Maladaptive Processes Research Articles

Community-engaged research: Bringing the science of developmental psychopathology into the real world.

The science of developmental psychopathology has made outstanding progress over the past 40 years in understanding adaptive and maladaptive developmental processes across the life span. Yet most of this work has been researcher driven with little involvement of community partners in the research process, limiting the potential public health significance of our work. To continue to advance the field we must move beyond the physical and conceptual walls of our research laboratories and into the real world. In this article, we define and describe the importance of community-engaged research, and present our overarching principles for engaging the community including practicing respect, shared power and decision-making, prioritizing the needs of the community, and engaging in consistent and transparent communication. We present several associated recommendations for best practice and highlight examples from our own research that is grounded in a developmental psychopathology perspective to illustrate these practices. Recommendations for the future of the discipline of development and psychopathology, with emphasis on training and continuing education, are described.

아동기 애착외상 경험이 있는 한 성인의 가족관계 경험과 회복에 대한 자문화기술지

Objectives: The purpose of this study is to explore the impact of childhood attachment trauma experiences in the original family on the experience of family relationships after marriage and the experience of restoring family relationships in the process of post-traumatic recovery from an insider's point of view, to help understand those who have experienced such trauma and to suggest counseling implications. Methods: For this purpose, we applied autoethnography, a qualitative research method, to collect data such as memory data, diary data including self-observation and self-analysis, and family interviews. The collected data were subjected to value coding, emotion coding, and longitudinal coding during data analysis. Results: As a result, it was confirmed that the experience of attachment trauma continues across generations and that maladaptive psychological processes resulting from the traumatic experience are repeated in family relationships after marriage. Moreover, the changing factors that appeared in the process of recovering family relationships were identified. Conclusions: The significance and limitations of this study were presented.

Intravital imaging of pulmonary lymphatics in inflammation and metastatic cancer.

Intravital microscopy has enabled the study of immune dynamics in the pulmonary microvasculature, but many key events remain unseen because they occur in deeper lung regions. We therefore developed a technique for stabilized intravital imaging of bronchovascular cuffs and collecting lymphatics surrounding pulmonary veins in mice. Intravital imaging of pulmonary lymphatics revealed ventilation-dependence of steady-state lung lymph flow and ventilation-independent lymph flow during inflammation. We imaged the rapid exodus of migratory dendritic cells through lung lymphatics following inflammation and measured effects of pharmacologic and genetic interventions targeting chemokine signaling. Intravital imaging also captured lymphatic immune surveillance of lung-metastatic cancers and lymphatic metastasis of cancer cells. To our knowledge, this is the first imaging of lymph flow and leukocyte migration through intact pulmonary lymphatics. This approach will enable studies of protective and maladaptive processes unfolding within the lungs and in other previously inaccessible locations.

The role of rumination and metamemory beliefs in posttraumatic growth and posttraumatic stress

The risk of developing posttraumatic stress symptoms following exposure to traumatic events is well documented, however, emerging research also lends support to the potential development of growth in some people. Rumination and memory have been identified as important factors in post-trauma outcomes, yet, current research in this area is limited, particularly in the context of a multidimensional view of rumination (i.e., intrusive and deliberate rumination) and metamemory beliefs. This study explored the association between rumination styles, beliefs about memory, and posttraumatic stress symptoms and posttraumatic growth. Participants (N = 151) who experienced a traumatic event completed relevant measures online. Path analysis showed that intrusive rumination was significantly related to higher levels of posttraumatic stress symptoms (β = 0.19, p < 0.01), while deliberate rumination was related to higher levels of both posttraumatic growth (β = .52, p < 0.001) and posttraumatic stress symptoms (β = 0.15, p < 0.05). Additionally, negative beliefs about memory were significantly related to higher posttraumatic stress symptoms (β = 0.48, p < 0.001). No significant associations were found for positive beliefs about memory. The findings suggest that rumination may be understood as multidimensional, incorporating both adaptive and maladaptive processes. Further, the present study contributes to the limited literature concerning metamemory beliefs and may provide an increased understanding of factors contributing to stress or growth.

Direct Cardiac Reprogramming in the Age of Computational Biology.

Heart disease continues to be one of the most fatal conditions worldwide. This is in part due to the maladaptive remodeling process by which ischemic cardiac tissue is replaced with a fibrotic scar. Direct cardiac reprogramming presents a unique solution for restoring injured cardiac tissue through the direct conversion of fibroblasts into induced cardiomyocytes, bypassing the transition through a pluripotent state. Since its inception in 2010, direct cardiac reprogramming using the transcription factors Gata4, Mef2c, and Tbx5 has revolutionized the field of cardiac regenerative medicine. Just over a decade later, the field has rapidly evolved through the expansion of identified molecular and genetic factors that can be used to optimize reprogramming efficiency. The integration of computational tools into the study of direct cardiac reprogramming has been critical to this progress. Advancements in transcriptomics, epigenetics, proteomics, genome editing, and machine learning have not only enhanced our understanding of the underlying mechanisms driving this cell fate transition, but have also driven innovations that push direct cardiac reprogramming closer to clinical application. This review article explores how these computational advancements have impacted and continue to shape the field of direct cardiac reprogramming.

The Role of Alexithymia and Moral Disengagement in Childhood Physical Abuse and Depressive Symptoms: A Comparative Study Among Rural and Urban Chinese College Students.

There is robust evidence indicating the adverse association between childhood abuse and depressive symptoms. However, the ways in which childhood physical abuse is indirectly associated with adulthood depressive symptoms by alexithymia and moral disengagement remain poorly understood, particularly in the context of China. The present study aims to investigate how childhood physical abuse may be associated with depressive symptoms via the serial mediation effects of alexithymia and moral disengagement among college students in China. A total of 686 college students (female: 53.2%) aged from 17 to 28 years old (M = 21.33; SD = 2.53) were recruited from mainland China to participate in an online survey assessing the variables of interest. Structural equation modeling and multiple group analysis were performed using Mplus 7.0 to investigate the hypothesized model. College students' experiences with childhood physical abuse was significantly associated with their depressive symptoms. This relationship was partially mediated by alexithymia and then by moral disengagement. Meanwhile, alexithymia and moral disengagement had a chain mediating effect on childhood physical abuse and depressive symptoms. Furthermore, multigroup analysis revealed that the association between alexithymia and depressive symptoms was stronger among rural students compared to urban students. Furthermore, the mediation model involving moral disengagement applies exclusively to rural students. Alexithymia and moral disengagement exerted serial mediating effect on the association between childhood physical abuse and depressive symptoms. This pattern was particularly pronounced among rural students. These findings underscore the importance of addressing both childhood adversity and maladaptive cognitive processes in the prevention and treatment of depression.

Brain Age Gap in Early Illness Schizophrenia and the Clinical High-Risk Syndrome: Associations With Experiential Negative Symptoms and Conversion to Psychosis.

Brain development/aging is not uniform across individuals, spawning efforts to characterize brain age from a biological perspective to model the effects of disease and maladaptive life processes on the brain. The brain age gap represents the discrepancy between estimated brain biological age and chronological age (in this case, based on structural magnetic resonance imaging, MRI). Structural MRI studies report an increased brain age gap (biological age > chronological age) in schizophrenia, with a greater brain age gap related to greater negative symptom severity. Less is known regarding the nature of this gap early in schizophrenia (ESZ), if this gap represents a psychosis conversion biomarker in clinical high-risk (CHR-P) individuals, and how altered brain development and/or aging map onto specific symptom facets. Using structural MRI, we compared the brain age gap among CHR-P (n = 51), ESZ (n = 78), and unaffected comparison participants (UCP; n = 90), and examined associations with CHR-P psychosis conversion (CHR-P converters n = 10; CHR-P non-converters; n = 23) and positive and negative symptoms. ESZ showed a greater brain age gap relative to UCP and CHR-P (Ps < .010). CHR-P individuals who converted to psychosis showed a greater brain age gap (P = .043) relative to CHR-P non-converters. A larger brain age gap in ESZ was associated with increased experiential (P = .008), but not expressive negative symptom severity. Consistent with schizophrenia pathophysiological models positing abnormal brain maturation, results suggest abnormal brain development is present early in psychosis. An increased brain age gap may be especially relevant to motivational and functional deficits in schizophrenia.

Social Dysfunction and Apathy: Transdiagnostic Domains in Late-Life Cognitive Disorders.

Social dysfunction is a maladaptive process of coping, problem solving, and achieving one's goals. A new definition of apathy was cross-linked to social dysfunction, with a reduced goal-directed behavior and social interaction as a separate dimension. We hypothesized that these two neuropsychiatric symptoms may be included in the mild behavioral impairment diagnostic framework, operationalizing and standardizing late-life neuropsychiatric symptom assessment, to improve risk determination of dementia. Social dysfunction and apathy were transdiagnostic and prodromic for late-life cognitive disorders. A transdiagnostic approach could provide a useful mean for a better understanding of apathy and related conditions such as social behavior.

The mediator role of negative and positive automatic thoughts between attachment quality towards significant others and adolescents’ internalizing problems

Previous studies found that the insecure attachment of adolescents towards their mother, father, and peers leads to more internalizing problems and maladaptive cognitive processes (for example, low self-esteem). However, the dynamic between the attachment of adolescents, negative and positive automatic thoughts, and internalizing problems of adolescents is not well understood. The present study proposed and tested a theoretical model in which positive and negative automatic thoughts mediate the relationship between the attachment of adolescents towards their parents and peers and the internalizing problems of adolescents. A clinical sample of adolescents (N=105; mean age = 16.60), diagnosed with internalizing disorders, have filled out the evaluations for this study. All analyses were conducted in RStudio, and the mediation models were tested using Partial Least Square Structural Equation Modeling. Our main results are that positive and negative automatic thoughts mediate the relationship between adolescents’ parents- and peer-related attachment and internalizing problems. The biological sex and age of adolescents did not moderate any of the paths in the model. Parents and peer attachment, along with positive and negative automatic thoughts, explained 57 % of the variance in the internalizing problems of adolescents. The main findings of the paper are discussed, and the main caveats are underlined.

Molecular Pathway Changes Associated with Different Post-Conditioning Exercise Interventions After Experimental TBI.

Traumatic brain injury (TBI) causes complex, time-dependent molecular and cellular responses, which include adaptive changes that promote repair and recovery, as well as maladaptive processes such as chronic inflammation that contribute to chronic neurodegeneration and neurological dysfunction. Hormesis is a well-established biological phenomenon in which exposure to low-dose toxins or stressors results in protective responses to subsequent higher-level stressors or insults. Hormetic stimuli show a characteristic U-shaped or inverted J-shaped dose-response curve, as well as being time and exposure-frequency dependent, similar to pre-conditioning and post-conditioning actions. Voluntary exercise interventions, before or after injury, appear to follow these general hormetic principles. But the molecular alterations associated with exercise interventions or more general hormetic responses have received only limited attention. In this study, we used a well-characterized mouse TBI model to assess the effects of different post-conditioning exercise-intervention paradigms on diverse molecular pathways, including neuroinflammation regulators, and post-traumatic neurological deficits. We generated high-throughput gene expression data and associated molecular pathway analyses to assess the potential molecular mechanisms associated with time- and duration-dependent voluntary exercise intervention, as well as time after treatment. Importantly, we also used newer analytical methods to more broadly assess the impact of exercise on diverse molecular pathways. TBI caused long-term changes in multiple neuroinflammation markers and chronic cognitive dysfunction. Notably, all delayed, post-conditioning exercise interventions reduced post-traumatic neuroinflammation and/or attenuated the related cognitive changes, albeit with different pathway specificity and effects magnitude. Exercise comprehensively reversed injury-associated effects in the hippocampus across both activated inflammatory and inhibited neuronal pathways, consistent with a return toward the noninjured, homeostatic state. In contrast, the cortex showed a less consistent pattern with more limited attenuation of inflammatory pathway activation and an amplification in the injury-dependent inhibition of select noninflammatory pathways, indicating less effective and potentially detrimental responses to exercise. Exercise intervention beginning 2 weeks after injury and lasting 2 weeks was less effective than exercise continuing for 4 weeks. Exercise initiated at a more delayed timepoint of 6 weeks after injury and continuing for 4 weeks was more effective than that during the acute phase. The delayed paradigm was also more effective than exercise initiated at 10 weeks after injury and continuing for 8 weeks, consistent with hormetic responses in other models and species. Overall, our study delineates regional and interventional parameters, as well as related molecular pathway changes, associated with post-conditioning exercise treatment, which may help inform future translational interventional strategies.

Integrated Long Noncoding RNA and Messenger RNA Expression Analysis Identifies Molecules Specifically Associated With Resiliency and Susceptibility to Depression and Antidepressant Response

BackgroundDepression involves maladaptive processes impairing an individual’s ability to interface with the environment appropriately. Long noncoding RNAs (lncRNAs) are gaining traction for their role in higher-order brain functioning. Recently, we reported that lncRNA coexpression modules may underlie abnormal responses to stress in rats showing depression-like behavior. The current study explored the global expression regulation of lncRNAs and messenger RNAs (mRNAs) in the hippocampus of rats showing susceptibility (learned helplessness [LH]) or resiliency (non-LH) to depression and fluoxetine response to LH (LH+FLX). MethodsMultiple comparison analysis was performed with an analysis of variance via the aov and summary function in the R platform to identify the differential expression of mRNAs and lncRNAs among LH, non-LH, tested control, and LH+FLX groups. Weighted gene coexpression network analysis was used to identify distinctive modules and pathways associated with each phenotype. A machine learning analysis was conducted to screen the critical target genes. Based on the combined analysis, the regulatory effects of lncRNAs on mRNA expression were explored. ResultsMultiple comparison analyses revealed differentially expressed mRNAs and lncRNAs with each phenotype. Integrated bioinformatics analysis identified novel transcripts, specific modules, and regulatory pairs of mRNA-lncRNA in each phenotype. In addition, the machine learning approach predicted lncRNA-regulated Spp2 and Olr25 genes in developing LH behavior, whereas joint analysis of mRNA-lncRNA pairs identified Mboat7, Lmod1, Il18, and Rfx5 genes in depression-like behavior and Adam6 and Tpra1 in antidepressant response. ConclusionsThe study shows a novel role for lncRNAs in the development of specific depression phenotypes and in identifying newer targets for therapeutic development.

Serial Mediation Analysis of Psychological Inflexibility and Daytime Insomnia Rumination in the Relationship Between Dysfunctional Beliefs About Sleep and Insomnia in College Students.

Emerging research suggests that psychological inflexibility may be a factor contributing to the development and maintenance of insomnia. However, less is known about the potential cognitive pathways that may explain this relationship. In this study, we investigated the serial mediating effects of psychological inflexibility and daytime insomnia-related rumination on the association between dysfunctional beliefs and attitudes about sleep (DBAS) and insomnia symptoms. The sample included 490 college students who underwent assessments at two time points over a 1-month period. The results of our mediational tests yielded significant indirect effects, supporting the prediction that psychological inflexibility and daytime insomnia rumination serially mediate the relationship between DBAS and insomnia. The study provides insights into potential mechanisms for insomnia, emphasizing the role of psychological inflexibility in perpetuating maladaptive cognitive processes associated with insomnia. Future researchers should explore other maladaptive responses to insomnia-related concerns and distress, such as worry and safety behaviors, and replicate findings in clinically elevated insomnia samples.

The Role of Speckle Tracking Echocardiography in the Evaluation of Advanced-Heart-Failure Patients.

Health care is currently showing a fall in heart failure (HF) incidence and prevalence, particularly in developed countries, but with only a subset receiving appropriate therapy to protect the heart against maladaptive processes such as fibrosis and hypertrophy. Appropriate markers of advanced HF remain unidentified, which would help in choosing the most suitable therapy and avoid major compliance problems. Speckle tracking echocardiography (STE) is a good choice, being a non-invasive imaging technique which is able to assess cardiac deformation in a variety of conditions. Several multicenter studies and meta-analyses have demonstrated the clinical application and accuracy of STE in early and late stages of HF, as well as its association with both left ventricular (LV) filling pressures and myocardial oxygen consumption. Furthermore, STE assists in assessing right ventricular free-wall longitudinal strain (RVFWLS), which is a solid predictor of right ventricle failure (RVF) following LV assist device (LVAD) implantation. However, STE is known for its limitations; despite these, it has been shown to explain symptoms and signs and also to be an accurate prognosticator. The aim of this review is to examine the advantages of STE in the early evaluation of myocardial dysfunction and its correlation with right heart catheterization (RHC) parameters, which should have significant clinical relevance in the management of HF patients.

Aberrant TSC-Rheb axis in Oxytocin receptor+ cells mediate stress-induced anxiety.

Stress is a major risk for the onset of several maladaptive processes including pathological anxiety, a diffuse state of heightened apprehension over anticipated threats1. Pathological anxiety is prevalent in up to 59% of patients with Tuberous Sclerosis complex (TSC)2, a neurodevelopmental disorder (NDD) caused by loss-of-function mutations in genes for Tuberin (Tsc2) and/or Hamartin (Tsc1) that together comprise the eponymous protein complex. Here, we generated cell type-specific heterozygous knockout of Tsc2 in cells expressing oxytocin receptor (OTRCs) to model pathological anxiety-like behaviors observed in TSC patient population. The stress of prolonged social isolation induces a sustained negative affective state that precipitates behavioral avoidance, often by aberrant oxytocin signaling in the limbic forebrain3,4. In response to social isolation, there were striking sex differences in stress susceptibility in conditional heterozygote mice when encountering situations of approach-avoidance conflict. Socially isolated male mutants exhibited behavioral avoidance in anxiogenic environments and sought more social interaction for buffering of stress. In contrast, female mutants developed resilience during social isolation and approached anxiogenic environments, while devaluing social interaction. Systemic and medial prefrontal cortex (mPFC)-specific inhibition of downstream effector of TSC, the integrated stress response (ISR), rescued behavioral approach toward anxiogenic environments and conspecifics in male and female mutant mice respectively. Further, we found that Tsc2 deletion in OTRCs leads to OTR-signaling elicited network suppression, i.e., hypofrontality, in male mPFC, which is relieved by inhibiting the ISR. Our findings present evidence in support of a sexually dimorphic role of prefrontal OTRCs in regulating emotional responses in anxiogenic environments, which goes awry in TSC. Our work has broader implications for developing effective treatments for subtypes of anxiety disorders that are characterized by cell-autonomous ISR and prefrontal network suppression.

Unraveling the Cardiac Matrix: From Diabetes to Heart Failure, Exploring Pathways and Potential Medications.

Myocardial infarction (MI) often leads to heart failure (HF) through acute or chronic maladaptive remodeling processes. This establishes coronary artery disease (CAD) and HF as significant contributors to cardiovascular illness and death. Therefore, treatment strategies for patients with CAD primarily focus on preventing MI and lessening the impact of HF after an MI event. Myocardial fibrosis, characterized by abnormal extracellular matrix (ECM) deposition, is central to cardiac remodeling. Understanding these processes is key to identifying new treatment targets. Recent studies highlight SGLT2 inhibitors (SGLT2i) and GLP-1 receptor agonists (GLP1-RAs) as favorable options in managing type 2 diabetes due to their low hypoglycemic risk and cardiovascular benefits. This review explores inflammation's role in cardiac fibrosis and evaluates emerging anti-diabetic medications' effectiveness, such as SGLT2i, GLP1-RAs, and dipeptidyl peptidase-4 inhibitors (DPP4i), in preventing fibrosis in patients with diabetes post-acute MI. Recent studies were analyzed to identify effective medications in reducing fibrosis risk in these patients. By addressing these areas, we can advance our understanding of the potential benefits of anti-diabetic medications in reducing cardiac fibrosis post-MI and improve patient outcomes in individuals with diabetes at risk of HF.

An examination of the mediating role of maladaptive emotion regulation strategies in the complex relationship between interpersonal needs and suicidal behavior.

Studies have shown that psychological factors, notably interpersonal needs and emotion regulation, play a significant role in suicidal behavior. Interpersonal needs are significant contextual components that affect emotion regulation and contribute to a wide range of dysfunctional behaviors, such as suicidal behavior. It has been postulated that emotion regulation mediates the associations between proximal and distal risk factors of suicidal behavior. The sample consisted of 340 community-dwelling individuals (62.5% women; SD = 0.48) with an age range of 18 through 55 (M = 30.23; SD = 8.54) who completed the interpersonal needs questionnaire, the suicide behaviors questionnaire-revised, and the cognitive emotion regulation questionnaire. The Structural Equation Modeling (SEM) approach was utilized to evaluate a mediation model. The findings indicate that interpersonal needs (i.e., perceived burdensomeness r = .55, p <.01 and thwarted belongingness r = .25, p <.01) and putatively maladaptive cognitive emotion regulation strategies (i.e., self-blame; r = .38, p <.01, catastrophizing; r = .55, p <.01, rumination; r = .40, p <.01, and other blame; r = .44, p <.01) have strong associations with suicidal behavior, and these strategies have a mediating effect on the association between interpersonal needs and suicidal behavior. Our findings show that contextual-interpersonal needs, which underpin suicidal behavior, are significantly influenced by maladaptive emotional processes. Thus, therapeutic outcomes might be enhanced by focusing on the content of the associated cognitions and trying to reduce maladaptive regulatory processes like rumination and catastrophization.

Analysis of the Relationship Between Emotion Regulation Difficulties and Impulsivity and Cognitive/Metacognitive Skills in Adolescents Diagnosed with Major Depressive Disorder.

Major depressive disorder (MDD) is a significant psychiatric disorder among children and adolescents. It is important that the relationship with depression is analyzed in adolescents in which cognitive and metacognitive processes are different from adult individuals. Forty-five patients and 44 healthy controls were included in our study. Participants were administered Difficulties in Emotion Regulation Scale (DERS), Barratt Impulsivity Scale, Behavior Rating Inventory of Executive Function (BRIEF), and Stroop test. When the DERS total scores were evaluated, a statistically significant difference was found between the 2 groups in terms of DERS scores. In the healthy controls, the emotion regulation skills were significantly higher compared with the MDD group. In the Stroop test, particularly in the fifth section, the control group displayed a statistically significant better performance in both total duration and the number of mistakes made compared with the study group. In the BRIEF test a statistically significant difference was found between the control group and the study group in all 3 areas. In order to determine the efficient factors related to the statistical difference between the BRIEF scores, the multiple linear regression analysis was used. It was found that depression scores and Stroop performance influence executive functions. Given that Stoop performance can overlap with executive functions, this outcome was expected. However, the impact of depression scores affecting executive functions is also anticipated, considering that these scores particularly affect attention among the cognitive and maladaptive cognitive processes, such as rumination.

Immunomodulatory Effects of Clozapine: More Than Just a Side Effect in Schizophrenia.

Recent evidence suggests a possible relationship between the immune system and schizophrenia spectrum disorders (SSDs), as neuroinflammation appears to play a role in major psychiatric conditions. Neuroinflammation is as a broad concept representing a physiological protective response to infection or injury, but in some cases, especially if chronic, it may represent an expression of maladaptive processes, potentially driving to clinical dysfunction and neurodegeneration. Several studies are concurrently highlighting the importance of microglia, the resident immune cells of the central nervous system, in a huge number of neurodegenerative diseases, including multiple sclerosis, Alzheimer's and Parkinson's diseases, as well as SSDs. A more fundamental phenomenon of maladaptive coupling of microglia may contribute to the genesis of dysfunctional brain inflammation involved in SSDs, from the onset of their neurophenomenological evolution. Clozapine and other antipsychotic drugs seem to express a provable immunomodulant effect and a more specific action on microglia, while neuroactive steroids and nonsteroidal anti-inflammatory drugs may reduce some SSDs symptoms in add-on therapy. Given these theoretical premises, this article aims to summarize and interpret the available scientific evidence about psychotropic and anti-inflammatory drugs that could express an immunomodulant activity on microglia.

Dynamic reporters for probing real-time activation of human fibroblasts from single cells to populations.

Activation of fibroblasts is pivotal for wound healing; however, persistent activation leads to maladaptive processes and is a hallmark of fibrosis, where disease mechanisms are only partially understood. Human in vitro model systems complement in vivo animal models for both hypothesis testing and drug evaluation to improve the identification of therapeutics relevant to human disease. Despite advances, a challenge remains in understanding the dynamics of human fibroblast responses to complex microenvironment stimuli, motivating the need for more advanced tools to investigate fibrotic mechanisms. This work established approaches for assessing the temporal dynamics of these responses using genetically encoded fluorescent reporters of alpha smooth muscle actin expression, an indicator of fibroblast activation. Specifically, we created a toolset of human lung fibroblast reporter cell lines from different origins (male, female; healthy, idiopathic pulmonary fibrosis) and used three different versions of the reporter with the fluorescent protein modified to exhibit different temporal stabilities, providing temporal resolution of protein expression processes over a range of timescales. Using this toolset, we demonstrated that reporters provide insight into population shifts in response to both mechanical and biochemical cues that are not detectable by traditional end point assessments with differential responses based on cell origin. Furthermore, individual cells can also be tracked over time, with opportunities for comparison to complementary end point measurements. The establishment of this reporter toolset enables dynamic cell investigations that can be translated into more complex synthetic culture environments for elucidating disease mechanisms and evaluating therapeutics for lung fibrosis and other complex biological processes more broadly.

Cardiac Remodeling and Ventricular Pacing: From Genes to Mechanics.

Cardiac remodeling and ventricular pacing represent intertwined phenomena with profound implications for cardiovascular health and therapeutic interventions. This review explores the intricate relationship between cardiac remodeling and ventricular pacing, spanning from the molecular underpinnings to biomechanical alterations. Beginning with an examination of genetic predispositions and cellular signaling pathways, we delve into the mechanisms driving myocardial structural changes and electrical remodeling in response to pacing stimuli. Insights into the dynamic interplay between pacing strategies and adaptive or maladaptive remodeling processes are synthesized, shedding light on the clinical implications for patients with various cardiovascular pathologies. By bridging the gap between basic science discoveries and clinical translation, this review aims to provide a comprehensive understanding of cardiac remodeling in the context of ventricular pacing, paving the way for future advancements in cardiovascular care.