Intermittent glucocorticoid treatment improves muscle metabolism via the PGC1α/Lipin1 axis in an aging-related sarcopenia model.

Sarcopenia burdens the older population through loss of muscle energy and mass, yet treatments to functionally rescue both parameters are lacking. The glucocorticoid prednisone remodels muscle metabolism on the basis of frequency of intake, but its mechanisms in sarcopenia are unknown. We found that once-weekly intermittent prednisone administration rescued muscle quality in aged 24-month-old mice to a level comparable to that seen in young 4-month-old mice. We discovered an age- and sex-independent glucocorticoid receptor transactivation program in muscle encompassing peroxisome proliferator-activated receptor γ coactivator 1 α (PGC1α) and its cofactor Lipin1. Treatment coordinately improved mitochondrial abundance through isoform 1 and muscle mass through isoform 4 of the myocyte-specific PGC1α, which was required for the treatment-driven increase in carbon shuttling from glucose oxidation to amino acid biogenesis. We also probed myocyte-specific Lipin1 as a nonredundant factor coaxing PGC1α upregulation to the stimulation of both oxidative and anabolic effects. Our study unveils an aging-resistant druggable program in myocytes for the coordinated rescue of energy and mass in sarcopenia.

Antibiotic lock solutions as adjunct therapy for catheter-related blood stream infections in pediatric hemodialysis patients.

The predominant use of intravenous catheters as primary access type in the pediatric hemodialysis population is associated with an increased risk of catheter related blood stream infections. While strict adherence to catheter placement and long-term care guidelines have helped to decrease the incidence of these infections, blood stream infections remain an infection burden in pediatric patients with long term hemodialysis catheters. The formation of biofilms on the surfaces of these catheters has been shown to be a source of microbes causing blood stream infections. One of the strategies for preventing bacterial colonization, inhibiting microbial multiplication, and suppressing the seeding of these microbes from biofilms upon maturation, has been the use of antibiotic-based lock solutions in-between dialysis treatments. Although clinical guidelines for the use of antibiotic lock solutions are yet to be developed, available evidence suggests a beneficial role of antibiotic lock solutions in the management of catheter related blood stream infections. Additionally, a clear understanding of how biofilms are formed and their role in the pathogenesis of catheter related bloodstream infection will facilitate the development of solutions that can prevent biofilm formation and inhibit their multiplication, maturation and seeding into the bloodstream.

MCUb is an inducible regulator of calcium-dependent mitochondrial metabolism and substrate utilization in muscle.

Mitochondria use the electron transport chain to generate high-energy phosphate from oxidative phosphorylation, a process also regulated by the mitochondrial Ca2+ uniporter (MCU) and Ca2+ levels. Here, we show that MCUb, an inhibitor of MCU-mediated Ca2+ influx, is induced by caloric restriction, where it increases mitochondrial fatty acid utilization. To mimic the fasted state with reduced mitochondrial Ca2+ influx, we generated genetically altered mice with skeletal muscle-specific MCUb expression that showed greater fatty acid usage, less fat accumulation, and lower body weight. In contrast, mice lacking Mcub in skeletal muscle showed increased pyruvate dehydrogenase activity, increased muscle malonyl coenzyme A (CoA), reduced fatty acid utilization, glucose intolerance, and increased adiposity. Mechanistically, pyruvate dehydrogenase kinase 4 (PDK4) overexpression in muscle of Mcub-deleted mice abolished altered substrate preference. Thus, MCUb is an inducible control point in regulating skeletal muscle mitochondrial Ca2+ levels and substrate utilization that impacts total metabolic balance.

Glucocorticoid intermittence coordinates rescue of energy and mass in aging-related sarcopenia through the myocyte-autonomous PGC1alpha-Lipin1 transactivation.

Sarcopenia burdens the elderly population through loss of muscle energy and mass, yet treatments to functionally rescue both parameters are missing. The glucocorticoid prednisone remodels muscle metabolism based on frequency of intake, but its mechanisms in sarcopenia are unknown. We found that once-weekly intermittent prednisone rescued muscle quality in aged 24-month-old mice to levels comparable to young 4-month-old mice. We discovered an age- and sex-independent glucocorticoid receptor transactivation program in muscle encompassing PGC1alpha and its co-factor Lipin1. Treatment coordinately improved mitochondrial abundance through isoform 1 and muscle mass through isoform 4 of the myocyte-specific PGC1alpha, which was required for the treatment-driven increase in carbon shuttling from glucose oxidation to amino acid biogenesis. We also probed the myocyte-specific Lipin1 as non-redundant factor coaxing PGC1alpha upregulation to the stimulation of both oxidative and anabolic capacities. Our study unveils an aging-resistant druggable program in myocytes to coordinately rescue energy and mass in sarcopenia.

Canine models of Charcot-Marie-Tooth: MTMR2, MPZ, and SH3TC2 variants in golden retrievers with congenital hypomyelinating polyneuropathy.

Congenital hypomyelinating polyneuropathy (HPN) restricted to the peripheral nervous system was reported in 1989 in two Golden Retriever (GR) littermates. Recently, four additional cases of congenital HPN in young, unrelated GRs were diagnosed via neurological examination, electrodiagnostic evaluation, and peripheral nerve pathology. Whole-genome sequencing was performed on all four GRs, and variants from each dog were compared to variants found across >1,000 other dogs, all presumably unaffected with HPN. Likely causative variants were identified for each HPN-affected GR. Two cases shared a homozygous splice donor site variant in MTMR2, with a stop codon introduced within six codons following the inclusion of the intron. One case had a heterozygous MPZ isoleucine to threonine substitution. The last case had a homozygous SH3TC2 nonsense variant predicted to truncate approximately one-half of the protein. Haplotype analysis using 524 GR established the novelty of the identified variants. Each variant occurs within genes that are associated with the human Charcot-Marie-Tooth (CMT) group of heterogeneous diseases, affecting the peripheral nervous system. Testing a large GR population (n = >200) did not identify any dogs with these variants. Although these variants are rare within the general GR population, breeders should be cautious to avoid propagating these alleles.

Phenobarbital versus benzodiazepines in alcohol withdrawal syndrome.

AIM: Phenobarbital, a long-acting barbiturate, presents an alternative to conventional benzodiazepine treatment for alcohol withdrawal syndrome (AWS). Currently, existing research offers only modest guidance on the safety and effectiveness of phenobarbital in managing AWS in hospital settings. The study objective was to assess if a phenobarbital protocol for the treatment of AWS reduces respiratory complications when compared to a more traditionally used benzodiazepine protocol. METHODS: A retrospective cohort study analyzing adults who received either phenobarbital or benzodiazepine-based treatment for AWS over a 4-year period, 2015-2019, in a community teaching hospital in a large academic medical system. RESULTS: A total of 147 patient encounters were included (76 phenobarbital and 71 benzodiazepine). Phenobarbital was associated with a significantly decreased risk of respiratory complications, defined by the occurrence of intubation (15/76 phenobarbital [20%] vs. 36/71 benzodiazepine [51%]) and decreased incidence of the requirement of six or greater liters of oxygen when compared with benzodiazepines (10/76 [13%] vs. 28/71 [39%]). There was a significantly higher incidence of pneumonia in benzodiazepine patients (15/76 [20%] vs. 33/71 [47%]). Mode Richmond Agitation Sedation Scale (RASS) scores were more frequently at goal (0 to -1) between 9 and 48 h after the loading dose of study medication for phenobarbital patients. Median hospital and ICU length of stay were significantly shorter for phenobarbital patients when compared with benzodiazepine patients (5 vs. 10 days and 2 vs. 4 days, respectively). CONCLUSION: Parenteral phenobarbital loading doses with an oral phenobarbital tapered protocol for AWS resulted in decreased risk of respiratory complications when compared to standard treatment with benzodiazepines.

Isaac Syndrome with Intractable Neuropathic Pain Features: A Case Report.

Isaac syndrome (IS) is a peripheral nerve hyperexcitability state associated with voltage-gated potassium channel (VGKC) complex antibodies. Major manifestations are muscle twitching, stiffness, hypertrophy, and dysautonomic features such as hyperhidrosis [Ahmed and Simmons. Muscle Nerve. 2015;52(1):5-12]. Neuropathic pain is a rare manifestation. We describe a case of IS characterized by muscle twitching and intractable neuropathic pain. Diagnostic workup included elevated VGKC complex antibodies and EMG/NC that showed neuromyotonic discharges. Neuropathic pain was initially difficult to relieve even after using multiple medications, including opiates, benzodiazepines, anticonvulsants, and intravenous immunoglobulin (IVIg). Moderate pain control was eventually achieved with long-term use of carbamazepine and subcutaneous immunoglobulin (SCIg). Common manifestations of IS are muscle twitching, stiffness hypertrophy, and dysautonomia [Ahmed and Simmons. Muscle Nerve. 2015;52(1):5-12]. Sensory manifestations such as neuropathic pain are rare, but, as illustrated by our patient, can be the most distressing symptom. In our patient, not only was neuropathic pain disabling but it also showed the least response to IVIg. The use of 200 mg of long-acting carbamazepine twice daily with weekly SCIg demonstrated the best response. This case highlights an uncommon but potentially resistant symptom of IS.

Neuropsychological Test Performances and Depression in Early-Stage De Novo Parkinson's Disease.

OBJECTIVE: Evaluate neuropsychological test performance in depressed patients with early-stage Parkinson's disease. METHOD: Data from 422 participants from the Parkinson's Progression Marker Initiative were examined. The Geriatric Depression Scale-15 was used to categorize depressed and non-depressed participants. Neuropsychological tests measured verbal learning/memory, processing speed, visuospatial ability, verbal fluency, and working memory. Demographic and clinical variables were compared using independent samples t tests and chi-square analyses.Linear regression models were fit to adjust for age, years of education, and symptom duration. RESULTS: The non-depressed group (n = 280) was significantly older; t(246.08) = 2.25, p = .026 and had higher education; t(420) = 2.35, p = .019; and longer duration of PD symptoms; t(170.58) = -2.13, p = .035 than the depressed group (n = 142). The non-depressed group performed better on a working memory task than the depressed group, t(420) = 2.05, p = .041, but the results did not appear to be of clinical significance. There was no significant difference between other cognitive domains. The results were not influenced by age, education, or disease duration. CONCLUSIONS: Among patients with early-stage, untreated Parkinson's disease, depression does not appear to affect neuropsychological test performance. Clinicians should demonstrate caution in over-interpreting the influence of depression on cognition in this population.

Clinical and molecular features of subungual melanomas are site-specific and distinct from acral melanomas.

Subungual melanomas (SUM) arise beneath the nails of the hands and feet, and account for 0.7-3.5% of all malignant melanomas. Most studies include SUM in the category of acral melanoma, but understanding the specific features of SUM is critical for improving patient care. In this study, we performed a site-specific comparison of the clinical and molecular features between 54 cases of SUM and 78 cases of nonsubungual acral melanoma. Compared to patients with acral melanoma, patients with SUM were younger at diagnosis, had a higher prevalence of primary melanomas on the hand, and had more frequent reports of previous trauma at the tumor site. SUM was deeper than acral melanoma at diagnosis, which correlated with an increased frequency of metastases. Analysis of common melanoma driver genes revealed KIT and KRAS mutations were predominantly found in SUM, whereas BRAF and NRAS mutations occurred almost exclusively in acral melanoma. We also discovered molecular differences in the cell cycle pathway, where CDK4/CCND1 amplifications were more frequent in SUM and CDKN2A/B loss occurred mostly in acral melanoma, and in the PI3K/mTOR pathway, where RICTOR amplification and TSC1 K587R mutations were exclusively in SUM and PTEN loss and AKT1 mutations were exclusively in acral melanoma. Comparison of hand versus foot tumors revealed more frequent ulceration of SUM foot tumors, which correlated with more distal metastases and poorer overall survival. In summary, we find SUM are both clinically and molecularly distinct from acral melanoma, and our data suggest KIT, CDK4/6, and mTOR inhibitors may be particularly relevant and effective treatments for patients with SUM.

Electrocardiogram Standards for Children and Young Adults Using Z-Scores.

BACKGROUND: Normative ECG values for children are based on relatively few subjects and are not standardized, resulting in interpersonal variability of interpretation. Recent advances in digital technology allow a more quantitative, reproducible assessment of ECG variables. Our objective was to create the foundation of normative ECG standards in the young utilizing Z-scores. METHODS: One hundred two ECG variables were collected from a retrospective cohort of 27 085 study subjects with no known heart condition, ages 0 to 39 years. The cohort was divided into 16 age groups by sex. Median, interquartile range, and range were calculated for each variable adjusted to body surface area. RESULTS: Normative standards were developed for all 102 ECG variables including heart rate; P, R, and T axis; R-T axis deviation; PR interval, QRS duration, QT, and QTc interval; P, Q, R, S, and T amplitudes in 12 leads; as well as QRS and T wave integrals. Incremental Z-score values between -2.5 and 2.5 were calculated to establish upper and lower limits of normal. Historical ECG interpretative concepts were reassessed and new concepts observed. CONCLUSIONS: Electronically acquired ECG values based on the largest pediatric and young adult cohort ever compiled provide the first detailed, standardized, quantitative foundation of traditional and novel ECG variables. Expression of ECG variables by Z-scores lends an objective and reproducible evaluation without interpreter bias that can lead to more confident establishment of ECG-disease correlations and improved automated ECG readings in high-volume cardiac screening efforts in the young. Graphic Abstract: A graphic abstract is available for this article.

True Colors: Commercially-acquired morphological genotypes reveal hidden allele variation among dog breeds, informing both trait ancestry and breed potential.

Direct-to-consumer canine genetic testing is becoming increasingly popular among dog owners. The data collected therein provides intriguing insight into the current status of morphological variation present within purebred populations. Mars WISDOM PANELTM data from 11,790 anonymized dogs, representing 212 breeds and 4 wild canine species, were evaluated at genes associated with 7 coat color traits and 5 physical characteristics. Frequencies for all tested alleles at these 12 genes were determined by breed and by phylogenetic grouping. A sub-set of the data, consisting of 30 breeds, was divided into separate same-breed populations based on country of collection, body size, coat variation, or lineages selected for working or conformation traits. Significantly different (p ≤ 0.00167) allele frequencies were observed between populations for at least one of the tested genes in 26 of the 30 breeds. Next, standard breed descriptions from major American and international registries were used to determine colors and tail lengths (e.g. genetic bobtail) accepted within each breed. Alleles capable of producing traits incongruous with breed descriptions were observed in 143 breeds, such that random mating within breeds has probabilities of between 4.9e-7 and 0.25 of creating undesirable phenotypes. Finally, the presence of rare alleles within breeds, such as those for the recessive black coloration and natural bobtail, was combined with previously published identity-by-decent haplotype sharing levels to propose pathways by which the alleles may have spread throughout dog breeds. Taken together, this work demonstrates that: 1) the occurrence of low frequency alleles within breeds can reveal the influence of regional or functional selection practices; 2) it is possible to visualize the potential historic connections between breeds that share rare alleles; and 3) the necessity of addressing conflicting ideals in breed descriptions relative to actual genetic potential is crucial.

A Whole Methylome Study of Ethanol Exposure in Brain and Blood: An Exploration of the Utility of Peripheral Blood as Proxy Tissue for Brain in Alcohol Methylation Studies.

BACKGROUND: Recent reviews have highlighted the potential use of blood-based methylation biomarkers as diagnostic and prognostic tools of current and future alcohol use and addiction. Due to the substantial overlap that often exists between methylation patterns across different tissues, including blood and brain, blood-based methylation may track methylation changes in brain; however, little work has explored the overlap in alcohol-related methylation in these tissues. METHODS: To study the effects of alcohol on the brain methylome and identify possible biomarkers of these changes in blood, we performed a methylome-wide association study in brain and blood from 40 male DBA/2J mice that received either an acute ethanol (EtOH) or saline intraperitoneal injection. To investigate all 22 million CpGs in the mouse genome, we enriched for the methylated genomic fraction using methyl-CpG binding domain (MBD) protein capture followed by next-generation sequencing (MBD-seq). We performed association tests in blood and brain separately followed by enrichment testing to determine whether there was overlapping alcohol-related methylation in the 2 tissues. RESULTS: The top result for brain was a CpG located in an intron of Ttc39b (p = 5.65 × 10-08 ), and for blood, the top result was located in Espnl (p = 5.11 × 10-08 ). Analyses implicated pathways involved in inflammation and neuronal differentiation, such as CXCR4, IL-7, and Wnt signaling. Enrichment tests indicated significant overlap among the top results in brain and blood. Pathway analyses of the overlapping genes converge on MAPKinase signaling (p = 5.6 × 10-05 ) which plays a central role in acute and chronic responses to alcohol and glutamate receptor pathways, which can regulate neuroplastic changes underlying addictive behavior. CONCLUSIONS: Overall, we have shown some methylation changes in brain and blood after acute EtOH administration and that the changes in blood partly mirror the changes in brain suggesting the potential for DNA methylation in blood to be biomarkers of alcohol use.

Comparison of Two Lidocaine Administration Techniques on Perceived Pain From Bedside Procedures: A Randomized Clinical Trial.

BACKGROUND: Lidocaine is used to alleviate procedural pain but paradoxically increases pain during injection. Pain perception can be modulated by non-noxious stimuli such as temperature or touch according to the gate control theory of pain. We postulated that lidocaine dripped onto the skin prior to injection would cool or add the sensation of touch at the skin surface to reduce pain perception from the procedure. METHODS: A randomized clinical trial of patients referred to the procedure service from February 2011 through March 2015 was conducted. All patients received 1% subcutaneous lidocaine injection. Patients randomized to the intervention group had approximately 1 to 2 ml of lidocaine squirted onto the skin surface prior to subcutaneous lidocaine injection. Patients were blinded to the details of the intervention and were surveyed by a blinded investigator to document the primary outcome (severity of pain from the procedure) using a visual analog scale. RESULTS: A total of 481 patients provided consent and were randomized to treatment. There was a significant improvement in the primary outcome of procedural pain (control, 16.6 ± 24.8 mm vs 12.2 ± 19.4 mm; P = .03) with the intervention group as assessed by using the visual analog scale score. Pain scores were primarily improved for peripherally inserted central catheters (control, 18.8 ± 25.6 mm vs 12.2 ± 18.2 mm; P = .02) upon subgroup analysis. CONCLUSIONS: Bedside procedures are exceedingly common. Data regarding the severity of procedural pain and strategies to mitigate it are important for the informed consent process and patient satisfaction. Overall, pain reported from common bedside procedures is low, but pain can be further reduced with the addition of lidocaine onto the skin surface to modulate pain perception. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT01330134; URL: www.clinicaltrials.gov.

Reasons for Electronic Cigarette Use Among Middle and High School Students - National Youth Tobacco Survey, United States, 2016.

Electronic cigarettes (e-cigarettes) were the most commonly used tobacco product among U.S. middle school and high school students in 2016 (1). CDC and the Food and Drug Administration (FDA) analyzed data from the 2016 National Youth Tobacco Survey (NYTS) to assess self-reported reasons for e-cigarette use among U.S. middle school (grades 6-8) and high school (grades 9-12) student e-cigarette users. Among students who reported ever using e-cigarettes in 2016, the most commonly selected reasons for use were 1) use by "friend or family member" (39.0%); 2) availability of "flavors such as mint, candy, fruit, or chocolate" (31.0%); and 3) the belief that "they are less harmful than other forms of tobacco such as cigarettes" (17.1%). The least commonly selected reasons were 1) "they are easier to get than other tobacco products, such as cigarettes" (4.8%); 2) "they cost less than other tobacco products such as cigarettes" (3.2%); and 3) "famous people on TV or in movies use them" (1.5%). Availability of flavors as a reason for use was more commonly selected by high school users (32.3%) than by middle school users (26.8%). Efforts to prevent middle school and high school students from initiating the use of any tobacco product, including e-cigarettes, are important to reduce tobacco product use among U.S. youths (2).

Study design and rationale to assess Doxycycline Efficacy in preventing coronary Artery Lesions in children with Kawasaki disease (DEAL trial) - A phase II clinical trial.

BACKGROUND: Kawasaki disease (KD) is the most common acquired heart disease in children of the developed world, and triggers progressive coronary artery lesions (CAL) in 30% of cases if left untreated. Despite standard anti-inflammatory treatment for KD, CAL (dilation or aneurysm) still occurs in 5-10% of children, increasing their risk for fatal coronary artery complications. CAL is mediated by enhanced matrix metalloproteinase activity and elastin breakdown induced by the inflammatory process in the coronary artery wall. Doxycycline is an effective inhibitor of matrix metalloproteinases, and has been shown to reduce elastin breakdown and CAL in a mouse model of KD, but has not been evaluated in patients. OBJECTIVE: We aim to evaluate the efficacy of doxycycline in the prevention of CAL in children during the acute phase of KD. DESIGN: This is a phase II prospective, randomized, double-blinded, clinical trial in two steps. In Step 1, any child older than 1month with the diagnosis of KD will be included. Children with KD will be included in Step 2 if they develop coronary artery dilation (z-score≥2.5) within 20days from the onset of fever. Study subjects in Step 2 will be randomized to receive a 3-week course of doxycycline or placebo. EVALUATION: The efficacy of a 3-week doxycycline course during the acute phase of KD will be evaluated by measuring the decline in coronary artery z-scores from baseline with doxycycline treatment compared to placebo. CLINICAL TRIAL REGISTRATION: This study was registered on clinicaltrials.gov (NCT01917721).

Thrombocytopenia and CD34 expression is decoupled from α-granule deficiency with mutation of the first growth factor-independent 1B zinc finger.

Essentials The phenotypes of different growth factor-independent 1B (GFI1B) variants are not established. GFI1B variants produce heterogeneous clinical phenotypes dependent on the site of mutation. Mutation of the first non-DNA-binding zinc-finger causes a mild platelet and clinical phenotype. GFI1B regulates the CD34 promoter; platelet CD34 expression is an indicator of GFI1B mutation. SUMMARY: Background Mutation of the growth factor-independent 1B (GFI1B) fifth DNA-binding zinc-finger domain causes macrothrombocytopenia and α-granule deficiency leading to clinical bleeding. The phenotypes associated with GFI1B variants disrupting non-DNA-binding zinc-fingers remain uncharacterized. Objectives To determine the functional and phenotypic consequences of GFI1B variants disrupting non-DNA-binding zinc-finger domains. Methods The GFI1B C168F variant and a novel GFI1B c.2520 + 1_2520 + 8delGTGGGCAC splice variant were identified in four unrelated families. Phenotypic features, DNA-binding properties and transcriptional effects were determined and compared with those in individuals with a GFI1B H294 fs mutation of the fifth DNA-binding zinc-finger. Patient-specific induced pluripotent stem cell (iPSC)-derived megakaryocytes were generated to facilitate disease modeling. Results The DNA-binding GFI1B variant C168F, which is predicted to disrupt the first non-DNA-binding zinc-finger domain, is associated with macrothrombocytopenia without α-granule deficiency or bleeding symptoms. A GFI1B splice variant, c.2520 + 1_2520 + 8delGTGGGCAC, which generates a short GFI1B isoform that lacks non-DNA-binding zinc-fingers 1 and 2, is associated with increased platelet CD34 expression only, without quantitative or morphologic platelet abnormalities. GFI1B represses the CD34 promoter, and this repression is attenuated by different GFI1B zinc-finger mutations, suggesting that deregulation of CD34 expression occurs at a direct transcriptional level. Patient-specific iPSC-derived megakaryocytes phenocopy these observations. Conclusions Disruption of GFI1B non-DNA-binding zinc-finger 1 is associated with mild to moderate thrombocytopenia without α-granule deficiency or bleeding symptomatology, indicating that the site of GFI1B mutation has important phenotypic implications. Platelet CD34 expression appears to be a common feature of perturbed GFI1B function, and may have diagnostic utility.

Electronic cigarette use among US adults in the Population Assessment of Tobacco and Health (PATH) Study, 2013-2014.

BACKGROUND: Electronic cigarette (e-cigarette) use in the USA is increasing. As such, it is critical to understand who uses e-cigarettes, how e-cigarettes are used and what types of products are prevalent. This study assesses patterns of current e-cigarette use among daily and non-daily adult users in the 2013-2014 Population Assessment of Tobacco and Health (PATH) Study. METHODS: We examined the proportion of current adult e-cigarette users (n=3642) reporting infrequent use (use on 'some days' and use on 0-2 of the past 30 days), moderate use (use on 'some days' and use on >2 of the past 30 days) and daily use. We examined demographic characteristics, use of other tobacco products and e-cigarette product characteristics overall and by use category. Adjusted prevalence ratios (aPRs) were calculated using Poisson regression to assess correlates of daily e-cigarette use. RESULTS: Among the 5.5% of adult current e-cigarette users in the PATH Study, 42.2% reported infrequent use, 36.5% reported moderate use and 21.3% reported daily use. Cigarette smokers who quit in the past year were more likely to report daily e-cigarette use, compared with current smokers (aPR=3.21, 95% CI=2.75 to 3.76). Those who reported using rechargeable or refillable devices were more likely to report daily use compared with those who did not use these devices (aPR=1.95, 95% CI=1.44 to 2.65 and aPR=2.10, 95% CI=1.75 to 2.52, respectively). CONCLUSIONS: The majority of e-cigarette users in this study reported less than daily use. Compared with non-daily use, daily use was associated with being a former smoker; however, cross-sectional data limits our ability to establish the temporality or directionality of such associations.

Receptivity to Tobacco Advertising and Susceptibility to Tobacco Products.

BACKGROUND AND OBJECTIVES: Non-cigarette tobacco marketing is less regulated and may promote cigarette smoking among adolescents. We quantified receptivity to advertising for multiple tobacco products and hypothesized associations with susceptibility to cigarette smoking. METHODS: Wave 1 of the nationally representative PATH (Population Assessment of Tobacco and Health) study interviewed 10 751 adolescents who had never used tobacco. A stratified random selection of 5 advertisements for each of cigarettes, e-cigarettes, smokeless products, and cigars were shown from 959 recent tobacco advertisements. Aided recall was classified as low receptivity, and image-liking or favorite ad as higher receptivity. The main dependent variable was susceptibility to cigarette smoking. RESULTS: Among US youth, 41% of 12 to 13 year olds and half of older adolescents were receptive to at least 1 tobacco advertisement. Across each age group, receptivity to advertising was highest for e-cigarettes (28%-33%) followed by cigarettes (22%-25%), smokeless tobacco (15%-21%), and cigars (8%-13%). E-cigarette ads shown on television had the highest recall. Among cigarette-susceptible adolescents, receptivity to e-cigarette advertising (39.7%; 95% confidence interval [CI]: 37.9%-41.6%) was higher than for cigarette advertising (31.7%; 95% CI: 29.9%-33.6%). Receptivity to advertising for each tobacco product was associated with increased susceptibility to cigarette smoking, with no significant difference across products (similar odds for both cigarette and e-cigarette advertising; adjusted odds ratio = 1.22; 95% CI: 1.09-1.37). CONCLUSIONS: A large proportion of US adolescent never tobacco users are receptive to tobacco advertising, with television advertising for e-cigarettes having the highest recall. Receptivity to advertising for each non-cigarette tobacco product was associated with susceptibility to smoke cigarettes.

Susceptibility to tobacco product use among youth in wave 1 of the population Assessment of tobacco and health (PATH) study.

The purpose of this study was to investigate susceptibility and ever use of tobacco products among adolescents and young adults in the US. Cross-sectional analysis of Wave 1(2013-2014) adolescent (12-17year-olds; n=13,651) and young adult (18-24year-olds; n=9112) data from the nationally-representative Population Assessment of Tobacco and Health (PATH) Study was conducted. At 12years, 5% were ever tobacco users and 36% were susceptible to use. Seventy percent were susceptible at age 17years, and the same proportion were ever users at age 22years. Susceptibility levels were comparable for cigarettes and e-cigarette (28.6% and 27.4%, respectively), followed by hookah (22.0%), pipes (17.5%), cigars (15.2%), and smokeless tobacco (9.7%). Non-Hispanic (NH) Black (Adjusted Odds Ratio [ORadj]=1.36; 95% Confidence Limit [CL], 1.18-1.56) and Hispanic (ORadj=1.34: 95% CL,1.19-1.49) adolescent never- users were more likely to be susceptible to future use of a tobacco product than NH Whites. Susceptibility was higher with age (15-17yrs. vs 12-14yrs.: ORadj=1.69; 95% CL, 1.55-1.85) and parental education (college graduates vs less than HS education: ORadj=1.22, 95% CL, 1.08-1.39). Compared to exclusive users of hookah, cigars, or smokeless products, larger proportions of exclusive e-cigarette ever users were also susceptible to cigarette use. Among adolescents, lower levels of ever use of tobacco products are often counterbalanced by higher levels of susceptibility for future use, which may suggest delayed initiation in some groups. Ever users of a given tobacco product were more susceptible to use other tobacco products, putting them at risk for future multiple tobacco product use.

It's complicated: Examining smokers' relationships with their cigarette brands.

Despite increased restrictions and taxes, decreased social acceptability, and widespread awareness of the harms of tobacco use, many in the U.S. continue to smoke cigarettes. Thus, understanding smokers' attitudes and motivations remains an important goal. This study adopts the consumer psychology concept of brand relationship to provide a new lens through which to examine smokers' attitudes about their cigarette use. Twelve focus groups (N = 143) were conducted with adult cigarette smokers from September to November, 2013. Using a semistructured moderator guide and "top of mind" worksheets, the discussion examined participants' attitudes toward (a) their own cigarette brand and (b) tobacco companies in general. Data were coded and analyzed following principles of thematic analysis. Adult smokers reported positive attitudes toward their cigarette brand, as their brand was strongly associated with the positive experience of smoking (e.g., satisfying craving and relief from withdrawal). In contrast, thinking about tobacco companies in general evoked negative reactions, revealing overwhelmingly negative attitudes toward the industry. Findings reveal a complicated relationship between smokers and their cigarette brand: simultaneously embracing their cigarettes and rejecting the industry that makes them. Taken together, these data suggest smokers maintain largely positive brand relationships, diverting negative feelings about smoking toward the tobacco industry. Finally, they highlight the synergy between branding and the subjective smoking experience, whereby positive brand attitudes are reinforced through withdrawal relief. Ultimately, this information could inform a more complete understanding of how smokers interpret and respond to tobacco communications, including marketing from their brand. (PsycINFO Database Record