123 research outputs found

    Dobutamine stress echocardiography for assessing the role of dynamic intraventricular obstruction in left ventricular ballooning syndrome

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    <p>Abstract</p> <p>Background</p> <p>Dynamic intraventricular obstruction has been observed in patients with left ventricular ballooning syndrome (LVBS) and has been hypothesized as a possible mechanism of the syndrome. The aim of this study was to assess the prevalence and significance of dynamic intraventricular obstruction in patients with LVBS.</p> <p>Methods and Results</p> <p>Dobutamine stress echocardiography was carried out in 22 patients with LVBS (82% apical), all women, aged 68 ± 9 years. At baseline 1 patient had a > 30 mmHg LV gradient; during stress a LV gradient > 30 mm Hg developed in 6/21 patients (28%) and was caused by systolic anterior motion of the mitral valve in the 3 patients with severe gradient (mean 116 ± 29 mmHg), who developed mitral regurgitation and impaired apical wall motion and by obstruction at mid-ventricular level in the other 3 with a moderate gradient (mean 46 ± 16 mmHg). Compared with patients without obstruction those with obstruction had a greater mean septal thickness (11.6 ± .6 vs 9.8. ± 3, p < .01), a higher prevalence of septal hypertrophy (71% vs 7%, p < .005) and a higher peak wall motion score index (1.62 ± .4 vs 1.08 ± .4, p < .01).</p> <p>Conclusion</p> <p>Spontaneous or dobutamine-induced dynamic LV obstruction is documented in 32% of patients with LVBS, is correlated with the presence of septal hypertrophy and may play a role in the development of LVBS in this subset of patients. In those without septal hypertrophy a dynamic obstruction is rarely induced with dobutamine and is unlikely to be a major pathogenetic factor of the syndrome.</p

    Shrimp Farming Practices in the Puttallam District of Sri Lanka: Implications for Disease Control, Industry Sustainability, and Rural Development

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    Shrimp farming has great potential to diversify and secure income in rural Sri Lanka, but production has significantly declined in recent years due to civil conflicts, some unsustainable practices and devastating outbreaks of disease. We examined management practices affecting disease prevention and control in the Puttalam district to identify extension services outputs that could support sustainable development of Sri Lankan shrimp farming. A survey on 621 shrimp farms (603 operational and 18 nonoperational) was conducted within the Puttalam district over 42 weeks comprising a series of three-day field visits from August 2008 to October 2009, covering two consecutive shrimp crops. Fundamental deficits in disease control, management, and biosecurity practices were found. Farmers had knowledge of biosecurity but the lack of financial resources was a major impediment to improved disease control. Smallholder farmers were disproportionately constrained in their ability to enact basic biosecurity practices due to their economic status. Basic breaches in biosecurity will keep disease as the rate limiting step in this industry. Plans to support this industry must recognize the socioeconomic reality of rural Sri Lankan aquaculture

    The diagnostic accuracy of pharmacological stress echocardiography for the assessment of coronary artery disease: a meta-analysis

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    <p>Abstract</p> <p>Background</p> <p>Recent American Heart Association/American College of Cardiology guidelines state that "dobutamine stress echo has substantially higher sensitivity than vasodilator stress echo for detection of coronary artery stenosis" while the European Society of Cardiology guidelines and the European Association of Echocardiography recommendations conclude that "the two tests have very similar applications". Who is right?</p> <p>Aim</p> <p>To evaluate the diagnostic accuracy of dobutamine versus dipyridamole stress echocardiography through an evidence-based approach.</p> <p>Methods</p> <p>From PubMed search, we identified all papers with coronary angiographic verification and head-to-head comparison of dobutamine stress echo (40 mcg/kg/min ± atropine) versus dipyridamole stress echo performed with state-of-the art protocols (either 0.84 mg/kg in 10' plus atropine, or 0.84 mg/kg in 6' without atropine). A total of 5 papers have been found. Pooled weight meta-analysis was performed.</p> <p>Results</p> <p>the 5 analyzed papers recruited 435 patients, 299 with and 136 without angiographically assessed coronary artery disease (quantitatively assessed stenosis > 50%). Dipyridamole and dobutamine showed similar accuracy (87%, 95% confidence intervals, CI, 83–90, vs. 84%, CI, 80–88, p = 0.48), sensitivity (85%, CI 80–89, vs. 86%, CI 78–91, p = 0.81) and specificity (89%, CI 82–94 vs. 86%, CI 75–89, p = 0.15).</p> <p>Conclusion</p> <p>When state-of-the art protocols are considered, dipyridamole and dobutamine stress echo have similar accuracy, specificity and – most importantly – sensitivity for detection of CAD. European recommendations concluding that "<it>dobutamine and vasodilators (at appropriately high doses) are equally potent ischemic stressors for inducing wall motion abnormalities in presence of a critical coronary artery stenosis</it>" are evidence-based.</p

    Genetic Interaction of Centrosomin and Bazooka in Apical Domain Regulation in Drosophila Photoreceptor

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    Cell polarity genes including Crumbs (Crb) and Par complexes are essential for controlling photoreceptor morphogenesis. Among the Crb and Par complexes, Bazooka (Baz, Par-3 homolog) acts as a nodal component for other cell polarity proteins. Therefore, finding other genes interacting with Baz will help us to understand the cell polarity genes' role in photoreceptor morphogenesis. mutation on developing eyes to determine its role in photoreceptor morphogenesis. We found that Cnn is dispensable for retinal differentiation in eye imaginal discs during the larval stage. However, photoreceptors deficient in Cnn display dramatic morphogenesis defects including the mislocalization of Crumbs (Crb) and Bazooka (Baz) during mid-stage pupal eye development, suggesting that Cnn is specifically required for photoreceptor morphogenesis during pupal eye development. This role of Cnn in apical domain modulation was further supported by Cnn's gain-of-function phenotype. Cnn overexpression in photoreceptors caused the expansion of the apical Crb membrane domain, Baz and adherens junctions (AJs). photoreceptor

    Post-exercise contractility, diastolic function, and pressure: Operator-independent sensor-based intelligent monitoring for heart failure telemedicine

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    <p>Abstract</p> <p>Background</p> <p>New sensors for intelligent remote monitoring of the heart should be developed. Recently, a cutaneous force-frequency relation recording system has been validated based on heart sound amplitude and timing variations at increasing heart rates.</p> <p>Aim</p> <p>To assess sensor-based post-exercise contractility, diastolic function and pressure in normal and diseased hearts as a model of a wireless telemedicine system.</p> <p>Methods</p> <p>We enrolled 150 patients and 22 controls referred for exercise-stress echocardiography, age 55 ± 18 years. The sensor was attached in the precordial region by an ECG electrode. Stress and recovery contractility were derived by first heart sound amplitude vibration changes; diastolic times were acquired continuously. Systemic pressure changes were quantitatively documented by second heart sound recording.</p> <p>Results</p> <p>Interpretable sensor recordings were obtained in all patients (feasibility = 100%). Post-exercise contractility overshoot (defined as increase > 10% of recovery contractility vs exercise value) was more frequent in patients than controls (27% vs 8%, p < 0.05). At 100 bpm stress heart rate, systolic/diastolic time ratio (normal, < 1) was > 1 in 20 patients and in none of the controls (p < 0.01); at recovery systolic/diastolic ratio was > 1 in only 3 patients (p < 0.01 vs stress). Post-exercise reduced arterial pressure was sensed.</p> <p>Conclusion</p> <p>Post-exercise contractility, diastolic time and pressure changes can be continuously measured by a cutaneous sensor. Heart disease affects not only exercise systolic performance, but also post-exercise recovery, diastolic time intervals and blood pressure changes – in our study, all of these were monitored by a non-invasive wearable sensor.</p

    Hundreds of variants clustered in genomic loci and biological pathways affect human height

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    Most common human traits and diseases have a polygenic pattern of inheritance: DNA sequence variants at many genetic loci influence the phenotype. Genome-wide association (GWA) studies have identified more than 600 variants associated with human traits, but these typically explain small fractions of phenotypic variation, raising questions about the use of further studies. Here, using 183,727 individuals, we show that hundreds of genetic variants, in at least 180 loci, influence adult height, a highly heritable and classic polygenic trait. The large number of loci reveals patterns with important implications for genetic studies of common human diseases and traits. First, the 180 loci are not random, but instead are enriched for genes that are connected in biological pathways (P = 0.016) and that underlie skeletal growth defects (P < 0.001). Second, the likely causal gene is often located near the most strongly associated variant: in 13 of 21 loci containing a known skeletal growth gene, that gene was closest to the associated variant. Third, at least 19 loci have multiple independently associated variants, suggesting that allelic heterogeneity is a frequent feature of polygenic traits, that comprehensive explorations of already-discovered loci should discover additional variants and that an appreciable fraction of associated loci may have been identified. Fourth, associated variants are enriched for likely functional effects on genes, being over-represented among variants that alter amino-acid structure of proteins and expression levels of nearby genes. Our data explain approximately 10% of the phenotypic variation in height, and we estimate that unidentified common variants of similar effect sizes would increase this figure to approximately 16% of phenotypic variation (approximately 20% of heritable variation). Although additional approaches are needed to dissect the genetic architecture of polygenic human traits fully, our findings indicate that GWA studies can identify large numbers of loci that implicate biologically relevant genes and pathways.

    A clinical and molecular characterisation of CRB1-associated maculopathy

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    To date, over 150 disease-associated variants in CRB1 have been described, resulting in a range of retinal disease phenotypes including Leber congenital amaurosis and retinitis pigmentosa. Despite this, no genotype–phenotype correlations are currently recognised. We performed a retrospective review of electronic patient records to identify patients with macular dystrophy due to bi-allelic variants in CRB1. In total, seven unrelated individuals were identified. The median age at presentation was 21 years, with a median acuity of 0.55 decimalised Snellen units (IQR = 0.43). The follow-up period ranged from 0 to 19 years (median = 2.0 years), with a median final decimalised Snellen acuity of 0.65 (IQR = 0.70). Fundoscopy revealed only a subtly altered foveal reflex, which evolved into a bull’s-eye pattern of outer retinal atrophy. Optical coherence tomography identified structural changes—intraretinal cysts in the early stages of disease, and later outer retinal atrophy. Genetic testing revealed that one rare allele (c.498_506del, p.(Ile167_Gly169del)) was present in all patients, with one patient being homozygous for the variant and six being heterozygous. In trans with this, one variant recurred twice (p.(Cys896Ter)), while the four remaining alleles were each observed once (p.(Pro1381Thr), p.(Ser478ProfsTer24), p.(Cys195Phe) and p.(Arg764Cys)). These findings show that the rare CRB1 variant, c.498_506del, is strongly associated with localised retinal dysfunction. The clinical findings are much milder than those observed with bi-allelic, loss-of-function variants in CRB1, suggesting this in-frame deletion acts as a hypomorphic allele. This is the most prevalent disease-causing CRB1 variant identified in the non-Asian population to date
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