Trial registration ClinicalTrials.gov. NCT03691545. Registered on October 1, 2018.Transition to new analytical systems and methods requires end-user verification to ensure acceptability for routine use. Our aim was to verify precision of MAGLUMI 800 immunoassay analyzer for 17-hydroxyprogesterone (17-OHP), 25-hydroxy vitamin D (25(OH)D), aldosterone, androstenedione, growth hormone (GH), insulin-like growth factor 1 (IGF-1), insulin-like growth factor-binding protein 3 (IGFBP-3) and renin, as well as to assess their comparability with the routinely used assays. Precision was evaluated at two levels following the CLSI EP15-A2 protocol. Method comparison included parallel analysis of 40 routine samples for each assay on MAGLUMI 800 and the routinely used automated or manual immunoassays. Within-run coefficients of variation (CV) ranged from 0.8% (androstenedione) to 14.5% (aldosterone), between-run CVs from 1.0% (IGFBP-3) to 12.8% (renin), while within-laboratory (total) precision CVs were from 2.1% (IGFBP-3) to 14.9% (renin). All assays with the exception of IGF-1 and 25(OH)D at the low concentration control level, satisfied biological variation criteria for imprecision. Passing-Bablok regression showed proportional difference for 17-OHP and aldosterone, constant for androstenedione, while both constant and proportional difference was revealed for 25(OH)D, GH and IGF-1. Statistically significant relative biases higher than the desirable biological variation acceptance criteria were observed for 17-OHP, 25(OH)D, aldosterone, androstenedione and IGF-1. The evaluated assays need further assessment as well as verification of reference intervals in order to be suitable for introduction into routine practice in our laboratory. Our study clearly demonstrates that we are still far from achieving immunoassay standardization and comparability of results.
Chronic pain affects one-fifth of US adults. Reductions in opioid prescribing have been associated with increased non-prescription opioid use and, chronologically, increased stimulant (methamphetamine and cocaine) use. While non-prescription opioid use is commonly attributed to pain self-management, the role of stimulants in managing pain is unclear.

We analyzed baseline data from a longitudinal study of patients with chronic non-cancer pain in an urban safety-net healthcare system who had been prescribed an opioid for ≥3 of the last 12 months, and had a history of non-prescription opioid, cocaine, or amphetamine use (
 = 300). We estimated the prevalence and identified correlates of stimulant use to treat pain among a subgroup of patients who reported past-year stimulant use (
 = 105). Data sources included computer-assisted questionnaire (demographics, substance use, pain), clinical exam and procedures (pain, pain tolerance), and chart abstraction (opioid prescriptions). We conducted bivariate analyseulant use in an era of reduced access to prescribed opioids.
Stimulants may be used for pain self-management, particularly for neuropathic pain and among women. Our findings suggest an underexplored motivation for stimulant use in an era of reduced access to prescribed opioids.5-Fluorouracil (5-FU) is a well-recognized anticancer drug used in the treatment of tumors of head, neck and breast. Drug pharmacokinetics is affected upon binding with protein, thus, making drug-protein interactions imperative to study. Present work investigates the interaction between 5-FU and human major antiproteinase-alpha-2-macroglobulin (α2M) by multi-spectroscopic, calorimetric and molecular docking techniques. UV/Visible absorption, intrinsic fluorescence and circular dichroism (CD) spectroscopic methods have been employed to unveil the mode and mechanism of 5-FU-α2M interaction. Synchronous fluorescence showed alteration in the microenvironment of tryptophan and tyrosine residues of protein. Far UV-CD spectra suggest slight alterations in the secondary structure of α2M by 5-FU. Thermodynamic parameters determined by fluorescence quenching experiments and isothermal titration calorimetry (ITC) suggested the involvement of hydrogen bonds and hydrophobic interactions. Moreover, ITC corroborate the spontaneous and exothermic nature of the interaction process. Molecular docking illustrates that 5-FU binds with moderate affinity and Asp953, Tyr1264, Lys1236, Thr1232, Tyr1323 and Leu951 were the main residues involved. Molecular dynamics simulation studies suggested that 5-FU was stabilizing the α2M structure and forming a stable complex. It was concluded that 5-FU lower the antiproteolytic activity of α2M significantly and causes disruption in the native structure and conformation of α2M.Communicated by Ramaswamy H. Sarma.
Mindfulness-based interventions (MBIs) are effective in adult substance-use treatment and may be helpful for adolescents and young adults (AYAs). One target of MBIs is to improve trait mindfulness, which has been associated with better lifestyle and health outcomes. To inform MBIs for reducing cannabis use in AYAs, we sought to identify how trait mindfulness was associated with cannabis-related problems and quit attempts, as well as with motivation to change use in youth who report frequent use.
Participants aged 15-24 years using cannabis ≥ 3x/week were recruited from AYA clinics in a northeastern US city to participate in a cannabis-use intervention pilot, randomized trial. At baseline, we assessed cannabis-use history, problems associated with use, attempts to quit, and trait mindfulness. All participants were offered two sessions of motivational enhancement therapy, during which they rated motivation to quit cannabis. Regression analyses were conducted to assess associations between trait mindfulnessattempts to quit, and motivation to change. Results Seventy participants, mean age 20.7 ± 1.9 years, enrolled. Sixty percent identified as female, 47% as Black non-Hispanic, and 31% as Hispanic. Participants started using cannabis at mean age 15.0 ± 2.8 years and were using ≥ 3x/week by 17.0 ± 2.3 years. Higher mindfulness scores were associated with fewer cannabis-related problems (p = 0.004) and fewer quit attempts (p = 0.035). The number of cannabis-related problems did not significantly mediate the relationship between mindfulness and quit attempts. Trait mindfulness did not predict motivation to change cannabis use. Conclusions Among AYAs using cannabis frequently, higher trait mindfulness was associated with both fewer cannabis use--related problems and fewer quit attempts. https://www.selleckchem.com/products/BKM-120.html Future research should assess whether trait mindfulness is an appropriate target for decreasing cannabis use and the utility of MBIs for reducing cannabis-use behaviors.
Trial registration ClinicalTrials.gov. NCT03691545. Registered on October 1, 2018.Transition to new analytical systems and methods requires end-user verification to ensure acceptability for routine use. Our aim was to verify precision of MAGLUMI 800 immunoassay analyzer for 17-hydroxyprogesterone (17-OHP), 25-hydroxy vitamin D (25(OH)D), aldosterone, androstenedione, growth hormone (GH), insulin-like growth factor 1 (IGF-1), insulin-like growth factor-binding protein 3 (IGFBP-3) and renin, as well as to assess their comparability with the routinely used assays. Precision was evaluated at two levels following the CLSI EP15-A2 protocol. Method comparison included parallel analysis of 40 routine samples for each assay on MAGLUMI 800 and the routinely used automated or manual immunoassays. Within-run coefficients of variation (CV) ranged from 0.8% (androstenedione) to 14.5% (aldosterone), between-run CVs from 1.0% (IGFBP-3) to 12.8% (renin), while within-laboratory (total) precision CVs were from 2.1% (IGFBP-3) to 14.9% (renin). All assays with the exception of IGF-1 and 25(OH)D at the low concentration control level, satisfied biological variation criteria for imprecision. Passing-Bablok regression showed proportional difference for 17-OHP and aldosterone, constant for androstenedione, while both constant and proportional difference was revealed for 25(OH)D, GH and IGF-1. Statistically significant relative biases higher than the desirable biological variation acceptance criteria were observed for 17-OHP, 25(OH)D, aldosterone, androstenedione and IGF-1. The evaluated assays need further assessment as well as verification of reference intervals in order to be suitable for introduction into routine practice in our laboratory. Our study clearly demonstrates that we are still far from achieving immunoassay standardization and comparability of results. Chronic pain affects one-fifth of US adults. Reductions in opioid prescribing have been associated with increased non-prescription opioid use and, chronologically, increased stimulant (methamphetamine and cocaine) use. While non-prescription opioid use is commonly attributed to pain self-management, the role of stimulants in managing pain is unclear. We analyzed baseline data from a longitudinal study of patients with chronic non-cancer pain in an urban safety-net healthcare system who had been prescribed an opioid for ≥3 of the last 12 months, and had a history of non-prescription opioid, cocaine, or amphetamine use (  = 300). We estimated the prevalence and identified correlates of stimulant use to treat pain among a subgroup of patients who reported past-year stimulant use (  = 105). Data sources included computer-assisted questionnaire (demographics, substance use, pain), clinical exam and procedures (pain, pain tolerance), and chart abstraction (opioid prescriptions). We conducted bivariate analyseulant use in an era of reduced access to prescribed opioids. Stimulants may be used for pain self-management, particularly for neuropathic pain and among women. Our findings suggest an underexplored motivation for stimulant use in an era of reduced access to prescribed opioids.5-Fluorouracil (5-FU) is a well-recognized anticancer drug used in the treatment of tumors of head, neck and breast. Drug pharmacokinetics is affected upon binding with protein, thus, making drug-protein interactions imperative to study. Present work investigates the interaction between 5-FU and human major antiproteinase-alpha-2-macroglobulin (α2M) by multi-spectroscopic, calorimetric and molecular docking techniques. UV/Visible absorption, intrinsic fluorescence and circular dichroism (CD) spectroscopic methods have been employed to unveil the mode and mechanism of 5-FU-α2M interaction. Synchronous fluorescence showed alteration in the microenvironment of tryptophan and tyrosine residues of protein. Far UV-CD spectra suggest slight alterations in the secondary structure of α2M by 5-FU. Thermodynamic parameters determined by fluorescence quenching experiments and isothermal titration calorimetry (ITC) suggested the involvement of hydrogen bonds and hydrophobic interactions. Moreover, ITC corroborate the spontaneous and exothermic nature of the interaction process. Molecular docking illustrates that 5-FU binds with moderate affinity and Asp953, Tyr1264, Lys1236, Thr1232, Tyr1323 and Leu951 were the main residues involved. Molecular dynamics simulation studies suggested that 5-FU was stabilizing the α2M structure and forming a stable complex. It was concluded that 5-FU lower the antiproteolytic activity of α2M significantly and causes disruption in the native structure and conformation of α2M.Communicated by Ramaswamy H. Sarma. Mindfulness-based interventions (MBIs) are effective in adult substance-use treatment and may be helpful for adolescents and young adults (AYAs). One target of MBIs is to improve trait mindfulness, which has been associated with better lifestyle and health outcomes. To inform MBIs for reducing cannabis use in AYAs, we sought to identify how trait mindfulness was associated with cannabis-related problems and quit attempts, as well as with motivation to change use in youth who report frequent use. Participants aged 15-24 years using cannabis ≥ 3x/week were recruited from AYA clinics in a northeastern US city to participate in a cannabis-use intervention pilot, randomized trial. At baseline, we assessed cannabis-use history, problems associated with use, attempts to quit, and trait mindfulness. All participants were offered two sessions of motivational enhancement therapy, during which they rated motivation to quit cannabis. Regression analyses were conducted to assess associations between trait mindfulnessattempts to quit, and motivation to change. Results Seventy participants, mean age 20.7 ± 1.9 years, enrolled. Sixty percent identified as female, 47% as Black non-Hispanic, and 31% as Hispanic. Participants started using cannabis at mean age 15.0 ± 2.8 years and were using ≥ 3x/week by 17.0 ± 2.3 years. Higher mindfulness scores were associated with fewer cannabis-related problems (p = 0.004) and fewer quit attempts (p = 0.035). The number of cannabis-related problems did not significantly mediate the relationship between mindfulness and quit attempts. Trait mindfulness did not predict motivation to change cannabis use. Conclusions Among AYAs using cannabis frequently, higher trait mindfulness was associated with both fewer cannabis use--related problems and fewer quit attempts. https://www.selleckchem.com/products/BKM-120.html Future research should assess whether trait mindfulness is an appropriate target for decreasing cannabis use and the utility of MBIs for reducing cannabis-use behaviors.
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