Osteoclastic resorptive capacity is suppressed in patients receiving hyperbaric oxygen therapy.

BACKGROUND AND PURPOSE: Hypoxia, necrosis, and bone loss are hallmarks of many skeletal diseases. Hyperbaric oxygen therapy (HBO) is often used as an adjunctive therapy in these cases. However the in vivo effect of HBO on osteoclast formation has not been fully established. We therefore carried out a longitudinal study to examine the effect of HBO on osteoclast formation and bone resorptive capacity in patients who were referred to the Plymouth Hyperbaric Medical Centre. METHODS: Osteoclast precursors were isolated from peripheral blood prior to and following 10 and 25 daily hyperbaric treatments (100% O2 at 2.4 atmospheres absolute ATA for 90 min) to determine osteoclast formation and resorptive capacity. The expression of key regulators of osteoclast differentiation RANK, Dc-STAMP, and NFATc1 was also assessed by quantitative real-time PCR. RESULTS: HBO reduced the ability of precursors to form osteoclasts and reduced bone resorption in a treatment-dependent manner. The initial suppressive effect of HBO was more pronounced on mononuclear osteoclast formation than on multinuclear osteoclast formation, and this was accompanied by reduction in the expression of key regulators of osteoclast formation, RANK and Dc-STAMP. INTERPRETATION: This study shows for the first time that in vivo, HBO suppresses the ability of monocytic precursors to form resorptive osteoclasts

Probing Evolutionary Repeatability: Neutral and Double Changes and the Predictability of Evolutionary Adaptation

The question of how organisms adapt is among the most fundamental in evolutionary biology. Two recent studies investigated the evolution of Escherichia coli in response to challenge with the antibiotic cefotaxime. Studying five mutations in the beta-lactamase gene that together confer significant antibiotic resistance, the authors showed a complex fitness landscape that greatly constrained the identity and order of intermediates leading from the initial wildtype genotype to the final resistant genotype. Out of 18 billion possible orders of single mutations leading from non-resistant to fully-resistant form, they found that only 27 (1.5x10(-7)%) pathways were characterized by consistently increasing resistance, thus only a tiny fraction of possible paths are accessible by positive selection. I further explore these data in several ways.Allowing neutral changes (those that do not affect resistance) increases the number of accessible pathways considerably, from 27 to 629. Allowing multiple simultaneous mutations also greatly increases the number of accessible pathways. Allowing a single case of double mutation to occur along a pathway increases the number of pathways from 27 to 259, and allowing arbitrarily many pairs of simultaneous changes increases the number of possible pathways by more than 100 fold, to 4800. I introduce the metric 'repeatability,' the probability that two random trials will proceed via the exact same pathway. In general, I find that while the total number of accessible pathways is dramatically affected by allowing neutral or double mutations, the overall evolutionary repeatability is generally much less affected.These results probe the conceivable pathways available to evolution. Even when many of the assumptions of the analysis of Weinreich et al. (2006) are relaxed, I find that evolution to more highly cefotaxime resistant beta-lactamase proteins is still highly repeatable

Veterinary Conduct and Animal Welfare

This paper is a lecture presented to the same Association but fifteen years later: the 131st Annual Congress in 1984. This second presentation contemplates two points: First, it tries to indicate how this criticism has gradually emerged and a historical outline is put forth of the development of veterinary medicine, a differentiation being made between a mythical, a technical, and a critical approach. Second, a discussion of how veterinarians have to associate themselves with this criticism in their professional conduct is presented. This discussion is necessary for two reasons. Veterinarians have increasingly become aware that they bear a professional responsibility not only for animal health but also for animal welfare; and, veterinarians are expected to give their views in concrete situations

Decomposition and nutrient release of leguminous plants in coffee agroforestry systems.

Leguminous plants used as green manure are an important nutrient source for coffee plantations, especially for soils with low nutrient levels. Field experiments were conducted in the Zona da Mata of Minas Gerais State, Brazil to evaluate the decomposition and nutrient release rates of four leguminous species used as green manures (Arachis pintoi, Calopogonium mucunoides, Stizolobium aterrimum and Stylosanthes guianensis) in a coffee agroforestry system under two different climate conditions. The initial N contents in plant residues varied from 25.7 to 37.0 g kg-1 and P from 2.4 to 3.0 g kg-1. The lignin/N, lignin/polyphenol and(lignin+polyphenol)/N ratios were low in all residues studied. Mass loss rates were highest in the first 15 days, when 25 % of the residues were decomposed. From 15 to 30 days, the decomposition rate decreased on both farms. On the farm in Pedra Dourada (PD), the decomposition constant k increased in the order C. mucunoides < S. aterrimum < S. guianensis < A. pintoi. On the farm in Araponga (ARA), there was no difference in the decomposition rate among leguminous plants. The N release rates varied from 0.0036 to 0.0096 d-1. Around 32 % of the total N content in the plant material was released in the first 15 days. In ARA, the N concentration in the S. aterrimum residues was always significantly higher than in the other residues. At the end of 360 days, the N released was 78 % in ARA and 89 % in PD of the initial content. Phosphorus was the most rapidly released nutrient (k values from 0.0165 to 0.0394 d-1). Residue decomposition and nutrient release did not correlate with initial residue chemistry and biochemistry, but differences in climatic conditions between the two study sites modified the decomposition rate constants

Hybrid materials based on polyethylene and MCM-41 microparticles functionalized with silanes: catalytic aspects of in situ polymerization, crystalline features and mechanical properties

New nanocomposites based on polyethylene have been prepared by in situ polymerization of ethylene in presence of mesoporous MCM-41. The polymerization reactions were performed using a zirconocene catalyst either under homogenous conditions or supported onto mesoporous MCM-41 particles, which are synthesized and decorated post-synthesis with two silanes before polymerization in order to promote an enhanced interfacial adhesion. The existence of polyethylene chains able to crystallize within the mesoporous channels in the resulting nanocomposites is figured out from the small endothermic process, located at around 80 C, on heating calorimetric experiments, in addition to the main melting endotherm. These results indicate that polyethylene macrochains can grow up during polymerization either outside or inside the MCM-41 channels, these keeping their regular hexagonal arrangements. Mechanical response is observed to be dependent on the content in mesoporous MCM-41 and on the crystalline features of polyethylene. Accordingly, stiffness increases and deformability decreases in the nanocomposites as much as MCM-41 content is enlarged and polyethylene amount within channels is raised. Ultimate mechanical performance improves with MCM-41 incorporation without varying the final processing temperature

Effectiveness and cost of radiofrequency ablation and stereotactic body radiotherapy for treatment of early‐stage hepatocellular carcinoma: An analysis of SEER‐medicare

IntroductionFor early‐stage hepatocellular carcinoma (HCC) patients, ablative strategies are potentially curative treatment options. Stereotactic body radiotherapy (SBRT) has emerged as a promising ablative therapy, although its comparison with radiofrequency ablation (RFA) remains confined to a single institution retrospective review. We sought to characterize the comparative outcomes and cost between the two treatment strategies.MethodsWe conducted a secondary analysis of the Surveillance, Epidemiology, and End Results (SEER)‐Medicare linked database (2004–2011) and identified adult patients with stage I or II HCC and treated with RFA or SBRT as the initial treatment within 6 months of diagnosis. Survival analysis was conducted using Kaplan–Meier curves and multivariate Cox proportional hazard analysis. Factors associated with overall survival and 90‐day hospital admission post‐treatment were identified using propensity score (PS) adjusted multivariate analysis. We performed costs analysis and calculated incremental cost‐effectiveness ratios (ICER).ResultsFour hundred and forty patients were identified, 408 treated with RFA and 32 SBRT. In the overall cohort, 90‐day hospitalization and 1‐year mortality were similar between groups but RFA patients had better overall survival (P < 0.001). Multivariate analysis showed advanced age, higher stage, decompensated cirrhosis, and treatment with SBRT (HR 1.80; 95%CI: 1.15–2.82) was associated with worse survival, but in the PS adjusted analysis, survival and costs were similar between the two groups.ConclusionIn a national cohort of early stage HCC patients, treatment with RFA vs SBRT resulted in no significant difference in survival, 90‐day hospitalization, or costs. These data highlight the need for a randomized clinical trial comparing these two modalities.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/146355/1/jmiro12754_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/146355/2/jmiro12754.pd

Massive stars as thermonuclear reactors and their explosions following core collapse

Nuclear reactions transform atomic nuclei inside stars. This is the process of stellar nucleosynthesis. The basic concepts of determining nuclear reaction rates inside stars are reviewed. How stars manage to burn their fuel so slowly most of the time are also considered. Stellar thermonuclear reactions involving protons in hydrostatic burning are discussed first. Then I discuss triple alpha reactions in the helium burning stage. Carbon and oxygen survive in red giant stars because of the nuclear structure of oxygen and neon. Further nuclear burning of carbon, neon, oxygen and silicon in quiescent conditions are discussed next. In the subsequent core-collapse phase, neutronization due to electron capture from the top of the Fermi sea in a degenerate core takes place. The expected signal of neutrinos from a nearby supernova is calculated. The supernova often explodes inside a dense circumstellar medium, which is established due to the progenitor star losing its outermost envelope in a stellar wind or mass transfer in a binary system. The nature of the circumstellar medium and the ejecta of the supernova and their dynamics are revealed by observations in the optical, IR, radio, and X-ray bands, and I discuss some of these observations and their interpretations.Comment: To be published in " Principles and Perspectives in Cosmochemistry" Lecture Notes on Kodai School on Synthesis of Elements in Stars; ed. by Aruna Goswami & Eswar Reddy, Springer Verlag, 2009. Contains 21 figure

Patient‐reported barriers are associated with lower hepatocellular carcinoma surveillance rates in patients with cirrhosis

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/136324/1/hep28770_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/136324/2/hep28770.pd

Corticotropin-releasing Factor (CRF) and Urocortin Promote the Survival of Cultured Cerebellar GABAergic Neurons Through the Type 1 CRF Receptor

Corticotropin releasing factor (CRF) is known to be involved in the stress response and in some degenerative brain disorders. In addition, CRF has a role as a neuromodulator in adult cerebellar circuits. Data from developmental studies suggest a putative role for CRF as a trophic factor during cerebellar development. In this study, we investigated the trophic role for CRF family of peptides by culturing cerebellar neurons in the presence of CRF, urocortin or urocortin II. Primary cell cultures of cerebella from embryonic day 18 mice were established, and cells were treated for either 1, 5 or 9 days with Basal Medium Eagles complete medium alone or complete medium with 1 µM CRF, urocortin, or urocortin II. The number of GABA-positive neurons in each treatment condition was counted at each culture age for monitoring the changes in neuronal survival. Treatment with 1 µM CRF or 1 µM urocortin increased the survival of GABAergic neurons at 6 days in vitro and 10 days in vitro, and this survival promoting effect was abolished by treatment with astressin in the presence of those peptides. Based on these data, we suggest that CRF or urocortin has a trophic role promoting the survival of cerebellar GABAergic neurons in cultures