Numerical assessment on the effective mechanical stimuli for matrix-associated metabolism in chondrocyte-seeded constructs

The self-regeneration capacity of articular cartilage is limited, due to its avascular and aneural nature. Loaded explants and cell cultures demonstrated that chondrocyte metabolism can be regulated via physiologic loading. However, the explicit ranges of mechanical stimuli that correspond to favourable metabolic response associated with extracellular matrix (ECM) synthesis are elusive. Unsystematic protocols lacking this knowledge produce inconsistent results. This study aims to determine the intrinsic ranges of physical stimuli that increase ECM synthesis and simultaneously inhibit nitric oxide (NO) production in chondrocyte-agarose constructs, by numerically re-evaluating the experiments performed by Tsuang et al. (2008). Twelve loading patterns were simulated with poro-elastic finite element models in ABAQUS. Pressure on solid matrix, von Mises stress, maximum principle stress and pore pressure were selected as intrinsic mechanical stimuli. Their development rates and magnitudes at the steady state of cyclic loading were calculated with MATLAB at the construct level. Concurrent increase in glycosaminoglycan and collagen was observed at 2300 Pa pressure and 40 Pa/s pressure rate. Between 0-1500 Pa and 0-40 Pa/s, NO production was consistently positive with respect to controls, whereas ECM synthesis was negative in the same range. A linear correlation was found between pressure rate and NO production (R = 0.77). Stress states identified in this study are generic and could be used to develop predictive algorithms for matrix production in agarose-chondrocyte constructs of arbitrary shape, size and agarose concentration. They could also be helpful to increase the efficacy of loading protocols for avascular tissue engineering. Copyright (c) 2010 John Wiley \& Sons, Ltd.

A simple, economical, and effective portable paediatric mock circulatory system

Ventricular assist devices (VADs) and total artificial hearts have been in development for the last 50 years. Since their inception, simulators of the circulation with different degrees of complexity have been produced to test these devices in vitro. Currently, a new path has been taken with the extensive efforts to develop paediatric VADs, which require totally different design constraints. This paper presents the manufacturing details of an economical simulator of the systemic paediatric circulation. This simulator allows the insertion of a paediatric VAD, includes a pumping ventricle, and is adjustable within the paediatric range. Rather than focusing on complexity and physiological simulation, this simulator is designed to be simple and practical for rapid device testing. The simulator was instrumented with medical sensors and data were acquired under different conditions with and without the new PediaFlowTM paediatric VAD. The VAD was run at different impeller speeds while simulator settings such as vascular resistance and stroke volume were varied. The hydraulic performance of the VAD under pulsatile conditions could be characterized and the magnetic suspension could be tested via manipulations such as cannula clamping. This compact mock loop has proven to be valuable throughout the PediaFlow development process and has the advantage that it is uncomplicated and can be manufactured cheaply. It can be produced by several research groups and the results of different VADs can then be compared easily.

Effective population size of an indigenous Swiss cattle breed estimated from linkage disequilibrium

Effective population size is an important parameter for the assessment of genetic diversity within a livestock population and its development over time. If pedigree information is not available, linkage disequilibrium (LD) analysis might offer an alternative perspective for the estimation of effective population size. In this study, 128 individuals of the Swiss Eringer breed were genotyped using the Illumina BovineSNP50 beadchip. We set bin size at 50 kb for LD analysis, assuming that LD for proximal single nucleotide polymorphism (SNP)-pairs reflects distant breeding history while LD from distal SNP-pairs would reflect near history. Recombination rates varied among different regions of the genome. The use of physical distances as an approximation of genetic distances (e.g. setting 1 Mb = 0.01 Morgan) led to an upward bias in LD-based estimates of effective population size for generations beyond 50, while estimates for recent history were unaffected. Correction for restricted sample size did not substantially affect these results. LD-based actual effective population size was estimated in the range of 87-149, whereas pedigree-based effective population size resulted in 321 individuals. For conservation purposes, requiring knowledge of recent history (<50 generations), approximation assuming constant recombination rate seemed adequate.

Integrated psychological therapy (IPT) for schizophrenia: is it effective?

Against the background of evidence-based treatments for schizophrenia, nowadays the implementation of specific cognitive and behavioral interventions becomes more important in the standard care of these patients. Over the past 25 years, research groups in 9 countries have carried out 30 independent evaluations of Integrated Psychological Therapy (IPT), a group program that combines neurocognitive and social cognitive interventions with social skills approaches for schizophrenic patients. The aim of the present study was to evaluate the effectiveness of IPT under varying treatment and research conditions in academic and nonacademic sites. In a first step, all 30 published IPT studies with the participation of 1393 schizophrenic patients were included in the meta-analysis. In a second step, only high-quality studies (HQS) (7 studies including 362 patients) were selected and analyzed to check whether they confirmed the results of the first step. Positive mean effect sizes favoring IPT over control groups (placebo-attention conditions, standard care) were found for all dependent variables, including symptoms, psychosocial functioning, and neurocognition. Moreover, the superiority of IPT continued to increase during an average follow-up period of 8.1 months. IPT obtained similarly favorable effects across the different outcome domains, assessment formats (expert ratings, self-reports, and psychological tests), settings (inpatient vs outpatient and academic vs nonacademic), and phases of treatment (acute vs chronic). The HQS confirmed the results of the complete sample. The analysis indicates that IPT is an effective rehabilitation approach for schizophrenia that is robust across a wide range of patients and treatment conditions.

Esophageal strictures in adult eosinophilic esophagitis: dilation is an effective and safe alternative after failure of topical corticosteroids

Strictures are a frequent complication of eosinophilic esophagitis. The efficacy and safety of topical corticosteroids and of dilation of eosinophilic esophagitis-associated strictures have not yet been thoroughly clarified. We present a retrospective analysis of 10 adult patients with eosinophilic esophagitis who had symptomatic esophageal stenosis that was unresponsive to topical corticosteroids, and who were treated using bougienage. Eight patients had one single stricture, one patient had two, and another had three strictures; mean stricture length was 2.1 cm (range 1 - 6 cm). Bougienage led to prompt symptom relief. Apart from transient postprocedural odynophagia, no severe complications occurred. During the follow-up (mean 6 months; range 2 - 11 months), all patients enjoyed sustained treatment response.

Transcutaneous electrical nerve stimulation: an effective treatment for refractory non-neurogenic overactive bladder syndrome?

PURPOSE: To assess the effect of transcutaneous electrical nerve stimulation (TENS) for treating refractory overactive bladder syndrome (OAB). PATIENTS AND METHODS: A consecutive series of 42 patients treated with TENS for refractory OAB was prospectively investigated at an academic tertiary referral centre. Effects were evaluated using bladder diary for at least 48 h and satisfaction assessment at baseline, after 12 weeks of TENS treatment, and at the last known follow-up. Adverse events related to TENS were also assessed. RESULTS: Mean age of the 42 patients (25 women, 17 men) was 48 years (range, 18-76). TENS was successful following 12 weeks of treatment in 21 (50 %) patients, and the positive effect was sustained during a mean follow-up of 21 months (range, 6-83 months) in 18 patients. Following 12 weeks of TENS treatment, mean number of voids per 24 h decreased significantly from 15 to 11 (p < 0.001) and mean voided volume increased significantly from 160 to 230 mL (p < 0.001). In addition, TENS completely restored continence in 7 (39 %) of the 18 incontinent patients. Before TENS, all 42 patients were dissatisfied or very dissatisfied; following 12 weeks of TENS treatment, 21 (50 %) patients felt satisfied or very satisfied (p < 0.001). No adverse events related to TENS were noted. CONCLUSIONS: TENS seems to be an effective and safe treatment for refractory OAB warranting randomized, placebo-controlled trials.

Thiazolides, a Novel Class of Anti-Infective Drugs, Effective Against Viruses, Bacteria, Intracellular and Extracellular Protozoan Parasites and Proliferating Mammalian Cells

The thiazolide nitazoxanide (2-acetolyloxy-N-(5-nitro 2-thiazolyl) benzamide; NTZ) is composed of a nitrothiazole- ring and a salicylic acid moiety, which are linked together through an amide bond. NTZ exhibits a broad spectrum of activities against a wide range of helminths, protozoa, enteric bacteria, and viruses infecting animals and humans. Since the first synthesis of the drug, a number of derivatives of NTZ have been produced, which are collectively named thiazolides. These are modified versions of NTZ, which include the replacement of the nitro group with bromo-, chloro-, or other functional groups, and the differential positioning of methyl- and methoxy-groups on the salicylate ring. The presence of a nitro group seems to be the prerequisite for activities against anaerobic or microaerophilic parasites and bacteria. Intracellular parasites and viruses, however, are susceptible to non-nitro-thiazolides with equal or higher effectiveness. Moreover, nitro- and bromo-thiazolides are effective against proliferating mammalian cells. Biochemical and genetic approaches have allowed the identification of respective targets and the molecular basis of resistance formation. Collectively, these studies strongly suggest that NTZ and other thiazolides exhibit multiple mechanisms of action. In microaerophilic bacteria and parasites, the reduction of the nitro group into a toxic intermediate turns out to be the key factor. In proliferating mammalian cells, however, bromo- and nitro-thiazolides trigger apoptosis, which may also explain their activities against intracellular pathogens. The mode of action against helminths may be similar to mammalian cells but has still not been elucidated.

Numerical corrections to the strong coupling effective Polyakov-line action for finite T Yang-Mills theory

We consider a three-dimensional effective theory of Polyakov lines derived previously from lattice Yang-Mills theory and QCD by means of a resummed strong coupling expansion. The effective theory is useful for investigations of the phase structure, with a sign problem mild enough to allow simulations also at finite density. In this work we present a numerical method to determine improved values for the effective couplings directly from correlators of 4d Yang-Mills theory. For values of the gauge coupling up to the vicinity of the phase transition, the dominant short range effective coupling are well described by their corresponding strong coupling series. We provide numerical results also for the longer range interactions, Polyakov lines in higher representations as well as four-point interactions, and discuss the growing significance of non-local contributions as the lattice gets finer. Within this approach the critical Yang-Mills coupling β c is reproduced to better than one percent from a one-coupling effective theory on N τ = 4 lattices while up to five couplings are needed on N τ = 8 for the same accuracy.