Prosthetic valve thrombosis despite seemingly-adequate anticoagulation: the dangers of transient lapses in anticoagulation

We report a 19-year-old woman with thrombosis of a prosthetic mitral valve that was most likely due to a short dip in anticoagulation in the days preceding the event. Interestingly, at presentation the Patient was super-therapeutic, most likely a result of hepatic congestion as the heart began to fail, creating an illusion of thrombosis despite adequate anti coagulation

An optimization method for solving mixed discrete-continuous programming problems

AbstractThis paper presents a heuristic approach for minimizing nonlinear mixed discrete-continuous problems with nonlinear mixed discrete-continuous constraints. The approach is an extension of the boundary tracking optimization that was developed by the authors to solve the minimum of nonlinear pure discrete programming problems with pure discrete constraints. The efficacy of the proposed approach is demonstrated by solving a number of test problems of the same class published in recent literature. Among these examples is the complex problem of minimizing the cost of a series–parallel structure with redundancies subject to reliability constraint. All tests conducted so far show that the proposed approach obtains the published minima of the respective test problems or finds a better minimum. While it is not possible to compare computation time due to the lack of data on the test problems, for all the tests the minimum is found in a reasonable time

Some approximation results for mild solutions of stochastic fractional order evolution equations driven by Gaussian noise

We investigate the quality of space approximation of a class of stochastic integral equations of convolution type with Gaussian noise. Such equations arise, for example, when considering mild solutions of stochastic fractional order partial differential equations but also when considering mild solutions of classical stochastic partial differential equations. The key requirement for the equations is a smoothing property of the deterministic evolution operator which is typical in parabolic type problems. We show that if one has access to nonsmooth data estimates for the deterministic error operator together with its derivative of a space discretization procedure, then one obtains error estimates in pathwise H\uf6lder norms with rates that can be read off the deterministic error rates. We illustrate the main result by considering a class of stochastic fractional order partial differential equations and space approximations performed by spectral Galerkin methods and finite elements. We also improve an existing result on the stochastic heat equation

Tunable and Multifunctional Eukaryotic Transcription Factors Based on CRISPR/Cas

Transcriptional regulation is central to the complex behavior of natural biological systems and synthetic gene circuits. Platforms for the scalable, tunable, and simple modulation of transcription would enable new abilities to study natural systems and implement artificial capabilities in living cells. Previous approaches to synthetic transcriptional regulation have relied on engineering DNA-binding proteins, which necessitate multistep processes for construction and optimization of function. Here, we show that the CRISPR/Cas system of Streptococcus pyogenes can be programmed to direct both activation and repression to natural and artificial eukaryotic promoters through the simple engineering of guide RNAs with base-pairing complementarity to target DNA sites. We demonstrate that the activity of CRISPR-based transcription factors (crisprTFs) can be tuned by directing multiple crisprTFs to different positions in natural promoters and by arraying multiple crisprTF-binding sites in the context of synthetic promoters in yeast and human cells. Furthermore, externally controllable regulatory modules can be engineered by layering gRNAs with small molecule-responsive proteins. Additionally, single nucleotide substitutions within promoters are sufficient to render them orthogonal with respect to the same gRNA-guided crisprTF. We envision that CRISPR-based eukaryotic gene regulation will enable the facile construction of scalable synthetic gene circuits and open up new approaches for mapping natural gene networks and their effects on complex cellular phenotypes

Genetic testing for inherited retinal degenerations: Triumphs and tribulations

Inherited retinal degenerations (IRDs) are a genotypically and phenotypically diverse group of conditions. Great strides have been made toward identifying the genetic basis for these conditions over the last 30 years—more than 270 different genes involved in syndromic and nonsyndromic forms of retinal dystrophies have now been identified. The identification of these genes and the improvement of clinical laboratory techniques have led to the identification of the genetic basis of disease in 56–76% of patients with IRDs through next generation sequencing and copy number variant analysis. Genetic testing is an essential part of clinical care for patients affected with IRDs and is required to confirm the diagnosis, understand the inheritance of the condition, and determine eligibility for gene‐specific treatments or clinical trials. Despite the success achieved in determining the genetic cause of these conditions, several challenges remain, which must be considered when providing genetic testing and genetic counseling to patients. For this reason, an integrated team of ophthalmic and genetic clinicians who are familiar with these challenges is necessary to provide optimal comprehensive care to these patients.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/162692/2/ajmgc31835.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/162692/1/ajmgc31835_am.pd

Polyphenols content and antioxidant power of fruits and leaves of Juniperus phoenicea L. From Tounfite (Morocco)

The natural antioxidants have attracted considerable attention of researchers because of their beneficial roles in human health. In the framework of the development of new antioxidants from natural sources, we are interested in this work in studying the phenolic compounds and evaluating the antioxidant properties of Juniperus phoenicea L. leaves and fruits collected in the mountains of Eastern High-Atlas (Tounfite). The phytochemical screening has allowed highlighting the existence of polyphenols, tannins, flavonoids, sterols and triterpenes, and oses and holosides in both studied samples. Mucilages are also present in these samples but in small quantities, while alkaloids and saponins are entirely absent. Extracts from leaves and fruits have been obtained by different extraction solvents: water, methanol, chloroform, ethyl acetate and n-butanol. The contents of total phenols and flavonoids were evaluated using gallic acid and quercetin as standard respectively. The ethyl acetate extracts of the leaves and fruits contain high levels of total phenolic estimated 2,91mg/g and 5,35mg/g equivalent of gallic acid (GAE) respectively. As for the flavonoid content, the ethyl acetate extracts have also reached the increased levels 11,82mg/g and 2,66mg/g equivalent of quercetin (QE). The antioxidant activities by DPPH test were quantified by spectrophotometry; the results showed that the ethyl acetate extracts from the leaves and fruits exhibit an antioxidant activity with inhibitory concentrations 50% (IC50) of 94,4μg/ml and 185,83μg/ml respectively compared to that of vitamin C (47,76μg/ml). The antioxidant test allowed concluding that the leaves and fruits have a strong anti-radical activity that was assumed to be related closely to the content of polyphenols, which are generally very good antioxidants and that the leaves show a higher activity than fruits.

Relationship between alcohol co-ingestion and outcome in profenofos self-poisoning - A prospective case series

<div><p>Introduction</p><p>The importance of alcohol co-ingestion for outcome in organophosphorus (OP) insecticide self-poisoning has only been studied for the relatively hydrophilic dimethyl insecticide, dimethoate. We aimed to assess the effect of alcohol in acute poisoning with the lipophilic S-alkyl OP insecticide, profenofos.</p><p>Methodology</p><p>Demographic and clinical data, including an alcohol history, were prospectively collected from all cases of acute poisoning with agricultural profenofos EC50 presenting to two Sri Lankan hospitals over seven years.</p><p>Results</p><p>Of 1859 patients with acute OP insecticide self-poisoning, 243 (13.1%) reported ingestion of profenofos (male 182/243, 74.9%). Alcohol co-ingestion was reported by 64/243 (26.3%). All patients reporting alcohol co-ingestion were male (64/64 [100%] vs 118/179 [65.9%] not reporting alcohol ingestion, p<0.001). More patients reporting alcohol co-ingestion died (10/64 [15.6%] vs 10/179 [5.6%]; p = 0.013) and required intubation (13/64 [20.3%] vs 16/179 [8.9%], p = 0.016) compared to those who did not co-ingest alcohol. Using multi-logistic regression, controlling for the estimated dose ingested, age (OR 11.1 [2.5 to 48.9] for age > 35 years vs ≤35 years) and alcohol co-ingestion (OR 3.1 [1.2 to 7.9]) were independently associated with increased risk of death. Increased risk of intubation was independently associated with age (OR 3.2 [1.6 to 6.6] for age > 35 years vs ≤35 years) and alcohol co-ingestion (OR 3.2 [1.6 to 6.4]).</p><p>Conclusion</p><p>A history of alcohol co-ingestion, as well as older age, is independently associated with worse outcome in patients’ self-poisoned with profenofos.</p></div