150 research outputs found

    Exploring metabolic consequences of CPS1 and CAD dysregulation in hepatocellular carcinoma by network reconstruction

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    Purpose: Hepatocellular carcinoma (HCC) is the fourth commonest cause of cancer-related mortality; it is associated with various genetic alterations, some involved in metabolic reprogramming. This study aimed to explore the potential metabolic impact of Carbamoyl Phosphate Synthase I (CPS1) and carbamoyl phosphate synthetase/aspartate transcarbamoylase/dihydroorotase (CAD) dysregulation through the reconstruction of a network that integrates information from the Kyoto Encyclopedia of Genes and Genomes (KEGG) database, Human Metabolome Database (HMDB) and Human Protein Atlas (HPA). Methods and Results: Existing literature was used to determine the roles of CPS1 and CAD in HCC. CPS1 downregulation is thought to play a role in hepatocarcinogenesis through an increased glutamine availability for de novo pyrimidine biosynthesis, which CAD catalyzes the first three steps for. KEGG, HMDB and HPA were used to reconstruct a network of relevant pathways, demonstrating the relationships between genes and metabolites using the MetaboSignal package in R. The network was filtered to exclude any duplicates, and those greater than three steps away from CPS1 or CAD. Consequently, a network of 18 metabolites, 28 metabolic genes and 1 signaling gene was obtained, which indicated expression profiles and prognostic information of each gene in the network. Conclusion: Information from different databases was collated to form an informative network that integrated different ‘-omics’ approaches, demonstrating the relationships between genetic and metabolic components of urea cycle and the de novo pyrimidine biosynthesis pathway. This study paves the way for further research by acting as a template to investigate the relationships between genes and metabolites, explore their potential roles in various diseases and aid the development of new screening and treatment methods through network reconstruction

    Pain Coping Skills Training for Patients Who Catastrophize About Pain Prior to Knee Arthroplasty: A Multisite Randomized Clinical Trial

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    BACKGROUND: Pain catastrophizing has been identified as a prognostic indicator of poor outcome following knee arthroplasty. Interventions to address pain catastrophizing, to our knowledge, have not been tested in patients undergoing knee arthroplasty. The purpose of this study was to determine whether pain coping skills training in persons with moderate to high pain catastrophizing undergoing knee arthroplasty improves outcomes 12 months postoperatively compared with usual care or arthritis education. METHODS: A multicenter, 3-arm, single-blinded, randomized comparative effectiveness trial was performed involving 5 university-based medical centers in the United States. There were 402 randomized participants. The primary outcome was the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Scale, measured at baseline, 2 months, 6 months, and 12 months following the surgical procedure. RESULTS: Participants were recruited from January 2013 to June 2016. In 402 participants, 66% were women and the mean age of the participants (and standard deviation) was 63.2 ± 8.0 years. Three hundred and forty-six participants (90% of those who underwent a surgical procedure) completed a 12-month follow-up. All 3 treatment groups had large improvements in 12-month WOMAC pain scores with no significant differences (p > 0.05) among the 3 treatment arms. No differences were found between WOMAC pain scores at 12 months for the pain coping skills and arthritis education groups (adjusted mean difference, 0.3 [95% confidence interval (CI), -0.9 to 1.5]) or between the pain coping and usual-care groups (adjusted mean difference, 0.4 [95% CI, -0.7 to 1.5]). Secondary outcomes also showed no significant differences (p > 0.05) among the 3 groups. CONCLUSIONS: Among adults with pain catastrophizing undergoing knee arthroplasty, cognitive behaviorally based pain coping skills training did not confer pain or functional benefit beyond the large improvements achieved with usual surgical and postoperative care. Future research should develop interventions for the approximately 20% of patients undergoing knee arthroplasty who experience persistent function-limiting pain. LEVEL OF EVIDENCE: Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence

    Opioid use prior to knee arthroplasty in patients who catastrophize about their pain: preoperative data from a multisite randomized clinical trial

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    Background: Opioid use rates prior to knee arthroplasty (KA) among people who catastrophize about their pain are unknown. We determined prevalence of opioid use and compared patterns of preoperative opioid use and oral morphine equivalent (OME), a measure of daily opioid dose, across varied geographic sites. We also determined which baseline variables were associated with opioid use and OME. Patients and methods: Preoperative opioid use data described type of opioid, dosage, and frequency among 397 patients scheduled for KA. Demographic, knee-related pain, and psychological distress dimensions were examined to identify variables associated with opioid use and opioid dose (OME). Opioid use prevalence and OME were compared across the four sites. A three-level censored regression determined variables associated with opioid use and OME. Results: The overall opioid use prevalence was 31.7% (95% confidence interval [CI] = 27.0, 36.3) and varied across sites from 15.9% (95% CI = 9.0, 22.8) to 51.2% (95% CI = 40.5, 61.9). After adjustment, patients using opioids were more likely to be younger, African American, and have higher self-efficacy and comorbidity scores (P < 0.05). The only variable independently associated with OME was lower depressive symptoms (P < 0.05). Conclusion: People who catastrophized prior to KA did not demonstrate increased preoperative opioid use based on current evidence, but variation in the prevalence of opioid use across study sites was substantial. Variables associated with opioid use were non-modifiable demographic and comorbidity variables

    Clinical-Community Collaboration: A Strategy to Improve Retention and Outcomes in Low-Income Minority Youth in Family-Based Obesity Treatment

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    Background: Clinical-community collaboration is a promising strategy for pediatric obesity treatment, but current research is limited. This study examined the effect of a family-based treatment program embedded in a primary care clinic on retention and changes in child weight status at 1 year. Methods: Children (2-16 years, BMI ≥85th percentile, 87.0% Hispanic) and their parents were recruited from a single pediatric clinic for Healthy Hawks Primary Plus (HHP+). Children were referred by physicians and enrolled by a bilingual clinic-based recruitment coordinator. Participants received 12 weekly 2-hour sessions focused on lifestyle modification and health behavior change and then received bimonthly follow-up visits with their clinic-based physician through 1-year follow-up. Child body mass index (BMI) percentage of the 95th percentile (%BMIp95) was measured as the primary outcome at baseline, postintervention, and 1-year follow-up. Random effect multilevel models assessed changes in child weight status over time accounting for clustering by family. To further evaluate the impact, HHP+ retention and changes in child weight status were compared to a standard 12-week treatment program only. Results: HHP+ participants had significantly better retention at 1 year (73.9%, p ≤ 0.001) compared to the standard treatment program (38.3%). In HHP+, physician visit attendance was significantly correlated with retention at 1 year (r = 0.69, p ≤ 0.001), and HHP+ completers had significant reductions in %BMIp95 between baseline and 1-year follow-up (p = 0.03). Conclusion: Clinical-community partnerships might be a promising strategy to improve retention and reduce child weight status in populations currently underrepresented in obesity treatment

    Disentangling trait versus state characteristics of the Pain Catastrophizing Scale and the PHQ-8 Depression Scale

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    Background: Research on the role of trait versus state characteristics of a variety of measures among persons experiencing pain has been a focus for the past few decades. Studying the trait versus state nature of the Pain Catastrophizing Scale (PCS) and the Patient Health Questionnaire (PHQ-8) depression scale would be highly informative given both are commonly measured in pain populations and neither scale has been studied for trait/state contributions. Methods: The PHQ-8 and PCS were obtained on persons undergoing knee arthroplasty at baseline, 2-, 6- and 12-month post-surgery (N = 402). The multi-trait generalization of the latent trait-state model was used to partition trait and state variability in PCS and PHQ-8 item responses simultaneously. A set of variables were used to predict trait catastrophizing and trait depression. Results: For total scores, the latent traits and latent states explain 63.2% (trait = 43.2%; state = 20.0%) and 50.2% (trait = 29.4%; state = 20.8%) of the variability in PCS and PHQ-8, respectively. Patients with a high number of bodily pain sites, high levels of anxiety, young patients and African-American patients had high levels of trait catastrophizing and trait depression. The PCS and the PHQ-8 consist of both enduring trait and dynamic state characteristics, with trait characteristics dominating for both measures. Conclusion: Clinicians and researchers using these scales should not assume the obtained measurements solely reflect either trait- or state-based characteristics. Significance: Clinicians and researchers using the PCS or PHQ-8 scales are measuring both state and trait characteristics and not just trait- or state-based characteristics

    Detecting longitudinal patterns of daily smoking following drastic cigarette reduction

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    To enhance prolonged smoking cessation or reduction, a better understanding of the process of change is needed. This study examines daily smoking rates following the end of an intensive smoking reduction program originally designed to evaluate the relationship of tobacco biomarkers with reduced levels of smoking. A novel pattern-oriented approach called time series-based typology is used to detect homogeneous smoking patterns in time-intensively (i.e., 40 occasions) observed smokers (n = 57), who were predominantly Caucasian (94.7%), male (52.6%), and on average 47.9 years old (SD = 11.3). The majority of the smokers exhibited a change in their daily smoking behavior over the course of 40 days with 47.4% increasing and 40.4% decreasing the number of cigarettes smoked per day, which is contrary to the results a group level approach would have found. Very few smokers (12.3%) maintained their average smoking rate, and exhibited an externally controlled smoking pattern. Trajectory type could be predicted by temporally proximal motivation and self-efficacy variables ((F(4, 106) =3.46, p = .011, η2 = .115), underscoring their importance in maintaining reduced smoking rates. Time series-based typology demonstrated good sensitivity to the identification of meaningfully different trajectories

    Psychometric properties of the Children’s Revised Impact of Events Scale (CRIES) with Bangladeshi children and adolescents

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    Identification of possible cases suffering post-traumatic stress disorder (PTSD) is important, especially in developing countries where traumatic events are typically prevalent. The Children’s Revised Impact of Events Scale is a reliable and valid measure that has two brief versions (13 items and 8 items) to assess reactions to traumatic events among young people. The current study evaluated the psychometric properties of both versions of the CRIES in a sample of 1,342 children and adolescents aged 9–17 years (M = 12.3 years, SD = 2.12) recruited from six districts of Bangladesh. A sub-group of 120 children from four schools was re-tested on the measures within 3.5 weeks. Confirmatory factor analysis supported factor structures similar to those found in other studies for both versions of the CRIES. Multiple group confirmatory factor analysis showed gender and age-group differences within the sample, supporting established age and gender differences in prevalence of PTSD symptoms. Analyses also indicated moderate to excellent internal consistency and test-retest reliability and clear discriminant and convergent validity. These data support use of both the CRIES-13 and CRIES-8 to provide quick and psychometrically sound assessment of symptoms of PTSD among children and adolescents from Bangla-speaking communities
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