Physiological Impact Research Articles

The Physiological and Psychological Impact of Race-Based Trauma: Implications for Counselor Education

The area of trauma has been well researched within counseling literature; however, discussions around race-based trauma have been proportionately minimal. Given the physiological, psychological, and behavioral impacts of race-based trauma it is imperative that counselors and counselor educators are equipped to broach and address client's experiences. Therefore, this article provides a review of race-based trauma literature and models. In addition, this article calls counseling professionals to action on exploring and addressing their own attitudes, beliefs, and biases, along with informing clinicians on how to advocate for people of color and translate their knowledge into their work.

Mountains and Waves: Fontan Circulation in Different Environmental Conditions.

As surgical options and medical care for patients with univentricular heart physiology continue to improve, leading to increased life expectancy and quality of life, a new population of Fontan patients is growing up with the desire to participate in leisure activities, including aquatic activities, high-altitude stays, and air travel. Due to significant data gaps and insufficient experience, current guidelines do not provide clear recommendations, leading to uncertainty and sometimes restrictive patient management. This review summarizes new insights and the current state of research on this subject and provides an overview of the long overdue change in policies toward less restrictive counseling for Fontan patients regarding swimming, diving, high-altitude stays, and air travel. The current review summarizes the physiologic impact of aquatic and high-altitude activities on the cardiovascular system and presents currently available data on this topic in Fontan patients. Patients with Fontan circulation in good clinical shape can tolerate activities in the water and in the mountains as well as air traveling without critical events. In order to be able to make general recommendations, further studies with larger numbers of cases must be carried out.

Is Greener Better? Quantifying the Impact of a Nature Walk on Stress Reduction Using HRV and Saliva Cortisol Biomarkers

The physiological impact of walking in nature was quantified via continuous heart rate variability (HRV), pre- and post-walk saliva cortisol measures, and self-reported mood and mindfulness scores for N = 17 participants who walked “The Green Road” at Walter Reed National Military Medical Center in Bethesda, Maryland. For N = 15 of the participants, HRV analysis revealed two main groups: group one individuals had a 104% increase (mean) in the root mean square standard deviation (RMSSD) and a 47% increase (mean) in the standard deviation of NN values (SDNN), indicating an overall reduction in physiological stress from walking the Green Road, and group two individuals had a decrease (mean) of 42% and 31% in these respective HRV metrics, signaling an increase in physiological stresses. Post-walk self-reported scores for vigor and mood disturbance were more robust for the Green Road than for a comparable urban road corridor and showed that a higher HRV during the walk was associated with improved overall mood. Saliva cortisol was lower after taking a walk for all participants, and it showed that walking the Green Road elicited a significantly larger reduction in cortisol of 53%, on average, when compared with 37% of walking along an urban road. It was also observed that the order in which individuals walked the Green Road and urban road also impacted their cortisol responses, with those walking the urban road before the Green Road showing a substantial reduction in cortisol, suggesting a possible attenuation effect of walking the Green Road first. These findings provide quantitative data demonstrating the stress-reducing effects of being in nature, thus supporting the health benefit value of providing access to nature more broadly in many settings.

A novel piglet model of esophageal stricture following variable segmental esophageal resection and re-anastomosis.

Esophageal strictures following esophageal atresia repair are a source of significant morbidity. To test new therapeutic approaches, we designed a piglet model of esophageal stricture by resecting variable lengths of esophagus with subsequent re-anastomosis. This study describes the model and validates its physiologic impact by blinded analysis of the weight gains of the piglets. A total of 24 two-week old Pietrain piglets had esophageal resections performed, ranging from 0 to 5 cm, with the goal of inducing postoperative esophageal strictures. Postoperative body-weights were evaluated by repeated analysis of variance followed by pairwise group-comparisons based on estimated marginal means. In addition, body weight was modeled by linear-mixed model regression. Different resection lengths were compared. The esophagi were evaluated postmortem for stricture. Of 24 operated piglets, 23 reached the endpoint, and 90% developed an esophageal stricture that was radiologically visible in a contrast study, as well as appreciable macroscopically in the necropsy. We found differences in pre- and postoperative body weights for all piglets (F (1, 18) = 298.54, p < 0.001), but no differences between resection lengths (F (4, 18) = 0.36, p = 0.837). Our model of postoperative esophageal stricture offers the opportunity to investigate potential treatments for strictures associated with esophageal atresia, since it reliably induces strictures and results in minimal loss of animals. The similar body weight gain in all groups indicates that stricture is mainly the result of esophageal resection and re-anastomosis, regardless of the length of the resected segment.

Screening and design of PARP12 inhibitors from traditional Chinese medicine small molecules using computational modeling and simulation

The poly (ADP-ribose) polymerase (PARP) family of enzymes plays a pivotal role in orchestrating a multitude of cellular processes, including DNA repair mechanisms, transcriptional regulation, and modulation of immune responses. Within this family, PARP12 emerges as a noteworthy candidate for targeted cancer therapeutics. Consequently, this investigation endeavors to screen and design potential PARP12 inhibitors derived from traditional Chinese medicinal compounds by employing sophisticated molecular modeling and computational medicinal chemistry approaches. The compound RBN2397 is utilized as a benchmark, and the binding efficacies of the newly identified small molecules are assessed against a spectrum of criteria, encompassing molecular interactions, binding free energy, and extensive post-simulation analyses. The outcomes demonstrated that the identified small molecules, specifically tcm8650 and its derivative XC-1, possess remarkable binding affinities and exhibit reduced binding free energies compared to RBN2397. The molecular docking and interaction profiles of these compounds were also comprehensively scrutinized. Moreover, ADMET profiling meticulously evaluated the pharmacokinetic profiles and physicochemical characteristics of these promising molecules and their projected human physiological impact. These computational studies indicated their potential therapeutic applicability and predicted acceptable safety profile, advocating their further exploration as viable candidates in cancer treatment.

The Influence of Regional Anesthesia on the Systemic Stress Response

Background: The systemic stress response to surgery is a complex physiological process characterized by neuroendocrine, sympathetic, and inflammatory activation. While necessary for survival, this response can lead to adverse outcomes such as hyperglycemia, immune suppression, cardiovascular complications, and delayed recovery. Regional anesthesia (RA) has been shown to modulate this stress response more effectively than general anesthesia (GA) by blocking nociceptive signaling and attenuating the release of stress mediators. Objectives: This review aims to elucidate how RA influences the systemic stress response, highlighting its clinical benefits in reducing postoperative pain, improving hemodynamic stability, minimizing inflammatory responses, and preserving immune function. Additionally, this review examines evidence from clinical trials supporting using RA to improve surgical outcomes, particularly in high-risk populations. Methods: A comprehensive narrative review of the literature was conducted to explore the physiological impact of RA on the systemic stress response and its associated clinical outcomes. Studies comparing RA to GA across various surgical procedures were evaluated, focusing on neuroendocrine modulation, sympathetic inhibition, inflammatory attenuation, and the implications for pain management, cardiovascular and pulmonary function, and immune preservation. Results: RA significantly attenuates the neuroendocrine response by reducing the release of cortisol and catecholamines, thereby improving hemodynamic stability and reducing myocardial oxygen consumption. RA also inhibits the sympathetic nervous system, leading to improved cardiovascular outcomes. Furthermore, RA mitigates the inflammatory response by reducing pro-inflammatory cytokine levels, reducing the risk of systemic inflammatory response syndrome (SIRS), sepsis, and pulmonary complications. Clinical studies and meta-analyses consistently demonstrate that RA reduces postoperative pain, opioid consumption, and the incidence of cardiovascular and pulmonary complications, particularly in elderly and high-risk patients. Conclusions: RA offers a significant advantage in modulating the systemic stress response to surgery, improving postoperative outcomes by reducing pain, enhancing cardiovascular stability, and preserving immune function. Its benefits are particularly pronounced in high-risk populations such as the elderly or those with pre-existing comorbidities. Given the growing evidence supporting its efficacy, RA should be considered a critical component of multimodal perioperative care strategies aimed at minimizing the systemic stress response and improving recovery. Future research should optimize RA techniques and identify patient-specific factors to enhance therapeutic benefits.

Anxiety and Depression among patients with chronic pain

Background: Chronic pain is a pervasive and debilitating state experienced by many individuals across the globe. It produces a wide range of physiological impact which are well documented in literature but the psychological impact which is also equally profound has not received much attention. This study aims to investigate severity of anxiety and depression in patients with chronic pain that contributes to the development of holistic and effective treatment approaches. Materials and Methods: A non-experimental descriptive cross-sectional design was adopted. Non probability purposive sampling was used to recruit a sample of 50 patients with chronic pain attending OPD services in a secondary hospital, Chittoor, Andhra Pradesh. Patients who aged between 20 and 70 years with a chronic pain for at least 3 months were included. Patients with malignant pain were excluded. Hospital Anxiety and Depression Scale (HADS) was used to capture data on anxiety and depression. Results: The mean anxiety score on HADS was 9.2 (SD-3.72) and depression score was 8.48 (SD-3.23). Nearly one third of participants (32%) reported abnormal level of anxiety and 26% had reported abnormal depression. There is no significant association found between level of anxiety and Sociodemographic variables such as age, gender, marital status, type of family, education and occupation. Level of depression showed a significant association with age (p=0.042). Conclusion: Patients with chronic pain experience varying degrees of anxiety and depression. Routine assessment of these attributes would help the healthcare team to plan patient-tailored interventions to manage pain and to prevent anxiety and depression.

Legal Impact Of Catcalling Perpetrators And Physiological Impact On Victims In Indonesia

This article aims to provide a comprehensive understanding of the legal framework related to catcalling perpetrators and their physiological impact on victims in Indonesia as well as more effective law enforcement efforts in tackling this phenomenon. The focus is on increasing awareness of legal protection for victims and supporting stronger law enforcement against perpetrators of catcalling. In the research context, catcalling often occurs in open public places, especially with the majority of victims being women who wear the hijab. Forms of catcalling include comments, teasing, gestures, and touching. The research method used is qualitative with a literature review study approach. Data regarding catcalling cases was obtained from the researcher's personal experience, supported by journal research highlighting similar cases in Indonesia. Catcalling is a serious form of sexual harassment, with detrimental impacts on victims such as feelings of insecurity and emotional stress. Strong legal protection, public awareness, and more specific regulations are needed to address this problem effectively. With these steps, it is hoped that we can create a safer environment and respect individual rights. In order to deal with the problem of catcalling, there needs to be a synergy between strengthening the existing legal framework, outreach campaigns, and improving regulations governing behavior in public spaces. In addition, the importance of support from authorities such as the police and other law enforcement agencies to ensure that catcalling cases are handled seriously and fairly. In addition, there is a need for a holistic approach that involves providing psychological and social support for victims to help them recover from the impact of the trauma they may have experienced. Overall, efforts to overcome the catcalling phenomenon require collaboration between the government, the community and various other stakeholders. Only with comprehensive and coordinated measures can we create a safer environment that respects individual rights, and prevent the recurrence of catcalling cases in the future.

Epigenetic Regulation of CXC Chemokine Expression by Environmental Electrophiles Through DNA Methyltransferase Inhibition.

Ubiquitously distributed environmental electrophiles covalently modify DNA and proteins, potentially leading to adverse health effects. However, the impacts of specific electrophiles on target proteins and their physiological roles remain largely unknown. In the present study, we focused on DNA methylation, which regulates gene expression and physiological responses. A total of 45 environmental electrophiles were screened for inhibitory effects on the activity of DNA methyltransferase 3B (DNMT3B), a key enzyme in DNA methylation, and four compounds were identified. We focused on 1,2-naphthoquinone (1,2-NQ), an air pollutant whose toxicity has been reported previously. Interestingly, we found that 1,2-NQ modified multiple lysine and histidine residues in DNMT3B, one of which was near the active site in DNMT3B. It was found that 1,2-NQ altered gene expression and evoked inflammatory responses in lung adenocarcinoma cell lines. Furthermore, we found that 1,2-NQ upregulated CXCL8 expression through DNA demethylation of the distal enhancer and promoted cancer cell growth. Our study reveals novel mechanisms of epigenetic regulation by environmental electrophiles through the inhibition of DNMT3B activity and suggests their physiological impact.

Improvement of endorgan function following tricuspid edge-to-edge repair

Abstract Background/Introduction Subjects with severe tricuspid regurgitation (TR) often suffer from impaired endorgan function. The potential to improve endorgan function is an important goal of treatment. Purpose To assess baseline endorgan function and changes in organ function following transcatheter edge-to-edge repair with the TriClip device in subjects with severe TR from the TRILUMINATE Pivotal randomized controlled trial. Methods Right heart catheterization was required prior to enrollment; medication history was collected. Changes in biomarkers, including MELD-XI, GGT, eGFR, BUN, and TR and KCCQ overall summary score were assessed at baseline and 12-month follow-up for all enrolled subjects. A 15% improvement in biomarker levels was considered clinically relevant. The odds of achieving a 15% improvement in biomarkers between baseline and 12-month follow-up was compared between the Device and Control groups (presented as OR [95% CI]). Results A total of 572 subjects were enrolled and randomized. At baseline, subjects had elevated levels of GGT (83.0±87.7 U/L) and MELD-XI score (10.3±5.2), low eGFR (56.7±21.0 mL/min/1.73m2), and elevated BUN (29.5±16.7 mg/dL). Nearly 90% of subjects were on loop diuretics, with approximately 50% taking these in combination with a thiazide or potassium-sparing diuretic. The average diuretic dosage was 71 mg (furosemide equivalent). Most subjects had normal left ventricle ejection fraction (only 5% with LVEF &amp;lt;40%). Subjects had well-managed blood pressure (systolic: 122±13 mmHg, diastolic: 69±10), slightly elevated central venous pressures (12±6 mmHg), systolic pulmonary artery pressures (40±10 mmHg) and pulmonary capillary wedge pressures (15±4 mmHg), and normal transpulmonary gradients (11±4 mmHg). The odds of achieving a 15% improvement in liver and renal function was higher in TriClip patients compared to control: MELD-XI score (1.79 [1.22, 2.63]), GGT (1.83 [1.21, 2.77]), and eGFR (1.81 [1.18, 2.77]) - Fig 1. The favorable changes in organ function observed were also reflected when stratifying subjects by residual TR severity: The odds of a 15% biomarker improvement favored subjects with moderate or less residual TR for MELD-XI score (2.05 [1.39, 3.00]), GGT (1.91 [1.26, 2.90]), and eGFR (1.83 [1.20, 2.80]) compared with subjects who had severe or worse residual TR. Lastly, improvement in these biomarkers also favored subjects with a 15-point or greater improvement in KCCQ compared with subjects with less than a 15-point KCCQ improvement. Conclusions Use of TriClip in subjects with severe tricuspid regurgitation was associated with improvement in kidney and liver function, and this improvement was associated with reduction in the severity of TR. These data provide the first objective evidence of the physiologic impact of TR reduction obtained in a randomized clinical trial.

Clean-up actions as catalysts for sustainability and physical activity promotion

Abstract Issue The convergence of global sustainability and health promotion implies integrated policies and actions. Initiatives like the European Green Deal and the UN’s Sustainable Development Goals emphasize the urgent need to address climate change while promoting health through behaviours such as physical activity (PA). Description We explore the relationship between PA, sustainability, and health outcomes, highlighting the European Green Deal’s impact on PA promotion and the 2030 Agenda for Sustainable Development’s alignment with health behaviours. In addition, we further discuss the concept of “green exercise” and provide insights about how eco-friendly initiatives (e.g., plogging) may have dual benefits in both individual and environmental domains. Results Emerging eco-friendly activities, including plogging, plalking and pliking, directly benefit the environment, while holding the potential to contribute to PA accumulation. Walking while picking up litter (i.e., plalking) can represent up to 4-5 metabolic equivalents (METs), which corresponds to performing a moderate-intensity PA. If other activities - running or cycling - are performed while picking up litter, the number of METs (i.e., &amp;gt;6 METs) involved may correspond to performing a vigorous-intensity PA. Lessons The physiological impact of eco-friendly activities, such as litter picking, reveals their potential as moderate to vigorous-intensity PA, favouring compliance with WHO PA recommendations (i.e., 150 min/week). Integrated policies and actions are needed to address global challenges effectively, emphasizing the interconnectedness of PA promotion, sustainability efforts, and health outcomes. Key messages • Engaging in green initiatives fosters PA and supports the United Nations’ goals for health and sustainability. • Plogging and similar eco-activities offer dual benefits: cleaner environments and healthier lifestyles.

Changes in health, lifestyle, and wellbeing of children with type 1 diabetes and their parents during the pandemic

ObjectiveThe COVID-19 pandemic restrictions have substantially affected people’s health and rapidly changed their daily routines. This is a prospective study that investigated the impact of the pandemic on primary school children with Type 1 diabetes and their parents during the first lockdown in Kuwait.MethodsA questionnaire battery related to mental health, well-being, and lifestyle was administered at baseline in Summer 2019 (face-to-face, at a diabetes outpatient clinic) and at follow-up during lockdown in Summer 2020 (via telephone, in adherence with COVID-19 restrictions). Data were collected for 70 dyads with children aged 9–12 years.ResultsSignificant differences were found in most scores for both children and parents. Their mental health worsened to a higher level of depression, anxiety, stress, and a poor level of wellbeing. The average scores on the follow-up tests fell within a clinical range on these measures. Significant differences in their lifestyle, compared to before the lockdown, included decreased levels of physical activity and lower healthy core nutritional intake.ConclusionsOur findings indicate that the COVID-19 lockdown has had a significant psychological and possibly physiological impact on children with Type 1 diabetes and their parents. We conclude that there is a need for mental health support services focusing on these groups. Although full lockdown restrictions will have stopped in the past year, post-pandemic stressors may be expected to continue to adversely affect this cohort.

Prominin-1 Knockdown Causes RPE Degeneration in a Mouse Model.

There are currently no effective treatments for retinal pigment epithelial (RPE) cell loss in atrophic AMD (aAMD). However, our research on Prominin-1 (Prom1), a known structural protein in photoreceptors (PRs), has revealed its distinct role in RPE and offers promising insights. While pathogenic Prom1 mutations have been linked to macular diseases with RPE atrophy, the broader physiological impact of dysfunctional Prom1 in RPE loss is unclear. We have shown that Prom1 plays a crucial role in regulating autophagy and cellular homeostasis in human and mouse RPE (mRPE) cells in vitro. Nevertheless, a comprehensive understanding of its in vivo expression and function in mRPE remains to be elucidated. To characterize Prom1 expression in RPE in situ, we used RNAscope assays and immunogold electron microscopy (EM). Our use of chromogenic and fluorescent RNAscope assays in albino and C57BL/6J mouse retinal sections has revealed Prom1 mRNA expression in perinuclear regions in mRPE in situ. Immunogold EM imaging showed Prom1 expression in RPE cytoplasm and mitochondria. To confirm Prom1 expression in RPE, we interrogated human RPE single-cell RNA-sequencing datasets using an online resource, Spectacle. Our analysis showed Prom1 expression in human RPE. To investigate Prom1's function in RPE homeostasis, we performed RPE-specific Prom1 knockdown (KD) using subretinal injections of AAV2/1.CMV.saCas9.U6.Prom1gRNA in male and female mice. Our data show that RPE-specific Prom1-KD in vivo resulted in abnormal RPE morphology, subretinal fluid accumulation, and secondary PR loss. These changes were associated with patchy RPE cell death and reduced a-wave amplitude, indicating retinal degeneration. Our findings underscore the central role of Prom1 in cell-autonomous mRPE homeostasis. The implications of Prom1-KD causing aAMD-like RPE defects and retinal degeneration in a mouse model are significant and could lead to novel treatments for aAMD.

The mask paradox between perception of discomfort and reality of physiological effects in healthy college students in China: a panel study

BackgroundDuring the COVID-19 pandemic, masks proved to be an effective measure in preventing virus transmission. However, many people have reported discomfort and negative perceptions toward wearing masks, especially during physical activity. This study aims to evaluate the discomfort and adverse perceptions related to various mask types among young, healthy adults during light exercise, including sitting, stationary stepping, and stair climbing. The study also examines the extent to which masks influence physiological indicators of physical well-being.MethodsThe study was conducted in two stages at the campus hospital of Shantou University. In Stage 1, 20 healthy college students (10 males, 10 females) were recruited to identify the mask with the most substantial physiological and psychological impact among four types: KN95 respirators, surgical masks, cloth masks, and 3D medical masks. These specific types were chosen due to their widespread use and varying levels of filtration and breathability. In Stage 2, 14 healthy college students (7 males, 7 females) were included to examine the effects of the identified mask across various levels of physical exertion. Subjective perceptions were measured using the Mask-Related Discomfort and Perception Score (MRDPS), and physiological parameters such as body temperature, blood pressure, pulse rate, and vital capacity were recorded.ResultsThe KN95 respirator and cloth mask were associated with the highest MRDPS, indicating significant discomfort among wearers (p < 0.05). The use of KN95 respirators had the largest impact on MRDPS during stair stepping (β = 10.357, 95% CI [5.755, 14.959]). Physiological parameters showed minor variations across different masks, with KN95 respirators significantly associated with reduced diastolic blood pressure (β=-7.806, 95% CI [-12.294, -3.318]) and pulse rate (β=-10.661, 95% CI [-18.896, -2.425]) in Stage 1. However, after controlling for exercise pace in Stage 2, wearing a KN95 respirator did not significantly affect these parameters.ConclusionsKN95 respirators and cloth masks were found to cause the most discomfort during light physical activity, with males reporting higher discomfort levels than females. While these masks are associated with varying levels of perceived discomfort, their impact on physiological indicators is relatively modest. Future research should include larger and more diverse samples , continuous monitoring of physiological parameters during exercise, and exploration of the underlying mechanisms of gender differences in mask discomfort.

Knock-out of the major regulator Flo8 in Komagataella phaffii results in unique host strain performance for methanol-free recombinant protein production

Flo8 is a main transcriptional regulator of flocculation and pseudohyphal growth in yeast. Disruption of FLO8 in the popular recombinant protein production host Komagataella phaffii (Pichia pastoris) prevents pseudohyphal growth and reduces cell-to-surface adherence, making the mutant an interesting platform for research and industry. However, knowledge of the physiological impact of the mutation remained scarce. In-depth analysis of transcriptome data from FLO8-deficient K. phaffii revealed that Flo8 affects genes involved in cell cycle, mating, respiration, and catabolite repression additionally to flocculation targets. One gene with considerably increased expression in flo8 was GTH1, encoding a high-affinity glucose transporter in K. phaffii. Its promoter (PG1) was previously established as a strong, glucose-regulatable alternative to methanol-induced promoters. PG1 and its improved derivatives PG1-3, D-PGS4 and D-PGS5, proved to be promising candidates for controlling recombinant protein production in the FLO8-deficient background. In small-scale screenings, PG13-controlled intracellular EGFP levels were 2.8-fold higher, and yields of different secreted recombinant proteins were up to 4.8-fold increased. The enhanced productivity of the flo8 mutant in combination with the PG1 variants was transferrable to glucose-limited fed-batch processes and could largely be attributed to higher transcriptional activity of the promoter, leading to a much higher productivity per chromosomally integrated gene copy. K. phaffii flo8 has many advantageous characteristics, such as reduced surface growth and increased transcriptional strength of glucose-regulatable promoters. These features turn the flo8 strain into a valuable new base strain for various experimental designs and establish flo8 as an excellent strain background for methanol-free recombinant protein production processes.

Naa80 is required for actin N-terminal acetylation and normal hearing in zebrafish.

Actin is a critical component of the eukaryotic cytoskeleton. In animals, actins undergo unique N-terminal processing by dedicated enzymes resulting in mature acidic and acetylated forms. The final step, N-terminal acetylation, is catalyzed by NAA80 in humans. N-terminal acetylation of actin is crucial for maintaining normal cytoskeletal dynamics and cell motility in human cell lines. However, the physiological impact of actin N-terminal acetylation remains to be fully understood. We developed a zebrafish naa80 knockout model and demonstrated that Naa80 acetylates both muscle and non-muscle actins in vivo. Assays with purified Naa80 revealed a preference for acetylating actin N-termini. Zebrafish lacking actin N-terminal acetylation exhibited normal development, morphology, and behavior. In contrast, humans with pathogenic actin variants can present with hypotonia and hearing impairment. Whereas zebrafish lacking naa80 showed no obvious muscle defects or abnormalities, we observed abnormal inner ear development, small otoliths, and impaired response to sound. In conclusion, we have established that zebrafish Naa80 N-terminally acetylates actins in vitro and in vivo, and that actin N-terminal acetylation is essential for normal hearing.

Interleukin 11 therapy causes acute left ventricular dysfunction.

Interleukin 11 (IL11) was initially thought important for platelet production, which led to recombinant IL11 being developed as a drug to treat thrombocytopenia. IL11 was later found to be redundant for haematopoiesis and its use in patients is associated with unexplained and severe cardiac side effects. Here we aim to identify, for the first time, direct cardiomyocyte toxicities associated with IL11, which was previously believed cardioprotective. We injected recombinant mouse lL11 (rmIL11) into mice and studied its molecular effects in the heart using immunoblotting, qRT-PCR, bulk RNA-seq, single nuclei RNA-seq (snRNA-seq) and ATAC-seq. The physiological impact of IL11 was assessed by echocardiography in vivo and using cardiomyocyte contractility assays in vitro. To determine the activity of IL11 specifically in cardiomyocytes we made two cardiomyocyte-specific Il11ra1 knockout (CMKO) mouse models using either AAV9-mediated and Tnnt2-restricted (vCMKO) or Myh6 (m6CMKO) Cre expression and an Il11ra1 floxed mouse strain. In pharmacologic studies, we studied the effects of JAK/STAT inhibition on rmIL11-induced cardiac toxicities. Injection of rmIL11 caused acute and dose-dependent impairment of left ventricular ejection fraction (saline: 62.4% ± 1.9; rmIL11: 32.6% ± 2.9, p<0.001, n=5). Following rmIL11 injection, myocardial STAT3 and JNK phosphorylation were increased and bulk RNA-seq revealed upregulation of pro-inflammatory pathways (TNFα, NFκB and JAK/STAT) and perturbed calcium handling. snRNA-seq showed rmIL11-induced expression of stress factors (Ankrd1, Ankrd23, Xirp2), activator protein-1 (AP-1) transcription factor genes and Nppb in the cardiomyocyte compartment. Following rmIL11 injection, ATAC-seq identified the Ankrd1 and Nppb genes and loci enriched for stress-responsive, AP-1 transcription factor binding sites. Cardiomyocyte-specific effects were examined in vCMKO and m6CMKO mice, which were both protected from rmIL11-induced left ventricular impairment and molecular pathobiologies. In mechanistic studies, inhibition of JAK/STAT signalling with either ruxolitinib or tofacitinib prevented rmIL11-induced cardiac dysfunction. Injection of IL11 directly activates IL11RA/JAK/STAT3 in cardiomyocytes to cause acute heart failure. Our data overturn the earlier assumption that IL11 is cardioprotective and explain the serious cardiac side effects associated with IL11 therapy.

Clinical prediction of wound re-epithelisation outcomes in non-severe burn injury using the plasma lipidome

Whilst wound repair in severe burns has received substantial research attention, non-severe burns (<20% total body surface area) remain relatively understudied, despite causing considerable physiological impact and constituting most of the hospital admissions for burns. Early prediction of healing outcomes would decrease financial and patient burden, and aid in preventing long-term complications from poor wound healing. Lipids have been implicated in inflammation and tissue repair and may play essential roles in burn wound healing. In this study, plasma samples were collected from 20 non-severe burn patients over 6 weeks from admission, including surgery, and analysed by liquid chromatography-tandem mass spectrometry and nuclear magnetic resonance spectroscopy to detect 850 lipids and 112 lipoproteins. Orthogonal projections to latent structures-discriminant analysis was performed to identify changes associated with re-epithelialisation and delayed re-epithelisation.We demonstrated that the lipid and lipoprotein profiles at admission could predict re-epithelisation outcomes at 2 weeks post-surgery, and that these discriminatory profiles were maintained up to 6 weeks post-burn. Inflammatory markers GlycB and C-reactive protein indicated divergent systemic responses to the burn injury at admission. Triacylglycerols, diacylglycerols and low-density lipoprotein subfractions were associated with delayed wound closure (p-value <0.02, Cliff’s delta >0.7), whilst high-density lipoprotein subfractions, phosphatidylinositols, phosphatidylcholines, and phosphatidylserines were associated with re-epithelisation at 2 weeks post-surgery (p-value <0.01, Cliff’s delta <-0.7). Further model validation will potentially lead to personalised intervention strategies to reduce the risk of chronic complications post-burn injury.

What Are the Perspectives and Experiences of Older Adults of Existing Integrated Care Services in the Mid-West Region of Ireland?

Abstract Background Substantial investment has been provided by the HSE in the form of The Integrated Care Programme for Older People (ICPOP) Community Specialist Teams (CSTs) for older people. These teams aim to provide timely specialist multi-disciplinary assessment and intervention to help maintain older adults’ independence and ability to live well at home. Little is known about older adult’s views or experiences of this service. This study aimed to resolve this research gap by exploring older adults’ experiences of CSTs within the Irish Healthcare context. Methods A qualitative descriptive research design was employed to explore this research area and a semi structured topic guide was developed. Purposive non-probability sampling was used to recruit 13 older adults who had completed intervention with the CSTs. Individual semi-structured interviews were completed with each participant and were transcribed verbatim. A reflexive approach to thematic analysis was used to guide analysis of the generated data. Results Four themes were identified, older people had limited knowledge of the service and experienced accessibility issues in attending CST within a HUB setting (Theme 1). Older people experienced positive and co-ordinated care by CST (Theme 2). Older people described that they valued the self-management education and support from attending CST that enabled to manage their long-term conditions effectively and maintain their independence (Theme 3). Once discharged from CST older people described positive emotional and physiological impact of CST that enabled them to be more confident to manage daily life at home (Theme 4). Conclusion It was evident from the data that CST had a positive impact on supporting older people to remain independent at home and increased their confidence in self- management of their long-term conditions. Further research would be beneficial to address ways to improve the delivery of care for the complex needs older persons within CSTs as they describe accessibility issues in attending the service.

Abstract B163: Researcher, Clinician, and Community Focus Groups to Inform an Understanding of Cancer Disparities in the Transgender and Gender Diverse

Abstract Background: A growing number of Americans identify as transgender or gender diverse (TGD). This population experiences barriers and challenges across to socio-ecological spectrum including healthcare. Simultaneously, there is limited data on cancer in TGD persons. While advances in data-capture provide promising opportunity for future research, a comprehensive understanding of cancer disparities for the TGD community is needed to inform clinically and socially relevant research questions – particularly on cancer prevention, risk, screening, and treatment. Our study aimed to develop a transdisciplinary (TDS) academic-community team to create a shared understanding of factors associated with cancer disparities in the TGD population with aid from discussion sessions and interviews with researchers, clinicians, and community members. Methods: The TDS team engaged in literature reviews and discussion to ground their collective understanding. The team also conducted focus groups and interviews with researchers, clinicians, and community members (N=55) to enrich the team’s understanding of factors associated with cancer disparities. Data were summarized and thematized and groups were compared. Results: Community organizations/members noted systemic issues such as insufficient training of healthcare providers and staff, individual mistrust, and not believing they would live long enough to worry about cancer development. Providers identified personal uncertainty working with TGD patients, knowledge of appropriate recommendations for cancer screening, and individual risk behaviors (i.e. tobacco and alcohol use) as potential causes for cancer disparities. Researchers indicated they had not considered including TGD individuals as a specific subject population, were unsure how to study given lack of mouse models for early-stage research and acknowledged the opportunity for future study inclusion. Further, community members discussed the persistent stress of existing as a TGD person during a time of increasingly aggressive anti-TNB legislation and social attitudes. Healthcare providers and researchers reflected on the behavioral and physiological impact of stress on an individual’s health and cancer risk. Conclusion: The findings from our focus groups elucidated areas of shared understanding between the three different audiences; however, they also highlighted concepts that were not shared which offer opportunities for further collaboration and learning by key stakeholders. Through our TDS and collaborative approach, we will continue deep learning between team members to identify specific research questions to address the root causes of TGD cancer disparities through TDS collaboration and innovative research. Citation Format: Tobi Cawthra, Chandler Cortina, laura Pinsoneault, Michael Munson, Andrew Petroll, Melinda Stolley. Researcher, Clinician, and Community Focus Groups to Inform an Understanding of Cancer Disparities in the Transgender and Gender Diverse [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr B163.