This project aimed to characterize the relationship between physical pain experienced at time of entry to residential treatment for substance use disorders (SUDs) and the frequency of treatment ...dropout. We hypothesized that both endorsement of recent pain and higher magnitude of endorsed pain intensity would be associated with higher dropout rates. We further hypothesized that these effects would be exacerbated among patients with opioid use disorder (OUD).
Participants included 1,095 individuals in residential treatment for SUD. Data were collected within 24 hours of treatment entry. Analyses were conducted using logistic regression with dropout as the dependent variable. Dropout was operationally defined as leaving treatment against medical advice or being discharged from treatment because of use of substances. Pain (including endorsement and intensity) was the primary independent variable in all analyses. Analyses included demographic and affective covariates and included both main effects of OUD and interaction terms between OUD and pain.
Pain endorsement was associated with greater frequency of dropout (odds ratio OR = 1.49,
= .04). Higher levels of pain intensity predicted increased rates of dropout (OR = 1.13,
< .01). In contrast with our hypothesis, no interactions between OUD and pain were observed.
These results underscore the import of integrating pain monitoring and pain interventions as core components of treatment for SUD. Our findings are highly consistent with a growing literature recognizing the impact of pain across a constellation of important treatment outcomes and provide novel data strongly suggesting that pain predicts early cessation of treatment.
Abstract
This study examined the urine and hair opiate profiles associated with the daily consumption of presumptive codeine-predominant poppy seed food products. Ten participants consumed one of ...five food products at breakfast for 10 consecutive days. Baseline urine and hair samples were collected on Day 1. The urine samples were collected 4, 8 and 12 h following poppy seed consumption on Days 1 and 10, and the first morning void urine samples were collected on Days 2–10. A second hair specimen was collected on Day 20 ± 2. Urine drug test results: Three of the food products were associated with opiate-negative urine drug test results at all time points at a 300 ng/mL cut-off. Two of the food products were associated with opiate-positive drug test results at all non-baseline time points at a 300 ng/mL cut-off. Of these, all samples (n = 60) were codeine-positive, and 27 (45%) were morphine-positive. Codeine concentrations exceeded morphine concentrations in every sample and always by multiples. Thirty-nine of the 60 samples (65%) were codeine-positive at a 2,000 ng/mL cut-off, while none of these samples were morphine-positive at this cut-off. None of the 60 samples reached an opiate threshold of 15,000 ng/mL, although one participant produced a maximum codeine concentration of 13,161 ng/mL (13,854 ng/mg creatinine). There was no clear trend toward increasing urinary opiate concentrations over the course of the study. Hair drug test results: The hair samples of two participants produced quantifiable codeine (41 pg/mg and 51 pg/mg), but no sample reached a common reporting threshold of 200 pg/mg for codeine or morphine.
The purpose was to investigate full-body kinematics and vertical ground reaction forces in the lower extremities of the delivery and to determine delivery changes over time after many deliveries in ...ten-pin bowling. Six male elite ten-pin bowlers completed six bouts of twelve bowling deliveries, all strike attempts, while measuring full-body kinematics and vertical ground reaction forces. Full-body joint angles, peak vertical ground reaction forces in the feet, vertical breaking impulse, centre of mass velocity, bowling score, and ball release velocity (BRvel) were measured. Results revealed that the BRvel was significantly decreased over bouts (p < 0.001). Additionally, increased flexion of the dominant wrist (p < 0.001) and elbow (p = 0.004) prior to ball release (BR) and increased pronation of the dominant wrist during BR (p = 0.034) were observed at later bouts. It was concluded that these kinematic changes in the dominant wrist and elbow prior to and during BR were performed to compensate for the change in traction between ball and lane during a bowling match. This, in turn, caused a decrease in BRvel. A conservation of energy perspective was discussed to highlight training applications and possibilities to enhance elite athletes’ bowling performance.
Preprocessing of functional magnetic resonance imaging (fMRI) involves numerous steps to clean and standardize the data before statistical analysis. Generally, researchers create ad hoc preprocessing ...workflows for each dataset, building upon a large inventory of available tools. The complexity of these workflows has snowballed with rapid advances in acquisition and processing. We introduce fMRIPrep, an analysis-agnostic tool that addresses the challenge of robust and reproducible preprocessing for fMRI data. fMRIPrep automatically adapts a best-in-breed workflow to the idiosyncrasies of virtually any dataset, ensuring high-quality preprocessing without manual intervention. By introducing visual assessment checkpoints into an iterative integration framework for software testing, we show that fMRIPrep robustly produces high-quality results on a diverse fMRI data collection. Additionally, fMRIPrep introduces less uncontrolled spatial smoothness than observed with commonly used preprocessing tools. fMRIPrep equips neuroscientists with an easy-to-use and transparent preprocessing workflow, which can help ensure the validity of inference and the interpretability of results.
Lignin, the second most abundant biopolymer, is a promising renewable energy source and chemical feedstock. A key element of lignin biosynthesis is unknown: how do lignin precursors (monolignols) get ...from inside the cell out to the cell wall where they are polymerized? Modeling indicates that monolignols can passively diffuse through lipid bilayers, but this has not been tested experimentally. We demonstrate significant monolignol diffusion occurs when laccases, which consume monolignols, are present on one side of the membrane. We hypothesize that lignin polymerization could deplete monomers in the wall, creating a concentration gradient driving monolignol diffusion. We developed a two-photon microscopy approach to visualize lignifying Arabidopsis thaliana root cells. Laccase mutants with reduced ability to form lignin polymer in the wall accumulated monolignols inside cells. In contrast, active transport inhibitors did not decrease lignin in the wall and scant intracellular phenolics were observed. Synthetic liposomes were engineered to encapsulate laccases, and monolignols crossed these pure lipid bilayers to form polymer within. A sink-driven diffusion mechanism explains why it has been difficult to identify genes encoding monolignol transporters and why the export of varied phenylpropanoids occurs without specificity. It also highlights an important role for cell wall oxidative enzymes in monolignol export.
Functional magnetic resonance imaging (fMRI) is a standard tool to investigate the neural correlates of cognition. fMRI noninvasively measures brain activity, allowing identification of patterns ...evoked by tasks performed during scanning. Despite the long history of this technique, the idiosyncrasies of each dataset have led to the use of ad-hoc preprocessing protocols customized for nearly every different study. This approach is time consuming, error prone and unsuitable for combining datasets from many sources. Here we showcase fMRIPrep (http://fmriprep.org), a robust tool to prepare human fMRI data for statistical analysis. This software instrument addresses the reproducibility concerns of the established protocols for fMRI preprocessing. By leveraging the Brain Imaging Data Structure to standardize both the input datasets (MRI data as stored by the scanner) and the outputs (data ready for modeling and analysis), fMRIPrep is capable of preprocessing a diversity of datasets without manual intervention. In support of the growing popularity of fMRIPrep, this protocol describes how to integrate the tool in a task-based fMRI investigation workflow.
Kristiansen, M, Sydow Krogh Pedersen, A-M, Sandvej, G, Jørgensen, P, Jakobsen, JV, de Zee, M, Hansen, EA, and Klitgaard, KK. Enhanced maximal upper-body strength increases performance in sprint ...kayaking. J Strength Cond Res 37(4): e305-e312, 2023-The association between upper-body strength and performance in 200-m flat-water sprint kayak is not fully elucidated. Therefore, the aim of study 1 was to investigate the relationship between upper-body strength and kayaking performance. In study 2, the aim was to perform a randomized training intervention to investigate whether a causal relationship was present between an increase in strength and an actual change in 200-m kayaking performance. In study 1, 37 (22 men and 15 women) elite kayak paddlers performed tests of maximal power output, isometric force, 1 repetition maximum (1RM), and 40 seconds of maximal repetition number in bench press and bench pull and a 30-second all-out on-water sprint kayak test. In study 2, 26 (16 men and 10 women) national elite junior A, U23, and senior kayak paddlers were allocated into 2 groups: a training group (TRAIN) and a maintenance group (MAIN). Each group completed a 6-week strength training intervention with the purpose of either increasing 1RM in bench press (TRAIN) or maintaining strength (MAIN). Pre- and posttests were performed in 200-m kayak ergometer sprint, 1RM bench press, and 1RM bench pull. In study 1, 1RM in bench press was the best predictor of 30-second on-water kayaking performance with a regression coefficient of 0.474. In study 2, TRAIN significantly increased 1RM strength in bench press (pre: 87.3 ± 21.2 kg, post: 93.9 ± 21.3 kg, p = 0.001) and bench pull (pre: 84.2 ± 15.3 kg, post: 86.0 ± 15.1 kg, p = 0.025). In the 200-m kayak ergometer sprint test, TRAIN significantly decreased the time to complete the test (pre: 44.8 ± 4.3 seconds, post: 44.3 ± 4.3 seconds, p = 0.042). In bench press, 1RM was the best predictor of 200-m kayaking, and an increase in bench press 1RM resulted in increased kayaking performance.
Fibrinogen, coagulation factor VII (FVII), and factor VIII (FVIII) and its carrier von Willebrand factor (vWF) play key roles in hemostasis. Previously identified common variants explain only a small ...fraction of the trait heritabilities, and additional variations may be explained by associations with rarer variants with larger effects. The aim of this study was to identify low-frequency (minor allele frequency MAF ≥0.01 and <0.05) and rare (MAF <0.01) variants that influence plasma concentrations of these 4 hemostatic factors by meta-analyzing exome chip data from up to 76 000 participants of 4 ancestries. We identified 12 novel associations of low-frequency (n = 2) and rare (n = 10) variants across the fibrinogen, FVII, FVIII, and vWF traits that were independent of previously identified associations. Novel loci were found within previously reported genes and had effect sizes much larger than and independent of previously identified common variants. In addition, associations at KCNT1, HID1, and KATNB1 identified new candidate genes related to hemostasis for follow-up replication and functional genomic analysis. Newly identified low-frequency and rare-variant associations accounted for modest amounts of trait variance and therefore are unlikely to increase predicted trait heritability but provide new information for understanding individual variation in hemostasis pathways.
•Twelve independent, novel, low-frequency (n = 2) and rare (n = 10) genetic variants were associated with fibrinogen, FVII, FVIII, or vWF.•Nine were within previously associated genes, and 3 novel candidate genes (KCNT1, HID1, and KATNB1) were confined to cohorts of African ancestry.
In their classic experiments, Olds and Milner showed that rats learn to lever press to receive an electric stimulus in specific brain regions. This led to the identification of mammalian reward ...centers. Our interest in defining the neuronal substrates of reward perception in the fruit fly Drosophila melanogaster prompted us to develop a simpler experimental approach wherein flies could implement behavior that induces self-stimulation of specific neurons in their brains. The high-throughput assay employs optogenetic activation of neurons when the fly occupies a specific area of a behavioral chamber, and the flies’ preferential occupation of this area reflects their choosing to experience optogenetic stimulation. Flies in which neuropeptide F (NPF) neurons are activated display preference for the illuminated side of the chamber. We show that optogenetic activation of NPF neuron is rewarding in olfactory conditioning experiments and that the preference for NPF neuron activation is dependent on NPF signaling. Finally, we identify a small subset of NPF-expressing neurons located in the dorsomedial posterior brain that are sufficient to elicit preference in our assay. This assay provides the means for carrying out unbiased screens to map reward neurons in flies.
Genome-wide association studies have identified multiple genomic loci associated with coronary artery disease, but most are common variants in non-coding regions that provide limited information on ...causal genes and etiology of the disease. To overcome the limited scope that common variants provide, we focused our investigation on low-frequency and rare sequence variations primarily residing in coding regions of the genome.
Using samples of individuals of European ancestry from ten cohorts within the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium, both cross-sectional and prospective analyses were conducted to examine associations between genetic variants and myocardial infarction (MI), coronary heart disease (CHD), and all-cause mortality following these events. For prevalent events, a total of 27,349 participants of European ancestry, including 1831 prevalent MI cases and 2518 prevalent CHD cases were used. For incident cases, a total of 55,736 participants of European ancestry were included (3,031 incident MI cases and 5,425 incident CHD cases). There were 1,860 all-cause deaths among the 3,751 MI and CHD cases from six cohorts that contributed to the analysis of all-cause mortality. Single variant and gene-based analyses were performed separately in each cohort and then meta-analyzed for each outcome. A low-frequency intronic variant (rs988583) in PLCL1 was significantly associated with prevalent MI (OR = 1.80, 95% confidence interval: 1.43, 2.27; P = 7.12 × 10-7). We conducted gene-based burden tests for genes with a cumulative minor allele count (cMAC) ≥ 5 and variants with minor allele frequency (MAF) < 5%. TMPRSS5 and LDLRAD1 were significantly associated with prevalent MI and CHD, respectively, and RC3H2 and ANGPTL4 were significantly associated with incident MI and CHD, respectively. No loci were significantly associated with all-cause mortality following a MI or CHD event.
This study identified one known locus (ANGPTL4) and four new loci (PLCL1, RC3H2, TMPRSS5, and LDLRAD1) associated with cardiovascular disease risk that warrant further investigation.
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