Novel experimental setup for megahertz X-ray diffraction in a diamond anvil cell at the High Energy Density (HED) instrument of the European X-ray Free-Electron Laser (EuXFEL).

The high-precision X-ray diffraction setup for work with diamond anvil cells (DACs) in interaction chamber 2 (IC2) of the High Energy Density instrument of the European X-ray Free-Electron Laser is described. This includes beamline optics, sample positioning and detector systems located in the multipurpose vacuum chamber. Concepts for pump-probe X-ray diffraction experiments in the DAC are described and their implementation demonstrated during the First User Community Assisted Commissioning experiment. X-ray heating and diffraction of Bi under pressure, obtained using 20 fs X-ray pulses at 17.8 keV and 2.2 MHz repetition, is illustrated through splitting of diffraction peaks, and interpreted employing finite element modeling of the sample chamber in the DAC.

Age attenuates leucine oxidation after eccentric exercise.

Aging may alter protein metabolism during periods of metabolic and physiologic challenge. The purpose of this study was to assess the effects of age on whole-body amino acid turnover in response to eccentric exercise and hyperglycemia-induced hyperinsulinemia. 16 healthy men were divided into young (N=8) and older (N=8) groups. Protein metabolism was assessed using a [1-13C]-leucine isotopic tracer approach. Measures were obtained under fasted basal conditions and during 3-h hyperglycemic clamps that were performed without (control) and 48 h after eccentric exercise. Exercise reduced leucine oxidation in the younger men (P<0.05), but not in older men. Insulin sensitivity was inversely correlated with leucine oxidation (P<0.05), and was lower in older men (P<0.05). Healthy aging is associated with an impaired capacity to adjust protein oxidation in response to eccentric exercise. The decreased efficiency of protein utilization in older men may contribute to impaired maintenance, growth, and repair of body tissues with advancing age.

X-ray emission spectroscopy of cerium across the γ-α volume collapse transition.

High-pressure x-ray emission measurements are used to provide crucial evidence in the longstanding debate over the nature of the isostructural (α, γ) volume collapse in elemental cerium. Extended local atomic model calculations show that the satellite of the Lγ emission line offers direct access to the total angular momentum observable (J(2)). This satellite experiences a 30% steplike decrease across the volume collapse, validating the Kondo model in conjunction with previous measurements. Direct comparisons are made with previous predictions by dynamical mean field theory. A general experimental methodology is demonstrated for analogous work on a wide range of strongly correlated f-electron systems.

Simultaneous imaging and diffraction in the dynamic diamond anvil cell.

The ability to visualize a sample undergoing a pressure-induced phase transition allows for the determination of kinetic parameters, such as the nucleation and growth rates of the high-pressure phase. For samples that are opaque to visible light (such as metallic systems), it is necessary to rely on x-ray imaging methods for sample visualization. Here, we present an experimental platform developed at beamline P02.2 at the PETRA III synchrotron radiation source, which is capable of performing simultaneous x-ray imaging and diffraction of samples that are dynamically compressed in piezo-driven diamond anvil cells. This setup utilizes a partially coherent monochromatic x-ray beam to perform lensless phase contrast imaging, which can be carried out using either a parallel- or focused-beam configuration. The capabilities of this platform are illustrated by experiments on dynamically compressed Ga and Ar. Melting and solidification were identified based on the observation of solid/liquid phase boundaries in the x-ray images and corresponding changes in the x-ray diffraction patterns collected during the transition, with significant edge enhancement observed in the x-ray images collected using the focused-beam. These results highlight the suitability of this technique for a variety of purposes, including melt curve determination.

Frailty and muscle metabolism dysregulation in the elderly.

The frailty syndrome is increasingly recognized by geriatricians to identify elders at an extreme risk of adverse health outcomes. The physiological changes that result in frailty are complex and up to now have been extremely difficult to characterize due to the frequent coexistence of acute and chronic illness. Frailty is characterized by an decline in the functional reserve with several alterations in diverse physiological systems, including lower energy metabolism, decreased skeletal muscle mass and quality, altered hormonal and inflammatory functions. This altered network leads to an extreme vulnerability for disease, functional dependency, hospitalization and death. One of the most important core components of the frailty syndrome is a decreased reserve in skeletal muscle functioning which is clinically characterized by a loss in muscle mass and strength (sarcopenia), in walking performance and in endurance associated with a perception of exhaustion and fatigue. There are a number of physiological changes that occur in senescent muscle tissues that have a critical effect on body metabolism. The causes of sarcopenia are multi-factorial and can include disuse, changing hormonal function, chronic diseases, inflammation, insulin resistance, and nutritional deficiencies. In this review, we will explore the dysregulation of some biological mechanisms that may contribute to the pathophysiology of the frailty syndrome through age-related changes in skeletal muscle mass and function.

Randomised controlled clinical trial for the use of deracoxib during intense rehabilitation exercises after tibial plateau levelling osteotomy.

During intense physical exercise, the cyclo-oxygenase-2 (COX-2) pathway is upregulated which contributes to soreness. The aim of this study was to determine if there was a clinical affect of deracoxib (COX-2 selective antagonist) on dogs engaged in intense rehabilitation following tibial plateau levelling osteotomy for cranial cruciate ligament rupture. Our hypothesis was that dogs receiving deracoxib would demonstrate less lameness, better range-of-motion (ROM), and faster muscle mass recovery than the control dogs. Thirty dogs were randomised to the treatment (deracoxib at 1-2 mg/kg once daily by mouth) or control (no treatment) group. Outcomes including gait analysis, thigh circumference, and goniometry, were measured by one investigator, who was masked to group preoperatively, and at the end of each intense rehabilitation week (3, 5, and 7 weeks postoperatively). The only difference between groups for any outcome measure at any time point was a greater preoperative stifle ROM in the group receiving deracoxib (p = 0.04). This study showed that treatment with deracoxib did not provide better outcomes when dogs were subjected to intense rehabilitation after tibial plateau levelling osteotomy. Each patient should be evaluated individually to determine if administration of deracoxib is appropriate.

Cachexia and aging: an update based on the Fourth International Cachexia Meeting.

This manuscript highlights the new developments in the pathophysiology of anorexia, cachexia and sarcopenia, based on presentations given at the Fourth International Cachexia Meeting. It stresses the importance of these conditions in older persons.

Double-blind placebo-controlled trial of adjuvant pamidronate with palliative radiotherapy and intravenous doxorubicin for canine appendicular osteosarcoma bone pain.

BACKGROUND: Canine osteosarcoma (OSA) causes focal malignant osteolysis leading to severe pain. Despite the documented efficacy of radiotherapy or IV aminobisphosphonates for managing cancer bone pain, their potential combined therapeutic value has not been reported in OSA-bearing dogs. HYPOTHESIS: Pamidronate combined with standardized palliative therapy will improve pain control and bone biologic effects in OSA-bearing dogs. ANIMALS: Fifty dogs with appendicular OSA treated with standardized palliative therapy and either pamidronate or sterile saline. METHODS: Randomized, prospective, double-blinded, placebo-controlled study. Treatment responses for dogs receiving standardized palliative therapy with (n = 26) or without (n = 24) adjuvant pamidronate were serially evaluated for changes in subjective pain scores, urine N-telopeptide (NTx) excretion, primary tumor relative bone mineral density (rBMD), and computerized pressure platform gait analysis. RESULTS: Median duration of subjective pain relief for dogs treated with adjuvant pamidronate or placebo was 76 and 75 days, respectively (P= .39). Forty percent (20/50; pamidronate [11/26] and placebo [9/24]) of dogs experienced durable analgesia, defined by pain alleviation > or =112 days. For patients achieving durable pain control, dogs treated with pamidronate achieved greater reductions in NTx excretion and larger increases in rBMD compared with placebo controls. Changes in peak vertical force assessed by computerized pressure platform gait analysis correlated with pain alleviation in OSA-bearing dogs. CONCLUSIONS AND CLINICAL IMPORTANCE: Combining pamidronate with standardized palliative therapy is safe, but does not clearly improve pain alleviation. However, in dogs achieving durable pain control, adjuvant pamidronate appears to decrease focal bone resorption in the local tumor microenvironment.

New dynamic diamond anvil cells for tera-pascal per second fast compression x-ray diffraction experiments.

Fast compression experiments performed using dynamic diamond anvil cells (dDACs) employing piezoactuators offer the opportunity to study compression-rate dependent phenomena. In this paper, we describe an experimental setup which allows us to perform time-resolved x-ray diffraction during the fast compression of materials using improved dDACs. The combination of the high flux available using a 25.6 keV x-ray beam focused with a linear array of compound refractive lenses and the two fast GaAs LAMBDA detectors available at the Extreme Conditions Beamline (P02.2) at PETRA III enables the collection of x-ray diffraction patterns at an effective repetition rate of up to 4 kHz. Compression rates of up to 160 TPa/s have been achieved during the compression of gold in a 2.5 ms fast compression using improved dDAC configurations with more powerful piezoactuators. The application of this setup to low-Z compounds at lower compression rates is described, and the high temporal resolution of the setup is demonstrated. The possibility of applying finely tuned pressure profiles opens opportunities for future research, such as using oscillations of the piezoactuator to mimic propagation of seismic waves in the Earth.

Comparison of three methods for the management of fragmented medial coronoid process in the dog. A systematic review and meta-analysis.

The objective of this review and analysis was to compare arthroscopy, medial arthrotomy and medical management for treating fragmented coronoid process in the dog. The data come from manuscripts published in peer-reviewed veterinary journals, and the study design is a systematic review followed by meta-analysis. The meta-analysis combines data from a set of studies so that surgical techniques and medial management can be compared in a single analysis. Several literature databases and veterinary texts were thoroughly searched to provide a list of over 400 candidate manuscripts. Inclusion criteria were used to filter the candidate manuscripts to a final set of four manuscripts that directly pertained to the clinical question. They were scored for their evidentiary value using a semi-objective measure. The results were that arthroscopy was superior to medial arthrotomy and medical management, but medial arthrotomy was not superior to medical management. Only one manuscript was a randomized controlled trial, hence the results must be tempered by the evidentiary value of the data.

A simple and portable multi-channel pyrometer allowing temperature measurements down to 800 K on the microsecond scale.

The measurement of transient temperatures less than 1000 K for samples in laser-heated diamond anvil cells remains a challenge. Here we present the design and performance characteristics of a multi-channel pyrometer that works in the near-infrared from 1200 to 2000 nm. It has a relatively small footprint, is portable, requires only low voltage power supplies, and can report temperatures down to 800 K on the millisecond scale or faster. A single data point without averaging can be acquired in 14 µs (sampling rate of 7 kilosamples per second). In conjunction with a diamond anvil cell, the system delivers accurate and rapid measurements down to ∼830 K. The pyrometer has been successfully interfaced several times with the combined x-ray diffraction and laser heating system at the High Pressure Collaborative Access Team at the Advanced Photon Source at Argonne National Laboratories.

Single crystal toroidal diamond anvils for high pressure experiments beyond 5 megabar.

Static compression experiments over 4 Mbar are rare, yet critical for developing accurate fundamental physics and chemistry models, relevant to a range of topics including modeling planetary interiors. Here we show that focused ion beam crafted toroidal single-crystal diamond anvils with ~9.0 µm culets are capable of producing pressures over 5 Mbar. The toroidal surface prevents gasket outflow and provides a means to stabilize the central culet. We have reached a maximum pressure of ~6.15 Mbar using Re as in situ pressure marker, a pressure regime typically accessed only by double-stage diamond anvils and dynamic compression platforms. Optimizing single-crystal diamond anvil design is key for extending the pressure range over which studies can be performed in the diamond anvil cell.

Anomalous elastic properties across the γ to α volume collapse in cerium.

The behavior of the f-electrons in the lanthanides and actinides governs important macroscopic properties but their pressure and temperature dependence is not fully explored. Cerium with nominally just one 4f electron offers a case study with its iso-structural volume collapse from the γ-phase to the α-phase ending in a critical point (p C, V C, T C), unique among the elements, whose mechanism remains controversial. Here, we present longitudinal (c L) and transverse sound speeds (c T) versus pressure from higher than room temperature to T C for the first time. While c L experiences a non-linear dip at the volume collapse, c T shows a step-like change. This produces very peculiar macroscopic properties: the minimum in the bulk modulus becomes more pronounced, the step-like increase of the shear modulus diminishes and the Poisson's ratio becomes negative-meaning that cerium becomes auxetic. At the critical point itself cerium lacks any compressive strength but offers resistance to shear.

Short-term moderate weight loss and resistance training do not affect insulin-stimulated glucose disposal in postmenopausal women.

OBJECTIVES: Moderate weight loss and exercise have been proposed as important tools in the treatment and prevention of type 2 diabetes. Therefore, we tested the hypothesis that short-term (4 weeks) moderate energy restriction (-750 kcal/day) would result in a significant increase in insulin-stimulated glucose disposal (40 mU x m(-2) x min(-1) hyperinsulinemic-euglycemic clamp) in moderately overweight postmenopausal women and that when combined with resistance training (RT) an even greater effect would be seen. RESEARCH DESIGN AND METHODS: Older women were randomly assigned to energy restriction (WLoss group; n = 9) or energy restriction plus RT (RT + WLoss group; n = 10). RESULTS: For the WLoss versus the RT + WLoss groups, changes in body weight (-3.0 +/- 0.2 kg vs. -3.2 +/- 0.3 kg), fat mass (FM) (-3.0 +/- 0.3 kg vs. -3.2 +/- 0.3 kg), and percent body fat (BF) (-2.1 +/- 0.4 vs. -2.4 +/- 0.3%) were not different between groups. Muscle mass (group-by-time interaction, P = 0.04) was preserved in RT + WLoss (0.40 +/- 0.40 kg) and reduced in WLoss (-0.64 +/- 0.18 kg). There were no changes in fat-free mass (FFM) and waist-to-hip ratio in either group. Whole body glucose disposal (WLoss 6.14 +/- 0.57 vs. 6.03 +/- 0.53, RT + WLoss 5.85 +/- 0.60 vs. 6.09 +/- 0.56 mg/kg of FFM/min) did not change in either group. CONCLUSIONS: The results of this study demonstrate that short-term energy restriction resulting in moderate decreases in body weight (4.0 +/- 0.3%) and FM (8.2 +/- 0.7%) did not improve insulin-stimulated glucose disposal. The addition of RT to the hypoenergetic diet preserved muscle mass but provided no synergistic effect on insulin action. These results suggest that a greater change in body weight or FM may be necessary to observe a significant improvement in insulin action.

Hormone and bone mineral status in endurance-trained and sedentary postmenopausal women.

Serum hormone levels and bone mineral status were studied in 18 sedentary and 15 endurance-trained postmenopausal women (mean age, 62 yr). The endurance-trained women had lower body weight, lower body fat, and higher aerobic capacity than the sedentary women (P less than 0.05). There were no differences in current calcium intake between the 2 groups, as assessed by a 7-day food record, but carbohydrate intake (grams per kg BW) was higher in the endurance-trained women (P less than 0.001). Bone mineral density (BMD) of the spine (L1-L3), proximal femur, and radius did not differ between the 2 groups; however, when normalized for body weight, the BMDs of the spine and radius were higher in the endurance-trained than in the sedentary women. Serum estrone and PTH levels were lower, and 1,25-dihydroxyvitamin D and somatomedin-C levels were higher in the endurance-trained than in the sedentary women. Serum GH tended to be higher in the endurance-trained than in the sedentary women (P = 0.08), and there was a postexercise increase in serum GH in the endurance-trained, but not in the sedentary, women (P less than 0.01). The major effect of habitual exercise was on body weight and hormone status. Although leanness and low serum estrone levels are risk factors for osteoporosis, these were not associated with lower BMD in endurance-trained women. Endurance-trained women may have improved calcium absorption as a result of higher carbohydrate intake and higher serum 1,25-dihydroxyvitamin D levels.

Bone mineral content and levels of gonadotropins and estrogens in amenorrheic running women.

Serum gonadotropin and estrogen levels and their relationship to bone mineral content in exercise-related amenorrhea were studied in 11 amenorrheic women and 24 eumenorrheic women, all of whom were runners. Serum estradiol, LH, FSH, estrone, and testosterone were measured in serial blood samples obtained at 15-min intervals for 4 h. The amenorrheic women had lower estradiol, LH, FSH; and estrone levels as well as a higher estrone-estradiol ratio than did the eumenorrheic women. There was no difference in testosterone levels. The amenorrheic women had lower LH pulse amplitudes, whereas no differences were found in FSH pulse amplitudes. LH and FSH pulse frequencies did not differ between the two groups. Bone mineral content of the lumbar spine was lower in amenorrheic women and was positively correlated with estradiol levels in all women. There was no difference in bone mineral content of the radius. These data suggest that, in exercise-related amenorrhea, low serum LH, FSH, and estrogen levels reflect an alteration in the hypothalamic control of gonadotropin release. Reduced circulating estrogen levels in amenorrheic running women may be a cause of low mineral content of the spine.

Skeletal muscle PGF(2)(alpha) and PGE(2) in response to eccentric resistance exercise: influence of ibuprofen acetaminophen.

PGs have been shown to modulate skeletal muscle protein metabolism as well as inflammation and pain. In nonskeletal muscle tissues, the over the counter analgesic drugs ibuprofen and acetaminophen function through suppression of PG synthesis. We previously reported that ibuprofen and acetaminophen inhibit the normal increase in skeletal muscle protein synthesis after high intensity eccentric resistance exercise. The current study examined skeletal muscle PG levels in the same subjects to further investigate the mechanisms of action of these drugs in exercised skeletal muscle. Twenty-four males (25 +/- 3 yr) were assigned to 3 groups that received the maximal over the counter dose of ibuprofen (1200 mg/d), acetaminophen (4000 mg/d), or a placebo after 10-14 sets of 10 eccentric repetitions at 120% of concentric 1 repetition maximum using the knee extensors. Preexercise and 24 h postexercise biopsies of the vastus lateralis revealed that the exercise-induced change in PGF(2alpha) in the placebo group (77%) was significantly different (P < 0.05) from those in the ibuprofen (-1%) and acetaminophen (-14%) groups. However, the exercise-induced change in PGE(2) in the placebo group (64%) was only significantly different (P < 0.05) from that in the acetaminophen group (-16%). The exercise-induced changes in PGF(2alpha) and PGE(2) were not different between the ibuprofen and acetaminophen groups. These results suggest that ibuprofen and acetaminophen have a comparable effect on suppressing the normal increase in PGF(2alpha) in human skeletal muscle after eccentric resistance exercise, which may profoundly influence the anabolic response of muscle to this form of exercise.

Effect of exercise and menstrual cycle status on plasma lipids, low density lipoprotein particle size, and apolipoproteins.

Habitual physical exercise has been reported to have beneficial effects on plasma lipoproteins. To examine this question in women, plasma cholesterol, triglyceride, and apolipoprotein (apo) A-I and B levels, and low density lipoprotein (LDL) particle size were determined in 25 women runners (9 of whom had exercise-related secondary amenorrhea) and 36 age-matched nonexercising women (controls). The eumenorrheic runners had significantly lower apo B levels and significantly greater mean apo A-I/apo B ratios and LDL particle sizes than did the control women (P less than 0.05). Lower apo B levels were correlated with decreased body mass index, a known exercise effect (P less than 0.0001). In addition, normally menstruating runners had cholesterol and triglyceride levels that were 7.6% and 25.4% lower, respectively, and apo A-I levels that were 6.4% higher than control women (P = NS). In amenorrheic runners all parameters were similar to values in control women, except that apo B levels were 20% lower (P less than 0.05). Amenorrheic runners had lower plasma apo A-I levels (13%) and significantly lower apo A-I/apo B ratios and estradiol levels than eumenorrheic runners, and serum estradiol values in the runners were correlated with apo A-I levels (P less than 0.01). These data indicate that the beneficial effects of strenuous exercise on plasma apo A-I levels and apo A-I/apo B ratios in women runners can be reversed by exercise-induced amenorrhea and decreased serum estradiol levels, and that women runners have lower apo B levels than nonexercising women, regardless of menstrual status.

Visible persistence decay rates for schizophrenics and substance abusers.

Information-processing deficits are consistently reported for schizophrenics. The findings from the majority of psychophysical tasks indicate that the deficit is specific to schizophrenics and thus may represent a marker for schizophrenia. The present study evaluated for specificity of impairment by including controls using methadone. A two-pulsed forced choice information-processing task that required the detection of a line or a blank-field during an interstimulus interval (ISI) indexed efficiency of processing (i.e., visible persistence). There were 19 schizophrenic, 9 schizoaffective, 8 depressed, 12 on methadone, and 12 normal subjects. The visual stimuli were low and high spatial frequency gratings. Either a line of equivalent width to those of the gratings or a blank field was presented during the ISI. The gratings were presented for 150 msec prior to and following an ISI of 30, 60, 90, 120, 150, and 350 msec. The results support previous findings for impaired processing during a 90-150 msec interval for schizophrenics. Also, the methadone-using controls were not significantly different from schizophrenics. Normal and depressed controls' profiles did not differ from each other, however, they were significantly different from the other groups. The results support an early information-processing deficit in schizophrenic individuals and may implicate dysregulation of dopaminergic neuromodulation.

Vitamin E, vitamin C, and exercise.

Exercise increases the generation of oxygen free radicals and lipid peroxidation. Strenuous exercise in a person who is unconditioned or unaccustomed to exercise will induce oxidative damage and result in muscle injury. However, aerobic exercise training strengthens the antioxidant defense system by increasing superoxide dismutase. Vitamin C and, especially, vitamin E are shown to decrease the exercise-induced increase in the rate of lipid peroxidation. No ergogenic effects of either vitamin C or E have been shown. Vitamin E was shown to significantly increase circulating neutrophils in older, but not younger, subjects performing eccentric exercise that causes an increase in skeletal muscle damage. In addition to its effect in augmenting the neutrophil response to eccentric exercise, vitamin E causes a greater increase in circulating creatine kinase activity, perhaps indicating increased skeletal muscle repair. Increased vitamin E intake has been associated with enhanced glucose tolerance and insulin action as well as improved lipoprotein status. Future research should examine the combined effects of exercise training and vitamins E and C on these health-related outcomes.