Secondary adrenal insufficiency and pituitary dysfunction in oral/transdermal opioid users with non-cancer pain.

Objective To evaluate pituitary function, sexual function and quality of life (QoL) in patients on oral or transdermal opioids. Design and methods Cross-sectional study comparing pituitary function, QoL and sexual function in people on long-term opioid therapy (n = 40) vs an age- and sex-matched control group (n = 25). Baseline pituitary function was assessed on blood samples collected prior to 0900 h. Further testing with corticotropin (250 µg IV) and metyrapone (30 mg/kg) stimulation tests was undertaken on participants with serum cortisol <250 nmol/L. Validated questionnaires completed to assess QoL, fatigue and sexual function. Results Secondary adrenal insufficiency (SAI) was identified on the basis of a failed stimulation test in 22.5% of opioid users vs no controls (P = 0.01). Opioid users with SAI had a higher median morphine-equivalent daily dose (MEDD), P = 0.037 - 50% with MEDD >200 mg and 0% with MEDD <60 mg had SAI. Among male participants, testosterone was inversely associated with BMI (P = 0.001) but not opioid use. A non-significant trend to low testosterone <8 nmol/L in male opioid users (11/24 opioid users vs 2/14 control, P = 0.08) suggests a small subgroup with opioid-induced androgen deficiency. Opioid users had greater fatigue, reduced quality of life in all subsections of the SF-36 and impaired sexual function in both males and females (all scores P < 0.001 compared to controls). Conclusion Long-term opioid therapy was associated with dose-related SAI in over 20% of chronic pain patients and is associated with poor quality of life, fatigue and sexual dysfunction. Obesity confounds the interpretation of opioid-induced male androgen deficiency.

Climate change leads to accelerated transformation of high-elevation vegetation in the central Alps.

High mountain ecosystems and their biota are governed by low-temperature conditions and thus can be used as indicators for climate warming impacts on natural ecosystems, provided that long-term data exist. We used data from the largest alpine to nival permanent plot site in the Alps, established in the frame of the Global Observation Research Initiative in Alpine Environments (GLORIA) on Schrankogel in the Tyrolean Alps, Austria, in 1994, and resurveyed in 2004 and 2014. Vascular plant species richness per plot increased over the entire period, albeit to a lesser extent in the second decade, because disappearance events increased markedly in the latter period. Although presence/absence data could only marginally explain range shift dynamics, changes in species cover and plant community composition indicate an accelerating transformation towards a more warmth-demanding and more drought-adapted vegetation, which is strongest at the lowest, least rugged subsite. Divergent responses of vertical distribution groups of species suggest that direct warming effects, rather than competitive displacement, are the primary causes of the observed patterns. The continued decrease in cryophilic species could imply that trailing edge dynamics proceed more rapidly than successful colonisation, which would favour a period of accelerated species declines.

Accelerated increase in plant species richness on mountain summits is linked to warming.

Globally accelerating trends in societal development and human environmental impacts since the mid-twentieth century 1-7 are known as the Great Acceleration and have been discussed as a key indicator of the onset of the Anthropocene epoch 6 . While reports on ecological responses (for example, changes in species range or local extinctions) to the Great Acceleration are multiplying 8, 9 , it is unknown whether such biotic responses are undergoing a similar acceleration over time. This knowledge gap stems from the limited availability of time series data on biodiversity changes across large temporal and geographical extents. Here we use a dataset of repeated plant surveys from 302 mountain summits across Europe, spanning 145 years of observation, to assess the temporal trajectory of mountain biodiversity changes as a globally coherent imprint of the Anthropocene. We find a continent-wide acceleration in the rate of increase in plant species richness, with five times as much species enrichment between 2007 and 2016 as fifty years ago, between 1957 and 1966. This acceleration is strikingly synchronized with accelerated global warming and is not linked to alternative global change drivers. The accelerating increases in species richness on mountain summits across this broad spatial extent demonstrate that acceleration in climate-induced biotic change is occurring even in remote places on Earth, with potentially far-ranging consequences not only for biodiversity, but also for ecosystem functioning and services.

Distribution of Prokaryotic Abundance and Microbial Nutrient Cycling Across a High-Alpine Altitudinal Gradient in the Austrian Central Alps is Affected by Vegetation, Temperature, and Soil Nutrients.

Studies of the altitudinal distributions of soil microorganisms are rare or have led to contradictory results. Therefore, we studied archaeal and bacterial abundance and microbial-mediated activities across an altitudinal gradient (2700 to 3500 m) on the southwestern slope of Mt. Schrankogel (Central Alps, Austria). Sampling sites distributed over the alpine (2700 to 2900 m), the alpine-nival (3000 to 3100 m), and the nival altitudinal belts (3200 to 3500 m), which are populated by characteristic plant assemblages. Bacterial and archaeal abundances were measured via quantitative real-time PCR (qPCR). Moreover, microbial biomass C, microbial activity (dehydrogenase), and enzymes involved in carbon (CM-cellulase), nitrogen (protease), phosphorus (alkaline phosphatase), and sulfur (arylsulfatase) cycling were determined. Abundances, microbial biomass C, and activities almost linearly decreased along the gradient. Archaeal abundance experienced a sharper decrease, thus pointing to pronounced sensitivity toward environmental harshness. Additionally, abundance and activities were significantly higher in soils of the alpine belt compared with those of the nival belt, whereas the alpine-nival ecotone represented a transitional area with intermediate values, thus highlighting the importance of vegetation. Archaeal abundance along the gradient was significantly related to soil temperature only, whereas bacterial abundance was significantly related to temperature and dissolved organic carbon (DOC). Soil carbon and nitrogen concentrations explained most of the variance in enzyme activities involved in the cycling of C, N, P, and S. Increasing temperature could therefore increase the abundances and activities of microorganisms either directly or indirectly via expansion of alpine vegetation to higher altitudes and increased plant cover.

Coarsening dynamics of domains in lipid membranes.

We investigate isothermal diffusion and growth of micron-scale liquid domains within membranes of free-floating giant unilamellar vesicles with diameters between 80 and 250 µm. Domains appear after a rapid temperature quench, when the membrane is cooled through a miscibility phase transition such that coexisting liquid phases form. In membranes quenched far from a miscibility critical point, circular domains nucleate and then progress within seconds to late stage coarsening in which domains grow via two mechanisms 1), collision and coalescence of liquid domains, and 2), Ostwald ripening. Both mechanisms are expected to yield the same growth exponent, α = 1/3, where domain radius grows as time(α). We measure α = 0.28 ± 0.05, in excellent agreement. In membranes close to a miscibility critical point, the two liquid phases in the membrane are bicontinuous. A quench near the critical composition results in rapid changes in morphology of elongated domains. In this case, we measure α = 0.50 ± 0.16, consistent with theory and simulation.

T(14;18)(q32;q21) involving IGH and MALT1 is a frequent chromosomal aberration in MALT lymphoma.

T(11;18)(q21;q21) is the most common structural abnormality in extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) leading to the fusion of the apoptosis inhibitor-2 (API2) gene and the MALT lymphoma-associated translocation (MALT1) gene. In 2 patients with MALT lymphoma of the liver and skin, respectively, t(14;18)(q32;q21) was observed by cytogenetic analysis. Subsequent fluorescence in situ hybridization (FISH) studies disclosed that the immunoglobulin heavy-chain locus (IGH) and the MALT1 gene were rearranged by this translocation. In order to screen a large series of MALT lymphomas for this aberration, a 2-color interphase FISH assay was established. Among a total of 66 cases, t(14;18)(q32;q21) involving IGH and MALT1 was detected in MALT lymphomas of the liver (4 of 4), skin (3 of 11), ocular adnexa (3 of 8), and salivary gland (2 of 11), but did not occur in MALT lymphomas of the stomach (n = 10), intestine (n = 9), lung (n = 7), thyroid (n = 4), or breast (n = 2). In total, 12 of 66 (18%) MALT lymphomas harbored t(14;18)(q32;q21); 7 additional cases of splenic marginal zone lymphoma tested negative. All of the 12 MALT lymphomas featuring the t(14;18)(q32;q21) were negative for t(11;18)(q21;q21) by reverse transcriptase-polymerase chain reaction (RT-PCR). However, trisomy 3 and/or 18 was found in 4 of 12 cases, suggesting that the t(14;18)(q32;q21) does not occur as the sole genetic abnormality. This study identifies IGH as a new translocation partner of MALT1 in MALT lymphomas, which tend to arise frequently at sites other than the gastrointestinal tract and lung. In contrast to t(11;18)(q21;q21)(+) MALT lymphomas, those with t(14;18)(q32;q21) may harbor additional genetic abnormalities.