Exercise Degrades Bone in Caloric Restriction, Despite Suppression of Marrow Adipose Tissue (MAT)

Marrow adipose tissue (MAT) and its relevance to skeletal health during caloric restriction (CR) is unknown: It remains unclear whether exercise, which is anabolic to bone in a calorie-replete state, alters bone or MAT in CR. We hypothesized that response of bone and MAT to exercise in CR differs from the calorie-replete state. Ten-week-old female B6 mice fed a regular diet (RD) or 30% CR diet were allocated to sedentary (RD, CR, n = 10/group) or running exercise (RD-E, CR-E, n = 7/group). After 6 weeks, CR mice weighed 20% less than RD, p < 0.001; exercise did not affect weight. Femoral bone volume (BV) via 3D MRI was 20% lower in CR versus RD (p < 0.0001). CR was associated with decreased bone by μCT: Tb.Th was 16% less in CR versus RD, p < 0.003, Ct.Th was 5% less, p < 0.07. In CR-E, Tb.Th was 40% less than RD-E, p < 0.0001. Exercise increased Tb.Th in RD (+23% RD-E versus RD, p <; 0.003) but failed to do so in CR. Cortical porosity increased after exercise in CR (+28%, p = 0.04), suggesting exercise during CR is deleterious to bone. In terms of bone fat, metaphyseal MAT/ BV rose 159% in CR versus RD, p = 0.003 via 3D MRI. Exercise decreased MAT/BV by 52% in RD, p < 0.05, and also suppressed MAT in CR (−121%, p = 0.047). Histomorphometric analysis of adipocyte area correlated with MAT by MRI (R2 = 0.6233, p < 0.0001). With respect to bone, TRAP and Sost mRNA were reduced in CR. Intriguingly, the repressed Sost in CR rose with exercise and may underlie the failure of CR-bone quantity to increase in response to exercise. Notably, CD36, a marker of fatty acid uptake, rose 4088% in CR (p < 0.01 versus RD), suggesting that basal increases in MAT during calorie restriction serve to supply local energy needs and are depleted during exercise with a negative impact on bone

Calcium and magnesium supplementation of ewes grazing pasture did not improve lamb survival

Context: Clinical deficiencies of calcium and magnesium may result in the metabolic disorders hypocalcaemia and hypomagnesaemia, resulting in ewe and lamb mortality. However, the contribution of subclinical deficiencies to perinatal lamb mortality in grazing flocks is unclear. Aims: To test the hypothesis that calcium and magnesium supplementation during the lambing period would increase lamb survival to marking age. Methods: In 2017, an on-farm study used five flocks across New South Wales, South Australia and Western Australia. On each farm, twin-bearing mature Merino ewes (n = 400–600) grazing pasture were allocated to two replicates of control and supplemented treatments. The supplemented groups were offered 30 g/ewe per day of a loose lick containing magnesium chloride (MgCl2(H2O)6), calcium sulfate (CaSO4·(H2O)2, and salt (NaCl), in the ratio 12.5:32.5:55.0, designed to have a low dietary cation–anion difference (−390 meq/100 g). A second study was conducted in 2018 on one farm to test the form of supplement. This study used two replicates of three treatments: control; a low-dietary cation–anion difference supplement as used in 2017; and a standard lime, Causmag (calcined MgO) and salt loose mix (ratio 1:1:1). Mature twin-bearing composite ewes (n = 600) were allocated to groups and those supplemented were offered minerals for the last month of pregnancy and during the lambing period. Blood and urine samples were collected in both experiments for analyses of mineral concentrations. Key results: In the 2017 study, only two flocks consumed >10 g/ewe of supplement per day, and supplementation did not increase lamb survival to marking age in these flocks. In the 2018 study, the mean consumption of supplement was 18 or 20 g/ewe per day. Of non-supplemented ewes, 61% were deficient in plasma calcium (≤90 mg/L) and 17% were deficient in magnesium (≤18 mg/L) at Day 140 after the start of joining. Lamb survival was not increased by supplementation and was 77 ± 3.8% in both treatments. Conclusions: Calcium and magnesium supplementation did not increase lamb survival. Implications: Lamb survival was not increased by calcium and magnesium supplementation; however, evaluation under a wider range of grazing conditions with adequate supplement intake is required

Influenza vaccine effectiveness in patients on hemodialysis: An analysis of a natural experiment

Background Although the influenza vaccine is recommended for patients with end-stage renal disease, little is known about its effectiveness. Observational studies of vaccine effectiveness (VE) are challenging because vaccinated subjects may be healthier than unvaccinated subjects. Methods Using US Renal Data System data, we estimated VE for influenza-like illness, influenza/pneumonia hospitalization, and mortality in adult patients undergoing hemodialysis by using a natural experiment created by the year-to-year variation in the match of the influenza vaccine to the circulating virus. We compared vaccinated patients in matched years (1998, 1999, and 2001) with a mismatched year (1997) using Cox proportional hazards models. Ratios of hazard ratios compared vaccinated patients between 2 years and unvaccinated patients between 2 years. We calculated VE as 1 − effect measure. Results Vaccination rates were less than 50% each year. Conventional analysis comparing vaccinated with unvaccinated patients produced average VE estimates of 13%, 16%, and 30% for influenza-like illness, influenza/pneumonia hospitalization, and mortality, respectively. When restricted to the preinfluenza period, results were even stronger, indicating bias. The pooled ratio of hazard ratios comparing matched seasons with a placebo season resulted in a VE of 0% (95% CI, −3% to 2%) for influenza-like illness, 2% (−2% to 5%) for hospitalization, and 0% (−3% to 3%) for death. Conclusions Relative to a mismatched year, we found little evidence of increased VE in subsequent well-matched years, suggesting that the current influenza vaccine strategy may have a smaller effect on morbidity and mortality in the end-stage renal disease population than previously thought. Alternate strategies (eg, high-dose vaccine, adjuvanted vaccine, and multiple doses) should be investigated

Lipid testing trends in the us before and after the release of the 2013 cholesterol treatment guidelines

Background: The 2013 ACC/AHA cholesterol treatment guidelines removed the recom-mendation to treat adults at risk of cardiovascular disease to goal levels of low-density lipoprotein cholesterol (LDL-C). We anticipated that the frequency of LDL-C testing in clinical practice would decline as a result. To test this hypothesis, we evaluated the frequency of LDL-C testing before and after the guideline release. Methods: We used the MarketScan® Commercial and Medicare Supplemental claims data (1/1/2007–12/31/2016) to identify four cohorts: 1) statin initiators (any intensity), 2) high-intensity statin initiators, 3) ezetimibe initiators, and 4) patients at very high cardiovascular risk (≥2 hospitalizations for myocardial infarction or ischemic stroke, with prevalent statin use). Rates of LDL-C testing by calendar year quarter were estimated for each cohort. To estimate rates in the absence of a guideline change, we fit a time-series model to the pre-guideline rates and extrapolated to the post-guideline period, adjusting for covariates, seasonality, and time trend. Results: Pre-and post-guideline rates (LDL-C tests per 1,000 persons per quarter) were 248 and 235, respectively, for 3.9 million statin initiators; 263 and 246 for 1.3 million high-intensity statin initiators; 277 and 261 for 323,544 ezetimibe initiators; and 180 and 158 for 42,108 very high-risk patients. For all cohorts, observed post-guideline rates were similar to model-predicted rates. On average, the difference between observed and predicted rates was 8.5 for patients initiating any statin; 2.6 for patients initiating a high-intensity statin; 11.4 for patients initiating ezetimibe, and −0.5 for high-risk patients. Conclusion: We observed no discernible impact of the release of the 2013 ACC/AHA guidelines on LDL-C testing rates. Rather, there was a gradual decline in testing rates starting prior to the guideline change and continuing throughout the study period. Our findings suggest that the guidelines had little to no impact on use of LDL-C testing

Modeling magnetospheric fields in the Jupiter system

The various processes which generate magnetic fields within the Jupiter system are exemplary for a large class of similar processes occurring at other planets in the solar system, but also around extrasolar planets. Jupiter's large internal dynamo magnetic field generates a gigantic magnetosphere, which is strongly rotational driven and possesses large plasma sources located deeply within the magnetosphere. The combination of the latter two effects is the primary reason for Jupiter's main auroral ovals. Jupiter's moon Ganymede is the only known moon with an intrinsic dynamo magnetic field, which generates a mini-magnetosphere located within Jupiter's larger magnetosphere including two auroral ovals. Ganymede's magnetosphere is qualitatively different compared to the one from Jupiter. It possesses no bow shock but develops Alfv\'en wings similar to most of the extrasolar planets which orbit their host stars within 0.1 AU. New numerical models of Jupiter's and Ganymede's magnetospheres presented here provide quantitative insight into the processes that maintain these magnetospheres. Jupiter's magnetospheric field is approximately time-periodic at the locations of Jupiter's moons and induces secondary magnetic fields in electrically conductive layers such as subsurface oceans. In the case of Ganymede, these secondary magnetic fields influence the oscillation of the location of its auroral ovals. Based on dedicated Hubble Space Telescope observations, an analysis of the amplitudes of the auroral oscillations provides evidence that Ganymede harbors a subsurface ocean. Callisto in contrast does not possess a mini-magnetosphere, but still shows a perturbed magnetic field environment. Callisto's ionosphere and atmospheric UV emission is different compared to the other Galilean satellites as it is primarily been generated by solar photons compared to magnetospheric electrons.Comment: Chapter for Book: Planetary Magnetis

An Emerging Natural History in the Development, Mechanisms and Worldwide Prevalence of Major Mental Disorders

Conciliating recent findings from molecular genetics, evolutionary biology, and clinical observations together point to new understandings regarding the mechanism, development and the persistent worldwide prevalence of major mental disorders (MMDs), which should be considered the result of an evolutionary downside trade off. Temperamental/trait variability, by facilitating choices for individual and group responses, confers robustness flexibility and resilience crucial to success of our species. Extreme temperamental variants, originating evolutionarily from the asocial aspect of human nature, also constitute the premorbid personality of the disorders. The latter create vulnerable individuals out of whom some will develop MMDs but at much higher rate to that of the general population. Significantly, similar temperamental “lopsidedness� enables many of these vulnerable individuals, if intelligent, tenacious, and curious, to be creative and contribute to our survival while some may also develop MMDs. All have a common neural-developmental origin and share characteristics in their clinical expression and pharmacological responses also expressed as mixed syndromes or alternating ones over time. Over-pruning of synaptic neurons may be considered the trigger of such occurrences or conversely, the failure to prevent them in spite of it. The symptoms of the major mental disorders are made up of antithetical substitutes as an expression of a disturbed over-all synchronizing property of brain function for all higher faculties previously unconsidered in their modeling. The concomitant presence of psychosis is a generic common occurrence

Measurement of the B0-anti-B0-Oscillation Frequency with Inclusive Dilepton Events

The $B^0$-$\bar B^0$ oscillation frequency has been measured with a sample of 23 million \B\bar B pairs collected with the BABAR detector at the PEP-II asymmetric B Factory at SLAC. In this sample, we select events in which both B mesons decay semileptonically and use the charge of the leptons to identify the flavor of each B meson. A simultaneous fit to the decay time difference distributions for opposite- and same-sign dilepton events gives $\Delta m_d = 0.493 \pm 0.012{(stat)}\pm 0.009{(syst)}$ ps$^{-1}$.Comment: 7 pages, 1 figure, submitted to Physical Review Letter

The PHENIX Experiment at RHIC

The physics emphases of the PHENIX collaboration and the design and current status of the PHENIX detector are discussed. The plan of the collaboration for making the most effective use of the available luminosity in the first years of RHIC operation is also presented.Comment: 5 pages, 1 figure. Further details of the PHENIX physics program available at http://www.rhic.bnl.gov/phenix

Anaerobic bacteria cultured from cystic fibrosis airways correlate to milder disease: A multisite study

Anaerobic and aerobic bacteria were quantitated in respiratory samples across three cystic fibrosis (CF) centres using extended culture methods. Subjects aged 1–69 years who were clinically stable provided sputum (n=200) or bronchoalveolar lavage (n=55). 18 anaerobic and 39 aerobic genera were cultured from 59% and 95% of samples, respectively; 16 out of 57 genera had a 5% prevalence across centres. Analyses of microbial communities using co-occurrence networks in sputum samples showed groupings of oral, including anaerobic, bacteria, whereas typical CF pathogens formed distinct entities. Pseudomonas was associated with worse nutrition and F508del genotype, whereas anaerobe prevalence was positively associated with pancreatic sufficiency, better nutrition and better lung function. A higher total anaerobe/ total aerobe CFU ratio was associated with pancreatic sufficiency and better nutrition. Subjects grouped by factor analysis who had relative dominance of anaerobes over aerobes had milder disease compared with a Pseudomonas-dominated group with similar proportions of subjects that were homozygous for F508del. In summary, anaerobic bacteria occurred at an early age. In sputum-producing subjects anaerobic bacteria were associated with milder disease, suggesting that targeted eradication of anaerobes may not be warranted in sputum-producing CF subjects

Lambda Hyperons in 2 A*GeV Ni + Cu Collisions

A sample of Lambda's produced in 2 A*GeV Ni + Cu collisions has been obtained with the EOS Time Projection Chamber at the Bevalac. Low background in the invariant mass distribution allows for the unambiguous demonstration of Lambda directed flow. The transverse mass spectrum at mid-rapidity has the characteristic shoulder-arm shape of particles undergoing radial transverse expansion. A linear dependence of Lambda multiplicity on impact parameter is observed, from which a total Lambda + Sigma^0 production cross section of $112 +/- 24 mb is deduced. Detailed comparisons with the ARC and RVUU models are made.Comment: Revised version accepted for publication in Phys. Lett.