Expression of atrophy mRNA relates to tendon tear size in supraspinatus muscle

Skeletal muscle atrophy and fatty infiltration develop after tendon tearing. The extent of atrophy serves as one prognostic factor for the outcome of surgical repair of rotator cuff tendon tears. We asked whether mRNA of genes involved in regulation of degradative processes leading to muscle atrophy, ie, FOXOs, MSTN, calpains, cathepsins, and transcripts of the ubiquitin-proteasome pathway, are overexpressed in the supraspinatus muscle in patients with and without rotator cuff tears. We evaluated biopsy specimens collected during surgery of 53 consecutive patients with different sizes of rotator cuff tendon tears and six without tears. The levels of corresponding gene transcripts in total RNA extracts were assessed by semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR) analysis. Supraspinatus muscle atrophy was assessed by MRI. The area of muscle tissue (or atrophy), decreased (increased) with increasing tendon tear size. The transcripts of CAPN1, UBE2B, and UBE3A were upregulated more than twofold in massive rotator cuff tears as opposed to smaller tears or patients without tears. These atrophy gene products may be involved in cellular processes that impair functional recovery of affected muscles after surgical rotator cuff repair. However, the damaging effects of gene products in their respective proteolytic processes on muscle structures and proteins remains to be investigated.

Wear particles and surface topographies are modulators of osteoclastogenesis in vitro

Prosthetic and osteosynthetic implants from metal alloys will be indispensable in orthopedic surgery, as long as tissue engineering and biodegradable bone substitutes do not lead to products that will be applied in clinical routine for the repair of bone, cartilage, and joint defects. Therefore, the elucidation of the interactions between the periprosthetic tissues and the implant remains of clinical relevance and several factors are known to affect the longevity of implants. Within this study, the effects of metal particles and surface topography on the recruitment of osteoclasts was investigated in vitro in a coculture of osteoblasts and bone marrow cells. The cells were grown in the presence of particles of different sizes and chemical composition or on metal discs with polished or sandblasted surfaces, respectively. At the end of the culture, newly formed osteoclasts were counted. Osteoclastogenesis was reduced when particles were added directly to the coculture. The effect depended on the size of the particles, small particles exerting stronger effects than larger ones. The chemical composition of the particles, however, did not affect the development of osteoclasts. In cocultures grown on sandblasted surfaces, osteoclasts developed at higher rates than they did in cultures on polished surfaces. The data demonstrate that wear particles and implant surfaces affect osteoclastogenesis and thus may be involved in the induction of local bone resorption and the formation of osteolytic lesions, leading eventually to the loosening of orthopedic implants.

The role of ocean transport in the uptake of anthropogenic CO2

We compare modeled oceanic carbon uptake in response to pulse CO2 emissions using a suite of global ocean models and Earth system models. In response to a CO2 pulse emission of 590 Pg C (corresponding to an instantaneous doubling of atmospheric CO2 from 278 to 556 ppm), the fraction of CO2 emitted that is absorbed by the ocean is: 37±8%, 56±10%, and 81±4% (model mean ±2σ ) in year 30, 100, and 1000 after the emission pulse, respectively. Modeled oceanic uptake of pulse CO2 on timescales from decades to about a century is strongly correlated with simulated present-day uptake of chlorofluorocarbons (CFCs) and CO2 across all models, while the amount of pulse CO2 absorbed by the ocean from a century to a millennium is strongly correlated with modeled radiocarbon in the deep Southern and Pacific Ocean. However, restricting the analysis to models that are capable of reproducing observations within uncertainty, the correlation is generally much weaker. The rates of surface-to-deep ocean transport are determined for individual models from the instantaneous doubling CO2 simulations, and they are used to calculate oceanic CO2 uptake in response to pulse CO2 emissions of different sizes pulses of 1000 and 5000 Pg C. These results are compared with simulated oceanic uptake of CO2 by a number of models simulations with the coupling of climate-ocean carbon cycle and without it. This comparison demonstrates that the impact of different ocean transport rates across models on oceanic uptake of anthropogenic CO2 is of similar magnitude as that of climate-carbon cycle feedbacks in a single model, emphasizing the important role of ocean transport in the uptake of anthropogenic CO2.

Flow disturbances in stent-related coronary evaginations: a computational fluid-dynamic simulation study

Aims: Angiographic ectasias and aneurysms in stented segments have been associated with late stent thrombosis. Using optical coherence tomography (OCT), some stented segments show coronary evaginations reminiscent of ectasias. The purpose of this study was to explore, using computational fluid-dynamic (CFD) simulations, whether OCT-detected coronary evaginations can induce local changes in blood flow. Methods and results: OCT-detected evaginations are defined as outward bulges in the luminal vessel contour between struts, with the depth of the bulge exceeding the actual strut thickness. Evaginations can be characterised cross ectionally by depth and along the stented segment by total length. Assuming an ellipsoid shape, we modelled 3-D evaginations with different sizes by varying the depth from 0.2-1.0 mm, and the length from 1-9 mm. For the flow simulation we used average flow velocity data from non-diseased coronary arteries. The change in flow with varying evagination sizes was assessed using a particle tracing test where the particle transit time within the segment with evagination was compared with that of a control vessel. The presence of the evagination caused a delayed particle transit time which increased with the evagination size. The change in flow consisted locally of recirculation within the evagination, as well as flow deceleration due to a larger lumen - seen as a deflection of flow towards the evagination. Conclusions: CFD simulation of 3-D evaginations and blood flow suggests that evaginations affect flow locally, with a flow disturbance that increases with increasing evagination size.

Is there good simulation basic training for end-to-side vascular microanastomoses?

BACKGROUND Microvascular anastomosis is the cornerstone of free tissue transfers. Irrespective of the microsurgical technique that one seeks to integrate or improve, the time commitment in the laboratory is significant. After extensive previous training on several animal models, we sought to identify an animal model that circumvents the following issues: ethical rules, cost, time-consuming and expensive anesthesia, and surgical preparation of tissues required to access vessels before performing the microsurgical training, not to mention that laboratories are closed on weekends. METHODS Between January 2012 and April 2012, a total of 91 earthworms were used for 150 microsurgical training exercises to simulate vascular end-to-side microanastomosis. The training sessions were divided into ten periods of 7 days. Each training session included 15 simulations of end-to-side vascular microanastomoses: larger than 1.5 mm (n=5), between 1.0 and 1.5 mm (n=5), and smaller than 1.0 mm (n=5). A linear model with the main variables being the number of weeks (as a numerical covariate) and the size of the animal (as a factor) was used to determine the trend in time of anastomosis over subsequent weeks as well as the differences between the different size groups. RESULTS The linear model shows a significant trend (p<0.001) in time of anastomosis in the course of the training, as well as significant differences (p<0.001) between the groups of animals of different sizes. For microanastomoses larger than 1.5 mm, the mean anastomosis time decreased from 19.3±1.0 to 11.1±0.4 min between the first and last week of training (decrease of 42.5%). For training with smaller diameters, the results showed a decrease in execution time of 43.2% (diameter between 1.0 and 1.5 mm) and 40.9% (diameter<1.0 mm) between the first and last periods. The study demonstrates an improvement in the dexterity and speed of nodes execution. CONCLUSION The earthworm appears to be a reliable experimental model for microsurgical training of end-to-side microanastomoses. Its numerous advantages are discussed here and we predict training on earthworms will significantly grow and develop in the near future. LEVEL OF EVIDENCE III This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

An integrated system for 3D hip joint reconstruction from 2D X-rays: a preliminary validation study

The acquisition of conventional X-ray radiographs remains the standard imaging procedure for the diagnosis of hip-related problems. However, recent studies demonstrated the benefit of using three-dimensional (3D) surface models in the clinical routine. 3D surface models of the hip joint are useful for assessing the dynamic range of motion in order to identify possible pathologies such as femoroacetabular impingement. In this paper, we present an integrated system which consists of X-ray radiograph calibration and subsequent 2D/3D hip joint reconstruction for diagnosis and planning of hip-related problems. A mobile phantom with two different sizes of fiducials was developed for X-ray radiograph calibration, which can be robustly detected within the images. On the basis of the calibrated X-ray images, a 3D reconstruction method of the acetabulum was developed and applied together with existing techniques to reconstruct a 3D surface model of the hip joint. X-ray radiographs of dry cadaveric hip bones and one cadaveric specimen with soft tissue were used to prove the robustness of the developed fiducial detection algorithm. Computed tomography scans of the cadaveric bones were used to validate the accuracy of the integrated system. The fiducial detection sensitivity was in the same range for both sizes of fiducials. While the detection sensitivity was 97.96% for the large fiducials, it was 97.62% for the small fiducials. The acetabulum and the proximal femur were reconstructed with a mean surface distance error of 1.06 and 1.01 mm, respectively. The results for fiducial detection sensitivity and 3D surface reconstruction demonstrated the capability of the integrated system for 3D hip joint reconstruction from 2D calibrated X-ray radiographs.

EVALUATION OF THE QUANTITATIVE ACCURACY OF A COMMERCIALLY-AVAILABLE POSITRON EMISSION MAMMOGRAPHY SCANNER

Objective: The PEM Flex Solo II (Naviscan, Inc., San Diego, CA) is currently the only commercially-available positron emission mammography (PEM) scanner. This scanner does not apply corrections for count rate effects, attenuation or scatter during image reconstruction, potentially affecting the quantitative accuracy of images. This work measures the overall quantitative accuracy of the PEM Flex system, and determines the contributions of error due to count rate effects, attenuation and scatter. Materials and Methods: Gelatin phantoms were designed to simulate breasts of different sizes (4 – 12 cm thick) with varying uniform background activity concentration (0.007 – 0.5 μCi/cc), cysts and lesions (2:1, 5:1, 10:1 lesion-to-background ratios). The overall error was calculated from ROI measurements in the phantoms with a clinically relevant background activity concentration (0.065 μCi/cc). The error due to count rate effects was determined by comparing the overall error at multiple background activity concentrations to the error at 0.007 μCi/cc. A point source and cold gelatin phantoms were used to assess the errors due to attenuation and scatter. The maximum pixel values in gelatin and in air were compared to determine the effect of attenuation. Scatter was evaluated by comparing the sum of all pixel values in gelatin and in air. Results: The overall error in the background was found to be negative in phantoms of all thicknesses, with the exception of the 4-cm thick phantoms (0%±7%), and it increased with thickness (-34%±6% for the 12-cm phantoms). All lesions exhibited large negative error (-22% for the 2:1 lesions in the 4-cm phantom) which increased with thickness and with lesion-to-background ratio (-85% for the 10:1 lesions in the 12-cm phantoms). The error due to count rate in phantoms with 0.065 μCi/cc background was negative (-23%±6% for 4-cm thickness) and decreased with thickness (-7%±7% for 12 cm). Attenuation was a substantial source of negative error and increased with thickness (-51%±10% to -77% ±4% in 4 to 12 cm phantoms, respectively). Scatter contributed a relatively constant amount of positive error (+23%±11%) for all thicknesses. Conclusion: Applying corrections for count rate, attenuation and scatter will be essential for the PEM Flex Solo II to be able to produce quantitatively accurate images.

Surface-patterned micromechanical elements by polymer injection molding with hybrid molds

Hybrid molds enable the fabrication of polymeric parts with features of different length scales by injection molding. The resulting polymer microelements combine optical or biological functionalities with designed mechanical properties. Two applications are chosen for illustration of this concept: As a first example, microelements for optical communication via fiber-to-fiber coupling are manufactured by combining two molds to a small mold insert. Both molds are fabricated using lithography and electroplating. As a second example, microcantilevers (μCs) for chemical sensing are surface patterned using a modular mold composed of a laser-machined cavity defining the geometry of the μCs, and an opposite flat tool side which is covered by a patterned polymer foil. Injection molding results in an array of 35 μm-thick μCs with microscale surface topographies. In both cases, when the mold is assembled and closed, reliefs are transferred onto one surface of the molded element whose outlines are defined by the micromold cavity. The main advantage of these hybrid methods lies in the simple integration of optical surface structures and gratings onto the surface of microcomponents with different sizes and orientations. This allows for independent development of functional properties and combinations thereof.

Increase of Caffeine and Decrease of Corticosteroids for Extremely Low Birthweight Infants with Respiratory Failure from 1997 to 2011

AIM To compare treatment strategies for respiratory failure in extremely low birth weight (ELBW) infants in Germany in 1997 to Germany, Austria and Switzerland in 2011. METHODS A detailed questionnaire about treatment strategies for ELBW infants was sent to all German centres treating ELBW infants in 1997. A follow-up survey was conducted in 2011 in Germany, Austria and Switzerland. RESULTS In 1997 and 2011, 63.6% and 66.2% of the hospitals responded. In 2011 the response rate was higher in Switzerland than in Germany, and in university hospitals versus non-university hospitals. Treatment strategies did not differ between university and non-university hospitals as well as NICUs of different sizes in 2011. Differences between Germany, Austria and Switzerland were minimal. Administration of caffeine increased significantly, whereas theophylline and doxapram declined (all p<0.001). While the use of dexamethasone decreased and the use of hydrocortisone increased, the overall use of corticosteroids declined (all p<0.001). Between 1997 and 2011 therapy with inhalations and mucolytics decreased (both p<0.001) whereas the use application of diuretics did not change significantly. In mechanically ventilated infants the application of muscle relaxants and sedation declined significantly (p=0.009 and p<0.001), whereas analgesia use did not change. CONCLUSION Treatment strategies for respiratory failure in ELBW infants have changed significantly between 1997 and 2011. This article is protected by copyright. All rights reserved.

Mus Hs 771 - No 1.: während der Reise : im Auftrag S:. Ehrw:. M: v.: St. componirte ich diese zwei Lieder zum 2ten Grad um, und [unleserlich] führte selbige den 27ten August 5830 [!], zum erstenmale aus. in [Stein als ein Symbol für Freimaurerei] Socrates

[Carl Oestreich]

Un modèle animal simple pour l'apprentissage des techniques de microanastomoses vasculaires de congruences diefférentes

BACKGROUND Since the pioneering work of Jacobson and Suarez, microsurgery has steadily progressed and is now used in all surgical specialities, particularly in plastic surgery. Before performing clinical procedures it is necessary to learn the basic techniques in the laboratory. OBJECTIVE To assess an animal model, thereby circumventing the following issues: ethical rules, cost, anesthesia and training time. METHODS Between July 2012 and September 2012, 182 earthworms were used for 150 microsurgical trainings to simulate discrepancy microanastomoses. Training was undertaken over 10 weekly periods. Each training session included 15 simulations of microanastomoses performed using the Harashina technique (earthworm diameters >1.5 mm [n=5], between 1.0 mm and 1.5 mm [n=5], and <1.0 mm [n=5]). The technique is presented and documented. A linear model with main variable as the number of the week (as a numeric covariate) and the size of the animal (as a factor) was used to determine the trend in time of anastomosis over subsequent weeks as well as differences between the different size groups. RESULTS The linear model showed a significant trend (P<0.001) in time of anastomosis in the course of the training, as well as significant differences (P<0.001) between the groups of animal of different sizes. For diameter >1.5 mm, mean anastomosis time decreased from 19.6±1.9 min to 12.6±0.7 min between the first and last week of training. For training involving smaller diameters, the results showed a reduction in execution time of 36.1% (P<0.01) (diameter between 1.0 mm and 1.5 mm) and 40.6% (P<0.01) (diameter <1.0 mm) between the first and last weeks. The study demonstrates an improvement in the dexterity and speed of nodes' execution. CONCLUSION The earthworm appears to be a reliable experimental model for microsurgical training of discrepancy microanastomoses. Its numerous advantages, as discussed in the present report, show that this model of training will significantly grow and develop in the near future.

AMS-C14 analysis of graphite obtained with an Automated Graphitization Equipment (AGE III) from aerosol collected on quartz filters

AMS-14C applications often require the analysis of small samples. Such is the case of atmospheric aerosols where frequently only a small amount of sample is available. The ion beam physics group at the ETH, Zurich, has designed an Automated Graphitization Equipment (AGE III) for routine graphite production for AMS analysis from organic samples of approximately 1 mg. In this study, we explore the potential use of the AGE III for graphitization of particulate carbon collected in quartz filters. In order to test the methodology, samples of reference materials and blanks with different sizes were prepared in the AGE III and the graphite was analyzed in a MICADAS AMS (ETH) system. The graphite samples prepared in the AGE III showed recovery yields higher than 80% and reproducible 14C values for masses ranging from 50 to 300 lg. Also, reproducible radiocarbon values were obtained for aerosol filters of small sizes that had been graphitized in the AGE III. As a study case, the tested methodology was applied to PM10 samples collected in two urban cities in Mexico in order to compare the source apportionment of biomass and fossil fuel combustion. The obtained 14C data showed that carbonaceous aerosols from Mexico City have much lower biogenic signature than the smaller city of Cuernavaca.

Mode of action of claudin peptidomimetics in the transient opening of cellular tight junction barriers

In epithelial/endothelial barriers, claudins form tight junctions, seal the paracellular cleft, and limit the uptake of solutes and drugs. The peptidomimetic C1C2 from the C-terminal half of claudin-1's first extracellular loop increases drug delivery through epithelial claudin-1 barriers. However, its molecular and structural mode of action remains unknown. In the present study, >100 μM C1C2 caused paracellular opening of various barriers with different claudin compositions, ranging from epithelial to endothelial cells, preferentially modulating claudin-1 and claudin-5. After 6 h incubation, C1C2 reversibly increased the permeability to molecules of different sizes; this was accompanied by redistribution of claudins and occludin from junctions to cytosol. Internalization of C1C2 in epithelial cells depended on claudin-1 expression and clathrin pathway, whereby most C1C2 was retained in recyclosomes >2 h. In freeze-fracture electron microscopy, C1C2 changed claudin-1 tight junction strands to a more parallel arrangement and claudin-5 strands from E-face to P-face association - drastic and novel effects. In conclusion, C1C2 is largely recycled in the presence of a claudin, which explains the delayed onset of barrier and junction loss, the high peptide concentration required and the long-lasting effect. Epithelial/endothelial barriers are specifically modulated via claudin-1/claudin-5, which can be targeted to improve drug delivery.

Birth date predicts alternative life-history pathways in a fish with sequential reproductive tactics

1.In species with plastic expression of alternative reproductive tactics (ARTs), individuals of the same sex, usually males, can adopt different reproductive tactics depending on factors such as body size. 2.The ‘birth date hypothesis’ proposes that condition-dependent expression of ARTs may ultimately depend on birth date, because individuals born at different times of the year may achieve different sizes and express different reproductive tactics accordingly. However, this has rarely been tested. 3.Here, we tested this hypothesis in a fish with ARTs, the peacock blenny (Salaria pavo). A long-term (6 years) mark–recapture study demonstrated that ARTs in the peacock blenny were sequential and that males may follow at least two alternative life-history pathways: a nest-holder pathway, in which males express the nest-holder tactic from their first breeding season onwards, and a parasitic pathway, where males reproduce on their first breeding season as sneaker males and subsequently as nest-holders. 4.We have found evidence of a birth date effect on the expression of ARTs in the peacock blenny. Males following the nest-holder pathway are born earlier and are larger at the first breeding season than males following the parasitic pathway, but they have similar growth curves. 5.The mechanisms underlying a birth date effect are far from clear and might be diverse. We have not found support for a mechanism of body size threshold triggering sexual maturation and subsequent ARTs. A mechanism of tactic determination that is strictly based on timing of first maturation is also unlikely. 6.A proxy of lifetime reproductive success shows crossing (body size associated) fitness curves for the two main life-history pathways.

Calibration of cosmogenic noble gas production based on ³⁶Cl-³⁶Ar ages. Part 2. The ⁸¹Kr-Kr dating technique

We calibrated the ⁸¹Kr-Kr dating system for ordinary chondrites of different sizes using independent shielding-corrected ³⁶Cl-³⁶Ar ages. Krypton concentrations and isotopic compositions were measured in bulk samples from 14 ordinary chondrites of high petrologic type and the cosmogenic Kr component was obtained by subtracting trapped Kr from phase Q. The thus-determined average cosmogenic ⁷⁸Kr/⁸³Kr, ⁸⁰Kr/⁸³Kr, ⁸²Kr/⁸³Kr, and ⁸4Kr/⁸³Kr ratiC(Lavielle and Marti 1988; Wieler 2002). The cosmogenic ⁷⁸Kr/⁸³Kr ratio is correlated with the cosmogenic 22Ne/21Ne ratio, confirming that ⁷⁸Kr/⁸³Kr is a reliable shielding indicator. Previously, ⁸¹Kr-Kr ages have been determined by assuming the cosmogenic production rate of ⁸¹Kr, P(⁸¹Kr)c, to be 0.95 times the average of the cosmogenic production rates of ⁸⁰Kr and ⁸²Kr; the factor Y = 0.95 therefore accounts for the unequal production of the various Kr isotopes (Marti 1967a). However, Y should be regarded as an empirical adjustment. For samples whose ⁸⁰Kr and ⁸²Kr concentrations may be affected by neutron-capture reactions, the shielding-dependent cosmogenic (⁷⁸Kr/⁸³Kr)c ratio has been used instead to calculate P(⁸¹Kr)/P(⁸³Kr), as for some lunar samples, this ratio has been shown to linearly increase with (⁷⁸Kr/⁸³Kr)c (Marti and Lugmair 1971). However, the ⁸¹Kr-Kr ages of our samples calculated with these methods are on average ~30% higher than their ³⁶Cl-³⁶Ar ages, indicating that most if not all the ⁸¹Kr-Kr ages determined so far are significantly too high. We therefore re-evaluated both methods to determine P(⁸¹Kr)c/P(⁸³Kr)c. Our new Y value of 0.70 ± 0.04 is more than 25% lower than the value of 0.95 used so far. Furthermore, together with literature data, our data indicate that for chondrites, P(⁸¹Kr)c/P(⁸³Kr)c is rather constant at 0.43 ± 0.02, at least for the shielding range covered by our samples ([⁷⁸Kr/⁸³Kr]c = 0.119–0.185; [22Ne/21Ne]c = 1.083–1.144), in contrast to the observations on lunar samples. As expected considering the method used, ⁸¹Kr-Kr ages calculated either directly with this new P(⁸¹Kr)c/P(⁸³Kr)c value or with our new Y value both agree with the corresponding ³⁶Cl-³⁶Ar ages. However, the average deviation of 2% indicates the accuracy of both new ⁸¹Kr-Kr dating methods and the precision of the new dating systems of ~10% is demonstrated by the low scatter in the data. Consequently, this study indicates that the ⁸¹Kr-Kr ages published so far are up to 30% too high.