[Detoxification after use of new psychoactive substances purchased online]. / Avrusning etter bruk av nye rusmidler fra internett.

Background: The knowledge base on new psychoactive substances (NPS) is generally limited. This introduces new challenges and increased unpredictability in substance abuse treatment. Case presentation: A man in his thirties was submitted to detoxification after reportedly using flubromazolam, a high potency designer benzodiazepine, which he had purchased on the dark web. Extensive drug testing of serum, urine and hair, and the remains in a dropper bottle delivered by the patient, did not reveal flubromazolam or possible metabolites, but did reveal several common drugs of abuse, and 8-aminoclonazolam, a metabolite of clonazolam, another designer benzodiazepine sold on the dark web. The detoxification was uncomplicated. An excessive treatment protocol based on the patient's information, involving high preparedness and increased resources, both clinically and analytically, turned out to be unnecessary. Interpretation: The drug use and clinical course in this case proved to be more common than the unit prepared for. The case history illustrates both the challenges with users of NPS and the general unpredictability in substance abuse treatment.

Unexpected high retention of 15 N-labeled nitrogen in a tropical legume forest under long-term nitrogen enrichment.

The responses of forests to nitrogen (N) deposition largely depend on the fates of deposited N within the ecosystem. Nitrogen-fixing legume trees widely occur in terrestrial forests, but the fates of deposited N in legume-dominated forests remain unclear, which limit a global evaluation of N deposition impacts and feedbacks on carbon sequestration. Here, we performed the first ecosystem-scale 15 N labeling experiment in a typical legume-dominated forest as well as in a nearby non-legume forest to determine the fates of N deposition between two different forest types and to explore their underlying mechanisms. The 15 N was sprayed bimonthly for 1 year to the forest floor in control and N addition (50 kg N ha-1  year-1 for 10 years) plots in both forests. We unexpectedly found a strong capacity of the legume forest to retain deposited N, with 75 ± 5% labeled N recovered in plants and soils, which was higher than that in the non-legume forest (56 ± 4%). The higher 15 N recovery in legume forest was mainly driven by uptake by the legume trees, in which 15 N recovery was approximately 15% more than that in the nearby non-legume trees. This indicates higher N-demand by the legume than non-legume trees. Mineral soil was the major sink for deposited N, with 39 ± 4% and 34 ± 3% labeled N retained in the legume and non-legume forests, respectively. Moreover, N addition did not significantly change the 15 N recovery patterns of both forests. Overall, these findings indicate that legume-dominated forests act as a strong sink for deposited N regardless of high soil N availability under long-term atmospheric N deposition, which suggest a necessity to incorporate legume-dominated forests into N-cycling models of Earth systems to improve the understanding and prediction of terrestrial N budgets and the global N deposition effects.

Dynamics and multi-annual fate of atmospherically deposited nitrogen in montane tropical forests.

The effects of nitrogen (N) deposition on forests largely depend on its fate after entering the ecosystem. While several studies have addressed the forest fate of N deposition using 15 N tracers, the long-term fate and redistribution of deposited N in tropical forests remains unknown. Here, we applied 15 N tracers to examine the fates of deposited ammonium ( NH 4 + ) and nitrate ( NO 3 - ) separately over 3 years in a primary and a secondary tropical montane forest in southern China. Three months after 15 N tracer addition, over 60% of 15 N was retained in the forests studied. Total ecosystem retention did not change over the study period, but between 3 months and 3 years following deposition 15 N recovery in plants increased from 10% to 19% and 13% to 22% in the primary and secondary forests, respectively, while 15 N recovery in the organic soil declined from 16% to 2% and 9% to 2%. Mineral soil retained 50% and 35% of 15 N in the primary and secondary forests, with retention being stable over time. The total ecosystem retention of the two N forms did not differ significantly, but plants retained more 15 NO 3 - than 15 NH 4 + and the organic soil more 15 NH 4 + than NO 3 - . Mineral soil did not differ in 15 NH 4 + and 15 NO 3 - retention. Compared to temperate forests, proportionally more 15 N was distributed to mineral soil and plants in these tropical forests. Overall, our results suggest that atmospherically deposited NH 4 + and NO 3 - is rapidly lost in the short term (months) but thereafter securely retained within the ecosystem, with retained N becoming redistributed to plants and mineral soil from the organic soil. This long-term N retention may benefit tropical montane forest growth and enhance ecosystem carbon sequestration.

Exploring the role of ectomycorrhizal fungi in soil carbon dynamics.

The extent to which ectomycorrhizal (ECM) fungi enable plants to access organic nitrogen (N) bound in soil organic matter (SOM) and transfer this growth-limiting nutrient to their plant host, has important implications for our understanding of plant-fungal interactions, and the cycling and storage of carbon (C) and N in terrestrial ecosystems. Empirical evidence currently supports a range of perspectives, suggesting that ECM vary in their ability to provide their host with N bound in SOM, and that this capacity can both positively and negatively influence soil C storage. To help resolve the multiplicity of observations, we gathered a group of researchers to explore the role of ECM fungi in soil C dynamics, and propose new directions that hold promise to resolve competing hypotheses and contrasting observations. In this Viewpoint, we summarize these deliberations and identify areas of inquiry that hold promise for increasing our understanding of these fundamental and widespread plant symbionts and their role in ecosystem-level biogeochemistry.

Fate of atmospherically deposited NH4+ and NO3- in two temperate forests in China: temporal pattern and redistribution.

The impacts of anthropogenic nitrogen (N) deposition on forest ecosystems depend in large part on its fate. However, our understanding of the fates of different forms of deposited N as well as the redistribution over time within different ecosystems is limited. In this study, we used the 15 N-tracer method to investigate both the short-term (1 week to 3 months) and long-term (1-3 yr) fates of deposited NH4+ or NO3- by following the recovery of the 15 N in different ecosystem compartments in a larch plantation forest and a mixed forest located in northeastern China. The results showed similar total ecosystem retention for deposited NH4+ and NO3- , but their distribution within the ecosystems (plants vs. soil) differed distinctly particularly in the short-term, with higher 15 NO3- recoveries in plants (while lower recoveries in organic layer) than found for 15 NH4+ . The different short-term fate was likely related to the higher mobility of 15 NO3- than 15 NH4+ in soils instead of plant uptake preferences for NO3- over NH4+ . In the long-term, differences between N forms became less prevalent but higher recoveries in trees (particularly in the larch forest) of 15 NO3- than 15 NH4+ tracer persisted, suggesting that incoming NO3- may contribute more to plant biomass increment and forest carbon sequestration than incoming NH4+ . Differences between the two forests in recoveries were largely driven by a higher 15 N recovery in the organic layer (both N forms) and in trees (for 15 NO3- ) in the larch forest compared to the mixed forest. This was due to a more abundant organic layer and possibly higher tree N demand in the larch forest than in the mixed forest. Leachate 15 N loss was minor (<1% of the added 15 N) for both N forms and in both forests. Total 15 N recovery averaged 78% in the short-term and decreased to 55% in the long-term but with increasing amount of 15 N label (re)-redistributed into slow turn-over pools (e.g., trees and mineral soil). The different retention dynamics of deposited NH4+ and NO3- may have implications in environmental policy related to the anthropogenic emissions of the two N forms.

Long-term serum platinum changes and their association with cisplatin-related late effects in testicular cancer survivors.

BACKGROUND: The long-term toxicities after cisplatin-based chemotherapy (CBCT) reveal a remarkable inter-individual variation among testicular cancer survivors (TCSs). Therefore, we assessed long-term platinum (Pt) changes and their associations with CBCT-related late effects in TCSs. MATERIAL AND METHODS: In 77 TCSs treated with CBCT from 1984 to 1990, blood samples for analyses of Pt and a questionnaire including self-reported neuro- and ototoxicity (NTX) symptoms were collected during two follow-up surveys at median 12 (Survey I; SI) and 20 (Survey II; SII) years after treatment. Information about second cancers after SII was retrieved from the Norwegian Cancer Registry. RESULTS: A larger Pt decline from SI to SII was associated with a decreased risk of a second cancer diagnosis (HR 0.78, 95% CI 0.62-0.99 per 10 ng/L/year), and worsening of paresthesias in hands (OR 1.98, 95% CI 1.09-3.59 per 10 ng/L/year) and tinnitus (OR 1.51, 95% CI 1.01-2.27 per 10 ng/L/year). CONCLUSION: In summary, we found a significant association between a larger Pt decline and a reduced risk of second cancers and deterioration of paresthesias in hands and tinnitus.

Long-term ototoxicity in women after cisplatin treatment for ovarian germ cell cancer.

OBJECTIVE: Evaluate long-term cisplatin-induced ototoxicity in women treated for malignant ovarian germ cell tumors (MOGCT). METHODS: Seventy-four women treated for MOGCT in Norway (1980-2009) were analyzed: 41 had received cisplatin-based chemotherapy (CBCT) ("Cases") and 33 had no CBCT ("Controls"). Median follow-up was 15years. Hearing was assessed by pure tone audiometry and by the SCIN questionnaire. Air conduction thresholds were reported as absolute hearing thresholds and age-adjusted thresholds. Absolute and age-adjusted hearing loss were defined as thresholds of >20dB at any frequency. Tinnitus was evaluated using the Tinnitus Handicap Inventory. Serum Platinum Concentration (SPC) was determined. RESULTS: Absolute hearing loss was identified in 21 Cases (51%) and 24 Controls (73%). After adjusting for age, only 9 Cases (22%) and 5 Controls (15%) remained. Age-adjusted hearing thresholds at 4, 6 and 8kHz were slightly but significantly higher in Cases compared to Controls. Subjective hearing loss was reported by 27% of Cases and 21% of Controls, who were significantly older. Elevated SPC values were detected up to 20years after CBCT, but SPC did not correlate significantly with age-adjusted hearing loss. The rate of tinnitus was similar in Cases and Controls. CONCLUSION: Long-term MOGCT survivors treated with CBCT have small but significant reductions in age-adjusted hearing thresholds at 4, 6 and 8kHz versus Controls. Approximately one in four women experienced subjective hearing loss. To avoid overestimation of clinically relevant cisplatin-induced ototoxicity, absolute hearing thresholds should be age-adjusted and compared to an age-matched control group.

High retention of 15 N-labeled nitrogen deposition in a nitrogen saturated old-growth tropical forest.

The effects of increased reactive nitrogen (N) deposition in forests depend largely on its fate in the ecosystems. However, our knowledge on the fates of deposited N in tropical forest ecosystems and its retention mechanisms is limited. Here, we report the results from the first whole ecosystem 15 N labeling experiment performed in a N-rich old-growth tropical forest in southern China. We added 15 N tracer monthly as 15 NH415 NO3 for 1 year to control plots and to N-fertilized plots (N-plots, receiving additions of 50 kg N ha-1  yr-1 for 10 years). Tracer recoveries in major ecosystem compartments were quantified 4 months after the last addition. Tracer recoveries in soil solution were monitored monthly to quantify leaching losses. Total tracer recovery in plant and soil (N retention) in the control plots was 72% and similar to those observed in temperate forests. The retention decreased to 52% in the N-plots. Soil was the dominant sink, retaining 37% and 28% of the labeled N input in the control and N-plots, respectively. Leaching below 20 cm was 50 kg N ha-1  yr-1 in the control plots and was close to the N input (51 kg N ha-1  yr-1 ), indicating N saturation of the top soil. Nitrogen addition increased N leaching to 73 kg N ha-1  yr-1 . However, of these only 7 and 23 kg N ha-1  yr-1 in the control and N-plots, respectively, originated from the labeled N input. Our findings indicate that deposited N, like in temperate forests, is largely incorporated into plant and soil pools in the short term, although the forest is N-saturated, but high cycling rates may later release the N for leaching and/or gaseous loss. Thus, N cycling rates rather than short-term N retention represent the main difference between temperate forests and the studied tropical forest.

Afforestation effects on SOC in former cropland: oak and spruce chronosequences resampled after 13 years.

Chronosequences are commonly used to assess soil organic carbon (SOC) sequestration after land-use change, but SOC dynamics predicted by this space-for-time substitution approach have rarely been validated by resampling. We conducted a combined chronosequence/resampling study in a former cropland area (Vestskoven) afforested with oak (Quercus robur) and Norway spruce (Picea abies) over the past 40 years. The aims of this study were (i) to compare present and previous chronosequence trends in forest floor and top mineral soil (0-25 cm) C stocks; (ii) to compare chronosequence estimates with current rates of C stock change based on resampling at the stand level; (iii) to estimate SOC changes in the subsoil (25-50 cm); and (iv) to assess the influence of two tree species on SOC dynamics. The two chronosequence trajectories for forest floor C stocks revealed consistently higher rates of C sequestration in spruce than oak. The chronosequence trajectory was validated by resampling and current rates of forest floor C sequestration decreased with stand age. Chronosequence trends in topsoil SOC in 2011 did not differ significantly from those reported in 1998, however, there was a shift from a negative rate (1998: -0.3 Mg C ha(-1) yr(-1) ) to no change in 2011. In contrast SOC stocks in the subsoil increased with stand age, however, not significantly (P = 0.1), suggesting different C dynamics in and below the former plough layer. Current rates of C change estimated by repeated sampling decreased with stand age in forest floors but increased in the topsoil. The contrasting temporal change in forest floor and mineral soil C sequestration rates indicate a shift in C source-sink strength after approximately 40 years. We conclude that afforestation of former cropland within the temperate region may induce soil C loss during the first decades followed by a recovery phase of yet unknown duration.

Ecologically implausible carbon response?

Magnani et al. present a very strong correlation between mean lifetime net ecosystem production (NEP, defined as the net rate of carbon (C) accumulation in ecosystems) and wet nitrogen (N) deposition. For their data in the range 4.9-9.8 kg N ha(-1) yr(-1), on which the correlation largely depends, the response is approximately 725 kg C per kg N in wet deposition. According to the authors, the maximum N wet deposition level of 9.8 kg N ha(-1) yr(-1) is equivalent to a total deposition of 15 kg N ha(-1 )yr(-1), implying a net sequestration near 470 kg C per kg N of total deposition. We question the ecological plausibility of the relationship and show, from a multi-factor analysis of European forest measurements, how interactions with site productivity and environment imply a much smaller NEP response to N deposition.

Retrospective screening of new psychoactive substances (NPS) in post mortem samples from 2014 to 2021.

Systematic retrospective processing of previously analysed biological samples has been proven to be a valuable tool in the search for new drugs (e.g. new psychoactive substances (NPS)) and for quality assessment in clinical and forensic toxicology. In a previous study, we developed a strategy for retrospective data-analysis using a personalized library of synthetic cannabinoids, designer benzodiazepines and synthetic opioids obtained from the crowdsourced database HighResNPS (https://highresnps.com). In this study, the same strategy was employed for the compounds within the groups of NPS that were not previously included such as synthetic cathinones, phenethylamines, aminoindanes, arylalkylamines, piperazine derivates, piperidines, pyrrolidines, indolalkylamines and arylcyclohexylamines. Synthetic opioids and designer benzodiazepines, which were not part of the previous study, were also included. To enhance the effectiveness of the retrospective analysis, a predicted retention time was included for all entries. Data files from the analysis of 2186 forensic post mortem samples with an Agilent Technologies 6540 ultra-high pressure liquid chromatography quadrupole time-of-flight mass spectrometry (UHPLC-QTOF-MS) performed in the laboratory from January 2014 to December 2021 were retrospectively processed with the up-to-date library. Tentative findings were classified in two groups: The findings where MS/MS data was acquired for library match (category 1) and the less certain findings where such data lacked (category 2). Five compounds of category 1 (three synthetic cathinones and two indolalkylamines) were identified in 12 samples. Only one of the findings, 4-MEAPP (4-methyl-α-ethylaminopentiophenone), was deemed plausible after reviewing case information. As many as 501 presumably positive category 2 findings were detected. Using the predicted retention time as an additional criterion the number was significantly reduced but still too high for a manual review. This work has demonstrated that the strategy developed in the previous study can be applied to other NPS groups. However, it is important to note the limitations such a method may have in detecting compounds at very low concentrations.

Findings of the neuromuscular blocking agent rocuronium in blood from deceased subjects several months after exposure: A report of two cases.

Rocuronium is a neuromuscular blocking agent mainly used in anesthetic procedures. Two patients who died 53 and 76 days, respectively, after their last rocuronium exposure had low (0.002-0.007 mg/L) levels of the drug in femoral blood, urine and vitreous humor samples obtained at autopsy. In neither case, the cause of death was related to the exposure to rocuronium. Here, these two cases are presented and the implications of the findings discussed.

Dramatic changes in ectomycorrhizal community composition, root tip abundance and mycelial production along a stand-scale nitrogen deposition gradient.

• Nitrogen (N) availability is known to influence ectomycorrhizal fungal components, such as fungal community composition, biomass of root tips and production of mycelia, but effects have never been demonstrated within the same forest. • We measured concurrently the abundance of ectomycorrhizal root tips and the production of external mycelia, and explored the changes in the ectomycorrhizal community composition, across a stand-scale N deposition gradient (from 27 to 43 kg N ha⁻¹ yr⁻¹) at the edge of a spruce forest. The N status was affected along the gradient as shown by a range of N availability indices. • Ectomycorrhizal root tip abundance and mycelial production decreased five and 10-fold, respectively, with increasing N deposition. In addition, the ectomycorrhizal fungal community changed and the species richness decreased. The changes were correlated with the measured indices of N status, in particular N deposition and N leaching. • The relationship between the altered ectomycorrhizal community, root tip abundance and mycelial production is discussed in the context of the N parameters. We suggest that increased N deposition to forests will cause large changes in ectomycorrhizal fungal community structure and functioning, which, in turn, may result in reduced N uptake by roots and fungi, and increased losses of N by leaching.

Metformin serum concentrations during pregnancy and post partum - A clinical study in patients with polycystic ovary syndrome.

BACKGROUND AND OBJECTIVES: Metformin is used to treat gestational diabetes. It is also used to treat women with polycystic ovary syndrome and has been shown to prevent late miscarriage and preterm birth. However, increased renal clearance during pregnancy causes a decline in serum concentrations of metformin. The aim of this study was to explore the time course of the pregnancy-related changes in metformin pharmacokinetics and the return to the non-pregnant state. METHOD: A subgroup of women in the PregMet2 study (n = 73) agreed to provide serum samples at three time-points in pregnancy (gestational weeks 19, 28 and 32) and once in post partum, (either 2, 4 or 8 weeks after delivery). Serum metformin concentrations were compared using a four-parameter logistic model. FINDINGS: The mean steady-state serum concentration of metformin during pregnancy was 9.39 µmoL/L, whereas the post partum concentration was 12.36 µmoL/L, an increase of 32% (p = 0,019). This change took place already during the first 2 weeks post partum. CONCLUSION: Clinicians who treat pregnant women with metformin should be aware of the significant decrease in metformin concentration mediated by pregnancy, and the rapid increase after delivery, as it may impact both the therapeutic efficacy and the risk of adverse drug reactions.

Retention of deposited ammonium and nitrate and its impact on the global forest carbon sink.

The impacts of enhanced nitrogen (N) deposition on the global forest carbon (C) sink and other ecosystem services may depend on whether N is deposited in reduced (mainly as ammonium) or oxidized forms (mainly as nitrate) and the subsequent fate of each. However, the fates of the two key reactive N forms and their contributions to forest C sinks are unclear. Here, we analyze results from 13 ecosystem-scale paired 15N-labelling experiments in temperate, subtropical, and tropical forests. Results show that total ecosystem N retention is similar for ammonium and nitrate, but plants take up more labelled nitrate ([Formula: see text]%) ([Formula: see text]) than ammonium ([Formula: see text]%) while soils retain more ammonium ([Formula: see text]%) than nitrate ([Formula: see text]%). We estimate that the N deposition-induced C sink in forests in the 2010s  is [Formula: see text] Pg C yr-1, higher than previous estimates because of a larger role for oxidized N and greater rates of global N deposition.

Negative effects of long-term phosphorus additions on understory plants in a primary tropical forest.

Human activities have disturbed global phosphorus (P) cycling by introducing substantial amounts of P to natural ecosystems. Although natural P gradients and fertilization studies have found that plant community traits are closely related to P availability, it remains unclear how increased P supply affects plant growth and diversity in P-deficient tropical forests. We used a decadal P-addition experiment (2007-2017) to study the effects of increased P input on plant growth and diversity in understory layer in tropical forests. We monitored the dynamics of seedling growth, survival rate, and diversity of understory plants throughout the fertilization period under control and P addition at 15 g P m-2 yr-1. To identify the drivers of responses, P concentration, photosynthesis rate and nonstructural carbon were analyzed. Results showed that long-term P addition significantly increased P concentrations both in soil pools and plant tissues. However, P addition did not increase the light-saturated photosynthesis rate or growth rate of the understory plants. Furthermore, P addition significantly decreased the survival rate of seedlings and reduced the species richness and density of understory plants. The negative effects of P addition may be attributed to an increased carbon cost due to the tissue maintenance of plants with higher P concentrations. These findings indicate that increased P supply alone is not necessary to benefit the growth of plants in ecosystems with low P availability, and P inputs can inhibit understory plants and may alter community composition. Therefore, we appeal to a need for caution when inputting P to tropical forests ecosystems.

Environmental services provided from riparian forests in the Nordic countries.

Riparian forests (RF) growing along streams, rivers and lakes comprise more than 2% of the forest area in the Nordic countries (considering a 10 m wide zone from the water body). They have special ecological functions in the landscape. They receive water and nutrients from the upslope areas, are important habitats for biodiversity, have large soil carbon stores, but may emit more greenhouse gases (GHG) than the uplands. In this article, we present a review of the environmental services related to water protection, terrestrial biodiversity, carbon storage and greenhouse gas dynamics provided by RF in the Nordic countries. We discuss the benefits and trade-offs when leaving the RF as a buffer against the impacts from upland forest management, in particular the impacts of clear cutting. Forest buffers are effective in protecting water quality and aquatic life, and have positive effects on terrestrial biodiversity, particularly when broader than 40 m, whereas the effect on the greenhouse gas exchange is unclear.

Retrospective screening of synthetic cannabinoids, synthetic opioids and designer benzodiazepines in data files from forensic post mortem samples analysed by UHPLC-QTOF-MS from 2014 to 2018.

The introduction of new psychoactive substances (NPS) on the illicit drug market has led to major challenges for the analytical laboratories. Keeping screening methods up to date with all relevant drugs is hard to achieve and the risk of missing important findings in biological samples is a matter of concern. Aiming for an extended retrospective data analysis, diagnostic fragment ions from synthetic cannabinoids (n=251), synthetic opioids (n=88) and designer benzodiazepines (n=26) not included in our original analytical method were obtained from the crowdsourced database HighResNPS.com and converted to a personalized library in a format compatible with the analytical instrumentation. Data files from the analysis of 1314 forensic post mortem samples with an Agilent 6540 ultra high pressure liquid chromatography quadrupole time-of-flight mass spectrometry (UHPLC-QTOF-MS) performed in our laboratory from January 2014 to December 2018 were retrieved and retrospectively processed with the new personalized library. Potentially positive findings were grouped in two: The most confident findings contained MS/MS data for library match (category 1) whereas the less confident findings lacked such data (category 2). Five new category 1 findings were identified: Flubromazepam in two data files from 2015 and 2016, respectively, phenibut (4-amino-3-phenylbutyric acid) in one data file from 2015, fluorofentanyl in one data file from 2016 and cyclopropylfentanyl in one data file from 2018. Retention time matches with reference standards further strengthened these findings. A list of 35 presumably positive category 2 findings was generated. Of these, only one finding of phenibut was considered plausible after checking retention times and signal-to-noise ratios. This study shows that new compounds can be detected retrospectively in data files from QTOF-MS using an updated library containing diagnostic fragment ions. Automatic screening procedures can be useful, but a manual re-evaluation of positive findings will always be necessary.