Genome-wide expression analysis of vegetative organs during developmental and herbicide-induced whole plant senescence in Arabidopsis thaliana.

BACKGROUND: Whole plant senescence represents the final stage in the life cycle of annual plants, characterized by the decomposition of aging organs and transfer of nutrients to seeds, thereby ensuring the survival of next generation. However, the transcriptomic profile of vegetative organs during this death process remains to be fully elucidated, especially regarding the distinctions between natural programmed death and artificial sudden death induced by herbicide. RESULTS: Differential genes expression analysis using RNA-seq in leaves and roots of Arabidopsis thaliana revealed that natural senescence commenced in leaves at 45-52 days after planting, followed by roots initiated at 52-60 days. Additionally, both organs exhibited similarities with artificially induced senescence by glyphosate. Transcription factors Rap2.6L and WKRY75 appeared to serve as central mediators of regulatory changes during natural senescence, as indicated by co-expression networks. Furthermore, the upregulation of RRTF1, exclusively observed during natural death, suggested its role as a regulator of jasmonic acid and reactive oxygen species (ROS) responses, potentially triggering nitrogen recycling in leaves, such as the glutamate dehydrogenase (GDH) shunt. Root senescence was characterized by the activation of AMT2;1 and GLN1;3, facilitating ammonium availability for root-to-shoot translocation, likely under the regulation of PDF2.1. CONCLUSIONS: Our study offers valuable insights into the transcriptomic interplay between phytohormones and ROS during whole plant senescence. We observed distinct regulatory networks governing nitrogen utilization in leaf and root senescence processes. Furthermore, the efficient allocation of energy from vegetative organs to seeds emerges as a critical determinant of population sustainability of annual Arabidopsis.

Repurposing thioridazine for inducing immunogenic cell death in colorectal cancer via eIF2α/ATF4/CHOP and secretory autophagy pathways.

BACKGROUND: Colorectal cancer (CRC) is a highly prevalent cancer type with limited targeted therapies available and 5-year survival rate, particularly for late-stage patients. There have been numerous attempts to repurpose drugs to tackle this problem. It has been reported that autophagy inducers could augment the effect of certain chemotherapeutic agents by enhancing immunogenic cell death (ICD). METHODS: In this study, we employed bioinformatics tools to identify thioridazine (THD), an antipsychotic drug, and found that it could induce autophagy and ICD in CRC. Then in vitro and in vivo experiments were performed to further elucidate the molecular mechanism of THD in CRC. RESULTS: THD was found to induce endoplasmic reticulum (ER) stress in CRC cells by activating the eIF2α/ATF4/CHOP axis and facilitating the accumulation of secretory autophagosomes, leading to ICD. In addition, THD showed a remarkable ICD-activating effect when combined with oxaliplatin (OXA) to prevent tumor progression in the mouse model. CONCLUSIONS: Together, our findings suggest that the repurposed function of THD in inhibiting CRC involves the upregulation of autophagosomes and ER stress signals, promoting the release of ICD markers, and providing a potential candidate to enhance the clinical outcome for CRC treatment. Video Abstract.

CHOIRBM: An R package for exploratory data analysis and interactive visualization of pain patient body map data.

Body maps are commonly used to capture the location of a patient's pain and thus reflect the extent of pain throughout the body. With increasing electronic capture body map information, there is an emerging need for clinic- and research-ready tools capable of visualizing this data on individual and mass scales. Here we propose CHOIRBM, an extensible and modular R package and companion web application built on the grammar of graphics system. CHOIRBM provides functions that simplify the process of analyzing and plotting patient body map data integrated from the CHOIR Body Map (CBM) at both individual patient and large-dataset levels. CHOIRBM is built on the popular R graphics package, ggplot2, which facilitates further development and addition of functionality by the open-source development community as future requirements arise. The CHOIRBM package is distributed under the terms of the MIT license and is available on CRAN. The development version of the package with the latest functions may be installed from GitHub. Example analysis using CHOIRBM demonstrates the functionality of the modular R package and highlights both the clinical and research utility of efficiently producing CBM visualizations.

Validation of cardiac output estimation using the fourth-generation FloTrac/EV1000™ system in patients undergoing robotic-assisted off-pump coronary artery bypass surgery.

The pulmonary artery catheter (PAC)-despite its invasiveness-remains the gold standard for cardiac output (CO) monitoring. The FloTrac system, a less invasive hemodynamic monitor has been developed, which estimates CO using arterial pressure waveform analysis without external calibration. Recently, an upgraded version of FloTrac system with improved algorithm to follow changes in vascular resistance was introduced into the market. The aim of this study was to assess the reliability of the CO estimated from the fourth-generation FloTrac/EV1000 system (COFT) compared to that measured with PAC using the thermodilution method (COPAC) during robotic-assisted off-pump coronary artery bypass (OPCAB) surgery. COFT and COPAC were obtained simultaneously at 4 predefined time points during robotic-assisted OPCAB: 5 min after the induction of general anesthesia (T1), after starting one-lung ventilation (T2), after capnothorax (T3), and after mini-thoracotomy was performed (T4). The agreement of data was investigated by Bland-Altman analysis. Thirty-four patients were initially enrolled. After exclusion, 32 patients and a total of 128 paired CO measurements were obtained. The overall bias was 1.46 L/min, the 95% limits of agreements were - 3.40 to 6.33 L/min, and the percentage error was 72.98%. Regression analysis of the systemic vascular resistance index (SVRI) and the bias between COPAC and COFT showed that the bias was moderately correlated with the SVRI (r2 = 0.43; p < 0.0001). Despite a software upgrade, the reliability of the fourth-generation FloTrac/EV1000™ system during robotic-assisted OPCAB to estimate CO was not acceptable, especially in patients with low SVRI.

Baicalein suppresses HER2-mediated malignant transformation of HER2-overexpressing ovarian cancer cells by downregulating HER2 gene expression.

The upregulation of the HER2 oncogene is associated with a variety of human cancers and is associated with poor prognosis. Baicalein is reported to have anti-tumor activity, but the molecular mechanism of this effect in HER2-positive cancer cells has not been studied. In this study, our data showed that baicalein can inhibit the proliferation and transformation potential of ovarian cancer cells overexpressing HER2. Baicalein treatment caused a dose-dependent inhibition of HER2 gene expression at the transcriptional level. Baicalein acted on ovarian cancer cells overexpressing HER2 to downregulate the PI3K/Akt signaling pathway downstream of HER2 and inhibit the expression or activity of downstream targets, such as VEGF and cyclin D1 and MMP2. Oral administration of baicalein supplemented with a pharmaceutical excipient significantly inhibited the growth of HER2-overexpressing ovarian SKOV-3 cancer xenografts in mice. These results suggest that downregulation of HER2 gene expression by baicalein at the transcriptional level contributes to inhibit the in vitro and in vivo proliferation and HER2-mediated malignant transformation of HER2-overexpressing ovarian cancer cells.

Immune Checkpoint Inhibitor, Nivolumab, Combined with Chemotherapy Improved the Survival of Unresectable Advanced and Metastatic Esophageal Squamous Cell Carcinoma: A Real-World Experience.

Patients with advanced esophageal squamous cell carcinoma (SCC) have a poor prognosis when treated with standard chemotherapy. Programmed death ligand 1 (PD-L1) expression in esophageal cancer has been associated with poor survival and more advanced stage. Immune checkpoint inhibitors, such as PD-1 inhibitors, showed benefits in advanced esophageal cancer in clinical trials. We analyzed the prognosis of patients with unresectable esophageal SCC who received nivolumab with chemotherapy, dual immunotherapy (nivolumab and ipilimumab), or chemotherapy with or without radiotherapy. Patients who received nivolumab with chemotherapy had a better overall response rate (ORR) (72% vs. 66.67%, p = 0.038) and longer overall survival (OS) (median OS: 609 days vs. 392 days, p = 0.04) than those who received chemotherapy with or without radiotherapy. In patients receiving nivolumab with chemotherapy, the duration of the treatment response was similar regardless of the treatment line they received. According to clinical parameters, liver and distant lymph nodes metastasis showed a trend of negative and positive impacts, respectively, on treatment response in the whole cohort and in the immunotherapy-containing regimen cohort. Nivolumab add-on treatment showed less gastrointestinal and hematological adverse effects, compare with chemotherapy. Here, we showed that nivolumab combined with chemotherapy is a better choice for patients with unresectable esophageal SCC.

Baicalein Induces G2/M Cell Cycle Arrest Associated with ROS Generation and CHK2 Activation in Highly Invasive Human Ovarian Cancer Cells.

Ovarian cancer is a lethal gynecological cancer because drug resistance often results in treatment failure. The CHK2, a tumor suppressor, is considered to be an important molecular target in ovarian cancer due to its role in DNA repair. Dysfunctional CHK2 impairs DNA damage-induced checkpoints, reduces apoptosis, and confers resistance to chemotherapeutic drugs and radiation therapy in ovarian cancer cells. This provides a basis for finding new effective agents targeting CHK2 upregulation or activation to treat or prevent the progression of advanced ovarian cancer. Here, the results show that baicalein (5,6,7-trihydroxyflavone) treatment inhibits the growth of highly invasive ovarian cancer cells, and that baicalein-induced growth inhibition is mediated by the cell cycle arrest in the G2/M phase. Baicalein-induced G2/M phase arrest is associated with an increased reactive oxygen species (ROS) production, DNA damage, and CHK2 upregulation and activation. Thus, baicalein modulates the expression of DNA damage response proteins and G2/M phase regulatory molecules. Blockade of CHK2 activation by CHK2 inhibitors protects cells from baicalein-mediated G2/M cell cycle arrest. All the results suggest that baicalein has another novel growth inhibitory effect on highly invasive ovarian cancer cells, which is partly related to G2/M cell cycle arrest through the ROS-mediated DNA breakage damage and CHK2 activation. Collectively, our findings provide a molecular basis for the potential of baicalein as an adjuvant therapeutic agent in the treatment of metastatic ovarian cancer.

Engagement in Prescription Opioid Tapering Research: the EMPOWER Study and a Coproduction Model of Success.

Patients with chronic pain experience stigma within the healthcare system. This stigma is compounded for those taking long-term prescription opioids. Often, public messaging and organizational policies have telegraphed that opioid treatment is a problem to be solved by focusing only on medication reduction efforts. Lack of data has contributed to misperceptions and poor opioid policies. In part, data collection remains poor because patients feel fractured from systems of care and are often not interested in engaging with opioid reduction mandates and research. Similarly, clinicians may fail to engage with opioid stewardship and research due to complexities that exceed their training or capacities. The EMPOWER study applies a coproduction model that engages researchers, patients, clinicians, managers, and other health system users. Key stakeholders shaped the design of the study to best ensure acceptability and engagement of the "end users"-patients who enroll in the study and the clinicians who implement the opioid tapers. Targeting the needs of any stakeholder group in isolation is suboptimal. Accordingly, we detail the EMPOWER patient-centered opioid tapering clinical research framework and specific strategies to address stakeholder concerns. We also discuss how this framework may be applied to enhance engagement in healthcare research broadly.

Functional Outcomes and Physical Performance of Knee Osteoarthritis Patients After Ultrasound-Guided Genicular Nerve Radiofrequency Ablation.

OBJECTIVE: To elucidate the effectiveness of ultrasound-guided genicular nerve radiofrequency ablation in alleviating pain as well as its effects on functional outcomes, quality of life and physical performance in knee osteoarthritis patients. DESIGN: Prospective observational study. SETTING: Patients were recruited within one community hospital. SUBJECTS: Patients with knee osteoarthritis. METHODS: The subjects underwent ultrasound-guided radiofrequency ablation of genicular nerves after showing a positive response to a diagnostic block. Outcome assessments were performed at baseline and at 2 and 12 weeks posttreatments using the 36-item Short Form Health Survey (SF-36), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and a physical performance evaluation including balance tests, quadriceps muscle strength test, two-minute walking test and knee joint proprioception test. RESULTS: Thirteen out of 38 patients were eligible for genicular nerve radiofrequency ablation. There were significant improvements from baseline to posttreatment in the numeric rating scale score, physical health domain score of SF-36, and pain and stiffness domain scores of the WOMAC. Regarding physical performance, the step test result significantly improved over the 12 weeks of follow-up. On the other hand, no significant deteriorations in the single leg stance test, isokinetic quadriceps muscle strength test, knee joint proprioception test or two-minute walking test results were observed after radiofrequency ablation of genicular nerves. CONCLUSIONS: Radiofrequency ablation of genicular nerves may significantly alleviate pain and improve functional outcomes in knee osteoarthritis patients. More importantly, static balance control and quadriceps muscle strength were preserved and there was a change of proprioception in the good direction.

Dysregulation of cystathionine γ-lyase promotes prostate cancer progression and metastasis.

Hydrogen sulfide (H2 S), an endogenous signaling gaseous molecule, is involved in various physiological activities, including vessel relaxation, regulation of cellular bioenergetics, inflammation, and angiogenesis. By using xenograft orthotopic implantation of prostate cancer PC3 cells and subsequently comparing bone metastatic with primary tumor-derived cancer cells, we find that H2 S-producing enzyme cystathionine γ-lyase (CTH) is upregulated in bone-metastatic PC3 cells. Clinical data further reveal that the expression of CTH is elevated in late-stage prostate cancer patients, and higher CTH expression correlates with poor survival from The Cancer Genome Atlas (TCGA) prostate cancer RNA-seq datasets. CTH promotes NF-κB nuclear translocation through H2 S-mediated sulfhydration on cysteine-38 of the NF-κB p65 subunit, resulting in increased IL-1ß expression and H2 S-induced cell invasion. Knockdown of CTH in PC3 cells results in the suppression of tumor growth and distant metastasis, while overexpression of CTH in DU145 cells promotes primary tumor growth and lymph node metastasis in the orthotopic implanted xenograft mouse model. Together, our findings provide evidence that CTH generated H2 S promotes prostate cancer progression and metastasis through IL-1ß/NF-κB signaling pathways.

Anesthesia and Long-term Oncological Outcomes: A Systematic Review and Meta-analysis.

BACKGROUND: Whether propofol elicits a survival benefit over volatile anesthetics during cancer surgery remains inconclusive. The primary aim of this systematic review and meta-analysis is to compare the effects of propofol-based total intravenous anesthesia (TIVA) with any volatile anesthesia on long-term oncological outcomes. The secondary aim is to compare propofol-based TIVA with specific volatile agents on long-term oncological outcomes. METHODS: We searched PubMed, Embase, Scopus, Web of Science, and Cochrane Library from inception through March 3, 2020. Randomized control trials and observational studies that compared the effects of propofol-based TIVA and volatile anesthesia on long-term oncological outcomes, which also reported hazard ratios (HR) as effect estimates, were considered eligible for inclusion. Using the inverse variance method with a random-effects model, HR and 95% confidence intervals (CI) were calculated. Trial sequential analysis was incorporated to test if the results were subject to a type I or type II error. RESULTS: Nineteen retrospective observational studies were included. Patients who received propofol-based TIVA during cancer surgery were associated with significantly better overall survival than those who received volatile anesthesia (HR = 0.79, 95% CI, 0.66-0.94, P = .008, I2 = 82%). In contrast, no statistically significant difference was observed in recurrence-free survival between patients who received propofol-based TIVA and volatile anesthesia during cancer surgery (HR = 0.81, 95% CI, 0.61-1.07, P = .137, I2 = 85%). In the subgroup analysis by different volatile anesthetics, patients who received propofol-based TIVA were associated with better overall survival than those who received desflurane (HR = 0.54, 95% CI, 0.36-0.80, P = .003, I2 = 80%). In contrast, there was no statistically significant difference in overall survival between patients who received propofol-based TIVA and those who received sevoflurane (HR = 0.92, 95% CI, 0.74-1.14, P = .439, I2 = 70%). In the trial sequential analysis of overall survival, the cumulative Z curve reached the required heterogeneity-adjusted information size and crossed the traditional significance boundary. In contrast, in the trial sequential analysis of recurrence-free survival, the cumulative Z curve did not cross the traditional significance boundary. However, the required heterogeneity-adjusted information size has not yet been reached. CONCLUSIONS: Propofol-based TIVA is generally associated with better overall survival than volatile anesthesia during cancer surgery. Further large-scaled, high-quality randomized control trials are warranted to confirm our findings.

Pre-operative proteinuria, postoperative acute kidney injury and mortality: A systematic review and meta-analysis.

OBJECTIVE: To investigate the association of pre-operative proteinuria with postoperative acute kidney injury (AKI) development as well as the requirement for a renal replacement therapy (RRT) and mortality at short-term and long-term follow-up. BACKGROUND: Postoperative AKI is associated with surgical morbidity and mortality. Pre-operative proteinuria is potentially a risk factor for postoperative AKI and mortality. However, the results in literature are conflicting. METHODS: We searched PubMed, Embase, Scopus, Web of Science and Cochrane Library from the inception through to 3 June 2020. Observational cohort studies investigating the association of pre-operative proteinuria with postoperative AKI development, requirement for RRT, and all-cause mortality at short-term and long-term follow-up were considered eligible. Using inverse variance method with a random-effects model, the pooled effect estimates and 95% confidence interval (CI) were calculated. RESULTS: Twenty-eight studies were included. Pre-operative proteinuria was associated with postoperative AKI development [odds ratio (OR) 1.74, 95% CI, 1.45 to 2.09], in-hospital RRT (OR 1.70, 95% CI, 1.25 to 2.32), requirement for RRT at long-term follow-up [hazard ratio (HR) 3.72, 95% CI, 2.03 to 6.82], and long-term all-cause mortality (hazard ratio 1.50, 95% CI, 1.30 to 1.73). In the subgroup analysis, pre-operative proteinuria was associated with increased odds of postoperative AKI in both cardiovascular (OR 1.77, 95% CI, 1.47 to 2.14) and noncardiovascular surgery (OR 1.63, 95% CI, 1.01 to 2.63). Moreover, there is a stepwise increase in OR of postoperative AKI development when the quantity of proteinuria increases from trace to 3+. CONCLUSION: Pre-operative proteinuria is significantly associated with postoperative AKI and long-term mortality. Pre-operative anaesthetic assessment should take into account the presence of proteinuria to identify high-risk patients. PROSPERO REGISTRATION: CRD42020190065.

Dual down-regulation of EGFR and ErbB2 by berberine contributes to suppression of migration and invasion of human ovarian cancer cells.

The overexpression of EGFR and/or ErbB2 occurs frequently in ovarian cancers and is associated with poor prognosis. The purpose of this study was to examine the anticancer effects and molecular mechanisms of berberine on human ovarian cancer cells with different levels of EGFR and/or ErbB2. We found that berberine reduced the motility and invasiveness of ovarian cancer cells. Berberine depleted both EGFR and ErbB2 in ovarian cancer cells. Furthermore, berberine suppressed the activation of the EGFR and ErbB2 downstream targets cyclin D1, MMPs, and VEGF by down-regulating the EGFR-ErbB2/PI3K/Akt signaling pathway. The berberine-mediated inhibition of MMP-2 and MMP-9 activity could be rescued by co-treatment with EGF. Finally, we demonstrated that berberine induced ErbB2 depletion through ubiquitin-mediated proteasome degradation. In conclusion, the suppressive effects of berberine on the ovarian cancer cells that differ in the expression of EGFR and ErbB2 may be mediated by the dual depletion of EGFR and/or ErbB2.

Ganoderma tsugae suppresses the proliferation of endometrial carcinoma cells via Akt signaling pathway.

Ganoderma is one of the common medicinal mushrooms in traditional Chinese medicine. Previous researches have unveiled the multifaceted biological activity of Ganoderma extract. Ganoderma tsugae has been investigated the potential on curing prostate, colon, lung, epidermoid, breast and ovarian cancers, but not including endometrial cancer. Endometrial cancer is a gynecological malignant tumor with serious drug resistance problem in clinical cancer treatment. This study aimed to demonstrate the first study of Ganoderma on treating endometrial cancer. The Ganoderma tsugae ethanol extract (GTEE) could suppress the proliferation of endometrial cancer cells HEC-1-A, KLE, and AN3 CA. GTEE also induced G1/S phase arrest and mitochondria-mediated apoptosis in endometrial cancer cells. Furthermore, the Akt signaling pathway could be suppressed by GTEE. Therefore, our results suggest for the first time that GTEE has the potential to be an adjuvant therapeutic agent in the treatment of endometrial cancer.

Dynamic tongue base thickness measured by drug-induced sleep ultrasonography in patients with obstructive sleep apnea.

BACKGROUND/PURPOSE: The aim of this study was to determine the value of drug-induced sleep ultrasonography (DISU) for evaluating tongue base thickness (TBT) from the awake state to drug-induced sleep, to further understand the impact of dynamic changes in TBT in obstructive sleep apnoea (OSA) patients. METHODS: From May 2017 to May 2018, thirty patients with OSA were prospectively recruited. Sleep was induced with propofol via use of a target-controlled infusion (TCI) system. The depth of sedation was monitored by the bispectral (BIS) index with BIS levels ranging from 50 to 70. The dynamic change in the tongue base from the awake state to drug-induced sleep was recorded. The correlation between TBT in the awake state and in drug-induced sleep with OSA severity was analysed. RESULTS: The mean TBT in drug-induced sleep was significantly greater than that in the awake state (66.2 ± 4.8 mm vs 61.6 ± 4.6 mm, P < 0.001). TBT in drug-induced sleep was more correlated with AHI compared to TBT in the awake state (r = 0.50 vs r = 0.40). This study showed that TBT in drug-induced sleep had the largest AUC (Area Under the Curve) in the ROC (Receiver Operating Characteristics) analysis (0.875), providing a cut-off point of 63.20 mm with 95% sensitivity for diagnosis of moderate versus severe OSA. CONCLUSION: Our findings validate the use of DISU in objectively assessing the tongue base collapse in OSA patients. It provides a convenient and non-invasive way to evaluate the upper airway changes in OSA patients in the future.

Spin Wave Injection and Propagation in a Magnetic Nanochannel from a Vortex Core.

Spin waves can be used as information carriers with low energy dissipation. The excitation and propagation of spin waves along reconfigurable magnonic circuits is the subject of much interest in the field of magnonic applications. Here we experimentally demonstrate an effective excitation of spin waves in reconfigurable magnetic textures at frequencies as high as 15 GHz and wavelengths as short as 80 nm from Ni80Fe20 (Py) nanodisk-film hybrid structures. Most importantly, we demonstrate these spin wave modes, which were previously confined within a nanodisk, can now couple to and propagate along a nanochannel formed by magnetic domain walls at zero magnetic bias field. The tunable high-frequency, short-wavelength, and propagating spin waves may play a vital role in energy efficient and programmable magnonic devices at the nanoscale.

Hyperlipidemia patients with long-term statin treatment are associated with a reduced risk of progression of benign prostatic enlargement.

OBJECTIVE: To evaluate the impacts of statin treatment on the risk of benign prostatic enlargement (BPE) progression in hyperlipidemia patients. METHODS: Newly diagnosed hyperlipidemia patients (n = 7961), identified from Taiwan's National Health Insurance Research Database, were divided into four statin cohorts (statin use >365 days, n = 1604; statin use 181-365 days, n = 813; statin use 91-180 days, n = 739; and statin use 31-90 days, n = 713) and one control cohort (cohort that used no statins, n = 4092). Study endpoint was occurrence of BPE progression (BPE diagnosis plus receiving BPE-related medications or surgery). Relative risks of BPE progression in the statin cohorts compared to the control cohort were analyzed. RESULTS: Multivariable Cox proportional hazards regression analyses demonstrated that BPE progression risk in the cohort used statins for >365 days was significantly lower than the control cohort (adjusted hazard ratio: 0.70, 95% confidence interval: 0.58 ∼ 0.85, p < .001). However, BPE progression risks of the other three statin cohorts did not significantly differ from the control cohort. Trend analysis revealed that the effects of statin treatment on decreasing BPE progression risk were significantly related to statin treatment duration (p = .001). CONCLUSIONS: Hyperlipidemia patients with long-term statin treatment (more than 365 days) are associated with a reduced risk of BPE progression.

Smoking Is Associated with Pain in All Body Regions, with Greatest Influence on Spinal Pain.

OBJECTIVE: Examine the interrelationship between smoking and pain in the US population. DESIGN: A cross-sectional population-based study. SETTING: Nationwide survey. METHODS: Comprehensive pain reports categorically defined as head, spine, trunk, and limb pain; smoking history; demographics; medical history from a total of 2,307 subjects from the 2003-2004 National Health and Nutrition Examination Survey obtained from the Centers for Disease Control were analyzed. Unpaired t tests were used to analyze independent continuous variables, and chi-square tests were used to analyze categorical variables between smoker and nonsmoker groups. Weighted multivariate logistic regression analyses determined the association of current smoking with the presence of pain in various body regions. RESULTS: Smoking is most strongly associated with spine pain (odds ratio [OR] = 2.89, 95% confidence interval [CI] = 2.21-3.77), followed by headache (OR = 2.47, 95% CI = 1.73-3.53), trunk pain (OR = 2.17, 95% CI = 1.45-2.74), and limb pain (OR = 1.99, 95% CI = 1.45-2.73). CONCLUSIONS: Current smoking is associated with pain in every region of the body. This association is strongest for spine and head pain. Given that pain is a strong motivator and that current smoking was associated with pain in all body regions, we recommend that these results be used to further raise public awareness about the potential harms of smoking.

Comparative Effectiveness of Cognitive Behavioral Therapy for Chronic Pain and Chronic Pain Self-Management within the Context of Voluntary Patient-Centered Prescription Opioid Tapering: The EMPOWER Study Protocol.

OBJECTIVE: Evidence to date, while sparse, suggests that patients taking long-term opioids require special considerations and protections to prevent potential iatrogenic harms from opioid de-prescribing, such as increased pain or suffering. Following this study protocol, the EMPOWER study seeks to address multiple unmet needs of patients with chronic pain who desire to reduce long-term opioid therapy, and provide the clinical evidence on effective methodology. METHODS: EMPOWER applies patient-centered methods for voluntary prescription opioid reduction conducted within a comprehensive, multi-state, 3-arm randomized controlled comparative effectiveness study of three study arms (1) group cognitive behavioral therapy for chronic pain; (2) group chronic pain self-management; and (3) usual care (taper only). Specialized electronic data capture systems collect patient reported symptoms and satisfaction data weekly and monthly during the taper, with real-time clinical alerts and electronic feedback loops informing, documenting, and steering needed care actions. CONCLUSION: The EMPOWER study seeks to provide granular evidence on patient response to voluntary opioid tapering, and will provide evidence to inform clinical systems changes, clinical care, patient satisfaction, and patient outcomes for opioid reduction.

Cytotoxic and Anti-inflammatory Terpenoids from the Whole Plant of Vaccinium emarginatum.

Two new Δ12 ursene-type triterpenoid coumaroyl esters (1: and 2: ), one new Δ7,15 isopimarane-type diterpenoid glycoside (20: ), and two new irido-δ-lactone-type iridoids (21: and 22: ), together with 17 known pentacyclic triterpenoids (3:  - 19: ), were isolated during the phytochemical investigation of a methanol extract of the whole plant of Vaccinium emarginatum. Their structures were determined by detailed analysis of standard spectroscopic data (MS, IR, 1D, and 2D NMR) and comparison with data of known analogs. The isolates were evaluated for their cytotoxicity against the PC-3 and Du145 prostate cancer cell lines (as assessed by an MTT cell proliferation assay), as well as for their anti-inflammatory activity via the inhibition of nitric oxide production in lipopolysaccharide-induced murine macrophage RAW 264.7 cells. Among the isolates, the triterpenoid coumaroyl and feruloyl esters (1, 3: , and 4: ) exhibited strong cytotoxicity against PC-3 prostate cancer cells, with 85.6 - 90.2% inhibition at 10.0 µg/mL. The pomolic acid coumaroyl and feruloyl esters (1: and 3: ) also showed moderate anti-inflammatory activity against nitric oxide production in lipopolysaccharide-induced RAW 264.7 cells, with 59.2 (± 1.0) and 47.1% (± 0.2) inhibition at 12.5 µg/mL, respectively.