Striosomes Mediate Value-Based Learning Vulnerable in Age and a Huntington's Disease Model.

Learning valence-based responses to favorable and unfavorable options requires judgments of the relative value of the options, a process necessary for species survival. We found, using engineered mice, that circuit connectivity and function of the striosome compartment of the striatum are critical for this type of learning. Calcium imaging during valence-based learning exhibited a selective correlation between learning and striosomal but not matrix signals. This striosomal activity encoded discrimination learning and was correlated with task engagement, which, in turn, could be regulated by chemogenetic excitation and inhibition. Striosomal function during discrimination learning was disturbed with aging and severely so in a mouse model of Huntington's disease. Anatomical and functional connectivity of parvalbumin-positive, putative fast-spiking interneurons (FSIs) to striatal projection neurons was enhanced in striosomes compared with matrix in mice that learned. Computational modeling of these findings suggests that FSIs can modulate the striosomal signal-to-noise ratio, crucial for discrimination and learning.

Chronic Stress Alters Striosome-Circuit Dynamics, Leading to Aberrant Decision-Making.

Effective evaluation of costs and benefits is a core survival capacity that in humans is considered as optimal, "rational" decision-making. This capacity is vulnerable in neuropsychiatric disorders and in the aftermath of chronic stress, in which aberrant choices and high-risk behaviors occur. We report that chronic stress exposure in rodents produces abnormal evaluation of costs and benefits resembling non-optimal decision-making in which choices of high-cost/high-reward options are sharply increased. Concomitantly, alterations in the task-related spike activity of medial prefrontal neurons correspond with increased activity of their striosome-predominant striatal projection neuron targets and with decreased and delayed striatal fast-firing interneuron activity. These effects of chronic stress on prefronto-striatal circuit dynamics could be blocked or be mimicked by selective optogenetic manipulation of these circuits. We suggest that altered excitation-inhibition dynamics of striosome-based circuit function could be an underlying mechanism by which chronic stress contributes to disorders characterized by aberrant decision-making under conflict. VIDEO ABSTRACT.

Comparative effectiveness research trial for antidepressant incomplete and non-responders with treatment resistant depression (ASCERTAIN-TRD) a randomized clinical trial.

Further research is needed to help improve both the standard of care and the outcome for patients with treatment-resistant depression. A particularly critical evidence gap exists with respect to whether pharmacological or non-pharmacological augmentation is superior to antidepressant switch, or vice-versa. The objective of this study was to compare the effectiveness of augmentation with aripiprazole or repetitive transcranial magnetic stimulation versus switching to the antidepressant venlafaxine XR (or duloxetine for those not eligible to receive venlafaxine) for treatment-resistant depression. In this multi-site, 8-week, randomized, open-label study, 278 subjects (196 females and 82 males, mean age 45.6 years (SD 15.3)) with treatment-resistant depression were assigned in a 1:1:1 fashion to treatment with either of these three interventions; 235 subjects completed the study. 260 randomized subjects with at least one post-baseline Montgomery-Asberg Depression Rating (MADRS) assessment were included in the analysis. Repetitive transcranial magnetic stimulation (score change (standard error (se)) = -17.39 (1.3) (p = 0.015) but not aripiprazole augmentation (score change (se) = -14.9 (1.1) (p = 0.069) was superior to switch (score change (se) = -13.22 (1.1)) on the MADRS. Aripiprazole (mean change (se) = -37.79 (2.9) (p = 0.003) but not repetitive transcranial magnetic stimulation augmentation (mean change (se) = -42.96 (3.6) (p = 0.031) was superior to switch (mean change (se) = -34.45 (3.0)) on the symptoms of depression questionnaire. Repetitive transcranial magnetic stimulation augmentation was shown to be more effective than switching antidepressants in treatment-resistant depression on the study primary measure. In light of these findings, clinicians should consider repetitive transcranial magnetic stimulation augmentation early-on for treatment-resistant depression.Trial registration: ClinicalTrials.gov, NCT02977299.

Activity-regulated gene expression across cell types of the mouse hippocampus.

Activity-regulated gene (ARG) expression patterns in the hippocampus (HPC) regulate synaptic plasticity, learning, and memory, and are linked to both risk and treatment responses for many neuropsychiatric disorders. The HPC contains discrete classes of neurons with specialized functions, but cell type-specific activity-regulated transcriptional programs are not well characterized. Here, we used single-nucleus RNA-sequencing (snRNA-seq) in a mouse model of acute electroconvulsive seizures (ECS) to identify cell type-specific molecular signatures associated with induced activity in HPC neurons. We used unsupervised clustering and a priori marker genes to computationally annotate 15,990 high-quality HPC neuronal nuclei from N = 4 mice across all major HPC subregions and neuron types. Activity-induced transcriptomic responses were divergent across neuron populations, with dentate granule cells being particularly responsive to activity. Differential expression analysis identified both upregulated and downregulated cell type-specific gene sets in neurons following ECS. Within these gene sets, we identified enrichment of pathways associated with varying biological processes such as synapse organization, cellular signaling, and transcriptional regulation. Finally, we used matrix factorization to reveal continuous gene expression patterns differentially associated with cell type, ECS, and biological processes. This work provides a rich resource for interrogating activity-regulated transcriptional responses in HPC neurons at single-nuclei resolution in the context of ECS, which can provide biological insight into the roles of defined neuronal subtypes in HPC function.

Quantifying side effects and caregiver burdens of pediatric pulmonary hypertension therapies.

BACKGROUND AND OBJECTIVES: Pulmonary hypertension (PH) is a rare, but serious disease among children. However, PH has been primarily evaluated among adults. Consequently, treatment therapies have not been fully evaluated among pediatric populations and are used in an 'off label' manner. The purpose of this study was to estimate the side effect profiles of the most commonly prescribed pediatric PH therapies and to understand the burdens placed upon families caring for children living with PH. METHODS: Participants were recruited online through the "Families of children with pulmonary hypertension" Facebook group and asked to complete a survey about PH treatments. RESULTS: A total of 139 parents of a child living with PH completed the survey. Almost all children used ≥ 1 medication to treat PH, with 52% using ≥ 3 medications. The highest average number of side effects was reported by users of Treprostinil, Selexipag and type-5 phosphodiesterase (PDE5) inhibitors. The most common side effects were skin flushing, headache, nasal congestion, joint/muscle pain, and nausea. In terms of accessing care, 81% travel ≥ 20 miles and 68% travel for ≥ 60 min to receive care. CONCLUSIONS: We found an array of treatment combinations employed to mitigate symptoms of PH in children, with a wide range of side effects. We also found a large, unseen economic, emotional, and time burden of caring for a child living with PH. Further research is warranted to understand the clinical implications of these side effects to move towards labeled usage of these therapies rather than post-hoc off-label usage.

Labeling of a mutant estrogen receptor with an Affimer in a breast cancer cell line.

Mutations of the intracellular estrogen receptor alpha (ERα) is implicated in 70% of breast cancers. Therefore, it is of considerable interest to image various mutants (L536S, Y537S, D538G) in living cancer cell lines, particularly as a function of various anticancer drugs. We therefore developed a small (13 kDa) Affimer, which, after fluorescent labeling, is able to efficiently label ERα by traveling through temporary pores in the cell membrane, created by the toxin streptolysin O. The Affimer, selected by a phage display, predominantly labels the Y537S mutant and can tell the difference between L536S and D538G mutants. The vast majority of Affimer-ERαY537S is in the nucleus and is capable of an efficient, unrestricted navigation to its target DNA sequence, as visualized by single-molecule fluorescence. The Affimer can also differentiate the effect of selective estrogen receptor modulators. More generally, this is an example of a small binding reagent-an Affimer protein-that can be inserted into living cells with minimal perturbation and high efficiency, to image an endogenous protein.

Preventative practices and effects of the COVID-19 pandemic on caregivers of children with pediatric pulmonary hypertension.

BACKGROUND: Pulmonary hypertension (PH) is a serious and life-threatening disease characterized by elevated mean arterial pressure and pulmonary vascular resistance. COVID-19 may exacerbate PH, as evidenced by higher mortality rates among those with PH. The objective of this study was to understand the unique burdens that the COVID-19 pandemic has placed upon families of children living with PH. METHODS: Participants were recruited online through the "Families of children with pulmonary hypertension" Facebook group and asked to complete a survey about their experiences during the COVID-19 pandemic. RESULTS: A total of 139 parents/caregivers of children living with PH completed the online survey. Almost all (85.6%) of parents/caregivers had received the COVID-19 vaccine, though only 59.7% reported a willingness to vaccinate their child with PH against COVID-19. Over 75% of parents/caregivers felt that they practiced preventative measures (e.g., wearing a facemask, social distancing, and avoiding gatherings) more than those in the community where they live. They also reported several hardships related to caring for their child with PH during the pandemic such as financial duress, loss of work, and affording treatment costs. CONCLUSIONS: These findings indicate that parents/caregivers of children at higher risk for COVID-19 complications may be more willing to act on clinical recommendations themselves as proxy for protecting those at high risk. The economic, emotional and social impacts of COVID-19 are significantly greater for high-risk individuals.

Long drives and red tape: mapping rural veteran access to primary care using causal-loop diagramming.

BACKGROUND: Rural veterans experience more challenges than their urban peers in accessing primary care services, which can negatively impact their health and wellbeing. The factors driving this disparity are complex and involve patient, clinic, health system, community and policy influences. Federal policies over the last decade have relaxed requirements for some veterans to receive primary care services from community providers through their VA benefits, known as community care. METHODS: We used a participatory systems mapping approach involving causal-loop diagramming to identify interrelationships between variables underlying challenges to veteran access to primary care and potential opportunities for change-known as leverage points in systems science. Our methods involved a secondary analysis of semi-structured qualitative interviews with rural veterans, VA staff, non-VA clinic staff and providers who serve rural veterans, and veteran service officers (VSOs) in the Northwest region of the US, followed by a two-part participatory modeling session with a study advisory board. We then applied Meadows's leverage point framework to identify and categorize potential interventions to improve rural veteran access to primary care. RESULTS: The final model illustrated challenges at the veteran, clinic, and system levels as experienced by stakeholders. Main components of the diagram pertained to the choice of VA or non-VA primary care, veteran satisfaction with the VA, enrollment in VA benefits and other insurance, community care authorization, reimbursement of non-VA care, referrals to specialty care, record sharing and communication between VA and non-VA providers, institutional stability of the VA, and staffing challenges. Fourteen interventions, including administrative and communications changes, were identified by analyzing the model using the leverage points framework. CONCLUSIONS: Our findings illustrate how challenges rural veterans face accessing health care are interconnected and persist despite recent changes to federal law pertaining to the VA health care system in recent years. Systems mapping and modeling approaches such as causal-loop diagramming have potential for engaging stakeholders and supporting intervention and implementation planning.

VeVaPy, a Python Platform for Efficient Verification and Validation of Systems Biology Models with Demonstrations Using Hypothalamic-Pituitary-Adrenal Axis Models.

In order for mathematical models to make credible contributions, it is essential for them to be verified and validated. Currently, verification and validation (V&V) of these models does not meet the expectations of the system biology and systems pharmacology communities. Partially as a result of this shortfall, systemic V&V of existing models currently requires a lot of time and effort. In order to facilitate systemic V&V of chosen hypothalamic-pituitary-adrenal (HPA) axis models, we have developed a computational framework named VeVaPy-taking care to follow the recommended best practices regarding the development of mathematical models. VeVaPy includes four functional modules coded in Python, and the source code is publicly available. We demonstrate that VeVaPy can help us efficiently verify and validate the five HPA axis models we have chosen. Supplied with new and independent data, VeVaPy outputs objective V&V benchmarks for each model. We believe that VeVaPy will help future researchers with basic modeling and programming experience to efficiently verify and validate mathematical models from the fields of systems biology and systems pharmacology.

Development of a novel model of cholecystectomy in subsequently ovariectomized mice and characterization of metabolic and gastrointestinal phenotypes: a pilot study.

BACKGROUND: Cholecystectomy (XGB) is the most common abdominal surgery performed in the United States and is associated with an increased post-surgery incidence of metabolic and gastrointestinal (GI) diseases. Two main risk factors for XGB are sex (female) and age (40-50 yr), corresponding with onset of menopause. Post-menopausal estrogen loss alone facilitates metabolic dysfunction, but the effects of XGB on metabolic and GI health have yet to be investigated in this population. Study objectives were to (1) identify possible short-term effects of XGB and (2) develop a novel murine model of XGB in human menopause via subsequent ovariectomy (OVX) and assess longitudinal effects of OVX on metabolism, GI physiology, and GI microbiota in XGB mice. METHODS: Female C57BL/6 mice were utilized in two parallel studies (S1&S2). In S1, XGB mice were compared to a non-XGB baseline group after six wk. In S2, mice were XGB at wk0, either sham (SHM) or OVX at wk6, and sacrificed at wk12, wk18, and wk24. Body composition assessment and fresh fecal collections were conducted periodically. Serum and tissues were collected at sacrifice for metabolic and GI health endpoints. RESULTS: Compared to baseline, XGB increased hepatic CYP7A1 and decreased HMGCR relative expression, but did not influence BW, fat mass, or hepatic triglycerides after six wk. In S2, XGB/OVX mice had greater BW and fat mass than XGB/SHM. Cecal microbiota alpha diversity metrics were lower in XGB/OVX mice at wk24 compared the XGB/SHM. No consistent longitudinal patterns in fasting serum lipids, fecal microbial diversity, and GI gene expression were observed between S2 groups. CONCLUSIONS: In addition to developing a novel, clinically-representative model of XGB and subsequent OVX, our results suggest that OVX resulted in the expected phenotype to some extent, but that XGB may modify or mask some responses and requires further investigation.

Suppression of breast cancer metastasis and extension of survival by a new antiestrogen in a preclinical model driven by mutant estrogen receptors.

PURPOSE: Many human breast tumors become resistant to endocrine therapies and recur due to estrogen receptor (ERα) mutations that convey constitutive activity and a more aggressive phenotype. Here, we examined the effectiveness of a novel adamantyl antiestrogen, K-07, in suppressing the growth of breast cancer metastases containing the two most frequent ER-activating mutations, Y537S and D538G, and in extending survival in a preclinical metastatic cancer model. METHODS: MCF7 breast cancer cells expressing luciferase and Y537S or D538G ER were injected into NOD-SCID-gamma female mice, and animals were treated orally with the antiestrogen K-07 or control vehicle. Comparisons were also made with the antiestrogen Fulvestrant. The development of metastases was monitored by in vivo bioluminescence imaging with phenotypic characterization of the metastases in liver and lung by immunohistochemical and biochemical analyses. RESULTS: These breast cancer cells established metastases in liver and lung, and K-07 treatment reduced the metastatic burden. Mice treated with K-07 also survived much longer. By day 70, only 28% of vehicle-treated mice with mutant ER metastases were alive, whereas all K-07-treated D538G and Y537S mice were still alive. K-07 also markedly reduced the level of metastatic cell ER and the expression of ER-regulated genes. CONCLUSION: The antiestrogen K-07 can reduce in vivo metastasis of breast cancers and extend host survival in this preclinical model driven by constitutively active mutant ERs, suggesting that this compound may be suitable for further translational examination of its efficacy in suppression of metastasis in breast cancers containing constitutively active mutant ERs.

Resonant inelastic X-ray scattering using a miniature dispersive Rowland refocusing spectrometer.

X-ray absorption spectroscopy (XAS) beamlines worldwide are steadily increasing their emphasis on full photon-in/photon-out spectroscopies, such as resonant inelastic X-ray scattering (RIXS), resonant X-ray emission spectroscopy (RXES) and high energy resolution fluorescence detection XAS (HERFD-XAS). In such cases, each beamline must match the choice of emission spectrometer to the scientific mission of its users. Previous work has recently reported a miniature tender X-ray spectrometer using a dispersive Rowland refocusing (DRR) geometry that functions with high energy resolution even with a large X-ray spot size on the sample [Holden et al. (2017). Rev. Sci. Instrum. 88, 073904]. This instrument has been used in the laboratory in multiple studies of non-resonant X-ray emission spectroscopy using a conventional X-ray tube, though only for preliminary measurements at a low-intensity microfocus synchrotron beamline. This paper reports an extensive study of the performance of a miniature DRR spectrometer at an unfocused wiggler beamline, where the incident monochromatic flux allows for resonant studies which are impossible in the laboratory. The results support the broader use of the present design and also suggest that the DRR method with an unfocused beam could have important applications for materials with low radiation damage thresholds and that would not survive analysis on focused beamlines.

Acute exposure to physiological doses of triiodothyronine does not induce gonadal caspase 3 activity in goldfish in vitro.

Seasonally spawning fish rely on a dynamic and complex hormonal interplay to regulate cycles of gonadal development and the regression. Thyroid hormones have been shown to be a key player during gonadal development, and can regulate the activity of a number of essential reproductive hormones. Apoptosis is a vital cellular process that contributes to the hormonal control of gonadal development and regression, but the roles of thyroid hormones on gonadal apoptosis in goldfish have not been explored. The present study examines the role of acute T3 exposure on caspase 3-dependent apoptosis in dispersed goldfish gonadal tissue in vitro. We examined the levels of caspase 3 activity in early, mid, and late recrudescent gonadal tissue after exposure to physiological doses of T3 for up to 24 h. Acute treatment with T3 did not alter basal caspase 3 activity in goldfish gonads in vitro in these reproductive stages. This initial study suggests that transient increases in T3 levels are unlikely to directly contribute to basal caspase 3-dependent apoptosis in the gonadal tissue of goldfish, although we cannot rule out an interaction of T3 with other hormones involved in the control of apoptosis in the testis and ovary.

Resolution of Recurrent Oro-facial Herpes Simplex Using a Topical Botanical Gel: A Case Report.

Oral herpes labialis, more commonly known as cold sores, are a common encountered viral infection involving herpes simplex virus-1 (HSV-1). Although relatively benign, these lesions can be both unsightly and clinically difficult to manage. Prescription standards of care and over-the-counter agents, such as docosonal, have often shown only limited efficacy in both decreasing lesional pain and reducing duration of lesional symptomology and are not without potential side effects. Despite some success with acute remediation, recurrent episodes often occur, with seemingly no imparted protection or suppression against future outbreaks. This case report involves the successful treatment of oro-facial herpes labialis with a synergistic botanical blend with marked reduction in symptoms, pain score, and lesion duration. Monitoring and evaluation post-treatment and application during future prodromal symptoms was also performed demonstrating additional reduction in the frequency of subsequent outbreaks. This case report supports the use of this treatment for prodromal and acute treatment of oro-facial herpes infection and appears to impart a reduction in the frequency of future outbreaks.

Neural response to stress and perceived stress differ in patients with left temporal lobe epilepsy.

Patients with epilepsy are often able to predict seizure occurrence subsequent to an acute stress experience. However, neuroimaging investigations into the neural basis of this relationship or the potential influence of perceived life stress are limited. The current study assessed the relationship between perceived stress and the neurobehavioral response to stress in patients with left temporal lobe epilepsy (LTLE) and healthy controls (HCs) using heart rate, salivary cortisol level, and functional magnetic resonance imaging and compared these effects between HCs and LTLE. Matched on perceived stress levels, groups of 36 patients with LTLE and 36 HCs completed the Montreal Imaging Stress Task, with control and stress math task conditions. Among LTLEs, 27 reported that prior (acute) stress affected their seizures (LTLES+), while nine did not (LTLES-). The results revealed that increased perceived stress was associated with seizure frequency in LTLE. Further, cortisol secretion was greater in LTLE, but did not vary with perceived stress as observed in HCs. A linear mixed-effects analysis revealed that as perceived stress increased, activation in the hippocampal complex (parahippocampal gyrus and hippocampus) decreased during stressful math in the LTLES+, increased in HCs, but did not vary in the LTLES-. Task-based functional connectivity analyses revealed LTLE differences in hippocampal functional connectivity with sensory cortex specific to stressor modalities. We argue that the current study demonstrates an inhibitory hippocampal mechanism underlying differences in resilience to stress between HCs and LTLE, as well as LTLE patients who report stress as a precipitant of seizures.

Health Education Training Embedded in a Microfinance Platform Associated with Safer Sexual Behavior in Haitian Women.

Sexual health education interventions have generally yielded modest impact, but may be more successful when integrated into programs designed to alleviate poverty and empower women. Between December 2017 and February 2018, we interviewed 304 Haitian female microfinance clients, 75 of whom had received health education training delivered within their regular meetings. Participants reported six key sexual health outcomes. We used log-binomial models to estimate the association between health education training and each outcome, and tested for interaction by age and literacy status. Women with health education training reported more condom use with unfaithful partners [PR (95% CI) 1.78 (1.04, 3.02)], more HIV testing [PR (95% CI) 1.56 (1.28, 1.90)], and fewer STI symptoms [PR (95% CI) 0.37 (0.19, 0.73)], compared to women with no training. Some of the associations were stronger among older women [e.g. HIV testing: PR (95% CI) 2.09 (1.49, 2.82)] and illiterate women [e.g. condom use: PR (95% CI) 3.46 (1.05, 11.38)]. These findings add to the growing body of evidence demonstrating the potential to use microfinance programs as platforms for health education delivery, and provide the first evidence for the association in Haiti.

Knowledge and perceptions of Zika virus transmission in the community of Puerto Plata, Dominican Republic.

BACKGROUND: Zika virus is associated with increased cases of both microcephaly and Guillain-Barré syndrome. Community knowledge, perceptions and practices to prevent infection with the Zika virus are not well understood, particularly among high risk populations living in resource-poor and Zika-endemic areas. Our objective was to assess knowledge of symptoms, health effects and prevention practices associated with Zika virus in rural communities on the northern coast of the Dominican Republic. METHODS: Study participants were contacted while attending community events such as free medical clinics and invited to be interviewed regarding their knowledge, attitudes, and perceptions of Zika virus using the World Health Organization's Zika survey tool. RESULTS: Of the 75 Dominicans that participated, 33% did not know who could become infected with Zika. In addition, only 40% of respondents were able to identify mosquitoes or sexual transmission as the primary routes of infection though 51% of respondents thought that Zika was an important issue in their community. CONCLUSIONS: This study found that general knowledge regarding the basic risks and transmission of Zika were not well understood among a sample of rural Dominicans. Our findings highlight disparities in knowledge and perception of risk from Zika in rural areas compared to previous studies conducted in the Dominican Republic. Education about the basic risks and transmission of Zika are critically needed in these remote populations to reduce Zika transmission.

Zika knowledge and prevention practices among U.S. travelers: a large cross-sectional survey study.

BACKGROUND: The aim of this study was to investigate what factors predict knowledge about Zika transmission, symptomology, and treatment among U.S. travelers and, additionally, to evaluate how Zika knowledge influences the adoption of personal protective behaviors. METHODS: Data were collected as part of a cross-sectional survey study using a probability-based internet panel of U.S. travelers in June 2017. We ran logistic regression models of factors predicting Zika knowledge (high vs. low) and of knowledge predicting adoption of personal protective measures. RESULTS: We found that traveling to a Zika endemic country and travelers' gender were both significantly predictive of higher Zika knowledge (odds ratio (OR): 1.48, 95% confidence interval (CI): 1.14-1.93 and OR: 1.44, 95% CI: 1.08-1.92), adjusting for age, race, education, income, and trip purpose. Additionally, among travelers to Zika endemic countries, individuals with higher Zika knowledge had significantly higher odds of engaging in preventive behaviors compared to those with lower knowledge. However, few travelers knew about the sexual transmission of Zika and adopted sexual prevention measures. CONCLUSIONS: Our findings suggest that there are gaps in knowledge about the risks and transmission of Zika and travelers with low knowledge are less likely to engage in the appropriate prevention methods. Significantly, few U.S. travelers have knowledge of the sexual transmission of Zika and, accordingly, there is less overall engagement with prevention measures for this transmission mechanism than for vector-borne transmission.

Knowledge of the Sexual Transmission of Zika Virus and Preventive Practices Against Zika Virus Among U.S. Travelers.

Individuals are often at increased risk of acquiring infectious disease while traveling. We sought to understand knowledge, attitudes and practices (KAP) regarding Zika virus among travelers from the United States. A total of 1043 study participants were recruited from a probability-based internet panel. Participants self-reported their knowledge of Zika infection and modes of transmission, and identified actions they had taken to prevent Zika infection and transmission including actions to prevent unintentional pregnancy since becoming aware of the Zika virus. Logistic regression was used to model the odds of taking preventive actions against Zika infection with adjustment for potential confounding factors. Knowledge of the sexual transmissibility of Zika virus significantly increased the odds of taking a preventive action against Zika infection, especially condom use or sexual abstention. Participants reported preferences for receiving information about Zika from private doctors and from the Internet. Discrepancies between where travelers seek information about Zika and how they would like to receive information regarding Zika were also found. These findings suggest that improving targeted messaging through online media may increase awareness of the sexual transmissibility of Zika as well as improve health communications with U.S. travelers. Travelers who are unaware of potential disease risks are less likely to adopt personal protective measures to protect themselves and reduce disease spread. Thus, future work should focus on improving communication and providing education to adopt effective prevention strategies while traveling.

Abstention from Drug Use and Delinquency Increasing among Youth in the United States, 2002-2014.

BACKGROUND: Trends in abstaining from substance use and delinquency among adolescent's ages 12-17 in the United States was examined. METHODS: Data was derived from the National Survey on Drug Use and Health (NSDUH) involving non-Hispanic white, African American, and Hispanic respondents (n = 98,620) and spanning the years 2002-2014. Logistic regression was used to examine significance of trend year and correlates of low-risk and high-risk behavioral groups relative to abstaining. RESULTS: Overall, the prevalence of abstaining was 47.56% between 2002 and 2014. Prevalence increased significantly among all adolescents from 44.85% in 2002 to 53.58% in 2014. Relative to abstainers nonabstaining youth were more likely to be male, and report lower household income, poorer grades, depression, and lower levels of parental affirmation and control. CONCLUSIONS: Findings indicate that there is a corresponding increase in abstaining mirroring the recent decreases found in adolescent drug use found in national surveys.