Atmospheric nitrogen (N) deposition has been shown to decrease plant species richness along regional deposition gradients in Europe and in experimental manipulations. However, the general response of ...species richness to N deposition across different vegetation types, soil conditions, and climates remains largely unknown even though responses may be contingent on these environmental factors. We assessed the effect of N deposition on herbaceous richness for 15,136 forest, woodland, shrubland, and grassland sites across the continental United States, to address how edaphic and climatic conditions altered vulnerability to this stressor. In our dataset, with N deposition ranging from 1 to 19 kg N·ha−1·y−1, we found a unimodal relationship; richness increased at low deposition levels and decreased above 8.7 and 13.4 kg N·ha−1·y−1 in open and closed-canopy vegetation, respectively. N deposition exceeded critical loads for loss of plant species richness in 24% of 15,136 sites examined nationwide. There were negative relationships between species richness and N deposition in 36% of 44 community gradients. Vulnerability to N deposition was consistently higher in more acidic soils whereas the moderating roles of temperature and precipitation varied across scales. We demonstrate here that negative relationships between N deposition and species richness are common, albeit not universal, and that fine-scale processes can moderate vegetation responses to N deposition. Our results highlight the importance of contingent factors when estimating ecosystem vulnerability to N deposition and suggest that N deposition is affecting species richness in forested and nonforested systems across much of the continental United States.
Substance-use disorders are a global public health problem that arises from behavioral misallocation between drug use and more adaptive behaviors maintained by nondrug alternatives (e.g., food or ...money). Preclinical drug self-administration procedures that incorporate a concurrently available nondrug reinforcer (e.g., food) provide translationally relevant and distinct dependent measures of behavioral allocation (i.e., to assess the relative reinforcing efficacy of the drug) and behavioral rate (i.e., to assess motor competence). In particular, preclinical drug versus food ‘choice’ procedures have produced increasingly concordant results with both human laboratory drug self-administration studies and double-blind placebo-controlled clinical trials. Accordingly, here we provide a heuristic framework of substance-use disorders based on a behavioral-centric perspective and recent insights from these preclinical choice procedures.
Multiple models describe the formation and evolution of distinct microbial phylogenetic groups. These evolutionary models make different predictions regarding how adaptive alleles spread through ...populations and how genetic diversity is maintained. Processes predicted by competing evolutionary models, for example, genome-wide selective sweeps vs gene-specific sweeps, could be captured in natural populations using time-series metagenomics if the approach were applied over a sufficiently long time frame. Direct observations of either process would help resolve how distinct microbial groups evolve. Here, from a 9-year metagenomic study of a freshwater lake (2005-2013), we explore changes in single-nucleotide polymorphism (SNP) frequencies and patterns of gene gain and loss in 30 bacterial populations. SNP analyses revealed substantial genetic heterogeneity within these populations, although the degree of heterogeneity varied by >1000-fold among populations. SNP allele frequencies also changed dramatically over time within some populations. Interestingly, nearly all SNP variants were slowly purged over several years from one population of green sulfur bacteria, while at the same time multiple genes either swept through or were lost from this population. These patterns were consistent with a genome-wide selective sweep in progress, a process predicted by the 'ecotype model' of speciation but not previously observed in nature. In contrast, other populations contained large, SNP-free genomic regions that appear to have swept independently through the populations prior to the study without purging diversity elsewhere in the genome. Evidence for both genome-wide and gene-specific sweeps suggests that different models of bacterial speciation may apply to different populations coexisting in the same environment.
Clinical evidence suggest that men are more sensitive than women to the abuse-related effects of mu-opioid agonists. In contrast, preclinical studies suggest the opposite sex difference. The aim of ...the present study was to clarify this discrepancy using a fentanyl vs. diluted Ensure
choice procedure to assess sex differences in opioid reinforcement. Sex differences in intravenous (IV) fentanyl self-administration were examined under a fixed-ratio (FR5) schedule, a multi-day progressive-ratio (PR) schedule for behavioral economic analysis, and a concurrent (choice) schedule of fentanyl and diluted Ensure
reinforcement in Sprague-Dawley male and female rats. The fentanyl dose-effect function under the FR5 schedule was significantly shifted upward in females compared to males. Similarly, the reinforcing effectiveness of both fentanyl (3.2 and 10 µg/kg per injection, IV) and diluted Ensure
(18 and 56%) were greater in females than in males as assessed using behavioral economic analysis, irrespective of dose or concentration. However, under a fentanyl vs. foodchoice procedure, males chose 3.2 µg/kg per injection fentanyl injections over 18%, but not 56%, diluted Ensure
at a higher percentage compared to females. Overall, these results suggest that the expression of sex differences in opioid reinforcement depends upon the schedule of reinforcement and that preclinical opioid vs. food choice procedures provide a translationally relevant measure (i.e., behavioral allocation) consistent with the direction of sex differences reported in the clinical literature.
Existing guidelines and systematic reviews lack clear recommendations for prevention of low back pain (LBP).
To investigate the effectiveness of interventions for prevention of LBP.
MEDLINE, EMBASE, ...Physiotherapy Evidence Database Scale, and Cochrane Central Register of Controlled Trials from inception to November 22, 2014.
Randomized clinical trials of prevention strategies for nonspecific LBP.
Two independent reviewers extracted data and assessed the risk of bias. The Physiotherapy Evidence Database Scale was used to evaluate the risk-of-bias. The Grading of Recommendations Assessment, Development, and Evaluation system was used to describe the quality of evidence.
The primary outcome measure was an episode of LBP, and the secondary outcome measure was an episode of sick leave associated with LBP. We calculated relative risks (RRs) and 95% CIs using random-effects models.
The literature search identified 6133 potentially eligible studies; of these, 23 published reports (on 21 different randomized clinical trials including 30,850 unique participants) met the inclusion criteria. With results presented as RRs (95% CIs), there was moderate-quality evidence that exercise combined with education reduces the risk of an episode of LBP (0.55 0.41-0.74) and low-quality evidence of no effect on sick leave (0.74 0.44-1.26). Low- to very low-quality evidence suggested that exercise alone may reduce the risk of both an LBP episode (0.65 0.50-0.86) and use of sick leave (0.22 0.06-0.76). For education alone, there was moderate- to very low-quality evidence of no effect on LBP (1.03 0.83-1.27) or sick leave (0.87 0.47-1.60). There was low- to very low-quality evidence that back belts do not reduce the risk of LBP episodes (1.01 0.71-1.44) or sick leave (0.87 0.47-1.60). There was low-quality evidence of no protective effect of shoe insoles on LBP (1.01 0.74-1.40).
The current evidence suggests that exercise alone or in combination with education is effective for preventing LBP. Other interventions, including education alone, back belts, and shoe insoles, do not appear to prevent LBP. Whether education, training, or ergonomic adjustments prevent sick leave is uncertain because the quality of evidence is low.
Mu opioid receptor (MOR) agonists produce locomotor hyperactivity in mice as one sign of opioid-induced motor disruption. The goal of this study was to evaluate the degree of MOR efficacy required to ...produce this hyperactivity. Full dose-effect curves were determined for locomotor activation produced in male and female Institute of Cancer Research (ICR) mice by (1) eight different single-molecule opioids with high to low MOR efficacy and (2) a series of fixed-proportion fentanyl/naltrexone mixtures with high to low fentanyl proportions. Data from the mixtures were used to quantify the efficacy requirement for MOR agonist-induced hyperactivity relative to efficacy requirements determined previously for other MOR agonist effects. Specifically, efficacy requirement was quantified as the EP50 value, which is the "Effective Proportion" of fentanyl in a fentanyl/naltrexone mixture that produces a maximal effect equal to 50% of the maximal effect of fentanyl alone. Maximal hyperactivity produced by each drug and mixture in the present study correlated with previously published data for maximal stimulation of GTPɣS binding in MOR-expressing Chinese hamster ovary cells as an in vitro measure of relative efficacy. Additionally, the EP
value for hyperactivity induced by fentanyl/naltrexone mixtures indicated that opioid-induced hyperactivity in mice has a relatively high efficacy requirement in comparison with some other MOR agonist effects, and in particular is higher than the efficacy requirement for thermal antinociception in mice or fentanyl discrimination in rats. Taken together, these data show that MOR agonist-induced hyperactivity in mice is efficacy dependent and requires relatively high levels of MOR agonist efficacy for its full expression. SIGNIFICANCE STATEMENT: Mu opioid receptor (MOR) agonist-induced hyperlocomotion in mice is dependent on the MOR efficacy of the agonist and requires a relatively high degree of efficacy for its full expression.
Pooling data from thigh-worn accelerometers across multiple studies has great potential to advance evidence on the health benefits of physical activity. This requires harmonization of information on ...body postures, physical activity types, volumes and time patterns across different brands of devices. The aim of this study is to compare the physical behavior estimates provided by three different brands of thigh-worn accelerometers.
Twenty participants volunteered for a 7-day free-living measurement. Three accelerometers - ActiGraph GT3X+, Axivity AX3 and ActivPAL Micro4 - were randomly placed in a vertical line on the midsection of the right thigh. Raw data from each accelerometer was processed and classified into 8 physical activities and postures using the Acti4 software. Absolute differences between estimates and the respective coefficient of variation (CV) were calculated.
We observed very minor differences between physical behavior estimates from three different accelerometer brands. When averaged over 24 h (1,440 min), the absolute difference (CV) between accelerometers were: 1.2 mins (0.001) for lying/sitting, 3.4 mins (0.02) for standing, 3.5 mins (0.06) for moving, 1.9 mins (0.03) for walking, 0.1 mins (0.19) for running, 1.2 mins (0.19) for stair climbing, 1.9 mins (0.07) for cycling. Moreover, there was an average absolute difference of 282 steps (0.03) per 24 h.
Physical behaviors were classified with negligible difference between the accelerometer brands. These results support harmonization of data from different thigh-worn accelerometers across multiple cohorts when analyzed in an identical manner.
Objective
To develop standardized treatment regimens for chronic nonbacterial osteomyelitis (CNO), also known as chronic recurrent multifocal osteomyelitis (CRMO), to enable comparative effectiveness ...treatment studies.
Methods
Virtual and face‐to‐face discussions and meetings were held within the CNO/CRMO subgroup of the Childhood Arthritis and Rheumatology Research Alliance (CARRA). A literature search was conducted, and CARRA membership was surveyed to evaluate available treatment data and identify current treatment practices. Nominal group technique was used to achieve consensus on treatment plans for CNO refractory to nonsteroidal antiinflammatory drug (NSAID) monotherapy and/or with active spinal lesions.
Results
Three consensus treatment plans (CTPs) were developed for the first 12 months of therapy for CNO patients refractory to NSAID monotherapy and/or with active spinal lesions. The 3 CTPs are methotrexate or sulfasalazine, tumor necrosis factor inhibitors with optional methotrexate, and bisphosphonates. Short courses of glucocorticoids and continuation of NSAIDs are permitted for all regimens. Consensus was achieved on these CTPs among CARRA members. Consensus was also reached on subject eligibility criteria, initial evaluations that should be conducted prior to the initiation of CTPs, and data items to collect to assess treatment response.
Conclusion
Three consensus treatment plans were developed for pediatric patients with CNO refractory to NSAIDs and/or with active spinal lesions. Use of these CTPs will provide additional information on efficacy and will generate meaningful data for comparative effectiveness research in CNO.
Cocaine use disorder is a global public health problem for which there are no Food and Drug Administration-approved pharmacotherapies. Emerging preclinical evidence has implicated both serotonin ...(5-HT) 2C and 2A receptors as potential mechanisms for mediating serotonergic attenuation of cocaine abuse-related neurochemical and behavioral effects. Therefore, the present study aim was to determine whether repeated 7-day treatment with the 5-HT
agonist lorcaserin (0.1-1.0 mg/kg per day, intramuscular; 0.032-0.1 mg/kg/h, intravenous) or the 5-HT
inverse agonist/antagonist pimavanserin (0.32-10 mg/kg per day, intramuscular) attenuated cocaine reinforcement under a concurrent 'choice' schedule of cocaine and food availability in rhesus monkeys. During saline treatment, cocaine maintained a dose-dependent increase in cocaine vs food choice. Repeated pimavanserin (3.2 mg/kg per day) treatments significantly increased small unit cocaine dose choice. Larger lorcaserin (1.0 mg/kg per day and 0.1 mg/kg/h) and pimavanserin (10 mg/kg per day) doses primarily decreased rates of operant behavior. Coadministration of ineffective lorcaserin (0.1 mg/kg per day) and pimavanserin (0.32 mg/kg per day) doses also failed to significantly alter cocaine choice. These results suggest that neither 5-HT
receptor activation nor 5-HT
receptor blockade are sufficient to produce a therapeutic-like decrease in cocaine choice and a complementary increase in food choice. Overall, these results do not support the clinical utility of 5-HT
agonists and 5-HT
inverse agonists/antagonists alone or in combination as candidate anti-cocaine use disorder pharmacotherapies.
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