Negative exercise stress test Does it mean anything?

Despite its low sensitivity and specificity (67% and 72%, respectively), exercise testing has remained one of the most widely used noninvasive tests to determine the prognosis in patients with suspected or established coronary disease.As a screening test for coronary artery disease, the exercise stress test is useful in that it is relatively simple and inexpensive. It has been considered particularly helpful in patients with chest pain syndromes who have moderate probability for coronary artery disease, and in whom the resting electrocardiogram (ECG) is normal. The following case presentation and discussion will question the predictive value of a negative stress testing in patients with moderate probability for coronary artery disease

First macrobiota biomineralisation was environmentally triggered

Why large and diverse skeletons first appeared ca 550 Ma is not well understood. Many Ediacaran skeletal biota show evidence of flexibility, and bear notably thin skeletal walls with simple, non-hierarchical microstructures of either aragonite or high-Mg calcite. We present evidence that the earliest skeletal macrobiota, found only in carbonate rocks, had close soft-bodied counterparts hosted in contemporary clastic rocks. This includes the calcareous discoidal fossil Suvorovella, similar to holdfasts of Ediacaran biota taxa previously known only as casts and moulds, as well as tubular and vase-shaped fossils. In sum, these probably represent taxa of diverse affinity including unicellular eukaryotes, total group cnidarians and problematica. Our findings support the assertion that the calcification was an independent and derived feature that appeared in diverse groups where an organic scaffold was the primitive character, which provided the framework for interactions between the extracellular matrix and mineral ions. We conclude that such skeletons may have been acquired with relative ease in the highly saturated, high alkalinity carbonate settings of the Ediacaran, where carbonate polymorph was further controlled by seawater chemistry. The trigger for Ediacaran biomineralization may have been either changing seawater Mg/Ca and/or increasing oxygen levels. By the Early Cambrian, however, biomineralization styles and the range of biominerals had significantly diversified, perhaps as an escalating defensive response to increasing predation pressure. Indeed skeletal hardparts had appeared in clastic settings by Cambrian Stage 1, suggesting independence from ambient seawater chemistry where genetic and molecular mechanisms controlled biomineralization and mineralogy had become evolutionarily constrained

Induction of Inflammation by West Nile virus Capsid through the Caspase-9 Apoptotic Pathway

West Nile virus (WNV) is a member of the Flaviviridae family of vector-borne pathogens. Clinical signs of WNV infection include neurologic symptoms, limb weakness, and encephalitis, which can result in paralysis or death. We report that the WNV-capsid (Cp) by itself induces rapid nuclear condensation and cell death in tissue culture. Apoptosis is induced through the mitochondrial pathway resulting in caspase-9 activation and downstream caspase-3 activation. Capsid gene delivery into the striatum of mouse brain or interskeletal muscle resulted in cell death and inflammation, likely through capsid-induced apoptosis in vivo. These studies demonstrate that the capsid protein of WNV may be responsible for aspects of viral pathogenesis through induction of the apoptotic cascade

Homogenized stiffness matrices for mineralized collagen fibrils and lamellar bone using unit cell finite element models

Mineralized collagen fibrils have been usually analyzed like a two phase composite material where crystals are considered as platelets that constitute the reinforcement phase. Different models have been used to describe the elastic behavior of the material. In this work, it is shown that, when Halpin-Tsai equations are applied to estimate elastic constants from typical constituent properties, not all crystal dimensions yield a model that satisfy thermodynamic restrictions. We provide the ranges of platelet dimensions that lead to positive definite stiffness matrices. On the other hand, a finite element model of a mineralized collagen fibril unit cell under periodic boundary conditions is analyzed. By applying six canonical load cases, homogenized stiffness matrices are numerically calculated. Results show a monoclinic behavior of the mineralized collagen fibril. In addition, a 5-layer lamellar structure is also considered where crystals rotate in adjacent layers of a lamella. The stiffness matrix of each layer is calculated applying Lekhnitskii transformations and a new finite lement model under periodic boundary conditions is analyzed to calculate the homogenized 3D anisotropic stiffness matrix of a unit cell of lamellar bone. Results are compared with the rule-of-mixtures showing in general good agreement.The authors acknowledge the Ministerio de Economia y Competitividad the financial support given through the project DPI2010-20990 and the Generalitat Valenciana through the Programme Prometeo 2012/023. The authors thank Ms. Carla Gonzalez Carrillo by her help in the development of some of the numerical models.Vercher Martínez, A.; Giner Maravilla, E.; Arango Villegas, C.; Tarancón Caro, JE.; Fuenmayor Fernández, FJ. (2014). Homogenized stiffness matrices for mineralized collagen fibrils and lamellar bone using unit cell finite element models. 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Drawing-writing culture: the truth-fiction spectrum of an ethno-graphic novel on the Sri Lankan civil war and migration

With our focus on an “ethno‐graphic novel” on the Sri Lankan civil war and the forcible displacement and migration of Tamil survivors, we make two main propositions while reflecting on the “graphic narrative turn” that has emerged in anthropology in recent years. First, we inscribe drawing into the “writing of cultures” where words have held a superior status in ethnographic representations. Rather than seeing drawings as perceptive tools for recording scenes in fieldwork alone, we extend them to a representational practice where they can have a deep, intricate, and equivalent entanglement with words to create synchronous affective intensities among a larger audience. Our second proposal follows Jean Rouch on cinéma vérité to interrogate assumptions about truth and fiction as portrayed by film representations. We propose a theory and practice for graphic novel production that we have termed vérités graphiques (literally, graphic realities). This describes the collaborative and interactive engagement with people's contributions and views, and their distillation and fictionalization through the ethno‐graphic form. We diverge from cinéma vérité, however, by highlighting a truth‐fiction spectrum that further challenges the presumed objectivity of what is seen, experienced, co‐created, and revealed

Ionophore A23187 induced reductions in toad urinary bladder epithelial cell oxidative phosphorylation and viability

The divalent cation ionophore A23187 increased oxygen consumption by isolated epithelial cells from toad urinary bladder, an increase similar to that seen with 2,4-dinitrophenol, a classic uncoupler of mitochondrial oxidative phosphorylation. This respiratory stimulation was not seen in calcium-free incubation media. That this A23187 induced rise in cell oxygen consumption was due to a primary uncoupling action on mitochondrial oxidative phosphorylation rather than secondary to stimulation of cellular transport processes and mediated via increased cellular ADP levels was suggested by the ability of A23187 to release the inhibition of cellular respiration by oligomycin, an inhibitor of the mitochondrial proton ATPase which blocks the stimulation of mitochondrial respiration by ADP. Since active transepithelial ion transport and cellular energy production are closely linked processes, the uncoupling action of A23187 in the presence of extracellular calcium is sufficient to account for an acute decline in active ion transport across epithelia without invoking other calcium-mediated processes. Furthermore, isolated epithelial cells exposed to A23187 for 90 min had greater than 50% loss of viability, as measured by failure of Trypan blue exclusion. The subacute A23187 induced declines in transepithelial transport, therefore, may be secondary to its non-specific effects on cell viability.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/47447/1/424_2004_Article_BF00658484.pd

Calcified Algae for Tissue Engineering.

This book presents the latest advances in marine structures and related biomaterials for applications in both soft- and hard-tissue engineering, as well as controlled drug delivery

Autoantibodies to αS1-Casein Are Induced by Breast-Feeding

BACKGROUND: The generation of antibodies is impaired in newborns due to an immature immune system and reduced exposure to pathogens due to maternally derived antibodies and placental functions. During nursing, the immune system of newborns is challenged with multiple milk-derived proteins. Amongst them, caseins are the main constituent. In particular, human αS1-casein (CSN1S1) was recently shown to possess immunomodulatory properties. We were thus interested to determine if auto-antibodies to CSN1S1 are induced by breast-feeding and may be sustained into adulthood. METHODS: 62 sera of healthy adult individuals who were (n = 37) or were not (n = 25) breast-fed against human CSN1S1 were investigated by a new SD (surface display)-ELISA. For cross-checking, these sera were tested for anti Epstein-Barr virus (EBV) antibodies by a commercial ELISA. RESULTS: IgG-antibodies were predominantly detected in individuals who had been nursed. At a cut-off value of 0.4, the SD-ELISA identified individuals with a history of having been breast-fed with a sensitivity of 80% and a specificity of 92%. Under these conditions, 35 out of 37 sera from healthy donors, who where breast-fed, reacted positively but only 5 sera of the 25 donors who were not breast-fed. The duration of breast-feeding was of no consequence to the antibody reaction as some healthy donors were only short term breast-fed (5 days minimum until 6 weeks maximum), but exhibited significant serum reaction against human CSN1S1 nonetheless. CONCLUSION: We postulate that human CSN1S1 is an autoantigen. The antigenicity is orally determined, caused by breast-feeding, and sustained into adulthood

Prediction of Long-Term Benefits of Inhaled Steroids by Phenotypic Markers in Moderate-to-Severe COPD:A Randomized Controlled Trial

BACKGROUND:The decline in lung function can be reduced by long-term inhaled corticosteroid (ICS) treatment in subsets of patients with chronic obstructive pulmonary disease (COPD). We aimed to identify which clinical, physiological and non-invasive inflammatory characteristics predict the benefits of ICS on lung function decline in COPD. METHODS:Analysis was performed in 50 steroid-naive compliant patients with moderate to severe COPD (postbronchodilator forced expiratory volume in one second (FEV1), 30-80% of predicted, compatible with GOLD stages II-III), age 45-75 years, >10 packyears smoking and without asthma. Patients were treated with fluticasone propionate (500 μg bid) or placebo for 2.5 years. Postbronchodilator FEV1, dyspnea and health status were measured every 3 months; lung volumes, airway hyperresponsiveness (PC20), and induced sputum at 0, 6 and 30 months. A linear mixed effect model was used for analysis of this hypothesis generating study. RESULTS:Significant predictors of attenuated FEV1-decline by fluticasone treatment compared to placebo were: fewer packyears smoking, preserved diffusion capacity, limited hyperinflation and lower inflammatory cell counts in induced sputum (p<0.04). CONCLUSIONS:Long-term benefits of ICS on lung function decline in patients with moderate-to-severe COPD are most pronounced in patients with fewer packyears, and less severe emphysema and inflammation. These data generate novel hypotheses on phenotype-driven therapy in COPD. TRIAL REGISTRATION:ClinicalTrials.gov NCT00158847