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PubMedDate not supplied

Fructosamine measurement in ponies: validation and response following experimental cyathostome infection.

Validation of an assay for measurement of fructosamine in equine serum and plasma utilised blood samples collected from 24 British native breed ponies. The results indicated that fructosamine can be measured easily using an assay which is precise and accurate. Paired plasma and serum fructosamine measurements were highly correlated, however, greater variations were observed within serum compared with those in plasma. A reference range for fructosamine in plasma was calculated to be 256.9 +/- 60.6 mumol litre-1 (mean +/- 2 SD). In order to assess the fructosamine response following experimental cyathostome infection, nine British native breed ponies were allocated to one of three groups: Group 1 (3.9 million third-stage cyathostome larvae (L3) over a nine-week-period), Group 2 (3.15 million L3 over seven weeks) and Group 3 (uninfected controls). From four weeks prior to infection, blood was obtained, once weekly, from all animals for measurement of plasma fructosamine, plasma albumin and serum globulin concentrations. Plasma fructosamine concentrations decreased in all infected ponies post-infection due to enteric protein loss and/or altered protein composition and/or increased protein turnover.

Aging↗

PubMed2000

A spot check for estimating stereophotogrammetric errors.

Good practice rules in the management of a movement analysis laboratory recommend that photogrammetric measurement errors are assessed, prior to every experimental session, using an ad hoc experiment referred to as a spot check. The paper proposes an inexpensive and easy to make spot check. The test uses a rigid rod carrying two markers and a target point taken on the line joining them and coinciding with the rod tip. The latter point is placed in a fixed and measured position in the laboratory frame and the markers are tracked while the rod is kept stationary and while it is manually made to rotate about the target point. Several target points are used within the measurement volume. The instantaneous errors with which the laboratory co-ordinates of the latter points are reconstructed are determined and submitted to statistical analysis. A normalisation procedure is illustrated that aims at making the test results independent from the geometry of the test object. The experimental and analytical methods underlying the proposed spot check were validated experimentally in two movement analysis laboratories using repeated tests. A rod, 1.5 m long, carrying four markers was used. In this way, several test-object geometries were tested. Results confirmed that the photogrammetric error could be divided into a zero-mean random and a systematic component. It was shown that the normalisation procedure was effective for the standard deviation of both error components when the two markers were located at a distance between them 1.5 times larger than the distance of their centroid from the tip of the rod. The systematic component bias could not be normalised, however a conservative value of it could be estimated. The two above-mentioned normalised standard deviations and the bias value can be taken as descriptors of the photogrammetric error of the specific measuring system tested. These parameters may also be used to assess the precision and the accuracy with which the laboratory position of a target point, defined relative to any specified marker cluster, may be reconstructed during movement analysis.

Humans↗

PubMed2026

Identification of potential key genes involved in iron deficiency for sepsis: A retrospective cohort and transcriptomic study.

Iron overload has been associated with sepsis, but the role of iron deficiency and its molecular links remain unclear. We investigated the association between iron deficiency and sepsis and identified candidate genes potentially linking these conditions. MIMIC-IV data were used to assess the association between serum iron and sepsis status. Transcriptomic datasets from dietary iron-deficient mice (GSE10421), LPS-induced septic mice (GSE267388), and a human blood sepsis cohort (GSE137340) were sequentially analyzed to identify and externally evaluate candidate genes. IEU Open GWAS summary statistics were used for exploratory Mendelian randomization (MR). Exploratory drug prediction was performed using L1000FWD, followed by molecular docking analysis. Patients with sepsis had significantly lower serum iron levels, and restricted cubic spline analysis showed a nonlinear association between serum iron and the odds of sepsis. Cross-tissue transcriptomic analysis identified Sqle, Lss, and Rdh11 as candidate genes. In the human blood cohort, SQLE and RDH11 were significantly increased, whereas LSS was not significantly altered. Exploratory MR showed that genetically proxied SQLE expression was associated with higher odds of sepsis (odds ratio [OR] = 1.23, P = 1.67 × 10-3), whereas LSS expression was associated with lower odds (OR = 0.97, P = 8.90 × 10-4); RDH11 showed no significant association (OR = 1.01, P = .90). Drug prediction identified ML106 as the top-ranked candidate drug, and molecular docking predicted potential binding poses with SQLE and LSS. Serum iron showed a nonlinear association with sepsis status. SQLE, LSS, and RDH11 emerged as candidate genes, with concordant expression changes of SQLE and RDH11 observed in human blood. MR findings for SQLE and LSS were exploratory and require further validation. ML106 was identified through exploratory drug prediction and requires experimental validation before its therapeutic relevance can be established.

Sepsis↗

PubMed2026

Redox Rewiring in Nicotine-Driven Gastric Carcinogenesis: Uncovering ROS-Dependent Oncogenic Circuits.

SIGNIFICANCE: Nicotine from tobacco products, secondhand smoke, and emerging delivery systems remains a major but underappreciated driver of gastric carcinogenesis (GC). Although reactive oxygen species (ROS) have long been implicated in tumor biology, current models incompletely explain how chronic nicotine selectively reprograms gastric epithelial signaling. This review advances the concept of redox rewiring, whereby nicotine establishes a persistent oxidative state that orchestrates multiple oncogenic programs via spatially compartmentalized NOX signaling. RECENT ADVANCES: We synthesize evidence for a unified model wherein nicotine activates nAChR/β-AR signaling, Ca2+ influx, PKC, and compartmentalized NOX-derived ROS to generate distinct oncogenic outputs. Beyond the established NOX/ROS/NF-κB/MAPK-driven IL-8 and MMP-9 axes, we integrate emerging evidence into three interconnected modules governing EMT/metastasis (ABL1/STAT3/COX-2/periostin), survival/chemoresistance (ERK/GLI1/Bcl-2), and invasion/immune evasion (miR-21/PDCD4). Collectively, these circuits suggest that ROS function not merely as damaging byproducts but as spatially organized signaling mediators dictating tumor behavior. CRITICAL ISSUES: A major challenge is distinguishing established mechanisms from incompletely validated models. The three proposed axes are testable hypotheses requiring experimental validation. Most data derive from in vitro studies with nonphysiologic nicotine concentrations, and artifacts from nonspecific ROS probes are common. Compensatory pathway activation and multi-target effects of natural products remain underexplored. FUTURE DIRECTIONS: We outline a precision-redox oncology roadmap linking pathway-specific biomarkers, mechanistically matched natural products, and biomarker-enriched trials. Priorities include genetic validation of the three axes, time-resolved ROS imaging, and pulsed natural product regimens. By reframing nicotine-driven GC as adaptive redox network remodeling, this review provides a framework for prevention, stratification, and next-generation therapy. Antioxid. Redox Signal. 00, 000-000.

gastric cancer↗

PubMed2005

Gene finding in the chicken genome.

BACKGROUND: Despite the continuous production of genome sequence for a number of organisms, reliable, comprehensive, and cost effective gene prediction remains problematic. This is particularly true for genomes for which there is not a large collection of known gene sequences, such as the recently published chicken genome. We used the chicken sequence to test comparative and homology-based gene-finding methods followed by experimental validation as an effective genome annotation method. RESULTS: We performed experimental evaluation by RT-PCR of three different computational gene finders, Ensembl, SGP2 and TWINSCAN, applied to the chicken genome. A Venn diagram was computed and each component of it was evaluated. The results showed that de novo comparative methods can identify up to about 700 chicken genes with no previous evidence of expression, and can correctly extend about 40% of homology-based predictions at the 5' end. CONCLUSIONS: De novo comparative gene prediction followed by experimental verification is effective at enhancing the annotation of the newly sequenced genomes provided by standard homology-based methods.

Animals↗

PubMed1997

Effect of the selective serotonin reuptake inhibitor fluvoxamine on CCK-4 induced panic attacks.

Data from animal studies suggest a functional relationship between the cholecystokinin-ergic (CCK) and the serotonergic (5-HT) system. There is increasing evidence that the cholecystokinin-4 (CCK4) challenge test could be a valid experimental model for panic attacks in man. The aim of the present study is twofold; 1) to validate this model further and 2) to shed more light on the putative CCK/5-HT interaction. To this end, we studied the effect of the selective serotonin reuptake inhibitor (SSRI) fluvoxamine on CCK4-induced panic attacks. Twenty-six panic disorder (PD) patients received, before and after a double blind 8-week treatment period with fluvoxamine (n = 17) or placebo (n = 9), a single blind bolus injection with 50 micrograms CCK4. Treatment with fluvoxamine (150 mg daily) significantly decreased the sensitivity of PD patients for CCK4 while placebo was without effect. Of the patients who responded to treatment, 83% no longer experienced a panic attack when rechallenged with CCK4, whereas in the non-responders group this was only 28%. In the fluvoxamine group the treatment response evaluated by the Hamilton Anxiety Scale (HAS) showed a statistically significant treatment effect. The results of this study strengthen the validity of the CCK4 test as an experimental human model for panic attacks and yield evidence supporting the hypothesis that both CCK and serotonin are implicated in the regulation of anxiety.

Adult↗

PubMed1978

A probabilistic model of intensive designs.

Without internal validity, experimental data are uninterpretable. With intensive designs, most methods presented to quantify a design's internal validity have been subject to criticism. A probabilistic model of intensive designs is presented that demonstrates the high degree of internal validity of these designs without relying on adaptations from traditional inferential statistics. Where the experimenter is able to conform to the restrictions of the model, the equations provide an estimation of internal validity for either reversal or multiple-baseline designs. More importantly, the model provides mathematical bases for some of the common recommendations and design considerations in intensive research (such as the desirability of within-subject replications and of four or more multiple baselines).

Journal Article↗

PubMed2004

An optimised split-and-recombine micro-mixer with uniform chaotic mixing.

A second generation micro-mixer, being a further optimised version of a first prototype, relying on the consequent utilisation of the split-and-recombine principle is presented. We show that the mixing can be characterized by a positive finite-time Lyapunov exponent although being highly regular and uniform. Using computational fluid dynamics (CFD) we investigate the mixing performance for Reynolds numbers in the range of about 1 to about 100. In particular for low Reynolds numbers (Re < 15) the CFD results predict an almost ideal multi-lamination. Thus, the developed mixer is especially suited for efficient mixing of highly viscous fluids. Furthermore, the numerical results are experimentally validated by investigations of mixing of water-glycerol solutions. The experimental results are found to be in excellent agreement with the numerical data and prove the high mixing efficiency.

Journal Article↗

PubMed2000

Pressure-derived fractional flow reserve to assess serial epicardial stenoses: theoretical basis and animal validation.

Background-Fractional flow reserve (FFR) is an index of stenosis severity validated for isolated stenoses. This study develops the theoretical basis and experimentally validates equations for predicting FFR of sequential stenoses separately. Methods and Results-For 2 stenoses in series, equations were derived to predict FFR (FFR(pred)) of each stenosis separately (ie, as if the other one were removed) from arterial pressure (P(a)), pressure between the 2 stenoses (P(m)), distal coronary pressure (P(d)), and coronary occlusive pressure (P(w)). In 5 dogs with 2 stenoses of varying severity in the left circumflex coronary artery, FFR(pred) was compared with FFR(app) (ratio of the pressure just distal to that just proximal to each stenoses) and to FFR(true) (ratio of the pressures distal to proximal to each stenosis but after removal of the other one) in case of fixed distal and varying proximal stenoses (n=15) and in case of fixed proximal and varying distal stenoses (n=20). The overestimation of FFR(true) by FFR(app) was larger than that of FFR(true) by FFR(pred) (0.070+/-0.007 versus 0.029+/-0.004, P<0.01 for fixed distal stenoses, and 0.114+/-0.01 versus 0.036+/-0. 004, P<0.01 for fixed proximal stenoses). This overestimation of FFR(true) by FFR(app) was larger for fixed proximal than for fixed distal stenoses. Conclusions-The interaction between 2 stenoses is such that FFR of each lesion separately cannot be calculated by the equation for isolated stenoses (P(d)/P(a) during hyperemia) applied to each separately but can be predicted by more complete equations taking into account P(a), P(m), P(d), and P(w).

Animals↗

PubMed1992

ELF exposure facility for human testing.

A laboratory facility specifically designed for controlled human exposure to 60-Hz electric (0 to 16 kV/m) and magnetic (0 to 32 A/m, B = 0 to 40 microT) fields has been constructed. The facility presents uniform fields under controlled temperature and humidity. Special control systems allow collection of physiological data during, as well as before and after, exposure to electric fields at strengths to 16 kV/m under verified double-blind control. Exposure to continuous or intermittent fields is possible in the facility. The capability of obtaining physiological data during actual exposure to constant or intermittent, 60-Hz fields, and of doing so without either the subject or the experimenter being aware of actual field conditions, is a critical factor in valid experimentation.

Electromagnetic Fields↗

PubMed2003

Anaesthetists' Non-Technical Skills (ANTS): evaluation of a behavioural marker system.

BACKGROUND: Non-technical skills are critical for good anaesthetic practice but are not addressed explicitly in normal training. Realization of the need to train and assess these skills is growing, but these activities must be based on properly developed skills frameworks and validated measurement tools. A prototype behavioural marker system was developed using human factors research techniques. The aim of this study was to conduct an experimental evaluation to establish its basic psychometric properties and usability. METHOD: The Anaesthetists' Non-Technical Skills (ANTS) system prototype comprises four skill categories (task management, team working, situation awareness, and decision making) divided into 15 elements, each with example behaviours. To investigate its experimental validity, reliably and usability, 50 consultant anaesthetists were trained to use the ANTS system. They were asked to rate the behaviour of a target anaesthetist using the prototype system in eight videos of simulated anaesthetic scenarios. Data were collected from the ratings forms and an evaluation questionnaire. RESULTS: The results showed that the system is complete, and that the skills are observable and can be rated with acceptable levels of agreement and accuracy. The internal consistency of the system appeared sound, and responses regarding usability were very positive. CONCLUSIONS: The findings of the evaluation indicated that the ANTS system has a satisfactory level of validity, reliability and usability in an experimental setting, provided users receive adequate training. It is now ready to be tested in real training environments, so that full guidelines can be developed for its integration into the anaesthetic curriculum.

Adult↗

PubMed2004

Differences in LexA regulon structure among Proteobacteria through in vivo assisted comparative genomics.

The LexA regulon encompasses an ensemble of genes involved in preserving cell viability under massive DNA damage and is present in most bacterial phyla. Up to date, however, the scope of this network had only been assessed in the Gamma Proteobacteria. Here, we report the structure of the LexA regulon in the Alpha Proteobacteria, using a combined approach that makes use of in vitro and in vivo techniques to assist and validate the comparative genomics in silico methodology. This leads to the first experimentally validated description of the LexA regulon in the Alpha Proteobacteria, and comparison of regulon core structures in both classes suggests that a least common multiple set of genes (recA, ssb, uvrA and ruvCAB) might be a defining property of the Proteobacteria LexA network.

Algorithms↗

PubMed2025

The role of stochasticity in fungal community assembly: explaining apparent stochasticity with field experiments.

Stochasticity is a main process in community assembly. However, experimental studies rarely target stochasticity in natural communities, and hence experimental validation of stochasticity estimates in observational studies is lacking. Here, we combine experimental and observational data to unravel the role of stochasticity in the assembly of wood-inhabiting fungi. We carried out a replicated field experiment where the natural colonization of a focal fungal species was simulated through inoculation, and the local fungal communities were monitored through DNA metabarcoding before and after the inoculations. The amount of stochasticity in fungal colonization was less pronounced than expected from the amount of unpredictability in observational data, suggesting that stochasticity may play a smaller role in fungal occurrence than previously anticipated, or that it may be a stronger influence in the dispersal and establishment phases than in colonization per se. Stochasticity was more prominent in the initial phase of community succession, with the earliest successional stage involving a higher level of stochasticity than the later stage after 2 years. We conclude that experimentally measuring the role of stochasticity in community assembly is feasible for species-rich communities under natural conditions and highlight the importance of experimentally testing the accuracy of stochasticity estimates based on observational data.

Stochastic Processes↗

PubMed1997

[Anatomo-functional consideration of an aponeurosis on the caudal radiocarpus in the tiger, lion and domestic cat (Panthera tigris, Panthera leo and Felis catus)].

This study describes a strong aponeurosis on the caudal surface of the antebrachium, between the Mm. Flexoris and the M. pronator quadratus. This aponeurosis has not been experimentally validated. By dissection and macroscopic examination of formaldehyde-prepared material, and experimental surgical transection of the structure in F. catus, the aponeurosis is described and its functional capacity is determined. The origin of the aponeurosis is the Facies caudalis, Margo medialis of the Radius and distal Ulna and inserts on the Crista transversa of the Radius and the Ligg. radiocarpeum palmare and ulno-carpeum palmare, and a strong Pars radialis. Its disposition is similar to that of the supernumerary M. anterior radialis brevis in humans. Surgical transection of the aponeurosis in F. catus resulted in hyperextension of the Manus and a decrease in the Carpus in its weight-bearing ability. These findings indicate the anatomico-functional importance of the aponeurosis in providing support to the claws.

Animals↗

PubMed2002

Experimental studies of a drumlike silencer.

The theoretical finding of the broadband performance of a reactive silencer is validated experimentally. The silencer consists of two highly stretched membranes lining part of the duct and backed by two long and shallow cavities. The test rig was built with a small square duct of 5 cm in dimension, and each cavity is 5 cm deep and 25 cm long. Two types of metal foils, stainless steel and copper, were used, and the lowest membrane-to-air mass ratio was 1.3. A transmission loss in excess of 10 dB was achieved over more than one octave band. For one configuration close to the optimal parameters, the predicted ratio of the frequency band limits is 2.47, while the experiment gave 2.35. Three spectral peaks were found in the stopband, as predicted, but the peaks were broader than prediction, indicating the presence of significant sound energy dissipation mechanisms. Comparison with theoretical simulation shows that the cavity damping dominates over membrane friction. Tests using heavier membranes and membrane with different levels of tension also agree with predictions. Issues of practical implementation of the concept as a flow-through silencer are also addressed.

Journal Article↗

PubMed2003

Integrated computational and experimental approach for lead optimization and design of compstatin variants with improved activity.

A novel structure-activity-based combinatorial computational optimization methodology for the design of peptides that are candidates to become therapeutics is presented. This methodology has been successfully applied in the design of a 7-fold more active analogue, among other active analogues, in the case of the complement inhibitor compstatin. The main steps of the approach involve the availability of NMR-derived structural templates, combinatorial selection of sequences based on optimization of parametrized pairwise residue interaction potentials, prediction of fold stabilities using deterministic global optimization, and experimental validation with immunological activity measurements. This work is direct evidence that an integrated experimental and theoretical approach can make the engineering of compounds with enhanced immunological properties possible.

Amino Acid Sequence↗

PubMed2006

Basic setup for breast conductivity imaging using magnetic resonance electrical impedance tomography.

We present a new medical imaging technique for breast imaging, breast MREIT, in which magnetic resonance electrical impedance tomography (MREIT) is utilized to get high-resolution conductivity and current density images of the breast. In this work, we introduce the basic imaging setup of the breast MREIT technique with an investigation of four different imaging configurations of current-injection electrode positions and pathways through computer simulation studies. Utilizing the preliminary findings of a best breast MREIT configuration, additional numerical simulation studies have been carried out to validate breast MREIT at different levels of SNR. Finally, we have performed an experimental validation with a breast phantom on a 3.0 T MREIT system. The presented results strongly suggest that breast MREIT with careful imaging setups could be a potential imaging technique for human breast which may lead to early detection of breast cancer via improved differentiation of cancerous tissues in high-resolution conductivity images.

Algorithms↗

PubMed1986

Serial xenotransplantation of a human embryonal carcinoma in experimental urology.

The rare incidence of testicular germ cell tumours makes it necessary for clinicians to look for a valid experimental model to investigate basic tumour properties and different therapeutic modalities preclinically in order to improve clinical cure rates. A human embryonal carcinoma with hCG-production was successfully established in nude mice for more than 40 passages. We were able to show striking maintenance of histological and ultrastructural features, tumour markers (Beta-hCG) and DNA indices of the original tumour during subsequent xenograft passages as well as stability of tumour growth. Dedifferentiation of the tumour with changing growth fractions or loss of hCG production was not evident.

Animals↗