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Background: The ways in which young people learn about cannabis product availability and where they obtain cannabis products are important to understand for prevention and intervention efforts., Methods: Young adults who reported past month cannabis use (N = 758) completed an online survey in 2018-2019 on how they obtained cannabis and the products they used in a newly legalized market in Los Angeles (mean age 21.6; 44% Hispanic, 27% white, 15% Asian)., Results: Overall, 59.1% obtained cannabis from recreational cannabis retailers (RCRs), 51.5% from family or friends, 39.1% from medical cannabis dispensaries (MCDs), and 5.5% from strangers or dealers in the past month. Compared to those getting cannabis from family or friends, those getting cannabis from MCDs or RCRs spent more money, used more cannabis products, were more likely to use alone, used greater quantities of bud/flower, and reported more consequences from use. Further, those obtaining cannabis from MCDs were more likely to screen positive for cannabis use disorder (CUD). For type of products, those obtaining cannabis from MCDs or RCRs were more likely to use joints, bongs, pipes, dabs, vape, and consume edibles relative to those obtaining from family or friends. Subgroup differences were found for both source patterns and cannabis-related outcomes. Males and those with a cannabis medical card reported spending more money on cannabis, using more types of products, and indicated more frequent use and greater CUD symptoms and consequences. Compared to Whites, Blacks spent more money on cannabis and used more products, and Hispanics reported using more products and greater quantities of cannabis bud/flower., Conclusions: Findings highlight the different ways that young adults obtain cannabis, and how young adults with a medical cannabis card may be at greater risk for problems compared to young adults who use cannabis recreationally., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Tertiary lymphoid structures (TLS) are ectopic lymphoid aggregates that phenotypically resemble conventional secondary lymphoid organs and are commonly found at sites of chronic inflammation. They are also found in a wide variety of primary and metastatic human tumors. The presence of tumor-associated TLS (TA-TLS) is associated with prolonged patient survival, higher rates of disease-free survival, and a favorable response to current cancer therapies. However, the immune responses that occur in these structures, and how they contribute to improved clinical outcomes, remain incompletely understood. In addition, it is unknown how heterogeneity in TA-TLS cellular composition, structural organization, and anatomic location influences their functionality and prognostic significance. Understanding more about TA-TLS development, formation, and function may offer new therapeutic options to modulate antitumor immunity., (©2020 American Association for Cancer Research.)

Background: Substantial investment has gone into research on the efficacy and effectiveness of pharmaceutical and nonpharmacologic interventions for chronic pain. However, synthesizing this extensive literature is challenging because of differences in the outcome measures used in studies of similar or competing interventions. The absence of a common metric makes it difficult to replicate findings, pool data from multiple studies, resolve conflicting conclusions, or reach consensus when interpreting findings., Methods: This study has a seven-member Advisory Council of chronic pain experts. Preliminary analyses will be performed on data from several large existing datasets; intermediate analyses will be performed using primary data collected from Amazon's Mechanical Turk (MTurk); and cross-validation will use primary data collected from a nationally-representative, probability-based panel. Target sample size for both primary datasets is 1500. The three study aims are as follows: Aim 1 will develop and evaluate links between the 29-item Patient-Reported Outcomes Measurement Information System (PROMIS®-29) and legacy measures used for chronic pain such as the Roland-Morris Disability Questionnaire (RMDQ) and the Oswestry Disability Index (ODI). We will assess the best method of score linking and create crosswalk tables. Aim 2 will evaluate and refine the Impact Stratification Score (ISS) based on 9 PROMIS-29 items and proposed by the NIH Research Task Force on chronic low back pain. We will evaluate the ISS in terms of other indicators of condition severity and patient prognosis and outcomes and identify cut-points to stratify chronic pain patients into subgroups. Aim 3 will evaluate the strengths and limitations of MTurk as a data collection platform for estimating chronic pain by comparing its data to other data sources., Discussion: The accomplishment of Aims 1 and 2 will allow direct comparison of results across past and future studies of chronic pain. These comparisons will help us to understand different results from seemingly similar studies, and to determine the relative effectiveness of all pharmaceutical and nonpharmacologic interventions for chronic pain across different trials. Aim 3 findings will provide valuable information to researchers about the pros and cons of using the MTurk platform for research-based data collection., Trial Registration: ClinicalTrials.gov: NCT04426812 ; June 10, 2020.

Purpose: This study provides information on how the coronavirus disease 2019 (COVID-19) outbreak is affecting emerging adults currently or recently homeless in terms of engagement in protective behaviors, mental health, substance use, and access to services., Methods: Ninety participants in an ongoing clinical trial of a risk reduction program for homeless, aged 18-25 years, were administered items about COVID-19 between April 10 and July 9, 2020., Results: Most participants reported engaging in COVID-19 protective behaviors. Past week mental health symptoms were reported by 38%-48% of participants, depending on symptoms. Among those who used substances before the outbreak, 16%-28% reported increased use of alcohol, tobacco, and marijuana. More than half of the participants reported increased difficulty meeting basic needs (e.g., food), and approximately 32%-44% reported more difficulty getting behavioral health services since the outbreak., Conclusions: Innovative strategies are needed to address the increased behavioral health needs of young people experiencing homelessness during events such as the COVID-19 outbreak., (Copyright © 2020 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.)

Background: Intensive lifestyle interventions (LI) improve outcomes in obesity and type 2 diabetes but are not currently available in usual care., Objective: To compare the effectiveness and costs of two group LI programs, in-person LI and telephone conference call (telephone LI), to medical nutrition therapy (MNT) on weight loss in primary care patients with type 2 diabetes., Design: A randomized, assessor-blinded, practice-based clinical trial in three community health centers and one hospital-based practice affiliated with a single health system., Participants: A total of 208 primary care patients with type 2 diabetes, HbA1c 6.5 to < 11.5, and BMI > 25 kg/m 2 (> 23 kg/m 2 in Asians)., Interventions: Dietitian-delivered in-person or telephone group LI programs with medication management or MNT referral., Main Measures: Primary outcome: mean percent weight change., Secondary Outcomes: 5% and 10% weight loss, change in HbA1c, and cost per kilogram lost., Key Results: Participants' mean age was 62 (SD 10) years, 45% were male, and 77% were White, with BMI 35 (SD 5) kg/m 2 and HbA1c 7.7 (SD 1.2). Seventy were assigned to in-person LI, 72 to telephone LI, and 69 to MNT. The mean percent weight loss (95% CI) at 6 and 12 months was 5.6% (4.4-6.8%) and 4.6% (3.1-6.1%) for in-person LI, 4.6% (3.3-6.0%) and 4.8% (3.3-6.2%) for telephone LI, and 1.1% (0.2-2.0%) and 2.0% (0.9-3.0%) for MNT, with statistically significant differences between each LI arm and MNT (P < 0.001) but not between LI arms (P = 0.63). HbA1c improved in all participants. Compared with MNT, the incremental cost per kilogram lost was $789 for in-person LI and $1223 for telephone LI., Conclusions: In-person LI or telephone group LI can achieve good weight loss outcomes in primary care type 2 diabetes patients at a reasonable cost., Clinical Trial Registration: ClinicalTrials.gov Identifier: NCT02320253.

Background: Young people experiencing homelessness have alarmingly high rates of alcohol and other drug (AOD) use, which is associated with sexual risk behaviors such as unprotected sex, trading sex, and sex with multiple casual partners. Few risk reduction programs for this population have been developed and rigorously evaluated, particularly those that address both of these interrelated behaviors, use a collaborative and non-judgmental approach, and are feasible to deliver in settings where homeless young people seek services. This paper describes the protocol of a study evaluating a four-session Motivational Interviewing (MI)-based group risk reduction intervention for this population. The protocol has been shown to be efficacious in pilot work over 3 months with 200 homeless young adults [1]. The current study seeks to refine the intervention protocol and evaluate the program on a larger scale., Methods/design: In a cluster-cross-over randomized controlled trial, 18-25 year olds will receive the AWARE risk reduction program (n = 200) or standard care (n = 200) at one of three drop-in centers serving homeless youth in the Los Angeles area. We will evaluate intervention effects on primary outcomes of AOD use and sexual risk behavior, as well as secondary outcomes of health-related quality of life and social stability, over a 12-month period., Discussion: This project has the potential to fill a significant gap in prevention services by demonstrating that a brief intervention, feasible to deliver within settings where young people experiencing homelessness typically seeks services, can significantly reduce the interrelated problems of AOD use and sexual risk behavior. Trial registration ClinicalTrials.gov Identifier: NCT03735784. Registered November 18, 2018, https://clinicaltrials.gov/ct2/show/record/NCT03735784 (retrospectively registered).

The changing legal landscape of cannabis in the USA has coincided with changes in how cannabis is used, including its co-use with other substances. This study analyzed 10 years of data from a diverse cohort of youth (N = 2429; 54% Hispanic, 16% Asian, 16% white, 3% black, 10% multiracial) to examine predictors in early and late adolescence of co-use of alcohol with cannabis (AC) and tobacco with cannabis (TC) at age 21. Two forms of co-use were examined: concurrent (use of both substances in past month) and sequential (use of one substance right after the other). Analyses focused on four predictor domains: individual (e.g., resistance self-efficacy), peer (e.g., time spent around peers who use), family (e.g., sibling use), and neighborhood (i.e., perceived alcohol and drug problems in neighborhood). For each co-use combination (AC or TC), we estimated parallel process piecewise latent growth models in a structural equation modeling framework using Mplus v8. The final AC and TC co-use models included all predictor variables from the four domains. Increases in positive expectancies and time spent around peers who use AC, as well as steeper decreases in resistance self-efficacy, were all related to a greater likelihood of AC co-use in young adulthood. Increases in sibling TC use and time spent around peers who use TC, as well as steeper decreases in resistance self-efficacy, were all related to a greater likelihood of TC co-use in young adulthood. Overall, findings highlight the importance of addressing peer influence in prevention programming during both early and late adolescence.

Pericyte loss and deficient vascular platelet-derived growth factor receptor-β (PDGFRβ) signaling are prominent features of the blood-brain barrier breakdown described in Alzheimer's disease (AD) that can predict cognitive decline yet have never been studied in the retina. Recent reports using noninvasive retinal amyloid imaging, optical coherence tomography angiography, and histological examinations support the existence of vascular-structural abnormalities and vascular amyloid β-protein (Aβ) deposits in retinas of AD patients. However, the cellular and molecular mechanisms of such retinal vascular pathology were not previously explored. Here, by modifying a method of enzymatically clearing non-vascular retinal tissue and fluorescent immunolabeling of the isolated blood vessel network, we identified substantial pericyte loss together with significant Aβ deposition in retinal microvasculature and pericytes in AD. Evaluation of postmortem retinas from a cohort of 56 human donors revealed an early and progressive decrease in vascular PDGFRβ in mild cognitive impairment (MCI) and AD compared to cognitively normal controls. Retinal PDGFRβ loss significantly associated with increased retinal vascular Aβ 40 and Aβ 42 burden. Decreased vascular LRP-1 and early apoptosis of pericytes in AD retina were also detected. Mapping of PDGFRβ and Aβ 40 levels in pre-defined retinal subregions indicated that certain geometrical and cellular layers are more susceptible to AD pathology. Further, correlations were identified between retinal vascular abnormalities and cerebral Aβ burden, cerebral amyloid angiopathy (CAA), and clinical status. Overall, the identification of pericyte and PDGFRβ loss accompanying increased vascular amyloidosis in Alzheimer's retina implies compromised blood-retinal barrier integrity and provides new targets for AD diagnosis and therapy.

Background: An increasing number of states have laws for the legal sale of recreational and medical cannabis out of brick-and-mortar storefront locations. Given the proliferation of cannabis outlets and their potential for impact on local economies, neighborhood structures, and individual patterns of cannabis use, it is essential to create practical and thorough methods to capture the location of such outlets for research purposes. However, methods used by researchers vary greatly between studies and often do not include important information about the retailer's license status and storefront signage., Objective: The aim of this study was to find methods for locating and observing cannabis outlets in Los Angeles County after the period when recreational cannabis retailers were granted licenses and allowed to be open for business., Methods: The procedures included searches of online cannabis outlet databases, followed by methods to verify each outlet's name, address, license information, and open status. These procedures, conducted solely online, resulted in a database of 531 outlets. To further verify each outlet's information and collect signage data, we conducted direct observations of the 531 identified outlets., Results: We found that 80.9% (430/531) of these outlets were open for business, of which 37.6% (162/430) were licensed to sell cannabis. Unlicensed outlets were less likely to have signage indicating the store sold cannabis, such as a green cross, which was the most prevalent form of observed signage. Co-use of cannabis and tobacco/nicotine has been found to be a substantial health concern, and we observed that 40.6% (175/430) of cannabis outlets had a tobacco/nicotine outlet within sight of the cannabis outlet. Most (350/430, 81.4%) cannabis outlets were located within the City of Los Angeles, and these outlets were more likely to be licensed than outlets outside the city., Conclusions: The findings of this study suggest that online searches and observational methods are both necessary to best capture accurate and detailed information about cannabis outlets. The methods described here can be applied to other metropolitan areas to more accurately capture the availability of cannabis in an area., (©Eric R R Pedersen, Caislin Firth, Jennifer Parker, Regina A Shih, Steven Davenport, Anthony Rodriguez, Michael S Dunbar, Lisa Kraus, Joan S Tucker, Elizabeth J D'Amico. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 26.02.2020.)

Background: Although most young adults drink alcohol, there are specific drinking contexts that are associated with increased risk for alcohol-related consequences. One such drinking context is pregaming, which typically involves heavy drinking in brief periods of time and has consistently been linked to consequences within the pregaming event itself, on a night after pregaming, and in the long-term. Intervention efforts that specifically target this risky behavior are needed, but these efforts need to be informed by empirical work to better understand what behaviors young people engage in that can protect them from pregaming-related harms. Purpose: We designed this study to create a measure of protective behavioral strategies that young people use before, during, and after pregaming to inform future intervention work. Methods: We tested an item pool with 363 young adult college students who engaged in pregaming in the past year and conducted exploratory factor analysis to develop a 19-item Protective Behavioral Strategies for Pregaming (PBSP) scale, which featured four subscales of safety and familiarity, setting drink limits, pacing strategies, and minimizing intoxication. Results: Each subscale negatively and significantly correlated with measures of alcohol use and consequences, though subscales differed in their associations with specific pregaming outcomes and by sex. Conclusion: This initial exploratory examination of the PBSP scale's psychometric properties suggests that use of protective behavioral strategies used specifically during pregaming events may protect young people from heavy drinking and harms. More research with the PBSP scale is encouraged to determine its practical utility as a clinical and assessment tool with young people.

Aims: We investigated associations between the density of medical marijuana dispensaries (MMDs) around young adults' homes and marijuana use outcomes., Design: Secondary data analysis., Setting: Los Angeles County, CA, USA., Participants: A total of 1887 participants aged 18-22 years, surveyed online in 2016-17., Measurements: Outcomes were past-month marijuana use (number of days used, number of times each day), positive expectancies and perceived peer use. Density was measured as the total number of MMDs and number of MMDs with storefront signage indicative of marijuana sales, within 4 miles of respondents' homes., Findings: Eighty-four per cent of respondents had 10 or more MMDs within 4 miles of their homes. Multiple linear regression analyses that adjusted for individual-level socio-demographic characteristics and neighborhood socio-economic status indicated that living near a higher number of MMDs was associated with greater number of days used in the past month [β = 0.025; 95% confidence interval (CI) = 0.001, 0.049; P = 0.04] and higher positive marijuana expectancies (β = 0.003; 95% CI = 0.001, 0.007; P = 0.04). Living near more MMDs with storefront signage had a four- to six-fold larger effect on number of times used per day and positive expectancies, respectively, compared with associations with the total MMD count. Adjusting for medical marijuana card ownership attenuated the association with number of days used in the past month and positive expectancies, and an unexpected association emerged between higher MMD density and fewer number of times used each day (β = -0.005; 95% CI = -0.009, -0.001; P = 0.03)., Conclusions: For young adults in Los Angeles County, living near more medical marijuana dispensaries (MMDs) is positively associated with more frequent use of marijuana within the past month and greater expectations of marijuana's positive benefits. MMDs with signage show stronger associations with number of times used each day and positive expectancies., (© 2019 Society for the Study of Addiction.)

A total of 67 pairs of female roommates were randomized into a diet condition: (1) both ate normally; (2) one dieted, the other ate normally; and (3) both dieted. Adherence, weight loss, anxiety, depression, disordered eating symptoms, and stress were measured. Dieters lost more weight than non-dieters, but average loss was <1 pound. Pairs where both dieted reported higher anxiety, depression, and disordered eating than one-dieter pairs. Structural equation models revealed an interrelated network of stress, anxiety, depression, and disordered eating. This was weakest when one roommate dieted. The "buddy system" may not promote weight loss, but living with a non-dieting partner may buffer consequences.

Objective: Studies have documented greater risk for heavy marijuana use and consequences among adolescents and young adults who have acquired medical marijuana cards. With the cards, they are enrolled in their state's medical marijuana program and granted access to medical marijuana dispensaries. It is unknown, however, what factors influence young people to acquire medical marijuana cards, such as whether they seek out medical marijuana cards for the mental and physical health concerns that marijuana is targeted to address or whether they seek out medical marijuana cards solely because they are heavier users., Method: There were 264 participants (54% female) in the current study, which used longitudinal data (Time 1 and Time 2, 1 year later) to compare young adult marijuana users who did not have a medical marijuana card at either time point (n = 215) with marijuana users who reported acquiring a medical marijuana card by Time 2 (n = 49; 19% of the sample). We used logistic regression to predict participants' acquisition of a medical marijuana card at Time 2 from Time 1 demographic factors, mental health symptoms of anxiety and depression, reports of poor physical health and symptoms, and frequency of use., Results: Analyses indicated that young adults who were male (odds ratio = 2.91) and who reported more frequent marijuana use (odds ratio = 1.07) were at greater odds of acquiring a medical marijuana card over the study period. None of the mental or physical health concerns predicted card acquisition., Conclusions: Findings suggest that more frequent use, not necessarily mental and physical health concerns, is a main influence on medical marijuana card acquisition.

Background: Cannabis and tobacco co-use is a growing concern, yet little is known about its developmental course or associated outcomes during emerging adulthood. This study examines developmental trajectories of cannabis and tobacco co-use from adolescence to emerging adulthood, associations of co-use trajectories with four domains of functioning, and differences across racial/ethnic groups., Methods: Survey data come from a racially/ethnically diverse and predominantly California-based cohort that completed 10 surveys from 2008 (wave 1: mean age 11.5; n = 6,509) to 2018 (wave 10: mean age 20.7; n = 2,429). Co-use was defined as use of both cannabis and tobacco (cigarettes or smokeless tobacco) in the past 30 days. Trajectories of use were examined using latent growth modeling in a structural equation modeling framework., Results: Prevalence of cannabis and tobacco co-use increased from 0.3% at wave 1 to 9.5% at wave 10, with average probabilities of co-use higher among non-Hispanic white versus Hispanic or Asian participants. Higher average probability of co-use was associated with greater delinquency, more mental health symptoms, and poorer physical health during emerging adulthood. Higher rate of change in the probability of co-use over time was associated with greater delinquency, but better social functioning and less physical ailments. There was some evidence of racial/ethnic disparities in functioning, even at similar levels of co-use., Conclusions: Cannabis and tobacco co-use deserves greater attention, especially regarding its effects on functioning during emerging adulthood. Results also emphasize the need for future research to focus on racial/ethnic disparities related to co-use and associated outcomes., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Purpose: To investigate specific effects of denervation and stimulation of the internal carotid nerve (ICN) on the choroid and retina., Methods: Female Sprague Dawley rats underwent unilateral ICN transection (n = 20) or acute ICN electrical stimulation (n = 7). Rats in the denervation group were euthanized 6 weeks after nerve transection, and eyes were analyzed for changes in choroidal vascularity (via histomorphometry) or angiogenic growth factors and inflammatory markers (via ELISA). Rats in the stimulation group received acute ICN electrical stimulation with a bipolar cuff electrode over a range of stimulus amplitudes, frequencies, and pulse widths. Choroidal blood flow and pupil diameter were monitored before, during, and after stimulation., Results: Six weeks after unilateral ICN transection, sympathectomized choroids exhibited increased vascularity, defined as the percentage of choroidal surface area occupied by blood vessel lumina. Vascular endothelial growth factor (VEGF) and VEGF receptor-2 (VEGFR-2) protein levels in denervated choroids were 61% and 124% higher than in contralateral choroids, respectively. TNF-α levels in denervated retinas increased by 3.3-fold relative to levels in contralateral retinas. In animals undergoing acute ICN electrical stimulation, mydriasis and reduced choroidal blood flow were observed in the ipsilateral eye. The magnitude of the reduction in blood flow correlated positively with stimulus frequency., Conclusions: Modulation of ICN activity reveals a potential role of the ocular sympathetic system in regulating endpoints related to neovascular diseases of the eye.

Objective: To understand role of barrier molecules in melanomas., Background: We have reported poor patient survival and low immune infiltration of melanomas that overexpress a set of genes that include filaggrin (FLG), dystonin (DST), junction plakoglobin (JUP), and plakophilin-3 (PKP3), and are involved in cell-cell adhesions. We hypothesized that these associations are causal, either by interfering with immune cell infiltration or by enhancing melanoma cell growth., Methods: FLG and DST were knocked out by CRISPR/Cas9 in human DM93 and murine B16-F1 melanoma cells. PKP3 and JUP were overexpressed in murine B16-AAD and human VMM39 melanoma cells by lentiviral transduction. These cell lines were evaluated in vitro for cell proliferation and in vivo for tumor burden, immune composition, cytokine expression, and vascularity., Results: Immune infiltrates were not altered by these genes. FLG/DST knockout reduced proliferation of human DM93 melanoma in vitro, and decreased B16-F1 tumor burden in vivo. Overexpression of JUP, but not PKP3, in B16-AAD significantly increased tumor burden, increased VEGF-A, reduced IL-33, and enhanced vascularity., Conclusions: FLG and DST support melanoma cell growth in vitro and in vivo. Growth effects of JUP were only evident in vivo, and may be mediated, in part, by enhancing angiogenesis. In addition, growth-promoting effects of FLG and DST in vitro suggest that these genes may also support melanoma cell proliferation through angiogenesis-independent pathways. These findings identify FLG, DST, and JUP as novel therapeutic targets whose down-regulation may provide clinical benefit to patients with melanoma.

Objective: The current study examines longitudinal sleep patterns in relation to risky sexual behaviors in a racially/ethnically diverse sample of adolescents., Method: The sample comprises 1,850 youth (mean age at first wave = 16.21; 57% female). Sleep duration, sleep variability (difference between weekend and weekday sleep duration), and sleep quality were collected over four annual assessments from 2013 to 2017. Risky sexual behaviors (i.e., sex without condom use or sex after using drugs or alcohol) were examined at the fourth follow-up assessment when youth were 19 years old. Longitudinal latent class analysis characterized patterns of individual sleep dimensions over time, as well as the combination of sleep dimensions, and examined how emergent sleep classes associated with subsequent risky sexual behavior, after adjustment for sociodemographics and mental health., Results: After covariate adjustment, persistent "short" weekend sleepers were 2.2 times more likely to engage in risky sexual behaviors, compared to youth with sufficient weekend sleep duration. Contrary to expectations, adolescents with more consistent weekend/weekday sleep were 1.6-2 times more likely to engage in risky sexual behaviors, compared to those with greater variability; however, lack of variability may be an indicator of chronic insufficient sleep, both weekdays and weekends. There were no significant differences in risky sexual behavior according to classes of weekday sleep duration or quality. In the combined class model, those with persistently short and poor-quality sleep were at marginally greater risk for engaging in risky sexual behaviors., Conclusion: Insufficient sleep in adolescents may increase risk for sexual risk-taking and may set the stage for accelerated health risk trajectories into adulthood. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Background: Dysregulations in maternal hypothalamus-pituitary-adrenal function and the end product, cortisol, have been associated with a heightened risk for stress-related health complications during pregnancy and post partum. Given the adverse health impact that maternal cortisol may have on expectant mothers and their infants, empirically-based prenatal interventions are needed to target optimal management of stress and its biological effects in at-risk pregnant women, a primary example of which is cognitive behavioral stress management (CBSM). This randomized-controlled trial examined the effects of a prenatal CBSM intervention on reduction in perceived stress and regulation of salivary cortisol patterns [i.e., overall cortisol output (area under the curve), cortisol awakening response (CAR), diurnal slope] during pregnancy and the early postpartum period, as compared to a control group., Methods: One hundred low-income pregnant women (71% Latina; 76% annual income < $20 K) with low or high anxiety during pregnancy were randomized (stratified by anxiety) to either an eight-week CBSM group intervention (n = 55) or a control group (n = 45). They provided seven salivary cortisol samples (four am samples, 12 pm, 4 pm, and 8 pm samples on one collection day) at baseline (1 st trimester; < 17 weeks of gestation), after their prenatal program (2 nd trimester), and also in the third trimester and at three months post partum., Results: Women receiving CBSM had lower perceived stress levels throughout pregnancy and early post partum compared to women in the control group (p = .020). Among women with high prenatal anxiety, those in CBSM showed a steeper decline in their diurnal cortisol at three months post partum compared to those in the control group (p = .015). Further, non-Latina women in CBSM had a lower CAR at three months post partum compared to non-Latina women in the control group (p = .025); these randomization group differences on the CAR were not observed among Latina women., Conclusions: These findings provide preliminary support for the efficacy of prenatal CBSM interventions in improving stress outcomes among low-income pregnant women and suggest the need to test the effects of these interventions on a larger scale for improving maternal and infant health outcomes long-term., (Published by Elsevier Ltd.)

Background: Aims: The REAL HEALTH Diabetes Study is a practice-based randomized clinical trial that compares the effectiveness of lifestyle intervention aimed at weight reduction to medical nutrition therapy in primary care patients with type 2 diabetes. This paper describes a tiered approach to recruitment, the resultant enrollment rates of sequentially more intensive recruitment strategies, and identifies barriers to participation., Methods: Potential participants were identified using patient health registries and classified by recruitment site. Four recruitment strategies were used to achieve target enrollment: (1) mail/telephone outreach; (2) direct referral from providers; (3) orientation sessions; and (4) media/advertising. Reasons for ineligibility and non-participation were tracked., Results: Fifteen thousand two hundred sixty-nine (15,269) potential participants were identified from all sources, with the clear majority coming from patient registries. Mail/telephone outreach alone had the lowest enrollment rate (1.2%). Direct referral and orientation sessions superimposed on mail/telephone outreach was used for fewer participants but had greater enrollment rates (27% and 52%.) Media/advertising was ineffective. The most commonly reported reasons for non-participation were not wanting to be in a research (30%) or a weight loss program (22%); time commitment (20%); and distance/transportation (14%)., Conclusions: The use of population registries to identify potential participants coupled with successively more intensive recruitment strategies, executed in a tiered approach moving toward personal engagement to establish trust and credibility, maximized recruitment enrollment rates. Our findings regarding facilitators and barriers to recruitment could be used to inform other practice-based research or to engage patients in group interventions in usual care settings., Clinical Trial Registration: NCT02320253.

Lymphatic and blood vessels are formed by specialized lymphatic endothelial cells (LEC) and blood endothelial cells (BEC), respectively. These endothelial populations not only form peripheral tissue vessels, but also critical supporting structures in secondary lymphoid organs, particularly the lymph node (LN). Lymph node LEC (LN-LEC) also have been shown to have important immunological functions that are not observed in LEC from tissue lymphatics. LN-LEC can maintain peripheral tolerance through direct presentation of self-antigen via MHC-I, leading to CD8 T cell deletion; and through transfer of self-antigen to dendritic cells for presentation via MHC-II, resulting in CD4 T cell anergy. LN-LEC also can capture and archive foreign antigens, transferring them to dendritic cells for maintenance of memory CD8 T cells. The molecular basis for these functional elaborations in LN-LEC remain largely unexplored, and it is also unclear whether blood endothelial cells in LN (LN-BEC) might express similar enhanced immunologic functionality. Here, we used RNA-Seq to compare the transcriptomic profiles of freshly isolated murine LEC and BEC from LN with one another and with freshly isolated LEC from the periphery (diaphragm). We show that LN-LEC, LN-BEC, and diaphragm LEC (D-LEC) are transcriptionally distinct from one another, demonstrating both lineage and tissue-specific functional specializations. Surprisingly, tissue microenvironment differences in gene expression profiles were more numerous than those determined by endothelial cell lineage specification. In this regard, both LN-localized endothelial cell populations show a variety of functional elaborations that suggest how they may function as antigen presenting cells, and also point to as yet unexplored roles in both positive and negative regulation of innate and adaptive immune responses. The present work has defined in depth gene expression differences that point to functional specializations of endothelial cell populations in different anatomical locations, but especially the LN. Beyond the analyses provided here, these data are a resource for future work to uncover mechanisms of endothelial cell functionality.

Background: This study compared young adults with and without a medical marijuana (MM) recommendation from a provider ("MM card") on their developmental trajectories of frequent marijuana use and marijuana-related problems in young adulthood., Methods: The analytic sample consists of young adult past month marijuana users (N = 671) who were part of a larger, diverse, and predominantly California cohort. Analyses are based on data from seven surveys completed from ages 13-19., Results: At age 19, 28% of participants reported having an MM card to legally purchase marijuana from an MM dispensary. A multiple group latent growth model indicated that young adults who had an MM card showed steeper increases in frequent marijuana use (i.e., 20-30 days of use in the past month) from ages 13-19 compared to young adults who did not have an MM card. Logistic regression models that matched MM cardholders and non-MM cardholders on individual sociodemographic characteristics found that MM cardholders were more likely to report marijuana negative consequences, selling marijuana/hashish, and driving under the influence of marijuana in the past year. In addition, MM cardholders were more likely to have tried cutting down or quitting in the past 3-months., Conclusions: Among young adult marijuana users, those with an MM card had a higher risk profile for marijuana use and related problems compared to those without an MM card. Given expanding state legalization of MM, this issue warrants further attention., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background/aims: The REAL HEALTH -Diabetes Study is a practice-based clinical trial that adapted the Look AHEAD lifestyle intervention for implementation in primary care settings. The trial will compare the effectiveness and cost-effectiveness of in-person group lifestyle intervention, telephone group lifestyle intervention, and individual medical nutrition therapy (MNT), the current recommended standard of care in type 2 diabetes. The primary outcome is percent weight loss at 6 months with outcomes also measured at 12, 18, 24 (intervention completion), and 36 months. Here, we describe the adaptation, trial design, implementation strategies, and baseline characteristics of enrolled participants., Methods: The study is a three-arm, patient-level, randomized trial conducted in three community health centers (CHCs) and one diabetes practice affiliated with one academic medical center., Results: The study used existing clinical infrastructure to recruit participants from study sites. Strategies for successful conduct of the trial included partnering with health-center based co-investigator clinicians, engaging primary care providers, and accommodating clinical workflows. Of 248 eligible patients who attended a screening visit, 211 enrolled, with 70 randomly assigned to in-person group lifestyle intervention, 72 to telephone group lifestyle intervention, and 69 to MNT. The cohort was 55% female, 29% non-white, with mean age 62 years and mean BMI 35 kg/m 2 . Enrollment rates were higher at CHC sites., Conclusions: A practice-based randomized trial of a complex behavioral lifestyle intervention for type 2 diabetes can be implemented in community health and usual clinical settings. Participant and provider engagement was higher at local CHC sites reflecting the study implementation focus., Clinical Trial Registration: NCT02320253., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Marijuana use during adolescence is associated with neurocognitive deficits and poorer functioning across several domains. It is likely that more states will pass both medical and recreational marijuana legalization laws in the coming elections; therefore, we must begin to look more closely at the longitudinal effects of medical marijuana (MM) advertising on marijuana use among adolescents so that we can better understand effects that this advertising may have on their subsequent marijuana use and related outcomes., Methods: We followed two cohorts of 7th and 8th graders (mean age 13) recruited from school districts in Southern California from 2010 until 2017 (mean age 19) to examine effects of MM advertising on adolescents' marijuana use, cognitions, and consequences over seven years. Latent growth models examined trajectories of self-reported exposure to medical marijuana ads in the past three months and trajectories of use, cognitions, and consequences., Results: Higher average exposure to MM advertising was associated with higher average use, intentions to use, positive expectancies, and negative consequences. Similarly, higher rates of change in MM advertising exposure were associated with higher rates of change in use, intentions, expectancies, and consequences over seven years., Conclusions: Results suggest that exposure to MM advertising may not only play a significant role in shaping attitudes about marijuana, but may also contribute to increased marijuana use and related negative consequences throughout adolescence. This highlights the importance of considering regulations for marijuana advertising, similar to regulations in place for the promotion of tobacco and alcohol in the U.S., (Copyright © 2018. Published by Elsevier B.V.)

Purpose: Cigarette smoking among youth is associated with poorer health and psychosocial outcomes. However, few studies address how smoking may differentially relate to the emergence of disparities in functioning across races/ethnicities over adolescence., Methods: Youth (n = 2,509) were surveyed eight times from ages 11 to 18. We measured cigarette use, academic and social functioning, mental and physical health, and delinquency. Sequelae of change models controlled for sociodemographic factors, and tested whether intercept and slope for smoking trajectories were associated with outcomes at the end of high school, and examined racial/ethnic differences in outcomes assuming similar smoking trajectories across groups., Results: Youth were 45% Hispanic, 20% Asian, 20% white, 10% multiethnic, 2% black, and 1% other ethnicities. Higher average probability of smoking and steeper slopes of smoking trajectories were associated with poorer outcomes in multiple domains. Controlling for smoking trajectories, we observed the following disparities (vs. white youth; all p's < .05): black, Hispanic, and multiethnic youth reported lower academic performance; Asian, black, and multiethnic youth reported higher academic unpreparedness; Asian and multiethnic youth reported poorer mental health; Asian, Hispanic, and multiethnic youth reported poorer physical health; and Asian youth reported higher delinquency and poorer social functioning., Conclusions: Statistically adjusting for similar smoking trajectories, racial/ethnic minority youth demonstrated poorer outcomes in multiple domains compared with white peers. Smoking may be a particularly robust marker for risk of negative outcomes in racial/ethnic minority youth. Screening for cigarette use and intervening on smoking and associated risk behaviors among minority youth may help reduce disparities in functioning., (Copyright © 2017 The Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.)

Limited representation of intratumoral immune cells is a major barrier to tumor control. However, simply enhancing immune responses in tumor-draining lymph nodes or through adoptive transfer may not overcome the limited ability of tumor vasculature to support effector infiltration. An alternative is to promote a sustained immune response intratumorally. This idea has gained traction with the observation that many tumors are associated with tertiary lymphoid structures (TLS), which organizationally resemble lymph nodes. These peri- and intratumoral structures are usually, but not always, associated with positive prognoses in patients. Preclinical and clinical data support a role for TLS in modulating immunity in the tumor microenvironment. However, there appear to be varied functions of TLS, potentially based on their structure or location in relation to the tumor or the origin or location of the tumor itself. Understanding more about TLS development, composition, and function may offer new therapeutic opportunities to modulate antitumor immunity., (Copyright © 2018 by The American Association of Immunologists, Inc.)

Tertiary lymphoid structures (TLS) are transient ectopic lymphoid aggregates that often share structural similarities to conventional secondary lymphoid organs. In a variety of solid cancers, the presence of these structures commonly correlates with high densities of tumor-infiltrating T lymphocytes and prolonged patient survival. These observations suggest that TLS act as sites for the development of beneficial antitumor immune responses. However, few murine tumor models have been described that could enable a more comprehensive understanding of the functionality of TLS in solid cancers. We previously reported that murine B16-F1 melanoma or Lewis lung carcinoma cells transfected to express the model antigen ovalbumin form intratumoral TLS after implantation into the peritoneal cavity of C57BL/6 mice. In this chapter, we describe immunofluorescent microscopy and flow cytometry approaches for identifying and characterizing intratumoral TLS. Additionally, we describe an adoptive transfer method for demonstrating the infiltration of naïve T cells into B16-OVA melanoma tumors via the lymph node-like vasculature, which is an essential functional feature of tumor-associated TLS.

Bifactor measurement models are increasingly being applied to personality and psychopathology measures (Reise, 2012). In this work, authors generally have emphasized model fit, and their typical conclusion is that a bifactor model provides a superior fit relative to alternative subordinate models. Often unexplored, however, are important statistical indices that can substantially improve the psychometric analysis of a measure. We provide a review of the particularly valuable statistical indices one can derive from bifactor models. They include omega reliability coefficients, factor determinacy, construct reliability, explained common variance, and percentage of uncontaminated correlations. We describe how these indices can be calculated and used to inform: (a) the quality of unit-weighted total and subscale score composites, as well as factor score estimates, and (b) the specification and quality of a measurement model in structural equation modeling. (PsycINFO Database Record, ((c) 2016 APA, all rights reserved).)

Students with intellectual and developmental disabilities (IDD) are routinely excluded from algebra and other high-level mathematics courses. High school students with IDD take courses in arithmetic and life skills rather than having an opportunity to learn algebra. Yet algebra skills can support the learning of money and budgeting skills. This study explores the feasibility of algebra instruction for adults with IDD through an experimental curriculum. Ten individuals with IDD participated in a 6-week course framing mathematics concepts within the context of everyday challenges in handling money. The article explores classroom techniques, discusses student strategies, and proposes possible avenues for future research analyzing mathematics instructional design strategies for individuals with IDD.

Primate lentiviruses exhibit narrow host tropism, reducing the occurrence of zoonoses but also impairing the development of optimal animal models of AIDS. To delineate the factors limiting cross-species HIV-1 transmission, we passaged a modified HIV-1 in pigtailed macaques that were transiently depleted of CD8(+) cells during acute infection. During adaptation over four passages in macaques, HIV-1 acquired the ability to antagonize the macaque restriction factor tetherin, replicated at progressively higher levels, and ultimately caused marked CD4(+) T cell depletion and AIDS-defining conditions. Transient treatment with an antibody to CD8 during acute HIV-1 infection caused rapid progression to AIDS, whereas untreated animals exhibited an elite controller phenotype. Thus, an adapted HIV-1 can cause AIDS in macaques, and stark differences in outcome can be determined by immunological perturbations during early infection., (Copyright © 2014, American Association for the Advancement of Science.)

Purpose: To investigate whether oxidative stress modulates vascular endothelial growth factor (VEGF)-A and VEGF-C expression and polarized secretion in a human retinal pigment epithelium cell line (ARPE-19)., Methods: Long-term culture of ARPE-19 cells in Dulbecco's modified Eagle medium (DMEM)/F12 containing 1% fetal bovine serum (FBS) on transwell filters (12 mm or 6 mm, pore size 0.4 microm) was performed to produce polarized retinal pigment epithelium (RPE) monolayers. The integrity of polarized monolayer was established by measurement of transepithelial resistance (TER) and presence of tight junctions assessed by zonula occludens (ZO-1) and occludin expression and apical Na/K ATPase localization. Paracellular permeability was studied using radiolabeled mannitol. Confluent cells were treated with tertiary butyl hydrogen peroxide (tBH) for varying durations (0-5 h) and doses (50-200 microM). VEGF-A and -C expression was evaluated by western blot and quantitative RT-PCR, while secretion to the apical and basolateral surfaces was quantitated by ELISA., Results: Polarity of ARPE-19 cells was verified by the localization of tight junction proteins, ZO-1 and its binding partner occludin by confocal microscopy as well as by localization of Na,K-ATPase at the apical surface. The TER in confluent ARPE-19 cells averaged 48.7+/-2.1 Omega. cm(2) and tBH treatment (0-5 h) did not alter TER significantly (46.9+/-1.9 Omega. cm(2); p>0.05 versus controls) or ZO-1 expression. Whole cell mRNA in nonpolarized ARPE-19 increased with tBH at 5 h both for VEGF-A and VEGF-C and the increase was significant (p<0.05 vs controls). A similar, maximal increase at 5 h tBH treatment was also observed for VEGF-A and VEGF-C cellular protein levels. The secretion of VEGF-A and VEGF-C in nonpolarized ARPE showed an increase with tBH exposure. The levels of secretion of VEGF-A and -C were significantly higher in polarized monolayers and were stimulated significantly with tBH at both apical and basolateral domains. The secretion of VEGF-A increased with 150 microM of tBH treatment as a function of time (1-5 h) with maximal increases at 5 h from 410 to 2080 pg/10(6) cells on the apical and 290 to 1680 pg/10(6) cells on basolateral domains. The pattern of VEGF-C secretion was similar. VEGF-A secretion was dose-dependent for the tBH range of 50-200 microM and apical secretion tended to be higher than basolateral secretion., Conclusions: Our data show that oxidative stress to RPE from tBH upregulates secretion of both VEGF-A and C. The secretion to the apical side was higher than that of basolateral side for VEGF-A and C. Given the role of VEGF in choroidal neovascularization, these data may be of value in understanding pathogenic mechanisms and designing antiangiogenic therapies.