From Bioreactor to Bulk Rheology: Achieving Scalable Production of Highly Concentrated Circular DNA.

DNA serves as a model system in polymer physics due to its ability to be obtained as a uniform polymer with controllable topology and nonequilibrium behavior. Currently, a major obstacle in the widespread adoption of DNA is obtaining it on a scale and cost basis that accommodates bulk rheology and high-throughput screening. To address this, recent advancements in bioreactor-based plasmid DNA production is coupled with anion exchange chromatography producing a unified approach to generating gram-scale quantities of monodisperse DNA. With this method, 1.1 grams of DNA is obtained per batch to generate solutions with concentrations up to 116 mg mL-1. This solution of uniform supercoiled and relaxed circular plasmid DNA, is roughly 69 times greater than the overlap concentration. The utility of this method is demonstrated by performing bulk rheology measurements at sample volumes up to 1 mL on DNA of different lengths, topologies, and concentrations. The measured elastic moduli are orders of magnitude larger than those previously reported for DNA and allowed for the construction of a time-concentration superposition curve that spans 12 decades of frequency. Ultimately, these results can provide important insights into the dynamics of ring polymers and the nature of highly condensed DNA dynamics.

Understanding the Haemodynamics of Hypertension.

PURPOSE OF REVIEW: This article introduces the haemodynamic principles that underpin the pathophysiology of hypertension and introduces a rational physiological approach to appropriate pharmacologic treatment. RECENT FINDINGS: Outdated understanding of haemodynamics based on previous measurement systems can no longer be applied to our understanding of the circulation. We question the current view of hypertension as defined by a predominantly systolic blood pressure and introduce the concept of vasogenic, cardiogenic and mixed-origin hypertension. We postulate that failure to identify the individual's haemodynamic pattern may lead to the use of inappropriate medication, which in turn may be a major factor in patient non-compliance with therapeutic strategies. A population-based approach to treatment of hypertension may lead to suboptimal functional dynamics in the individual patient. Finally, we question the validity of current guidelines and published evidence relating morbidity and mortality to the future treatment of hypertension. The importance of individual haemodynamic profiles may be pivotal in the understanding, diagnosis and treatment of hypertension if optimal control with minimal adverse effects is to be achieved. Research based on individual haemodynamic patterns is overdue.

Stroke Volume Monitoring: Novel Continuous Wave Doppler Parameters, Algorithms and Advanced Noninvasive Haemodynamic Concepts.

PURPOSE OF REVIEW: Adequate oxygen delivery is essential for life, with hypoxia resulting in dysfunction, and ultimately death, of the cells, organs and organism. Blood flow delivers the oxygen bound in the blood, while haemodynamics is the science of blood flow. Stroke volume (SV) is the fundamental unit of blood flow, and reflects the interdependent performance of the heart, the vessels and the autonomic nervous system. However, haemodynamic management remains generally poor and predominantly guided by simple blood pressure observations alone. RECENT FINDINGS: Doppler ultrasound measures SV with unequalled clinical precision when operated by trained personnel. Combining SV with BP measurements allows calculation of flow-pressure based measures which better reflect cardiovascular performance and allows personalised physiologic and pathophysiologic modelling consistent with Frank's and Starling's observations. SUMMARY: Doppler SV monitoring and novel flow-pressure parameters may improve our understanding of the cardiovascular system and lead to improved diagnosis and therapy. This review examines the physics and practice of Doppler SV monitoring and its application in advanced haemodynamics.

Protothecosis in hematopoietic stem cell transplantation: case report and review of previous cases.

Prototheca species are achlorophyllus algae. Prototheca wickerhamii and Prototheca zopfii cause human disease. In immunocompetent individuals, they cause soft tissue infections and olecranon bursitis, but in transplant recipients, these organisms can cause disseminated disease. We report a fatal case of disseminated P. zopfii infection in an hematopoietic stem cell transplant (HSCT) recipient with bloodstream infection and involvement of multiple soft tissue sites. We review all previous cases of protothecosis in HSCT reported in the literature. Protothecosis is uncommon after HSCT, but has a disseminated presentation that is frequently fatal. It is commonly misidentified as a yeast. Tumor necrosis factor-alpha inhibitors and contamination of central venous catheters may contribute to development of protothecosis. Optimal treatment approaches are yet to be defined. New agents such as miltefosine may be possible future therapies.

Non-invasive method for rapid bedside estimation of inotropy: theory and preliminary clinical validation.

BACKGROUND: There are numerous techniques which attempt to quantify inotropy (or myocardial contractility). None has yet found general acceptance in anaesthesia and critical care as a practical method. We report a novel approach to the determination of inotropy as a bedside procedure which could identify low inotropy states in patients with clinical heart failure. METHODS: We estimated the potential and kinetic energy delivered by the left ventricle using continuous-wave Doppler ultrasound (ultrasonic cardiac output monitor, Uscom, Sydney, Australia) and data available at the point of care. A formula to calculate effective inotropy [Smith-Madigan inotropy index (SMII)] was tested against historical haemodynamic data for 250 control subjects (ASA I patients from preoperative clinic) and 83 patients with acute left ventricular failure (LVF) of New York Heart Association Grade 4 (LVF group). The ratio of potential to kinetic energy (PKR) was investigated as a measure of arterial impedance. RESULTS: Significant differences were found between the control and LVF groups for cardiac index, mean (range)=3.37 (2.84-5.32) vs 1.84 (1.43-2.26) litre min(-1) m(-2); stroke volume index (SVI), 49.2 (39-55) vs 34.3 (23-37) ml m(-2); systemic vascular resistance, 893 (644-1242) vs 1960 (1744-4048) dyn s cm(-5); SMII, 1.78 (1.35-2.24) vs 0.73 (0.43-0.97) W m(-2); and PKR, 29:1 (24-35:1) vs 124:1 (96-174:1), P<0.001 in each case. Normal ranges were calculated for SMII and PKR as mean (+/-1.96) standard deviations, yielding 1.6-2.2 W m(-2) for SMII, and 25-34:1 for PKR. CONCLUSION: The method clearly identified the two clinical groups with no overlap of data points. The discriminant power of SMII and PKR may offer valuable diagnostic methods and monitoring tools in anaesthesia and critical care. This is the first report of normal ranges for SMII and PKR.