Relations Between Sexual and Gender Minority Stress, Personal Hardiness, and Psychological Stress in Emerging Adulthood: Examining Indirect Effects via Human-Animal Interaction

Introduction: Although there is emerging evidence that companion animals are important sources of comfort and support for many LGBTQ+ (lesbian, gay, bisexual, transgender and other sexual and gender minority identities) individuals, little is known about the interplay between sexual and gender minority (SGM) stress, human-animal interaction (HAI), and psychological adjustment in this population. To address this gap in the literature, the current study examined the role of HAI in relations between SGM stress (i.e., microaggressions, victimization) and psychological adjustment (i.e., self-efficacy, psychological stress) during emerging adulthood. Methods: Our sample included LGBTQ+ young adults between the ages of 18 and 21 years (N = 136; 37.5% racial/ethnic minority; 49.2% transgender or gender-expansive; 98.5% sexual minority). Participants were recruited via convenience sampling methods in partnership with community agencies. We tested a mediation model using structural equation modeling with a bootstrapping approach to examine direct and indirect associations between SGM stress, HAI, and psychological adjustment, controlling for the effects of demographic factors. Results: The hypothesized mediation model fit the data well (Χ2/df = 1.71, CFI = 0.96, TLI = 0.93, RMSEA = 0.07, SRMR = 0.04). Results indicated that SGM microaggressions were significantly associated with HAI (β = 0.45, p \u3c .001, 95% CI [0.24, 0.62]) and psychological stress (β = 0.36, p \u3c .001, 95% CI [0.19, 0.54]), but not self-efficacy. Victimization was not significantly associated with HAI, self-efficacy, or psychological stress. HAI was significantly and positively associated with self-efficacy (β = 0.31, p \u3c .001, 95% CI [0.13, 0.47]), but was not significantly related to psychological stress. Finally, we found evidence of only one indirect-only effect of SGM microaggressions on self-efficacy via HAI (β = 0.14, p = .001, 95% CI [0.07, 0.24]). Conclusion: This is the first study, to our knowledge, that explored the potential mediating role of HAI in the relations between SGM microaggressions, victimization, self-efficacy, and psychological stress. Results of this study suggest that exposure to SGM stress may lead LGBTQ+ young adults to seek out relationships with pets, which in turn, may promote self-efficacy, a factor associated with resilience. However, due to the cross-sectional nature of our data, we cannot infer causation. Further research is needed to explore the longitudinal reciprocal associations between SGM stress, HAI, and psychological adjustment over time, and mechanisms through which HAI may promote resilience in this population.https://scholarscompass.vcu.edu/gradposters/1129/thumbnail.jp

The Moderating Effect of Comfort from Companion Animals and Social Support on the Relationship between Microaggressions and Mental Health in LGBTQ+ Emerging Adults

Introduction: Sexual and/or gender minority (SGM; e.g., lesbian, transgender, nonbinary, LGBTQ+) individuals are frequently exposed to various forms of minority stress that impact their mental health and wellbeing. Microaggressions, a form of minority stress, are defined as unconscious behaviors or statements directed at members of marginalized groups that reflect a hostile or discriminatory message. Microaggressions have been associated with several detrimental outcomes, such as depression and anxiety. Social support has been found to be an important protective factor for SGM emerging adults. Additionally, relationships with companion animals are an underexplored source of support that may be important for SGM individuals. This study aims to explore whether, and to what extent, social support from humans and comfort from companion animals moderates the relationship between SGM-related microaggressions and depressive and anxiety symptoms. Methods: We partnered with five community organizations to recruit our sample, which consisted of 134 SGM emerging adults between the ages of 18 and 21 (Mage = 19.31). Approximately 98.5% of our sample identified with a sexual minority identity, 49.5% identified with a gender minority identity, and 37.3% identified as a racial/ethnic minority. All participants had lived with a companion animal within the past year, with the majority of participants living with a dog and/or a cat. We conducted eight simple moderation analyses to explore whether, and to what extent, comfort from companion animals and human social support individually moderated the relationship between two forms of microaggressions (i.e., interpersonal, environmental) and anxiety and depressive symptoms. Further, we ran four additive moderation analyses to investigate whether comfort from companion animals and social support from humans moderated the relationship between each form of microaggressions and mental health symptoms, when the other moderator was held constant. Results: The results of our simple moderation analyses indicated that social support moderated the relationship between both forms of microaggressions and depressive symptoms (interpersonal: ΔR2 = 0.03, F(1, 125) = 4.74, ꞵ = -0.17, t(125) = -2.18, p = .03; environmental: ΔR2 = 0.02, F(1, 124) = 3.93, ꞵ = -0.19, t(124) = -1.98, p = .05). Our findings suggest that social support acted as a protective factor, because the relationship between exposure to microaggressions and depressive symptoms was not significant when participants reported high levels of social support. Comfort from companion animals also moderated the relationship between interpersonal microaggressions and depressive symptoms (ΔR2 = 0.03, F(1, 125) = 4.78, ꞵ = 0.18, t(125) = 2.19, p = .03). However, comfort from companion animals seemed to exacerbate the association between interpersonal microaggressions and depressive symptoms, as there was a positive and significant relationship between these two variables when participants reported medium or high levels of comfort from companion animals. The results of the additive moderation analyses found that the relationship between exposure to microaggressions and depressive symptoms was positive and significant when social support was low or medium and comfort from companion animals was high or medium. However, when social support was high, the relationship was no longer significant, regardless of the level of comfort from companion animals. Discussion: Our results suggest that social support from humans may be a key protective factor that buffers the relationship between microaggressions and depressive symptoms. Further, these findings also highlight the need to continue investigating the complex role of relationships with companion animals on mental health outcomes for SGM emerging adults. In particular, longitudinal studies are needed to clarify the direction of these relationships, as we are unable to make causal inferences with this cross-sectional study. The results from this study have important implications for future research in this area and practice with SGM populations.https://scholarscompass.vcu.edu/gradposters/1142/thumbnail.jp

The Acute Effects of 5 Fluorouracil on Skeletal Muscle Resident and Infiltrating Immune Cells in Mice

5 fluorouracil (5FU) has been a first-choice chemotherapy drug for several cancer types (e.g., colon, breast, head, and neck); however, its efficacy is diminished by patient acquired resistance and pervasive side effects. Leukopenia is a hallmark of 5FU; however, the impact of 5FU-induced leukopenia on healthy tissue is only becoming unearthed. Recently, skeletal muscle has been shown to be impacted by 5FU in clinical and preclinical settings and weakness and fatigue remain among the most consistent complaints in cancer patients undergoing chemotherapy. Monocytes, or more specifically macrophages, are the predominate immune cell in skeletal muscle which regulate turnover and homeostasis through removal of damaged or old materials as well as coordinate skeletal muscle repair and remodeling. Whether 5FU-induced leukopenia extends beyond circulation to impact resident and infiltrating skeletal muscle immune cells has not been examined. The purpose of the study was to examine the acute effects of 5FU on resident and infiltrating skeletal muscle monocytes and inflammatory mediators. Male C57BL/6 mice were given a physiologically translatable dose (35 mg/kg) of 5FU, or PBS, i.p. once daily for 5 days to recapitulate 1 dosing cycle. Our results demonstrate that 5FU reduced circulating leukocytes, erythrocytes, and thrombocytes while inducing significant body weight loss (\u3e5%). Flow cytometry analysis of the skeletal muscle indicated a reduction in total CD45+ immune cells with a corresponding decrease in total CD45+CD11b+ monocytes. There was a strong relationship between circulating leukocytes and skeletal muscle CD45+ immune cells. Skeletal muscle Ly6cHigh activated monocytes and M1-like macrophages were reduced with 5FU treatment while total M2-like CD206+CD11c- macrophages were unchanged. Interestingly, 5FU reduced bone marrow CD45+ immune cells and CD45+CD11b+ monocytes. Our results demonstrate that 5FU induced body weight loss and decreased skeletal muscle CD45+ immune cells in association with a reduction in infiltrating Ly6cHigh monocytes. Interestingly, the loss of skeletal muscle immune cells occurred with bone marrow cell cycle arrest. Together our results highlight that skeletal muscle is sensitive to 5FU’s off-target effects which disrupts both circulating and skeletal muscle immune cells

Social Difficulties in Youth with Autism With and Without Anxiety and ADHD Symptoms

Social difficulties inherent to autism spectrum disorder are often linked with co‐occurring symptoms of anxiety and attention deficit hyperactivity disorder (ADHD). The present study sought to examine the relation between such co‐occurring symptoms and social challenges. Parents of adolescents with autism (N = 113) reported upon social challenges via the social responsiveness scale (SRS) and anxiety and ADHD symptomatology via the Child Behavior Checklist. Results revealed differences in SRS scores across co‐occurring symptom subgroups (Anxiety, ADHD, Both, Neither)—namely, adolescents with autism and anxiety as well as those with autism, anxiety, and ADHD showed greater scores on the SRS than the other groups. Implications for research and clinical practice are discussed and recommendations are offered. Lay Summary Anxiety and attention deficit hyperactivity disorder (ADHD) symptoms are related to greater social challenges for adolescents with autism spectrum disorder. The present study found that autism with anxiety and autism with anxiety and ADHD, was related to greater social difficulties than autism alone. Findings provide further support for the intertwined nature of anxiety and ADHD symptoms in autism. What this may mean for research and clinical practice is considered and recommendations are suggested

Social Difficulties in Youth with Autism With and Without Anxiety and ADHD Symptoms

Social difficulties inherent to autism spectrum disorder are often linked with co‐occurring symptoms of anxiety and attention deficit hyperactivity disorder (ADHD). The present study sought to examine the relation between such co‐occurring symptoms and social challenges. Parents of adolescents with autism (N = 113) reported upon social challenges via the social responsiveness scale (SRS) and anxiety and ADHD symptomatology via the Child Behavior Checklist. Results revealed differences in SRS scores across co‐occurring symptom subgroups (Anxiety, ADHD, Both, Neither)—namely, adolescents with autism and anxiety as well as those with autism, anxiety, and ADHD showed greater scores on the SRS than the other groups. Implications for research and clinical practice are discussed and recommendations are offered. Lay Summary Anxiety and attention deficit hyperactivity disorder (ADHD) symptoms are related to greater social challenges for adolescents with autism spectrum disorder. The present study found that autism with anxiety and autism with anxiety and ADHD, was related to greater social difficulties than autism alone. Findings provide further support for the intertwined nature of anxiety and ADHD symptoms in autism. What this may mean for research and clinical practice is considered and recommendations are suggested

Measurement of H₂O₂ within living drosophila during aging using a ratiometric mass spectrometry probe targeted to the mitochondrial matrix

Hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>) is central to mitochondrial oxidative damage and redox signaling, but its roles are poorly understood due to the difficulty of measuring mitochondrial H<sub>2</sub>O<sub>2</sub> in vivo. Here we report a ratiometric mass spectrometry probe approach to assess mitochondrial matrix H<sub>2</sub>O<sub>2</sub> levels in vivo. The probe, MitoB, comprises a triphenylphosphonium (TPP) cation driving its accumulation within mitochondria, conjugated to an arylboronic acid that reacts with H<sub>2</sub>O<sub>2</sub> to form a phenol, MitoP. Quantifying the MitoP/MitoB ratio by liquid chromatography-tandem mass spectrometry enabled measurement of a weighted average of mitochondrial H<sub>2</sub>O<sub>2</sub> that predominantly reports on thoracic muscle mitochondria within living flies. There was an increase in mitochondrial H<sub>2</sub>O<sub>2</sub> with age in flies, which was not coordinately altered by interventions that modulated life span. Our findings provide approaches to investigate mitochondrial ROS in vivo and suggest that while an increase in overall mitochondrial H<sub>2</sub>O<sub>2</sub> correlates with aging, it may not be causative

TFEB is a master regulator of tumor-associated macrophages in breast cancer

BACKGROUND: Tumor-associated macrophages (TAMs) play key roles in the development of many malignant solid tumors including breast cancer. They are educated in the tumor microenvironment (TME) to promote tumor growth, metastasis, and therapy resistance. However, the phenotype of TAMs is elusive and how to regulate them for therapeutic purpose remains unclear; therefore, TAM-targeting therapies have not yet achieved clinical success. The purposes of this study were to examine the role of transcription factor EB (TFEB) in regulating TAM gene expression and function and to determine if TFEB activation can halt breast tumor development. METHODS: Microarrays were used to analyze the gene expression profile of macrophages (MΦs) in the context of breast cancer and to examine the impact of TFEB overexpression. Cell culture studies were performed to define the mechanisms by which TFEB affects MΦ gene expression and function. Mouse studies were carried out to investigate the impact of MΦ TFEB deficiency or activation on breast tumor growth. Human cancer genome data were analyzed to reveal the prognostic value of TFEB and its regulated genes. RESULTS: TAM-mimic MΦs display a unique gene expression profile, including significant reduction in TFEB expression. TFEB overexpression favorably modulates TAM gene expression through multiple signaling pathways. Specifically, TFEB upregulates suppressor of cytokine signaling 3 (SOCS3) and peroxisome proliferator-activated receptor γ (PPARγ) expression and autophagy/lysosome activities, inhibits NLRP3 (NLR Family Pyrin Domain Containing 3) inflammasome and hypoxia-inducible factor (HIF)-1α mediated hypoxia response, and thereby suppresses an array of effector molecules in TAMs including arginase 1, interleukin (IL)-10, IL-1β, IL-6 and prostaglandin E2. MΦ-specific TFEB deficiency promotes, while activation of TFEB using the natural disaccharide trehalose halts, breast tumor development by modulating TAMs. Analysis of human patient genome database reveals that expression levels of TFEB, SOCS3 and PPARγ are positive prognostic markers, while HIF-1α is a negative prognostic marker of breast cancer. CONCLUSIONS: Our study identifies TFEB as a master regulator of TAMs in breast cancer. TFEB controls TAM gene expression and function through multiple autophagy/lysosome-dependent and independent pathways. Therefore, pharmacological activation of TFEB would be a promising therapeutic approach to improve the efficacy of existing treatment including immune therapies for breast cancer by favorably modulating TAM function and the TME

Characterization, Bio-Uptake and Toxicity of Polymer-Coated Silver Nanoparticles and Their Interaction with Human Peripheral Blood Mononuclear Cells

Silver nanoparticles (AgNPs) are widely used in medical applications due to their antibacterial and antiviral properties. Despite the extensive study of AgNPs, their toxicity and their effect on human health is poorly understood, as a result of issues such as poor control of NP properties and lack of proper characterization. The aim of this study was to investigate the combined characterization, bio-uptake, and toxicity of well-characterized polyvinylpyrrolidone (PVP)-coated AgNPs in exposure media during exposure time using primary human cells (peripheral blood mononuclear cells (PBMCs)). AgNPs were synthesized in-house and characterized using a multimethod approach. Results indicated the transformation of NPs in RPMI medium with a change in size and polydispersity over 24 h of exposure due to dissolution and reprecipitation. No aggregation of NPs was observed in the RPMI medium over the exposure time (24 h). A dose-dependent relationship between PBMC uptake and Ag concentration was detected for both AgNP and AgNO3 treatment. There was approximately a two-fold increase in cellular Ag uptake in the AgNO3 vs the NP treatment. Cytotoxicity, using LDH and MTS assays and based on exposure concentrations was not significantly different when comparing NPs and Ag ions. Based on differential uptake, AgNPs were more toxic after normalizing toxicity to the amount of cellular Ag uptake. Our data highlights the importance of correct synthesis, characterization, and study of transformations to obtain a better understanding of NP uptake and toxicity. Statistical analysis indicated that there might be an individual variability in response to NPs, although more research is required