Dexamethasone leads to Zn2+ accumulation and increased unbound Zn2+ in C2C12 muscle and 3T3-L1 adipose cells.

Skeletal muscle atrophy is associated with increases in circulating glucocorticoid levels and insulin resistance. Zinc accumulates in atrophic muscle, but the relationship between atrophy, insulin resistance, and Zn2+ homeostasis remains unclear. In this study, the effect of the glucocorticoid dexamethasone (DEX) on insulin and Zn2+ homeostasis was explored. Treatment of differentiated C2C12 skeletal myotubes and 3T3-L1 adipocytes with DEX significantly increased mRNA expression of the metal-binding proteins Mt1 and 2 and altered energy storage as shown by the increased size of lipid droplets in 3T3-L1 cells. In C2C12 cells the total cellular Zn2+ was higher after DEX treatment, and in both C2C12 and 3T3-L1 adipocytes, free unbound Zn2+ was increased. Insulin treatment led to a gradual increase in free Zn2+ in C2C12 cells, and no significant change in DEX-treated cells such that concentrations were similar 10 min after insulin treatment. These data demonstrate that DEX disturbs Zn2+ homeostasis in muscle and fat cells. Further study of the molecular pathways involved to identify novel therapeutic targets for treatment of skeletal muscle atrophy is warranted.

Non-daily Cigarette Smoking: Stability and Transition to Abstinence in Young Adults.

INTRODUCTION: There is increasing recognition that non-daily cigarette smoking is common in early adulthood but less is known about its stability over time, or what influences transitions to heavier or nonsmoking. We examined the stability of non-daily smoking in a sample of young adults, and tested whether social and cognitive factors predicted transitions to other smoking patterns over time. AIMS AND METHODS: Participants were 579 young adults (18-24 years old at enrollment, 52% male) who were non-daily and never-daily cigarette smokers and California residents. Participants completed 13 waves of assessment over 3 years. We used descriptive statistics to evaluate the frequency of consistent abstinence, defined as no cigarette use at two consecutive waves and no cigarette use at any subsequent waves. Cox and logistic regression were used to test predictors of consistent abstinence. RESULTS: We found that 55% of participants smoked intermittently throughout the study, while 43% were consistently abstinent by the end of the study; few transitioned to daily smoking. Stopping smoking was associated with having fewer smoking friends, smoking less in social situations, having lower positive reinforcement expectancies for smoking, and having stronger intent to quit. Post hoc analyses indicated those who stopped smoking tended to report reductions in positive reinforcement expectancies and increased intent to quit in the 6 months before stopping. CONCLUSIONS: Findings suggest a substantial minority of young adult non-daily smokers may stop on their own, but that the majority continue smoking and may require intervention. Interventions for this population should address social motives and reinforcement expectancies. IMPLICATIONS: The majority of young adults who are non-daily cigarette smokers appear to maintain this habit over an extended period and may require intervention. Interventions that focus on reducing expectancies for positive effects of and social motives for cigarette use and on increasing intent to quit smoking may be most effective.

Sympathetic Nervous System and Atherosclerosis.

Atherosclerosis is characterized by the narrowing of the arterial lumen due to subendothelial lipid accumulation, with hypercholesterolemia being a major risk factor. Despite the recent advances in effective lipid-lowering therapies, atherosclerosis remains the leading cause of mortality globally, highlighting the need for additional therapeutic strategies. Accumulating evidence suggests that the sympathetic nervous system plays an important role in atherosclerosis. In this article, we reviewed the sympathetic innervation in the vasculature, norepinephrine synthesis and metabolism, sympathetic activity measurement, and common signaling pathways of sympathetic activation. The focus of this paper was to review the effectiveness of pharmacological antagonists or agonists of adrenoceptors (α1, α2, ß1, ß2, and ß3) and renal denervation on atherosclerosis. All five types of adrenoceptors are present in arterial blood vessels. α1 blockers inhibit atherosclerosis but increase the risk of heart failure while α2 agonism may protect against atherosclerosis and newer generations of ß blockers and ß3 agonists are promising therapies against atherosclerosis; however, new randomized controlled trials are warranted to investigate the effectiveness of these therapies in atherosclerosis inhibition and cardiovascular risk reduction in the future. The role of renal denervation in atherosclerosis inhibition in humans is yet to be established.

Access to Effective Communication Aids and Services among American Sign Language Users across North Carolina: Disparities and Strategies to Address Them.

OBJECTIVE: To examine the extent to which communication aids and services used by American Sign Language (ASL) users and their healthcare providers aligns with preferences, satisfaction, and unmet needs; and to elicit from stakeholders strategies to address disparities. METHODS: A cross-sectional study was conducted of ASL users in North Carolina. Respondents completed an online survey presented in ASL and English (N = 189). McNemar's tests were used to compare rates of preferred and actual methods of communication. Logistic regression models explored relationships of accessible communication with dissatisfaction and unmet need. Qualitative interviews explored satisfaction with communication and reflections on what works, what does not, and outcomes (N = 54). RESULTS: While 45% of respondents used a professional sign language interpreter, 65% of respondents preferred to do so. Accessible communication was associated with lower odds of dissatisfaction with communication (OR = .19, p < .05). Dissatisfaction with communication was associated with greater odds of unmet need for healthcare (OR = 8.95, p < .05). Interview respondents emphasized their preference for on-site interpreters, explaining how video remote interpreting was subject to technical difficulties while writing back-and-forth led to important gaps in understanding. CONCLUSIONS: While ASL users prefer to use professional, on-site sign language interpreters to communicate with providers, most use some other form of communication instead. Findings emphasize the need for policy strategies to facilitate access to high quality, well-functioning professional interpreter services and to have those services delivered on-site to overcome disparities.

Impulsivity-Related Personality Traits as Predictors of E-Cigarette Use among Young Adults over Time.

Introduction: There has been rising concern about e-cigarette usage among teenagers and young adults. As knowledge about the adverse health effects of e-cigarettes accumulates, it is critical to identify factors that may increase risk of vaping initiation and frequency of use. One potential risk factor known to increase risk for other substance use is impulsivity. This study tested the hypothesis that impulsivity prospectively predicts vaping over time. Methods: Active e-cigarette users (n = 137; 51.8% male; Mean age 20 years at baseline) completed 8 waves of assessment over 21 months (2017-2020). The S-UPPS-P impulse behavior scale was used at baseline to measure impulsivity, and frequency of e-cigarette, cigarette, marijuana and alcohol use was calculated at each wave thereafter. Results: Vaping frequency declined over time [Incidence Rate Ratio (IRR) = 0.92]. There were significant, stable, positive associations between e-cigarette use and lack of premeditation (IRR = 1.06) and sensation seeking (IRR = 1.09). Vaping frequency was inversely associated with negative urgency (IRR = 0.95). Positive urgency and lack of perseverance were not associated with frequency of vaping. Conclusion: These findings suggest that young adults who have higher impulsivity of certain types may use e-cigarettes more frequently. Thus, vaping interventions for young adults should address these factors to ensure the greatest impact on public health.

Auditory and olfactory findings in patients with USH2A-related retinal degeneration-Findings at baseline from the rate of progression in USH2A-related retinal degeneration natural history study (RUSH2A).

Sensorineural hearing loss (SNHL) is characteristic of Usher syndrome type 2 (USH2), but less is known about SNHL in nonsyndromic autosomal recessive retinitis pigmentosa (ARRP) and olfaction in USH2A-associated retinal degeneration. The Rate of Progression of USH2A-related Retinal Degeneration (RUSH2A) is a natural history study that enrolled 127 participants, 80 with USH2 and 47 with ARRP. Hearing was measured by pure-tone thresholds and word recognition scores, and olfaction by the University of Pennsylvania Smell Identification Test (UPSIT). SNHL was moderate in 72% of USH2 participants and severe or profound in 25%, while 9% of ARRP participants had moderate adult-onset SNHL. Pure-tone thresholds worsened with age in ARRP but not in USH2 participants. The degree of SNHL was not associated with other participant characteristics in either USH2 or ARRP. Median pure-tone thresholds in ARRP participants were significantly higher than the normative population (p < 0.001). Among 14 USH2 participants reporting newborn hearing screening results, 7 reported passing. Among RUSH2A participants, 7% had mild microsmia and 5% had moderate or severe microsmia. Their mean (±SD) UPSIT score was 35 (±3), similar to healthy controls (34 [±3]; p = 0.39). Olfaction differed by country (p = 0.02), but was not significantly associated with clinical diagnosis, age, gender, race/ethnicity, smoking status, visual measures, or hearing. Hearing loss in USH2A-related USH2 did not progress with age. ARRP patients had higher pure-tone thresholds than normal. Newborn hearing screening did not identify all USH2A-related hearing loss. Olfaction was not significantly worse than normal in participants with USH2A-related retinal degeneration.

Polytobacco use among young adult smokers: prospective association with cigarette consumption.

BACKGROUND: The risks of polytobacco use among young adults are unclear because we know relatively little about the consistency of multiproduct patterns over time and how these patterns impact cigarette smoking. The purpose of this study was to examine changes in multiple tobacco product use over time and associations with cigarette smoking quantity. METHODS: Participants (n=335; 55% male) were 18-24 years old non-daily cigarette smokers living in California. Polytobacco use patterns were assessed quarterly for 2 years. RESULTS: Transition analyses showed that while the number of products that had been used recently was volatile, the most common pattern was stability between timepoints. A longitudinal negative binomial regression model indicated that those who used more non-cigarette products also reported greater cigarette quantity. The strength of this relationship increased over time. CONCLUSIONS: Findings suggest that individuals who use more tobacco products are at greater risk for increased cigarette smoking and maintaining a multiple product use pattern.

Associations Between Self-Reported and Biological Measures of Nicotine Consumption Among Young Adult Nondaily Cigarette Smokers.

BACKGROUND AND OBJECTIVES: Intermittent, dual use of cigarettes and e-cigarettes is a common pattern among youth and young adults. However, little is known about the validity of self-report measures of nicotine consumption in these populations. The goal of the present study was to examine associations between self-reported frequency of cigarette and e-cigarette use and nicotine levels in hair samples at two assessments 1 year apart. METHODS: Participants (n = 90; 65% female) were 19- to 25-year-old intermittent cigarette smokers recruited from the community for a longitudinal study of tobacco use. They submitted hair samples via mail, 1 and 2 years after enrollment in the parent study. RESULTS: Findings indicated that days of use of both cigarettes and e-cigarettes in the past 30 days independently predicted hair nicotine in the full sample, and when examining only timepoints at which any cigarette use was reported. Timepoints when any e-cigarette use was reported, hair nicotine was positively associated with e-cigarette but not cigarette frequency. DISCUSSION AND CONCLUSIONS: Data suggest that self-report measures are valid methods of assessing intermittent use of both cigarettes and e-cigarettes. Findings also suggest that dual users may tend to consume more nicotine and thus be at greater risk for dependence than single product users. SCIENTIFIC SIGNIFICANCE: These results are among the first to indicate that hair analysis can be used to detect intermittent nicotine exposure via both cigarettes and e-cigarettes. (Am J Addict 2020;29:471-475).

Co-occurring Use of Cannabis and Tobacco and the Presence of Acute Respiratory Symptoms among Young Adult Light and Intermittent Smokers.

BACKGROUND: Cannabis use and intermittent smoking are becoming increasingly prevalent among young adults. Thus, identifying health consequences of co-occurring use of these substances represents an emerging research priority. Purpose/Objectives: This study evaluated the relationship between tobacco/cannabis co-use and acute symptoms of respiratory illness among young adult intermittent smokers. We hypothesized that tobacco/cannabis co-use would be more strongly associated with respiratory symptoms relative to use of neither or one product. Methods: A secondary analysis of a three-year observational study was conducted. Non-daily smokers (n = 563) aged 18-24 were recruited via social media and completed electronic surveys at baseline and annually for two years, producing three total assessments. Past-two-week use of tobacco and cannabis was measured at each assessment, as was severity of six acute respiratory symptoms. The respiratory measure was dichotomized to indicate the presence or absence of symptoms. Results: Tobacco/cannabis co-use decreased from 54.8% at baseline to 43.4% at year two (p < .001). Mean respiratory symptoms also declined significantly over time (ps < .05). At each timepoint, co-use was more strongly associated with presence of respiratory symptoms than the use of neither product (aORs = 2.73-4.39, ps ≤ .013). Co-users were also 38%-183% more likely to endorse the presence of respiratory symptoms than single product users at each timepoint (aORs = 1.38-2.83, ps = .023-.212). Conclusions/Importance: Although co-occurring use of tobacco and cannabis by young adults may represent experimental use of multiple substances, it may also promote or exacerbate acute symptoms of respiratory illness. Further exploration with more granular patterns of co-use and across different routes of administration is warranted.

Effect of acclimation temperature and substrate type on selected temperature, movement and activity of juvenile spiny softshell turtles (Apalone spinifera) in an aquatic thermal gradient.

In some turtle species, temperature selection may be influenced by environmental conditions, including acclimation temperature and substrate quality. These factors may be particularly important for softshell turtles that are highly aquatic and often thermoregulate by burying in the substrate in shallow water microhabitats. We tested for effects of acclimation temperature (22 °C or 27 °C) and substrate type (sand or gravel) on the selected temperature and movement patterns of 20 juvenile spiny softhshell turtles (Apalone spinifera; Reptilia: Trionychidae) in an aquatic thermal gradient of 14-34 °C. Among 7-11 month old juvenile softshell turtles, acclimation temperature and substrate type did not influence temperature selection, nor alter activity and movement patterns. During thermal gradient tests, both 22- and 27 °C-acclimated turtles selected the warmest temperature (34 °C) available most frequently, regardless of substrate type (sand or gravel). Similarly, acclimation temperature and substrate type did not influence movement patterns of turtles, nor the number of chambers used in the gradient tests. These results suggest that juvenile Apalone spinifera are capable of detecting small temperature increments and prefer warm temperatures that may positively influence growth and metabolism, and that thermal factors more significantly influence aquatic thermoregulation in this species than does substrate type.

Drinking refusal self-efficacy: Impacts on outcomes from a multi-site early intervention trial.

This study examines relationships between drink refusal self-efficacy (DRSE) and outcomes in Project Options (PO), an adolescent alcohol use early intervention. 1171 US high school students (39.3% Hispanic, 59.3% girls) participated in PO, reporting their demographics, alcohol use, and drinking reduction efforts at baseline, 30 days and three months later. Items from the Drug Taking Confidence Questionnaire for Adolescents (DTCQ-A) assessed DRSE. DRSE corresponded negatively with drinking at 30 days and, among drinkers, predicted fewer use reduction attempts at 30 days and three months. Results indicate that, unlike in treatment settings, DRSE may not correspond to improved early intervention outcomes.

Combination nicotine replacement therapy: strategies for initiation and tapering.

Several studies and meta-analyses have demonstrated the efficacy of combination nicotine replacement therapy (NRT) for patients who wish to quit smoking. However, there is limited guidance with respect to initiation and tapering of combination NRT. We attempt to review the evidence and rationale behind combination NRT, present the dosing used in combination NRT studies, and propose a step-down approach for tapering of combination NRT with integration of behavioral strategies.

Does e-cigarette use predict cigarette escalation? A longitudinal study of young adult non-daily smokers.

Recent studies suggest that e-cigarette use among youth may be associated with increased risk of cigarette initiation. The goal of this study was to test the hypothesis that use of e-cigarettes among young adult non-daily cigarette smokers would be associated with increased cigarette consumption. Participants (n=391; 52% male) were 18-24year-old non-daily cigarette smokers recruited from across California. Cigarette and e-cigarette use were assessed online or via mobile phone every three months for one year between March 2015 and December 2016. Longitudinal negative binomial regression models showed that, adjusted for propensity for baseline e-cigarette use, non-daily smokers who reported more frequent use of e-cigarettes upon study entry reported greater quantity and frequency of cigarette smoking at baseline and greater increases in cigarette quantity over 12months than non-daily cigarette only smokers (ps<0.01). During the 12months of assessment, more consistent consumption of e-cigarettes was associated with greater quantity and frequency of cigarette use (ps<0.01); these effects did not vary over time. Findings suggest that among non-daily smokers, young adults who use e-cigarettes tend to smoke more cigarettes and to do so more frequently. Such individuals may be at greater risk for chronic tobacco use and dependence.

A pilot investigation of audiovisual processing and multisensory integration in patients with inherited retinal dystrophies.

BACKGROUND: In this study, we examined audiovisual (AV) processing in normal and visually impaired individuals who exhibit partial loss of vision due to inherited retinal dystrophies (IRDs). METHODS: Two groups were analyzed for this pilot study: Group 1 was composed of IRD participants: two with autosomal dominant retinitis pigmentosa (RP), two with autosomal recessive cone-rod dystrophy (CORD), and two with the related complex disorder, Bardet-Biedl syndrome (BBS); Group 2 was composed of 15 non-IRD participants (controls). Audiovisual looming and receding stimuli (conveying perceptual motion) were used to assess the cortical processing and integration of unimodal (A or V) and multimodal (AV) sensory cues. Electroencephalography (EEG) was used to simultaneously resolve the temporal and spatial characteristics of AV processing and assess differences in neural responses between groups. Measurement of AV integration was accomplished via quantification of the EEG's spectral power and event-related brain potentials (ERPs). RESULTS: Results show that IRD individuals exhibit reduced AV integration for concurrent audio and visual (AV) stimuli but increased brain activity during the unimodal A (but not V) presentation. This was corroborated in behavioral responses, where IRD patients showed slower and less accurate judgments of AV and V stimuli but more accurate responses in the A-alone condition. CONCLUSIONS: Collectively, our findings imply a neural compensation from auditory sensory brain areas due to visual deprivation.

Impact of Ethnic Composition on Mechanisms of Change in School-Based Substance Use Intervention Groups.

Delivering alcohol use intervention services in the school setting represents a key approach to engaging youth of all backgrounds, particularly underserved populations, in such programming. Relative progress has been made toward implementing culturally responsive services for youth; however, little is known about the role of ethnic composition on group processes purported to underlie mechanisms of change. We examined associations between ethnic group composition and therapeutic processes within a voluntary, school-based alcohol use intervention at seven schools across three cities (N groups = 353). Ethnic composition was characterized as: group ethnic diversity on a continuum, group ethnic homogeneity (i.e., where at least 66% of participants shared the same ethnicity), and comparing groups where one of the three largest ethnicities in the sample reached the majority (i.e., African-American vs. Hispanic vs. non-Hispanic white). Ratings on group processes were obtained from participants (satisfaction; belonging), facilitators (empathy; rapport), and coders (engagement; responsiveness). Mixed-effects models revealed that students in groups with African-American and Hispanic majorities reported a higher sense of satisfaction compared to groups with non-Hispanic white majorities. Facilitators endorsed expressing empathy more frequently with majority African-American and Hispanic groups than with non-Hispanic white groups. Study findings highlight the importance of considering different dimensions of ethnic composition when examining mechanisms of change in group intervention research.

Factors Associated With Accepting Assistance for Smoking Cessation Among Military Veterans.

INTRODUCTION: Cigarette smoking remains a significant health risk for Veterans. Increased understanding of factors that influence the tobacco cessation referral process within Veterans Affairs medical facilities is useful for enhancing utilization of smoking cessation treatment. The present study examined the association of demographic and health variables with whether smokers accepted referral for medication and/or tobacco cessation clinic. METHODS: Electronic medical record data (2011-2013) were obtained for a sample of US military Veterans who accepted cessation assistance from their health care provider. Demographic and diagnostic variables were examined to identify predictors of the types of assistance accepted (medication only, clinic referral only, or both). RESULTS: The sample includes 2941 Veterans, 10.3% female, 19.9% African American, 10.7% Hispanic, and 57.9% non-Hispanic white. Veterans averaged of 50.69 years of age (SD = 14.01), 31.5% had a substance use disorder diagnosis and 54.1% had a psychiatric diagnosis. Demographic and diagnostic information was compared across types of assistance accepted. Significant differences were found between those who accepted medications only and those who accepted either clinic referral or both medication and clinic referral. Veterans in the latter two categories were younger and more likely to have a psychiatric diagnosis than those accepting medication only. Women Veterans were significantly more likely than men to accept clinic referral plus medication. However, in contrast to men, almost none of the variables examined were associated with the type of assistance accepted by women. CONCLUSION: These findings indicate significant gender differences in influences on accepting assistance for smoking cessation among Veterans. IMPLICATIONS: Existing research identifies factors associated with unassisted quitting. However, little is known regarding the referral process, which is critical in connecting smokers with treatment. The present work is unique in employing electronic medical record data to examine factors associated with accepting different types of smoking cessation treatment referrals. This study represents an initial effort to elucidate the smoking cessation treatment referral process. These findings highlight the need to examine sex specific influences on smoking cessation treatment utilization and the importance of focusing on smokers with psychiatric disorders.

Feasibility and Reliability of a Coding System to Capture In-Session Group Behavior in Adolescents.

Limited research has explored the role of in-session behavior during motivational enhancement (ME) in group formats. The current study presents initial feasibility of assessing behavior of high school students (N = 425) attending Project Options, a voluntary secondary drug and alcohol prevention program utilizing ME techniques. Building on previous research exploring client language supporting/opposing health behavior, student group behavior was coded live at the specific utterance and global level; group leader behavior was also coded globally. Interrater reliability of the coding system was assessed, and preliminary validity of the coding system was examined by exploring associations between characteristics of group members and in-session group behavior. Initial reliability estimates were excellent for the specific behavior codes. Reliability of the global codes was mixed, with raters demonstrating good reliability on support for unhealthy behavior, opposition to unhealthy behavior, and support for healthy behavior. Reliability of the group leader codes was fair to poor. Greater percent healthy talk was associated with a lower percentage of group members reporting lifetime alcohol use. The results of the current study suggest that some in-session behavior at the group level can be coded reliably via live observation and that in-session behavior at the group level is associated with alcohol use prior to attending the program. Future research is needed to explore the utility of in-session behavior in terms of predicting future behavior at the group and individual level.

Smoking prevalence in urban and rural populations: findings from California between 2001 and 2012.

BACKGROUND: Tobacco smoking and related health problems are still major public health concerns in the United States despite the declining smoking prevalence. OBJECTIVES: This study explored differences in smoking prevalence between urban and rural areas potentially relevant to tobacco control efforts in California. METHODS: Public use adult smoking data from the California Health Interview Survey (CHIS) between 2001 and 2011-2012 were analyzed. A total of 282 931 adults were surveyed across the six CHIS cycles. A ZIP code-based geographic classification (Urban, Second-City, Suburban, and Town/Rural) was used to examine the association between smoking prevalence and area of residency. RESULTS: The overall smoking prevalence in California decreased from 17.0% in 2001 to 13.8% in 2011-2012. Within each CHIS cycle, the Town/Rural areas had the highest smoking prevalence, followed by Urban and Second-City areas, and Suburban areas had the lowest. Pooled data from all CHIS cycles showed a similar pattern, with rates in Urban, Second-City, Suburban and Town/Rural areas being 15.2%, 15.2%, 13.1% and 17.3%, respectively. Weighted multivariate logistic regression analysis indicated significantly higher odds of smoking in Urban, Second-City and Town/Rural areas compared to Suburban areas (all adjusted odds ratios > 1.10), although this trend varied by race/ethnicity, being present in non-Hispanic Whites and not present in Hispanics. CONCLUSIONS: Town/Rural and Urban populations of California are consistently at higher risk of smoking than Suburban populations. These results indicate a need for population-specific tobacco control approaches that address the lifestyle, behavior, and education of disparate populations within the same state or region.

Immunohistochemical analysis of pancreatic islets of platypus (Ornithorhynchus anatinus) and echidna (Tachyglossus aculeatus ssp.).

Monotremes have undergone remarkable changes to their digestive and metabolic control system; however, the monotreme pancreas remains poorly characterized. Previous work in echidna demonstrated the presence of pancreatic islets, but no information is available for platypus and the fine structure has not been described for either monotreme. Based on our recent finding that monotremes lack the ghrelin gene, which is expressed in mouse and human pancreatic islets, we investigated the structure of monotreme islets in more detail. Generally, as in birds, the islets of monotremes were smaller but greater in number compared with mouse. ß-cells were the most abundant endocrine cell population in platypus islets and were located peripherally, while α-cells were observed both in the interior and periphery of the islets. δ-cells and pancreatic polypeptide (PP)-cells were mainly found in the islet periphery. Distinct PP-rich (PP-lobe) and PP-poor areas (non-PP-lobe) are present in therian mammals, and we identified these areas in echidna but not platypus pancreas. Interestingly, in some of the echidna islets, α- and ß-cells tended to form two poles within the islets, which to our knowledge is the first time this has been observed in any species. Overall, monotreme pancreata share the feature of consisting of distinct PP-poor and PP-rich islets with other mammals. A higher number of islets and α- or ß-cell only islets are shared between monotremes and birds. The islets of monotremes were larger than those of birds but smaller compared with therian mammals. This may indicate a trend of having fewer larger islets comprising several endocrine cell types during mammalian evolution.

A Single Dose Respiratory Recombinant Adenovirus-Based Vaccine Provides Long-Term Protection for Non-Human Primates from Lethal Ebola Infection.

As the Ebola outbreak in West Africa continues and cases appear in the United States and other countries, the need for long-lasting vaccines to preserve global health is imminent. Here, we evaluate the long-term efficacy of a respiratory and sublingual (SL) adenovirus-based vaccine in non-human primates in two phases. In the first, a single respiratory dose of 1.4×10(9) infectious virus particles (ivp)/kg of Ad-CAGoptZGP induced strong Ebola glycoprotein (GP) specific CD8+ and CD4+ T cell responses and Ebola GP-specific antibodies in systemic and mucosal compartments and was partially (67%) protective from challenge 62 days after immunization. The same dose given by the SL route induced Ebola GP-specific CD8+ T cell responses similar to that of intramuscular (IM) injection, however, the Ebola GP-specific antibody response was low. All primates succumbed to infection. Three primates were then given the vaccine in a formulation that improved the immune response to Ebola in rodents. Three primates were immunized with 2.0×10(10) ivp/kg of vaccine by the SL route. Diverse populations of polyfunctional Ebola GP-specific CD4+ and CD8+ T cells and significant anti-Ebola GP antibodies were present in samples collected 150 days after respiratory immunization. The formulated vaccine was fully protective against challenge 21 weeks after immunization. While diverse populations of Ebola GP-specific CD4+ T cells were produced after SL immunization, antibodies were not neutralizing and the vaccine was unprotective. To our knowledge, this is the first time that durable protection from a single dose respiratory adenovirus-based Ebola vaccine has been demonstrated in primates.