Intermittent compression of the calf muscle as a countermeasure to protect blood pressure and brain blood flow in upright posture in older adults.

PURPOSE: Orthostatic hypotension, leading to cerebral hypoperfusion, can result in postural instability and falls in older adults. We determined the efficacy of a novel, intermittent pneumatic compression system, applying pressure around the lower legs, as a countermeasure against orthostatic stress in older adults. METHODS: Data were collected from 13 adults (4 male) over 65 years of age. Non-invasive ultrasound measured middle cerebral artery blood velocity (MCAv) and finger photoplethysmography measured mean arterial blood pressure (MAP). Intermittent lower leg compression was applied in a peristaltic manner in the local diastolic phase of each cardiac cycle to optimize venous return during 1-min of seated rest and during a sit-to-stand transition to 1-min of quiet standing with compression initiated 15 s before transition. RESULTS: During seated rest, compression resulted in a 4.5 ± 6.5 mmHg increase in MAP, and 2.3 ± 2.1 cm/s increase in MCAv (p < 0.05). MAP and MCAv increased during the 15 s of applied compression before the posture transition (2.3 ± 7.2 mmHg and 2.1 ± 4.0 cm/s, respectively, p < 0.05) with main effects for both variables confirming continued benefit during the transition and quiet stand periods. CONCLUSIONS: Application of carefully timed, intermittent compression to the lower legs of older adults increased MAP and MCAv during seated rest and maintained an elevated MAP and MCAv during a transition to standing posture. Future research could assess the benefits of this technology for persons at risk for orthostatic hypotension on standing and while walking in an effort to reduce injurious, unexplained falls in older adults.

Bio-based Algae Oil: an oxidation and structural analysis.

OBJECTIVE: In search of natural components, vegetal oils are increasingly becoming more popular in cosmetics. However, high oxidation instability, presence of potential allergens and synthetic anti-oxidants have limited their applications so far. Therefore, a need exists for a natural emollient with high oxidation stability. In this work, we report on a novel sustainably produced triglyceride containing primarily three monounsaturated oleic acid chains, dubbed 'Bio-Based Algae Oil' hereafter, as a natural emollient for cosmetic formulations. To produce Bio-Based Algae Oil, simple sugars are converted into triglyceride oils using microalgae fermentation with minimal environmental impact. METHODS: Bio-Based Algae Oil was compared to other commonly used triglyceride-based emollients in the skincare industry in terms of thermal/oxidation stability, composition and moisturizing properties. Oxidation stability of emollients was compared using Rancimat and pressurized differential scanning calorimetry (PDSC) techniques. Fatty acid composition of each oil was analysed using proton nuclear magnetic resonance (1 H-NMR) and gas chromatography (GC) techniques to correlate unsaturation level of each oil to its oxidation stability. We also conducted an in vivo moisturizing study in which skin hydration level of human subjects was compared before and after application of emollient up to 24 h. RESULTS: Results showed that Bio-Based Algae Oil was the most stable emollient in thermal and oxidation stability studies given its low unsaturation and high anti-oxidant content determined by 1 H-NMR and GC techniques. It also provided the highest skin hydration level when applied on skin demonstrating its efficacy as a moisturizing emollient in cosmetic formulations. CONCLUSIONS: Compositional analysis of Bio-Based Algae revealed that it is a triglyceride containing primarily three monounsaturated oleic acid chains with very low polyunsaturated fatty acid content resulting in high oxidation stability and consequently prolonged shelf-life. Given its sustainability, high oxidation stability and skin health benefits such as moisturization demonstrated during an in vivo study, we envision to utilize Bio-Based Algae Oil in many cosmetic formulations across skincare, suncare and bath and shower markets.

OBJECTIF: Dans la quête de composants naturels, les huiles végétales deviennent de plus en plus prisées en cosmétique. Toutefois, la forte instabilité à l'oxydation, la présence d'allergènes potentiels et d'antioxydants synthétiques ont contribué à la réduction de leurs demandes jusqu'ici. Par conséquent, il existe un besoin en émollient naturel doté d'une stabilité à l'oxydation élevée. Dans le cadre de ces travaux, nous présentons un nouveau triglycéride produit de manière durable contenant principalement trois chaînes d'acide oléique mono-insaturées, appelé « Huile d'algues d'origine biologique ¼ comme étant un émollient naturel pour les produits cosmétiques. Pour obtenir de l'Huile d'algues d'origine biologique, des sucres rapides sont transformés en huiles triglycérides par fermentation de microalgues avec un impact environnemental minimal. MÉTHODES: L'huile d'algues d'origine biologique a été comparée à d'autres émollients à base de triglycérides fréquemment utilisés dans l'industrie des soins de la peau en matière de stabilité thermique ou d'oxydation, de composition et de propriétés hydratantes. Stabilité thermique ou oxydation, composition et propriétés hydratantes. La stabilité à l'oxydation des émollients a été comparée grâce au Rancimat et à des techniques de calorimétrie différentielle à balayage haute pression (PDSC). La composition des acides gras de chaque huile a été analysée grâce aux techniques de résonance magnétique nucléaire du proton (1 H-NMR) et de chromatographie en phase gazeuse (CPG) afin de créer une corrélation entre le taux d'insaturation de chaque huile et sa stabilité à l'oxydation. Nous avons également procédé à une étude in vivo de l'hydratation au cours de laquelle le niveau d'hydratation de la peau des patients humains a été comparé avant et après l'utilisation de l'émollient sur une période allant jusqu'à 24 h. RÉSULTATS: Les résultats ont démontré que l'huile d'algues d'origine biologique était l'émollient le plus stable lors des études sur la stabilité thermique et la stabilité à l'oxydation, en raison de sa faible insaturation et de sa teneur élevée en antioxydants déterminés par les techniques 1 H-NMR et GC. Elle a également produit le taux d'hydratation de la peau le plus élévé, lorsqu'appliqué à la peau, ce qui démontre son efficacité comme émollient hydratant dans les produits cosmétiques. CONCLUSIONS: L'analyse de la composition de l'huile d'algues d'origine biologique a révélé qu'il s'agit d'un triglycéride contenant principalement trois chaînes d'acide oléique mono-insaturées avec une très faible teneur en acides gras polyinsaturés, ce qui entraîne une stabilité à l'oxydation élevée et par conséquent une durée de vie prolongée. Compte tenu de sa durabilité, sa stabilité à l'oxydation élevée et ses bienfaits pour la santé de la peau, notamment l'hydratation démontrée au cours d'une étude in vivo, nous envisageons d'utiliser l'huile d'algues d'origine biologique dans de nombreuses formulations cosmétiques présentes sur le marché des soins de la peau, des produits solaires et des bains et douches.

Comparison of portable blood-warming devices under simulated pre-hospital conditions: a randomised in-vitro blood circuit study.

Pre-hospital transfusion of blood products is a vital component of many advanced pre-hospital systems. Portable fluid warmers may be utilised to help prevent hypothermia, but the limits defined by manufacturers often do not reflect their clinical use. The primary aim of this randomised in-vitro study was to assess the warming performance of four portable blood warming devices (Thermal Angel, Hypotherm X LG, °M Warmer, Buddy Lite) against control at different clinically-relevant flow rates. The secondary aim was to assess haemolysis rates between devices at different flow rates. We assessed each of the four devices and the control, at flow rates of 50 ml.min-1 , 100 ml.min-1 and 200 ml.min-1 , using a controlled perfusion circuit with multisite temperature monitoring. Free haemoglobin concentration, a marker of haemolysis, was measured at multiple points during each initial study run with spectrophotometry. At all flow rates, the four devices provided superior warming performance compared with the control (p < 0.001). Only the °M Warmer provided a substantial change in temperature at all flow rates (mean (95%CI) temperature change of 21.1 (19.8-22.4) °C, 20.4 (19.1-21.8) °C and 19.4 (17.7-21.1) °C at 50 ml.min-1 , 100 ml.min-1 and 200 ml.min-1 , respectively). There was no association between warming and haemolysis with any device (p = 0.949) or flow rate (p = 0.169). Practical issues, which may be relevant to clinical use, also emerged during testing. Our results suggest that there were significant differences in the performance of portable blood warming devices used at flow rates encountered in clinical practice.

Spontaneous debulking of middle fossa chordoma extension after transnasal petroclival biopsy--report of a case.

BACKGROUND: Clival chordomas are difficult tumors to treat, particularly when they have already grown beyond the confines of the clivus. PATIENT: We report the case of a 52-year-old man with a clival mass consistent with a chordoma with a prominent extension into the right middle fossa. At the patient's request, he underwent a simple endonasal biopsy to confirm the diagnosis. A second debulking procedure was planned to debulk the remnant tumor. However, follow-up magnetic resonance imaging showed that much of the middle fossa tumor had decompressed itself through the clival defect into the patient's pharynx. RESULTS: The patient underwent additional clival debulking and proton-beam therapy. After 44 months of follow-up, he had no clinical or radiographic progression of disease. CONCLUSION: It is intriguing to think that leaving a path for easy egress for a chordoma from the clivus may prevent it from building up in the bone and spreading.

TOPAS-nBio validation for simulating water radiolysis and DNA damage under low-LET irradiation.

The chemical stage of the Monte Carlo track-structure simulation code Geant4-DNA has been revised and validated. The root-mean-square (RMS) empirical parameter that dictates the displacement of water molecules after an ionization and excitation event in Geant4-DNA has been shortened to better fit experimental data. The pre-defined dissociation channels and branching ratios were not modified, but the reaction rate coefficients for simulating the chemical stage of water radiolysis were updated. The evaluation of Geant4-DNA was accomplished with TOPAS-nBio. For that, we compared predicted time-dependentGvalues in pure liquid water for·OH, e-aq, and H2with published experimental data. For H2O2and H·, simulation of added scavengers at different concentrations resulted in better agreement with measurements. In addition, DNA geometry information was integrated with chemistry simulation in TOPAS-nBio to realize reactions between radiolytic chemical species and DNA. This was used in the estimation of the yield of single-strand breaks (SSB) induced by137Csγ-ray radiolysis of supercoiled pUC18 plasmids dissolved in aerated solutions containing DMSO. The efficiency of SSB induction by reaction between radiolytic species and DNA used in the simulation was chosen to provide the best agreement with published measurements. An RMS displacement of 1.24 nm provided agreement with measured data within experimental uncertainties for time-dependentGvalues and under the presence of scavengers. SSB efficiencies of 24% and 0.5% for·OH and H·, respectively, led to an overall agreement of TOPAS-nBio results within experimental uncertainties. The efficiencies obtained agreed with values obtained with published non-homogeneous kinetic model and step-by-step Monte Carlo simulations but disagreed by 12% with published direct measurements. Improvement of the spatial resolution of the DNA damage model might mitigate such disagreement. In conclusion, with these improvements, Geant4-DNA/TOPAS-nBio provides a fast, accurate, and user-friendly tool for simulating DNA damage under low linear energy transfer irradiation.

Adenohypophysial transmembrane potentials: polarity reversal by elevated external potassium ion concentration.

Incubation of rat adenohypophyses in potassium ion of sufficient concentration to provoke the release of several of the adenohypophysial trophic hormones produces a reversed, positive transmembrane potential in more than half the cells. This finding is consistent with a process of "stimulus-secretion coupling" in which hypothalamic releasing factors act by selective depolarization of their "target" cells. The positive potentials may be due to a prolonged preferential permeability to calcium ions triggered by an initial depolarization of the cell membrane to a threshold value by increased external potassium ion.

Celestial mechanics on a microscopic scale.

Classical and semiclassical methods are unrivaled in providing an intuitive and computationally tractable approach to the study of atomic, molecular, and nuclear dynamics. An important advantage of such methods is their ability to uncover in a single picture underlying structures that may be hard to extract from the profusion of data supplied by detailed quantum calculations. Modern trends in semiclassical mechanics are described, particularly the combination of group theoretical methods with techniques of nonlinear dynamics. Application is made to intramolecular energy transfer and to the electronic structure of atomic Rydberg states in external electric and magnetic fields.

Potassium, corticosterone, and adrenocorticotropic hormone release in vitro.

Incubation of rat adenohypophyses in a high concentration of potassium increases adrenocorticotropic hormone release. This increased release is suppressed by the addition of corticosterone to the incubating medium. Our findings are consistent with a process of "stimulus-secretion coupling" proposed for other glands and suggest that corticosterone may operate directly on the adenohypophysial cell membrane to inhibit releasing mechanisms.

A New Standard DNA Damage (SDD) Data Format.

Our understanding of radiation-induced cellular damage has greatly improved over the past few decades. Despite this progress, there are still many obstacles to fully understand how radiation interacts with biologically relevant cellular components, such as DNA, to cause observable end points such as cell killing. Damage in DNA is identified as a major route of cell killing. One hurdle when modeling biological effects is the difficulty in directly comparing results generated by members of different research groups. Multiple Monte Carlo codes have been developed to simulate damage induction at the DNA scale, while at the same time various groups have developed models that describe DNA repair processes with varying levels of detail. These repair models are intrinsically linked to the damage model employed in their development, making it difficult to disentangle systematic effects in either part of the modeling chain. These modeling chains typically consist of track-structure Monte Carlo simulations of the physical interactions creating direct damages to DNA, followed by simulations of the production and initial reactions of chemical species causing so-called "indirect" damages. After the induction of DNA damage, DNA repair models combine the simulated damage patterns with biological models to determine the biological consequences of the damage. To date, the effect of the environment, such as molecular oxygen (normoxic vs. hypoxic), has been poorly considered. We propose a new standard DNA damage (SDD) data format to unify the interface between the simulation of damage induction in DNA and the biological modeling of DNA repair processes, and introduce the effect of the environment (molecular oxygen or other compounds) as a flexible parameter. Such a standard greatly facilitates inter-model comparisons, providing an ideal environment to tease out model assumptions and identify persistent, underlying mechanisms. Through inter-model comparisons, this unified standard has the potential to greatly advance our understanding of the underlying mechanisms of radiation-induced DNA damage and the resulting observable biological effects when radiation parameters and/or environmental conditions change.

Kinetic behavior of the reaction between hydroxyl radical and the SV40 minichromosome.

Aqueous solutions containing the minichromosomal form of the virus SV40 and the radical scavenger DMSO were subjected to gamma-irradiation, and the resulting formation of single strand breaks (SSB) was quantified. Under the irradiation conditions, most SSBs were produced as a consequence of hydroxyl radical ((•)OH) reactions. By controlling the competition between DMSO and the viral DNA substrate for (•)OH, we are able to estimate the rate coefficient for the reaction of (•)OH with the SV40 minichromosome. The results cannot be described adequately by homogeneous competition kinetics, but it is possible to describe the rate coefficient for the reaction as a function of the scavenging capacity of the solution. The experimentally determined rate coefficient lies in the range 1×10(9) - 2×10(9) L mol(-1) s(-1) at 10(7) s(-1), and increases with increasing scavenging capacity.

Repair of oxidative DNA damage by amino acids.

Guanyl radicals, the product of the removal of a single electron from guanine, are produced in DNA by the direct effect of ionizing radiation. We have produced guanyl radicals in DNA by using the single electron oxidizing agent (SCN)2-, itself derived from the indirect effect of ionizing radiation via thiocyanate scavenging of OH. We have examined the reactivity of guanyl radicals in plasmid DNA with the six most easily oxidized amino acids cysteine, cystine, histidine, methionine, tryptophan and tyrosine and also simple ester and amide derivatives of them. Cystine and histidine derivatives are unreactive. Cysteine, methionine, tyrosine and particularly tryptophan derivatives react to repair guanyl radicals in plasmid DNA with rate constants in the region of approximately 10(5), 10(5), 10(6) and 10(7) dm3 mol(-1) s(-1), respectively. The implication is that amino acid residues in DNA binding proteins such as histones might be able to repair by an electron transfer reaction the DNA damage produced by the direct effect of ionizing radiation or by other oxidative insults.

Evaluation of lesion clustering in irradiated plasmid DNA.

PURPOSE: To measure the yield of DNA strand breaks and clustered lesions in plasmid DNA irradiated with protons, helium nuclei, and y-rays. MATERIALS AND METHODS: Plasmid DNA was irradiated with 1.03, 19.3 and 249 MeV protons (linear energy transfer = 25.5, 2.7, and 0.39 keV microm(-1) respectively), 26 MeV helium nuclei (25.5 keV microm) and gamma-rays (137Cs or 60Co) in phosphate buffer containing 2 mM or 200 mM glycerol. Single-and double-strand breaks (SSB and DSB) were measured by gel electrophoresis, and clustered lesions containing base lesions were quantified by converting them into irreparable DSB in transformed bacteria. RESULTS: For protons, SSB yield decreased with increasing LET (linear energy transfer). The yield of DSB and all clustered lesions seemed to reach a minimum around 3 keV microm(-1). There was a higher yield of SSB, DSB and total clustered lesions for protons compared to helium nuclei at 25.5 keV microm(-1). A difference in the yields between 137Cs and 60Co gamma-rays was also observed, especially for SSB. CONCLUSION: In this work we have demonstrated the complex LET dependence of clustered-lesion yields, governed by interplay of the radical recombination and change in track structure. As expected, there was also a significant difference in clustered lesion yields between various radiation fields, having the same or similar LET values, but differing in nanometric track structure.

Using RecA protein to enhance kinetic rates of DNA circuits.

While DNA circuits are becoming increasingly useful as signal transducers, their utility is inhibited by their slow catalytic rate. Here, we demonstrate how RecA, a recombination enzyme that catalyzes sequence specific strand exchange, can be used to increase circuit rates up to 9-fold. We also show how the introduction of RNA into DNA circuits further controls the specificity of RecA strand exchange, improving signal-to-noise.

Prevention of neonatal respiratory distress syndrome by tracheal instillation of surfactant: a randomized clinical trial.

With a randomized clinical trial, the possibility was assessed that a tracheal instillation of pulmonary surfactant prior to the first breath might prevent the development of some of the signs of neonatal respiratory distress syndrome. Of the 72 infants in the trial, all born at a gestational age of less than 30 weeks, 39 received 3 or 4 mL of surfactant, prepared from the lipids extracted from calf lung lavage. The treatment resulted in a significantly improved gas exchange during the first 72 hours of life. On the average, the arterial/alveolar PO2 ratio was 0.15 higher for the treated infants, and only about half as much extra oxygen had to be supplied. The respiratory support (peak inspiratory pressure X frequency) could be lowered significantly. Pulmonary interstitial emphysema occurred in 13 of the 33 control infants, but in only three of the 39 treated infants. Six of the control infants died in the neonatal period, but only one treated infant died. It is concluded that surfactant supplementation prior to the first breath is feasible and is of value as protection against the respiratory distress syndrome and the negative effects of hypoxia and ventilatory support.

Yield of single-strand breaks due to attack on DNA by scavenger-derived radicals.

We have measured the yield of single-strand breaks (SSBs) in plasmid DNA after 137Cs gamma irradiation, in the presence of dimethyl sulfoxide (DMSO). In the presence of oxygen, the formation of SSBs is due to hydroxyl radical attack. As the DMSO concentration is increased from 10(-4) mol dm-3 to 1 mol dm-3, the SSB yield in the presence and absence of oxygen decreases by over 100-fold and less than 10-fold, respectively. From the DMSO and DNA concentration dependencies of the SSB yield in the absence of oxygen, the second-order rate constant for the reaction of the methyl radical (derived from DMSO) and DNA can be estimated as k2 = 8.8 x 10(4) dm3 mol-1 s-1. Several other scavengers were compared with DMSO under anoxia. Radicals derived from isopropyl alcohol and glycerol also caused SSB formation in DNA, while those from 2-deoxyribose, thymine, 1,3-dimethylthymine and 1,3-dimethyluracil did not. In the case of the scavenger tert-butyl alcohol, it is unclear whether the hydrogen atom (H.) or an organic radical is responsible for the higher SSB yield under anoxic conditions.

Variation of single-strand break yield with scavenger concentration for plasmid DNA irradiated in aqueous solution.

We have measured the yield of single-strand breaks (SSBs), induced by 137Cs gamma radiation as assayed by agarose gel electrophoresis, for three plasmids and SV40 DNA irradiated in aerobic aqueous solution. DNA SSBs are caused mainly by the hydroxyl radical under these conditions. To characterize the reactivity of DNA with the hydroxyl radical, we investigated the variation of the G value for SSBs [G(SSB)] with the concentration of added hydroxyl radical scavengers. We find that simple competition kinetics does not describe our results, but that a nonhomogeneous kinetics model is in good agreement. At a DNA concentration of 50 micrograms cm-3, G(SSB) for the direct effect is about 1 x 10(-5) mumol J-1 for the DNA substrates studied. This is equivalent to 2 x 10(-10) SSB Gy-1 Da-1. Estimates of the efficiency of SSB induction per OH. radical interaction with DNA (0.32-0.44) reveal that all plasmids are essentially equal in reactivity.

Variation of single-strand break yield with scavenger concentration for the SV40 minichromosome irradiated in aqueous solution.

We have measured the yield of single-strand breaks (SSBs) induced in aerobic aqueous solution by 137Cs gamma irradiation for the SV40 minichromosome as measured by agarose gel electrophoresis. Under these conditions, DNA SSBs are caused mainly by the hydroxyl radical. To characterize the reactivity of the SV40 minichromosome with the hydroxyl radical and to compare its behavior with that of naked DNA, we examined the variation of the G value for SSB formation, G(SSB), with the concentration of added hydroxyl radical scavengers. We find that simple competition kinetics is not applicable, but that a nonhomogeneous kinetics model is in much better agreement. Estimates of the efficiency of SSB induction per OH radical interaction with the SV40 minichromosome (0.04-0.05) indicate that this substrate is about five times more radioresistant than naked DNA at scavenging capacities < 10(8) s-1. At a DNA concentration of 50 micrograms ml-1, G(SSB) for the direct effect in the minichromosome is about 1 x 10(-5) mumol J-1 (2 x 10(-10) SSB Gy-1 Da-1), essentially equal to that for naked DNA.

The effect of superhelical density on the yield of single-strand breaks in gamma-irradiated plasmid DNA.

Using agarose gel electrophoresis, the formation of DNA single-strand breaks (SSBs) by 137Cs gamma irradiation was quantified in negatively supercoiled topological isomers of plasmid pUC18. The G value for SSB formation falls slightly from 1 x 10(8) to 8 x 10(-9) SSB Gy-1 Da-1 as the superhelical density varies from 0.00 to -0.08. This result is not in agreement with recent observations by others which suggest that increasing the negative superhelical density of plasmid DNA increases its sensitivity to X irradiation.

The difference that linear energy transfer makes to precursors of DNA strand breaks.

Using agarose gel electrophoresis, we have measured the yields of DN A single- and double-strand breaks (SSBs and DSBs) for plasmid DNA irradiated in aerobic aqueous solution with either 137Cs gamma rays or 4He ions with a mean LET of 94 or 150 keV micron-1. The presence of dimethyl sulfoxide (DMSO) resulted in a decrease in the yields of both SSBs and DSBs, with a greater decrease being apparent for gamma irradiation than for 4He-ion irradiation. Irradiation by 4He ions in the presence of N-(2-thioethyl)- 1,3-diaminopropane (WR-1065) resulted in a decrease in the yield of SSBs and a slightly larger decrease in the yield of DSBs. Together with results obtained previously, these observations suggest a substantial contribution to the formation of SSBs and DSBs by 4He ions by species containing at least two radicals and more than two radicals, respectively.

Yield of strand breaks as a function of scavenger concentration and LET for SV40 irradiated with 4He ions.

We have measured by gel electrophoresis the yields of single- and double-strand breaks (SSBs and DSBs) induced in aqueous solutions of SV40 DNA and the SV40 minichromosome by 137Cs gamma rays (mean LET 0.3 keV micron-1) and 4He ions (mean LETs 85, 102, and 152 keV microns-1). DNA SSBs are caused mainly by the hydroxyl radicals under these conditions and are reduced in yield as either the hydroxyl radical scavenger concentration or the LET is increased (over the range studied). The G(SSB) for 4He ion irradiation is less by a factor of up to 10 than the G(SSB) for gamma irradiation, depending upon the scavenger concentration. The difference in the yields of SSBs agrees well with the difference in the yields of hydroxyl radicals for the radiations in question. In contrast, the yields of DSBs are similar for gamma and 4He ion irradiation over much of the range of scavenging capacity studied. However, at the highest scavenger concentrations the yields of DSBs are greater for 4He ion irradiation. In addition, the yields of DSBs remain almost constant with increasing LET (over the range studied). Therefore the relative yield of DSBs per SSB increases with increasing LET, supporting the hypothesis that increasing LET leads to an increased clustering of damage in DNA.