Low-Density Lipoprotein Cholesterol Testing Following Myocardial Infarction Hospitalization Among Medicare Beneficiaries.

Background: Low-density lipoprotein cholesterol (LDL-C) is used to guide lipid-lowering therapy after a myocardial infarction (MI). Lack of LDL-C testing represents a missed opportunity for optimizing therapy and reducing cardiovascular risk. Objectives: The purpose of this study was to estimate the proportion of Medicare beneficiaries who had their LDL-C measured within 90 days following MI hospital discharge. Methods: We conducted a retrospective cohort study of Medicare beneficiaries ≥66 years of age with an MI hospitalization between 2016 and 2020. The primary analysis used data from all beneficiaries with fee-for-service coverage and pharmacy benefits (532,767 MI hospitalizations). In secondary analyses, we used data from a 5% random sample of beneficiaries with fee-for-service coverage without pharmacy benefits (10,394 MI hospitalizations), and from beneficiaries with Medicare Advantage (176,268 MI hospitalizations). The proportion of beneficiaries who had their LDL-C measured following MI hospital discharge was estimated accounting for the competing risk of death. Results: In the primary analysis (mean age 76.9 years, 84.4% non-Hispanic White), 29.9% of beneficiaries had their LDL-C measured within 90 days following MI hospital discharge. Among Hispanic, Asian, non-Hispanic White, and non-Hispanic Black beneficiaries, the 90-day postdischarge LDL-C testing was 33.8%, 32.5%, 30.0%, and 26.0%, respectively. Postdischarge LDL-C testing within 90 days was highest in the Middle Atlantic (36.4%) and lowest in the West North Central (23.4%) U.S. regions. In secondary analyses, the 90-day postdischarge LDL-C testing was 26.9% among beneficiaries with fee-for-service coverage without pharmacy benefits, and 28.6% among beneficiaries with Medicare Advantage coverage. Conclusions: LDL-C testing following MI hospital discharge among Medicare beneficiaries was low.

Intertumoral lineage diversity and immunosuppressive transcriptional programs in well-differentiated gastroenteropancreatic neuroendocrine tumors.

Neuroendocrine tumors (NETs) are rare cancers that most often arise in the gastrointestinal tract and pancreas. The fundamental mechanisms driving gastroenteropancreatic (GEP)-NET growth remain incompletely elucidated; however, the heterogeneous clinical behavior of GEP-NETs suggests that both cellular lineage dynamics and tumor microenvironment influence tumor pathophysiology. Here, we investigated the single-cell transcriptomes of tumor and immune cells from patients with gastroenteropancreatic NETs. Malignant GEP-NET cells expressed genes and regulons associated with normal, gastrointestinal endocrine cell differentiation, and fate determination stages. Tumor and lymphoid compartments sparsely expressed immunosuppressive targets commonly investigated in clinical trials, such as the programmed cell death protein-1/programmed death ligand-1 axis. However, infiltrating myeloid cell types within both primary and metastatic GEP-NETs were enriched for genes encoding other immune checkpoints, including VSIR (VISTA), HAVCR2 (TIM3), LGALS9 (Gal-9), and SIGLEC10. Our findings highlight the transcriptomic heterogeneity that distinguishes the cellular landscapes of GEP-NET anatomic subtypes and reveal potential avenues for future precision medicine therapeutics.

Activation of Tumor-Cell STING Primes NK-Cell Therapy.

Activation of the stimulator of interferon genes (STING) pathway promotes antitumor immunity but STING agonists have yet to achieve clinical success. Increased understanding of the mechanism of action of STING agonists in human tumors is key to developing therapeutic combinations that activate effective innate antitumor immunity. Here, we report that malignant pleural mesothelioma cells robustly express STING and are responsive to STING agonist treatment ex vivo. Using dynamic single-cell RNA sequencing of explants treated with a STING agonist, we observed CXCR3 chemokine activation primarily in tumor cells and cancer-associated fibroblasts, as well as T-cell cytotoxicity. In contrast, primary natural killer (NK) cells resisted STING agonist-induced cytotoxicity. STING agonists enhanced migration and killing of NK cells and mesothelin-targeted chimeric antigen receptor (CAR)-NK cells, improving therapeutic activity in patient-derived organotypic tumor spheroids. These studies reveal the fundamental importance of using human tumor samples to assess innate and cellular immune therapies. By functionally profiling mesothelioma tumor explants with elevated STING expression in tumor cells, we uncovered distinct consequences of STING agonist treatment in humans that support testing combining STING agonists with NK and CAR-NK cell therapies.

Evaluating a Simple Approach to Identify Adults Meeting the 2018 AHA/ACC Cholesterol Guideline Definition of Very High Risk for Atherosclerotic Cardiovascular Disease.

PURPOSE: The 2018 American Heart Association/American College of Cardiology (AHA/ACC) cholesterol guideline defines very high atherosclerotic cardiovascular disease (ASCVD) risk as a history of ≥ 2 major ASCVD events or 1 major ASCVD event and multiple high-risk conditions. We tested if a simplified approach, having a history of a major ASCVD event, would identify a high proportion of patients that meet the 2018 AHA/ACC cholesterol guideline criteria for very high risk. METHODS: We analyzed data from US adults with health insurance in the MarketScan database who had experienced an acute coronary syndrome in the past year (recent ACS, n = 3626), a myocardial infarction (MI) other than a recent ACS (n = 7572), an ischemic stroke (n = 3551), or symptomatic peripheral artery disease (PAD, n = 5919). Patients were followed from January 1, 2016, through December 31, 2017, for recurrent ASCVD events. RESULTS: Among 16,344 patients with a history of a major ASCVD event, 94.0% met the 2018 AHA/ACC cholesterol guideline definition for very high risk including 92.9%, 96.5%, 93.1%, and 96.2% with a recent ACS, history of MI, history of stroke, and symptomatic PAD, respectively. The incidence of ASCVD events per 1000 person-years was 50.4 (95% CI: 47.6-53.3) among all patients with a history of a major ASCVD event versus 53.1 (95% CI: 50.1-56.1) among patients who met the 2018 AHA/ACC cholesterol guideline definition of very high risk. CONCLUSION: The vast majority of patients with a recent ACS, history of MI, ischemic stroke, or symptomatic PAD meet the 2018 AHA/ACC cholesterol guideline definition of very high risk.

Molecular correlates of response to eribulin and pembrolizumab in hormone receptor-positive metastatic breast cancer.

Immune checkpoint inhibitors (ICIs) have minimal therapeutic effect in hormone receptor-positive (HR+ ) breast cancer. We present final overall survival (OS) results (n = 88) from a randomized phase 2 trial of eribulin ± pembrolizumab for patients with metastatic HR+ breast cancer, computationally dissect genomic and/or transcriptomic data from pre-treatment tumors (n = 52) for molecular associations with efficacy, and identify cytokine changes differentiating response and ICI-related toxicity (n = 58). Despite no improvement in OS with combination therapy (hazard ratio 0.95, 95% CI 0.59-1.55, p = 0.84), immune infiltration and antigen presentation distinguished responding tumors, while tumor heterogeneity and estrogen signaling independently associated with resistance. Moreover, patients with ICI-related toxicity had lower levels of immunoregulatory cytokines. Broadly, we establish a framework for ICI response in HR+ breast cancer that warrants diagnostic and therapeutic validation. ClinicalTrials.gov Registration: NCT03051659.

A phase II study of efficacy, toxicity, and the potential impact of genomic alterations on response to eribulin mesylate in combination with trastuzumab and pertuzumab in women with human epidermal growth factor receptor 2 (HER2)+ metastatic breast cancer.

PURPOSE: There are limited data on trastuzumab-pertuzumab (HP)-based treatments beyond the first-line, HER2+ metastatic breast cancer (MBC) setting. We conducted a phase II study of eribulin mesylate, which extends survival in MBC, with HP in patients with previously treated HER2+ MBC to evaluate efficacy, toxicity, and genomic alterations driving therapeutic response. METHODS: After a run-in phase for eribulin dosing, two cohorts were enrolled (Cohort A-no prior pertuzumab; Cohort B-prior pertuzumab). All patients received eribulin 1.4 mg/m2 on days 1, 8 with standard-dose HP on day 1 (21-day cycles). The primary endpoint was objective response rate (ORR). Genomic characterization via whole exome sequencing (WES) was completed on tumor DNA and matched germline DNA from 19 patients. RESULTS: The six-patient run-in established a dose of eribulin 1.4 mg/m2 with HP. Cohorts A and B enrolled 17 and 7 patients, respectively. Accrual stopped early due to an evolving treatment landscape and slow enrollment. The ORR was 26.3% (95% Confidence Interval [CI] 9.2-51.2%) in Cohort A and 0% in Cohort B (95% CI 0-41.0%). WES revealed more frequent alterations in TP53 (p < 0.05, q > 0.05) in patients without clinical benefit (disease control for < 24 weeks) which was not significant after multiple hypothesis correction. CONCLUSION: Eribulin-HP had manageable toxicity and modest clinical activity in patients without prior pertuzumab exposure. This study provides a preliminary landscape of somatic alterations in this patient cohort. Our data add to the literature on how genomic alterations may predict for therapy response/resistance, as we work to individualize choices in a quickly evolving HER2+ MBC treatment landscape. TRIAL REGISTRATION: www.clinicaltrials.gov , NCT01912963. Registered 24 July 2013.

Effectiveness of Blood Lipid Management in Patients With Peripheral Artery Disease.

BACKGROUND: Low-density lipoprotein cholesterol (LDL-C) is associated with heightened risk of major adverse cardiovascular events (MACE) and major adverse limb events (MALE) in peripheral artery disease (PAD). Lipid-lowering therapies (LLT) that reduce LDL-C decrease this risk. OBJECTIVES: The authors examined LLT use and actual achieved LDL-C in PAD. METHODS: PAD patients in MarketScan from 2014 to 2018 were identified. Outcomes included LLT use, defined as high-intensity (HI) (high-intensity statin, statin plus ezetimibe, or PCSK9 inhibitor), low-intensity (any other lipid regimen), or no therapy, and follow-up LDL-C. Factors associated with LDL-C <70 mg/dl were identified with multivariable logistic regression. RESULTS: Among 250,103 PAD patients, 20.5% and 39.5% were treated at baseline with HI and low-intensity LLT, respectively; 40.0% were on no LLT. Over a 15-month median follow-up period, HI LLT use increased by 1.5%. Among 18,747 patients with LDL-C data, at baseline, 25.1% were on HI LLT, median LDL-C was 91 mg/dl, and 24.5% had LDL-C <70 mg/dl. Within the HI LLT subgroup, median LDL-C was 81 mg/dl, and 64% had LDL-C ≥70 mg/dl. At follow-up, HI LLT use increased by 3.7%, median LDL-C decreased by 4.0 mg/dl, and an additional 4.1% of patients had LDL-C <70 mg/dl. HI LLT use was greater after follow-up MACE (55.0%) or MALE (41.0%) versus no ischemic event (26.1%). After MACE or MALE, LDL-C was <70 mg/dl in 41.5% and 36.1% of patients, respectively, versus 27.1% in those without an event. Factors associated with follow-up LDL-C <70 mg/dl included smoking, hypertension, diabetes, prior lower extremity revascularization, and prior myocardial infarction but not prior acute or critical limb ischemia. CONCLUSIONS: In PAD, LLT use is suboptimal, LDL-C remains elevated, and LLT intensity is a poor surrogate for achieved LDL-C. Less aggressive lipid management was observed in PAD versus cardiovascular disease, highlighting missed opportunities for implementation of proven therapies in PAD.

Tumor and immune reprogramming during immunotherapy in advanced renal cell carcinoma.

Immune checkpoint blockade (ICB) results in durable disease control in a subset of patients with advanced renal cell carcinoma (RCC), but mechanisms driving resistance are poorly understood. We characterize the single-cell transcriptomes of cancer and immune cells from metastatic RCC patients before or after ICB exposure. In responders, subsets of cytotoxic T cells express higher levels of co-inhibitory receptors and effector molecules. Macrophages from treated biopsies shift toward pro-inflammatory states in response to an interferon-rich microenvironment but also upregulate immunosuppressive markers. In cancer cells, we identify bifurcation into two subpopulations differing in angiogenic signaling and upregulation of immunosuppressive programs after ICB. Expression signatures for cancer cell subpopulations and immune evasion are associated with PBRM1 mutation and survival in primary and ICB-treated advanced RCC. Our findings demonstrate that ICB remodels the RCC microenvironment and modifies the interplay between cancer and immune cell populations critical for understanding response and resistance to ICB.

Clinical Efficacy and Molecular Response Correlates of the WEE1 Inhibitor Adavosertib Combined with Cisplatin in Patients with Metastatic Triple-Negative Breast Cancer.

PURPOSE: We report results from a phase II study assessing the efficacy of the WEE1 inhibitor adavosertib with cisplatin in metastatic triple-negative breast cancer (mTNBC). PATIENTS AND METHODS: Patients with mTNBC treated with 0-1 prior lines of chemotherapy received cisplatin 75 mg/m2 i.v. followed 21 days later by cisplatin plus adavosertib 200 mg oral twice daily for five doses every 21 days. The study had 90% power to detect the difference between null (20%) and alternative (40%) objective response rates (ORR) with a one-sided type I error of 0.1: an ORR >30% was predefined as making the regimen worthy of further study. RNA sequencing and multiplex cyclic immunofluorescence on pre- and post-adavosertib tumor biopsies, as well as targeted next-generation sequencing on archival tissue, were correlated with clinical benefit, defined as stable disease ≥6 months or complete or partial response. RESULTS: A total of 34 patients initiated protocol therapy; median age was 56 years, 2 patients (6%) had BRCA2 mutations, and 14 (41%) had one prior chemotherapy. ORR was 26% [95% confidence interval (CI), 13-44], and median progression-free survival was 4.9 months (95% CI, 2.3-5.7). Treatment-related grade 3-5 adverse events occurred in 53% of patients, most commonly diarrhea in 21%. One death occurred because of sepsis, possibly related to study therapy. Tumors from patients with clinical benefit demonstrated enriched immune gene expression and T-cell infiltration. CONCLUSIONS: Among patients with mTNBC treated with 0-1 prior lines, adavosertib combined with cisplatin missed the prespecified ORR cutoff of >30%. The finding of immune-infiltrated tumors in patients with clinical benefit warrants validation.

Ischemic Event Rates in Very-High-Risk Adults.

BACKGROUND: The 2018 American Heart Association/American College of Cardiology (AHA/ACC) cholesterol guideline includes recommendations for intensive lipid-lowering therapy in patients at very high risk for atherosclerotic cardiovascular disease (ASCVD) events. OBJECTIVES: This study sought to estimate event rates among adults with a history of ASCVD who met and did not meet the definition of very high risk in the 2018 AHA/ACC cholesterol guideline. METHODS: Data from U.S. adults with health insurance in the MarketScan database who had a history of ASCVD on January 1, 2016 (n = 27,775) were analyzed. Very high risk for ASCVD events was defined as a history of ≥2 major ASCVD events or 1 event and ≥2 high-risk conditions. Patients were followed through December 31, 2017, for ASCVD events, including myocardial infarction, ischemic stroke, and major adverse limb events. RESULTS: Overall, 15,366 patients (55.3%) with ASCVD met the definition of very high risk. Among patients with and without very high risk, the ASCVD event rate per 1,000 person-years was 53.1 (95% confidence interval [CI]: 50.1 to 56.1) and 17.0 (95% CI: 15.2 to 18.9), respectively. Among patients with ≥2 major ASCVD events and with 1 event and ≥2 high-risk conditions, the ASCVD event rate per 1,000 person-years was 89.8 (95% CI: 82.2 to 98.0) and 41.3 (95% CI: 38.3 to 44.4), respectively. The age- and sex-adjusted hazard ratios for ASCVD events among patients with very high risk, overall, with ≥2 major ASCVD events and with 1 event and ≥2 high-risk conditions versus those without very high risk were 2.98 (95% CI: 2.63 to 3.37), 4.89 (95% CI: 4.22 to 5.66), and 2.33 (95% CI: 2.04 to 2.66), respectively. CONCLUSIONS: The 2018 AHA/ACC cholesterol guideline directs intensive lipid-lowering therapy to adults with a very high ASCVD event rate.

Brain activity associated with social exclusion overlaps with drug-related frontal-striatal circuitry in cocaine users: A pilot study.

BACKGROUND: Exposure to various types of stress can elevate craving for cocaine and hasten relapse among substance dependent individuals. This investigation evaluated the effects of social exclusion on brain activity in cocaine dependent individuals. METHOD: Forty three individuals (18 crack-cocaine users, 25 controls) were recruited from the community to participate in functional neuroimaging study in which they performed a simulated 3 person ball-tossing game (Cyberball). Each participant was told that the other 2 players were in nearby MRI scanners. Task blocks included: Inclusion (likelihood of our participant receiving the ball = 50%), Exclusion (likelihood gradually decreases to 0%), and Rest. Self-worth variables (e.g self-esteem, locus of control) were measured before and after the ball-tossing game. General linear model-based statistics were used to measure the brain response to inclusion and exclusion within and between the groups with respect to rest. RESULTS: Relative to controls, cocaine users had significantly more activity during Exclusion versus Inclusion in 3 areas: the right medial frontal gyrus (Brodmann Area 9,10), left ventral lateral frontal gyrus (Brodmann Area 10,47) and right caudate. This was driven by a higher response to social exclusion in the cocaine users. There was no difference between groups in the brain reactivity to social inclusion. CONCLUSION: Cocaine dependent individuals have an amplified brain response to social exclusion stress in cortical regions associated with emotional regulation, arousal, craving and perception of physical pain. These data suggest that there may be a neurological basis for the well-established relationship between social stress and addiction.

Anxiety, sedation, and simulated driving in binge drinkers.

The current study evaluated the relationships among trait anxiety, subjective response to alcohol, and simulated driving following a simulated alcohol binge. Sixty drinkers with a binge history completed the State Trait Anxiety Inventory (STAI), the Alcohol Use Questionnaire, and subsequently completed a driving simulation. Participants were then administered 0.2 g/kg ethanol at 30-min intervals (cumulative dose 0.8 g/kg). Following alcohol consumption, the Biphasic Alcohol Effects Scale (BAES) and visual analog scales of subjective impairment and driving confidence were administered, after which simulated driving was reassessed. Due to the emphasis on simulated driving after drinking in the current study, subjective response to alcohol (i.e., self-reported sedation, stimulation, impairment, and confidence in driving ability) was assessed once following alcohol consumption, as this is the time when drinkers tend to make decisions regarding legal driving ability. Alcohol increased driving speed, speeding tickets, and collisions. Sedation following alcohol predicted increased subjective impairment and decreased driving confidence. Subjective impairment was not predicted by sensitivity to stimulation or trait anxiety. High trait anxiety predicted low driving confidence after drinking and this relationship was mediated by sedation. Increased speed after alcohol was predicted by sedation, but not by trait anxiety or stimulation. Anxiety, combined with the sedating effects of alcohol, may indicate when consumption should cease. However, once driving is initiated, sensitivity to sedation following alcohol consumption is positively related to simulated driving speed.

Impulsivity, attention, memory, and decision-making among adolescent marijuana users.

RATIONALE: Marijuana is a popular drug of abuse among adolescents, and they may be uniquely vulnerable to resulting cognitive and behavioral impairments. Previous studies have found impairments among adolescent marijuana users. However, the majority of this research has examined measures individually rather than multiple domains in a single cohesive analysis. This study used a logistic regression model that combines performance on a range of tasks to identify which measures were most altered among adolescent marijuana users. OBJECTIVES: The purpose of this research was to determine unique associations between adolescent marijuana use and performances on multiple cognitive and behavioral domains (attention, memory, decision-making, and impulsivity) in 14- to 17-year-olds while simultaneously controlling for performances across the measures to determine which measures most strongly distinguish marijuana users from nonusers. METHODS: Marijuana-using adolescents (n = 45) and controls (n = 48) were tested. Logistic regression analyses were conducted to test for: (1) differences between marijuana users and nonusers on each measure, (2) associations between marijuana use and each measure after controlling for the other measures, and (3) the degree to which (1) and (2) together elucidated differences among marijuana users and nonusers. RESULTS: Of all the cognitive and behavioral domains tested, impaired short-term recall memory and consequence sensitivity impulsivity were associated with marijuana use after controlling for performances across all measures. CONCLUSIONS: This study extends previous findings by identifying cognitive and behavioral impairments most strongly associated with adolescent marijuana users. These specific deficits are potential targets of intervention for this at-risk population.

Enhanced inhibition of Listeria monocytogenes by a combination of cold pressed terpeneless Valencia orange oil and antibiotics.

This study was designed to evaluate the ability of cold pressed terpeneless Valencia orange oil (CPTVO) to enhance the effectiveness of antibiotics against 10 strains of Listeria monocytogenes. Disc diffusion assays were performed to determine the effects of CPTVO and two antibiotics with different mechanisms of action (i.e., penicillin and chloramphenicol) individually and in combination with CPTVO. CPTVO alone produced zones ranging from 16.5 to 19.9 mm. Penicillin at 2 or 10 units produced zones ranging from <6 to 13.4 mm, and from 16 to 19.5 mm, respectively. Chloramphenicol at 5 or 30 µg had zones ranging from <6 to 6.9 mm, and from 10.8 to 15.9 mm, respectively. Penicillin (2 and 10 units) plus CPTVO produced zones ranging from 20.2 to 25.3 mm, and from 21.9 to 28 mm, respectively. Chloramphenicol (5 or 30 µg) plus CPTVO produced zones of from 20.1 to 26.6 mm, and from 19.5 to 23.9 mm, respectively. In conclusion, the combination of antibiotics with CPTVO increases their ability to inhibit L. monocytogenes.

Alcohol effects on simulated driving in frequent and infrequent binge drinkers.

OBJECTIVE: Compared with non­bingers, binge drinkers are more likely to drive while intoxicated. The extent to which binge frequency impacts confidence in driving and subsequent driving impairment is unknown. This study compared the effects of an experimenter­delivered alcohol binge on subjective impairment and simulated driving ability in female high­frequency and low­frequency bingers. METHODS: Female drinkers were assigned to high­frequency (n = 30) or low­frequency (n = 30) binge groups based on their Alcohol Use Questionnaire responses. At 30­min intervals within a 2­h period, participants received either a placebo drink (n = 15 per group) or a 0.2 g/kg dose of alcohol (n = 15 per group; cumulative dose 0.8 g/kg). Self­reported impairment, driving confidence, and simulated driving were then measured. RESULTS: Self­reported confidence in driving was significantly lower after alcohol than after placebo in low­frequency but not highfrequency bingers. Self­reported impairment and collisions during simulated driving were significantly greater after alcohol than after placebo in both low­frequency and high­frequency bingers. CONCLUSIONS: The impairing effects of a single alcohol binge on driving ability in women are not influenced by binge frequency. However, high binge frequency may be associated with a less cautious approach to post­binge driving.

Response inhibition impairments predict alcohol-induced sedation.

AIMS: The aim of this study was to probe the relationship between the subjective effects of alcohol and impulsive behavior in social drinkers. METHODS: Fifty social drinkers performed a response-inhibition task before consuming alcohol. A 0.8-g/kg dose of alcohol was administered in a binge-like fashion (0.2 g/kg every 30 min) to the participants over a 2-h time period. Participants then completed questionnaires measuring stimulation, sedation and mood following consumption of alcohol. Linear regression analyses were performed by examining the relationship between performance on the response inhibition impulsivity task and subjective responses to alcohol (i.e. stimulation, sedation and arousal). RESULTS: There was a significant positive relationship found between impulsive responding and self-reported sedation following alcohol consumption. Additionally, there was a significant negative relationship between behavioral impulsivity and self-reported stimulation and arousal following alcohol consumption. CONCLUSION: These results suggest that higher levels of impulsivity are associated with experiencing greater sedating than stimulating effects of alcohol. Individuals with high levels of impulsivity may be less sensitive to the stimulating effects of a specified dose of alcohol, which could lead to these individuals consuming more alcohol to experience the stimulating effects of alcohol.

Inhibition of Listeria monocytogenes by exposure to a combination of nisin and cold-pressed terpeneless Valencia oil.

Listeria monocytogenes is an important foodborne pathogen and its control in foods is a significant challenge. This study evaluated the effectiveness of nisin and cold-pressed terpeneless Valencia oil (CPTVO) on limiting L. monocytogenes growth. Disk diffusion assays were performed to determine the effects of CPTVO and nisin individually and in combination. Together, these antimicrobials produced a zone of inhibition that was significantly larger (P < 0.05) than zones correlating to CPTVO or nisin individually. Furthermore, L. monocytogenesΔsigB had an increased sensitivity to the combination treatment. Growth experiments performed in brain heart infusion (BHI) broth revealed the effects of nisin and CPTVO, individually and in combination on L. monocytogenes growth rate. When L. monocytogenes was grown in BHI containing 0.025% CPTVO and 26 IU/mL nisin, no growth inhibition was observed relative to the control. However, exposure to CPTVO at 0 h followed by the introduction of nisin at 15 h resulted in a statistically significant (P < 0.05) reduction in growth. This approach to inhibiting L. monocytogenes has potential as an all-natural, generally-recognized-as-safe multiple hurdle intervention that may be applicable for ready-to-eat products in which L. monocytogenes is likely to cause foodborne illness.

Efficacy of cold-pressed terpeneless Valencia oil and its primary components on inhibition of Listeria species by direct contact and exposure to vapors.

This study used disk diffusion assays to evaluate the effectiveness of cold-pressed terpeneless Valencia oil (CPTVO) and its primary components (linalool, citral, and decanal) at inhibiting Listeria via direct contact or exposure to vapors. In general, all Listeria strains tested responded similarly to CPTVO and its components. Direct contact with linalool produced zones of inhibition that were significantly smaller (P < 0.0001) than those associated with all other antimicrobials tested. Zones of inhibition for sealed plates were significantly larger (P < 0.0001) than those observed for unsealed plates, although the method for sealing the plates was insignificant. Exposure to CPTVO vapors resulted in zones of inhibition that were significantly smaller than those resulting from decanal vapors (P < 0.0001). The difference observed between the zones of inhibition produced by antimicrobial exposure via vapors or direct contact was only slightly significant (P = 0.02). Antimicrobial essential oil (EO) vapors may be an effective alternative to direct contact EOs to safely and effectively inhibit microorganisms while minimizing undesired organoleptic changes sometimes associated with EO contact. CPTVO and its primary components, decanal and citral, may have potential in the food industry as all natural, generally recognized as safe antimicrobials used in modified atmosphere packaging designed to inhibit Listeria without requiring direct contact with food products.

Teenagers do not always lie: characteristics and correspondence of telephone and in-person reports of adolescent drug use.

Because of the widespread use of drugs by adolescents, there is demand for scientific rigor in sampling and accuracy in methods for ascertaining drug use patterns. The present study: (1) characterized adolescents who responded to advertisements for marijuana users; (2) compared rates of drug use reported on the telephone versus an on-site interview; and (3) examined drug use patterns as a function of parental awareness of drug use. Adolescents, identifying themselves as marijuana users during telephone interviews, reported more use of other drugs than those denying marijuana use. There was a high degree of correspondence between telephone and on-site interviews for all drugs except alcohol, which was reported at a higher rate on-site. Of those reporting marijuana use in the past week, 69% tested positive for marijuana in their urine-drug screens. Finally, marijuana and alcohol use patterns were higher among adolescents whose parents were aware of drug use than those whose parents indicated that their adolescent did not use marijuana. These results indicate that adolescents are willing to self-identify as marijuana users and report drug and alcohol use during telephone interviews. Additionally, parents appear to become more aware of their adolescent's drug use with increased frequency of use.