Neddylation orchestrates the complex transcriptional and posttranscriptional program that drives Schwann cell myelination.

Myelination is essential for neuronal function and health. In peripheral nerves, >100 causative mutations have been identified that cause Charcot-Marie-Tooth disease, a disorder that can affect myelin sheaths. Among these, a number of mutations are related to essential targets of the posttranslational modification neddylation, although how these lead to myelin defects is unclear. Here, we demonstrate that inhibiting neddylation leads to a notable absence of peripheral myelin and axonal loss both in developing and regenerating mouse nerves. Our data indicate that neddylation exerts a global influence on the complex transcriptional and posttranscriptional program by simultaneously regulating the expression and function of multiple essential myelination signals, including the master transcription factor EGR2 and the negative regulators c-Jun and Sox2, and inducing global secondary changes in downstream pathways, including the mTOR and YAP/TAZ signaling pathways. This places neddylation as a critical regulator of myelination and delineates the potential pathogenic mechanisms involved in CMT mutations related to neddylation.

An Investigation of Age-Differentiated Conversations About Electronic Nicotine Delivery Systems on Reddit.

Introduction: This study analyzes age-differentiated Reddit conversations about ENDS. Methods: This study combines 2 methods to (1) predict Reddit users' age into 2 categories (13-20 years [underage] and 21-54 years [of legal age]) using a machine learning algorithm and (2) qualitatively code ENDS-related Reddit posts within the 2 groups. The 25 posts with the highest karma score (number of upvotes minus number of downvotes) for each keyword search (i.e., query) and each predicted age group were qualitatively coded. Results: Of 9, the top 3 topics that emerged were flavor restriction policies, Tobacco 21 policies, and use. Opposition to flavor restriction policies was a prominent subcategory for both groups but was more common in the 21-54 group. The 13-20 group was more likely to discuss opposition to minimum age laws as well as access to flavored ENDS products. The 21-54 group commonly mentioned general vaping use behavior. Conclusions: Users predicted to be in the underage group posted about different ENDS-related topics on Reddit than users predicted to be in the of-legal-age group.

Hepatic levels of S-adenosylmethionine regulate the adaptive response to fasting.

There has been an intense focus to uncover the molecular mechanisms by which fasting triggers the adaptive cellular responses in the major organs of the body. Here, we show that in mice, hepatic S-adenosylmethionine (SAMe)-the principal methyl donor-acts as a metabolic sensor of nutrition to fine-tune the catabolic-fasting response by modulating phosphatidylethanolamine N-methyltransferase (PEMT) activity, endoplasmic reticulum-mitochondria contacts, ß-oxidation, and ATP production in the liver, together with FGF21-mediated lipolysis and thermogenesis in adipose tissues. Notably, we show that glucagon induces the expression of the hepatic SAMe-synthesizing enzyme methionine adenosyltransferase α1 (MAT1A), which translocates to mitochondria-associated membranes. This leads to the production of this metabolite at these sites, which acts as a brake to prevent excessive ß-oxidation and mitochondrial ATP synthesis and thereby endoplasmic reticulum stress and liver injury. This work provides important insights into the previously undescribed function of SAMe as a new arm of the metabolic adaptation to fasting.

Vivencias académicas y salud mental en tres cohortes universitarias bajo emergencia covid-19

(analítico) La inesperada irrupción del covid-19 tuvo profundas consecuencias para los/las estudiantes universitarios, quienes se vieron forzados/as a desarrollar sus carreras remotamente. Particularmente en Chile, las cohortes de ingreso 2019, 2020 y 2021 conformaron un caso único debido a las diferentes condiciones bajo las cuales se produjo su incorporación. Esta investigación tuvo por fin determinar las diferencias y la relación entre las variables personales y las vivencias académicas en una muestra de 331 estudiantes ad-hoc. Los resultados obtenidos estadísticamente mediante una estrategia asociativa e inferencial permiten concluir que no existen diferencias entre cohortes respecto a su salud mental, salvo en la vivencia con la carrera entre 2020 y 2021. Se presentan sugerencias para su abordaje personal y académico, así como para el desarrollo de estrategias focalizadas en la salud mental universitaria.

(analytical) The unexpected irruption of COVID-19 had profound consequences for university students, who were forced to develop their careers remotely. Particularly in Chile, the 2019, 2020 and 2021 entry cohorts formed a unique case due to the different conditions under which their incorporation took place. This research aimed to determine the differences and the relationship between personal variables and academic experiences in a sample of 331 ad-hoc students. The results obtained statistically through an associative and inferential strategy, allow us to conclude that there are no differences between cohorts with respect to their mental health, except in the experience with the career between 2020 and 2021. Suggestions are presented for their personal and academic approach, as well as for the development of strategies focused on university mental health.

(analítico) A inesperada irrupção do Covid-19 teve consequências profundas para os estudantes universitários, que foram forçados a desenvolver as suas carreiras remotamente. Particularmente no Chile, as coortes de entrada de 2019, 2020 e 2021 foram únicas devido às diferentes condições sob as quais entra-ram. Esta investigação visava determinar as diferenças e a relação entre as variáveis pessoais e as experiências académicas numa amostra de 331 estudantes ad-hoc. Os resultados obtidos estatisticamente através de uma estratégia associativa e inferencial, permitemnos concluir que não existem diferenças entre os coortes no que respeita à sua saúde mental, excepto na experiência com a carreira entre 2020 e 2021. São apresentadas sugestões para abordagens pessoais e académicas, bem como para o desenvolvimento de estratégias centradas na saúde mental universitária.

U.S. digital tobacco marketing and youth: A narrative review.

We describe findings from peer-reviewed articles on digital tobacco marketing (DTM) using U.S. data related to youth, including research that examines use of age restrictions, DTM exposure and engagement, and associated tobacco use. We searched PubMed, EMBASE, Web of Science, and EBSCOhost in May 2019 and May 2020 for published English language peer-reviewed articles examining DTM that were published from January 2016 to May 2020. Inclusion coding occurred in three stages. The first search identified 519 articles; 167 were coded for inclusion. The second search identified 189 articles; 67 were coded for inclusion. Two coders then assessed whether the included articles mentioned youth (age 18 and younger) or age restrictions in the method and results sections of the full text. Ultimately, 47 articles were included in this review. A codebook was developed and tested through training. Each article was coded for age restrictions, youth exposure to DTM, youth engagement with DTM, and youth tobacco use associated with DTM exposure or engagement. The studies reviewed indicate that DTM on social media was infrequently age-restricted and the stringency of age restriction varied by tobacco product, site owner, and channel. Youth reported being exposed to DTM frequently via the Internet. While youth reported less frequently engaging with DTM compared to being exposed, engagement increased over time. DTM exposure and engagement were associated with tobacco product use. The studies reviewed document an association between DTM exposure and engagement and future tobacco use; thus, DTM may be contributing to the youth tobacco epidemic.

Protein misfolding and clearance in the pathogenesis of a new infantile onset ataxia caused by mutations in PRDX3.

Peroxiredoxin 3 (PRDX3) encodes a mitochondrial antioxidant protein, which is essential for the control of reactive oxygen species homeostasis. So far, PRDX3 mutations are involved in mild-to-moderate progressive juvenile onset cerebellar ataxia. We aimed to unravel the molecular bases underlying the disease in an infant suffering from cerebellar ataxia that started at 19 months old and presented severe cerebellar atrophy and peripheral neuropathy early in the course of disease. By whole exome sequencing, we identified a novel homozygous mutation, PRDX3 p.D163E, which impaired the mitochondrial ROS defense system. In mouse primary cortical neurons, the exogenous expression of PRDX3 p.D163E was reduced and triggered alterations in neurite morphology and in mitochondria. Mitochondrial computational parameters showed that p.D163E led to serious mitochondrial alterations. In transfected HeLa cells expressing the mutation, mitochondria accumulation was detected by correlative light electron microscopy. Mitochondrial morphology showed severe changes, including extremely damaged outer and inner membranes with a notable cristae disorganization. Moreover, spherical structures compatible with lipid droplets were identified, which can be associated with a generalized response to stress and can be involved in the removal of unfolded proteins. In the patient's fibroblasts, PRDX3 expression was nearly absent. The biochemical analysis suggested that the mutation p.D163E would result in an unstable structure tending to form aggregates that trigger unfolded protein responses via mitochondria and endoplasmic reticulum. Altogether, our findings broaden the clinical spectrum of the recently described PRDX3-associated neurodegeneration and provide new insight into the pathological mechanisms underlying this new form of cerebellar ataxia.

Adolescent risk perceptions of ENDS use: Room for change in tobacco education.

Electronic Nicotine Delivery Systems (ENDS) have surpassed combustible cigarettes as the most commonly used tobacco product among U.S. middle and high school students, and research shows that youth do not perceive great risk of harm from regular ENDS use. FDA's public education campaigns help educate youth about the potential risks of using tobacco products and three separate experimental copy testing/ad testing studies (N = 1907) were conducted in support of the FDAs "The Real Cost" (TRC) Cigarette and ENDS Campaigns. These studies provided data for the current investigation which used harm perception items to assess perceived risks of cigarette or ENDS use among adolescents after viewing a public health education advertisement. Eligible youth aged 13-17 who were susceptible, or experimenting, with cigarettes or vaping products were recruited online and randomized into either an ad viewing exposure group, or a non-ad viewing control group. The ads focused on health effects, addiction, or both. Effect sizes on key harm perception measures between groups were computed and standardized to allow for comparisons. Both TRC Cigarette and TRC ENDS ads were able to change harm and addiction perceptions (p < .05); however, effect sizes were significantly larger for items related to health effects for ENDS vs cigarettes (p < .05). When designing youth focused ENDS education campaigns, practitioners should present novel facts in order to take advantage of large effect sizes. Evaluators of early campaign efforts to educate youth about these products may anticipate significant increases in health-related risk perceptions.

Unpacking Cigar Product Familiarity and Terminology among Black and Hispanic Youth: It's All about Blunts.

The prevalence rate of Cigar, Little Cigar, and Cigarillo (CLCC) use among youth rose above the rate of cigarettes for the first time in 2019, and Black and Hispanic youth remain disproportionately more susceptible and likely to use these products compared to White youth. Addressing this disparity through education requires a clearer understanding of the ways youth refer to, and group, CLCCs. Twenty-eight virtual focus groups with youth ages 13-17 (n = 105) were conducted across the U.S. Groups were split by race/ethnicity, with 14 Black and 14 Hispanic groups, and further divided by CLCC experimenters and susceptible users. Youth participants discussed CLCC use behaviors, harm and risk perceptions, and knowledge, attitudes, and beliefs about CLCC products. When shown photos of CLCC products during focus groups, youth across groups identified and labeled these products into four subcategories. Large cigars were universally labeled "cigars". Little cigars were unfamiliar and guessed to be cigarettes. Tipped cigarillos were synonymous with the brand Black and Mild and considered tobacco. Untipped cigarillos were most referred to as "blunts" and used with marijuana. Understanding the nuances of language and use patterns of CLCCs is critical to ensuring the accuracy of measurement and impact of public health communications.

Non-classical Notch signaling by MDA-MB-231 breast cancer cell-derived small extracellular vesicles promotes malignancy in poorly invasive MCF-7 cells.

Aberrant Notch signaling is implicated in breast cancer progression, and recent studies have demonstrated links between the Notch pathway components Notch1 and Notch1 intracellular domain (N1ICD) with poor clinical outcomes. Growing evidence suggests that Notch signaling can be regulated by small extracellular vesicles (SEVs). Here, we used breast cancer cell models to examine whether SEVs are involved in functional Notch signaling. We found that Notch components are packaged into MDA-MB-231- and MCF-7-derived SEVs, although higher levels of N1ICD were detected in SEVs from the more aggressive MDA-MB-231 cell line than from poorly invasive MCF-7 cells. SEV-Notch components were functional, as SEVs cargo from MDA-MB-231 cells induced the expression of Notch target genes in MCF-7 cells and triggered a more invasive and proliferative phenotype concomitant with the acquisition of mesenchymal features. Neutralization of the N1ICD cargo in MDA-MB-231-derived SEVs significantly reduced their potential to enhance the aggressiveness of MCF-7 cells in vitro and in a xenograft model. Overall, our results indicate that a SEV-mediated non-classical pathway of Notch signal transduction in breast cancer models bypasses the need for classical ligand-receptor interactions, which may have important implications in cancer.

OPTIMIZING A PLATELET-RICH PLASMA CONCENTRATION PROTOCOL FOR SOUTH AMERICAN SEA LIONS (OTARIA FLAVESCENS).

Accelerated healing in wild or captive South American sea lions (Otaria flavescens) is a key tool to help minimize infection and complications associated with open wounds, dental disease, and ocular pathology. Platelet-rich plasma (PRP) is an autogenous source for growth factors based on platelet concentration, which can be obtained by centrifuging whole blood collected in sodium citrate anticoagulant. Currently, there are well-defined PRP concentration protocols for humans and most domestic companion animal species. However, there is no clear centrifugation protocol for obtaining PRP in most marine mammal species. This study aimed to optimize the platelet concentration protocol based on whole blood centrifugation using speeds ranging from 500 to 5,000 rpm and times ranging from 3 to 6 min. Blood was drawn from seven adult South American sea lions, placed into 1-ml sodium citrate tubes, and centrifuged following 12 different centrifugation protocols. PRP was designated as the lower third fraction of the centrifuged plasma. Platelet counts were performed using flow cytometry and statistical analysis was carried out to establish a well-defined protocol for efficient PRP production. Transmission electron microscopy (TEM) analysis was performed to evaluate possible platelet degranulation during the different centrifugation protocols and measure platelet areas. Maximum concentration of platelets in PRP was 4.73-fold higher than the number of platelets in equal volume of whole blood, and significant differences in the concentrations obtained were found between the 12 centrifugation protocols evaluated using different speed and time combinations. The best one-step centrifugation protocol resulted from using 900-rpm speed for 3 min. The highest-fold increase was achieved using a two-step centrifugation protocol, which combined the most efficient one-step centrifugation protocol (900 rpm, 3 min) with a second centrifugation using 2,000-rpm speed for 6 min. TEM analysis confirmed that platelets were complete and maintained integrity after the proposed protocol.

Correction: Predicting Age Groups of Reddit Users Based on Posting Behavior and Metadata: Classification Model Development and Validation.

[This corrects the article DOI: 10.2196/25807.].

The Pseudomonas aeruginosa substrate-binding protein Ttg2D functions as a general glycerophospholipid transporter across the periplasm.

In Pseudomonas aeruginosa, Ttg2D is the soluble periplasmic phospholipid-binding component of an ABC transport system thought to be involved in maintaining the asymmetry of the outer membrane. Here we use the crystallographic structure of Ttg2D at 2.5 Å resolution to reveal that this protein can accommodate four acyl chains. Analysis of the available structures of Ttg2D orthologs shows that they conform a new substrate-binding-protein structural cluster. Native and denaturing mass spectrometry experiments confirm that Ttg2D, produced both heterologously and homologously and isolated from the periplasm, can carry two diacyl glycerophospholipids as well as one cardiolipin. Binding is notably promiscuous, allowing the transport of various molecular species. In vitro binding assays coupled to native mass spectrometry show that binding of cardiolipin is spontaneous. Gene knockout experiments in P. aeruginosa multidrug-resistant strains reveal that the Ttg2 system is involved in low-level intrinsic resistance against certain antibiotics that use a lipid-mediated pathway to permeate through membranes.

Predicting Age Groups of Reddit Users Based on Posting Behavior and Metadata: Classification Model Development and Validation.

BACKGROUND: Social media are important for monitoring perceptions of public health issues and for educating target audiences about health; however, limited information about the demographics of social media users makes it challenging to identify conversations among target audiences and limits how well social media can be used for public health surveillance and education outreach efforts. Certain social media platforms provide demographic information on followers of a user account, if given, but they are not always disclosed, and researchers have developed machine learning algorithms to predict social media users' demographic characteristics, mainly for Twitter. To date, there has been limited research on predicting the demographic characteristics of Reddit users. OBJECTIVE: We aimed to develop a machine learning algorithm that predicts the age segment of Reddit users, as either adolescents or adults, based on publicly available data. METHODS: This study was conducted between January and September 2020 using publicly available Reddit posts as input data. We manually labeled Reddit users' age by identifying and reviewing public posts in which Reddit users self-reported their age. We then collected sample posts, comments, and metadata for the labeled user accounts and created variables to capture linguistic patterns, posting behavior, and account details that would distinguish the adolescent age group (aged 13 to 20 years) from the adult age group (aged 21 to 54 years). We split the data into training (n=1660) and test sets (n=415) and performed 5-fold cross validation on the training set to select hyperparameters and perform feature selection. We ran multiple classification algorithms and tested the performance of the models (precision, recall, F1 score) in predicting the age segments of the users in the labeled data. To evaluate associations between each feature and the outcome, we calculated means and confidence intervals and compared the two age groups, with 2-sample t tests, for each transformed model feature. RESULTS: The gradient boosted trees classifier performed the best, with an F1 score of 0.78. The test set precision and recall scores were 0.79 and 0.89, respectively, for the adolescent group (n=254) and 0.78 and 0.63, respectively, for the adult group (n=161). The most important feature in the model was the number of sentences per comment (permutation score: mean 0.100, SD 0.004). Members of the adolescent age group tended to have created accounts more recently, have higher proportions of submissions and comments in the r/teenagers subreddit, and post more in subreddits with higher subscriber counts than those in the adult group. CONCLUSIONS: We created a Reddit age prediction algorithm with competitive accuracy using publicly available data, suggesting machine learning methods can help public health agencies identify age-related target audiences on Reddit. Our results also suggest that there are characteristics of Reddit users' posting behavior, linguistic patterns, and account features that distinguish adolescents from adults.

Those who believe they can, do: The relationship between smoking avoidance beliefs, perceived risks of smoking, and behavior in a sexual and gender minority young adult sample.

An individual's beliefs in their perceived risk and ability to resist smoking have been found to be associated with smoking behavior. The current study explores the effects of confidence in one's ability to avoid smoking, measured by avoidance beliefs, on the relationship between perceived risks of smoking and behavior. This analysis was done using 2016 baseline data collected among 4057 participants aged 18-24 for the evaluation of a large-scale public education campaign in the U.S. aimed at reducing tobacco use among sexual and gender minority young adults. The analytic sample included roughly 3493 participants per analysis. Analyses used the following measures: (1) perceived risks of smoking (e.g., smoking cigarettes will shorten my life); (2) confidence to avoid smoking in various situations (i.e., avoidance beliefs), and (3) past 30-day cigarette smoking. Binary logistic regression models with interaction analyses assessed the relationship between perceived risks of smoking and past 30-day smoking behavior using the interaction term of avoidance beliefs. An interaction between perceived risks of smoking and avoidance behaviors interaction emerged, such that the negative relationship between perceived risks of smoking and smoking behavior was stronger for those who believed that they could avoid smoking in various situations. This suggests that the relationship between perceived risk and smoking behavior can be bolstered if one's beliefs about their ability to avoid smoking are strong. Campaigns that build smoking avoidance confidence may enhance the effects of tobacco outcome expectations-related messaging on smoking.

Influencer prevalence and role on cigar brand Instagram pages.

PURPOSE: Influencers market products for tobacco companies on social media. This is the first study to systematically examine leading cigar brands' use of influencers on their brand Instagram pages. METHODS: We identified 24 leading cigar brands, using July 2017-June 2018 US retail data. We identified cigar brands that had official appearing Instagram pages, with at least one influencer in the past 20 posts. We coded characteristics of the past three posts from each of five brand pages that contained influencers, such as setting and what the influencer was doing. Finally, we described influencer characteristics. RESULTS: Approximately one-third of the 24 brands had official Instagram accounts with at least one influencer in the past 20 posts. We identified 28 influencers, typically people of colour from the hip-hop music industry, some with millions of followers. Influencers included Bella Thorne (@bellathorne), Shaquille O'Neal (@shaq) and T.I. (@troubleman31). Brands' posts that contained influencers showed the influencer using/holding a product, wearing branded merchandise or appearing in photos with a brand watermark. Three brands' pages posted sponsored event photos (ie, concerts and events using branded backgrounds). DISCUSSION: Cigar brands commonly use influencers to market their products on brand Instagram pages. Results are consistent with previous findings that cigar companies' marketing may target younger African Americans and highlight the potential utility of education campaigns that similarly engage influencers.

Caspase Activation and Caspase-Mediated Cleavage of APP Is Associated with Amyloid ß-Protein-Induced Synapse Loss in Alzheimer's Disease.

Amyloid ß-protein (Aß) toxicity is hypothesized to play a seminal role in Alzheimer's disease (AD) pathogenesis. However, it remains unclear how Aß causes synaptic dysfunction and synapse loss. We hypothesize that one mechanism of Aß-induced synaptic injury is related to the cleavage of amyloid ß precursor protein (APP) at position D664 by caspases that release the putatively cytotoxic C31 peptide. In organotypic slice cultures derived from mice with a knock-in mutation in the APP gene (APP D664A) to inhibit caspase cleavage, Aß-induced synaptic injury is markedly reduced in two models of Aß toxicity. Loss of dendritic spines is also attenuated in mice treated with caspase inhibitors. Importantly, the time-dependent dendritic spine loss is correlated with localized activation of caspase-3 but is absent in APP D664A cultures. We propose that the APP cytosolic domain plays an essential role in Aß-induced synaptic damage in the injury pathway mediated by localized caspase activation.

Social media use by leading US e-cigarette, cigarette, smokeless tobacco, cigar and hookah brands.

BACKGROUND: Youth and young adults frequently use social media and are susceptible to tobacco use. This study is the first to provide a systematic overview of how leading tobacco product brands use popular social media platforms. METHODS: We identified 112 leading brands of e-cigarettes, hookah, cigars, cigarettes and smokeless tobacco based on sales and self-report user data. We searched for each brand on six platforms: Instagram, Facebook, Twitter, YouTube, Pinterest and Tumblr. In early 2019, we conducted a content analysis of each page, coding: age restrictions, warning display, page characteristics and post characteristics. RESULTS: Cigarette brands were generally not present. Most e-cigarettes, hookah and cigar brands had pages on at least two platforms. One-third of smokeless brands had pages on at least one platform. Few brands had pages on Pinterest and Tumblr. Most pages had existed for 3-5 years. Overall, brand pages rarely used age gating, did not display health warnings, generally posted images of a product alone and often used hashtags unrelated to tobacco. Brands commonly used special features like ephemeral posts on Instagram and pop-up chat windows on Facebook. Many pages displayed images of young people and mentioned flavour. Median followers per brand ranged from about 1 000-10 000, and total followers summed across brands reached over 5 million on Facebook and Instagram alone. CONCLUSIONS: Leading brands of most tobacco product types use social media extensively. Several findings identify issues related to youth exposure to and appeal of tobacco social media marketing. Findings can inform tobacco education efforts and regulation.

Limited efficacy of zonisamide in the treatment of refractory infantile spasms.

A series of relatively small studies collectively suggest that zonisamide may be effective in the treatment of infantile spasms. Using a large single-center cohort of children with infantile spasms, we set out to evaluate the efficacy and safety of zonisamide. We retrospectively identified all patients with infantile spasms who were treated with zonisamide at our center. For each patient, we recorded dates of birth, infantile spasms onset, response (if any), and most recent follow-up. To quantify zonisamide exposure, we recorded daily dosage and patient weight at each sequential encounter so as to allow calculation of peak and weighted-average weight-based dosage. We identified 87 children who were treated with zonisamide, of whom 78 had previously been treated with hormonal therapy or vigabatrin. Peak and weighted-average zonisamide dosage were 7.1 (interquartile range 3.6, 10.2) and 5.4 (interquartile range 3.0, 8.9) mg/kg/day, respectively. Whereas five (6%) patients exhibited resolution of epileptic spasms, only two (2%) patients exhibited video-EEG confirmed resolution of both epileptic spasms and hypsarrhythmia (electroclinical response). Importantly, both electroclinical responders had not previously been treated with hormonal therapy or vigabatrin; in contrast, none of the 78 children with prior failure of hormonal therapy or vigabatrin subsequently responded to zonisamide. Zonisamide was well tolerated, and there were no deaths. This study suggests that zonisamide exhibits favorable tolerability but very limited efficacy among patients who do not respond to first-line therapy.

Felbamate in the treatment of refractory epileptic spasms.

Several small case series provide conflicting impressions of the efficacy of felbamate for treatment of epileptic spasms. Using a large single-center cohort of children with epileptic spasms, we retrospectively evaluated the efficacy and safety of felbamate. We identified all patients with video-EEG confirmed epileptic spasms who were treated with felbamate at our center. We quantified felbamate exposure by calculating peak and weighted-average weight-based dose. Clinical response was defined as resolution of epileptic spasms for at least 28 days, beginning not more than 3 months after felbamate initiation. Electroclinical response was defined as clinical response accompanied by overnight video-EEG demonstrating freedom from epileptic spasms and hypsarrhythmia. Among a cohort of 476 infants, we identified 62 children who were treated with felbamate, of whom 58 had previously failed treatment with hormonal therapy or vigabatrin. Median peak and weighted-average felbamate dosages were 47 and 40 mg/kg/day, respectively. Five (8%) children were classified as clinical responders and two (3%) children were classified as electroclinical responders. Among 17 patients with latency from epileptic spasms onset to felbamate initiation of less than 12 months, we observed 4 (24%) clinical responders. This study suggests that felbamate may be efficacious for treatment of epileptic spasms and that further rigorous study is warranted.

Who Uses Tobacco Products? Using Peer Crowd Segmentation to Identify Youth at Risk for Cigarettes, Cigar Products, Hookah, and E-Cigarettes.

Background: Understanding which adolescents are at greatest risk for cigarettes and other tobacco products is critical to inform tailored and targeted interventions. Objectives: We used peer crowds (macro-level subcultures) to identify subgroups of adolescents at-risk for using and being open to using cigarettes; cigars, cigarillos, and little cigars (cigar products); hookah; e-cigarettes; any tobacco product; and multiple products. Methods: In 2017, youth ages 12-17 in five U.S. states completed cross-sectional surveys (n = 1,167). Participants provided data on cigarette use (experimentation) and openness to use (susceptibility); cigar product, hookah, and e-cigarette use (ever use) and openness to use (curiosity); and identification with five peer crowds (Alternative, Country, Hip Hop, Mainstream, Popular). We used chi-square tests to compare rates by peer crowd, and multivariate logistic regressions to assess odds of use and openness for each crowd (reference: Mainstream). Results: Risk differed by peer crowd. Hip Hop youth reported high rates of use, ranging from 12.8% (cigarettes) to 33.4% (e-cigarettes). Regressions revealed increased odds of use for Hip Hop compared to Mainstream for all products, especially cigar products and multi-product use. Popular (cigar products, e-cigarettes) and Alternative (cigarettes) demonstrated increased odds of use compared to Mainstream. We also observed elevated odds of cigarette openness among Alternative, Country, and Hip Hop youth, and of hookah openness among Hip Hop and Popular youth compared to Mainstream. Conclusions/Importance: Peer crowd-tailored cigarette education campaigns can be extended to address other tobacco product risk, especially for higher-risk peer crowds such as Hip Hop.