Stress Levels Research Articles

A multigenerational study can detect the evolutionary response to BaP exposure in the non-biting freshwater midge Chironomus riparius

The release of polycyclic aromatic hydrocarbons (PAHs) into the environment is posing a threat to ecosystems and human health. Benzo(a)pyrene (BaP) is considered a biomarker of PAH exposure and is classified as a Group 1 carcinogen. However, it was not known whether BaP is mutagenic, i.e. induces inherited germline mutations. In this study, we used a recently established method, which combines short-term mutation accumulation lines (MAL) with whole genome sequencing (WGS) to assess mutagenicity in the non-biting midge Chironomus riparius. The mutagenicity analysis was supplemented by an evaluation of the development of population fitness in three successive generations in the case of chronic exposure to BaP at a high concentration (100 μg/L). In addition, the level of ROS-induced oxidative stress was examined in vivo. Exposure to the higher BaP concentration led to an increase in germline mutations relative to the control, while the lower concentration showed no mentionable effect. Against expectations, BaP exposure decreased ROS-level compared to the control and is thus probably not responsible for the increased mutation rate. Likewise, the higher BaP concentration decreased fitness measured as population growth rate per day (PGR) significantly over all generations, without signs of rapid evolutionary adaptations. Our results thus highlighted that high BaP exposure may influence the evolutionary trajectory of organisms.

The Psychological Impact on Romanian Women Infected with SARS-CoV-2 during Pregnancy.

It is well-known that the uncertainty about the COVID-19 pandemic has an indirect negative impact on pregnant women's mental health, given the fact that pregnant women are more vulnerable emotionally and psychologically than non-pregnant women. The aim of this study was to evaluate the maternal psychological impact on Romanian women who were infected with SARS-CoV-2 during pregnancy and their concerns and to determine which are the best measures to prevent negative outcomes. A 40-item questionnaire was created for data collection and was shared on social platforms (Facebook and Instagram) and also with obstetric communities between February 2021 and January 2023. Our cross-sectional survey recruited 317 Romanian pregnant women who suffered from SARS-CoV-2 infection. Among general questions about their life and pregnancy during the pandemic, the survey included questions about their SARS-CoV-2 infection during pregnancy, their concerns and how they perceived this period in order to evaluate their emotional status. Of 317 women recruited, 91% of them had a mild to moderate form of COVID-19, and 2% had serious symptoms. Only 9% of women were hospitalized, 4% of women considered that the SARS-CoV-2 infection affected their physical condition to a great extent, and 8% considered to be affected in terms of mental state to a great extent. The main negative feelings of pregnant women during the COVID-19 disease were the fear regarding the possibility of affecting the pregnancy and the concern for their life (51.4%). These increase the risk of developing anxiety or depression. Pregnant women who contracted SARS-CoV-2 infection faced negative feelings, especially those with a severe form of the disease or who recovered with difficulty after the disease. Patients who required hospitalization reported an impairment of the mental state to a great extent and to a very great extent with a frequency of approximately two times and four times higher than non-hospitalized patients, respectively (p < 0.05 and p < 0.001, respectively). Also, giving birth during SARS-CoV-2 and the difficulty of accessing medical services represented a high level of stress. Also, 47% of patients who reported difficulty accessing medical services during the illness evaluated their mental state significantly less favorably. Preventive measures are essential to minimizing the negative psychological impact of COVID-19 disease during pregnancy among pregnant women. The medical treatment of COVID-19 disease during pregnancy should be prioritized, but emotional and mental health support must also be provided.

Early pyridoxine administration rescues autism-like behavior in the BTBR T+tf/J autistic model

Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder characterized by social impairment and repetitive, stereotyped behaviors. An imbalanced oxidative stress status and neuroinflammation are involved in ASD development. In this study, we investigated the effects of pyridoxine, a form of vitamin B6 with potent anti-oxidant and anti-inflammatory features, on autism-like behavior in BTBR T + ltpr3tf/J (BTBR) mice, a model of autism. Mice received pyridoxine from postnatal days 7 to 14. Behavioral tests were conducted on 8-week-old male mice, and the inflammatory status and oxidative stress levels were also assessed in the mouse hippocampus. Postnatal pyridoxine treatment significantly improved social deficits, stereotyped behaviors, and cognitive deficits in BTBR mice. In addition, pyridoxine treatment alleviated neuroinflammation in the hippocampus manifested by reduced Iba1+ microglia and inflammatory factors, such as interleukin-1β (IL-1β), IL-6, TNF-α, and NF-κB. Further, pyridoxine-treated BTBR mice had elevated Nrf2 and HO-1 in the hippocampus. Postnatal pyridoxine administration might improve autistic-like behaviors in BTBR mice via attenuating oxidative stress and neuroinflammation in the hippocampus.

Effect of Clemizole on Alpha-Synuclein-Preformed Fibrils-Induced Parkinson's Disease Pathology: A Pharmacological Investigation.

Parkinson's disease (PD) is a neurodegenerative disorder associated with mitochondrial dysfunctions and oxidative stress. However, to date, therapeutics targeting these pathological events have not managed to translate from bench to bedside for clinical use. One of the major reasons for the lack of translational success has been the use of classical model systems that do not replicate the disease pathology and progression with the same degree of robustness. Therefore, we employed a more physiologically relevant model involving alpha-synuclein-preformed fibrils (PFF) exposure to SH-SY5Y cells and Sprague Dawley rats. We further explored the possible involvement of transient receptor potential canonical 5 (TRPC5) channels in PD-like pathology induced by these alpha-synuclein-preformed fibrils with emphasis on amelioration of oxidative stress and mitochondrial health. We observed that alpha-synuclein PFF exposure produced neurobehavioural deficits that were positively ameliorated after treatment with the TRPC5 inhibitor clemizole. Furthermore, Clemizole also reduced p-alpha-synuclein and diminished oxidative stress levels which resulted in overall improvements in mitochondrial biogenesis and functions. Finally, the results of the pharmacological modulation were further validated using siRNA-mediated knockdown of TRPC5 channels, which also decreased p-alpha-synuclein expression. Together, the results of this study could be superimposed in the future for exploring the beneficial effects of TRPC5 channel modulation for other neurodegenerative disorders and synucleopathies.

Oxidative stress in patients with coronavirus disease and end-stage renal disease: a pilot study

BackgroundOxidative stress, an imbalance between reactive oxygen species production and antioxidant capacity, increases in patients with coronavirus disease (COVID-19) or renal impairment. We investigated whether combined COVID-19 and end-stage renal disease (ESRD) would increase oxidative stress levels compared to each disease alone.MethodsOxidative stress was compared among three groups. Two groups comprised patients with COVID-19 referred to the hospital with or without renal impairment (COVID-ESRD group [n = 18]; COVID group [n = 17]). The third group (ESRD group [n = 18]) comprised patients without COVID-19 on maintenance hemodialysis at a hospital.ResultsThe total oxidative stress in the COVID-ESRD group was lower than in the COVID group (p = 0.047). The total antioxidant status was higher in the COVID-ESRD group than in the ESRD (p < 0.001) and COVID (p < 0.001) groups after controlling for covariates. The oxidative stress index was lower in the COVID-ESRD group than in the ESRD (p = 0.001) and COVID (p < 0.001) groups. However, the three oxidative parameters did not differ significantly between the COVID and COVID-ESRD groups.ConclusionsThe role of reactive oxygen species in the pathophysiology of COVID-19 among patients withESRD appears to be non-critical. Therefore, the provision of supplemental antioxidants may not confer a therapeutic advantage, particularly in cases of mild COVID-19 in ESRD patients receiving hemodialysis. Nonetheless, this area merits further research.

ECG and EEG based machine learning models for the classification of mental workload and stress levels for women in different menstrual phases, men, and mixed sexes

ECG and EEG based machine learning models for the classification of mental workload and stress levels for women in different menstrual phases, men, and mixed sexes

A cross-sectional mental-health survey of Chinese postgraduate students majoring in stomatology post COVID-19 restrictions.

The psychological status of Chinese postgraduate students majoring in stomatology after the COVID-19 restrictions still remains unclear. The objective of this study is to evaluate the mental status through a cross-sectional survey and gather related theoretical evidence for psychological intervention on postgraduate students majoring in stomatology. An online survey was administered, and subjective well-being, anxiety, stress and depression symptoms were assessed using the 5-item World Health Organization Well-Being Index (WHO-5), item Generalized Anxiety Disorder Scale (GAD-7), 10-item Perceived Stress Scale (PSS-10), and Patient Health Questionnaire-9 (PHQ-9), respectively, wherein suicidal ideation and sleep-related problems were measured with PHQ-9 and Insomnia Severity Index (ISI). A total of 208 participants who completed one questionnaire were considered as valid. It was found that female respondents generally exhibited significantly higher levels of PSS-10, PHQ-9, and GAD-7 scores and shorter physical activity hours than male students. Students from rural areas demonstrated significantly higher levels of PHQ-9, suicidal ideation, and less portion of good or fair family economic support. Additionally, individuals from only-child families reported increased levels of activity hours (1.78 ± 2.07, p = 0.045) and a higher portion (55.10%, p = 0.007) of having clear future plan as compared with multiple-child families. The risk factors for anxiety symptoms (GAD-7 score) were higher scores of PSS-10 (OR = 1.15, 95% CI = 1.09-1.22), PHQ-9 (OR = 1.35, 95% CI = 1.22-1.49), and ISI-7 (OR = 1.14, 95% CI = 1.06-1.23), while owning a clear graduation plan was the protective factor (OR = 0.55, 95% CI = 0.31-0.98). Moreover, the risk factors for depressive symptoms (PHQ-9) included PSS-10 (OR = 1.10, 95% CI = 1.04-1.16), GAD-7 (OR = 1.38, 95% CI = 1.25-1.52), suicidal ideation (OR = 5.66, 95% CI = 3.37-9.51), and ISI-7 (OR = 1.17, 95% CI = 1.09-1.25). Approximately 98.08% of Chinese postgraduates studying stomatology reported experiencing at least moderate stress after the COVID-19 restrictions. Within the limitations of this study, senior students were more inclined to stress, while anxiety symptoms were related to severer levels of stress, depression, and insomnia. Depressive symptoms were associated with higher levels of stress, anxiety, insomnia, suicidal ideation, and lower levels of self-reported well-being. Thus, psychological interventions for postgraduates should be timely and appropriately implemented by strengthening well-being, reasonably planning for the future, and good physique, thereby mitigating the psychological issues after COVID-19 restrictions.

Tobacco Use and Perceived Stress Among Male College Students in Bangalore, India

BACKGROUND: More than 250 million individuals use tobacco in some form on a daily basis in India and adolescents make up a significant proportion of that number. The period of adolescence is critical in the initiation of smoking or tobacco use as well as its progression from experimentation to dependency. In this study, the role of psychological stress was explored with respect to cigarette consumption and level of addiction or dependence. METHODS: A total of 183 male college students (mean age= 19.8 years) from Bangalore, India completed the questionnaire booklet which included a Cigarette use screening form, the Perceived Stress Scale and the Autonomy over Smoking Scale. Of the 183 participants, there were 85 (46.2%) current smokers and 98 (53.7%) nonsmokers, and their scores on the perceived stress scale were compared using analysis of variance and independent samples _t_ tests. The relationship between levels of stress and dependence on tobacco (loss of autonomy) was also explored using Pearson’s product moment correlation (_r_). RESULTS: There was no significant difference between current smokers and nonsmokers on perceived stress (_t_[181] = -1.26, _p_ &gt;0.05), The same result was extended when the group of nonsmokers was divided into three (Never smokers, experimental smokers and former regular smokers) and the differences in scores were tested again between all four groups (_F_[3, 179]=.642, _p_ &gt;0.05). There was, however, a significant positive correlation between level of dependence on tobacco and perceived stress (_r_=.743, _p_ &lt;0.01). CONCLUSION: The study found that there was no difference in perceived stress levels between smokers and nonsmokers, although there was a positive relationship between the level of perceived stress and level of tobacco dependence (loss of autonomy) among the current smokers.

A psychological insight of Moroccan adults' immunisation behaviour towards emergency vaccines.

The psychology of vaccination behaviour explains how thoughts and feelings influence people's willingness to receive vaccines. Understanding vaccination behaviour is crucial to successfully managing vaccination campaigns. Investigating factors associated with immunisation stress among students at Mohammed First University. This study was conducted on students at Mohammed First University institutions. This study is a descriptive and analytical cross-sectional study. It was conducted on 305 students at Mohammed First University institutions using a 90-item questionnaire. Three hundred and five participants have been included in this survey. Overall, 65.5% of the students in our sample had a positive perception towards COVID-19 vaccines. Nevertheless, 34.5% had a negative opinion regarding immunisation. According to the analysis of perceived stress scale, 40% (n = 122) of students expressed moderate to high stress regarding vaccination. Students with a negative perception of vaccine showed a higher level of stress than those with a positive one. Stressed students tended to be older than others, coming from other institutions, other than the medical faculty, and were renting alone. Vaccine accessibility was the less significant reason associated with stress regarding vaccination. Moreover, participants with high levels of confidence in social media, exhibited higher stress. Nevertheless, those who believed in scientific journals were significantly less stressed. These results reflect a positive perception and acceptance of vaccines, with a considerable level of stress regarding vaccination.Contribution: This study suggests emphasising the mental health of Moroccan young adults, to better sensitise and inform them about immunisation.

Seed coating with minerals and plant growth-promoting bacteria enhances drought tolerance in fennel (Foeniculum vulgare L.)

The seeds of many plants, including fennel (Foeniculum vulgare L.), are tiny and have low food reserves. Therefore, planting them accurately in the soil to achieve optimal yields is challenging. The present research aimed to study the impact of bio-priming and seed coating on seedling and vegetative growth of fennel plants under drought stress. The experiments were conducted in laboratory and greenhouse conditions triplicate using a completely randomized design (CRD). These experiments applied mineral and biological coating treatments as the first factor and drought tolerance at three levels (0, −0.3, and −0.6 MPa) as the second factor. Perlite (P), Vermiculite (V), and Kaolin (K) were used as a mineral coating. The mineral coating mixture was P10V10K5. The numbers mean the material (gr) ratio based on the seed weight. Combinational treatments of seed coating were CHA0 + coating, PF56 + coating, T39 + coating, T36 + coating, and non-coating (as control). Pseudomonas fluorescens P.F56, P. fluorescens CHA0, and Trichoderma harzianum T36 and T. harzianum T39 were employed as biological treatments. Experimental results showed that at 0 and -0.3 MPa osmotic potential levels, the T39 + coated seeds had the highest percentage of seedling emergences. At the −0.3 MPa level, the T39 + coated seeds had an increased seedling emergence percentage by 24% compared to un-inoculated seeds. At all levels of drought stress, the CHA0 + coated treatment had the highest level of chlorophyll a content, CAT, and APX enzyme activity. Seed coating with CHA0 and T39 enhanced fennel's early vegetative growth and biochemical characteristics under normal and drought stress and mitigated drought stress.

Investigation Into The Stress-Coping Levels of Parents of Children with Autism Who Receive Physical Education

The aim of the study is to evaluate the demographic characteristics, stress and coping with stress levels of families with children with autism who receive services from autism sports club associations depending on various factors. A total of 134 people, 97 women (49,65±6,15) and 37 men (49,40±6,28) participated in the study. Personal Information Form (PIS), Stress Coping Styles Scale (SCSS) and Parent Stress Scale (PSS) were used as data collection tools. SPSS 22 package program was used to analyze the data obtained. Percentage and frequency values were used to analyze demographic characteristics. The t-test was used for the gender variable of the SPSAS, One-Way Anova test was used for all other variables and Post Hoc Tukey test was used to determine the source of the difference. As a result of the study, there was no statistically significant difference between the sub-dimensions of the SBSAS according to the variables of gender, educational status and gender of the child with autism (p&amp;gt;0.05); when analyzed according to the age variable, a significant difference was found between the groups aged 25-35 years (2.66±0.58) and 45 years and over (2.30±0.71) in the helpless approach sub-dimension (p&amp;lt;0.05). A statistically significant difference was found in families with male children (50.29±5.66) in the comparison of the PBSS according to gender variable (p&amp;lt;0.05). According to the results of the study, it was found that parents felt more helpless as they got older and parents with male children with autism experienced more stress than parents with female children with autism.

Metabolic Status Influences Probiotic Efficacy for Depression-PRO-DEMET Randomized Clinical Trial Results.

Probiotics may represent a safe and easy-to-use treatment option for depression or its metabolic comorbidities. However, it is not known whether metabolic features can influence the efficacy of probiotics treatments for depression. This trial involved a parallel-group, prospective, randomized, double-blind, controlled design. In total, 116 participants with depression received a probiotic preparation containing Lactobacillus helveticus Rosell®-52 and Bifidobacterium longum Rosell®-175 or placebo over 60 days. The psychometric data were assessed longitudinally at five time-points. Data for blood pressure, body weight, waist circumference, complete blood count, serum levels of C-reactive protein, cholesterol, triglycerides, and fasting glucose were measured at the beginning of the intervention period. There was no advantage of probiotics usage over placebo in the depression score overall (PRO vs. PLC: F(1.92) = 0.58; p = 0.45). However, we found a higher rate of minimum clinically important differences in patients supplemented with probiotics than those allocated to placebo generally (74.5 vs. 53.5%; X2(1,n = 94) = 4.53; p = 0.03; NNT = 4.03), as well as in the antidepressant-treated subgroup. Moreover, we found that the more advanced the pre-intervention metabolic abnormalities (such as overweight, excessive central adipose tissue, and liver steatosis), the lower the improvements in psychometric scores. A higher baseline stress level was correlated with better improvements. The current probiotic formulations may only be used as complementary treatments for depressive disorders. Metabolic abnormalities may require more complex treatments. ClinicalTrials.gov identifier: NCT04756544.

Assessment of Surgeons' Stress Levels with Digital Sensors during Robot-Assisted Surgery: An Experimental Study.

Robot-Assisted Minimally Invasive Surgery (RAMIS) marks a paradigm shift in surgical procedures, enhancing precision and ergonomics. Concurrently it introduces complex stress dynamics and ergonomic challenges regarding the human-robot interface and interaction. This study explores the stress-related aspects of RAMIS, using the da Vinci XI Surgical System and the Sea Spikes model as a standard skill training phantom to establish a link between technological advancement and human factors in RAMIS environments. By employing different physiological and kinematic sensors for heart rate variability, hand movement tracking, and posture analysis, this research aims to develop a framework for quantifying the stress and ergonomic loads applied to surgeons. Preliminary findings reveal significant correlations between stress levels and several of the skill-related metrics measured by external sensors or the SURG-TLX questionnaire. Furthermore, early analysis of this preliminary dataset suggests the potential benefits of applying machine learning for surgeon skill classification and stress analysis. This paper presents the initial findings, identified correlations, and the lessons learned from the clinical setup, aiming to lay down the cornerstones for wider studies in the fields of clinical situation awareness and attention computing.

Assessment of Stress and Well-Being of Japanese Employees Using Wearable Devices for Sleep Monitoring Combined With Ecological Momentary Assessment: Pilot Observational Study.

Poor sleep quality can elevate stress levels and diminish overall well-being. Japanese individuals often experience sleep deprivation, and workers have high levels of stress. Nevertheless, research examining the connection between objective sleep assessments and stress levels, as well as overall well-being, among Japanese workers is lacking. This study aims to investigate the correlation between physiological data, including sleep duration and heart rate variability (HRV), objectively measured through wearable devices, and 3 states (sleepiness, mood, and energy) assessed through ecological momentary assessment (EMA) and use of rating scales for stress and well-being. A total of 40 office workers (female, 20/40, 50%; mean age 40.4 years, SD 11.8 years) participated in the study. Participants were asked to wear a wearable wristband device for 8 consecutive weeks. EMA regarding sleepiness, mood, and energy levels was conducted via email messages sent by participants 4 times daily, with each session spaced 3 hours apart. This assessment occurred on 8 designated days within the 8-week timeframe. Participants' stress levels and perception of well-being were assessed using respective self-rating questionnaires. Subsequently, participants were categorized into quartiles based on their stress and well-being scores, and the sleep patterns and HRV indices recorded by the Fitbit Inspire 2 were compared among these groups. The Mann-Whitney U test was used to assess differences between the quartiles, with adjustments made for multiple comparisons using the Bonferroni correction. Furthermore, EMA results and the sleep and HRV indices were subjected to multilevel analysis for a comprehensive evaluation. The EMA achieved a total response rate of 87.3%, while the Fitbit Inspire 2 wear rate reached 88.0%. When participants were grouped based on quartiles of well-being and stress-related scores, significant differences emerged. Specifically, individuals in the lowest stress quartile or highest subjective satisfaction quartile retired to bed earlier (P<.001 and P=.01, respectively), whereas those in the highest stress quartile exhibited greater variation in the midpoint of sleep (P<.001). A multilevel analysis unveiled notable relationships: intraindividual variability analysis indicated that higher energy levels were associated with lower deviation of heart rate during sleep on the preceding day (β=-.12, P<.001), and decreased sleepiness was observed on days following longer sleep durations (β=-.10, P<.001). Furthermore, interindividual variability analysis revealed that individuals with earlier midpoints of sleep tended to exhibit higher energy levels (β=-.26, P=.04). Increased sleep variabilities, characterized by unstable bedtime or midpoint of sleep, were correlated with elevated stress levels and diminished well-being. Conversely, improved sleep indices (eg, lower heart rate during sleep and earlier average bedtime) were associated with heightened daytime energy levels. Further research with a larger sample size using these methodologies, particularly focusing on specific phenomena such as social jet lag, has the potential to yield valuable insights. UMIN-CTR UMIN000046858; https://center6.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000053392.

Influence of physical exercise on negative emotions in college students: chain mediating role of sleep quality and self-rated health.

Negative emotions in college students are a significant factor affecting mental health, with suicide behaviors caused by negative emotions showing an annual increasing trend. Existing studies suggest that physical exercise is essential to alleviate negative feelings, yet the intrinsic mechanisms by which it affects negative emotions have not been fully revealed. Negative emotions in college students represent a significant issue affecting mental health. This study investigates the relationship between physical exercise and negative emotions among college students, incorporating sleep quality and self-rated health (SRH) as mediators to analyze the pathway mechanism of how physical exercise affects students' negative emotions. A cross-sectional study design was utilized, employing online questionnaires for investigation. The scales included the Physical Activity Rating Scale-3 (PARS-3), the Depression Anxiety Stress Scales-21 (DASS-21), the Pittsburgh Sleep Quality Index (PSQI), and the 12-Item Short Form Health Survey (SF-12), resulting in the collection of 30,475 valid questionnaires, with a validity rate of 91%. Chain mediation tests and Bootstrap methods were applied for effect analysis. The proportions of university students engaged in low, medium, and high levels of physical exercise were 77.6, 13.1, and 9.3%, respectively. The proportions of students experiencing "very severe" levels of stress, anxiety, and depression were 4.5, 10.9, and 3.6%, respectively. Physical exercise was significantly positively correlated with self-rated health (r = 0.194, p < 0.01), significantly negatively correlated with sleep quality (r = -0.035, p < 0.01), and significantly negatively correlated with stress, anxiety, and depression (r = -0.03, p < 0.01; r = -0.058, p < 0.01; r = -0.055, p < 0.01). Sleep quality was significantly negatively correlated with self-rated health (r = -0.242, p < 0.01). Mediation effect testing indicated that sleep quality and self-rated health partially mediated the relationship between physical exercise and negative emotions, with total effect, total direct effect, and total indirect effect values of -1.702, -0.426, and - 1.277, respectively. College students primarily engage in low-intensity physical activity. Sleep quality and self-rated health mediate the impact of physical exercise on students' negative emotions. A certain level of physical activity can directly affect students' emotional states and indirectly influence their negative emotions via sleep and self-rated health. Regular engagement in physical activities primarily positively impacts emotional states by enhancing mood stability and overall emotional resilience.

Addressing Environmental Factors for SDG 3-Health and Wellbeing: Perceived Stress, Sleep Quality, and Coping among Medical Students in Pakistan

The objective of this study was to investigate the interplay between perceived stress, sleep quality, and coping mechanisms among medical students, with a view to understand their implications for Sustainable Development Goal 3 (SDG 3) - "Good Health and Well-being," and considering environmental factors. Conducted as a cross-sectional study and 300 medical university students (152 men, 148 women), aged 18 to 25 years (mean age = 22.73, SD = 1.78), were selected using stratified random sampling based on their academic year. The study employed the Perceived Stress Scale, General Sleep Scale, and Brief COPE to assess the study variables. The results revealed gender differences in coping strategies, with female students exhibiting higher scores in avoidant and emotion-focused coping, while male students leaned towards problem-focused coping. Notably, perceived stress and avoidant coping emerged as significant predictors of poor sleep quality (p&lt;.05) among the participants. This study found significant relationship among use of green spaces, stress, sleep quality, and coping strategies among medical students, aligning with SDG 3's objective of ensuring healthy lives and promoting well-being for all. Furthermore, while the study did not directly address environmental factors, it indirectly emphasizes the importance of creating conducive environments for health and well-being. Environmental considerations such as access to green spaces and a healthy physical environment can influence individuals' stress levels and sleep quality, contributing to holistic health outcomes. Given these findings, the study recommends that counseling centers in universities develop strategies for managing students' stress and sleep quality, while promoting healthy coping skills. By addressing these factors comprehensively, universities can contribute to enhancing students' psychological well-being and advancing progress towards SDG 3 and create sustainable and healthy environments, as outlined in SDG 13 (Climate Action), to complement initiatives focused on fostering sustainable environments conducive to health and well-being.

Abstract PO3-26-11: Enhancing endoplasmic reticulum stress for treating endocrine therapy resistant breast cancers driven by mutant estrogen receptors

Abstract Background: Estrogen receptor alpha (ERα) mutations are common (30-40%) in metastatic endocrine therapy-resistant breast cancers (ETR-BC), enable resistance to endocrine therapies and are the molecular drivers of ETR-BC. We had previously shown that an oligobenzamide, ERX-41, could enhance endoplasmic reticulum stress in ETR-BCs driven by mutant (MT) ERα, resulting in cancer cell death in vitro and and in vivo. To enable clinical translation of ERX-41, we performed lead optimization, followed by preclinical and IND-enabling studies. Methods: Over 2000 oligo-benzamides were designed, synthesized and tested in multiple BC models including those that express WT-ERα (MCF7, and ZR75) and BC models with acquired resistance (MCF7-Tam, and MCF7-LTLT) and engineered models that express MT-ERα (MCF7-ERα-D538G, MCF7-ERα-Y537S, ZR75-ERα-D538G, ZR75-ERα-Y537S). For our lead compound, mechanistic validation studies were performed using CRISPR LIPA mutants, RT-qPCR and Western blotting. Explants, organoids, cell line-(CDX) and patient-derived (PDX) xenografts were used to test the ex vivo and in vivo effectiveness of our lead compound as a monotherapy and in combination with abemaciclib. Results: Testing of &amp;gt;2000 synthesized oligo-benzamides identified a lead compound, ERX-315, that had broad and potent activity (IC50 between 20-100 nM) against both WT and MT (mutant) ERα-driven BC cells in in vitro assays. CRISPR KO of LIPA (which encodes lysosomal acid lipase (LAL) in BC cells abrogated cytotoxic response to ERX-315, validating LIPA as the molecular target of ERX-315. Ultrastructural and molecular studies confirm that ERX-315 induces significant endoplasmic reticulum stress, leading to a shutdown of de novo protein synthesis and apoptotic cell death in BC. Importantly, ERX-315 does not induce endoplasmic reticulum stress or cell death in normal cells and is non-toxic in animal models. We have shown that this capacity of ERX-315 to induce endoplasmic reticulum stress is unique among drugs targeting ERα, including selective ERα modulators and degraders, such as GDC-0180, AZD-9496 and fulvestrant. ERX-315 has potent anti-proliferative activity against MT-ERα-driven BC, as seen in genetically modified cell lines both grown as monolayer or spheroids in vitro, patient derived explants (PDEs) ex vivo and cell line derived (CDX) and patient-derived (PDX) xenografts in vivo. The combination of ERX-315 and CDK4/6 inhibitor abemaciclib was synergistic in decreasing the proliferation of both endocrine therapy-sensitive and endocrine therapy-resistant BC cells, in vitro, in xenograft models in vivo, and in primary patient-derived explants ex vivo. We are currently optimizing both the synthesis of ERX-315 using GMP process for kilogram scale production and validated methods for pharmacokinetic studies. We have developed formulations for both intravenous and oral administration with favorable pharmacokinetic parameters and proven utility of the formulated ERX-315 against CDX and PDX tumors in vivo. Toxicity studies in dogs and rodents have demonstrated &amp;gt;8-fold therapeutic to toxicity window. A phase I clinical trial is planned to be open to enrollment by Q1 2024. Conclusions: We have identified a lead compound ERX-315, which represents a novel class of agent that induce catastrophic levels of ER stress resulting in cancer cell death and that can effectively work against multiple forms of ETR-BC, including those driven by MT-ERα. Preclinical studies, GMP manufacturing, formulation and IND-enabling studies are being completed in time for the commencement of the phase I clinical trial by Q1 2024. Citation Format: Suryavathi Viswanadhapalli, Karla Parra, Tae-Kyung Lee, Rahul Gopalam, Kara Kassees, Tanner Reese, Gaurav Sharma, Xihui Liu, Xue Yang, ChiaYuan Chen, Carlos Roggero, Liping Chen, Sautam Bhattacharya, Uday Pratap, Russell Hayward, Sharron Gargosky, Jung-Mo Ahn, Ganesh V. Raj, Ratna Vadlamudi. Enhancing endoplasmic reticulum stress for treating endocrine therapy resistant breast cancers driven by mutant estrogen receptors [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-26-11.

Kids+ Parent Infant Program (PIP): a community model for supporting partnerships in early developmental follow-up and support.

High-risk infants are discharged home from hospital with increased care needs and the potential for the emergence of developmental disabilities, contributing to high levels of parental stress and anxiety. To enable optimal outcomes for high-risk infants and their families, developmental follow-up programs need to continue following hospital discharge. However, current follow-up care for high-risk infants is variable in terms of type, access and equity, and there seems to be a gap in existing services such as supporting the transition home, parental support, and inclusion of all at-risk infants regardless of causality. Routine follow-up that identifies developmental delays or neuromotor concerns can facilitate timely referral and access to targeted intervention during critical periods of development. The Kids+ Parent Infant Program (PIP) is a unique model of developmental follow-up that shares some characteristics with established programs, but also includes additional key elements for a seamless, wrap-around service for all high-risk infants and their families living in a regional area of Australia. This community-based program provides integrated assessment and intervention of infants, alongside parent support and education, embracing a holistic model that accounts for the complexity and interrelatedness of infant, parent, medical and developmental factors. By prioritising the well-being of high-risk infants and their families, the Kids+ PIP paves the way for improved developmental outcomes and provides an innovative model for developmental follow-up, with the potential for reproduction in other healthcare settings.

Optimization of Phloretin-loaded Nanospanlastics for Targeting of FAS/SREBP1c/AMPK/ OB-Rb Signaling Pathway in HFD-induced Obesity.

Obese patients are at increased risk for CVD, which is the main cause of premature death and has been a major cause of disability and ill health in recent years. PTN, a natural dihydrochalcone flavonoid, has a variety of pharmacological characteristics. This article aimed to prepare PTN-NSLs to evaluate their anti-obesity activity. Morphology, Particle size, zeta potential, UV-vis, entrapment efficiency, FT-IR spectra, and an in vitro release study of PTN-NSLs were described. PTN-NSLs were also tested for their anti-obesity properties in obese rats. The LD50 of PTN-NSLs was calculated, as was the 1/20 LD50 prepared for the treatment of obese rats. Also, the level of glycemic, oxidative stress and inflammatory biomarkers were estimated in the obese rat's model. The synthesized PTN-NSLs were uniform, spherically shaped, and well dispersed with no aggregation noted, with a size range of 114.06 ± 8.35 nm. The measured zeta potential value of PTN-NSLs was -32.50.8 mv. Also, the UV spectra of PTN and PTN-NSLs have strong absorption at 225 and 285 nm. Also, the LD50 of PTN-NSLs was found to be 2750 mg/kg.b.w. Moreover, administrating obese rats with PTN-NSLs resulted in improved glycemic features as well as GSH, SOD, GPx, GR, IL10, TBARs, and IL-6 levels, as well as attenuated FAS, SREBP1c, AMPK, ACO, CPT1, and OB-Rb gene expression. Administration of PTN-NSLs significantly attenuated the levels of glycemic, oxidative stress, and inflammatory biomarkers. The biochemical and PCR findings are aided by histological investigations. Also, the present findings imply that PTN-NSLs might be a promising pharmacological tool for the treatment of obesity-related diseases.

Abstract PO4-24-05: Fluid forces and hormone levels during mammary gland development drive changes in breast epithelium that are relevant to the progression of postpartum breast cancer

Abstract Postpartum breast cancer (PPBC), diagnosed in the 5-10 years after childbirth, has an elevated risk of metastasis and death. Poor outcomes are thought to be due to factors involved in mammary gland involution, an important stage of mammary gland development. Involution functions to return the mammary gland to the normal post-lactation state and involves activation of multiple processes such as inflammation, wound healing, and lymphangiogenesis. Previously, these processes have been linked to mechanical forces induced by fluid flowing past cells, known as fluid shear stress (FSS). We and others have shown FSS impacts processes associated with lactation and breast cancer metastasis. Herein, we describe the results of a cell model for mimicking lactation and the cessation of lactation as an investigative tool for probing the mechanisms involved in PPBC development and progression. We identified changing levels of FSS as a potential physiologic biomarker through which pathways associated with the progression of PPBC could be identified. The role of fluid shear stress in the progression of cancer remains relatively unexplored, mostly due to practical research barriers. Since FSS cannot be accurately measured in vivo, most research to date has relied on in vitro modelling. In contrast, the role of the involuting mammary gland on the progression of breast cancer has often been studied using rodent models. As a result, studying the interactions between fluid shear stress and involution poses a novel engineering challenge. To address this problem, we developed a bioreactor cell model to enable cell exposure to fluid flow, mimicking forces experienced during lactation, in presence of lactogenic hormones (dexamethasone, insulin, prolactin). Previous work has induced FSS using parallel plate flow chambers, and induced lactation in mammary epithelial cells grown in vitro using lactogenic hormone treatment. To our knowledge, this is the first time these experimental conditions have been studied in combination. We established three distinct stages of treatment, consistent with the fluid shear stress and hormonal levels expected in (1) lactation, (2) cessation of lactation, and (3) involution. To determine whether the model mimicked expected in vivo conditions in the postpartum mammary gland, we used morphological markers and measured the protein expression of β-casein (CSN2), a milk protein that is an established marker of lactation. Each stage was validated and analyzed using proteomic and genomic sequencing. Generated datasets were further analyzed using unsupervised clustering, combining publicly available datasets with our data. We determined that β-casein levels were highest when protein was collected after the lactation stage, followed by an initial drop-off in β-casein expression when fluid shear stress were lowered during the cessation period. The β-casein levels continued at a constant, low level during the involution period, despite a reintroduction of fluid shear stress. This suggests that breast cancer cells are initially responsive to shear stress stimulation, consistent with what would be expected in the postpartum mammary gland in vivo. Proteomic and genomic datasets generated from cells exposed to FSS demonstrated that multiple pathways associated with metastasis are upregulated, as compared to static controls. When combined with publicly available involution datasets, pathways involved in extracellular matrix remodeling, inflammation, and lymphangiogenesis emerged. Multiple targets identified through this analysis have been previously linked to metastatic activities during breast cancer, suggesting that FSS and involution are relevant physiologic biomarkers in the context of PPBC. Work to validate hormonal and fluid shear stress conditions in combination is ongoing. Future work will use the validated model to test relevant targets identified from analysis of generated datasets. Citation Format: Maya Stibbards-Lyle, Kristina Rinker, Laura Hall, Seleem Badawy, Kathy Zhan. Fluid forces and hormone levels during mammary gland development drive changes in breast epithelium that are relevant to the progression of postpartum breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-24-05.