Effective Rheology of Bubbles Moving in a Capillary Tube

We calculate the average volumetric flux versus pressure drop of bubbles moving in a single capillary tube with varying diameter, finding a square-root relation from mapping the flow equations onto that of a driven overdamped pendulum. The calculation is based on a derivation of the equation of motion of a bubble train from considering the capillary forces and the entropy production associated with the viscous flow. We also calculate the configurational probability of the positions of the bubbles.Comment: 4 pages, 1 figur

Meta-Analysis of Genome-Wide Association Studies for Abdominal Aortic Aneurysm Identifies Four New Disease-Specific Risk Loci

Rationale: Abdominal aortic aneurysm (AAA) is a complex disease with both genetic and environmental risk factors. Together, 6 previously identified risk loci only explain a small proportion of the heritability of AAA. Objective: To identify additional AAA risk loci using data from all available genome-wide association studies (GWAS). Methods and Results: Through a meta-analysis of 6 GWAS datasets and a validation study totalling 10,204 cases and 107,766 controls we identified 4 new AAA risk loci: 1q32.3 (SMYD2), 13q12.11 (LINC00540), 20q13.12 (near PCIF1/MMP9/ZNF335), and 21q22.2 (ERG). In various database searches we observed no new associations between the lead AAA SNPs and coronary artery disease, blood pressure, lipids or diabetes. Network analyses identified ERG, IL6R and LDLR as modifiers of MMP9, with a direct interaction between ERG and MMP9. Conclusions: The 4 new risk loci for AAA appear to be specific for AAA compared with other cardiovascular diseases and related traits suggesting that traditional cardiovascular risk factor management may only have limited value in preventing the progression of aneurysmal disease

Prostaglandin D2-supplemented “functional eicosanoid testing and typing” assay with peripheral blood leukocytes as a new tool in the diagnosis of systemic mast cell activation disease: an explorative diagnostic study

Background: Systemic mast cell activation disease (MCAD) is characterized by an enhanced release of mast cell-derived mediators, including eicosanoids, which induce a broad spectrum of clinical symptoms. Accordingly, the diagnostic algorithm of MCAD presupposes the proof of increased mast cell mediator release, but only a few mediators are currently established as routine laboratory parameters. We thus initiated an explorative study to evaluate in vitro typing of individual eicosanoid pattern of peripheral blood leukocytes (PBLs) as a new diagnostic tool in MCAD. Methods: Using the “functional eicosanoid testing and typing” (FET) assay, we investigated the balance (i.e. the complex pattern of formation, release and mutual interaction) of prostaglandin E2 (PGE2) and peptido-leukotrienes (pLT) release from PBLs of 22 MCAD patients and 20 healthy individuals. FET algorithms thereby consider both basal and arachidonic acid (AA)-, acetylsalicylic acid (ASA)-, and substance P (SP)-triggered release of PGE2 and pLT. The FET assay was further supplemented by analyzing prostaglandin D2 (PGD2), as mast cell-specific eicosanoid. Results: We observed marked PGE2-pLT imbalances for PBLs of MCAD patients, as indicated by a markedly enhanced mean FET value of 1.75 ± 0.356 (range: 1.14–2.36), compared to 0.53 ± 0.119 (range: 0.36-0.75) for healthy individuals. In addition, mean PGD2 release from PBLs of MCAD patients was significantly, 6.6-fold higher than from PBLs of healthy individuals (946 ± 302.2 pg/ml versus 142 ± 47.8 pg/ml; P < 0.001). In contrast to healthy individuals, PGD2 release from PBLs of MCAD patients was markedly triggered by SP (mean: 1896 ± 389.7 pg/ml; P < 0.001), whereas AA and ASA caused individually varying effects on both PGD2 and pLT release. Conclusions: The new in-vitro FET assay, supplemented with analysis of PGD2, demonstrated that the individual patterns of eicosanoid release from PBLs can unambiguously distinguish MCAD patients from healthy individuals. Notably, in our analyses, the FET value and both basal and triggered PGD2 levels were not significantly affected by MCAD-specific medication. Thus, this approach may serve as an in-vitro diagnostic tool to estimate mast cell activity and to support individualized therapeutic decision processes for patients suffering from MCAD

2017 HRS/EHRA/ECAS/APHRS/SOLAECE expert consensus statement on catheter and surgical ablation of atrial fibrillation: executive summary.

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Cognitive Aging in Zebrafish

BACKGROUND: Age-related impairments in cognitive functions represent a growing clinical and social issue. Genetic and behavioral characterization of animal models can provide critical information on the intrinsic and environmental factors that determine the deterioration or preservation of cognitive abilities throughout life. METHODOLOGY/PRINCIPAL FINDINGS: Behavior of wild-type, mutant and gamma-irradiated zebrafish (Danio rerio) was documented using image-analysis technique. Conditioned responses to spatial, visual and temporal cues were investigated in young, middle-aged and old animals. The results demonstrate that zebrafish aging is associated with changes in cognitive responses to emotionally positive and negative experiences, reduced generalization of adaptive associations, increased stereotypic and reduced exploratory behavior and altered temporal entrainment. Genetic upregulation of cholinergic transmission attenuates cognitive decline in middle-aged achesb55/+ mutants, compared to wild-type siblings. In contrast, the genotoxic stress of gamma-irradiation accelerates the onset of cognitive impairment in young zebrafish. CONCLUSIONS/SIGNIFICANCE: These findings would allow the use of powerful molecular biological resources accumulated in the zebrafish field to address the mechanisms of cognitive senescence, and promote the search for therapeutic strategies which may attenuate age-related cognitive decline

Association of an INSIG2 obesity allele with cardiovascular phenotypes is gender and age dependent

Background: The INSIG2 gene has been implicated in cholesterol metabolism and a single nucleotide polymorphism (SNP) near INSIG2 has been shown to be associated with obesity. We sought to determine the relationship of the INSIG2 SNP to cardiovascular disease (CVD) related phenotypes.Methods and Results: Nine hundred forty six patients undergoing percutaneous coronary intervention (PCI) in wave 5 of the multicenter NHLBI Dynamic Registry were genotyped using RT-PCR/TaqMan/allelic discrimination for the rs7566605 SNP near the INSIG2 gene. Clinical variables analyzed include demographics, medical history, and procedural details. The prevalence of peripheral vascular disease (PVD) was significantly higher in older men (≥65 years) who were either homozygous or carriers of the obesity/lipid risk allele ("C") compared to non-carriers (odds ratio 3.4, p = 0.013) using a logistic regression model incorporating history of hypercholesterolemia, history of hypertension, cerebrovascular disease, history of diabetes, and BMI. A similar relationship with cerebrovascular disease was found in older (>65) women (odds ratio 3.4, p = 0.013). The INSIG2 SNP was not associated with BMI, nor with other clinical variables.Conclusion: Age and gender may influence the association of the INSIG2 obesity SNP with PVD and cerebrovascular disease in patients with pre-existing CVD. © 2010 Skelding et al; licensee BioMed Central Ltd

The Identification of Zebrafish Mutants Showing Alterations in Senescence-Associated Biomarkers

There is an interesting overlap of function in a wide range of organisms between genes that modulate the stress responses and those that regulate aging phenotypes and, in some cases, lifespan. We have therefore screened mutagenized zebrafish embryos for the altered expression of a stress biomarker, senescence-associated β-galactosidase (SA-β-gal) in our current study. We validated the use of embryonic SA-β-gal production as a screening tool by analyzing a collection of retrovirus-insertional mutants. From a pool of 306 such mutants, we identified 11 candidates that showed higher embryonic SA-β-gal activity, two of which were selected for further study. One of these mutants is null for a homologue of Drosophila spinster, a gene known to regulate lifespan in flies, whereas the other harbors a mutation in a homologue of the human telomeric repeat binding factor 2 (terf2) gene, which plays roles in telomere protection and telomere-length regulation. Although the homozygous spinster and terf2 mutants are embryonic lethal, heterozygous adult fish are viable and show an accelerated appearance of aging symptoms including lipofuscin accumulation, which is another biomarker, and shorter lifespan. We next used the same SA-β-gal assay to screen chemically mutagenized zebrafish, each of which was heterozygous for lesions in multiple genes, under the sensitizing conditions of oxidative stress. We obtained eight additional mutants from this screen that, when bred to homozygosity, showed enhanced SA-β-gal activity even in the absence of stress, and further displayed embryonic neural and muscular degenerative phenotypes. Adult fish that are heterozygous for these mutations also showed the premature expression of aging biomarkers and the accelerated onset of aging phenotypes. Our current strategy of mutant screening for a senescence-associated biomarker in zebrafish embryos may thus prove to be a useful new tool for the genetic dissection of vertebrate stress response and senescence mechanisms

Femtosecond Coherence and Quantum Control of Single Molecules at Room Temperature

Quantum mechanical phenomena, such as electronic coherence and entanglement, play a key role in achieving the unrivalled efficiencies of light-energy conversion in natural photosynthetic light-harvesting complexes, and triggered the growing interest in the possibility of organic quantum computing. Since biological systems are intrinsically heterogeneous, clear relations between structural and quantum-mechanical properties can only be obtained by investigating individual assemblies. However, single-molecule techniques to access ultrafast coherences at physiological conditions were not available so far. Here we show by employing femtosecond pulse-shaping techniques that quantum coherences in single organic molecules can be created, probed, and manipulated at ambient conditions even in highly disordered solid environments. We find broadly distributed coherence decay times for different individual molecules giving direct insight into the structural heterogeneity of the local surroundings. Most importantly, we induce Rabi-oscillations and control the coherent superposition state in a single molecule, thus performing a basic femtosecond single-qubit operation at room temperature

Single Nucleotide Polymorphisms in IL1B and the Risk of Acute Coronary Syndrome: A Danish Case-Cohort Study

BACKGROUND: Interleukin-1B (IL-1B) is a key pro-inflammatory cytokine that has been associated with the development of atherosclerosis and myocardial infarction. However, the prospective associations between functional single nucleotide polymorphisms (SNPs) in IL1B and incident acute coronary syndrome (ACS) have not been thoroughly investigated. The aims of this study were to examine the associations between individual SNPs in and SNP haplotypes of the promoter region of IL1B and incident ACS in a prospective study. Furthermore, we wanted to explore potential interactions with other risk factors for ACS on an additive scale. METHODOLOGY/PRINCIPAL FINDINGS: The present study was based on the Danish prospective study Diet, Cancer and Health comprising more than 57 000 participants aged 50-64 at baseline. During a median follow-up of 7.2 years we identified 989 cases of incident ACS (755 men and 234 women). All cases were validated by review of medical records, and information on covariates was collected by study technicians. The study was conducted according to a case-cohort study design including ACS cases and a sex-stratified sub cohort of 1663 participants drawn randomly from the entire cohort. Weighted Cox proportional hazard models with age as time axis were used in the statistical analyses. Individual IL1B SNPs, SNP haplotypes, or haplotype combinations were not significantly associated with incident ACS, and, likewise, we found no evidence of interaction on an additive scale between IL1B haplotypes and risk factors, respectively. CONCLUSIONS/SIGNIFICANCE: Genetic variation in the promoter region of IL1B may not be associated with incident ACS in men or women above the age of 50 years

Impact of age and comorbidities on health-related quality of life for patients with prostate cancer: evaluation before a curative treatment

<p>Abstract</p> <p>Background</p> <p>Interpretation of comparative health-related quality of life (HRQOL) studies following different prostate cancer treatments is often difficult due to differing patient ages. Furthermore, age-related changes can hardly be discriminated from therapy-related changes. The evaluation of age-and comorbidity-related changes was in focus of this study.</p> <p>Methods</p> <p>HRQOL of 528 prostate cancer patients was analysed using a validated questionnaire (Expanded Prostate Cancer Index Composite) before a curative treatment. Patients were divided into age groups ≤65, 6670, 7175 and >75 years. The impact of specific comorbidities and the Charlson Comorbidity Index (CCI) were evaluated. The questionnaire comprises 50 items concerning the urinary, bowel, sexual and hormonal domains for function and bother. For assessment of sexual and hormonal domains, only patients without prior hormonal treatment were included (n = 336).</p> <p>Results</p> <p>Urinary incontinence was observed increasingly with higher age (mean function scores of 92/88/85/87 for patients ≤65, 6670, 7175 and >75 years) complete urinary control in 78%/72%/64%/58% (p < 0.01). Sexual function scores decreased particularly (48/43/35/30), with erections sufficient for intercourse in 68%/50%/36%/32% (p < 0.01) a decrease of more than a third comparing patients ≤65 vs. 6670 (36%) and 6670 vs. 7175 years (39%). The percentage of patients with comorbidities was lowest in the youngest group (48% vs. 66%/68%/63% for ages 6670/7175/>75 years; p < 0.05). A multivariate analysis revealed an independent influence of both age and comorbidities on urinary incontinence, specifically diabetes on urinary bother, and both age and diabetes on sexual function/bother. Rectal domain scores were not significantly influenced by age or comorbidities. A CCI>5 particularly predisposed for lower urinary and sexual HRQOL scores.</p> <p>Conclusion</p> <p>Urinary continence and sexual function are the crucial HRQOL domains with age-related and independently comorbidity-related decreasing scores. The results need to be considered for the interpretation of comparative studies or longitudinal changes after a curative treatment.</p