Microbial and viral communities transform the chemistry of Earth's ecosystems, yet the specific reactions catalyzed by these biological engines are hard to decode due to the absence of a scalable, ...metabolically resolved, annotation software. Here, we present DRAM (Distilled and Refined Annotation of Metabolism), a framework to translate the deluge of microbiome-based genomic information into a catalog of microbial traits. To demonstrate the applicability of DRAM across metabolically diverse genomes, we evaluated DRAM performance on a defined, in silico soil community and previously published human gut metagenomes. We show that DRAM accurately assigned microbial contributions to geochemical cycles and automated the partitioning of gut microbial carbohydrate metabolism at substrate levels. DRAM-v, the viral mode of DRAM, established rules to identify virally-encoded auxiliary metabolic genes (AMGs), resulting in the metabolic categorization of thousands of putative AMGs from soils and guts. Together DRAM and DRAM-v provide critical metabolic profiling capabilities that decipher mechanisms underpinning microbiome function.
The global bacteriophage population is large, dynamic, old, and highly diverse genetically. Many phages are tailed and contain double-stranded DNA, but these remain poorly characterized genomically. ...A collection of over 1,000 phages infecting
reveals the diversity of phages of a common bacterial host, but their relationships to phages of phylogenetically proximal hosts are not known. Comparative sequence analysis of 79 phages isolated on
shows these also to be diverse and that the phages can be grouped into 14 clusters of related genomes, with an additional 14 phages that are "singletons" with no closely related genomes. One group of six phages is closely related to Cluster A mycobacteriophages, but the other
phages are distant relatives and share only 10% of their genes with the mycobacteriophages. The
phage genomes vary in genome length (17.1 to 103.4 kb), percentage of GC content (47 to 68.8%), and genome architecture and contain a variety of features not seen in other phage genomes. Like the mycobacteriophages, the highly mosaic
phages demonstrate a spectrum of genetic relationships. We show this is a general property of bacteriophages and suggest that any barriers to genetic exchange are soft and readily violable.
Despite the numerical dominance of bacteriophages in the biosphere, there is a dearth of complete genomic sequences. Current genomic information reveals that phages are highly diverse genomically and have mosaic architectures formed by extensive horizontal genetic exchange. Comparative analysis of 79 phages of
shows them to not only be highly diverse, but to present a spectrum of relatedness. Most are distantly related to phages of the phylogenetically proximal host
, although one group of
phages is more closely related to mycobacteriophages than to the other
phages. Phage genome sequence space remains largely unexplored, but further isolation and genomic comparison of phages targeted at related groups of hosts promise to reveal pathways of bacteriophage evolution.
Study objective This study seeks to determine whether health information exchange reduces repeated diagnostic imaging and related costs in emergency back pain evaluation. Methods This was a ...longitudinal data analysis of health information exchange patient-visit data. All repeated emergency department (ED) patient visits for back pain with previous ED diagnostic imaging to a Memphis metropolitan area ED between August 1, 2007, and July 31, 2009, were included. Use of a regional health information exchange by ED personnel to access the patient's record during the emergency visit was the primary independent variable. Main outcomes included repeated lumbar or thoracic diagnostic imaging (radiograph, computed tomography CT, or magnetic resonance imaging MRI) and total patient-visit estimated cost. Results One hundred seventy-nine (22.4%) of the 800 qualifying repeated back pain visits resulted in repeated diagnostic imaging (radiograph 84.9%, CT 6.1%, and MRI 9.5%). Health information exchange use in the study population was low, at 12.5%, and health care providers as opposed to administrative/nursing staff accounted for 80% of the total health information exchange use. Health information exchange use by any ED personnel was associated with reduced repeated diagnostic imaging (odds ratio 0.36; 95% confidence interval 0.18 to 0.71), as was physician or nurse practitioner health information exchange use (odds ratio 0.47; 95% confidence interval 0.23 to 0.96). No cost savings were associated with health information exchange use because of increased CT imaging when health care providers used health information exchange. Conclusion Health information exchange use is associated with 64% lower odds of repeated diagnostic imaging in the emergency evaluation of back pain. Health information exchange effect on estimated costs was negligible. More studies are needed to evaluate specific strategies to increase health information exchange use and further decrease potentially unnecessary diagnostic imaging and associated costs of care.
Rationale
Anecdotally, both acute and chronic cannabis use have been associated with apathy, amotivation, and other reward processing deficits. To date, empirical support for these effects is ...limited, and no previous studies have assessed both acute effects of Δ-9-tetrahydrocannabinol (THC) and cannabidiol (CBD), as well as associations with cannabis dependence.
Objectives
The objectives of this study were (1) to examine acute effects of cannabis with CBD (Cann + CBD) and without CBD (Cann-CBD) on effort-related decision-making and (2) to examine associations between cannabis dependence, effort-related decision-making and reward learning.
Methods
In study 1, 17 participants each received three acute vaporized treatments, namely Cann-CBD (8 mg THC), Cann + CBD (8 mg THC + 10 mg CBD) and matched placebo, followed by a 50 % dose top-up 1.5 h later, and completed the Effort Expenditure for Rewards Task (EEfRT). In study 2, 20 cannabis-dependent participants were compared with 20 non-dependent, drug-using control participants on the EEfRT and the Probabilistic Reward Task (PRT) in a non-intoxicated state.
Results
Cann-CBD reduced the likelihood of high-effort choices relative to placebo (
p
= 0.042) and increased sensitivity to expected value compared to both placebo (
p
= 0.014) and Cann + CBD (
p
= 0.006). The cannabis-dependent and control groups did not differ on the EEfRT. However, the cannabis-dependent group exhibited a weaker response bias than the control group on the PRT (
p
= 0.007).
Conclusions
Cannabis acutely induced a transient amotivational state and CBD influenced the effects of THC on expected value. In contrast, cannabis dependence was associated with preserved motivation alongside impaired reward learning, although confounding factors, including depression, cannot be disregarded. This is the first well powered, fully controlled study to objectively demonstrate the acute amotivational effects of THC.
ImportanceSurgical treatment can bring seizure remission in people with focal epilepsy but requires careful selection of candidates.ObjectivesTo determine which preoperative factors are associated ...with postoperative seizure outcome.DesignWe audited seizure outcome of 693 adults who had resective epilepsy surgery between 1990 and 2010 and used survival analysis to detect preoperatively identifiable risk factors of poor seizure outcome.ResultsSeven factors were significantly associated with increased probability of recurrence of seizures with impaired awareness postsurgery: MRI findings (eg, HR adjusted for other variables in the model 2.5; 95% CI 1.6 to 3.8 for normal MRI compared with hippocampal sclerosis), a history of secondarily generalised convulsive seizures (2.3; 95% CI 1.7 to 3.0 for these seizures in the previous year vs never), psychiatric history (1.3; 95% CI 1.1 to 1.7), learning disability (1.8; 95% CI 1.2 to 2.6) and extratemporal (vs temporal) surgery (1.4; 95% CI 1.02, 2.04). People with an older onset of epilepsy had a higher probability of seizure recurrence (1.01; 95% CI 1.00, 1.02) as did those who had used more antiepileptic drugs (1.05; 95% CI 1.01 to 1.09). Combinations of variables associated with seizure recurrence gave overall low probabilities of 5-year seizure freedom (eg, a normal MRI and convulsive seizures in the previous year has a probability of seizure freedom at 5 years of approximately 0.19).Conclusions and relevanceReadily identified clinical features and investigations are associated with reduced probability of good outcome and need consideration when planning presurgical evaluation.
Abstract
Background
Despite the current shift towards permissive cannabis policies, few studies have investigated the pleasurable effects users seek. Here, we investigate the effects of cannabis on ...listening to music, a rewarding activity that frequently occurs in the context of recreational cannabis use. We additionally tested how these effects are influenced by cannabidiol, which may offset cannabis-related harms.
Methods
Across 3 sessions, 16 cannabis users inhaled cannabis with cannabidiol, cannabis without cannabidiol, and placebo. We compared their response to music relative to control excerpts of scrambled sound during functional Magnetic Resonance Imaging within regions identified in a meta-analysis of music-evoked reward and emotion. All results were False Discovery Rate corrected (P<.05).
Results
Compared with placebo, cannabis without cannabidiol dampened response to music in bilateral auditory cortex (right: P=.005, left: P=.008), right hippocampus/parahippocampal gyrus (P=.025), right amygdala (P=.025), and right ventral striatum (P=.033). Across all sessions, the effects of music in this ventral striatal region correlated with pleasure ratings (P=.002) and increased functional connectivity with auditory cortex (right: P< .001, left: P< .001), supporting its involvement in music reward. Functional connectivity between right ventral striatum and auditory cortex was increased by cannabidiol (right: P=.003, left: P=.030), and cannabis with cannabidiol did not differ from placebo on any functional Magnetic Resonance Imaging measures. Both types of cannabis increased ratings of wanting to listen to music (P<.002) and enhanced sound perception (P<.001).
Conclusions
Cannabis dampens the effects of music in brain regions sensitive to reward and emotion. These effects were offset by a key cannabis constituent, cannabidol.
•Frontal dysfunction predicts depression and anxiety symptoms following TLE surgery.•Mood disturbance at time of surgery increases risk of postsurgical depression.•Anxiety symptoms improve within the ...year following TLE surgery.
Predictors of psychiatric outcome following TLE surgery have proved elusive and represent a current challenge in the practice of TLE surgery. This prospective study investigated whether frontal lobe dysfunction is predictive of poorer psychiatric outcomes.
Forty-nine unilateral TLE surgical patients were assessed using the Beck Depression Inventory–Fast Screen (BDI-FS) and Beck Anxiety Inventory (BAI) preoperatively and 6 and 12 months postoperatively. Measures of intellectual function, semantic knowledge, memory and executive function were completed preoperatively, at 6 and 12 months following surgery.
Preoperatively, 33 (67%) patients had minimal depressive symptoms, 8 (16%) were mildly depressed, 2 (4%) were moderately depressed, and 6 (12%) reported severe depressive morbidity. Twenty-three (47%) patients reported minimal anxiety, 18 (37%) were mildly anxious, 6 (12%) were moderately anxious and 2 (4%) patients reported severe anxiety symptoms. A mixed-model repeated-measures analysis was performed on the BDI-FS and BAI scores, adjusting for pertinent covariates identified in univariable analyses. At a year following TLE surgery, anxiety symptoms significantly improved but depressive morbidity did not. Indicators of frontal lobe dysfunction moderated the magnitude and direction of mood change. Specifically, pre-surgical cognitive measures of frontal lobe dysfunction predicted increased depression and anxiety symptoms following surgery. There was no relationship between preoperative BDI-FS or BAI scores and seizure outcome at 12 months or change in affective morbidity and seizure outcome.
This is the first longitudinal study to provide evidence that specific pre-surgical cognitive and behavioural indices of frontal dysfunction are predictive of poorer psychiatric outcome following TLE surgery. In addition, our findings highlight the potential utility of a dysexecutive behavioural rating scale (DEX) as an assessment tool in epilepsy. Examination of executive functioning in pre-surgical evaluations may lead to an increase in the power of prognostic models used to predict the psychiatric outcome of TLE surgery.
Abstract Objective Older adults in the U.S. have high rates of obesity. Despite the demonstrated efficacy of lifestyle interventions among older adults, lifestyle interventions are not widely ...implemented in community settings. Program delivery by lay health educators (LHEs) might support greater dissemination because of lower delivery cost and greater accessibility. We examined the costs of a LHE-delivered translation of the Diabetes Prevention Program (DPP) evidence-based lifestyle intervention for older adults in Arkansas senior centers. Methods This examination of costs used data from a cluster randomized control trial (conducted 2008–2010) in which 7 senior centers (116 participants) were randomized to implement a LHE-delivered 12-session translation of the DPP lifestyle intervention. We compiled direct lifestyle intervention implementation costs, including training, recruitment, materials, and ongoing intervention implementation support. Weight loss data (at 4-month follow-up) were collected from participants. Results Participant weight loss averaged 3.7 kg at 4-months. The total estimated cost to implement the lifestyle intervention is $2731 per senior center, or $165 per participant. The implementation cost per kilogram lost is $45. Conclusions A LHE-delivered DPP translation in senior centers is effective in achieving weight loss at low cost and offers promise for the dissemination of this evidence-based intervention.
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