Choroid plexus volumes and auditory verbal learning scores are associated with conversion from mild cognitive impairment to Alzheimer's disease.

PURPOSE: Mild cognitive impairment (MCI) can be the prodromal phase of Alzheimer's disease (AD) where appropriate intervention might prevent or delay conversion to AD. Given this, there has been increasing interest in using magnetic resonance imaging (MRI) and neuropsychological testing to predict conversion from MCI to AD. Recent evidence suggests that the choroid plexus (ChP), neural substrates implicated in brain clearance, undergo volumetric changes in MCI and AD. Whether the ChP is involved in memory changes observed in MCI and can be used to predict conversion from MCI to AD has not been explored. METHOD: The current study used data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database to investigate whether later progression from MCI to AD (progressive MCI [pMCI], n = 115) or stable MCI (sMCI, n = 338) was associated with memory scores using the Rey Auditory Verbal Learning Test (RAVLT) and ChP volumes as calculated from MRI. Classification analyses identifying pMCI or sMCI group membership were performed to compare the predictive ability of the RAVLT and ChP volumes. FINDING: The results indicated a significant difference between pMCI and sMCI groups for right ChP volume, with the pMCI group showing significantly larger right ChP volume (p = .01, 95% confidence interval [-.116, -.015]). A significant linear relationship between the RAVLT scores and right ChP volume was found across all participants, but not for the two groups separately. Classification analyses showed that a combination of left ChP volume and auditory verbal learning scores resulted in the most accurate classification performance, with group membership accurately predicted for 72% of the testing data. CONCLUSION: These results suggest that volumetric ChP changes appear to occur before the onset of AD and might provide value in predicting conversion from MCI to AD.

Chemical Composition of Electronic Vaping Products from School Grounds in California.

INTRODUCTION: The use of electronic vaping products (EVPs) containing nicotine, marijuana, and/or other substances remains prominent among youth; with EVPs containing nicotine being the most commonly used tobacco product among youth since 2014. However, a detailed understanding of the chemical composition of these products is limited. METHODS: During February 25th-March 15th, 2019, a total of 576 EVPs, including 233 e-cigarette devices (with 43 disposable vape pens) and 343 e-liquid cartridges/pods/bottled e-liquids, were found or confiscated from a convenience sample of 16 public high schools in California. Liquids inside 251 vape pens and cartridges/pods/bottled e-liquids were analyzed using a gas chromatography/mass spectrometry (GC/MS). For comparison, new JUUL pods, the most commonly used e-cigarette among youth during 2018-2019, with different flavorings and nicotine content were purchased and analyzed. RESULTS: For e-cigarette cartridges/pods/bottled e-liquids, nicotine was detected in 204 of 208 (98.1%) samples. Propylene glycol (PG) and vegetable glycerin (VG) were dominant solvents in nicotine-containing EVPs. Among 43 disposable vape pen devices, cannabinoids such as tetrahydrocannabinol (THC) or cannabidiol (CBD) were identified in 39 of 43 (90.1%) samples, of which 3 contained both nicotine and THC. Differences in chemical compositions were observed between confiscated or collected JUULs and purchased JUULs. Measured nicotine was inconsistent with labels on some confiscated or collected bottled e-liquids. CONCLUSIONS: EVPs from 16 participating schools were found to widely contain substances with known adverse health effects among youth, including nicotine and cannabinoids. There was inconsistency between labeled and measured nicotine on the products from schools. IMPLICATIONS: This study measured the main chemical compositions of EVPs found at 16 California public high schools. Continued efforts are warranted, including at the school-level, to educate, prevent and reduce youth use of EVPs.

Recommendations for intervertebral disc notochordal cell investigation: From isolation to characterization.

Background: Lineage-tracing experiments have established that the central region of the mature intervertebral disc, the nucleus pulposus (NP), develops from the embryonic structure called "the notochord". However, changes in the cells derived from the notochord which form the NP (i.e., notochordal cells [NCs]), in terms of their phenotype and functional identity from early developmental stages to skeletal maturation are less understood. These key issues require further investigation to better comprehend the role of NCs in homeostasis and degeneration as well as their potential for regeneration. Progress in utilizing NCs is currently hampered due to poor consistency and lack of consensus methodology for in vitro NC extraction, manipulation, and characterization. Methods: Here, an international group has come together to provide key recommendations and methodologies for NC isolation within key species, numeration, in vitro manipulation and culture, and characterization. Results: Recommeded protocols are provided for isolation and culture of NCs. Experimental testing provided recommended methodology for numeration of NCs. The issues of cryopreservation are demonstrated, and a pannel of immunohistochemical markers are provided to inform NC characterization. Conclusions: Together we hope this article provides a road map for in vitro studies of NCs to support advances in research into NC physiology and their potential in regenerative therapies.

Associations for subgroups of E-cigarette, cigarette, and cannabis use with asthma in a population sample of California adolescents.

Knowledge about the respiratory health consequences of adolescents' use of tobacco products with cannabis remains limited. We studied whether e-cigarettes, combustible cigarettes, and cannabis were independently associated with asthma in a population-based sample of 150,634 public high school students (10th and 12th graders), drawn in a two-stage design to be representative of the state of California in 2019-2020. Measures were obtained for use of e-cigarettes, combustible cigarettes, and cannabis; motives for use (three substances); method of use (for cannabis); ever being diagnosed with asthma; and having an asthma attack in past 12 months. Cross-classification indicated Nonuse for 64% of the sample; 15% Dual E-cigarette/Cannabis Use; 10% Exclusive Cannabis Use; 5% Exclusive E-cigarette Use; and 5% Triple Use. Multinomial logistic regression with a three-level criterion variable, controlling for age, sex, parental education, race/ethnicity, and three types of household use showed that compared with Nonuse, odds of Lifetime Asthma (vs. Never Had) was elevated for Triple Use (AOR = 1.14, CI 1.06-1.24), Dual E-cigarette/Cannabis Use (1.17, 1.12-1.23), Exclusive Cannabis Use (1.17, 1.11-1.23), and Exclusive E-cigarette Use (1.10, 1.02-1.18). Similar results were noted for Recent Asthma. Among persons who had used cannabis, 88% of the Triple group and 74% of the Dual E-cigarette/Cannabis group reported both smoking and vaping cannabis. Thus, co-occurrence of e-cigarette and cannabis use was a common pattern among adolescents in this study, and subgroups of cannabis and e-cigarette use showed similar associations with asthma. Preventive approaches should highlight the health implications of exclusive or combined e-cigarette and cannabis use.

Correspondence between BOLD fMRI task response and cerebrovascular reactivity across the cerebral cortex.

BOLD sensitivity to baseline perfusion and blood volume is a well-acknowledged fMRI confound. Vascular correction techniques based on cerebrovascular reactivity (CVR) might reduce variance due to baseline cerebral blood volume, however this is predicated on an invariant linear relationship between CVR and BOLD signal magnitude. Cognitive paradigms have relatively low signal, high variance and involve spatially heterogenous cortical regions; it is therefore unclear whether the BOLD response magnitude to complex paradigms can be predicted by CVR. The feasibility of predicting BOLD signal magnitude from CVR was explored in the present work across two experiments using different CVR approaches. The first utilized a large database containing breath-hold BOLD responses and 3 different cognitive tasks. The second experiment, in an independent sample, calculated CVR using the delivery of a fixed concentration of carbon dioxide and a different cognitive task. An atlas-based regression approach was implemented for both experiments to evaluate the shared variance between task-invoked BOLD responses and CVR across the cerebral cortex. Both experiments found significant relationships between CVR and task-based BOLD magnitude, with activation in the right cuneus (R 2 = 0.64) and paracentral gyrus (R 2 = 0.71), and the left pars opercularis (R 2 = 0.67), superior frontal gyrus (R 2 = 0.62) and inferior parietal cortex (R 2 = 0.63) strongly predicted by CVR. The parietal regions bilaterally were highly consistent, with linear regressions significant in these regions for all four tasks. Group analyses showed that CVR correction increased BOLD sensitivity. Overall, this work suggests that BOLD signal response magnitudes to cognitive tasks are predicted by CVR across different regions of the cerebral cortex, providing support for the use of correction based on baseline vascular physiology.

Direct machine learning reconstruction of respiratory variation waveforms from resting state fMRI data in a pediatric population.

In many functional magnetic resonance imaging (fMRI) studies, respiratory signals are unavailable or do not have acceptable quality due to issues with subject compliance, equipment failure or signal error. In large databases, such as the Human Connectome Projects, over half of the respiratory recordings may be unusable. As a result, the direct removal of low frequency respiratory variations from the blood oxygen level-dependent (BOLD) signal time series is not possible. This study proposes a deep learning-based method for reconstruction of respiratory variation (RV) waveforms directly from BOLD fMRI data in pediatric participants (aged 5 to 21 years old), and does not require any respiratory measurement device. To do this, the Lifespan Human Connectome Project in Development (HCP-D) dataset, which includes respiratory measurements, was used to both train a convolutional neural network (CNN) and evaluate its performance. Results show that a CNN can capture informative features from the BOLD signal time course and reconstruct accurate RV timeseries, especially when the subject has a prominent respiratory event. This work advances the use of direct estimation of physiological parameters from fMRI, which will eventually lead to reduced complexity and decrease the burden on participants because they may not be required to wear a respiratory bellows.

HARmonized Protocol Template to Enhance Reproducibility of hypothesis evaluating real-world evidence studies on treatment effects: A good practices report of a joint ISPE/ISPOR task force.

PROBLEM: Ambiguity in communication of key study parameters limits the utility of real-world evidence (RWE) studies in healthcare decision-making. Clear communication about data provenance, design, analysis, and implementation is needed. This would facilitate reproducibility, replication in independent data, and assessment of potential sources of bias. WHAT WE DID: The International Society for Pharmacoepidemiology (ISPE) and ISPOR-The Professional Society for Health Economics and Outcomes Research (ISPOR) convened a joint task force, including representation from key international stakeholders, to create a harmonized protocol template for RWE studies that evaluate a treatment effect and are intended to inform decision-making. The template builds on existing efforts to improve transparency and incorporates recent insights regarding the level of detail needed to enable RWE study reproducibility. The overarching principle was to reach for sufficient clarity regarding data, design, analysis, and implementation to achieve 3 main goals. One, to help investigators thoroughly consider, then document their choices and rationale for key study parameters that define the causal question (e.g., target estimand), two, to facilitate decision-making by enabling reviewers to readily assess potential for biases related to these choices, and three, to facilitate reproducibility. STRATEGIES TO DISSEMINATE AND FACILITATE USE: Recognizing that the impact of this harmonized template relies on uptake, we have outlined a plan to introduce and pilot the template with key international stakeholders over the next 2 years. CONCLUSION: The HARmonized Protocol Template to Enhance Reproducibility (HARPER) helps to create a shared understanding of intended scientific decisions through a common text, tabular and visual structure. The template provides a set of core recommendations for clear and reproducible RWE study protocols and is intended to be used as a backbone throughout the research process from developing a valid study protocol, to registration, through implementation and reporting on those implementation decisions.

Intersectional Disparities in Youth Tobacco Use by Sexual and/or Gender Minority Status and Race and/or Ethnicity.

INTRODUCTION: The current study applied an intersectional lens to examine societal factors, individual psychological outcomes, and youth combustible tobacco and vape use at the intersection of sexual and/or gender minority (SGM) status and race and/or ethnicity. AIMS AND METHODS: Data were drawn from 133 969 youth respondents surveyed in the 2019-2020 California Student Tobacco Survey, a representative school-based survey of 8th and 10th-grade public school students throughout California. The impact of multiple marginalized group membership using four mutually exclusive intersectional positions (non-SGM white, SGM white, racial minority only, and both SGM and racial minority), in addition to specific differences across ten SGM by race and/or ethnicity groups (e.g. non-SGM black or African American, SGM black or African American, etc.) were assessed. RESULTS: Compared to heterosexual and cisgender white youth, SGM and racial minority adolescents were shown to experience poorer school tobacco education quality and cessation support, lower school and family connectedness, and higher anxiety and depression symptoms. SGM and racial minority youth had a higher prevalence of ever-combustible tobacco use but were less likely to be current vape users compared to non-SGM white respondents. In examining specific group differences, results revealed that SGM teens had the highest risk of ever combustible tobacco use. This disparity was amplified for those belonging to multiple marginalized groups, with black or AA SGM teens evidenced to be at the highest risk of current combustible tobacco. CONCLUSIONS: Information from this study has useful implications for SGM measurement in surveillance systems and highlights the usefulness of adopting an intersectional approach to inform equity-driven public health policy and intervention. IMPLICATIONS: This representative study of California youth supports that identifying as a sexual and/or gender minority (SGM) is an important risk factor for combustible tobacco use. Particularly, observed SGM disparities were magnified for the youth belonging to marginalized groups, as black or African American SGM teens were shown to be at the highest risk of current combustible tobacco use. Findings support that Intersectionality Theory represents a useful framework for examining tobacco-related disparities and underscores the importance of assessing how the intersection of multiple social categories impacts youth tobacco use.

Prenatal Exposure to Tobacco and Cannabis in Six Race/Ethnicity Groups during the First Three Years after Legalization of Cannabis for Recreational Use in California.

There are known health concerns linked to prenatal tobacco and cannabis exposures. This study aims to objectively determine the level of exposure to tobacco and cannabis in pregnant individuals from six race/ethnicity groups (Black, Hispanic, Asian Indian, Native American, Vietnamese, and White) in the first three years following legalization of recreational marijuana use in 2018 in California. We used a cross-sectional sample of prenatal screening program participants (2018-2020) from southern and central California (N = 925). Exposures were estimated by a lab analysis of cotinine (tobacco) and 11-hydroxy-Δ9-tetrahydrocannabinol (OH-THC, cannabis) in banked serum. Disparities in tobacco exposure were evident, with Black subjects experiencing the highest smoking rate (16%) followed by Native American (10%) and White (8%) subjects, and ≤2% among Hispanic, Asian Indian, and Vietnamese subjects. Environmental tobacco exposure generally showed a similar pattern of exposure to tobacco smoking across race/ethnicity groups. Cannabis detection ranged from 5% among Hispanic subjects to 12% and 13% among White and Black subjects, respectively, and was higher among tobacco users and those exposed to environmental tobacco smoke than those with no cotinine detected. Tobacco and cannabis exposure were generally greatest in younger subjects and those with indices of a lower economic status; however, among Black subjects, cannabis exposure was greatest in older subjects and those with a higher socioeconomic status. Race/ethnicity, age, and socioeconomic factors can inform targeting of high-exposure groups for intervention.

HARmonized Protocol Template to Enhance Reproducibility of Hypothesis Evaluating Real-World Evidence Studies on Treatment Effects: A Good Practices Report of a Joint ISPE/ISPOR Task Force.

OBJECTIVES: Ambiguity in communication of key study parameters limits the utility of real-world evidence (RWE) studies in healthcare decision-making. Clear communication about data provenance, design, analysis, and implementation is needed. This would facilitate reproducibility, replication in independent data, and assessment of potential sources of bias. METHODS: The International Society for Pharmacoepidemiology (ISPE) and ISPOR-The Professional Society for Health Economics and Outcomes Research (ISPOR) convened a joint task force, including representation from key international stakeholders, to create a harmonized protocol template for RWE studies that evaluate a treatment effect and are intended to inform decision-making. The template builds on existing efforts to improve transparency and incorporates recent insights regarding the level of detail needed to enable RWE study reproducibility. The over-arching principle was to reach for sufficient clarity regarding data, design, analysis, and implementation to achieve 3 main goals. One, to help investigators thoroughly consider, then document their choices and rationale for key study parameters that define the causal question (e.g., target estimand), two, to facilitate decision-making by enabling reviewers to readily assess potential for biases related to these choices, and three, to facilitate reproducibility. STRATEGIES TO DISSEMINATE AND FACILITATE USE: Recognizing that the impact of this harmonized template relies on uptake, we have outlined a plan to introduce and pilot the template with key international stakeholders over the next 2 years. CONCLUSION: The HARmonized Protocol Template to Enhance Reproducibility (HARPER) helps to create a shared understanding of intended scientific decisions through a common text, tabular and visual structure. The template provides a set of core recommendations for clear and reproducible RWE study protocols and is intended to be used as a backbone throughout the research process from developing a valid study protocol, to registration, through implementation and reporting on those implementation decisions.

Approach for reporting master protocol study designs on ClinicalTrials.gov: qualitative analysis.

OBJECTIVE: To describe an approach for reporting master protocol research programs (MPRPs) that is consistent with existing good reporting practices and that uses structured information to convey the overall master protocol and design of each substudy. DESIGN: Qualitative analysis. DATA SOURCES: ClinicalTrials.gov trial registry. MAIN OUTCOME MEASURES: Established goals and related practices of the trial reporting system were outlined, examples and key characteristics of MPRPs were reviewed, and specific challenges in registering and reporting summary results to databases designed for traditional clinical trial designs that rely on a model of one study per protocol were identified. RESULTS: A reporting approach is proposed that accommodates the complex study design of MPRPs and their results. This approach involves the use of separate registration records for each substudy within one MPRP protocol (with potential exceptions noted). CONCLUSIONS: How the proposed approach allows for clear, descriptive, structured information about each substudy's prespecified design and supports timely reporting of results after completion of each substudy is described and illustrated. Although the focus is on reporting to ClinicalTrials.gov, the approach supports broader application across trial registries and results databases. This paper is intended to stimulate further discussion of this approach among stakeholders, build awareness about the need to improve reporting of MPRPs, and encourage harmonization across trial registries globally.

Nicotine vaping for relaxation and coping: Race/ethnicity differences and social connectedness mechanisms.

The current study examined race- and ethnicity-based differences in the reasons that youth report for vaping, with an emphasis on understanding the relationship between race/ethnicity and vaping for relaxation and stress/anxiety coping. This work also sought to go beyond examining race-based differences as a cause of tobacco-use disparities by assessing social connectedness factors that mediate relationships between race/ethnicity and vaping for relaxation and coping. Research questions were tested using data from the 2019-2020 California Student Tobacco Survey, a representative school-based survey of 10th and 12th grade public school students throughout schools in California. Overall, 7.78% of the sample reported using nicotine vapes in the past 30 days. The final sample included 11,112 high school student current vape users. The most important reason that youth vaped was for relaxation and stress/anxiety coping, with racial and ethnic minorities most likely to report this vaping motivation. Analyses of the structural mechanisms underlying the relationship between race/ethnicity and vaping reasons showed that minority youth reported lower school, peer, and family connectedness when compared to White youth. Lower school and family connectedness were in turn correlated with being motivated to vape to relax or relieve stress and anxiety, and lower overall mental health. Findings imply that future intervention efforts might profitably focus on reducing stressors associated with relaxation and stress/anxiety coping motivations and highlight the importance of connectedness for indirectly decreasing vape use risk by improving negative mood and mental health.

Are California's Local Flavored Tobacco Sales Restrictions Effective in Reducing the Retail Availability of Flavored Tobacco Products? A Multicomponent Evaluation.

INTRODUCTION: Flavored tobacco appeals to new users. This paper describes evaluation results of California's early ordinances restricting flavored tobacco sales. METHODS: A multicomponent evaluation of proximal policy outcomes involved the following: (a) tracking the reach of local ordinances; (b) a retail observation survey; and (c) a statewide opinion poll of tobacco retailers. Change in the population covered by local ordinances was computed. Retail observations compared availability of flavored tobacco at retailers in jurisdictions with and without an ordinance. Mixed models compared ordinance and matched no-ordinance jurisdictions and adjusted for store type. An opinion poll assessed retailers' awareness and ease of compliance with local ordinances, comparing respondents in ordinance jurisdictions with the rest of California. RESULTS: The proportion of Californians living in a jurisdiction with an ordinance increased from 0.6% in April 2015 to 5.82% by January 1, 2019. Flavored tobacco availability was significantly lower in ordinance jurisdictions than in matched jurisdictions: menthol cigarettes (40.6% vs. 95.0%), cigarillos/cigar wraps with explicit flavor descriptors (56.4% vs. 85.0%), and vaping products with explicit flavor descriptors (6.1% vs. 56.9%). Over half of retailers felt compliance was easy; however, retailers in ordinance jurisdictions expressed lower support for flavor sales restrictions. CONCLUSIONS: The proportion of California's population covered by a flavor ordinance increased nine-fold between April 2015 and January 2019. Fewer retailers in ordinance jurisdictions had flavored tobacco products available compared to matched jurisdictions without an ordinance, but many still advertised flavored products they could not sell. Comprehensive ordinances and retailer outreach may facilitate sales-restriction support and compliance.

Early post-treatment blood oxygenation level-dependent responses to emotion processing associated with clinical response to pharmacological treatment in major depressive disorder.

INTRODUCTION: Pre-treatment blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging (fMRI) has been used for the early identification of patients with major depressive disorder (MDD) who later respond or fail to respond to medication. However, BOLD responses early after treatment initiation may offer insight into early neural changes associated with later clinical response. The present study evaluated both pre-treatment and early post-treatment fMRI responses to an emotion processing task, to further our understanding of neural changes associated with a successful response to pharmacological intervention. METHODS: MDD patients who responded (n = 22) and failed to respond (n = 12) after 8 weeks of treatment with either citalopram or quetiapine extended release, and healthy controls (n = 18) underwent two fMRI scans, baseline (pre-treatment), and early post-treatment (one week after treatment commencement). Participants completed an emotional face matching task at both scans. RESULTS: Using threshold-free cluster enhancement (TFCE) and non-parametric permutation testing, fMRI activation maps showed that after one week of treatment, responders demonstrated increased activation in the left parietal lobule, precentral gyrus, and bilateral insula (all P < 0.05 threshold-free cluster enhancement (TFCE) family-wise error-corrected) to negative facial expressions. Non-responders showed some small increases in the precentral gyrus, while controls showed no differences between scans. Compared to non-responders, responders showed some increased activation in the superior parietal lobule and middle temporal gyrus at the post-treatment scan. There were no group differences between responders, non-responders, and controls at baseline. CONCLUSIONS: One week after treatment commencement, BOLD signal changes in the parietal lobules, insula, and middle temporal gyrus were related to clinical response to pharmacological treatment.

Vaping identity in adolescent e-cigarette users: A comparison of norms, attitudes, and behaviors.

INTRODUCTION: Using the tenets underlying social identity theory and the theory of planned behavior, the current study compared the perceptions, attitudes, and behaviors of e-cigarette users that reported vaping as self-defining ("vapers") compared to users that denied vaping was central to their identity ("non-vapers"). METHOD: Secondary analyses of data from the 2017-2018 California Student Tobacco Survey were utilized. A weighted, multivariable regression model (N = 82,217) compared the demographic characteristics, beliefs, and behaviors of vapers and non-vapers. A path analytic model examined whether norms and attitudes mediated the relationship between vaper identity and use behavior. RESULTS: Self-identified sexual and/or gender minority youth were more likely to identify as vapers compared to heterosexual and cisgender respondents. Youth that identified as vapers viewed e-cigarette use as more normative, held more favorable attitudes (i.e., lower harm beliefs), used e-cigarettes more frequently and in greater quantities, were more likely to use fruit and mint flavored e-cigarettes, and were more likely to acquire e-cigarettes from commercial sellers (i.e., vape/tobacco shops; all p < 0.05). Additionally, descriptive norms and attitudes mediated the relationship between vaper identity and use frequency/quantity. CONCLUSIONS: Differences in e-cigarette beliefs and behaviors were found for youth e-cigarette users that perceived vaping as self-defining versus those that did not view vaping as part of their self-concept. Future studies are needed to examine causal directionality between identity, norms, attitudes, and behavior. Tobacco control efforts might use these findings to further denormalize vaping using evidence-based media campaigns and policy implementation.

Chemical Composition of JUUL Pods Collected From Students in California High Schools.

PURPOSE: To examine the chemical composition of JUUL pods collected from a convenience sample of 16 high schools in California to identify possible consumer modification or counterfeit use. METHODS: Using Gas Chromatography-Mass Spectrometry, we quantitatively analyzed the nicotine, propylene glycol (PG), and vegetable glycerin (VG) in JUUL pods (n = 26) collected from California high schools and compared results to commercial 3% (n = 15) and 5% (n = 24) JUUL pods purchased online. RESULTS: Most of the collected JUUL pods (24/26 pods) had a nicotine concentration (43.3 mg/ml, 95% PI: 21.5-65.1) outside the prediction intervals (PI) of the 3% (33.5 mg/ml, 95% PI: 31.8-35.2) and 5% (55.0 mg/ml, 95% PI: 51.5-58.3) commercial JUUL pods. Most (73%) collected JUUL pods had VG concentrations (583.5 mg/ml, PI: 428.9-738.1) lower than the 3% (722.2 mg/ml, PI: 643.0-801.4) and 5% (710.5 mg/ml, PI: 653.1-767.8) commercial JUUL pods. CONCLUSIONS: Used JUUL products collected from high school students or found on school grounds were not chemically consistent with the manufacturer's stated formulations.

Cell sources proposed for nucleus pulposus regeneration.

Lower back pain (LBP) occurs in 80% of adults in their lifetime; resulting in LBP being one of the biggest causes of disability worldwide. Chronic LBP has been linked to the degeneration of the intervertebral disc (IVD). The current treatments for chronic back pain only provide alleviation of symptoms through pain relief, tissue removal, or spinal fusion; none of which target regenerating the degenerate IVD. As nucleus pulposus (NP) degeneration is thought to represent a key initiation site of IVD degeneration, cell therapy that specifically targets the restoration of the NP has been reviewed here. A literature search to quantitatively assess all cell types used in NP regeneration was undertaken. With key cell sources: NP cells; annulus fibrosus cells; notochordal cells; chondrocytes; bone marrow mesenchymal stromal cells; adipose-derived stromal cells; and induced pluripotent stem cells extensively analyzed for their regenerative potential of the NP. This review highlights: accessibility; expansion capability in vitro; cell survival in an IVD environment; regenerative potential; and safety for these key potential cell sources. In conclusion, while several potential cell sources have been proposed, iPSC may provide the most promising regenerative potential.

Race and ethnicity reporting for clinical trials in ClinicalTrials.gov and publications.

Inclusion and subsequent reporting of minority participants in clinical trials are critical for ensuring external validity and detecting differences among subgroups, however reports suggest that ongoing gaps persist. ClinicalTrials.gov began requiring the reporting of race/ethnicity information (if collected) during results submission for trials in April 2017. For this study, we downloaded and compared trial race/ethnicity information from ClinicalTrials.gov submitted before (N = 3540) and after (N = 3542) the requirement date. We found that 42.0% of pre-requirement trials compared to 91.4% of post-requirement trials reported race/ethnicity information in ClinicalTrials.gov; 8.6% of post-requirement trials indicated race/ethnicity information was not collected. Use of NIH/U.S. Office of Management and Budget (OMB) classification categories was slightly higher in the post-requirement (77.1%) compared to pre-requirement (72.8%) samples. Additionally, we examined two 10% random samples of post-requirement trials - one with customized race/ethnicity reporting in ClinicalTrials.gov and the other with corresponding results publications available in PubMed. In the first random sample, 95.9% of customized categories included race information and 52.7% included ethnicity information. In the other random sample, 33.1% had a corresponding results publication, of which 62.4% reported race/ethnicity information in the publication. Among trials without published race/ethnicity information, 90.0% reported race/ethnicity information on ClinicalTrials.gov. This analysis demonstrates that the requirement has advanced public availability of information on the inclusion of minorities in research, but that further work remains to systematically ensure collection and complete reporting of race/ethnicity information.

Age-related differences in cerebral blood flow and cortical thickness with an application to age prediction.

Cerebral cortex thinning and cerebral blood flow (CBF) reduction are typically observed during normal healthy aging. However, imaging-based age prediction models have primarily used morphological features of the brain. Complementary physiological CBF information might result in an improvement in age estimation. In this study, T1-weighted structural magnetic resonance imaging and arterial spin labeling CBF images were acquired in 146 healthy participants across the adult life span. Sixty-eight cerebral cortex regions were segmented, and the cortical thickness and mean CBF were computed for each region. Linear regression with age was computed for each region and data type, and laterality and correlation matrices were computed. Sixteen predictive models were trained with the cortical thickness and CBF data alone as well as a combination of both data types. The age explained more variance in the cortical thickness data (average R2 of 0.21) than in the CBF data (average R2 of 0.09). All 16 models performed significantly better when combining both measurement types and using feature selection, and thus, we conclude that the inclusion of CBF data marginally improves age estimation.