305 research outputs found
Climbing fiber regulation of spontaneous Purkinje cell activity and cerebellum-dependent blink responses
It has been known for a long time that GABAergic Purkinje cells in the cerebellar cortex, as well as their target neurons in the cerebellar nuclei, are spontaneously active. The cerebellar output will, therefore, depend on how input is integrated into this spontaneous activity. It has been shown that input from climbing fibers originating in the inferior olive controls the spontaneous activity in Purkinje cells. While blocking climbing fiber input to the Purkinje cells causes a dramatic increase in the firing rate, increased climbing fiber activity results in reduced Purkinje cell activity. However, the exact calibration of this regulation has not been examined systematically. Here we examine the relation between climbing fiber stimulation frequency and Purkinje cell activity in unanesthetized decerebrated ferrets. The results revealed a gradual suppression of Purkinje cell activity, starting at climbing fiber stimulation frequencies as low as 0.5 Hz. At 4 Hz, Purkinje cells were completely silenced. This effect lasted an average of 2 min after the stimulation rate was reduced to a lower level. We also examined the effect of sustained climbing fiber stimulation on overt behavior. Specifically, we analyzed conditioned blink responses, which are known to be dependent on the cerebellum, while stimulating the climbing fibers at different frequencies. In accordance with the neurophysiological data, the conditioned blink responses were suppressed at stimulation frequencies of =4 Hz
Long-Term Safety of Growth Hormone in Adults With Growth Hormone Deficiency:Overview of 15 809 GH-Treated Patients
Context Data on long-term safety of growth hormone (GH) replacement in adults with GH deficiency (GHD) are needed. Objective We aimed to evaluate the safety of GH in the full KIMS (Pfizer International Metabolic Database) cohort. Methods The worldwide, observational KIMS study included adults and adolescents with confirmed GHD. Patients were treated with GH (Genotropin [somatropin]; Pfizer, NY) and followed through routine clinical practice. Adverse events (AEs) and clinical characteristics (eg, lipid profile, glucose) were collected. Results A cohort of 15 809 GH-treated patients were analyzed (mean follow-up of 5.3 years). AEs were reported in 51.2% of patients (treatment-related in 18.8%). Crude AE rate was higher in patients who were older, had GHD due to pituitary/hypothalamic tumors, or adult-onset GHD. AE rate analysis adjusted for age, gender, etiology, and follow-up time showed no correlation with GH dose. A total of 606 deaths (3.8%) were reported (146 by neoplasms, 71 by cardiac/vascular disorders, 48 by cerebrovascular disorders). Overall, de novo cancer incidence was comparable to that in the general population (standard incidence ratio 0.92; 95% CI, 0.83-1.01). De novo cancer risk was significantly lower in patients with idiopathic/congenital GHD (0.64; 0.43-0.91), but similar in those with pituitary/hypothalamic tumors or other etiologies versus the general population. Neither adult-onset nor childhood-onset GHD was associated with increased de novo cancer risks. Neutral effects were observed in lipids/fasting blood glucose levels. Conclusion These final KIMS cohort data support the safety of long-term GH replacement in adults with GHD as prescribed in routine clinical practice
Reaction mechanism of dimethyl ether carbonylation to methyl acetate over mordenite: a combined DFT/experimental study
Dimethyl ether carbonylation to methyl acetate over mordenite was studied theoretically with density functional theory calculations and experimentally in a fixed bed flow reactor. A new reaction path to methyl acetate entirely in the 8 membered ring was discovered.</p
The metal contents of two groups of galaxies
The hot gas in clusters and groups of galaxies is continuously being enriched
with metals from supernovae and stars. It is well established that the
enrichment of the gas with elements from oxygen to iron is mainly caused by
supernova explosions. The origins of nitrogen and carbon are still being
debated. Possible candidates include massive, metal-rich stars, early
generations of massive stars, intermediate or low mass stars and Asymptotic
Giant Branch (AGB) stars. In this paper we accurately determine the metal
abundances of the gas in the groups of galaxies NGC 5044 and NGC 5813, and
discuss the nature of the objects that create these metals.
We mainly focus on carbon and nitrogen. We use spatially-resolved
high-resolution X-ray spectroscopy from XMM-Newton. For the spectral fitting,
multi-temperature hot gas models are used. The abundance ratios of carbon over
oxygen and nitrogen over oxygen that we find are high compared to the ratios in
the stars in the disk of our Galaxy. The oxygen and nitrogen abundances we
derive are similar to what was found in earlier work on other giant ellipticals
in comparable environments. We show that the iron abundances in both our
sources have a gradient along the cross-dispersion direction of the Reflection
Grating Spectrometer (RGS). We conclude that it is unlikely that the creation
of nitrogen and carbon takes place in massive stars, which end their lives as
core-collapse supernovae, enriching the medium with oxygen because oxygen
should then also be enhanced. Therefore we favour low-and intermediate mass
stars as sources of these elements. The abundances in the hot gas can best be
explained by a 30-40% contribution of type Ia supernovae based on the measured
oxygen and iron abundances and under the assumption of a Salpeter Initial Mass
Function (IMF).Comment: Accepted for publication in A&A, 12 pages, 10 figures. Data points on
which figs 4,5,8 and 9 are based are present as comment in the source fil
Senicapoc treatment in COVID-19 Patients with Severe Respiratory Insufficiency - A Randomized, Open-Label, Phase II Trial
BACKGROUND: The aim of the current study was to determine if treatment with senicapoc, improves the PaO(2)/FiO(2) ratio in patients with COVIDâ19 and severe respiratory insufficiency. METHODS: Investigatorâinitiated, randomized, openâlabel, phase II trial in four intensive care units (ICU) in Denmark. We included patients aged âĽ18âyears and admitted to an ICU with severe respiratory insufficiency due to COVIDâ19. The intervention consisted of 50âmg enteral senicapoc administered as soon as possible after randomization and again after 24âh. Patients in the control group received standard care only. The primary outcome was the PaO(2)/FiO(2) ratio at 72âh. RESULTS: Twenty patients were randomized to senicapoc and 26 patients to standard care. Important differences existed in patient characteristics at baseline, including more patients being on nonâinvasive/invasive ventilation in the control group (54% vs. 35%). The median senicapoc concentration at 72âh was 62.1âng/ml (IQR 46.7â71.2). The primary outcome, PaO(2)/FiO(2) ratio at 72âh, was significantly lower in the senicapoc group (mean 19.5 kPa, SD 6.6) than in the control group (mean 24.4 kPa, SD 9.2) (mean difference â5.1 kPa [95% CI â10.2, â0.04] p =â.05). The 28âday mortality in the senicapoc group was 2/20 (10%) compared with 6/26 (23%) in the control group (OR 0.36 95% CI 0.06â2.07, p =â.26). CONCLUSIONS: Treatment with senicapoc resulted in a significantly lower PaO(2)/FiO(2) ratio at 72âh with no differences for other outcomes
School performance of international adoptees better than expected from cognitive test results
Objective: To investigate school performance of international adoptees in relation to their cognitive competence. Method: From the population of all male Swedish residents born 1973â1976, registered in the census 1985 and with complete test scores from military conscription, the following study groups were identified: Korean adoptees (n = 320), non-Korean adoptees (n = 1,125), siblings (children born by adoptive parents, n = 190) and Swedish majority comparisons (n = 142,024). Global scores from intelligence tests at conscription were compared with grade points from the last compulsory school year (year 9). Linear and logistic regression was applied in statistical analyses. Results: The mean grade points in theoretical subjects were lower in non-Korean adoptees than in the majority population, but when global test scores from military conscription were adjusted for, outcomes were significantly better, equal for physics, than in the majority population. The grade points of Korean adoptees were higher than in the majority population and the same held true after adjusting for global test scores. When SES was taken into account, the risk of poor school performance (only completed lower subject levels) increased in non-Korean adoptees compared to models only adjusted for age and sex. Conclusion: Male international adoptees generally perform better in school than expected by their cognitive competence. A cognitive evaluation is important in the assessment of adoptees with learning difficulties
Fish Oil-Derived Fatty Acids in Pregnancy and Wheeze and Asthma in Offspring
Š 2016 Massachusetts Medical Society. Bisgaard, H., Stokholm, J., Chawes, B. L., Vissing, N. H., BjarnadĂłttir, E., Schoos, A.-M. M., ⌠Bønnelykke, K. (2016). Fish OilâDerived Fatty Acids in Pregnancy and Wheeze and Asthma in Offspring. New England Journal of Medicine, 375(26), 2530â2539. https://doi.org/10.1056/NEJMoa1503734BACKGROUND Reduced intake of n-3 long-chain polyunsaturated fatty acids (LCPUFAs) may be a contributing factor to the increasing prevalence of wheezing disorders. We assessed the effect of supplementation with n-3 LCPUFAs in pregnant women on the risk of persistent wheeze and asthma in their offspring. METHODS We randomly assigned 736 pregnant women at 24 weeks of gestation to receive 2.4 g of n-3 LCPUFA (fish oil) or placebo (olive oil) per day. Their children formed the Copenhagen Prospective Studies on Asthma in Childhood 2010 (COPSAC 2010) cohort and were followed prospectively with extensive clinical phenotyping. Neither the investigators nor the participants were aware of group assignments during follow-up for the first 3 years of the children's lives, after which there was a 2-year follow-up period during which only the investigators were unaware of group assignments. The primary end point was persistent wheeze or asthma, and the secondary end points included lower respiratory tract infections, asthma exacerbations, eczema, and allergic sensitization. RESULTS A total of 695 children were included in the trial, and 95.5% completed the 3-year, double-blind follow-up period. The risk of persistent wheeze or asthma in the treatment group was 16.9%, versus 23.7% in the control group (hazard ratio, 0.69; 95% confidence interval [CI], 0.49 to 0.97; P=0.035), corresponding to a relative reduction of 30.7%. Prespecified subgroup analyses suggested that the effect was strongest in the children of women whose blood levels of eicosapentaenoic acid and docosahexaenoic acid were in the lowest third of the trial population at randomization: 17.5% versus 34.1% (hazard ratio, 0.46; 95% CI, 0.25 to 0.83; P=0.011). Analyses of secondary end points showed that supplementation with n-3 LCPUFA was associated with a reduced risk of infections of the lower respiratory tract (31.7% vs. 39.1%; hazard ratio, 0.75; 95% CI, 0.58 to 0.98; P=0.033), but there was no statistically significant association between supplementation and asthma exacerbations, eczema, or allergic sensitization. CONCLUSIONS Supplementation with n-3 LCPUFA in the third trimester of pregnancy reduced the absolute risk of persistent wheeze or asthma and infections of the lower respiratory tract in offspring by approximately 7 percentage points, or one third. (Funded by the Lund-beck Foundation and others; ClinicalTrials.gov number, NCT00798226.)Lundbeck Foundatio
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