Individual Stress Response Research Articles

Mechanics and Morphology of Proliferating Cell Collectives with Self-Inhibiting Growth.

We study the dynamics of proliferating cell collectives whose microscopic constituents' growth is inhibited by macroscopic growth-induced stress. Discrete particle simulations of a growing collective show the emergence of concentric-ring patterns in cell size whose spatiotemporal structure is closely tied to the individual cell's stress response. Motivated by these observations, we derive a multiscale continuum theory whose parameters map directly to the discrete model. Analytical solutions of this theory show the concentric patterns arise from anisotropically accumulated resistance to growth over many cell cycles. This Letter shows how purely mechanical processes can affect the internal patterning and morphology of cell collectives, and provides a concise theoretical framework for connecting the micro- to macroscopic dynamics of proliferating matter.

Copeptin as an inflammatory marker in diagnosis and prognosis of neonatal sepsis

BackgroundCopeptin is an immediate biomarker of individual stress response; many life-threatening diseases are causing a high elevation of its concentration in plasma, such as myocardial infarction and cardiovascular shock. Moreover, copeptin is a promising marker in sepsis. We aimed to evaluate copeptin as a diagnostic and prognostic marker in neonatal sepsis for the early initiation of appropriate therapy and the prediction of mortality. A prospective case-control study involved 237 neonates (165 cases had neonatal sepsis, and 72 served as controls). Cases were admitted to the neonatal intensive care unit (NICU) and followed up for symptoms and signs of sepsis confirmed by laboratory data: complete blood count (CBC), c-reactive protein (CRP), and cultures. Serum copeptin level by the enzyme-linked immunosorbent assay (ELISA) was measured for all included neonates. We observed that the copeptin level was significantly higher in cases than control (3.51 ± 1.4, 1.61 ± 0.51 pmol/liter, respectively). The cut-off value of copeptin at which we can discriminate between cases and controls was above 2.065 pmol/liter. Among cases, copeptin was higher in early-onset sepsis (EOS) than late-onset sepsis (LOS) neonates, and there was a significant correlation between its level and all the following: age at admission, birth weight, gestational age, history of perinatal asphyxia, maternal chorioamnionitis, and premature rupture of membrane (PROM). Also, copeptin was strongly associated with CRP level and the poor prognosis of patients. Copeptin can predict the death of cases at a cut-off value above 2.995 pmol/liter.ConclusionSerum copeptin level can be used as a diagnostic and prognostic marker in neonatal sepsis.

Psychobiological Stress Response Profiles in Current and Remitted Depression: A Person-Centered, Multisystem Approach

BackgroundA dysregulated stress response, including exaggerated affective reactivity and abnormal hypothalamic–pituitary–adrenal (HPA) axis responsivity, has been implicated in the etiology, maintenance and relapse of major depressive disorder (MDD). Among adolescents, discordant affective and physiological stress response profiles have been linked to negative affective outcomes and increased risk for psychopathology. Whether these findings extend to adults with varying degree of MDD risk is unclear, as are possible links to various risk factors. MethodsWe used a person-centered, multisystem approach in a sample of 119 unmedicated adults with current or remitted MDD, as well as individuals without past MDD to evaluate psychobiological stress response profiles. Multi-trajectory modeling was applied to positive affect, negative affect, and salivary cortisol (CORT) levels in response to the Maastricht Acute Stress Test. ResultsAnalyses identified four within-person profiles, one typical, Normative (n=32, 26.9%); and three atypical: CORT Hyperreactivity Affective Stability (n=17, 14.3%), CORT Hyporeactivity Affective Reactivity #1 (n=45, 37.8%), and CORT Hyporeactivity Affective Reactivity #2 (n=25, 21.0%). Validating the assumption of a Normative profile and increased risk for psychopathology in non-normative stress-response profiles, coherent associations emerged between stress response profiles and clinical status, depression severity, anhedonia, perceived stress, childhood adversity and reports of well-being, suggesting increased risk for psychopathology for individuals with a hyperreactive or discordant hyporeactive stress response profiles. ConclusionThis work advances our understanding of stress response mechanisms in MDD and underscores the potential of targeted interventions to enhance resilience and reduce psychopathology based on individual stress response profiles.

Oral Supplementation of L-Carnosine Attenuates Acute-Stress-Induced Corticosterone Release and Mitigates Anxiety in CD157 Knockout Mice.

Corticosterone, an end product of the hypothalamic-pituitary-adrenal (HPA) axis, is a crucial stress hormone. A dysregulated HPA axis and corticosterone release play pivotal roles in the onset and persistence of symptoms of stress-related psychiatric disorders, such as anxiety. The intake of nutrients, probiotics, and prebiotic supplements decreases blood corticosterone levels. The dipeptide L-carnosine is composed of beta-alanine and L-histidine and is commercially available as a nutritional supplement for recovery from fatigue. L-carnosine is involved in stress-induced corticosterone responses and anxiety behaviors in rodents. Here, we assessed the effect of L-carnosine in CD157 knockout (KO) mice, a murine model of autism spectrum disorder (ASD). The uptake of L-carnosine suppressed the increase in plasma corticosterone levels in response to acute stress and attenuated anxiety-like behaviors in CD157 KO mice. These results suggest that L-carnosine supplementation may relieve anxiety by suppressing excessive stress responses in individuals with ASD.

Using Full Dive Virtual Reality to Operationalize Warfighter Resilience: From Proof of Concept and Usability of Hardware and Software to Upcoming Integrated Psychological Skills Training.

Modern warfare operations are volatile, highly complex environments, placing immense physiological, psychological, and cognitive demands on the warfighter. To maximize cognitive performance and warfighter resilience and readiness, training must address psychological stress to enhance performance. Resilience in the face of adversity is fundamentally rooted in an individual's psychophysiological stress response and optimized through decreased susceptibility to the negative impact of trauma exposure. The current project aims to optimize warfighter expertise, resilience, adaptability, and performance by utilizing a validated Full Dive Virtual Reality (FDVR) training platform to provide high-fidelity, safe, and scalable, controlled stress exposure in highly realistic simulated training scenarios with the most advanced, immersive technology available. Following Institutional Review Board approval and consent, 2 operators were fitted with high-fidelity virtual reality headsets with hand and eye tracking, full-body haptic feedback suits, a 360° omnidirectional treadmill, and Food and Drug Administration (FDA) cleared biometric monitors. Following acclimation, operators were placed in an industrial fire scenario and instructed to respond as a firefighter and paramedic, to search for and resuscitate any casualties, extinguish the fire, and exfiltrate safely. Following initial acclimation and after each demonstration (n = 2), 3 semistructured interviews asked operators their perceptions and experiences related to FDVR, focusing on usability, feasibility, and safety. Biometric data were continuously recorded using the Caretaker Medical VitalStream. Proof-of-concept (POC) testing proved that the FDVR training platform is usable, safe, and feasible. It creates an immersive environment with physiological responses to mimic realistic Mass Casualty Events (MCEs). Using a case study approach, transcript data were analyzed using thematic analysis. Three major themes emerged: Sensory deficits reduced realism, but sensory feedback improved fidelity, vestibular discord affected the virtual reality experience but only when the system did not respond naturally to operator movement after acclimation, and movement accommodations were made by operators to enhance usability, especially for fine motor movements. Biometric data analysis correlated timestamps from the VitalStream unit with operator responses to stress-inducing events (i.e., explosions, fires, and a deceased victim). Both operators exhibited significant physiological responses, including elevated heart rate, systolic blood pressure, and mean arterial pressure, particularly following explosions, encountering fire, and encountering the deceased victim within the training environment. The FDVR training platform overcomes the obstacles of in-person simulation training and provides the closest to real-life experience available. It will allow warfighters to train with their teams in immersive environments that replicate the conditions in which they are expected to perform their duties. The POC demonstrated that physiological responses can be mapped to scenario events to allow tracking of stress responses, cognitive load, as well as performance, and decision-making of the warfighter. The POC only involved 2 operators, but served to prove that the platform was safe and effective. Future testing plans to include 200 warfighters in operational teams of 10 to 12 to further validate the training effectiveness of the FDVR platform.

Oxidative Stress Responses in Obese Individuals Undergoing Bariatric Surgery: Impact on Carcinogenesis.

Obesity is a big public health problem that claims several thousand lives every year. Bariatric surgery has arisen as a suitable procedure for treating obesity, particularly morbid obesity. Oxidative stress, genotoxicity, apoptosis, and inflammatory responses are recognized as the most important occurrences in carcinogenesis, as they actively contribute to the multistep process. This study aimed to briefly review the connection between oxidative stress, genotoxicity, apoptosis, and inflammation in obese patients undergoing bariatric surgery, focusing on its impact on carcinogenesis. Regarding oxidative stress, bariatric surgery may inhibit the synthesis of reactive oxygen species. Moreover, a significant reduction in the inflammatory status after weight loss surgery was not observed. Bariatric surgery prevents apoptosis in several tissues, but the maintenance of low body weight for long periods is mandatory for mitigating DNA damage. In conclusion, the association between bariatric surgery and cancer risk is still premature. However, further studies are yet needed to elucidate the real association between bariatric surgery and a reduced risk of cancer.

Evaluating Serum Copeptin as a Promising Biomarker for Predicting Acute Ischaemic Stroke Severity: A Hospital-Based Study on Strokes.

Stroke is the second cause of mortality and the foremost leading cause of disability globally. Many potential biomarkers have been described to contribute to prognosticating the severity in the acute phase of stroke as well as help with risk stratification. Copeptin, an inactive peptide that is produced in an equimolar ratio to arginine vasopressin and adequately mirrors an individual's stress response to acute illnesses like acute ischaemic stroke as evidenced by elevated or increasing levels is being explored in this study to determine its relationship with acute stroke severity and infarct size on admission. This is a cross-sectional study of 80 neuroimaging-confirmed acute ischaemic patients who presented within seven days of symptom onset and 80 control subjects. The ischaemic stroke cases had stroke severity and infarct volume determined on admission by the National Institute of Health Stroke Scale (NIHSS) and neuroimaging (brain CT/MRI). A baseline serum copeptin level was measured in the study subjects. Spearman correlation and Kruskal Wallis test were used to determine the relationship between serum copeptin level with admission NIHSS and infarct size respectively. The receiver operating characteristic (ROC) curve was calculated to determine the sensitivity and specificity of copeptin to predict severity and outcome. The mean age of the study group was 61.3 ± 12.7 years with 55.0% males and 45.0% females. The serum level of copeptin was significantly higher in the stroke cases with a median of 28.6 pmol/L (interquartile range (IQR)- 15.4-31.6 pmol/L) versus 8.8 pmol/L (IQR- 3.2- 10.7 pmol/L) among the stroke-free controls (p= 0.001) at a statistically significant level. There was a weak correlation between copeptin and NIHSS calculated at admission to measure stroke severity (r- 0.02, p= 0.873). Patients with infarct sizes in the fourth quartile (infarct sizes greater than 18.78 cm3) had higher copeptin levels, though this was not statistically significant (H= 2.88; p= 0.410). Admission serum copeptin did not show a statistically significant prognostic value in predicting stroke severity and mortality in stroke patients who presented within seven days of symptomonset with an area under curve (AUC) of 0.51 (95% CI: 0.36-0.65; p= 0.982). In this study, copeptin was higher among the stroke cases compared with the stroke-free controls which suggests a significant prognostic value in risk stratification in the acute phase of stroke; however, this did not significantly correlate with stroke severity and thus warrants further study in this field to elucidate it's fascinating potential as a prognostic biomarker (especially in the acute period) as this may enable allocation of a better-focused therapy for stroke patients.

Autonomic nervous system and endocrine system response to upper or lower cervical spine mobilization in males with persistent post-concussion symptoms: a proof-of-concept trial

ABSTRACT Introduction The peripheral stress response, consisting of the autonomic nervous system (ANS) and hypothalamic pituitary adrenal-axis (HPA-axis), functions to maintain homeostasis in response to stressors. Cervical spine manual therapy has been shown to differentially modulate the stress response in healthy populations. No study has investigated whether cervical spine mobilizations can differentially modulate the stress response in individuals with persistent post-concussion symptoms (PPCS), a population characterized by a dysfunctional stress response. Methods A randomized, controlled, parallel design trial was performed to investigate whether upper or lower cervical spine mobilization can differentially modulate components of the stress response in individuals with PPCS. The outcomes were salivary cortisol (sCOR) concentration (primary) and the HRV metric, rMSSD, measured with a smartphone application (secondary). Nineteen males diagnosed with PPCS, aged 19–35, were included. Participants were randomly assigned into either intervention group, upper (n = 10) or lower (n = 9) cervical spine mobilization. Each outcome was collected at different time points, pre- and post-intervention. Statistical analyses were performed using the Friedman’s Two-Way ANOVA, Mann-Whitney U test, and Wilcoxon Signed Rank Test. Results There was a statistically significant within-group reduction in sCOR concentration 30 minutes following lower cervical spine mobilizations and statistically significant within-group increase in rMSSD 30 minutes following upper cervical spine mobilizations. Conclusion The results of this trial provide preliminary evidence for cervical spine mobilizations to differentially modulate components of the stress response at specific time points. Understanding the mechanisms of the effect of cervical spine mobilizations on the stress response provides a novel rationale for selecting cervical spine mobilizations to rehabilitate individuals with PPCS.

Sensorimotor Simulation's Influence on Stress: EEG and Autonomic Responses in Digital Interviews.

This study explored the role of sensorimotor simulation in modulating the stress response in individuals exposed to stressful digital simulated interviews. Participants were assigned to two different versions of a Digital Social Stress Test: a simulated version with a dynamic-realistic examining committee (Dyn-DSST) and a version with a static examining committee (Stat-DSST). During interview preparation, behavioral indices reflecting stress regulation and resistance, response times, and electroencephalographic (EEG) and autonomic indices were collected. Higher regulation scores were found for the Stat-DSST group compared to the Dyn-DSST group, probably induced by the presence of limited external sensory input in time and space, perceived as less stressful. The EEG results revealed a distinct contribution of the low- and high-frequency bands for both groups. Dyn-DSST required greater cognitive regulation effort due to the presence of a continuous flow of information, which can enhance sensory and motor activation in the brain. The SCR increased in the Dyn-DSST group compared to the Stat-DSST group, reflecting greater emotional involvement in the Dyn-DSST group and reduced sensory stimulation in the static version. In conclusion, the results suggest that sensorimotor simulation impacts the stress response differently in dynamic interviews compared to static ones, with distinct profiles based on behavioral, EEG, and autonomic measures.

Genetic Variability for Root and Shoot Morpho-physiological Traits Contributing to Seedling Drought Stress Tolerance in Parental Lines of Pearl Millet

Drought stress severely affects plant growth and development leading to substantial reduction in yield and biomass accumulation. Forty one Pearl millet parental lines were subjected to seedling drought stress and morpho–physiological attributes along with individual drought stress response indices were recorded. Significant genetic variability existed for all the traits and genotype ICMX 1410698-SB-11-1-1-2(B) ranked first based on combined drought stress response index. Principal component analysis indicated that first two PCs explained 86.4% of variation under drought conditions. GCV ranged from 13.84 to 23.47% under drought indicating genetic basis for variability. D2 statistics grouped the genotypes into seven clusters. The maximum inter-cluster distance was reported between the clusters III and VII while clusters III & I ranked second under drought stress. These are potential drought tolerant parental lines for hybrid breeding. Root/Shoot ratio has been the major contributor for genetic divergence under both control and drought stress.

Influences of sleep, cortisol reactivity, and risk/reward-based decision-making on suicide

Background and objectivesPoor sleep quality is a known contributor to suicidal thoughts and behaviors. This study examines whether sleep quality modulates the effect of an individual's stress response and risk/reward-based decision making on suicide risk. MethodsParticipants were 160 adults at a residential substance use treatment facility with lifetime exposure to trauma who completed a clinician-administered measure of suicide risk, the Iowa Gambling Task (IGT), and a self-report measure of sleep. Cortisol reactivity (i.e., changes in cortisol before and after a personalized trauma script) was used to measure stress response. We used quantile regression to examine the effects of sleep, cortisol, and risk/reward decision-making on suicide risk. ResultsWe found poor sleep quality to be increasingly salient in individuals at greater risk for suicide than those at lower risk for suicide. Furthermore, individuals with moderate to moderate-high levels of suicide risk seem to have greater cortisol reactivity. In the low-moderate quantile, we found suicide risk to be associated with both high stress reactivity and low-risk, high-reward decision-making, as well as low stress reactivity and high-risk/low-reward decision-making. LimitationsThese findings should be interpreted considering several methodological constraints, such as the use of a pre-determined sample and instruments not tailored for our hypotheses, the MINI ‘Suicide’ Module's limited differentiation between suicidal ideation and behavior, and variably timed cortisol sampling. ConclusionsDespite these limitations, the findings from this study support the use of evidence-based interventions focused on improving sleep quality and managing emotional reactivity to decrease suicide risk.

Loss of the ceramide synthase HYL-2 from Caenorhabditis elegans impairs stress responses and alters sphingolipid composition

Sphingolipids, essential membrane components and signaling molecules in cells, have ceramides at the core of their metabolic pathways. Initially termed as "longevity assurance genes", the encoding genes of ceramide synthases are closely associated with individual aging and stress responses, although the mechanisms remain unclear. This study aims to explore the alterations and underlying mechanisms of three ceramide synthases, HYL-1, HYL-2, and LAGR-1, in the aging and stress responses of Caenorhabditis elegans. Our results showed the knockdown of HYL-1 extends the lifespan and enhance stress resistance in worms, whereas the loss of HYL-2 function significantly impairs tolerances to heat, oxidation, and ultraviolet stress. Stress intolerance induced by HYL-2 deficiency may result from intracellular mitochondrial dysfunction, accumulation of reactive oxygen species, and abnormal nuclear translocation of DAF-16 under stress conditions. Loss of HYL-2 led to a significant reduction of predominant ceramides (d17:1/C20∼C23) as well as corresponding complex sphingolipids. Furthermore, the N-acyl chain length composition of sphingolipids underwent dramatic modifications, characterized by a decrease in C22 sphingolipids and an increase in C24 sphingolipids. Extra d18:1-ceramides resulted in diminished stress resilience in wild-type worms, while supplementation of d18:1/C16 ceramide to HYL-2-deficient worms marginally improved stress tolerance to heat and oxidation. These findings indicate the importance of appropriate ceramide content and composition in maintaining subcellular homeostasis and nuclear-cytoplasmic signal transduction during healthy aging and stress responses.

Human emergency behaviour and psychological stress characteristic mining based on large-scale emergencies

AbstractHuman emergency behaviour and psychological stress response in emergencies are important scientific issues in basic emergency management research. The analysis of the dynamic characteristics of large-scale human behaviour based on electronic footprint data provides a new method for quantitative research on this problem. Previous studies usually assumed that human behaviors were randomly distributed in time, but few studies have studied the psychological stress response of human groups under the influence of emergencies and carried out prediction methods through social media data. Based on the data from five emergencies and daily events in the Qzone, this paper explores the statistical characteristics of human communication behaviors such as time, space and social interaction. The research results reveal the psychological evolution of human groups when they encounter public security emergencies by analysing the causes of individual psychological stress responses in the group. We find that the time interval between people’s posting behaviour and interactive comment behaviour in mobile QQ space before and after an emergency can be approximately described by a power-law distribution. The time interval distribution of Posting and reply is an obvious heavy-tailed distribution. These behavioural characteristics are consistent with people’s psychological stress characteristics. Individual psychological stress responses gradually evolve into social-psychological responses with changes in behavioural characteristics. The greater the social-psychological stress response is, the more panic the public will be, which will cause the outbreak of group irrational behaviour. The research results are theoretically helpful in understanding the impact of emergencies on human communication behaviour patterns and reveal the psychological stress process of mass panic in large-scale emergencies.

Life-Stage and Contextual Factors of Advance Care Planning Among Older Adults With Limited Income.

Patient perspectives are essential to understand healthcare disparities such as low rates of advance care planning (ACP) among adults with limited income. We completed twenty semi-structured interviews using purposive and snowball sampling. Initial and final themes emerged from inductive inclusion of recurring codes and deductive application of the cumulative disadvantage theory. Four themes emerged: (1) structural, (2) life-stage, (3) social stressors and resources, and (4) individual stress responses and ACP readiness. ACP resources among participants included positive structural and social support and previous familial death experiences that were mitigated by stress avoidance and competing priorities. Structural resources and healthcare stressors should be addressed with policy and research to improve continuous healthcare participation and support early, comprehensive ACP.

StressME: Unified computing framework of Escherichia coli metabolism, gene expression, and stress responses.

Generalist microbes have adapted to a multitude of environmental stresses through their integrated stress response system. Individual stress responses have been quantified by E. coli metabolism and expression (ME) models under thermal, oxidative and acid stress, respectively. However, the systematic quantification of cross-stress & cross-talk among these stress responses remains lacking. Here, we present StressME: the unified stress response model of E. coli combining thermal (FoldME), oxidative (OxidizeME) and acid (AcidifyME) stress responses. StressME is the most up to date ME model for E. coli and it reproduces all published single-stress ME models. Additionally, it includes refined rate constants to improve prediction accuracy for wild-type and stress-evolved strains. StressME revealed certain optimal proteome allocation strategies associated with cross-stress and cross-talk responses. These stress-optimal proteomes were shaped by trade-offs between protective vs. metabolic enzymes; cytoplasmic vs. periplasmic chaperones; and expression of stress-specific proteins. As StressME is tuned to compute metabolic and gene expression responses under mild acid, oxidative, and thermal stresses, it is useful for engineering and health applications. The modular design of our open-source package also facilitates model expansion (e.g., to new stress mechanisms) by the computational biology community.

Cortisol in fish scales remains stable during extended periods of storage.

Measurement of cortisol in fish scales is attracting considerable attention as a non-invasive indicator of chronic stress in wild populations. For many fish species of management and conservation interest, extensive scale collections exist that could provide extended records of individual stress responses, by combining cortisol measurements with life history information. However, it is not yet known how well cortisol is preserved in the scale during storage. To investigate the stability of scale cortisol, we accelerated potential degradation by storing scales from an individual farmed Atlantic salmon (Salmo salar) in an oven at 50°C for between 2 and 12weeks. We found no significant relationship between scale cortisol concentration and either storage time or storage temperature. Cortisol concentrations in scales from the same fish were consistent (18.54-21.82ng. g-1; coefficient of variation(CV) = 3.6%), indicating that scale cortisol can be reliably quantified, even in scales stored for varying periods of time or under different conditions. We also examined the effects of storage in real time using Atlantic salmon scales that were stored in paper envelopes at room temperature for between 3 and 32years and found no significant relationship between scale cortisol concentration and storage time. Scale cortisol concentrations ranged from 4.05 to 135.37ng.g-1 and levels of between-individual variability were high (CV = 61%). Given that scale cortisol does not degrade during long-term storage, historical scale collections and associated data describing fish life histories could potentially be used to develop bioindicators of physiological responses in fish populations. Further research is needed to understand scale cortisol variability and its biological relevance.

Progesterone Attenuates the Stress Response in Individuals with Alcohol Dependence and Post-Traumatic Stress Disorder – A Pilot Study

Objective: Evidence from laboratory studies suggests that progesterone may be effective in reducing stress and craving, and may improve cognitive performance in smokers and individuals with cocaine dependence. The objective of this study was to examine if progesterone would attenuate stress-induced craving, anxiety, affect and physiological measures, as well as improve stress-induced cognitive performance (processing speed and selective attention) in individuals diagnosed with alcohol use disorder (AUD) and post traumatic stress disorder (PTSD). Methods: This laboratory study included (n = 13) participants who were diagnosed with current AUD and PTSD who were randomly assigned to recive either progesterone (200mg bid) or placebo in identical looking capsules for 3 days. On the fourth day they completed a laboratory session. In the morning of the test session, they received the last dose of medication and completed the rest of the laboratory procedures. The procedures included presentation in random order of personalized trauma and neutral scripts with relaxation in between. Main outcomes included measure of craving, anxiety, affect and cognitive performance. Results: Consistent with other research, trauma scripts produced significantly greater increases in craving, anxiety and negative affect when compared with neutral scripts. Progesterone significantly reduced stress-induced symptoms of craving, anxiety, fear, anger and sadness but had no effect on positive emotions (joy, relaxation). Progesterone was effective in ameliorating stress-induced decreases in cognitive performance. Conclusions: The findings from this study demonstrate that progesterone can be effective in reducing stress-induced craving, anxiety and negative affect in a laboratory setting in individuals with comorbid AUD and PTSD. Interestingly, progesterone also improved cognitive performance. These findings require replication in a larger clinical trial and may have implications for treatment among individuals with AUD and PTSD. This study was registered as NCT02187224, at www.clinicaltrials.gov

LIFE-COURSE AND CONTEXTUAL FACTORS OF ADVANCE CARE PLANNING AMONG OLDER ADULTS WITH LIMITED INCOME

Abstract Background Cumulative disadvantage across the lifespan can lead to income, health, and advance care planning (ACP) disparities, resulting in increased caregiver decisional distress and reduced healthcare equity during times of cognitive incapacity. ACP is the process of patient and familial learning, communication, and documentation of life-sustaining care and quality of life preferences after personal reflection, but ACP rates remain lower among older adults with limited income. To better understand how life-course factors influence these low ACP rates, we aimed to explore participant perceptions of healthcare and ACP barriers and facilitators through different life stages. Methods We sampled older adults (aged 50+) with limited income from six community-based sites (N=20). Qualitative descriptive design was utilized to perform semi-structured, in-person interviews. Results Themes emerged from the inductive inclusion of in-vivo codes and the deductive application of the Cumulative Disadvantage Theory. Mean age: 64.8 years old (SD: 6.8); 11 participants identified as female (55.0%); 16 identified as Black/African American (80.0%). Four themes emerged: 1) structural, life-stage, 2) social stressors and resources, 3) individual stress responses and 4) ACP readiness. Participants’ perceptions denoted that proactive planning inequities among older adults with limited income result from the dynamic interplay of multi-dimensional stressors, protective factors, and personal stress responses. Implications: Identified themes serve as a conceptual basis for future intervention development that is responsive to traumatic life-course experiences and supportive of building ACP resilience (i.e., adapting to ACP stress and actively planning for times of cognitive incapacity), as well as policy and practice implications.

LATENT VARIABLE MODELING FOR BIOLOGICALLY INFORMED PROGNOSIS IN STUDIES OF PHYSICAL RESILIENCE

Abstract Physical resilience – rebound in relevant functioning and biomarkers following a health stressor – is hypothesized to be rooted in the level of fitness of stress-response physiology defining one’s “physiological resilience capacity” (PRC). This physiology forms a dynamical system comprising specific modules (the individual stress response systems and their underlying components) and their dynamic interactions with each other via feedback and other protocols. Such a system can be modeled using differential equations whose parameters may then define the PRC. We do not yet know how to measure these parameters directly, however. Rather, they are conceptually defined “constructs” which must be inferred using indirect measures—ideally, stimulus response data probing multiple aspects of the relevant physiology. Latent variable models are ideally suited to this setting. Two challenges for their application in studies of resilience are presented: (1) Integrating specific scientific knowledge on the dynamical systems in modeling the co-distribution of the indirect measures. (2) Synergizing such models’ advantages for construct measurement with advantages of machine learning approaches to optimize accuracy for predicting resilient outcomes by inferred PRC. Challenges and their proposed solutions are illustrated using multifaceted stimulus response data being collected in an ongoing investigation on the physiological basis of resilience to clinical stressors in older adults, the Study of Physical Resilience in agING. The work aims to produce physiologically rooted measures providing effective risk predictors for older adults facing impending stressors as well as intervention candidates by which to promote PRC in the longer term.

Inter-patient heterogeneity in the hepatic ischemia-reperfusion injury transcriptome: Implications for research and diagnostics

Cellular responses induced by surgical procedure or ischemia-reperfusion injury (IRI) may severely alter transcriptome profiles and complicate molecular diagnostics. To investigate this effect, we characterized such pre-analytical effects in 143 non-malignant liver samples obtained from 30 patients at different time points of ischemia during surgery from two individual cohorts treated either with the Pringle manoeuvre or total vascular exclusion. Transcriptomics profiles were analyzed by Affymetrix microarrays and expression of selected mRNAs was validated by RT-PCR. We found 179 mutually deregulated genes which point to elevated cytokine signaling with NFκB as a dominant pathway in ischemia responses. In contrast to ischemia, reperfusion induced pro-apoptotic and pro-inflammatory cascades involving TNF, NFκB and MAPK pathways. FOS and JUN were down-regulated in steatosis compared to their up-regulation in normal livers. Surprisingly, molecular signatures of underlying primary and secondary cancers were present in non-tumor tissue. The reported inter-patient variability might reflect differences in individual stress responses and impact of underlying disease conditions. Furthermore, we provide a set of 230 pre-analytically highly robust genes identified from histologically normal livers (<2% covariation across both cohorts) that might serve as reference genes and could be particularly suited for future diagnostic applications.