Repeated Exposure Research Articles

Sex Differences in the Alcohol-Mediated Modulation of BLA Network States.

Alcohol use, reported by 85% of adults in the United States, is highly comorbid with mood disorders, like generalized anxiety disorder and major depression. The basolateral amygdala (BLA) is an area of the brain that is heavily implicated in both mood disorders and alcohol use disorder. Importantly, the modulation of BLA network/oscillatory states via parvalbumin (PV)-positive GABAergic interneurons has been shown to control the behavioral expression of fear and anxiety. Further, PV interneurons express a high density of δ subunit-containing GABAA receptors (GABAARs), which are sensitive to low concentrations of alcohol. Therefore, we hypothesized that the effects of alcohol may modulate BLA network states that have been associated with fear and anxiety behaviors via δ-GABAARs on PV interneurons in the BLA. Given the impact of ovarian hormones on the expression of δ-GABAARs, we also examined the ability of alcohol to modulate local field potentials in the BLA from male and female C57BL/6J and Gabrd−/− mice after acute and repeated exposure to alcohol. Here, we demonstrate that acute and repeated alcohol can differentially modulate oscillatory states in male and female C57BL/6J mice, a process that involves δ-GABAARs. This is the first study to demonstrate that alcohol is capable of altering network states implicated in both anxiety and alcohol use disorders.

Experimental substantiation of the tentatively safe level of diethyl disulfide in the air of the working area and the atmospheric air of populated areas

Introduction. Diethyl disulfide belongs to the group of dialkyl disulfides, is a part of disulfide oil and a mixture of dialkyl disulfides. As a result of industrial purification of hydrocarbon raw materials from mercaptans, tens of thousands of tons of dialkyldisulfides and their mixtures are accumulated annually, the toxicity and danger of which have not been fully studied. No hygiene standards have been developed for diethyl disulfide. Materials and methods. Studies of the effects of diethyl disulfide were carried out in non-linear animals (rats and mice). The toxic properties of diethyl disulfide were studied under the conditions of single and repeated exposure to the intragastric, intraperitoneal, inhalation and cutaneous routes of entry into the body. Results. Based on the studies carried out, the toxicometric parameters of diethyl disulfide were established. Average lethal dose with intragastric administration LD50 = 1575 mg/kg, average lethal concentration CL50 = 18700 mg/m3, coefficient of possible inhalation poisoning CPIP = 1.3, limit of acute inhalation action (Limac) is set at 120 mg/m3, acute zone Zac = 156, cumulation coefficient was 3.2. Diethyl disulfide does not have a skin-resorptive toxic effect, but it has a moderately pronounced irritating effect on the mucous membrane of the eyes. Limitations of the study. The results of the diethyl disulfide exposure assessment are given for two animal species and four main routes of entry. Conclusion. The data obtained indicate that diethyl disulfide is a moderately hazardous substance with a single intragastric, inhalation and cutaneous route of entry into the body. The cumulative properties of diethyl disulfide are moderately expressed. Based on the analysis of literature data, the results of experimental studies and mathematical forecasting, a value of 4.0 mg/m3 is recommended as an approximate safe level of exposure in the air of the working area, in the atmospheric air of urban and rural settlements - 0.04 mg/m3.

Heroin Addiction Induces Axonal Transport Dysfunction in the Brain Detected by In Vivo MRI.

Heroin is a highly addictive drug that causes axonal damage. Here, manganese-enhanced magnetic resonance imaging (MEMRI) was used to dynamically monitor axonal transport at different stages of heroin addiction. Rat models of heroin addiction (HA) and prolonged heroin addiction (PHA) were established by injecting rats with heroin at different stages. Heroin-induced learning and memory deficits were evaluated in the Morris water maze (MWM), and MEMRI was used to dynamically evaluate axonal transport in the olfactory pathway. The expression of proteins related to axonal structure and function was also assessed by Western blotting. Transmission electron microscopy (TEM) was used to observe ultrastructural changes, and protein levels of neurofilament heavy chain (NF-H) were analyzed by immunofluorescence staining. HA rats, especially PHA rats, exhibited worse spatial learning and memory than control rats. Compared with HA rats and control rats, PHA rats exhibited significantly longer escape latencies, significantly fewer platform-location crossings, and significantly more time in the target quadrant during the MWM test. Mn2+ transport was accelerated in HA rats. PHA rats exhibited severely reduced Mn2+ transport, and the axonal transport rate (ATR) was significantly lower in these rats than in control rats (P < 0.001). The levels of cytoplasmic dynein and kinesin-1 were significantly decreased in the PHA group than in the control group (P < 0.001); additionally, the levels of energy-related proteins, including cytochrome c oxidase (COX) IV and ATP synthase subunit beta (ATPB), were lower in the PHA group (P < 0.001). The brains of heroin-exposed rats displayed an abnormal ultrastructure, with neuronal apoptosis and mitochondrial dysfunction. Heroin exposure decreased the expression of NF-H, as indicated by significantly reduced staining intensities in tissues from HA and PHA rats (P < 0.05). MEMRI detected axonal transport dysfunction caused by long-term repeated exposure to heroin. The main causes of axonal transport impairment may be decreases in the levels of motor proteins and mitochondrial dysfunction. This study shows that MEMRI is a potential tool for visualizing axonal transport in individuals with drug addictions, providing a new way to evaluate addictive encephalopathy.

An Adjuvant-Free Mouse Model Using Skin Sensitization Without Tape-Stripping Followed by Oral Elicitation of Anaphylaxis: A Novel Pre-Clinical Tool for Testing Intrinsic Wheat Allergenicity.

Wheat is a major food allergen per the regulatory bodies of various nations. Hypersensitivity reactions to wheat have been steadily increasing for reasons that are not completely understood. Wheat-allergy models typically use adjuvants to induce sensitization to wheat proteins followed by an intraperitoneal challenge to elicit anaphylaxis. Although these models are very useful, they lack the ability to reveal the intrinsic allergenicity potential of wheat. To improve the mouse model of wheat allergy, we tested the hypothesis that repeated skin application of salt-soluble protein extract (SSPE) from durum wheat will clinically sensitize the mice to oral anaphylaxis to SSPE. Balb/c mice were bred and maintained on a plant-protein-free diet and used in the experiments. Adult female mice were exposed to SSPE once a week for 9 weeks via a solution on intact skin. Sensitization was measured by SSPE-specific IgE (sIgE) antibody and total IgE (tIgE) levels. Oral anaphylaxis was quantified by hypothermic shock response (HSR), and mucosal mast cell response (MMCR) was quantified by measuring MMCP-1 after oral challenge. Using single mouse data, correlation analyses were performed to determine the relationship among the allergenicity readouts. Spleen cytokines were quantified using a protein microarray method. Our results show that (i) repeated skin exposures to SSPE elicited robust increases in the sIgE and tIgE levels; (ii) skin exposure to SSPE was sufficient to sensitize mice for oral anaphylaxis and MMCR; (iii) both HSR and MMCR showed a strong correlation with each other, as well as with sIgE, and a modest correlation with tIgE levels; (iv) selected Th2/Th17/Th1 cytokines were elevated in skin-sensitized mice; and (v) oral allergen-challenged mice showed selective elevation of IL-6 and a panel of chemokines compared to saline-challenged mice. Together, we report the development and characterization of a novel adjuvant-free wheat-allergy mouse model that uses skin sensitization without tape-stripping followed by oral elicitation of anaphylaxis. Furthermore, validation of quantifiable wheat allergenicity readouts makes this model particularly suitable as a pre-clinical testing tool to assess the intrinsic sensitization/oral-anaphylaxis elicitation potential of novel wheat proteins (e.g., processed wheat) and to develop hypo/non-allergenic wheat products.

Preliminary longitudinal evidence for stability of maternal behavior and infant stress regulation among infants born preterm at 4 and 9 months during the Still Face paradigm

Stress regulation begins to develop in the first year of life through interactions with caregivers, particularly in the presence of stressors. High quality caregiving, characterized by maternal sensitivity and responsiveness to the infant’s emotional cues, is particularly important in the development of infant stress regulation. The purpose of this study was to assess the longitudinal stability of, and associations between, maternal interactive behavior and infant stress regulation (indexed by positive infant affect and cortisol reactivity) in response to the Still Face paradigm (SF) in a cohort of infants born preterm (< 32 weeks gestation, N = 22) at four months and nine months (adjusted age). The percent of time mothers spent using specific interaction styles (contingent maternal interaction (CMI), attention seeking, and watching) during Play/baseline, Reunion#1, and Reunion#2 SF episodes was calculated To assess infant stress regulation, two indices were obtained at both 4 and 9 months during the SF paradigm: the percent of positive affect displayed over each SF episode (0-100%) and a neuroendocrine stress response score based on salivary cortisol reactivity. We found three non-significant but medium-large effect size differences between 4 and 9 month variables, with more positive findings at 9 months. Regarding stability within the 4 month and 9 month episodes, maternal behavior and positive infant affect were non-significantly but moderately stable, with maternal watching behavior being particularly stable. Positive infant affect stability between Reunion#1 and Reunion#2 at 4 months was significantly greater than positive infant affect stability across these two episodes at 9 months. Regarding stability across 4 and 9 month (same) episodes, CMI and positive infant affect showed modest but non-significant stability across (same) 4 and 9 month episodes. Finally, with positive infant affect at Reunion#2 as the “outcome” of the Still Face, CMI at both 4 month Play and Reunion#1 episodes were significantly correlated with this “outcome.” Further, positive infant affect at Reunion#2 was more strongly correlated with CMI at both Play and Reunion#1 for 4 month old compared with 9 month old infants. Thus, sensitive care appears particularly important for younger infants born preterm, and mothers’ behavior early in a repeated stress exposure paradigm may be particularly important in maintaining positive infant affect and in the development of infants’ stress regulation more generally. Identifying the longer-term effects of early stress on infant stress regulation, and its relationship with maternal interaction, has important implications for understanding trajectories of regulatory patterns and deficits. A greater understanding of these relationships is particularly important given that greater emotion and neuroendocrine stress regulation in infancy have been directly associated with numerous positive outcomes throughout childhood.

Preventative Care in First Responder Mental Health: Focusing on Access and Utilization via Stepped Telehealth Care.

First responders are at high risk for disorders that arise from repeat exposure to stress and trauma (Post Traumatic Stress Disorder, depression, and problematic alcohol use). Although mental health treatments are available, first responders often do not access them, anchored by barriers that include: lack of knowledge, stigma, negative experience with mental health providers, and time-based burdens. In this study, we designed an intervention to address these barriers, extending a Planned-Action framework. Step 1 involved self-report screening for four mental health risks (PTSD, depression, anxiety, and alcohol use risk), delivered to all personnel electronically, who were free to either consent and participate or opt-out. The detection of risk(s) in Step 1 led to scheduling a Step 2 telehealth appointment with a trained clinician. We report descriptive statistics for participation/attrition/utilization in Steps 1 and 2, rates of risk on four mental health variables, and rate of adherence to follow-up treatment recommendations. Step 1: In total, 53.3% of personnel [229 of 429 full-time employees (221 males; eight females; 95% White; 48% paramedic or Emergency Medical Technician; 25% captain; 19% engineer; 7% other)] initially opted-in by consenting and completing the brief remote screening survey. Among those who opted-in and completed (n = 229), 43% screened positive for one or more of the following mental health risks: PTSD (7.9%); depression (9.6%); anxiety (13.5%); alcohol use (36.7%). Step 2: A maximum of three attempts were made to schedule "at risk" individuals into Step 2 (n = 99). Among the 99 who demonstrated a need for mental health treatment (by screening positive for one or more risk), 56 (56.6%) engaged in the telehealth appointment. Of the 56 who participated in Step 2 clinical appointments, 38 were recommended for further intervention (16.6% of full-time personnel who participated). Among the 38 firefighters who were recommended to seek further mental health services, 29 were adherent/followed through (76.3% of those who received recommendations for further services). Taken together, evidence-based, culturally conscious, stepped care models delivered via the virtual/telehealth medium can promote access, utilization, and cost-effective mental health services for first responders. Implications are for informing larger, more rigorous dissemination and implementation efforts.

A Sequenced, Relationship-Based Approach to the Treatment of Complex Posttraumatic Stress Disorder (CPTSD): The Hybrid Case Study of "Chloe"

Chronic and repeated exposure to relational and developmental trauma can result in a presentation that differs from posttraumatic stress disorder (PTSD), with a unique cluster of complicated symptoms, and has thus been labeled as complex PTSD (CPTSD). Many such individuals meet criteria for PTSD while also exhibiting additional symptomology not accounted for in a traditional PTSD diagnosis. This case study provides an overview of the differences between PTSD and CPTSD, using empirical evidence to illustrate the necessity of distinguishing between these two differing diagnoses and subsequently the need for differing treatment approaches. The purpose of this case study is to examine the benefits of using a three-phase, integrative model for an individual with CPTSD. Specifically, it explores the delivery of Courtois and Ford’s (2013) sequenced, relationship-based approach to the treatment of complex trauma. This model was chosen due to the emphasis on attachment and because it allows for clinicians to tailor interventions to the unique individual while also providing an overarching structure to treatment. This treatment analysis is demonstrated via the hybrid case of "Chloe,” who serves as a meaningful representation of a psychotherapy patient with a history of chronic relational and developmental trauma who presents to treatment with symptoms concurrent with a CPTSD diagnosis. Chloe’s composite case example is based on the author’s actual, de-identified psychotherapy cases in addition to clinical examples in the relevant literature. Using the format of a pragmatic case study (Fishman, 1999, 2013), Chloe’s case is analyzed through qualitative processes and quantitative measures. An in-depth illustration of this hybrid patient’s course of treatment provides an avenue for describing key clinical issues related to the treatment of CPTSD and the utility of an integrative treatment approach. Chloe’s case study is intended to be a resource for clinicians seeking more knowledge and understanding of the impact of chronic developmental and relational trauma and the implications this has for effective treatment.

Effects of repeated exposure to escalating versus constant punishment intensity on response allocation.

The present experiment investigated the effects of 1) repeated exposures to escalating punishment intensities and 2) repeated exposure to punishment after periods of vacation on response allocation between punished and unpunished responding in three groups of rats. The first group (intensity + vacation) experienced repeated exposures to escalating punishment intensities after a period of vacation (i.e., return to baseline) from punishment. The second group (intensity-only) experienced repeated exposures to escalating punishment intensities without vacation from punishment. The third group (vacation-only) experienced repeated exposures to a constant punishment intensity after a period of vacation from punishment. Results showed that superimposition of punishment on one of two concurrently available responses decreased allocation toward the punished response and increased allocation toward the unpunished response. Furthermore, greater changes in allocation were observed with the introduction of a moderate constant intensity than with the introduction of a low intensity that increased across sessions. Reexposure to punishment had different effects between the groups. Although there was evidence that high shock intensities can enhance the efficacy of lower intensities to shift allocation away from the punished response and toward the unpunished response, there was little evidence of changes in response allocation with reintroduction of punishment after a period of vacation.

FC090: Stevia as an Alternative Osmotic Agent for Peritoneal Dialysis Fluid

Abstract BACKGROUND AND AIMS Peritoneal dialysis (PD) is a renal replacement technique that requires repeated contact of the peritoneum with hyperosmolar fluids. Unfortunately, it generates metabolic and biomechanical insults that promote structural and functional alterations of the peritoneal membrane (PM). PM is lined by a mesothelial cells (MCs) monolayer that is in direct contact with the PD fluids (PDFs). Repeated PDF exposure causes a mesothelial–mesenchymal transition (MMT) of the MCs, as well as an inflammatory response, angiogenesis and fibrosis of the peritoneal tissue. For decades, glucose (Gl) has been the most commonly used osmotic agent, and Gl itself is responsible for the aforementioned changes. Furthermore, Gl degradation products (GDPs) contribute to deleterious effects on the PM [1]. Therefore, there is an unmet need for more biocompatible osmotic agents able to better maintain the structure and function of the PM. Here we evaluated the biocompatibility of Stevia (STV), a compound of natural origin with a mixture of glycosides. STV has a molecular weight close to the theoretical ideal weight for an osmotic agent in PD [2] and it was used instead of Gl for PDF. METHODS The osmotic capacity of STV-containing fluids was analysed using an in vitro device with artificial membranes and compared to Gl-based fluids. In order to investigate the STV biocompatibility, human omental peritoneal mesothelial cells (HOMCs) were cultured in the presence of different types of Gl-based PDFs (Conventional 4.25% Gl solution with a high GDP level and biocompatible 2.3% Gl solution with low GDPs level), STV-based fluids or TGF-b for 48 h. Mice submitted to surgery of an intraperitoneal catheter insertion were treated for 40 days with STV- or Gl-based PDFs. Peritoneal tissues were collected to determine thickness, MMT, angiogenesis and inflammatory markers, as well as effluents to analyse infiltrating cells. RESULTS Experimentally, using artificial membranes we demonstrated that 1, 0.75 and 0.5% STV-based fluids have a maintained and prolonged osmotic capacity similar to commercial PDFs containing Gl concentrations between 1.5 and 2.3%. Moreover, 1.5% STV-based fluid showed an osmotic capacity higher than a PDF with Gl 2.3% and reached values similar to Gl 4.25% at longer time points. In addition, HOMCs exposed to STV-based fluids showed higher viability and did not induce MMT. Gl-based fluids induced upregulation of mesenchymal markers (VEGF, fibronectin, snail) and also downregulation of the epithelial marker E-cadherin in the case of the highest concentration of Gl (4.25%). None of these markers were significantly affected by STV treatment. In vivo, STV-based fluids preserved MCs monolayer and induced less PM thickness (Figure 1), angiogenesis, leukocyte infiltration and MMT than Gl-based fluids. Furthermore, STV solutions did not promote the release of pro-inflammatory cytokines by HOMCs nor by cells present in mice parietal peritoneal tissue in contrast to Gl-based PDFs. CONCLUSIONS STV-based fluids showed better biocompatibility than Gl-based PDFs in vivo and ex vivo since STV did not induce PM thickness, MMT, angiogenesis or the release of pro-inflammatory cytokines.

PD53-08 E-CIGARETTE EXPOSURE IN MICE PROMOTES CHANGES IN DNA METHYLATION OF THE BLADDER UROTHELIUM

You have accessJournal of UrologyCME1 May 2022PD53-08 E-CIGARETTE EXPOSURE IN MICE PROMOTES CHANGES IN DNA METHYLATION OF THE BLADDER UROTHELIUM Ibardo Zambrano, Ujjawal Manocha, Weida Gong, Yi-Hsuan Tsai, Manhua Zhu, Melissa Herman, Marc Bjurlin, and William Kim Ibardo ZambranoIbardo Zambrano More articles by this author , Ujjawal ManochaUjjawal Manocha More articles by this author , Weida GongWeida Gong More articles by this author , Yi-Hsuan TsaiYi-Hsuan Tsai More articles by this author , Manhua ZhuManhua Zhu More articles by this author , Melissa HermanMelissa Herman More articles by this author , Marc BjurlinMarc Bjurlin More articles by this author , and William KimWilliam Kim More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002630.08AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: To date, no group has studied the epigenetic effects of e-cigarettes (EC) on the urothelium. DNA methylation changes appear to be one of the earliest events in bladder tumorigenesis and can be readily found in normal urothelium adjacent to bladder tumors. EC exposure causes urothelial hyperplasia in mice but not bladder tumors. We Vtherefore asked whether EC exposure results in early field alterations of DNA methylation in the bladder urothelium. METHODS: Mice (4 females, 4 males; 35 weeks old) were exposed to 12% nicotine in 1:1 polyethylene glycol: vegetable glycerol or vehicle daily: 3 hr sessions, 3 sec vape duration, 10 min interval between vapes. Plasma nicotine and cotinine serum concentrations were measured using LC-MS. Reduced-representation bisulfite sequencing (RRBS) was performed using DNA from microdissected urothelium harvested at 4 weeks (Zymo Research Kit). Number of loci covered by each sample was determined and data was filtered to only include loci with >10 reads. Differentially methylated loci were determined (p<0.01). Gene Set Enrichment Analysis was performed to contextualize the DNA methylation changes. RESULTS: No significant adverse events were observed in the mice during the exposure period to either vehicle or nicotine. Acute and repeated exposure resulted in significantly higher levels of nicotine and cotinine serum concentration in the nicotine vs. the vehicle group (Figure 1). No bladder tumors formed. RRBS analysis demonstrated that EC exposure resulted in hypermethylation of the promoters of 665 genes and hypomethylation of 285 genes after accounting for sex (p <0.05) Pathway analysis showed enrichment of MYC target genes in hypomethylated regions and enrichment of genes associated with oxidative phosphorylation, cilium assembly, and ciliopathies in hypermethylated loci. CONCLUSIONS: Significant changes of DNA methylation were observed in mice exposed to ECS vapor vs. vehicle control. EC metabolites in urine may result in aberrant methylation patterns in the bladder urothelium. Results are suggestive of a pre-malignant phenotype driven by EC exposure via stimulation of MYC targets and silencing of genes responsible for establishing primary cilia. Loss of primary cilia in epithelial cells has been associated with loss of cell polarity and increased cell migration. Source of Funding: NCI Geographical Management of Cancer Health Disparities Program (3P30-CA016086), UNC Lineberger Innovation Award 2020 © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e912 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Ibardo Zambrano More articles by this author Ujjawal Manocha More articles by this author Weida Gong More articles by this author Yi-Hsuan Tsai More articles by this author Manhua Zhu More articles by this author Melissa Herman More articles by this author Marc Bjurlin More articles by this author William Kim More articles by this author Expand All Advertisement PDF DownloadLoading ...

Inflammatory Markers in Substance Use and Mood Disorders: A Neuroimaging Perspective

Chronic exposure to addictive drugs in substance use disorders and stressors in mood disorders render the brain more vulnerable to inflammation. Inflammation in the brain, or neuroinflammation, is characterized by gliosis, microglial activation, and sustained release of cytokines, chemokines, and pro-inflammatory factors compromising the permeability of the blood-brain barrier. There is increased curiosity in understanding how substance misuse and/or repeated stress exposure affect inflammation and contribute to abnormal neuronal activity, altered neuroplasticity, and impaired cognitive control, which eventually promote compulsive drug-use behaviors and worsen mood disorders. This review will emphasize human imaging studies to explore the link between brain function and peripheral markers of inflammation in substance use disorders and mood disorders.

Partial recovery of voiding function in female mice following repeated psychological stress exposure.

Psychological stress causes bladder dysfunction in humans and in rodent models, with increased urinary frequency and altered contractile responses evident following repeated environmental stress exposure. However, whether these changes persist after removal of the stressor is unknown, and the aim of this study was to determine if stress-induced changes in voiding behaviour and bladder function recover following removal of the stressor. Adult female mice were allocated to three groups: Unstressed, Stressed or Stressed + Recovery. Animals in the stressed groups were exposed to water avoidance stress for 1h/day for 10-days, with unstressed animals age-matched and housed under normal conditions. For recovery studies, animals were housed without stress exposure for an additional 10-days. Voiding behaviour was assessed periodically and animals sacrificed on day 10 (Unstressed and Stressed) or day 20 (Unstressed and Stressed + Recovery). Isolated whole bladder studies were used to assess compliance, urothelial mediator release and contractile responses. Exposure to stress increased plasma corticosterone levels almost three-fold (P<0.05) but this returned to baseline during the recovery period. Contractile responses of the bladder to carbachol and KCl were also increased following stress, and again fully recovered after a 10-day stress-free period. In contrast, stress increased urinary frequency four-fold (P<0.001), but this did not return fully to baseline during the recovery period. Bladder compliance was unchanged by stress; however, it was increased in the stressed + recovery group (P<0.05). Thus, following a stress-free period there is partial recovery of voiding behaviour, with an increase in bladder compliance possibly contributing to the compensatory mechanisms.

From food preference development to responsive feeding – Selective studies to commemorate the life and work of Dr Leann Birch

Dr Leann Birch was a pioneer in conducting research on infant and child eating behaviour. At the beginning of her research career, Leann recognised a significant gap in the developmental psychology literature, namely that few studies had been conducted to understand infant eating and feeding behaviours. This seems an unusual omission given that food intake is essential and that developmental milestones from milk to solids, and from being fed to becoming an autonomous eater, are obvious to most caregivers. Leann paved the way for interdisciplinary research from psychology, paediatrics and public health to explore and apply this knowledge to infant and child appetite, eating behaviour, dietary patterns, food preferences, and obesity risk. Early studies in her laboratory demonstrated that children form food preferences through experience and socialisation. Experiments published in 1979 tested the role of familiarisation through repeat exposure, and the impact of instrumental and social learning on the acquisition of food preferences. In 1984, a presentation given to the British Feeding and Drinking Group (BFDG) in Brighton set out three organising principles for understanding how children acquire food preferences: genetically pre-programmed behavioural propensities; social constraints on experience with food; and social transmission resulting from direct social interaction. Building on these three organising principles, research on child eating behaviour has flourished, including the intersection between individual differences, food experience and environmental influences on children's food preferences, energy regulation, and weight outcomes. In this review, the initial groundwork set out by Leann Birch on food preference development in children is considered followed by a discussion of how this has since inspired an interdisciplinary, international and expanding field of research on children's food intake, appetite and body weight regulation.

Exploration of the Effects of Metallic Powder Handling and Storage Conditions on Flowability and Moisture Content for Additive Manufacturing Applications

Metal powder-based additive manufacturing (AM) relies on consistently successful processing of feedstock powder, necessitating through-process predictability in powder properties and behavior. However, routine powder handling and storage may degrade powder performance by influencing flowability and moisture content through exposure to ambient conditions. Therefore, this study aimed to evaluate the effects of repeated environmental exposure on the flowability and moisture content of Al 5056 and Ta powders for AM applications. Using Carney Funnel flow tests, thermogravimetric analysis, and particle size/shape analysis, powder characterization helped elucidate powder property and behavioral changes with exposure. Results indicated inconsistent flowability and moisture content changes for both material types when exposure conditions were altered. Correlational statistics highlighted the most influential particle characteristics on powder behavior after exposure; particle morphology was most impactful for the semi-spherical Al 5056, whereas moisture content and particle size were most significant for the angular Ta. While exposure to laboratory conditions minimally changed powder performance in this study, caution is advised when handling and storing powders in more “extreme” environments. Powder users are urged to implement quality controls alongside powder characterization to pinpoint how specific powders should be treated, handled, and stored in a given environment for successful processing in AM.

Superantigens and SARS-CoV-2.

It has been posited SARS-CoV-2 contains at least one unique superantigen-like motif not found in any other SARS or endemic coronaviruses. Superantigens are potent antigens that can send the immune system into overdrive. SARS-CoV-2 causes many of the biological and clinical consequences of a superantigen, and, in the context of reinfection and waning immunity, it is important to better understand the impact of a widely circulating, airborne pathogen that may be a superantigen, superantigen-like or trigger a superantigenic host response. Urgent research is needed to better understand the long-term risks being taken by governments whose policies enable widespread transmission of a potential superantigenic pathogen, and to more clearly define the vaccination and public health policies needed to protect against the consequences of repeat exposure to the pathogen.

618 Firefighter Resiliency Project: Survey Findings and Implications for a Program Model

IntroductionFirefighters are trained to respond to an array of acute emergencies that culminate in repeated exposure to trauma subsequently impacting their mental health. Yet, they often fail to seek services that could mitigate those adverse effects due to stigma, as well as a dearth of systematized resources and first responder proficient trained mental health professionals. This study explored work-related traumatic event exposure, PTSD symptomatology, levels of depression, anxiety, and suicide risk, and barriers to care for firefighters in a designated catchment area of a southeastern state. Results were used to inform local departments interested in culture change and intervention, as well as providing the basis for successfully obtaining federal grant monies.MethodsUsing Qualtrics, a web-based survey platform, researchers administered a cross-sectional survey to firefighters between Fall 2020 and Spring 2021. The survey included the PCL-5, PHQ-9, GAD-7, SBQ-R, and BACE. Descriptive statistics, correlations, and independent t-tests were run to determine the level of trauma exposure and clinically significant mental health symptomatology, associations between different types of trauma and mental health symptoms, and barriers to accessing care. The sample (N=511) primarily identified as Caucasian (n=421) and male (n=477). Mean age and time in fire service were 39.1 and 14.5 years, respectively.ResultsIn this sample, 18.7% met the criteria for a provisional diagnosis of PTSD based on the PCL-5; 24.4% met the criteria for moderate to severe depression based on the PHQ-9; 14.5% met the criteria for moderate to severe anxiety based on the GAD-7; and 13.7% reported a significant risk of suicidal behavior as measured by the SBQR. Firefighters also indicated the following as the most common barriers to accessing care: 1) being unsure of where to get care (47.3%); 2) thinking the problem would get better itself (41.8%), 3) feeling embarrassed or ashamed (39%), 4) concern that they might be seen as weak for having a mental health problem (36.2%), and 5) thinking they did not have a problem (34.3%).ConclusionsDue to the high levels of work-related trauma exposure, firefighters in this study were at an increased risk of developing mental health symptomatology including PTSD, depression, anxiety, and risk of suicidal behavior when compared to the general population. Additionally, perceived and actual barriers to care provided implications for the grant program application.

Effects of chronic, daily exposures to low intensity blue light on human retinal pigment epithelial cells: Implications for the use of personal electronic devices

• Repeated exposures of RPE cells to blue light can alter their physiology. • Daily exposure to blue light produced defects in all types of RPE cell layers. • Electronic devices could produce retinal damage over a lifetime of use.

Acute physiological and psychophysical responses to different modes of heat stress.

New Findings What is the central question of this study? What are the profiles of acute physiological and psychophysical strain during and in recovery from different modes of heating, and to what extent do these diminish after repeated exposure? What is the main finding and its importance? Mode of heating affects the strain profiles during heat stress and recovery. Exercise in the heat incurred the greatest cardiovascular strain during heating and recovery. Humid heat was poorly tolerated despite heat strain being no greater than in other heating modes, and tolerance did not improve with multiple exposures. Heat stress is common and arises endogenously and exogenously. It can be acutely hazardous while also increasingly advocated to drive health and performance‐related adaptations. Yet, the nature of strain (deviation in regulated variables) imposed by different heating modes is not well established, despite the potential for important differences. We, therefore, compared three modes of heat stress for thermal, cardiovascular and perceptual strain profiles during exposure and recovery when experienced as a novel stimulus and an accustomed stimulus. In a crossover design, 13 physically active participants (five females) underwent 5 days of 60‐min exposures to hot water immersion (40°C), sauna (55°C, 54% relative humidity) and exercise in the heat (40°C, 52% relative humidity), and a thermoneutral water immersion control (36.5°C), each separated by ≥4 weeks. Physiological (thermal, cardiovascular, haemodynamic) and psychophysical strain responses were assessed on days 1 and 5. Sauna evoked the warmest skin (40°C; P < 0.001) but exercise in the heat caused the largest increase in core temperature, sweat rate, heart rate (post hoc comparisons all P < 0.001) and systolic blood pressure (P ≤ 0.002), and possibly decrease in diastolic blood pressures (P ≤ 0.130), regardless of day. Thermal sensation and feeling state were more favourable on day 5 than on day 1 (P ≤ 0.021), with all modes of heat being equivalently uncomfortable (P ≥ 0.215). Plasma volume expanded the largest extent during immersions (P < 0.001). The current data highlight that exercising in the heat generates a more complex strain profile, while passive heat stress in humid heat has lower tolerance and more cardiovascular strain than hot water immersion.

Treatment of Spider Phobia Using Repeated Exposures and Adjunctive Repetitive Transcranial Magnetic Stimulation: A Proof-of-Concept Study.

BackgroundSpecific phobias represent the largest category of anxiety disorders. Previous work demonstrated that stimulating the ventromedial prefrontal cortex (vmPFC) with repetitive Transcranial Magnetic Stimulation (rTMS) may improve response to exposure therapy for acrophobia.ObjectiveTo examine feasibility of accelerating extinction learning in subjects with spider phobia using intermittent Theta Burst Stimulation (iTBS) rTMS of vmPFC.MethodsIn total, 17 subjects with spider phobia determined by spider phobia questionnaires [Spider Phobia Questionnaire (SPQ) and Fear of Spiders questionnaire (FSQ)] underwent ratings of fear of spiders as well as behavioral and skin conductance data during a behavioral avoidance test (BAT). Subjects then received a sequential protocol of in vivo spider exposure followed by iTBS for three sessions administered to either active or control treatment sites (vmPFC [n = 8] or vertex [n = 9], respectively), followed 1 week later by repetition of questionnaires and BAT.ResultsAll subjects improved significantly regardless of group across both questionnaires (FSQ η2 = 0.43, p = 0.004; SPQ η2 = 0.39, p = 0.008) and skin conductance levels during BAT (Wald χ2 = 30.9, p < 0.001). Subjects in the vmPFC group tolerated lower treatment intensity than in the control group, and there was a significant correlation between treatment intensity, BAT subjective distress improvement, and physiologic measures (all ρ > 0.5).ConclusionThis proof-of-concept study provides preliminary evidence that a sequential exposure and iTBS over vmPFC is feasible and may have rTMS intensity-dependent effects on treatment outcomes, providing evidence for future areas of study in the use of rTMS for phobias.

Leaf Pulp of Carpobrotus deliciousus Attenuate Sodium Arsenate Induced Toxicity

Carpobrotus deliciousus (CD) is reported to have numerous health benefits. This study determined the influence of the oral and repeated administration of leaf pulp of C. deliciousus (LPCD) on sodium arsenate (SA) (Na3AsO4) induced toxicity in Wistar rats. Thirty male Wistar rats were distributed into five groups of six rats each. Group 1 was given 5 mg/kg body weight (b.w) of SA for 7 days; group 2 was administered 0.5 mL of LPCD for 14 days. Group 3 received 5 mg/kg b.w of SA for 7 days followed by 0.5 mL LPCD for another 7 days, while group 4 was treated with 0.5 mL LPCD for 7 days followed by 5 mg/kg b.w of SA for another 7 days. Group 5 served as the control and received deionized water. After the last treatment, the blood, kidneys, and liver were collected for biochemical analysis. The alkaline phosphatase (ALP), AST, and GPT levels were all significantly (p &lt; 0.05) depleted in groups 1 and 2, while there was no significant (p &lt; 0.05) change in groups 3 and 4 when compared to the control. The HDL, LDL, cholesterol, and triglyceride levels were not significantly (p &lt; 0.05) altered for groups 3 and 4. These findings suggest that oral and repeated exposure to LPCD may ameliorate managing SA-induced toxicity.