative alterations within the population of peripheral blood B or T lymphocytes in the studied cultures.</p> <p>Conclusion</p> <p>Spinal manipulative treatment does not increase interleukin-2 -dependent polyclonal immunoglobulin synthesis by mitogen-activated B cells. However, antibody synthesis induced by interleukin-2 alone can be, at least temporarily, augmented following spinal manipulation. Thus, under certain physiological conditions spinal manipulative treatment might influence interleukin-2 -regulated biological responses.</p

Patterns of analgesic use, pain and self-efficacy: a cross-sectional study of patients attending a hospital rheumatology clinic

Background: Many people attending rheumatology clinics use analgesics and non-steroidal anti-inflammatories for persistent musculoskeletal pain. Guidelines for pain management recommend regular and pre-emptive use of analgesics to reduce the impact of pain. Clinical experience indicates that analgesics are often not used in this way. Studies exploring use of analgesics in arthritis have historically measured adherence to such medication. Here we examine patterns of analgesic use and their relationships to pain, self-efficacy and demographic factors. Methods: Consecutive patients were approached in a hospital rheumatology out-patient clinic. Pattern of analgesic use was assessed by response to statements such as 'I always take my tablets every day.' Pain and self-efficacy (SE) were measured using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and Arthritis Self-Efficacy Scale (ASES). Influence of factors on pain level and regularity of analgesic use were investigated using linear regression. Differences in pain between those agreeing and disagreeing with statements regarding analgesic use were assessed using t-tests. Results: 218 patients (85% of attendees) completed the study. Six (2.8%) patients reported no current pain, 26 (12.3%) slight, 100 (47.4%) moderate, 62 (29.4%) severe and 17 (8.1%) extreme pain. In multiple linear regression self efficacy and regularity of analgesic use were significant (p < 0.01) with lower self efficacy and more regular use of analgesics associated with more pain. Low SE was associated with greater pain: 40 (41.7%) people with low SE reported severe pain versus 22 (18.3%) people with high SE, p < 0.001. Patients in greater pain were significantly more likely to take analgesics regularly; 13 (77%) of those in extreme pain reported always taking their analgesics every day, versus 9 (35%) in slight pain. Many patients, including 46% of those in severe pain, adjusted analgesic use to current pain level. In simple linear regression, pain was the only variable significantly associated with regularity of analgesic use: higher levels of pain corresponded to more regular analgesic use (p = 0.003). Conclusion: Our study confirms that there is a strong inverse relationship between self-efficacy and pain severity. Analgesics are often used irregularly by people with arthritis, including some reporting severe pain

Dosage Regulation of the Active X Chromosome in Human Triploid Cells

In mammals, dosage compensation is achieved by doubling expression of X-linked genes in both sexes, together with X inactivation in females. Up-regulation of the active X chromosome may be controlled by DNA sequence–based and/or epigenetic mechanisms that double the X output potentially in response to autosomal factor(s). To determine whether X expression is adjusted depending on ploidy, we used expression arrays to compare X-linked and autosomal gene expression in human triploid cells. While the average X:autosome expression ratio was about 1 in normal diploid cells, this ratio was lower (0.81–0.84) in triploid cells with one active X and higher (1.32–1.4) in triploid cells with two active X's. Thus, overall X-linked gene expression in triploid cells does not strictly respond to an autosomal factor, nor is it adjusted to achieve a perfect balance. The unbalanced X:autosome expression ratios that we observed could contribute to the abnormal phenotypes associated with triploidy. Absolute autosomal expression levels per gene copy were similar in triploid versus diploid cells, indicating no apparent global effect on autosomal expression. In triploid cells with two active X's our data support a basic doubling of X-linked gene expression. However, in triploid cells with a single active X, X-linked gene expression is adjusted upward presumably by an epigenetic mechanism that senses the ratio between the number of active X chromosomes and autosomal sets. Such a mechanism may act on a subset of genes whose expression dosage in relation to autosomal expression may be critical. Indeed, we found that there was a range of individual X-linked gene expression in relation to ploidy and that a small subset (∼7%) of genes had expression levels apparently proportional to the number of autosomal sets

First administration to man of Org 25435, an intravenous anaesthetic: A Phase 1 Clinical Trial

BACKGROUND: Org 25435 is a new water-soluble alpha-amino acid ester intravenous anaesthetic which proved satisfactory in animal studies. This study aimed to assess the safety, tolerability and efficacy of Org 25435 and to obtain preliminary pharmacodynamic and pharmacokinetic data. METHODS: In the Short Infusion study 8 healthy male volunteers received a 1 minute infusion of 0.25, 0.5, 1.0, or 2.0 mg/kg (n = 2 per group); a further 10 received 3.0 mg/kg (n = 5) or 4.0 mg/kg (n = 5). Following preliminary pharmacokinetic modelling 7 subjects received a titrated 30 minute Target Controlled Infusion (TCI), total dose 5.8-20 mg/kg. RESULTS: Within the Short Infusion study, all subjects were successfully anaesthetised at 3 and 4 mg/kg. Within the TCI study 5 subjects were anaesthetised and 2 showed signs of sedation. Org 25435 caused hypotension and tachycardia at doses over 2 mg/kg. Recovery from anaesthesia after a 30 min administration of Org 25435 was slow (13.7 min). Pharmacokinetic modelling suggests that the context sensitive half-time of Org 25435 is slightly shorter than that of propofol in infusions up to 20 minutes but progressively longer thereafter. CONCLUSIONS: Org 25435 is an effective intravenous anaesthetic in man at doses of 3 and 4 mg/kg given over 1 minute. Longer infusions can maintain anaesthesia but recovery is slow. Hypotension and tachycardia during anaesthesia and slow recovery of consciousness after cessation of drug administration suggest this compound has no advantages over currently available intravenous anaesthetics

Logical gates in actin monomer

© 2017 The Author(s). We evaluate information processing capacity of a single actin molecule by calculating distributions of logical gates implemented by the molecule via propagating patterns of excitation. We represent a filamentous actin molecule as an excitable automaton network (F-actin automaton). where every atom updates its state depending on states of atoms its connected to with chemical bonds (hard neighbours) and atoms being in physical proximity to the atom (soft neighbours). A resting atom excites if a sum of its excited hard neighbours and a weighted sum of its soft neighbours belong to some specified interval. We demonstrate that F-actin automata implement OR, AND, XOR and AND-NOT gates via interacting patterns of excitation. Gate AND is the most common gate and gate XOR is the rarest. Using the architectures of gates discovered we implement one bit half-adder and controlled-not circuits in the F-actin automata. Speed and space values of the F-actin molecular computers are discussed

Ablation of Mrds1/Ofcc1 Induces Hyper-γ-Glutamyl Transpeptidasemia without Abnormal Head Development and Schizophrenia-Relevant Behaviors in Mice

Mutations in the Opo gene result in eye malformation in medaka fish. The human ortholog of this gene, MRDS1/OFCC1, is a potentially causal gene for orofacial cleft, as well as a susceptibility gene for schizophrenia, a devastating mental illness. Based on this evidence, we hypothesized that this gene could perform crucial functions in the development of head and brain structures in vertebrates. To test this hypothesis, we created Mrds1/Ofcc1-null mice. Mice were examined thoroughly using an abnormality screening system referred to as “the Japan Mouse Clinic”. No malformations of the head structure, eye or other parts of the body were apparent in these knockout mice. However, the mutant mice showed a marked increase in serum γ-glutamyl transpeptidase (GGT), a marker for liver damage, but no abnormalities in other liver-related measurements. We also performed a family-based association study on the gene in schizophrenia samples of Japanese origin. We found five single nucleotide polymorphisms (SNPs) located across the gene that showed significant transmission distortion, supporting a prior report of association in a Caucasian cohort. However, the knockout mice showed no behavioral phenotypes relevant to schizophrenia. In conclusion, disruption of the Mrds1/Ofcc1 gene elicits asymptomatic hyper-γ-glutamyl-transpeptidasemia in mice. However, there were no phenotypes to support a role for the gene in the development of eye and craniofacial structures in vertebrates. These results prompt further examination of the gene, including its putative contribution to hyper-γ-glutamyl transpeptidasemia and schizophrenia

Oynophagia in patients after dental extraction: surface electromyography study

OBJECTIVES: Surface electromyographic (sEMG) studies were performed on 40 adult patients following extraction of lower third and second molars to research the approach and limitations of sEMG evaluation of their odynophagia complaints. METHODS: Parameters evaluated during swallowing and drinking include the timing, number of swallows per 100 cc of water, and range (amplitude) of EMG activity of m. masseter, infrahyoid and submental-submandibular group. The above mentioned variables (mean + standard deviation) were measured for the group of dental patients (n = 40) and control group of healthy adults (n = 40). RESULTS: The duration of swallows and drinking in all tests showed increase in dental patients' group, in which this tendency is statistically significant. There was no statistically significant difference between male and female adults' duration and amplitude of muscle activity during continuous drinking in both groups (p = 0.05). The mean of electric activity (in μV) of m. masseter was significantly lower in the dental patients' group in comparison with control group. The electric activity of submental-submandimular and infrahyoid muscle groups was the same in both groups. CONCLUSION: Surface EMG of swallowing is a simple and reliable noninvasive method for evaluation of odynophagia/dysphagia complaints following dental extraction with low level of discomfort of the examination. The surface EMG studies prove that dysphagia following dental extraction and molar surgery has oral origin, does not affect pharingeal segment and submental-submandibular muscle group. This type of dysphagia has clear EMG signs: increased duration of single swallow, longer drinking time, low range of electric activity of m. masseter, normal range of activity of submental-submandibular muscle group, and the "dry swalow" aftereffect. The data can be used for evaluation of complaints and symptoms, as well as for comparison purposes in pre- and postoperative stages and in EMG monitoring during treatment of post-surgical oral cavity discomfort and dysphagia

A cross-national study on the antecedents of work–life balance from the fit and balance perspective

Drawing on the perceived work–family fit and balance perspective, this study investigates demands and resources as antecedents of work–life balance (WLB) across four countries (New Zealand, France, Italy and Spain), so as to provide empirical cross-national evidence. Using structural equation modelling analysis on a sample of 870 full time employees, we found that work demands, hours worked and family demands were negatively related to WLB, while job autonomy and supervisor support were positively related to WLB. We also found evidence that resources (job autonomy and supervisor support) moderated the relationships between demands and work–life balance, with high resources consistently buffering any detrimental influence of demands on WLB. Furthermore, our study identified additional predictors of WLB that were unique to some national contexts. For example, in France and Italy, overtime hours worked were negatively associated with WLB, while parental status was positively associated with WLB. Overall, the implications for theory and practice are discussed.Peer ReviewedPostprint (author's final draft

Future therapeutic targets in rheumatoid arthritis?

Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by persistent joint inflammation. Without adequate treatment, patients with RA will develop joint deformity and progressive functional impairment. With the implementation of treat-to-target strategies and availability of biologic therapies, the outcomes for patients with RA have significantly improved. However, the unmet need in the treatment of RA remains high as some patients do not respond sufficiently to the currently available agents, remission is not always achieved and refractory disease is not uncommon. With better understanding of the pathophysiology of RA, new therapeutic approaches are emerging. Apart from more selective Janus kinase inhibition, there is a great interest in the granulocyte macrophage-colony stimulating factor pathway, Bruton's tyrosine kinase pathway, phosphoinositide-3-kinase pathway, neural stimulation and dendritic cell-based therapeutics. In this review, we will discuss the therapeutic potential of these novel approaches