Youth use of electronic nicotine delivery systems (ENDS) in the Population Assessment of Tobacco and Health (PATH) Wave 6: Impact of survey mode.

BACKGROUND: The Population Assessment of Tobacco and Health (PATH) provides annual prevalence data on youth use of electronic nicotine delivery systems (ENDS). However, trends may be complicated by COVID-related changes in survey mode (self-completed vs. telephone interview) across 2019-2021. METHODS: Trends in past 30-day (P30D) ENDS use over PATH waves 5 (2019; 100 % self-completed), 5.5 (2020; 100 % telephone interview), and 6 (2021; 33.5 % self-completed, 66.5 % telephone interview) were examined among continuing youth, overall and within survey mode. Further analyses examined the nature of these changes by examining 1) potential response biases in social contexts of nicotine use, and 2) sources of ENDS over time. RESULTS: Telephone interviewees were less likely to report ENDS use (4.6 % vs. 8.6 % for self-completers), and more likely to report social disapproval of nicotine use, suggesting a reporting bias in telephone interviews. Survey-mode-naïve analyses suggested a large decline in P30D ENDS use prevalence between 2019-20 (10.2-4.6 %) followed by an apparent uptick in 2021 (5.9 %); however, comparing like-to-like survey modes showed a more modest decline (10.2 % in 2019; 8.6 % in 2021; self-completed) with no change between 2020 and 2021 (4.6 % in both; telephone interviews). Analyses suggested that the mode effects were partly, but not wholly, related to social desirability effects. DISCUSSION: Changes in PATH survey mode introduced artifacts into ENDS use prevalence, possibly due in part to social desirability bias suppressing reporting in telephone interviews, rather than a true uptick. It is essential to account for survey mode in PATH surveys.

A comparison of brief versus explicit descriptors for verbal rating scales: interrupted time series design.

BACKGROUND: Verbal rating scales (VRS) are widely used in patient-reported outcome (PRO) measures. At our institution, patients complete an online instrument using VRSs with a five-point brief response scale to assess symptoms as part of routine follow-up after ambulatory cancer surgery. We received feedback from patients that the brief VRS descriptors such as "mild" or "somewhat" were vague. We added explicit descriptors to our VRSs, for instance, "Mild: I can generally ignore my pain" for pain severity or "Somewhat: I can do some things okay, but most of my daily activities are harder because of fatigue" for fatigue interference. We then compared responses before and after this change was made. METHODS: The symptoms investigated were pain, fatigue and nausea. Our hypothesis was that the explicit descriptors would reduce overall variance. We therefore compared the coefficient of variation of scores and tested the association between symptoms scores and known predictors thereof. We also compared time to completion between questionnaires with and without the additional descriptors. RESULTS: A total of 17,500 patients undergoing 21,497 operations were assigned questionnaires in the period before the descriptors were added; allowing for a short transition period, 1,417 patients having 1436 operations were assigned questionnaires with the additional descriptors. Symptom scores were about 10% lower with the additional descriptors but the coefficient of variation was slightly higher. Moreover, the only statistically significant difference between groups for association with a known predictor favored the item without the additional language for nausea severity (p = 0.004). Total completion time was longer when the instrument included the additional descriptors, particularly the first and second time that the questionnaire was completed. CONCLUSIONS: Adding descriptors to a VRS of post-operative symptoms did not improve scale properties in patients undergoing ambulatory cancer surgery. We have removed the additional descriptors from our tool. We recommend further comparative psychometric research using data from PROs collected as part of routine clinical care.

Switching away from smoking at 12 months among adult JUUL users varying in recent history of quit attempts made with and without smoking cessation medication.

Some smokers switch away from smoking using e-cigarettes, but guidelines recommend trying approved medications first. We analyzed switching in adult smokers using JUUL by their recent history of quit attempts and use of smoking cessation medications. Participants were 8511 adult (21+) established smokers (at baseline), in which 50.3% are daily smokers, in a longitudinal observational study who completed a survey 12 months after first purchasing a JUUL Starter Kit. At baseline, participants reported attempts to quit smoking in the prior year and use of pharmacotherapy (nicotine replacement therapy [NRT] or prescription medication) in their most recent attempt. The outcomes were switching (self-reported no past-30-day smoking) and 50%+ reductions in cigarette consumption. Multivariable analyses were adjusted for baseline covariates. Two thirds of the participants had made a quit attempt in the year before purchasing JUUL. Overall, 59% [58%, 60%] had switched at 12 months. Switching was more likely in those who had used NRT and who attempted quitting without medication versus those who used prescription medications or made no quit attempt. In adjusted multivariable analyses, only making a past-year quit attempt (vs. not) was associated with higher odds of switching (OR = 1.15 [1.04, 1.28]). Over 60% of dual users reduced cigarette consumption by ≥50%. These associations were largely similar in daily smokers. Twelve months after purchasing JUUL, almost all smokers reported either switching or reducing their smoking by 50%+, including those who had recently failed to quit smoking with approved pharmacotherapies. E-cigarettes provide an alternative route to abstinence from smoking for smokers with a history of cessation and cessation treatment failure.

Patient-reported symptoms after minimally invasive hysterectomy and association with postoperative complications.

OBJECTIVE: To describe patient-reported postoperative symptoms and to evaluate the use of digital symptom tracking and alerts to detect postoperative complications. METHODS: We retrospectively reviewed patients who underwent a minimally invasive hysterectomy and enrolled in our Recovery Tracker program from 4/5/17-12/31/21. The Recovery Tracker is an at-home virtual tool used to track patient-reported postoperative symptoms for 10 days. Predefined thresholds for "red" and "yellow" alerts are based on symptom severity and timing. Data on patient demographics, surgery, and postoperative course were collected to evaluate the association of alerts with complications and compare outcomes of patients who did/did not enroll in the program. RESULTS: Of 2362 eligible patients, 1694 (71.7%) enrolled in the Recovery Tracker program. Pain was the most severe symptom, followed by fatigue. Eighty-seven patients experienced 102 complications (5.1% complication rate) and 32 experienced 39 grade ≥ 2 complications (1.9% severe complication rate). Excluding complications that occurred prior to Recovery Tracker use, 1673 patients experienced 28 grade ≥ 2 complications. Of 345 patients (20.6%) who triggered a red alert, 13 (3.8%) had a grade ≥ 2 complication. Of 1328 patients (79.4%) with no red alerts, 15 (1.13%) had a grade ≥ 2 complication. Relative risk of a grade ≥ 2 complication if a red alert was triggered was 3.25 (95% CI: 1.6-6.9, P = .002). Rate of severe complications was significantly higher among patients who did not use the tool (3.3% vs 1.9%; P = .04). CONCLUSIONS: The Recovery Tracker tool may assist in early identification of postoperative symptoms after minimally invasive hysterectomy.

Organometallic Pillarplexes That Bind DNA 4-Way Holliday Junctions and Forks.

Holliday 4-way junctions are key to important biological DNA processes (insertion, recombination, and repair) and are dynamic structures that adopt either open or closed conformations, the open conformation being the biologically active form. Tetracationic metallo-supramolecular pillarplexes display aryl faces about a cylindrical core, an ideal structure to interact with open DNA junction cavities. Combining experimental studies and MD simulations, we show that an Au pillarplex can bind DNA 4-way (Holliday) junctions in their open form, a binding mode not accessed by synthetic agents before. Pillarplexes can bind 3-way junctions too, but their large size leads them to open up and expand that junction, disrupting the base pairing, which manifests in an increased hydrodynamic size and lower junction thermal stability. At high loading, they rearrange both 4-way and 3-way junctions into Y-shaped forks to increase the available junction-like binding sites. Isostructural Ag pillarplexes show similar DNA junction binding behavior but lower solution stability. This pillarplex binding contrasts with (but complements) that of metallo-supramolecular cylinders, which prefer 3-way junctions and can rearrange 4-way junctions into 3-way junction structures. The pillarplexes' ability to bind open 4-way junctions creates exciting possibilities to modulate and switch such structures in biology, as well as in synthetic nucleic acid nanostructures. In human cells, the pillarplexes do reach the nucleus, with antiproliferative activity at levels similar to those of cisplatin. The findings provide a new roadmap for targeting higher-order junction structures using a metallo-supramolecular approach, as well as expanding the toolbox available to design bioactive junction binders into organometallic chemistry.

Youth patterns of use of electronic nicotine delivery systems (ENDS), Population Assessment of Tobacco and Health (PATH) waves 4-5.5.

INTRODUCTION: Youth use of electronic nicotine delivery systems (ENDS) is a continuing concern, making it important to assess evolving patterns, especially as non-tobacco, non-menthol (NTM) flavors were withdrawn for pod-based (but not disposable) ENDS in February 2020. METHODS: Trends in past-30-day (P30D) ENDS use and smoking prevalence, usual device type, flavor (tobacco, mint/menthol, or fruit/sweet/other), and regular/last-used brand in PATH Waves 4 (2017), 4.5 (2018), 5 (2019), and 5.5 (2020) were examined. Shifts between 2019 and 2020 in flavor use for pods and disposables were examined. RESULTS: P30D ENDS use peaked in 2019 at 8.6 % of all youth, subsequently declining by nearly half to 4.5 % in 2020. Meanwhile, P30D cigarette smoking declined to an all-time low (1.3 %) in 2020. Within this overall decline, consumption shifted to disposable ENDS, which increased nearly 10-fold (from 5.0 % to 49.2 % of P30D ENDS users). Relatedly, use of fruit/sweet/other flavors remained similar overall between 2019 and 2020 (approximately 75-80 % of P30D ENDS users), but the use of these flavors became concentrated in disposable ENDS in 2020 (a 12-fold increase from 4.4 % to 58.4 % of fruit/sweet/other-flavor users). CONCLUSIONS: PATH results show similar trends to other US national surveys in youth ENDS trends. The removal of non-tobacco, non-menthol flavors in pod-based ENDS (while remaining available in disposables) has likely driven youth towards disposable devices, resulting in continued high use of fruit/sweet/other flavors, which are now predominant in users of disposable ENDS. Wave 5.5 is uninformative regarding brand use because common disposable brands were not queried.

A New Questionnaire to Assess Respiratory Symptoms (The Respiratory Symptom Experience Scale): Quantitative Psychometric Assessment and Validation Study.

BACKGROUND: Smokers often experience respiratory symptoms (eg, morning cough), and those who stop smoking, including those who do so by switching completely to electronic nicotine delivery systems (ENDS), may experience reductions in symptoms. Existing respiratory symptom questionnaires may not be suitable for studying these changes, as they are intended for patient populations, such as those with chronic obstructive pulmonary disease (COPD). OBJECTIVE: This study aimed to develop a respiratory symptom questionnaire appropriate for current smokers and for assessing changes when smokers stop smoking. METHODS: The Respiratory Symptom Experience Scale (RSES) was derived from existing instruments and subject matter expert input and refined through cognitive debriefing interviews (n=49). Next, for purposes of the quantitative psychometric evaluation, the RSES was administered to smokers (n=202), former smokers (no tobacco use in >6 months; n=200), and switchers (n=208, smokers who switched to ENDS for >6 months), all of whom had smoked for at least 10 years (mean age 33 years). Participants, who averaged 62 (SD 12) years of age, included 28% (173/610) with respiratory allergy symptoms and 17% (104/610) with COPD. Test-retest reliability was assessed by repeat assessment after 1 week in 128 participants. RESULTS: A generalized partial credit model confirmed that the response options were ordered, and a parallel analysis using principal components confirmed that the scale was unidimensional. With allowance for 2 sets of correlated errors between pairs of items, a 1-factor graded response model fit the data. Discrimination parameters were approximately 1 or greater for all items. Scale reliability was 0.80 or higher across a broad range of severity (standardized scores -0.40 to 3.00). Test-retest reliability (absolute intraclass correlation) was good, at 0.89. RSES convergent validity was supported by substantial differences (Cohen d=0.74) between those with and without a diagnosis of respiratory disease (averaging 0.57 points, indicating that differences of this size or smaller represent meaningful differences). RSES scores also strongly differentiated those with and without COPD (d=1.52). Smokers' RSES scores were significantly higher than former smokers' scores (P<.001). Switchers' RSES scores were significantly lower than smokers' scores (P<.001) and no different from former smokers' scores (P=.34). CONCLUSIONS: The RSES fills an important gap in the existing toolkit of respiratory symptom questionnaires; it is a reliable and valid tool to assess respiratory symptoms in adult current and former smokers, including those who have switched to noncombusted nicotine products. This suggests that the scale is sensitive to respiratory symptoms that develop in smokers and to their remission when smokers quit or switch to noncombusted nicotine products intended to reduce the harm of smoking. The findings also suggest that switching from cigarettes to ENDS may improve respiratory health.

Presence of Magnetic Resonance Imaging-Defined Inflammation Particularly in Overweight and Obese Women Increases Risk of Radiographic Knee Osteoarthritis: The POMA Study.

OBJECTIVE: The present study was undertaken to assess whether the odds for incident radiographic osteoarthritis (OA) differ between men and women in regard to body mass index (BMI) and inflammatory magnetic resonance imaging (MRI) markers 1 and 2 years prior, and whether the presence of inflammation on MRI differs between normal-weight and overweight/obese individuals who develop radiographic OA up to 4 years prior. METHODS: We studied 355 knees from the Osteoarthritis Initiative study that developed incident radiographic OA and 355 matched controls. MRIs were read for effusion-synovitis and Hoffa-synovitis for up to 4 consecutive annual time points. Subjects were classified as normal-weight (BMI <25), overweight (BMI ≥25 and <30), or obese (BMI ≥30). Conditional logistic regression was used to assess odds of incident radiographic OA for effusion-synovitis and Hoffa-synovitis at 1 and 2 years prior to radiographic OA incidence (i.e., "P-1" and "P-2") considering BMI category. Bivariate logistic regression was used to assess odds of inflammation for cases only. RESULTS: One hundred seventy-eight (25.1%) participants were normal weight, 283 (39.9%) overweight, and 249 (35.1%) obese. At P-2, being overweight with Hoffa-synovitis, which had an odds ratio [OR] of 3.26 (95% confidence interval [95% CI] 1.39-7.65), or effusion-synovitis (OR 3.56 [95% CI 1.45-8.75]) was associated with greater odds of incident radiographic OA in women. For those with incident radiographic OA, there were no increased odds of synovitis in the overweight/obese subgroup for most time points, but increased odds for effusion-synovitis were observed at P-2 (OR 2.21 [95% CI 1.11-4.43]). CONCLUSION: Presence of inflammatory markers seems to play a role especially in overweight women, while obese women have increased odds for radiographic OA also in the absence of these markers.

Magnetic Resonance Imaging-Defined Osteophyte Presence and Concomitant Cartilage Damage in Knees With Incident Tibiofemoral Osteoarthritis: Data From the Pivotal Osteoarthritis Initiative Magnetic Resonance Imaging Analyses Study.

OBJECTIVE: To describe compartmental frequencies of magnetic resonance image (MRI)-defined osteophytes and co-localized cartilage damage and evaluate the associations of osteophyte size with any ipsicompartmental cartilage damage in knees with incident tibiofemoral radiographic knee osteoarthritis (OA). METHODS: We evaluated knees from the Osteoarthritis Initiative without radiographic knee OA at baseline that developed radiographic knee OA during a 4-year interval. Semiquantitative MRI scoring of osteophytes and cartilage damage was performed at the time point when radiographic knee OA was diagnosed, defined as Kellgren/Lawrence grade of ≥2, using the MRI Osteoarthritis Knee Score instrument. The frequencies of maximum osteophyte size and maximum grade of ipsicompartmental (i.e., patellofemoral, medial tibiofemoral, lateral tibiofemoral, posterior femur) cartilage damage were assessed. Generalized estimating equations were used to determine the association of MRI-defined maximum osteophyte size with presence of any (excluding focal superficial defects) ipsicompartmental cartilage damage. RESULTS: A total of 296 knees that did not have tibiofemoral radiographic knee OA at the baseline visit but developed radiographic knee OA during the 48-month observational period were included. In the patellofemoral, medial tibiofemoral, and lateral tibiofemoral compartments, the most frequent osteophyte grade was 1 (67.6%, 59.1%, and 51.7%, respectively) and was 0 (51.7%) in the posterior femur. For all compartments except the posterior femur, a linear trend was found between increasing maximum osteophyte size and the presence of any concomitant cartilage damage. CONCLUSION: In this sample of knees with incident tibiofemoral radiographic knee OA, the patellofemoral joint showed more severe cartilage damage than other compartments regardless of concomitant osteophyte size. In the posterior femur, cartilage damage was rare despite the presence or size of concomitant osteophytes.

Targeting structural features of viral genomes with a nano-sized supramolecular drug.

RNA targeting is an exciting frontier for drug design. Intriguing targets include functional RNA structures in structurally-conserved untranslated regions (UTRs) of many lethal viruses. However, computational docking screens, valuable in protein structure targeting, fail for inherently flexible RNA. Herein we harness MD simulations with Markov state modeling to enable nanosize metallo-supramolecular cylinders to explore the dynamic RNA conformational landscape of HIV-1 TAR untranslated region RNA (representative for many viruses) replicating experimental observations. These cylinders are exciting as they have unprecedented nucleic acid binding and are the first supramolecular helicates shown to have anti-viral activity in cellulo: the approach developed in this study provides additional new insight about how such viral UTR structures might be targeted with the cylinder binding into the heart of an RNA-bulge cavity, how that reduces the conformational flexibility of the RNA and molecular details of the insertion mechanism. The approach and understanding developed represents a new roadmap for design of supramolecular drugs to target RNA structural motifs across biology and nucleic acid nanoscience.

Supramolecular Cylinders Target Bulge Structures in the 5' UTR of the RNA Genome of SARS-CoV-2 and Inhibit Viral Replication*.

The untranslated regions (UTRs) of viral genomes contain a variety of conserved yet dynamic structures crucial for viral replication, providing drug targets for the development of broad spectrum anti-virals. We combine in vitro RNA analysis with molecular dynamics simulations to build the first 3D models of the structure and dynamics of key regions of the 5' UTR of the SARS-CoV-2 genome. Furthermore, we determine the binding of metallo-supramolecular helicates (cylinders) to this RNA structure. These nano-size agents are uniquely able to thread through RNA junctions and we identify their binding to a 3-base bulge and the central cross 4-way junction located in stem loop 5. Finally, we show these RNA-binding cylinders suppress SARS-CoV-2 replication, highlighting their potential as novel anti-viral agents.

Changes in Medial Meniscal Three-Dimensional Position and Morphology As Predictors of Knee Replacement in Rapidly Progressing Knee Osteoarthritis: Data From the Osteoarthritis Initiative.

OBJECTIVE: To assess whether quantitative changes in the meniscus predict progression from early knee osteoarthritis (OA) to knee replacement (KR). METHODS: A nested case-control study was conducted among Osteoarthritis Initiative participants: all 35 case knees with baseline Kellgren/Lawrence (K/L) grade ≤2 that had KR between 36 and 60 months were matched 1:1 by age, sex, and baseline K/L grade to 35 control knees without subsequent KR. Quantitative 3-dimensional medial meniscus position and morphologic measures were determined from magnetic resonance imaging at the visit just before KR and 2 years before. Paired t-tests and case-control odds ratios (ORs, standardized per SD of change in controls) were used to compare changes between groups. RESULTS: Cases (52% women, age 65 ± 7 years, body mass index [BMI] 30 ± 4 kg/m2 , K/L grades 0/1/2: 5/8/22 participants, respectively) and controls (52% women, age 64 ± 7 years, BMI 30 ± 5 kg/m2 , K/L grades 0/1/2: 9/4/22 participants, respectively) were similar. Compared to control knees, KR case knees displayed longitudinal changes, specifically, a decrease in tibial plateau coverage, an increase in meniscal extrusion, and a decrease in meniscal width. The odds for KR increased with greater reduction in the percentage of tibial plateau coverage (OR 2.28 [95% CI confidence interval (95% CI) 1.43, 3.64]), a greater increase in maximal extrusion (OR 1.40 [95% CI 1.12, 1.75]), and a greater reduction of mean meniscal width (OR 2.01 [95% CI 1.23, 3.26]). The odds for KR increased with medial compartment cartilage thickness loss (OR 2.86 [95% CI 1.51, 5.41]) for comparison. CONCLUSION: Quantitative measures of meniscal position and morphology are associated with subsequent KR in knees with rapidly progressing knee OA. These findings show that structural changes of the meniscus are related to an important clinical and economic outcome of knee OA.

Case study of the integration of electronic patient-reported outcomes as standard of care in a head and neck oncology practice: Obstacles and opportunities.

BACKGROUND: Patient-reported outcomes (PROs) allow for the direct measurement of functional and psychosocial effects related to treatment. However, technological barriers, survey fatigue, and clinician adoption have hindered the meaningful integration of PROs into clinical care. The objective of the authors was to develop an electronic PROs (ePROs) program that meets a range of clinical needs across a head and neck multidisciplinary disease management team. METHODS: The authors developed the ePROs module using literature review and stakeholder input in collaboration with health informatics. They designed an ePROs platform that was integrated as the standard of care for personalized survey delivery by diagnosis across the disease management team. Tableau software was used to create dashboards for data visualization and monitoring at the clinical enterprise, disease subsite, and patient levels. All patients who were treated for head and neck cancer were eligible for ePROs assessment as part of the standard of care. A descriptive analysis of ePROs program implementation is presented herein. RESULTS: The Head and Neck Service at Memorial Sloan Kettering Cancer Center has integrated ePROs into clinical care. Surveys are delivered via the patient portal at the time of diagnosis and longitudinally through care. From August 1, 2018, to February 1, 2020, a total of 4154 patients completed ePROs surveys. The average patient participation rate was 69%, with a median time for completion of 5 minutes. CONCLUSIONS: Integration of the head and neck ePROs program as part of clinical care is feasible and could be used to assess value and counsel patients in the future. Continued qualitative assessments of stakeholders and workflow will refine content and enhance the health informatics platform. LAY SUMMARY: Patients with head and neck cancer experience significant changes in their quality of life after treatment. Measuring and integrating patient-reported outcomes as a part of clinical care have been challenging given the multimodal treatment options, vast subsites, and unique domains affected. The authors present a case study of the successful integration of electronic patient-reported outcomes into a high-volume head and neck cancer practice.

Supramolecular Cylinders Target Bulge Structures in the 5' UTR of the RNA Genome of SARS-CoV-2 and Inhibit Viral Replication.

The untranslated regions (UTRs) of viral genomes contain a variety of conserved yet dynamic structures crucial for viral replication, providing drug targets for the development of broad spectrum anti-virals. We combine in vitro RNA analysis with molecular dynamics simulations to build the first 3D models of the structure and dynamics of key regions of the 5' UTR of the SARS-CoV-2 genome. Furthermore, we determine the binding of metallo-supramolecular helicates (cylinders) to this RNA structure. These nano-size agents are uniquely able to thread through RNA junctions and we identify their binding to a 3-base bulge and the central cross 4-way junction located in stem loop 5. Finally, we show these RNA-binding cylinders suppress SARS-CoV-2 replication, highlighting their potential as novel anti-viral agents.

Rotaxanating Metallo-supramolecular Nano-cylinder Helicates to Switch DNA Junction Binding.

A class of rotaxane is created, not by encapsulating a conventional linear thread, but rather by wrapping a large cucurbit[10]uril macrocycle about a three-dimensional, cylindrical, nanosized, self-assembled supramolecular helicate as the axle. The resulting pseudo-rotaxane is readily converted into a proper interlocked rotaxane by adding branch points to the helicate strands that form the surface of the cylinder (like branches and roots on a tree trunk). The supramolecular cylinder that forms the axle is itself a member of a unique and remarkable class of helicate metallo-drugs that bind Y-shaped DNA junction structures and induce cell death. While pseudo-rotaxanation does not modify the DNA-binding properties, proper, mechanically-interlocked rotaxanation transforms the DNA-binding and biological activity of the cylinder. The ability of the cylinder to de-thread from the rotaxane (and thus to bind DNA junction structures) is controlled by the extent of branching: fully-branched cylinders are locked inside the cucurbit[10]uril macrocycle, while cylinders with incomplete branch points can de-thread from the rotaxane in response to competitor guests. The number of branch points can thus afford kinetic control over the drug de-threading and release.

Silver(I) complexes of 3-methoxy-4-hydroxybenzaldehyde thiosemicarbazones and triphenylphosphine: structural, cytotoxicity, and apoptotic studies.

Novel silver(i) complexes of the type [AgCl(PPh3)2(L)] {PPh3 = triphenylphosphine; L = VTSC = 3-methoxy-4-hydroxybenzaldehyde thiosemicarbazone (1); VMTSC = 3-methoxy-4-[2-(morpholine-1-yl)ethoxy]benzaldehyde thiosemicarbazone (2); VPTSC = 3-methoxy-4-[2-(piperidine-1-yl)ethoxy]benzaldehyde thiosemicarbazone (3)} were synthesized and fully characterized by spectroscopic techniques. The molecular structures of complexes 2 and 3 were determined by single crystal X-ray diffraction. Compounds 1-3 exhibited appreciable cytotoxic activity against human tumor cells (lung A549, breast MDA-MB-231 and MCF-7) with IC50 values in 48 h of incubation ranging from 5.6 to 18 µM. Cellular uptake studies showed that complexes 1-3 were efficiently internalized after 3 hours of treatment in MDA-MB-231 cells. The effects of complex 1 on the cell morphology, cell cycle, induction of apoptosis, mitochondrial membrane potential (Δψm), and reactive oxygen species (ROS) production have been evaluated in triple negative breast cancer (TNBC) cells MDA-MB-231. Our results showed that complex 1 induced typical morphological alterations of cell death, an increase in cells at the sub-G1 phase, apoptosis, and mitochondrial membrane depolarization. Furthermore, DNA binding studies evidenced that 1 can bind to ct-DNA and does so without modifying the B-structure of the DNA, but that the binding is weak compared to that of Hoechst 33258.

Nonsteroidal Anti-Inflammatory Drug Use in Chronic Arthritis Pain: Variations by Ethnicity.

PURPOSE: Our objective was to determine if there are ethnic differences in the use of over-the-counter (OTC) and prescription oral nonsteroidal anti-inflammatory drugs (NSAIDs) and if observed ethnic differences persist after adjustment for sociodemographic and clinical factors. METHODS: Knee and hip osteoarthritis study participants were identified. Surveys were administered to collect sociodemographics, clinical information, and oral treatment methods for arthritis. Multivariable logistic regression models were created using a fully conditional method. RESULTS: Hispanics (n = 130), compared to non-Hispanic whites (n = 204), were less likely to have a high school education (26.9% vs 63.2%, P <0.001), less likely to have private medical insurance (P <0.001), and more likely to have worse health (P = 0.004). OTC oral NSAID use was less common (52.9% vs 66.3%, P = 0.019), whereas prescription oral NSAID use was more common (43.4% vs 31.7%, P = 0.042) among Hispanics than non-Hispanic whites in the last 6 months. The ethnic difference in using an OTC NSAID instead of not using any oral NSAID was attenuated and no longer significant when adjusted for age, sex, education, and medical insurance (odds ratio [OR] 0.54 [95% confidence interval [CI]: 0.28-1.02]). The odds of using a prescription instead of an OTC NSAID remained significantly higher among Hispanics than non-Hispanic whites when adjusted for the same variables (odds ratio 2.17 [95% confidence interval: 1.16-4.05]). CONCLUSIONS: Among patients with osteoarthritis, OTC NSAIDs were less commonly used but prescription NSAIDs were more commonly used by Hispanics than non-Hispanic whites. Sociodemographic factors partially mediate ethnic differences in the use of oral NSAIDs.

Modifiable Determinants of Exercise Use in a Diverse Ethnic Population With Osteoarthritis.

OBJECTIVE: To determine the extent of ethnic differences in the use of exercise for therapy and identify relevant modifiable determinants of exercise use among patients with knee/hip osteoarthritis (OA). METHODS: Knee/hip OA study participants were identified. Surveys were administered to collect patient sociodemographic and clinical information, and beliefs and attitudes about providers and treatments. Final multivariable logistic regression models were created using a fully conditional method. RESULTS: Hispanic participants (n = 130), compared to non-Hispanic participants (n = 232), were less likely to have private medical insurance (9.2% versus 31.0%) or to report having excellent/very good health (40.7% versus 52.6%). They were also less likely to report using exercise for OA treatment in the last 6 months (56% versus 73%; P = 0.003). When adjusted for age and disease severity, the difference in exercise use among ethnicities remained significant (odds ratio [OR] 0.59 [95% confidence interval (95% CI) 0.36-0.99]). In a multivariable logistic regression model designed to determine the most important determinants of exercise use for OA treatment, in the last 6 months the following were all associated with exercise use: having knee instead of hip OA (OR 2.83 [95% CI 1.51-5.29]), having family/friends who exercise (OR 3.20 [95% CI 1.76-5.84]), having a good understanding of what happens after exercise (OR 2.19 [95 CI 1.15-4.19]), and higher perceived benefit of exercise (OR 2.24 [95% CI 1.64-3.04]). CONCLUSION: Among patients with knee/hip OA, Hispanics were less likely to exercise for OA treatment. Increased knowledge about the benefits of exercise for treatment and improved familiarity with exercise as treatment for OA may increase exercise use.