Bestäubend schön Berlin

BESTÄUBEND SCHÖN BERLIN Bestäubend schön Berlin / Miller, Leif (Rights reserved) ( -

Relationship between matrix production by bronchial fibroblasts and lung function and AHR in asthma

SummaryThe reasons for enhanced deposition of extracellular matrix in the airways of asthmatic patients and the subsequent consequences on lung function are uncertain. Here, we investigated the synthesis of procollagen I and proteoglycans, the activity of various metalloproteinases (MMPs) and the production of their inhibitor TIMP-1 in biopsy-derived bronchial fibroblasts from eight patients with stable mild-to-moderate asthma, and how they are related to patients’ lung function and airway hyperreactivity (AHR).Following 24-h fibroblast incubation in 0.4% serum, procollagen I carboxyterminal propeptide (PICP), TIMP-1 and MMP-1 in cell media were analysed by ELISA, MMP-2, MMP-3, MMP-9 by zymography and total proteoglycan production by [35S]-sulphate-incorporation/ion chromatography.Patients’ FEV1% predicted and methacholine log PD20 negatively correlated with PICP synthesized by patients’ bronchial fibroblasts (r = −0.74 and r = −0.71, respectively). PICP and proteoglycan amounts positively correlated (0.8 ≤ r ≤ 0.9) with MMP-2 and MMP-3 activity. A positive correlation (r = 0.75) was also found between proteoglycan production and TIMP-1. There was no correlation between MMP-9 activity and PICP or proteoglycan production. MMP-9 activity positively correlated with patients’ FEV1% predicted (r = 0.97) and methacholine log PD20 (r = 0.86), whereas negative associations (−0.6 ≤ r ≤ −0.7) were observed for MMP-2 and MMP-3.In stable mild-to-moderate asthma, increased procollagen I synthesis and activity of MMP-2 and MMP-3 in bronchial fibroblasts may negatively affect patients’ lung function and AHR. In contrast, MMP-9 activity was not associated with procollagen or proteoglycan production, or worsening of patients’ lung function and AHR. An enhanced production of procollagen I and proteoglycans might be a result of a negative feedback from their degradation by MMP-2 and MMP-3

Extensive spontaneous plasticity of corticospinal projections after primate spinal cord injury.

Although axonal regeneration after CNS injury is limited, partial injury is frequently accompanied by extensive functional recovery. To investigate mechanisms underlying spontaneous recovery after incomplete spinal cord injury, we administered C7 spinal cord hemisections to adult rhesus monkeys and analyzed behavioral, electrophysiological and anatomical adaptations. We found marked spontaneous plasticity of corticospinal projections, with reconstitution of fully 60% of pre-lesion axon density arising from sprouting of spinal cord midline-crossing axons. This extensive anatomical recovery was associated with improvement in coordinated muscle recruitment, hand function and locomotion. These findings identify what may be the most extensive natural recovery of mammalian axonal projections after nervous system injury observed to date, highlighting an important role for primate models in translational disease research

Urinary CC16 after challenge with dry air hyperpnoea and mannitol in recreational summer athletes

Airway epithelial injury is regarded as a key contributing factor to the pathogenesis of exercise-induced bronchoconstriction (EIB) in athletes. The concentration of the pneumoprotein club cell (Clara cell) CC16 in urine has been found to be a non-invasive marker for hyperpnoea-induced airway epithelial perturbation. Exercise-hyperpnoea induces mechanical, thermal and osmotic stress to the airways. We investigated whether osmotic stress alone causes airway epithelial perturbation in athletes with suspected EIB. Twenty-four recreational summer sports athletes who reported respiratory symptoms on exertion performed a standard eucapnic voluntary hyperpnoea test with dry air and a mannitol test (osmotic challenge) on separate days. Median urinary CC16 increased from 120 to 310 ρg μmol creatinine-1 after dry air hyperpnoea (P = 0.002) and from 90 to 191 ρg μmol creatinine-1 after mannitol (P = 0.021). There was no difference in urinary CC16 concentration between athletes who did or did not bronchoconstrict after dry air hyperpnoea or mannitol. We conclude that, in recreational summer sports athletes with respiratory symptoms, osmotic stress per se to the airway epithelium induces a rise in urinary excretion of CC16. This suggests that hyperosmolarity of the airway surface lining perturbs the airway epithelium in symptomatic athletes.The study was independently supported financially by the World Anti Doping Agency (WADA). Pharmaxis Ltd. provided the mannitol kits free of charge and approved submission of the manuscript for publication

Alles im grünen Bereich!

ALLES IM GRÜNEN BEREICH! Alles im grünen Bereich! / Miller, Leif (Rights reserved) ( -

Anterior cingulate gamma-aminobutyric acid concentrations and electroconvulsive therapy

Objective The anticonvulsant hypothesis posits that ECT’s mechanism of action is related to enhancement of endogenous anticonvulsant brain mechanisms. Results of prior studies investigating the role of the inhibitory neurotransmitter gamma‐aminobutyric acid (“GABA+”, GABA and coedited macromolecules) in the pathophysiology and treatment of depression remain inconclusive. The aim of our study was to investigate treatment‐responsive changes of GABA+ in subjects with a depressive episode receiving electroconvulsive therapy (ECT). Methods In total, 41 depressed subjects (DEP) and 35 healthy controls (HC) were recruited at two independent sites in Norway and the USA. MEGA‐PRESS was used for investigation of GABA+ in the anterior cingulate cortex. We assessed longitudinal and cross‐sectional differences between DEP and HC, as well as the relationship between GABA+ change and change in depression severity and number of ECTs. We also assessed longitudinal differences in cognitive performance and GABA+ levels. Results Depressive episode did not show a difference in GABA+ relative to HC (t71 = −0.36, p = .72) or in longitudinal analysis (t36 = 0.97, p = .34). Remitters and nonremitters did not show longitudinal (t36 = 1.12, p = .27) or cross‐sectional differences in GABA+. GABA+ levels were not related to changes in antidepressant response (t35 = 1.12, p = .27) or treatment number (t36 = 0.05, p = .96). An association between cognitive performance and GABA+ levels was found in DEP that completed cognitive effortful testing (t18 = 2.4, p = .03). Conclusion Our results failed to support GABA as a marker for depression and abnormal mood state and provide no support for the anticonvulsant hypothesis of ECT. ECT‐induced change in GABA concentrations may be related to change in cognitive function.publishedVersio

γγ\gamma\gamma Event Generators

The report from the working group on '\gamma\gamma Event Generators' of the LEP 2 workshopComment: 42 pages, tared, gzipped, uuencoded. To be published in the proceedings of the LEP 2 Worksho

The onset of neoglaciation in Iceland and the 4.2 ka event

Publisher's version (útgefin grein)Strong similarities in Holocene climate reconstructions derived from multiple proxies (BSi, TOC – total organic carbon, δ13C, C∕N, MS – magnetic susceptibility, δ15N) preserved in sediments from both glacial and non-glacial lakes across Iceland indicate a relatively warm early to mid Holocene from 10 to 6 ka, overprinted with cold excursions presumably related to meltwater impact on North Atlantic circulation until 7.9 ka. Sediment in lakes from glacial catchments indicates their catchments were ice-free during this interval. Statistical treatment of the high-resolution multi-proxy paleoclimate lake records shows that despite great variability in catchment characteristics, the sediment records document more or less synchronous abrupt, cold departures as opposed to the smoothly decreasing trend in Northern Hemisphere summer insolation. Although all lake records document a decline in summer temperature through the Holocene consistent with the regular decline in summer insolation, the onset of significant summer cooling occurs ∼5 ka at high-elevation interior sites but is variably later at sites closer to the coast, suggesting that proximity to the sea may modulate the impact from decreasing summer insolation. The timing of glacier inception during the mid Holocene is determined by the descent of the equilibrium line altitude (ELA), which is dominated by the evolution of summer temperature as summer insolation declined as well as changes in sea surface temperature for coastal glacial systems. The glacial response to the ELA decline is also highly dependent on the local topography. The initial ∼5 ka nucleation of Langjökull in the highlands of Iceland defines the onset of neoglaciation in Iceland. Subsequently, a stepwise expansion of both Langjökull and northeast Vatnajökull occurred between 4.5 and 4.0 ka, with a second abrupt expansion ∼3 ka. Due to its coastal setting and lower topographic threshold, the initial appearance of Drangajökull in the NW of Iceland was delayed until ∼2.3 ka. All lake records reflect abrupt summer temperature and catchment disturbance at ∼4.5 ka, statistically indistinguishable from the global 4.2 ka event, and a second widespread abrupt disturbance at 3.0 ka, similar to the stepwise expansion of Langjökull and northeast Vatnajökull. Both are intervals characterized by large explosive volcanism and tephra distribution in Iceland resulting in intensified local soil erosion. The most widespread increase in glacier advance, landscape instability, and soil erosion occurred shortly after 2 ka, likely due to a complex combination of increased impact from volcanic tephra deposition, cooling climate, and increased sea ice off the coast of Iceland. All lake records indicate a strong decline in temperature ∼1.5 ka, which culminated during the Little Ice Age (1250–1850 CE) when the glaciers reached their maximum Holocene dimensions.This work was supported primarily by the Icelandic Center for Research through grants awarded to Áslaug Geirsdóttir and Gifford H. Miller (no. 130775051 and Grant of Excellence no. 141573052) and several grants awarded to Áslaug Geirsdóttir from the UI Research Fund. We thank Sædís Ólafsdóttir, Celene Blair, Sydney Gunnarson, Sarah Crump, Thorsteinn Jónsson, and Sveinbjörn Steinthorsson, who all contributed to this work by taking part in field work, laboratory analyses, and/or discussion. Thorough and constructive reviews from two anonymous reviewers have substantially improved the paper.Peer Reviewe

Gliadin Nanoparticles Induce Immune Tolerance to Gliadin in Mouse Models of Celiac Disease

Peer reviewe

Use of Quality Improvement Strategies Among Small to Medium-Size US Primary Care Practices

PURPOSE Improving primary care quality is a national priority, but little is known about the extent to which small to medium-size practices use quality improvement (QI) strategies to improve care. We examined variations in use of QI strategies among 1,181 small to medium-size primary care practices engaged in a national initiative spanning 12 US states to improve quality of care for heart health and assessed factors associated with those variations. METHODS In this cross-sectional study, practice characteristics were assessed by surveying practice leaders. Practice use of QI strategies was measured by the validated Change Process Capability Questionnaire (CPCQ) Strategies Scale (scores range from −28 to 28, with higher scores indicating more use of QI strategies). Multivariable linear regression was used to examine the association between practice characteristics and the CPCQ strategies score. RESULTS The mean CPCQ strategies score was 9.1 (SD = 12.2). Practices that participated in accountable care organizations and those that had someone in the practice to configure clinical quality reports from electronic health records (EHRs), had produced quality reports, or had discussed clinical quality data during meetings had higher CPCQ strategies scores. Health system–owned practices and those experiencing major disruptive changes, such as implementing a new EHR system or clinician turnover, had lower CPCQ strategies scores. CONCLUSION There is substantial variation in the use of QI strategies among small to medium-size primary care practices across 12 US states. Findings suggest that practices may need external support to strengthen their ability to do QI and to be prepared for new payment and delivery models