475 research outputs found
Diagnosis of hyperthyroidism in cats with mild chronic kidney disease
No full textOBJECTIVES: In cats with concurrent hyperthyroidism and non-thyroidal illnesses such as chronic kidney disease, total thyroxine concentrations are often within the laboratory reference range (19 to 55 nmol/l). The objective of the study was to determine total thyroxine, free thyroxine and/or thyroid-stimulating hormone concentrations in cats with mild chronic kidney disease. METHODS: Total thyroxine, free thyroxine and thyroid-stimulating hormone were measured in three groups. The hyperthyroidism-chronic kidney disease group (n=16) had chronic kidney disease and clinical signs compatible with hyperthyroidism but a plasma total thyroxine concentration within the reference range. These cats were subsequently confirmed to be hyperthyroid at a later date. The chronic kidney disease-only group (n=20) had chronic kidney disease but no signs of hyperthyroidism. The normal group (n=20) comprised clinically healthy senior (> 8 years) cats. RESULTS: In 4 of 20 euthyroid chronic kidney disease cats, free thyroxine concentrations were borderline or high (>= 40 pmol/l). In the hyperthyroidism-chronic kidney disease group, free thyroxine was high in 15 of 16 cats, while thyroid-stimulating hormone was low in 16 of 16 cats. Most hyperthyroidism-chronic kidney disease cats (14 of 16) had total thyroxine greater than 30 nmol/l, whereas all the chronic kidney disease-only cats had total thyroxine less than 30 nmol/l. CLINICAL SIGNIFICANCE: The combined measurement of free thyroxine with total thyroxine or thyroid-stimulating hormone may be of merit in the diagnosis of hyperthyroidism in cats with chronic kidney disease
Mosaic maternal uniparental disomy of chromosome 11 in a patient with Silver-Russell syndrome
No full textSilver-Russell syndrome (SRS) is a clinically heterogeneous disorder characterised mainly by intrauterine and postnatal growth retardation. While maternal uniparental disomy of chromosome 7 is found in 5-10% of SRS patients, recently genetic and epigenetic mutations affecting the imprinting centres on chromosome 11p15 have been reported in up to 64% of patients. Chromosome 11p15 abnormalities reported in SRS include methylation defects in the imprinting centre 1 (ICR1) and maternally inherited duplications involving all or part of the imprinted region of 11p15. Here we report the first published case of SRS with mosaic maternal uniparental disomy of chromosome 11
Subclinical hyperthyroidism in cats: A spontaneous model of subclinical toxic nodular goiter in humans?
No full textIntroduction and Objectives: Hyperthyroidism in cats, caused by nodular hyperplasia or adenomas, is clinically and histologically similar to toxic nodular goiter in humans. Subclinical hyperthyroidism in humans is defined as low thyrotropin (TSH) in conjunction with within-reference-range thyroid hormone concentrations, but has not previously been defined in cats. The objective of this study was to test the hypothesis that euthyroid senior cats with low TSH have histological evidence of thyroid nodular hyperplasia and/or adenoma. Design: Thyroid glands removed postmortem from four groups of cats (n = 73) were examined histologically and scored in a blinded fashion. Clinically euthyroid senior (> 7 years) cats were divided into two groups dependent on their TSH concentration-TSH below the limit of quantification (LOQ) of the assay (= 0.03 ng/mL; n = 31; DetectableTSH group)-using archived plasma samples, collected 0-6 months antemortem. Thyroids were also scored for two control groups: Young group (cats < 6 years old; n = 13) and Hyperthyroid group (clinically and biochemically hyperthyroid cats; n = 14). Main outcome: Cats in the UndetectableTSH group had a higher frequency of nodules, a greater percentage of abnormal thyroid tissue, and a higher overall histopathological grade than cats with detectable TSH had. Conclusion: Euthyroid (as defined by total thyroxine) senior cats with low TSH are likely to have histological evidence of nodular thyroid disease, and such cats could be considered to be subclinically hyperthyroid
Incidence and associations of hemiplegic shoulder pain poststroke: prospective population-based study
No full textAbstract not availableZoe Adey-Wakeling, Hisatomi Arima, Maria Crotty, James Leyden, Timothy Kleinig, Craig S. Anderson, Jonathon Newbury on behalf of the SEARCH Study Collaborativ
Flexodeal Lite: a compact three-dimensional musculoskeletal simulation framework
No full text<div>By default, the code simulates the active contraction of a unipennate block of muscle tissue (similar to a biopsy) by locally minimizing the system's energy. The stress response consists of an along-fibre component (Hill's equation, including force-length and force-velocity effects) and a base material component (Yeoh hyperelastic material). Flexodeal Lite can be the basis of many experiments, including but not limited to those using MRI-derived geometries, anisotropic fat distributions, more precise characterizations of the base material (such as including extra-cellular matrix and cellular components), user-defined fibre orientations, and muscle tissue impaired by neurological disorders (such as cerebral palsy). Moreover, this framework supports a range of tissues, including tendon and aponeurosis. Some of the works in which this framework has been used include:</div>
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<li>Rahemi, H., Nigam, N., & Wakeling, J. M. (2014). Regionalizing muscle activity causes changes to the magnitude and direction of the force from whole muscles—a modeling study. <em>Frontiers in physiology</em>, <em>5</em>, 103206.</li>
<li>Rahemi, H., Nigam, N., & Wakeling, J. M. (2015). The effect of intramuscular fat on skeletal muscle mechanics: implications for the elderly and obese. <em>Journal of The Royal Society Interface</em>, <em>12</em>(109), 20150365.</li>
<li>Wakeling, J. M., Ross, S. A., Ryan, D. S., Bolsterlee, B., Konno, R., Domínguez, S., & Nigam, N. (2020). The energy of muscle contraction. I. Tissue force and deformation during fixed-end contractions. <em>Frontiers in physiology</em>, <em>11</em>, 524359.</li>
<li>Ryan, D. S., Domínguez, S., Ross, S. A., Nigam, N., & Wakeling, J. M. (2020). The energy of muscle contraction. II. transverse compression and work. <em>Frontiers in Physiology</em>, <em>11</em>, 538522.</li>
<li>Ross, S. A., Domínguez, S., Nigam, N., & Wakeling, J. M. (2021). The energy of muscle contraction. III. Kinetic energy during cyclic contractions. <em>Frontiers in Physiology</em>, <em>12</em>, 628819.</li>
<li>Konno, R. N., Nigam, N., & Wakeling, J. M. (2021). Modelling extracellular matrix and cellular contributions to whole muscle mechanics. <em>Plos one</em>, <em>16</em>(4), e0249601.</li>
<li>Konno, R. N., Nigam, N., Wakeling, J. M., & Ross, S. A. (2022). The contributions of extracellular matrix and sarcomere properties to passive muscle stiffness in cerebral palsy. <em>Frontiers in Physiology</em>, <em>12</em>, 804188.</li>
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<div>The nonlinear system of partial differential equations is derived from a dynamic extension of a three-field elasticity formulation used for transversally-isotropic quasi-incompressible materials (although it is expected that volume changes will be small due to the stiffness of muscle tissue). Numerically speaking, the equations are solved using a dynamic time-stepping scheme and a finite element discretization on a hexahedral mesh using the library <a href="https://www.dealii.org/">deal.II</a> (v9.3 or higher). </div>
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<div>Review the README file for more information on how to use this code. If you use this software in your scientific articles, please cite the following references:</div>
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<li>Almonacid, J. A., Domínguez-Rivera, S. A., Konno, R. N., Nigam, N., Ross, S. A., Tam, C., & Wakeling, J. M. (2024). A three-dimensional model of skeletal muscle tissues. <em>SIAM Journal on Applied Mathematics</em>, S538-S566.</li>
<li>This Zenodo repository.</li>
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Insulin-like growth factor-1 receptor signalling and acquired resistance to gefitinib (ZD1839; IRESSATM) in MCF-7 human breast cancer cells
No full textSIRT1 affects DNA methylation of polycomb group protein target genes, a hotspot of the epigenetic shift observed in ageing
No full textThe Interactive Minority Game: a Web based investigation of human market interactions
No full textThe unprecedented access offered by the World Wide Web brings with it the potential to gather huge amounts of data on human activities. Here we exploit this by using a toy model of financial markets, the Minority Game (MG), to investigate human speculative trading behaviour and information capacity. Hundreds of individuals have played a total of tens of thousands of game turns against computer-controlled agents in the Web-based Interactive Minority Game. The analytical understanding of the MG permits fine-tuning of the market situations encountered, allowing for investigation of human behaviour in a variety of controlled environments. In particular, our results indicate a transition in players' decision-making, as the markets become more difficult, between deductive behaviour making use of short-term trends in the market, and highly repetitive behaviour that ignores entirely the market history, yet outperforms random decision-making.Experimental economics and financial markets; Decision theory and game theory; Information theory
Insulin-like growth factor-1 receptor signalling and acquired resistance to gefitinib (ZD1839; Iressa) in human breast and prostate cancer cells
No full textDe novo and acquired resistance to the anti-tumour drug gefitinib (ZD1839; Iressa), a specific epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) has been reported. We have determined whether signalling through the IGF-I receptor (IGF-1R) pathway plays a role in the gefitinib-acquired resistance phenotype. Continuous exposure of EGFR-positive MCF-7-derived tamoxifen resistant breast cancer cells (TAM-R) to 1 μM gefitinib resulted in a sustained growth inhibition (90%) for 4 months before the surviving cells resumed proliferation. A stable gefitinib-resistant subline (TAM/TKI-R) was established after a further 2 months and this showed no detectable basal phosphorylated EGFR activity. Compared with the parental TAM-R cells, the TAM/ TKI-R cells demonstrated (a) elevated levels of activated IGF-1R, AKT and protein kinase C (PKC)δ, (b) an increased sensitivity to growth inhibition by the IGF-1R TKI AG1024 and (c) an increased migratory capacity that was reduced by AG1024 treatment. Similarly, the EGFR-positive androgen-independent human prostate cancer cell line DU145 was also continuously challenged with 1 μM gefitinib and, although substantial growth inhibition (60%) was seen initially, a gefitinib-resistant variant (DU145/TKI-R) developed after 3 months. Like their breast cancer counterparts, the DU145/TKI-R cells showed increases in the levels of components of the IGF-1R signalling pathway and an elevated sensitivity to growth inhibition by AG1024 compared with the parent DU145 cell line. Additionally, DU145/TKI-R cell migration was also decreased by this inhibitor. We have therefore concluded that in breast and prostate cancer cells acquired resistance to gefitinib is associated with increased signalling via the IGF-1R pathway, which also plays a role in the invasive capacity of the gefitinib-resistant phenotype
Body composition and metabolism in adults with molecularly-confirmed Silver-Russell syndrome
No full textContext: Low birth weight, as seen in Silver-Russell syndrome (SRS), is associated with later cardiometabolic disease. Data on long-term outcomes and adult body composition in SRS are limited. Objective: To evaluate body composition and metabolic health in adults with SRS. Methods: This was an observational study of 25 individuals with molecularly confirmed SRS, aged ≥ 18 years, from research facilities across the UK. Body composition and metabolic health were assessed at a single appointment. Individuals with SRS were compared with unaffected men and women (from the Southampton Women's Survey [SWS]). Fat mass, lean mass, bone mineral density (BMD), blood pressure, lipids, and blood glucose were measured. Results: Twenty-five adults with SRS were included (52% female). The median age was 32.9 years (range, 22.0 to 69.7). Fat percentage was greater in the SRS group than the SWS cohort (44.1% vs 30.3%, P < .001). Fat mass index was similar (9.6 vs 7.8, P = .3). Lean mass percentage (51.8% vs 66.2%, P < .001) and lean mass index (13.5 kg/m2 vs 17.3 kg/m2, P < .001) were lower in the SRS group than the SWS cohort. BMD was lower in the SRS group than the SWS cohort (1.08 vs 1.24, P < .001; all median values). Total cholesterol was ≥ 5 mmol/L in 52.0%. Triglyceride levels were ≥ 1.7 mmol/L in 20.8%. Fasting blood glucose levels were ≥ 6.1 mmol/L in 25.0%. Hypertension was present in 33.3%. Conclusion: Adults with SRS have an unfavorable body composition and predisposition to cardiometabolic disease. These results support the need for a health surveillance strategy to mitigate adverse outcomes.</p
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