Can arterial stiffness parameters be measured in the sitting position?


Despite the introduction of arterial stiffness measurements in the European recommendation, pulse wave velocity (PWV) and augmentation index (AI) are still not used routinely in clinical practice. It would be of advantage if such measurements were done in the sitting position as is done for blood pressure. The aim of this study was to evaluate whether there is a difference in stiffness parameters in sitting vs. supine position. Arterial stiffness was measured in 24 healthy volunteers and 20 patients with cardiovascular disease using three different devices: SphygmoCor (Atcor Medical, Sydney, Australia), Arteriograph (TensioMed, Budapest, Hungary) and Vascular Explorer (Enverdis, Jena, Germany). Three measurements were performed in supine position followed by three measurements in sitting position. Methods were compared using correlation and Bland–Altman analysis. There was a significant correlation between PWV in supine and sitting position (Arteriograph: P<0.0001, r=0.93; Vascular Explorer; P<0.0001, r=0.87). There were significant correlations between AI sitting and AI supine using Arteriograph (P<0.0001, r=0.97), Vascular Explorer (P<0.0001, r=0.98) and SphygmoCor (P<0.0001, r=0.96). When analyzed by Bland–Altman, PWV and AI measurements in supine vs. sitting showed good agreement. There was no significant difference in PWV obtained with the three different devices (Arteriograph 7.5±1.6 m s−1, Vascular Explorer 7.3±0.9 m s−1, SphygmoCor 7.0±1.8 m s−1). AI was significantly higher using the Arteriograph (17.6±15.0%) than Vascular Explorer and SphygmoCor (10.2±15.1% and 10.3±18.1%, respectively). The close agreement between sitting and supine measurements suggests that both PWV and AI can be reliably measured in the sitting position.

source: nature

 

FDA Approves Drug to Prevent Preterm Delivery


Hydroxyprogesterone caproate (Makena) has been approved to reduce the risk for preterm delivery, the FDA announced.

The drug is intended for women with a singleton pregnancy who have had at least one spontaneous preterm delivery. It is not approved for women with a multiple pregnancy or other risk factors for preterm delivery.

Makena is injected into the hip once a week, beginning at 16 weeks of pregnancy and up to 21 weeks. In a trial of some 460 women, rates of delivery before 37 weeks were 37% in women randomized to Makena and 55% in controls. A follow-up study showed no developmental differences between children born to mothers in the two groups.

Reported side effects include pain, swelling, and itching at the injection site and hives, nausea, and diarrhea. Serious adverse reactions were uncommon: one case each of infection at the injection site and pulmonary embolism.

FDA news release

The Physical Effects Of Evolution Measured At Molecular Scale


A unique experiment at Rice University that forces bacteria into a head-to-head competition for evolutionary dominance has yielded new insights about the way Darwinian selection plays out at the molecular level. An exacting new analysis of the experiment has revealed precisely how specific genetic mutations impart a physical edge in the competition for survival.

The new research, which could lead to more effective strategies to combat antibiotic drug resistance, was the most downloaded article this month in the journal Molecular Systems Biology.

The research builds upon an ingenious 2005 study involving bacteria called “thermophiles,” which thrive at high temperatures. Researchers in the laboratory of Rice biochemist Yousif Shamoo “knocked out” a key gene that allowed the thermophiles to make energy at high temperatures. These crippled versions of the bacteria were then grown inside fermentors for several weeks. Each day, the temperature of the fermentors was increased. As a result, the bacteria were forced to either starve or adapt to survive at high temperature.

Of the hundreds of possible mutations, only five proved successful in allowing the cells to adapt and survive at high temperature. Each of these had mutations in a gene that creates a key enzyme that helps make energy at high temperature. Each of the five made a slightly different version of the enzyme.

“One of these five eventually won out entirely and drove all the others to extinction,” said Shamoo, associate professor of biochemistry and cell biology and director of Rice’s Institute of Biosciences and Bioengineering. “The question is what physical advantage did that particular mutant have? What were the precise physical changes to the enzyme that allowed that strain to outcompete its cousins?”

Finding the answer to that question was painstaking. While the genetic mutations were known from the earlier study, it fell to graduate student Matt Peña to find out how small changes in the DNA structure of the bacteria translated into specific enzymatic changes. He found that adaptation depended critically on simultaneously keeping the enzyme working while also increasing its resistance to inactivation as the temperatures increased.

He found that versions of the enzyme — which is a specific kind of protein — that became inactive were also subject to protein misfolding. In humans, an inability to maintain properly folded and active proteins has been linked to several human diseases, including Alzheimer’s.

“Studies like this can help us understand the physical basis for these kinds of diseases, and they can give us a better understanding for the molecular basis for adaptation,” Shamoo said. “For example, what we learn from these thermophiles carries over into our work on drug-resistant bacteria because the principles of adaptation are the same no matter whether you’re studying temperature, pH, antibiotic resistance or whatever,” he said.

Shamoo’s lab won funding from the National Institutes of Health in 2009 to study how bacteria evolve antibiotic resistance. One of the ultimate goals of the project is to predict how evolution will play out so that drugmakers can head off resistance before it arises.

“With the thermophile study we’ve shown that it is possible to build a fitness function — a mathematical expression — that translates enzyme performance into a specific measure of competitive advantage,” Shamoo said. “That’s important because if you can’t do that for one protein of interest, then there’s no way you’re going to be able to do it for a more complicated problem like antibiotic resistance, which involves simultaneous mutations to more than one gene.”

source: mednews today