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The structure and thermal motion of the B800-850 LH2 complex from Rps.acidophila at 2.0A resolution and 100K: new structural features and functionally relevant motions.

The structure at 100K of integral membrane light-harvesting complex II (LH2) from Rhodopseudomonas acidophila strain 10050 has been refined to 2.0A resolution. The electron density has been significantly improved, compared to the 2.5A resolution map, by high resolution data, cryo-cooling and translation, libration, screw (TLS) refinement. The electron density reveals a second carotenoid molecule, the last five C-terminal residues of the alpha-chain and a carboxy modified alpha-Met1 which forms the ligand of the B800 bacteriochlorophyll. TLS refinement has enabled the characterisation of displacements between molecules in the complex. B850 bacteriochlorophyll molecules are arranged in a ring of 18 pigments composed of nine approximate dimers. These pigments are strongly coupled and at their equilibrium positions the excited state dipole interaction energies, within and between dimers, are approximately 370cm(-1) and 280cm(-1), respectively. This difference in coupling energy is similar in magnitude to changes in interaction energies arising from the pigment displacements described by TLS tensors. The displacements appear to be non-random in nature and appear to be designed to optimise the modulation of pigment energy interactions. This is the first time that LH2 pigment displacements have been quantified experimentally. The calculated energy changes indicate that there may be significant contributions to inter-pigment energy interactions from molecular displacements and these may be of importance to photosynthetic energy transfer.

Bacterial Proteins↗

How accurate is visual assessment of synchronicity in myocardial motion? An In vitro study with computer-simulated regional delay in myocardial motion: clinical implications for rest and stress echocardiography studies.

Asynchronicity in echocardiographic images is normally assessed visually. No prior quantitative studies have determined the limitations of this approach. To quantify visual recognition of myocardial asynchronicity in echocardiographic images, computer-simulated delay phantom loops were generated from a 3.3 MHz digital image data from a normal left ventricular short-axis heart cycle acquired at 55 frames per second. Six expert observers visually assessed 30 abnormal and 3 normal loops with differing computer-induced delay patterns on 3 occasions and in this optimally simulated environment could recognize only single delays of 89 ms or more. This was improved to 71 ms or more by use of side-by-side (normal versus abnormal) comparative review. Thus visual assessment of clinically important regional delay in rest or stress echo images is limited.

Computer Simulation↗

The role of fetal breathing motions compared with gasping motions in pulmonary airway uptake of intra-amniotic iron dextran.

OBJECTIVE: We hypothesized that normal fetal breathing, not acute asphyxial gasping, results in the movement of iron dextran from the amniotic cavity into the fetal lungs. In addition, the amount of iron dextran moving into the fetal lungs is cumulative with time. STUDY DESIGN: Twelve pregnant New Zealand White rabbits at 25 days of gestation were sedated and underwent ultrasound-guided injections of iron dextran into the amniotic cavities of the rabbit fetuses in both horns of each pregnant doe. Oxygen saturation was maintained at >90% in the pregnant does. The 12 does were then equally assigned to four groups on the basis of the duration of fetal exposure to the dextran (0, 8, 16, and 24 hours). At the end of each time point, one half of the fetuses received an intracardiac injection of potassium chloride to induce gasping just before necropsy. Gasping was confirmed by ultrasound scanning. At necropsy, the fetal lungs were evaluated grossly and underwent histomorphometry for iron distribution and quantification in the fetal airways. RESULTS: In the animals that received iron dextran, there was no significant difference in iron accumulation at any time point between those animals that did and did not receive potassium chloride, which suggests that acute gasping does not increase the accumulation of amniotic fluid substances in the lungs. The amount of iron in the fetal airways increased significantly with progressive length of exposure. CONCLUSION: We conclude that normal fetal breathing, not acute asphyxial gasping, resulted in the movement of intra-amniotic iron dextran into the fetal lungs and that the amount of substances that move into the fetal lungs accumulated with time.

Amniotic Fluid↗

Nonisothermal Brownian motion: Thermophoresis as the macroscopic manifestation of thermally biased molecular motion.

A quiescent single-component gravity-free gas subject to a small steady uniform temperature gradient T, despite being at rest, is shown to experience a drift velocity UD=-D* gradient ln T, where D* is the gas's nonisothermal self-diffusion coefficient. D* is identified as being the gas's thermometric diffusivity alpha. The latter differs from the gas's isothermal isotopic self-diffusion coefficient D, albeit only slightly. Two independent derivations are given of this drift velocity formula, one kinematical and the other dynamical, both derivations being strictly macroscopic in nature. Within modest experimental and theoretical uncertainties, this virtual drift velocity UD=-alpha gradient ln T is shown to be constitutively and phenomenologically indistinguishable from the well-known experimental and theoretical formulas for the thermophoretic velocity U of a macroscopic (i.e., non-Brownian) non-heat-conducting particle moving under the influence of a uniform temperature gradient through an otherwise quiescent single-component rarefied gas continuum at small Knudsen numbers. Coupled with the size independence of the particle's thermophoretic velocity, the empirically observed equality, U=UD, leads naturally to the hypothesis that these two velocities, the former real and the latter virtual, are, in fact, simply manifestations of the same underlying molecular phenomenon, namely the gas's Brownian movement, albeit biased by the temperature gradient. This purely hydrodynamic continuum-mechanical equality is confirmed by theoretical calculations effected at the kinetic-molecular level on the basis of an existing solution of the Boltzmann equation for a quasi-Lorentzian gas, modulo small uncertainties pertaining to the choice of collision model. Explicitly, this asymptotically valid molecular model allows the virtual drift velocity UD of the light gas and the thermophoretic velocity U of the massive, effectively non-Brownian, particle, now regarded as the tracer particle of the light gas's drift velocity, to each be identified with the Chapman-Enskog "thermal diffusion velocity" of the quasi-Lorentzian gas, here designated by the symbol UM/M, as calculated by de la Mora and Mercer. It is further pointed out that, modulo the collective uncertainties cited above, the common velocities UD,U, and UM/M are identical to the single-component gas's diffuse volume current jv, the latter representing yet another, independent, strictly continuum-mechanical concept. Finally, comments are offered on the extension of the single-component drift velocity notion to liquids, and its application towards rationalizing Soret thermal-diffusion separation phenomena in quasi-Lorentzian liquid-phase binary mixtures composed of disparately sized solute and solvent molecules, with the massive Brownian solute molecules (e.g., colloidal particles) present in disproportionately small amounts relative to that of the solvent.

Journal Article↗

Motion--Laparoscopic Nissen fundoplication is more cost effective than oral PPI administration: arguments against the motion.

Discussion of the cost effectiveness of medical and surgical treatments of gastroesophageal reflux disease (GERD) is plagued by a number of logical fallacies. Several of these defects in reasoning are reviewed. For example, it is inappropriate to compare the costs of therapies unless they are equally effective. The relative cost effectiveness of various treatment options is difficult to determine because monetary expenditures and gains in health status cannot easily be measured in commensurate units. Not everything can be translated into incremental cost effectiveness ratios. Two decision analyses from European investigators seemed to show that Nissen fundoplication was more cost effective than long term acid-suppression therapy, but they failed to consider the costs of surgical complications and failures. The most comprehensive decision analysis, employing a Markov chain model, found that the two treatment options were roughly equivalent, at least during the first seven years of follow-up. Decision analyses often do not reflect actual practice patterns and cannot provide solutions to problems that cannot be solved by appropriate medical reasoning. Moreover, results that are reported by specialized surgical centres probably cannot be duplicated by less experienced surgeons. The increasing incidence of esophageal adenocarcinoma has been erroneously attributed to the use of potent acid-suppressant medications, but the actual cause has been shown to be the decreased prevalence of Helicobacter pylori. There are no significant differences in the incidence of this tumour after medical or surgical therapy of GERD. It is unlikely, however, that arguments will convince proponents of one treatment or another to change their opinions.

Costs and Cost Analysis↗

Motion - the available treatments for hepatitis C are cost effective: arguments for the motion.

The treatment of hepatitis C has evolved over the past decade, and a combination of interferon (IFN), pegylated or standard type, and ribavirin is now acknowledged as the therapy of choice. Questions remain, however, about the duration of treatment and which patients are the most likely to benefit from therapy. Cost effectiveness analyses (CEAs) have been employed to answer these questions. Before the results can be interpreted appropriately, however, clinicians must make themselves aware of the underlying assumptions and the nature of the 'reference' case. Moreover, certain parameters, including quality-of-life evaluations, may not be easily translated from one jurisdiction to another. The costs and benefits of treatment are often very sensitive to such factors as patient age, viral load, histological severity and the viral genotype. Randomized controlled clinical trials, and the CEAs on which they are based, have shown that combination therapy is more cost effective than IFN monotherapy, and that both are cost effective compared with no treatment. Ongoing research on the use of pegylated IFN, weight-adjusted dosing of ribavirin, and the treatment of relapsers and nonresponders will provide valuable data that could be incorporated into future CEAs. Health care resources are vast, but not limitless. Therefore, health care providers need to become aware of how best to allocate resources to the general population. CEAs can facilitate this process by determining which treatment strategies are likely to yield the greatest clinical benefits without excessive expenditures.

Antiviral Agents↗