Recurrent Injecting Drug Use as a Mediator between Psychiatric Disorder and Non-Fatal Overdose.

BACKGROUND: Unintentional drug overdose has increased markedly in the United States. Studies document an association between psychiatric disorder and unintentional overdose; we extend this research through a preliminary test of a causal model of recurrent injection drug use mediating this relationship. METHODS: In a cross-sectional study of 241 adults in New York City with a possible current substance use disorder, we conducted conventional and Imai's mediation analyses to examine if psychiatric disorder is associated with increased prevalence of ever overdosing and if recurrent injection drug use mediates this association. Our cross-sectional data permit the first step of assessing causal models: testing if statistical associations are consistent with the model. RESULTS: Fifty-eight percent of the sample endorsed previous psychiatric disorder diagnosis and 35.7% reported ever overdosing. Imai's mediation analysis showed that, adjusting for covariates, the total association between psychiatric diagnosis and ever overdosing (adjusted prevalence difference [aPD] = 0.16, 95% CI 0.04-0.28) was composed of a direct effect (aPD = 0.09, 95% CI -0.03 - 0.21, p = 0.136) and an indirect effect (aPD = 0.07, 95% CI 0.02-0.13). Recurrent injecting drug use contributed to 42% (ratio of indirect effect to total effect; 95% CI 12 - 100%, p = 0.02) of the association between psychiatric diagnosis and ever overdosing. Conventional mediation analysis produced similar results. CONCLUSIONS: Our results provide a warrant for taking the necessary next step for assessing a causal model using longitudinal data, potentially providing a strong rationale for intervening on psychiatric disorders to stem overdose.

Rapid point-of-care (POC) testing for Hepatitis C antibodies in a very high prevalence setting: persons injecting drugs in Tallinn, Estonia.

BACKGROUND: Between December 2018 and January of 2019, we evaluated the accuracy of the point-of-care Hepatitis C (HCV) antibody test (POC; OraQuick HCV) used at a community-based needle and syringe exchange program serving persons who inject drugs in Tallinn, Estonia. METHODS: We compared the results of screening for HCV antibodies by OraQuick (oral swab) and enzyme immunoassay (EIA; blood draw) and assessed test results implications in a high prevalence setting. Findings Of the 100 participants, 88 (88%) had reactive POC test results, and 93 were HCV antibody positive on EIA testing. Sensitivity, specificity and negative predictive value (NPV) for the POC assay with EIA as the relevant reference test were as follows: 94.6% (95% CI 90.0-99.2%), 100% and 58.3% (95% CI 30.4-86.2%). Of the 12 testing, HCV-negative with the POC only 7 (58.3%) were true negatives. CONCLUSIONS: Oral swab rapid testing HCV screening in this nonclinical setting was sensitive and specific but had unacceptably low NPV. In high prevalence settings, POC tests with high sensitivity and that directly measure HCV RNA may be warranted.

Synthesis of ( R)-Boc-2-methylproline via a Memory of Chirality Cyclization. Application to the Synthesis of Veliparib, a Poly(ADP-ribose) Polymerase Inhibitor.

( R)-Boc-2-methylproline (3a) was synthesized in good yield with excellent stereochemical control from alanine benzyl ester hydrochloride 11. The process, which is based on a modification of one described by Kawabata, proceeds in four steps and requires no chromatography. The product ( R)-Boc-2-methylproline (3a) was then carried forward in three steps to produce veliparib 1, a poly(ADP-ribose) polymerase inhibitor.

Discovery and Development of Metal-Catalyzed Coupling Reactions in the Synthesis of Dasabuvir, an HCV-Polymerase Inhibitor.

Dasabuvir (1) is an HCV polymerase inhibitor which has been developed as a part of a three-component direct-acting antiviral combination therapy. During the course of the development of the synthetic route, two novel coupling reactions were developed. First, the copper-catalyzed coupling of uracil with aryl iodides, employing picolinamide 16 as the ligand, was discovered. Later, the palladium-catalyzed sulfonamidation of aryl nonaflate 33 was developed, promoted by electron-rich palladium complexes, including the novel phosphine ligand, VincePhos (50). This made possible a convergent, highly efficient synthesis of dasabuvir that significantly reduced the mutagenic impurity burden of the process.

Implementing an Updated "Break the Cycle" Intervention to Reduce Initiating Persons into Injecting Drug Use in an Eastern European and a US "opioid epidemic" Setting.

We tested the hypothesis that an updated "Break the Cycle" (BtC) intervention, based in social cognitive theory and motivational interviewing, would reduce the likelihood that current persons who inject drugs (PWID) would assist persons who do not inject drugs (non-PWID) with first injections in Tallinn, Estonia and Staten Island, New York City. 402 PWID were recruited, a baseline interview covering demographics, drug use, and assisting non-PWID with first drug injections was administered, followed by BtC intervention. 296 follow-up interviews were conducted 6 months post-intervention. Percentages assisting with first injections declined from 4.7 to 1.3% (73% reduction) in Tallinn (p < 0.02), and from 15 to 6% (60% reduction) in Staten Island (p < 0.05). Persons assisted with first injections declined from 11 to 3 in Tallinn (p = 0.02) and from 32 to 13 in Staten Island. (p = 0.024). Further implementation research on BtC interventions is urgently needed where injecting drug use is driving HIV/HCV epidemics and areas experiencing opioid epidemics.

Testing a somatization hypothesis to explain the Black-White depression paradox.

PURPOSE: Epidemiologic studies document a lower prevalence of major depression in Blacks than Whites in the United States. This is paradoxical from the perspective of social stress theory. A long-standing claim in the (clinical) literature is that Blacks express depression more somatically than Whites. If true, the diagnostic algorithm may undercount depression in Blacks, since the screening symptoms privilege the psychological rather than somatic dimensions of depression. We test hypotheses that (1) Blacks express depression more somatically than Whites which (2) reduces their likelihood of endorsing screening symptoms, thereby undercounting Blacks' depression and explaining the Black-White depression paradox. METHODS: We use cross-sectional data collected in 1991-92 from the National Longitudinal Alcohol Epidemiologic Survey (n = 42,862) among Blacks and Whites endorsing at least one past-12-month depression symptom. We compare groups on depression somatization and test whether greater somatization in Blacks leads to lower endorsement of psychological screening symptoms, and therefore under-diagnosis. RESULTS: Blacks have higher mean depression somatization scores than Whites (0.28, SE 0.04 vs. 0.15, SE 0.02), t(122) = - 2.15, p = 0.03. This difference is small and driven by Blacks' higher endorsement of 1 somatic symptom (weight/appetite change) and Whites' greater propensity to endorse psychological symptoms. However, Blacks have the same odds as Whites of endorsing screening symptoms, before and after adjusting for somatization. CONCLUSIONS: We find minimal evidence that Blacks express depression more somatically than Whites. Furthermore, this small difference does not appear to inhibit endorsement of diagnostic depression screening symptoms among Blacks, and therefore does not resolve the Black-White depression paradox.

Feasibility of a simple and scalable cognitive-behavioral intervention to treat problem substance use.

OBJECTIVE: Our proof-of-concept study tested a simple cognitive-behavioral strategy based on experimental psychology research that draws on the concept of self-distancing and is consistent with mindfulness principles - using non-first person self-talk when facing substance use cues or cravings -- to help people achieve substance use goals. We evaluated participants' understanding, use, and utility of the intervention at follow-up. METHOD: We recruited 17 New York City residents who used drugs. At baseline, we collected demographic and substance use data and conducted the intervention. At one-week follow-up, participants were asked about their understanding, use, and perceived utility of the intervention, and asked to complete an anonymous five-item assessment of the intervention. RESULTS: Sixteen participants completed follow-up. Understanding was judged "acceptable" or better for 15; 11 used their scripts during follow-up; four described their scripts as very useful, one as moderately, five as a little, and one as not useful. Nine returned assessments; ratings were strongly favorable. CONCLUSIONS: Results from our pilot are encouraging and point to further research on this intervention. The intervention is suitable for integration into longer-term therapy and we envision non-first person self-talk as one strategy alongside others individuals can employ to moderate their substance use.

A qualitative study of persons who inject drugs but who have never helped others with first injections: how their views on helping contrast with the views of persons who have helped with first injections, and implications for interventions.

BACKGROUND: Transitioning from non-injection to injection drug use dramatically escalates health risks. Evidence suggests that people who inject drugs (PWID) help in a majority of others' first injections, yet these helpers represent only a minority of experienced PWID. Recent research has provided insight into this helping process, as reported by helpers. PWID who have never helped, although the majority of PWID, have not previously been the focus of study. To address this gap, we give primary voice to non-helpers' perspectives on the helping process, while also comparing their views with persons in our sample who have helped with first injections. Finally, we consider how non-helpers' perspectives can inform harm reduction interventions to reduce, or make safer, initiation into injecting drug use. METHODS: We conducted audio-recorded, qualitative interviews with 23 current opioid injectors on Staten Island, NY, where the opioid epidemic is pronounced. Seventeen had never helped with first injections and 6 had. Interviews were transcribed verbatim, and three coders used a consensus-developed codebook to code all interviews. Framework analysis was used to identify overarching themes. RESULTS: We identified three key themes in non-helpers' discourse around not helping: altruistic motivations to prevent immediate and delayed harms to individuals injecting for the first time; inhibition due to negative assessments of their own injecting skills; and absolutist ethical convictions against helping. Non-helpers differed from helpers on each theme. CONCLUSIONS: Because most PWID have never helped with first injections, their perspectives on helping warrant consideration and can inform harm reduction interventions to reduce, or make safer, transitions to injection drug use. Their perspectives can be used to broaden the factors PWID consider around questions of promoting injection and helping with others' first injections, including considerations of the moral issues involved in choosing to help or not to help.

Do racial patterns in psychological distress shed light on the Black-White depression paradox? A systematic review.

PURPOSE: Major epidemiologic studies in the US reveal a consistent "paradox" by which psychiatric outcomes such as major depressive disorder (MDD) are less prevalent among Blacks relative to Whites, despite greater exposure to social and economic stressors and worse physical health outcomes. A second paradox, which has received less attention and has never been systematically documented, is the discrepancy between these patterns and Black-White comparisons in psychological distress, which reveal consistently higher levels among Blacks. By systematically documenting the latter paradox, this paper seeks to inform efforts to explain the first paradox. METHODS: We conduct a systematic review of the literature estimating the prevalence of MDD and levels of psychological distress in Blacks and Whites in the US. RESULTS: The literature review yielded 34 articles reporting 54 relevant outcomes overall. Blacks have a lower prevalence of MDD in 8 of the 9 comparisons observed. In contrast, Blacks have higher levels of psychological distress (in terms of "high distress" and mean scores) than Whites in 42 of the 45 comparisons observed. Tests of statistical significance, where available, confirm this discrepant pattern. CONCLUSIONS: A systematic review of the epidemiologic evidence supports the existence of a "double paradox" by which Blacks' lower prevalence of MDD relative to Whites' is inconsistent with both the expectations of social stress theory and with the empirical evidence regarding psychological distress. Efforts to resolve the Black-White depression paradox should account for the discordant distress results, which seem to favor artifactual explanations.

Sexual orientation disparities in mental health: the moderating role of educational attainment.

PURPOSE: Mental health disparities between sexual minorities and heterosexuals remain inadequately understood, especially across levels of educational attainment. The purpose of the present study was to test whether education modifies the association between sexual orientation and mental disorder. METHODS: We compared the odds of past 12-month and lifetime psychiatric disorder prevalence (any Axis-I, any mood, any anxiety, any substance use, and comorbidity) between lesbian, gay, and bisexual (LGB) and heterosexual individuals by educational attainment (those with and without a bachelor's degree), adjusting for covariates, and tested for interaction between sexual orientation and educational attainment. Data are drawn from the National Epidemiologic Survey on Alcohol and Related Conditions, a nationally representative survey of non-institutionalized US adults (N = 34,653; 577 LGB). RESULTS: Sexual orientation disparities in mental health are smaller among those with a college education. Specifically, the disparity in those with versus those without a bachelor's degree was attenuated by 100 % for any current mood disorder, 82 % for any current Axis-I disorder, 76 % for any current anxiety disorder, and 67 % for both any current substance use disorder and any current comorbidity. Further, the interaction between sexual orientation and education was statistically significant for any current Axis-I disorder, any current mood disorder, and any current anxiety disorder. Our findings for lifetime outcomes were similar. CONCLUSIONS: The attenuated mental health disparity at higher education levels underscores the particular risk for disorder among LGBs with less education. Future studies should consider selection versus causal factors to explain the attenuated disparity we found at higher education levels.

An open label pilot study to evaluate the efficacy of Spanish black radish on the induction of phase I and phase II enzymes in healthy male subjects.

BACKGROUND: Humans are exposed to toxins which accumulate in the body, and are detoxified primarily in the liver. Studies have shown that cruciferous vegetables (such as radishes) may be beneficial to health by aiding detoxification of toxins in the liver. METHODS: This single-centre, open-label, pilot study investigated the effect of a dietary supplement containing Spanish Black Radish on hepatic function in healthy males by monitoring the profiles of plasma and urine acetaminophen metabolites and serum hormone concentrations at baseline and after 4 weeks of supplementation. A paired t-test was used to compare pre- and post-treatment of plasma and urine acetaminophen metabolite profiles, serum hormone concentrations and safety end points. RESULTS: Area under the curve (AUC) from 0 to 8 hours for the acetaminophen glucuronide metabolite and unchanged acetaminophen in plasma decreased from baseline to week 4 by 9% (P = 0.004) and 40% (P = 0.010), respectively. The AUC from 0 to 8 hours for acetaminophen sulfate and mercapturate metabolites in the urine increased by 11% (P = 0.010) and 37% (P = 0.024), respectively, from baseline to week 4. The AUC from 0 to 8 hours of serum estradiol-17ß decreased by 10% from baseline to week 4 (P = 0.005). All measures of clinical safety remained within acceptable laboratory ranges, however a significant reduction in plasma γ-glutamyl transferase levels was noted after 4 weeks of Spanish Black Radish treatment (P = 0.002). CONCLUSIONS: These changes in metabolite and hormone levels indicate that Spanish Black Radish supplements have a positive influence on the detoxification of acetaminophen suggesting up-regulation of phase I and phase II liver enzymes. This study was sponsored by Standard Process Inc. TRIAL REGISTRATION: ClinicalTrials.gov registration number NCT02137590 (Date of registration: May 12, 2014).

Racial differences in depression in the United States: how do subgroup analyses inform a paradox?

PURPOSE: Non-Hispanic Blacks in the US have lower rates of major depression than non-Hispanic Whites, in national household samples. This has been termed a "paradox," as Blacks suffer greater exposure to social stressors, a risk factor for depression. Subgroup analyses can inform hypotheses to explain this paradox. For example, it has been suggested that selection bias in household samples undercounts depression in Blacks; if selection is driving the paradox, Black-White differences should be most pronounced among young men with low education. METHODS: We examined Black-White differences in lifetime major depression in subgroups defined simultaneously by sex, age, and education using data from the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC) and the Collaborative Psychiatric Epidemiology Surveys (CPES). RESULTS: In NESARC and CPES, Blacks had lower odds than Whites of lifetime major depression in 21 and 23 subgroups, respectively, of 24. All statistically significant differences were in subgroups favoring Blacks, and lower odds in Blacks were more pronounced among those with more education. CONCLUSIONS: These results suggest that hypotheses to explain the paradox must posit global mechanisms that pertain to all subgroups defined by sex, age, and education. Results do not lend support for the selection bias hypothesis.

Adapted "Break the Cycle for Avant Garde" intervention to reduce injection assisting and promoting behaviours in people who inject drugs in Tallinn, Estonia: A pre- post trial.

In the context of established and emerging injection drug use epidemics, there is a need to prevent and avert injection drug use. We tested the hypothesis that an individual motivation and skills building counselling, adapted and enhanced from Hunt's Break the Cycle intervention targeting persons currently injecting drugs would lead to reduction in injection initiation-related behaviours among PWID in Tallinn, Estonia. For this quasi-experimental study, pre-post outcome measures included self-reported promoting behaviours (speaking positively about injecting to non-injectors, injecting in front of non-injectors, offering to give a first injection) and injection initiation behaviours (assisting with or giving a first injection) during the previous 6 months. Of 214 PWID recruited, 189 were retained (88.3%) for the follow-up at 6 months. The proportion of those who had injected in front of non-PWID significantly declined from 15.9% to 8.5%, and reporting assisting with 1st injection from 6.4% to 1.06%. Of the current injectors retained in the study, 17.5% reported not injecting drugs at the follow up. The intervention adapted for the use in the setting of high prevalence of HIV and relatively low prevalence of injection assisting, tested proved to be effective and safe.

Spanish black radish (Raphanus sativus L. Var. niger) diet enhances clearance of DMBA and diminishes toxic effects on bone marrow progenitor cells.

Vegetables of the Cruciferae family contain high levels of glucosinolates, metabolites of which are believed to enhance detoxification. Spanish black radishes (SBR) contain 4× more glucosinolates than other crucifers. This study examined whether feeding mice a diet containing 20% SBR for 2 wk could enhance metabolism of 7,12-dimethylbenz(a)anthracene (DMBA) and inhibit DMBA-mediated bone marrow toxicity. Expression of Phase I and II detoxification enzymes was significantly greater for mice fed SBR than control diet. Six hours after DMBA administration, the blood levels of DMBA in mice fed the SBR diet were significantly lower than mice fed a control diet. DMBA reduced bone marrow cells in mice fed control diet to a significantly greater extent than mice fed the SBR diet. Colony forming assays demonstrated that mice on the SBR diet had 1) less reduction in lymphoid CFU-preB progenitor cells, 2) greater recovery of CFU-preB progenitor cells at 168 h, and 3) less reduction of CFU-GM progenitor cells at 6 h. Therefore, mice fed a 20% SBR diet for 2 wk had greater expression of detoxification enzymes, faster metabolism of DMBA, and a reduction in DMBA-induced bone marrow toxicity. Overall, these results support the hypothesis that glucosinolates in SBR are protective against acute toxicity.

Disease-Specific Health Disparities: A Targeted Review Focusing on Race and Ethnicity.

BACKGROUND: Wide disparities in health status exist in the United States across race and ethnicity, broadly driven by social determinants of health-most notably race and ethnic group differences in income, education, and occupational status. However, disparities in disease frequency or severity remain underappreciated for many individual diseases whose distribution in the population varies. Such information is not readily accessible, nor emphasized in treatment guidelines or reviews used by practitioners. Specifically, a summary on disease-specific evidence of disparities from population-based studies is lacking. Our goal was to summarize the published evidence for specific disease disparities in the United States so that this knowledge becomes more widely available "at the bedside". We hope this summary stimulates health equity research at the disease level so that these disparities can be addressed effectively. METHODS: A targeted literature review of disorders in Pfizer's current pipeline was conducted. The 38 diseases included metabolic disorders, cancers, inflammatory conditions, dermatologic disorders, rare diseases, and infectious targets of vaccines under development. Online searches in Ovid and Google were performed to identify sources focused on differences in disease rates and severity between non-Hispanic Whites and Black/African Americans, and between non-Hispanic Whites and Hispanics. As a model for how this might be accomplished for all disorders, disparities in disease rates and disease severity were scored to make the results of our review most readily accessible. After primary review of each condition by one author, another undertook an independent review. Differences between reviewers were resolved through discussion. RESULTS: For Black/African Americans, 29 of the 38 disorders revealed a robust excess in incidence, prevalence, or severity. After sickle cell anemia, the largest excesses in frequency were identified for multiple myeloma and hidradenitis suppurativa. For Hispanics, there was evidence of disparity in 19 diseases. Most notable were metabolic disorders, including non-alcoholic steatohepatitis (NASH). CONCLUSIONS: This review summarized recent disease-specific evidence of disparities based on race and ethnicity across multiple diseases, to inform clinicians and health equity research. Our findings may be well known to researchers and specialists in their respective fields but may not be common knowledge to health care providers or public health and policy institutions. Our hope is that this effort spurs research into the causes of the many disease disparities that exist in the United States.

Correlation of tumor growth suppression and methionine aminopetidase-2 activity blockade using an orally active inhibitor.

This laboratory and others have shown that agents that inhibit the in vitro catalytic activity of methionine aminopeptidase-2 (MetAP2) are effective in blocking angiogenesis and tumor growth in preclinical models. However, these prototype MetAP2 inhibitors are clearly not optimized for therapeutic use in the clinic. We have discovered an orally active class of MetAP2 inhibitors, the anthranilic acid sulfonamides exemplified by A-800141, which is highly specific for MetAP2. This orally bioavailable inhibitor exhibits an antiangiogenesis effect and a broad anticancer activity in a variety of tumor xenografts including B cell lymphoma, neuroblastoma, and prostate and colon carcinomas, either as a single agent or in combination with cytotoxic agents. We also have developed a biomarker assay to evaluate in vivo MetAP2 inhibition in circulating mononuclear cells and in tumors. This biomarker assay is based on the N-terminal methionine status of the MetAP2-specific substrate GAPDH in these cells. In cell cultures in vitro, the sulfonamide MetAP2 inhibitor A-800141 caused the formation of GAPDH variants with an unprocessed N-terminal methionine. A-800141 blocked tumor growth and MetAP2 activity in a similar dose-response in mouse models, demonstrating the antitumor effects seen for A-800141 are causally connected to MetAP2 inhibition in vivo. The sulfonamide MetAP2 inhibitor and GAPDH biomarker in circulating leukocytes may be used for the development of a cancer treatment.

A Multistage Process Model of How a Person Who Currently Injects Drugs Comes to Assist Persons Who Do not Inject with Their First Injections.

Injecting drugs for the first time almost always requires assistance from an experienced person who injects drugs (PWID). While there has been moderate amount of research on PWID who assist with first injections, most of this research has focused on identifying characteristics of PWID who assist with first injections. We do not have a formal model that describes how the minority of PWID come to assist do so, while the majority never assist. Through comparison of persons who did or did not recently assist with first injections using data from PWID in Tallinn, Estonia (N = 286) and Staten Island, New York City (N = 101), we developed a formal multi-stage model of how PWID come to assist with first injections. The model had a primary pathway 1) of engaging in "injection promoting" behaviors, 2) being asked to assist, and 3) assisting. Statistical testing using odds ratios showed participation in each stage was strongly associated with participation in the next stage (all odds ratios >3.0) and the probabilities of assisting significantly increased with participation in the successive stages. We then used the model to compare engagement in the stages pre-vs. post participation in an intervention, and to compare persons who recently assisted to persons who had assisted in the past but had not recently assisted and to persons who had never assisted. Advantages of a formal model for how current PWID come to assist with first injections include: facilitating comparisons across different PWID populations and assessing strengths and limitations of interventions to reduce assisting with first injections.

Aqueous extracts from dietary supplements influence the production of inflammatory cytokines in immortalized and primary T lymphocytes.

BACKGROUND: Congaplex and Immuplex are dietary supplements that have been traditionally used to support immune system function. The purpose of these experiments was to determine whether Congaplex and Immuplex affect immune function using primary and immortalized T lymphocytes. METHODS: Immortalized CEM and Jurkat T lymphocytes and primary peripheral mononuclear blood cells (PBMCs) were treated with the aqueous extracts from Congaplex and Immuplex to determine the effects of these products on cytokine production in activated T lymphocytes. RESULTS: Congaplex enhanced phytohemagglutinin/phorbol 12-myristate 13-acetate (PHA/PMA) stimulation of both CEM and Jurkat cells as measured by the production of cytokines, while Immuplex suppressed PHA/PMA-induced production of cytokines, with the exception of interleukin (IL)-8 which was enhanced by Immuplex. In vitro treatment of PBMCs from 10 healthy donors with Congaplex or Immuplex decreased PHA-stimulated production of interferon (IFN)-gamma but increased the production of IL-13. CONCLUSIONS: While the effects of Congaplex and Immuplex differed in these two models, these data demonstrate that the aqueous extracts from these two dietary supplements can affect the inflammatory response of T lymphocytes.

Purple carrot (Daucus carota L.) polyacetylenes decrease lipopolysaccharide-induced expression of inflammatory proteins in macrophage and endothelial cells.

Carrots ( Daucus carota L.) contain phytochemicals including carotenoids, phenolics, polyacetylenes, isocoumarins, and sesquiterpenes. Purple carrots also contain anthocyanins. The anti-inflammatory activity of extracts and phytochemicals from purple carrots was investigated by determining attenuation of the response to lipopolysaccharide (LPS). A bioactive chromatographic fraction (Sephadex LH-20) reduced LPS inflammatory response. There was a dose-dependent reduction in nitric oxide production and mRNA of pro-inflammatory cytokines (IL-6, IL-1beta, TNF-alpha) and iNOS in macrophage cells. Protein secretions of IL-6 and TNF-alpha were reduced 77 and 66% in porcine aortic endothelial cells treated with 6.6 and 13.3 microg/mL of the LH-20 fraction, respectively. Preparative liquid chromatography resulted in a bioactive subfraction enriched in the polyacetylene compounds falcarindiol, falcarindiol 3-acetate, and falcarinol. The polyacetylenes were isolated and reduced nitric oxide production in macrophage cells by as much as 65% without cytotoxicity. These results suggest that polyacetylenes, not anthocyanins, in purple carrots are responsible for anti-inflammatory bioactivity.

Frequency and factors associated with providing injection initiation assistance in Tallinn, Estonia.

Injection drug use is expanding in numerous regions in the world. Persons who inject drugs (PWID) play an important role encouraging new persons into injecting, by providing injection initiation assistance ("assisting" behaviors) and stimulating interest in injection ("promoting" behaviors). OBJECTIVES: To describe the prevalence of assisting and promoting behaviors, and to identify factors associated with assisting, among PWID in Tallinn, Estonia. METHODS: In 2016, PWID were recruited through respondent-driven sampling (RDS), interviewed, and HIV tested. RDS weights were used to estimate the prevalence of assisting and promoting behaviors and, in multivariable regression modeling, to identify factors associated with assisting. RESULTS: Among 299 PWID recruited, 13.7% had ever assisted a non-PWID with their first injection. Regarding past-six-month promoting behaviors: 9.4% talked positively about injecting to non-PWID, 16.2% injected in front of non-PWID, and 0.6% offered to help with a first injection. Significant predictors of ever assisting with a first injection included: gender (men: aOR 6.31, 95% CI 2.02-19.74); age (30 years or younger: aOR 3.89, 95% CI 1.40-10.16); receptive sharing of syringes or needles (aOR 4.73, 95% CI 1.32-16.98); ever testing for HIV (aOR 8.44, 95% CI 1.15-62.07); and having peers who helped someone with their first injection (aOR 3.44, 95% CI 1.31-9.03). CONCLUSION: Demographic and drug-use related factors are associated with having initiated someone into injecting. Interventions targeting PWID and non-PWID are needed to prevent injection initiation.