Bars, Nightclubs, and Cancer Prevention: New Approaches to Reduce Young Adult Cigarette Smoking.

IntroductionTobacco contributes to multiple cancers, and it is largely preventable. As overall smoking prevalence in California declines, smoking has become concentrated among high-risk groups. Targeting social/cultural groups (i.e., "peer crowds") that share common values, aspirations, and activities in social venues like bars and nightclubs may reach high-risk young adult smokers. Lack of population data on young adult peer crowds limits the ability to assess the potential reach of such interventions.MethodsThis multimodal population-based household survey included young adults residing in San Francisco and Alameda counties. Data were collected in 2014 and analyzed in 2016. Multivariable logistic regressions assessed smoking by sociodemographic factors, attitudes, self-rated health, peer crowd affiliation, and bar/nightclub attendance.ResultsSmoking prevalence was 15.1% overall; 35.3% of respondents sometimes or frequently attended bars. In controlled analyses, bar attendance (AOR=2.13, 95% CI=1.00, 4.53) and binge drinking (AOR=3.17, 95% CI=1.59, 6.32) were associated with greater odds of smoking, as was affiliation with "Hip Hop" (AOR=4.32, 95% CI=1.48, 12.67) and "Country" (AOR=3.13, 95% CI=1.21, 8.09) peer crowds. Multivariable models controlling for demographics estimated a high probability of smoking among bar patrons affiliating with Hip Hop (47%) and Country (52%) peer crowds.ConclusionsBar attendance and affiliation with certain peer crowds confers significantly higher smoking risk. Interventions targeting Hip Hop and Country peer crowds could efficiently reach smokers, and peer crowd-tailored interventions have been associated with decreased smoking and binge drinking. Targeted interventions in bars and nightclubs may be an efficient way to address these cancer risks

QUERCETIN IMPROVES THE EFFICACY OF SORAFENIB IN TRIPLE NEGATIVE BREAST CANCER CELLS THROUGH THE MODULATION OF DRUG EFFLUX TRANSPORTERS EXPRESSIONS

Objective: This study aimed to investigate whether quercetin is able to improve the efficacy of sorafenib in triple negative breast cancer cells and explore the possibility of drug efflux transporters modulation by quercetin. Methods: We exposed MDA-MB-231, a triple negative breast cancer cell line, to several groups: sorafenib alone, quercetin alone, a combination of sorafenib-quercetin, and control. We determined cell viability over control weekly up to 4 w. At the end of the fourth week, mRNA expressions of drug efflux transporters (P-glycoprotein and breast cancer resistance protein [BCRP] and MRP2 [multidrug resistance-associated protein-2]) were examined. Results: Sorafenib alone was shown to maintain its efficacy for only two weeks, while quercetin alone was able to maintain its effect for four weeks. A combination of sorafenib-quercetin showed the best cytotoxicity effects compared with sorafenib or quercetin alone and was able to maintain its efficacy for four weeks. There were increased mRNA expressions of P-glycoprotein, BCRP, and MRP2 after four weeks of treatment with sorafenib, while treatment with quercetin decreased the drug efflux transporters expressions. A combination of sorafenib-quercetin decreased the mRNA expressions of both P-glycoprotein and BCRP, compared with sorafenib alone. Conclusion: We suggest that decreased expressions of both drug efflux transporters, P-glycoprotein and BCRP, mediated by quercetin ameliorate the efficacy of sorafenib in TNBC. Therefore, the addition of quercetin to sorafenib might be useful in the future in improving the therapeutic efficacy of sorafenib in triple negative breast cancer

THE EFFECT OF CURCUMIN ON THE PROLIFERATION AND EXTRACELLULAR MATRIX PRODUCTION IN ETHANOL-INDUCED HEPATIC STELLATE CELLS

Objectives: In various liver disease models, including those for alcoholic liver diseases, curcumin, a polyphenolic compound derived fromCurcuma longa, is known to have an hepatoprotective effect. However, the mechanism of action underlying its effects on alcohol-induced hepaticfibrosis remains unknown. We aimed to investigate the mechanisms of action underlying the effects of curcumin, mainly involving the transforminggrowth factor (TGF)-β/Smad pathway.Methods: Hepatic stellate cells (HSCs), LX2, were incubated with 50 mM ethanol with or without curcumin (1 and 10 μM). Viable HSCs were countedusing a LUNATM automated cell counter, whereas the expressions of TGF-β, Smad3, tissue inhibitor of metalloproteinases-1 (TIMP-1), and type 1collagen mRNA were measured using quantitative reverse transcriptase polymerase chain reactions.Results: Curcumin significantly suppressed ethanol-induced HSCs proliferation. The antiproliferative effect of curcumin appeared to be dosedependent. In addition, the mRNA expressions of TGF-β, Smad3, TIMP-1, and type 1 collagen decreased in the cells treated with curcumin.Conclusion: Curcumin seems to attenuate ethanol-induced HSCs proliferation through the suppression of TGF-β and appears to reduce the productionof extracellular matrix as shown by the decreased expression of type 1 collagen

Effect of intramuscular methadone on pharmacokinetic data and thermal and mechanical nociceptive thresholds in the cat

Objectives The aim of the study was to assess simultaneous pharmacokinetics and thermal and mechanical antinociception after intramuscular methadone (0.6 mg/kg) in 10 cats. Methods Thermal and mechanical threshold (TT and MT, respectively) testing and blood collection were conducted at baseline and up to 24 h after administration. Methadone plasma concentrations were determined by liquid chromatography–tandem mass spectrometry and pharmacokinetic parameters were estimated by a non-compartmental method. TT and MT were analysed using ANOVA ( P &lt;0.05). Time of maximum plasma concentration (Tmax), time of onset of antinociception and time of reaching cut-out threshold (TT 55°C; MT 30 Newtons [N]) were determined. Results TT and MT increased above baseline from 20–240 mins and 5–40 mins, respectively, after intramuscular (IM) administration ( P &lt;0.005). Mean maximum delta T (measured as TT minus baseline threshold) was 7.9°C (95% confidence interval [CI] 4.3–11.6) at 60 mins and mean maximum delta F (measured as MT minus baseline threshold) was 4.2 (95% CI 1.6–6.7) N at 45 mins. IM methadone concentration–time data decreased curvilinearly, and gave a clearance estimate of mean 9.1 ml/kg/min (range 5.2–15.7) with median Tmax at 20 mins (range 5–360 mins). Conclusions and relevance IM data followed classical disposition and elimination in all cats. Plasma concentrations after IM administration were associated with an antinociceptive effect, including negative hysteresis. These data can be used for devising dosing schedules for methadone in clinical feline practice. </jats:sec

Measuring case severity: a novel tool for benchmarking and clinical documentation improvement

BACKGROUND: Severity of illness (SOI) is an All Patients Refined Diagnosis Related Groups (APR DRG) modifier based on comorbidity capture. Tracking SOI helps hospitals improve performance and resource distribution. Furthermore, benchmarking SOI plays a key role in Quality Improvement (QI) efforts such as Clinical Documentation Improvement (CDI) programs. The current SOI system highly relies on the 3 M APR DRG grouper that is updated annually, making it difficult to track severity longitudinally and benchmark against hospitals with different patient populations. Here, we describe an alternative SOI scoring system that is grouper-independent and that can be tracked longitudinally. METHODS: Admission data for 2019-2020 U.S. News and World Report Honor Roll facilities were downloaded from the Vizient Clinical Database and split into training and testing datasets. Elixhauser comorbidities, body systems developed from the Healthcare Cost and Utilization Project (HCUP), and ICD-10-CM complication and comorbidity (CC/MCC) indicators were selected as the predictors for orthogonal polynomial regression models to predict patients\u27 admission and discharge SOI. Receiver operating characteristic (ROC) and Precision-Recall (PR) analysis, and prediction accuracy were used to evaluate model performance. RESULTS: In the training dataset, the full model including both Elixhauser comorbidities and body system CC/MCC indicators had the highest ROC AUC, PR AUC and predication accuracy for both admission (ROC AUC: 92.9%; PR AUC: 91.0%; prediction accuracy: 85.4%) and discharge SOI (ROC AUC: 93.6%; PR AUC: 92.8%; prediction accuracy: 86.2%). The model including only body system CC/MCC indicators had similar performance for admission (ROC AUC: 92.4%; PR AUC: 90.4%; prediction accuracy: 84.8%) and discharge SOI (ROC AUC: 93.1%; PR AUC: 92.2%; prediction accuracy: 85.6%) as the full model. The model including only Elixhauser comorbidities exhibited the lowest performance. Similarly, in the validation dataset, the prediction accuracy was 86.2% for the full model, 85.6% for the body system model, and 79.3% for the comorbidity model. With fewer variables and less model complexity, the body system model was more efficient and was determined to be the optimal model. The probabilities generated from this model, named J_Score and J_Score_POA, successfully measured SOI and had practical applications in assessment of CDI performance. CONCLUSIONS: The J_Scores generated from the body system model have significant value in evaluating admission and discharge severity of illness. We believe that this new scoring system will provide a useful tool for healthcare institutions to benchmark patients\u27 illness severity and augment Quality Improvement (QI) efforts

Field-tuned quantum tunneling in a supramolecule dimer [Mn4]2[Mn_4]_2

Field-tuned quantum tunneling in two single-molecule magnets coupled antiferromagnetically and formed a supramolecule dimer is studied. We obtain step-like magnetization curves by means of the numerically exact solution of the time-dependent Schr\H{o}dinger equation. The steps in magnetization curves show the phenomenon of quantum resonant tunneling quantitatively. The effects of the sweeping rate of applied field is discussed. These results obtained from quantum dynamical evolution well agree with the recent experiment[W.Wernsdorfer et al. Nature 416(2002)406].Comment: 11 pages, 4 figures, 2 tables. Submited to Phys. Rev.

Predicting adverse outcomes following catheter ablation treatment for atrial fibrillation

Objective: To develop prognostic survival models for predicting adverse outcomes after catheter ablation treatment for non-valvular atrial fibrillation (AF). Methods: We used a linked dataset including hospital administrative data, prescription medicine claims, emergency department presentations, and death registrations of patients in New South Wales, Australia. The cohort included patients who received catheter ablation for AF. Traditional and deep survival models were trained to predict major bleeding events and a composite of heart failure, stroke, cardiac arrest, and death. Results: Out of a total of 3285 patients in the cohort, 177 (5.3%) experienced the composite outcomeheart failure, stroke, cardiac arrest, deathand 167 (5.1%) experienced major bleeding events after catheter ablation treatment. Models predicting the composite outcome had high risk discrimination accuracy, with the best model having a concordance index > 0.79 at the evaluated time horizons. Models for predicting major bleeding events had poor risk discrimination performance, with all models having a concordance index < 0.66. The most impactful features for the models predicting higher risk were comorbidities indicative of poor health, older age, and therapies commonly used in sicker patients to treat heart failure and AF. Conclusions: Diagnosis and medication history did not contain sufficient information for precise risk prediction of experiencing major bleeding events. The models for predicting the composite outcome have the potential to enable clinicians to identify and manage high-risk patients following catheter ablation proactively. Future research is needed to validate the usefulness of these models in clinical practice.Comment: Under journal revie

Scintigraphic assessment of sympathetic innervation after transmural versus nontransmural myocardial infarction

To evaluate the feasibility of detecting denervated myocardium in the infarcted canine heart, the distribution of sympathetic nerve endings using 1–123 metaiodobenzylguanidine (MIBG) was compared with the distribution of perfusion using thallium-201, with the aid of color-coded computer functional map in 16 dogs. Twelve dogs underwent myocardial infarction by injection of vinyl latex into the left anterior descending coronary artery (transmural myocardial infarction, n = 6), or ligation of the left anterior descending coronary artery (nontransmural myocardial infarction, n = 6). Four dogs served as sham-operated controls. Image patterns were compared with tissue norepinephrine content and with histofluorescence microscopic findings in biopsy specimens.Hearts with transmural infarction showed zones of absent MIBG and thallium, indicating scar. Adjacent and distal regions showed reduced MIBG but normal thallium uptake, indicating viable but denervated myocardium. Denervation distal to infarction was confirmed by reduced norepinephrine content and absence of nerve fluorescence. Nontransmural myocardial infarction showed zones of wall thinning with decreased thallium uptake and a greater reduction or absence of MIBG localized to the region of the infarct, with minimal extension of denervation beyond the infarct. Norepinephrine content was significantly reduced in the infarct zone, and nerve fluorescence was absent.These findings suggest that 1) MIBG imaging can detect viable and perfused but denervated myocardium after infarction; and 2) as opposed to the distal denervation produced by transmural infarction, nontransmural infarction may lead to regional ischemic damage of sympathetic nerves, but may spare subepicardial nerve trunks that course through the region of infarction to provide a source of innervation to distal areas of myocardium

Structural and psycho-social limits to climate change adaptation in the great barrier reef region

Adaptation, as a strategy to respond to climate change, has limits: there are conditions under which adaptation strategies fail to alleviate impacts from climate change. Research has primarily focused on identifying absolute bio-physical limits. This paper contributes empirical insight to an emerging literature on the social limits to adaptation. Such limits arise from the ways in which societies perceive, experience and respond to climate change. Using qualitative data from multi-stakeholder workshops and key-informant interviews with representatives of the fisheries and tourism sectors of the Great Barrier Reef region, we identify psycho-social and structural limits associated with key adaptation strategies, and examine how these are perceived as more or less absolute across levels of organisation. We find that actors experience social limits to adaptation when: i) the effort of pursuing a strategy exceeds the benefits of desired adaptation outcomes; ii) the particular strategy does not address the actual source of vulnerability, and; iii) the benefits derived from adaptation are undermined by external factors. We also find that social limits are not necessarily more absolute at higher levels of organisation: respondents perceived considerable opportunities to address some psycho-social limits at the national-international interface, while they considered some social limits at the local and regional levels to be effectively absolute