Bidirectional modulation of negative emotional states by parallel genetically-distinct basolateral amygdala pathways to ventral striatum subregions.

Distinct basolateral amygdala (BLA) cell populations influence emotional responses in manners thought important for anxiety and anxiety disorders. The BLA contains numerous cell types which can broadcast information into structures that may elicit changes in emotional states and behaviors. BLA excitatory neurons can be divided into two main classes, one of which expresses Ppp1r1b (encoding protein phosphatase 1 regulatory inhibitor subunit 1B) which is downstream of the genes encoding the D1 and D2 dopamine receptors (drd1 and drd2 respectively). The role of drd1+ or drd2+ BLA neurons in learned and unlearned emotional responses is unknown. Here, we identified that the drd1+ and drd2+ BLA neuron populations form two parallel pathways for communication with the ventral striatum. These neurons arise from the basal nucleus of the BLA, innervate the entire space of the ventral striatum, and are capable of exciting ventral striatum neurons. Further, through three separate behavioral assays, we found that the drd1+ and drd2+ parallel pathways bidirectionally influence both learned and unlearned emotional states when they are activated or suppressed, and do so depending upon where they synapse in the ventral striatum - with unique contributions of drd1+ and drd2+ circuitry on negative emotional states. Overall, these results contribute to a model whereby parallel, genetically-distinct BLA to ventral striatum circuits inform emotional states in a projection-specific manner.

Testing the Shamiri Intervention and Its Components With Kenyan Adolescents During the COVID-19 Pandemic: Outcomes of a Universal, 5-Arm Randomized Controlled Trial.

OBJECTIVE: Mental health problems are prevalent among African adolescents, but professional treatment capacity is limited. Shamiri, an efficient lay provider-delivered intervention, has significantly reduced depression and anxiety symptoms in previous randomized controlled trials (RCTs). This trial investigated effects of the full Shamiri intervention and its components (growth-only, gratitude-only, and values-only) against a study skills control. METHOD: In a 5-group RCT with adolescents from Kenyan high schools, anxiety, depression, and well-being were self-reported through 8-month follow-up. The RCT occurred immediately after an unanticipated government-mandated COVID-19 shutdown forced 3 years of schoolwork into 2 years, escalating academic pressures. RESULTS: Participants (N = 1,252; 48.72% female) were allocated to: growth (n = 249), gratitude (n = 237), values (n = 265), Shamiri (n = 250), and study skills (n = 251) conditions. Longitudinal multilevel models showed that, across all conditions, anxiety scores significantly improved at midpoint (B = -0.847), end point (B = -2.948), 1-month (B = -1.587), 3-month (B = -2.374), and 8-month (B = -1.917) follow-ups. Depression scores also improved significantly at midpoint (B = -0.796), end point (B = -3.126), 1-month (B = -2.382), 3-month (B = -2.521), and 8-month (B = -2.237) follow-ups. Well-being scores improved significantly at midpoint (B = 1.73), end point (B = 3.44), 1-month (B = 2.21), 3-month (B = 1.78), and 8-month (B = 1.59) follow-ups. Symptom reduction with Shamiri matched that of pre-COVID-19 trials, but symptom reduction with study skills far outpaced that of trials before the COVID-19-related school shutdown (31% greater anxiety reduction and 60% greater depression reduction). Thus, in contrast to previous RCTs, this COVID-19-era trial showed no significant differences between outcomes in any intervention and active control groups. CONCLUSION: Our RCT conducted during a post-COVID-19 period of heightened academic pressure produced unexpected results. Improvements in youth-reported anxiety and depression were consistent with previous trials for Shamiri, but markedly larger than in previous trials for study skills. Control interventions teaching life skills may produce mental health benefits when they convey skills of particular contextual relevance. CLINICAL TRIAL REGISTRATION: Five-Arm Shamiri Trial; https://pactr.samrc.ac.za/; PACTR202104716135752.

Methods and associations of suicidality in Kenyan high school students: clinical and public health implications.

BACKGROUND: Most evidence on suicidal thoughts, plans and attempts comes from Western countries; prevalence rates may differ in other parts of the world. AIMS: This study determined the prevalence of suicidal thoughts, plans and attempts in high school students in three different regional settings in Kenya. METHOD: This was a cross-sectional study of 2652 high school students. We asked structured questions to determine the prevalence of various types of suicidality, the methods planned or effected, and participants' gender, age and form (grade level). We provided descriptive statistics, testing significant differences by chi-squared and Fisher's exact tests, and used logistic regression to identify relationships among different variables and their associations with suicidality. RESULTS: The prevalence rates of suicidal thoughts, plans and attempts were 26.8, 14.9 and 15.7%, respectively. These rates are higher than those reported for Western countries. Some 6.7% of suicide attempts were not associated with plans. The most common method used in suicide attempts was drinking chemicals/poison (18.8%). Rates of suicidal thoughts and plans were higher for older students and students in urban rather than rural locations, and attempts were associated with female gender and higher grade level - especially the final year of high school, when exam performance affects future education and career prospects. CONCLUSION: Suicidal thoughts, plans and attempts are prevalent in Kenyan high school students. There is a need for future studies to determine the different starting points to suicidal attempts, particularly for the significant number whose attempts are not preceded by thoughts and plans.

The application of PTR-MS and non-targeted analysis to characterize VOCs emitted from a plastic recycling facility fire.

BACKGROUND: On April 11th, 2023, the My Way Trading (MWT) recycling facility in Richmond, Indiana caught fire, mandating the evacuation of local residents and necessitating the U.S. Environmental Protection Agency (EPA) to conduct air monitoring. The EPA detected elevated levels of plastic combustion-related air pollutants, including hydrogen cyanide and benzene. OBJECTIVE: We aimed to identify these and other volatile organic compounds (VOCs) present as well as to identify the potential hazard of each compound for various human health effects. METHODS: To identify the VOCs, we conducted air monitoring at sites within and bordering the evacuation zone using proton transfer reaction mass spectrometry (PTR-MS) and non-targeted analysis (NTA). To facilitate risk assessment of the emitted VOCs, we used the EPA Hazard Comparison Dashboard. RESULTS: We identified 46 VOCs, within and outside the evacuation zone, with average detection levels above local background levels measured in Middletown, OH. Levels of hydrogen cyanide and 4 other VOCs were at least 1.8-fold higher near the incidence site in comparison to background levels and displayed unique temporal and spatial patterns. The 46 VOCs identified had the highest hazardous potential for eye and skin irritation, with approximately 45% and 39%, respectively, of the VOCs classified as high and very high hazards for these endpoints. Notably, all detected VOC levels were below the hazard thresholds set for single VOC exposures; however, hazard thresholds for exposure to VOC mixtures are currently unclear. IMPACT: This study serves as a proof-of-concept that PTR-MS coupled with NTA can facilitate rapid identification and hazard assessment of VOCs emitted following anthropogenic disasters. Furthermore, it demonstrates that this approach may augment future disaster responses to quantify additional VOCs present in complex combustion mixtures.

Factors Associated With Additional Axillary Disease in Patients With Positive Sentinel Lymph Nodes After Neoadjuvant Chemotherapy for Breast Cancer.

Background: In previous studies, breast cancer patients with positive sentinel lymph node(s) (SLN) after neoadjuvant chemotherapy (NAC) frequently had additional nonSLN involvement. Per guidelines, residual SLN disease warrants completion axillary lymph node dissection (cALND), which has increased morbidity. Given recent improvements in NAC, we hypothesized that nonSLN positivity may be lower than previously reported for certain subgroups.Methods: We retrospectively reviewed breast cancer patients who received NAC and had positive lymph nodes on SLN biopsy or targeted axillary dissection and underwent cALND at one institution in 1/2018-8/2023. Associations between nonSLN positivity and clinicopathologic factors were assessed with Fisher's exact test and multivariable logistic regression.Results: There were 122 female patients. Median age was 48 years. Initially, 15 patients (12.3%) were cN0 and 107 patients (87.7%) were cN1. Largest SLN deposit was macrometastasis in 96 patients (78.7%), micrometastasis in 23 patients (18.9%), and isolated tumor cells in 3 patients (2.5%). Overall, 53 patients (43.4%) had nonSLN involvement. NonSLN positivity was higher in patients with cN1, ER+ HER2-, ypT2-3, SLN macrometastasis, and multiple positive SLN. On multivariable analysis, cN1 and ER+ HER2- remained associated with nonSLN positivity.Discussion: Among patients with positive SLN after NAC, clinically node positive and ER+ HER2- patients were more likely to have nonSLN involvement. Our findings support guidelines to consider omitting cALND in clinically node negative patients. With improving NAC, optimal axillary sampling, and radiation, omitting cALND may be safe in some clinically node positive triple negative or HER2+ patients with low volume residual disease, but further research is needed.

Face-to-face bullying in and outside of schools and cyberbullying are associated with suicidality in Kenyan high school students: a public health issue.

BACKGROUND: Childhood bullying has been classified as a major public health concern by WHO, with negative effects on the health education and social outcomes of both bullies and victims. There is no current Kenyan data on the prevalence of face-to-face bullying and cyberbullying co-occurring in the same cohort of youth and how they are associated with different aspects of suicidality and socio-demographic characteristics. This study aims to fill these gaps in the Kenyan situation so as to inform current policy and practice. METHODOLOGY: This cross-sectional study involved 2,652 students from ten secondary schools in Kenya, selected from three regions representing different levels of public funded schools and socioeconomic spaces. The outcome variable was derived from the questionnaire which asked students questions related to self-harm, suicide thoughts, plans, and attempts. Predictor variables were based on response on experience of bullying in school, out of school, at home, and cyberbullying. Other variables such as gender, age, family background, and class were also collected from the self-reported questions. Data were analyzed using SPSS version 25, with descriptive summary statistics and chi-square tests used to examine variables, and logistic regression analysis used to determine the associations between suicidality and experience of bullying. RESULTS: The mean age was 16.13 years. More than half of the participants were male, with the largest proportion living in rural areas. Face-to-face bullying was more prevalent than cyberbullying, with 82% of participants experiencing bullying and 68% experiencing it almost daily in the past six months. Both face-to-face bullying and cyberbullying were associated with suicidal thoughts, plans, and attempts. Predictors of suicidal attempts included being bullied outside of school and being a victim of group bullying, while being bullied every day and being bullied by adult men were predictors of suicidal attempts in cyberbullying. CONCLUSION: There is a high prevalence of face-to-face bullying both in and outside schools. There is also a high prevalence of cyberbullying. Both face-to-face and cyberbullying are associated with suicidality in Kenyan high school students.

The perceived impact of climate change on mental health and suicidality in Kenyan high school students.

BACKGROUND: Climate change has psychological impacts but most of the attention has been focused on the physical impact. This study was aimed at determining the association of climate change with adolescent mental health and suicidality as reported by Kenyan high school students. METHODS: This was a cross sectional study with a sample size of 2,652. The participants were high school students selected from 10 schools in 3 regions of Kenya. A questionnaire was used to assess climate change experiences, mental health problems, and suicidality of the youth. Data were analyzed descriptively and with logistic regression to determine various associations of the different variables and the predictors of the various scores of SDQ and suicidality at 95% CI. RESULTS: Significant differences were observed between gender and two of the threats of climate change - worry and being afraid as subjectively experienced by the participants. Females were more worried and afraid of climate change than males. On univariate and multivariate logistic regression, we found that various experiences of climate change were significantly associated with various scores of SDQ and much fewer of the experiences predicted SDQ scores. The same pattern was reflected in suicidality. CONCLUSION: Climate change appears to be associated with mental health concerns and suicidality according to Kenyan high school students' reports with gender differences in some associations.

Raw diffraction data and reproducibility.

In recent years, there has been a major expansion in digital storage capability for hosting raw diffraction datasets. Naturally, the question has now arisen as to the benefits and costs for the preservation of such raw, i.e., experimental diffraction datasets. We describe the consultations made of the global structural chemistry, i.e., chemical crystallography community from the points of view of the International Union of Crystallography (IUCr) Committee on Data, of which JRH was the Chair until very recently, and the IUCrData Raw Data Letters initiative, for which LKB is the Main Editor. The monitoring by the CCDC of CSD depositions which cite the digital object identifiers of raw diffraction datasets provides interesting statistics by probe (x-ray, neutron, or electron) and by home lab vs central facility. Clearly, a better understanding of the reproducibility of current analysis procedures is at hand. Policies for publication requiring raw data have been updated in IUCr Journals for macromolecular crystallography, namely, that raw data should be made available for a new crystal structure or a new method as well as the wwPDB deposition. For chemical crystallography, such a step requiring raw data archiving has not yet been recommended by the IUCr Commission on Structural Chemistry.

Designing a Web-Based Navigation Tool to Support Access to Youth Mental Health Services: Qualitative Study.

BACKGROUND: Many young people with mental health problems do not readily seek help or receive treatment and support. One way to address low help-seeking behavior is to improve access to information on mental health services and how to navigate the mental health system via a web-based tool. Seeking input from the end users (young people and parents or caregivers) on key features of the tool is imperative to ensure that it is relevant, engaging, and likely to meet their needs and expectations. OBJECTIVE: This study aims to investigate young person and parent or caregiver views on the design, content, functioning, and user experience of a web-based mental health navigation tool to support connection to mental health services for children and young people aged up to 25 years. METHODS: A total of 4 online focus groups were conducted: 2 with young people aged 16 years and older (total n=15) and 2 with parents or caregivers (total n=13). Focus groups were structured around a series of guiding questions to explore participants' views on content, features, user experience, and design of a mental health navigation website. Focus groups were audio recorded with detailed notes taken. In addition, 53 young people aged 16-25 years and 97 parents or caregivers completed an online survey, comprising closed- and open-ended questions; open-ended responses were included with the focus group data in the qualitative analysis. All qualitative data were analyzed using thematic analysis. RESULTS: A total of 2 topic areas and 7 themes were developed. The first topic area covered the types of information needs of young people and parents. Identified themes concerned the scope of the navigation website, as well as the provision of up-to-date and practical information on how to navigate the whole help-seeking process. The second topic area covered website features that would be beneficial and included the consideration of the website design; search engines; supported navigation; and forums, reviews, and user accounts. CONCLUSIONS: This study provides important insights into the navigation needs of young people and parents or caregivers in seeking mental health services. Key findings identified through this research have directly informed the development of MindMap, a web-based youth navigation tool providing a searchable database of local services, including a clear description, their location, and potential wait times. The website can be navigated independently or with support.

Association of arsenic exposure with measles antibody titers in US children: Influence of sex and serum folate levels.

Exposure to arsenic during childhood is associated with various adverse health conditions. However, little is known about the effect of arsenic exposure on vaccine-related humoral immunity in children. We analyzed data from the National Health and Nutrition Examination Survey (2003-2004 and 2009-2010) to study the relationship between urinary arsenic and measles antibody levels in 476 US children aged 6-11. Multivariable linear regression was used to evaluate the association, adjusting for cycle, age, race, body mass index (BMI), serum cotinine, poverty index ratio, and vitamin B12 and selenium intakes. Stratified analyses were conducted by sex and serum folate levels using the median as cutoff (18.7 ng/mL). The measles antibody concentrations in the 3rd and 4th quartiles were found to have significantly decreased by 28.5 % (95 % Confidence Interval (CI) -47.6, -2.28) and 36.8 % (95 % CI -50.2, -19.5), compared to the lowest quartile among boys with serum folate levels lower than 18.7 ng/ml. The serum measles antibody titers significantly decreased by 16.7 % (95 %CI -25.0, -7.61) for each doubling of creatinine-corrected urinary total inorganic arsenic concentrations in the same group. No associations were found in boys with high serum folate levels or in girls. Further prospective studies are needed to validate these findings and develop interventions to protect children from infectious diseases.

Lactational transfer of sulforaphane-N-acetylcysteine in vivo and in human breast milk.

Sulforaphane (SFN) is a bioactive phytonutrient found in cruciferous vegetables. There is a lack of detailed information on the lactational transfer of SFN and SFN metabolites, and potential pharmacological effects on breastfeeding infants. We carried out two maternal supplementation studies in a mouse model, wherein lactating dams received either vehicle, 300 or 600 ppm SFN from postnatal day (PND) 1 to 5, or in a second experiment, vehicle or 600 ppm SFN from PND 1 to 14. The parent compound was only detectable in milk and plasma from dams receiving 600 ppm SFN for five days. The predominant metabolite SFN-N-acetylcysteine (SFN-NAC) was readily detected in milk from dams receiving 300 and 600 ppm SFN for five days or 600 ppm for 14 days. Maternal SFN-NAC plasma levels were elevated in both 600 ppm groups. Maternal hepatic and pulmonary expression of NRF2-related genes, Nqo1, Gsta2, Gstm1, and Gstp1, were significantly increased, generally following a dose-response; however, offspring induction varied. PND5 neonates in the 600-ppm group exhibited significantly elevated expression of Nqo1, Gsta2, and Gstp1 in liver, and Gstm1 and Gstp1 in lung. Findings support maternal dietary supplementation with SFN induces NRF2-related gene expression in neonates via lactational transfer of SFN-NAC. However, NQO1 enzyme activity was not significantly elevated, highlighting the need to optimize dosing strategy. Additionally, in a pilot investigation of lactating women consuming a typical diet, without any purified SFN supplementation, 7 out of 8 breast milk samples showed SFN-NAC above the limit of quantification (LOQ). Notably, the one sample below the LOQ was collected from the only participant who reported no consumption of cruciferous vegetables in the past 24 h. The parent compound was not detected in any of the human breast milk samples. Overall, these data indicate lactational transfer of SFN-NAC at dietary relevant levels. Future studies are needed to evaluate pharmacokinetics and pharmacodynamics of lactational transfer for potential preventive or therapeutic effects in breastfeeding children.

Psychometric properties of the Curiosity and Exploration Inventory-II among Kenyan adolescents.

Introduction: Curiosity is a fundamental trait that drives exploration, motivation, learning, and growth. However, research on this character strength in sub-Saharan African populations is very scarce. To address this gap in the literature, we sought to determine the psychometric properties of the Curiosity and Exploration Inventory- II (CEI-II), a measure for trait curiosity, to provide evidence of validity for its use in research among populations in sub-Saharan Africa. We also aimed to assess for demographic and psychosocial correlates of curiosity among Kenyan high school students. Methods: A sample of 375 participants in Kenya completed the CEI-II, as well as demographic information on sex, age, form in school, psychosocial measures of depression, anxiety, school climate, and social support. Using cross-sectional data, parallel analysis, scree plot, and structural equation modeling were used to determine the factor structure of the CEI-II among the Kenyan adolescent population. Results: A one-factor solution was found to be the best fitting model, differing from the two-factor structure found in the original development of the measure. Internal consistency, convergent and discriminant validity, and predictors of trait curiosity were also examined. The CEI-II demonstrated good internal consistency and convergent validity with social support from family, friends, significant others, and school climate. Discriminant validity was demonstrated by the non-significant correlation between curiosity and depression. A hierarchical regression model showed that curiosity was significantly predicted by social support from family, significant others, school climate, and anxiety, with males being more curious than females. Discussion: The CEI-II is a valid measurement tool to capture trait curiosity in Kenyan adolescents, and our findings provide insight into the relationship between curiosity and other psychosocial factors in this population.

Exploring Challenges Related to Breast Cancer to Identify Opportunities for Advocacy in Hawassa City, Southern Ethiopia: A Community-Based, Qualitative Study.

PURPOSE: The aim of this study was to explore breast cancer (BC) challenges to identify opportunities for advocacy in southern Ethiopia in 2022. METHODS: Twenty-five participants from four local districts (kebeles) in Hawassa City were selected as key contributors to future work. Semistructured in-depth interviews were held for two clinicians, two local health bureau managers, two media managers, and three religious leaders. Two focus group discussions were conducted: one included six BC survivors and a caregiver; the other included two health extension workers, three members of the Women's Development Group, two community volunteers, one kebele leader, and one traditional healer. RESULTS: To our knowledge, our study was the first time that most participants had assembled. Many referred to patients as victims and BC as a killer disease or curse. Community and religious leaders were concerned about challenges and willing to collaborate. Survivors, providers, and religious leaders were identified as key sources of information, positive messages, and leadership. CONCLUSION: Recommendations for advocacy work in Hawassa include lobbying for BC as a health priority; including BC within the health extension package; initiating programs for earlier detection; educating the community to remove stigmas of the disease and treatments; working with media to disseminate messages that are inclusive of people in remote areas and speaking different languages; improving availability, affordability, and access to care; and assisting patients with psychosocial support. A strategic collaboration between religious leaders and health care providers was identified to increase community awareness and support advocacy for patients.

Ventral striatal islands of Calleja neurons bidirectionally mediate depression-like behaviors in mice.

The ventral striatum is a reward center implicated in the pathophysiology of depression. It contains islands of Calleja, clusters of dopamine D3 receptor-expressing granule cells, predominantly in the olfactory tubercle (OT). These OT D3 neurons regulate self-grooming, a repetitive behavior manifested in affective disorders. Here we show that chronic restraint stress (CRS) induces robust depression-like behaviors in mice and decreases excitability of OT D3 neurons. Ablation or inhibition of these neurons leads to depression-like behaviors, whereas their activation ameliorates CRS-induced depression-like behaviors. Moreover, activation of OT D3 neurons has a rewarding effect, which diminishes when grooming is blocked. Finally, we propose a model that explains how OT D3 neurons may influence dopamine release via synaptic connections with OT spiny projection neurons (SPNs) that project to midbrain dopamine neurons. Our study reveals a crucial role of OT D3 neurons in bidirectionally mediating depression-like behaviors, suggesting a potential therapeutic target.

Costs and cost-effectiveness of Shamiri, a brief, layperson-delivered intervention for Kenyan adolescents: a randomized controlled trial.

BACKGROUND: Low- and middle-income countries (LMICs) have the highest socio-economic burden of mental health disorders, yet the fewest resources for treatment. Recently, many intervention strategies, including the use of brief, scalable interventions, have emerged as ways of reducing the mental health treatment gap in LMICs. But how do decision makers prioritize and optimize the allocation of limited resources? One approach is through the evaluation of delivery costs alongside intervention effectiveness of various types of interventions. Here, we evaluate the cost-effectiveness of Shamiri, a group- and school-based intervention for adolescent depression and anxiety that is delivered by lay providers and that teaches growth mindset, gratitude, and value affirmation. METHODS: We estimated the cost-effectiveness of Shamiri using the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) guidelines for economic evaluations. Changes in depression and anxiety were estimated using the Patient Health Questionnaire (PHQ-8) and Generalized Anxiety Disorder questionnaire (GAD-7) at treatment termination and 7-month follow-up using two definitions of treatment benefit. Cost-effectiveness metrics included effectiveness-cost ratios and cost per number needed to treat. RESULTS: Base case cost assumptions estimated that delivering Shamiri cost $15.17 (in 2021 U.S. dollars) per student. A sensitivity analysis, which varied cost and clinical change definitions, estimated it cost between $48.28 and $172.72 to help 1 student in Shamiri, relative to the control, achieve reliable and clinically significant change in depression and anxiety by 7-month follow-up. CONCLUSIONS: Shamiri appears to be a low-cost intervention that can produce clinically meaningful reductions in depression and anxiety. Lay providers can deliver effective treatment for a fraction of the training time that is required to become a licensed mental health provider (10 days vs. multiple years), which is a strength from an economic perspective. Additionally, Shamiri produced reliable and clinically significant reductions in depression and anxiety after only four weekly sessions instead of the traditional 12-16 weekly sessions necessary for gold-standard cognitive behavioral therapy. The school setting, group format, and economic context of a LMIC influenced the cost per student; however, broader conclusions about the cost-effectiveness of Shamiri have yet to be determined due to limited economic evaluations of mental health programs in LMICs. TRIAL REGISTRATION: This study was registered prior to participant enrollment in the Pan-African Clinical Trials Registry (PACTR201906525818462), registered 20 Jun 2019, https://pactr.samrc.ac.za/Search.aspx .

Air Pollutant Patterns and Human Health Risk following the East Palestine, Ohio, Train Derailment.

On February 3, 2023, a train carrying numerous hazardous chemicals derailed in East Palestine, OH, spurring temporary evacuation of residents and a controlled burn of some of the hazardous cargo. Residents reported health symptoms, including headaches and respiratory, skin, and eye irritation. Initial data from U.S. Environmental Protection Agency (EPA) stationary air monitors indicated levels of potential concern for air toxics based on hazard quotient calculations. To provide complementary data, we conducted mobile air quality sampling on February 20 and 21 using proton transfer reaction-mass spectrometry. Measurements were taken at 1 s intervals along routes designed to sample both close to and farther from the derailment. Mobile air monitoring indicated that average concentrations of benzene, toluene, xylenes, and vinyl chloride were below minimal risk levels for intermediate and chronic exposures, similar to EPA stationary monitoring data. Levels of acrolein were high relative to those of other volatile organic compounds, with spatial analyses showing levels in East Palestine up to 6 times higher than the local rural background. Nontargeted analyses identified levels of additional unique compounds above background levels, some displaying spatiotemporal patterns similar to that of acrolein and others exhibiting distinct hot spots. These initial findings warrant follow-up mobile air quality monitoring to characterize longitudinal exposure and risk levels.

The development of sniffing.

Sniffing is a commonly displayed behavior in rodents, yet how this important behavior adjusts throughout development to meet the sensory demands of the animals has remained largely unexplored. In this issue of Chemical Senses, Boulanger-Bertolus et al. investigates the ontogeny of odor-evoked sniffing through a longitudinal study of rats engaged in several olfactory paradigms from infancy to adulthood. The results of this study yield a cohesive picture of sniffing behavior across three developmental stages, while also providing direct comparisons within subjects between these timepoints. As we discuss herein, these results advance the field in relation to existing literature on the development of odor-evoked sniffing behavior in several important ways.

Strawberry Additive Increases Nicotine Vapor Sampling and Systemic Exposure But Does Not Enhance Pavlovian-Based Nicotine Reward in Mice.

Nicotine is an addictive drug whose popularity has recently increased, particularly among adolescents, because of the availability of electronic nicotine devices (i.e., "vaping") and nicotine e-liquids containing additives with rich chemosensory properties. Some efforts to understand the role of these additives in nicotine reward suggest that they increase nicotine reward and reinforcement, but the sensory contributions of additives, especially in their vapor forms, are largely untested. Here, to better understand how a fruit-flavored (i.e., strawberry) additive influences nicotine reward and aversion, we used a conditioned place preference (CPP) procedure in which nicotine and a strawberry additive were delivered as a vapor to male and female adolescent mice. We found that nicotine vapor alone can lead to a dose-dependent CPP when using a biased design. The strawberry additive did not produce CPP on its own, and we did not observe an effect of the strawberry additive on nicotine vapor-induced reward. Nevertheless, mice exposed to nicotine plus strawberry additive vapor had higher plasma cotinine concentrations, which did not appear to reflect altered nicotine metabolism. Instead, by directly measuring vapor sampling through respiration monitoring, we uncovered an increase in the amount of sniffing toward strawberry-containing nicotine vapor compared with nicotine vapor alone. Together these data indicate that chemosensory-rich e-liquid additives may enhance the perceived sensory profile of nicotine vapors rather than the reward value per se, which leads to overall increased nicotine exposure.

Maternal exposure to ultrafine particles enhances influenza infection during pregnancy.

BACKGROUND: Interactions between air pollution and infectious agents are increasingly recognized and critical to identify, especially to protect vulnerable populations. Pregnancy represents a vulnerable period for influenza infection and air pollution exposure, yet interactions during pregnancy remain unclear. Maternal exposure to ultrafine particles (UFPs, [Formula: see text] 100 nm diameter), a class of particulate matter ubiquitous in urban environments, elicits unique pulmonary immune responses. We hypothesized that UFP exposure during pregnancy would lead to aberrant immune responses to influenza enhancing infection severity. RESULTS: Building from our well-characterized C57Bl/6N mouse model employing daily gestational UFP exposure from gestational day (GD) 0.5-13.5, we carried out a pilot study wherein pregnant dams were subsequently infected with Influenza A/Puerto Rico/8/1934 (PR8) on GD14.5. Findings indicate that PR8 infection caused decreased weight gain in filtered air (FA) and UFP-exposed groups. Co-exposure to UFPs and viral infection led to pronounced elevation in PR8 viral titer and reduced pulmonary inflammation, signifying potential suppression of innate and adaptive immune defenses. Pulmonary expression of the pro-viral factor sphingosine kinase 1 (Sphk1) and pro-inflammatory cytokine interleukin-1ß (IL-1 [Formula: see text]) was significantly increased in pregnant mice exposed to UFPs and infected with PR8; expression correlated with higher viral titer. CONCLUSIONS: Results from our model provide initial insight into how maternal UFP exposure during pregnancy enhances respiratory viral infection risk. This model is an important first step in establishing future regulatory and clinical strategies for protecting pregnant women exposed to UFPs.