Maladaptive Responses Research Articles

Mitophagy Unveiled: Exploring the Nexus of Mitochondrial Health and Neuroendocrinopathy.

Mitochondria play a pivotal role in cellular metabolism, energy production, and apoptotic signaling, making mitophagy, the selective degradation of damaged mitochondria, crucial for mitochondrial health. Dysregulation of mitophagy has been implicated in various neuroendocrinopathies, yet the mechanisms linking these processes remain poorly understood. This review aims to explore the intersection between mitophagy and neuroendocrinopathy, addressing the critical gaps in knowledge regarding how mitochondrial dysfunction may contribute to the pathophysiology of neuroendocrine disorders. We conducted a comprehensive literature review of studies published on mitophagy and neuroendocrinopathies, focusing on data that elucidate the pathways involved and the clinical implications of mitochondrial health in neuroendocrine contexts. Our findings indicate that altered mitophagy may lead to the accumulation of dysfunctional mitochondria, contributing to neuroendocrine dysregulation. We present evidence linking impaired mitochondrial clearance to disease models of conditions such as metabolic syndrome, depression, and stress-related disorders, highlighting the potential for therapeutic interventions targeting mitophagy. While significant advances have been made in understanding mitochondrial biology, the direct interplay between mitophagy and neuroendocrinopathies remains underexplored. This review underscores the necessity for further research to elucidate these connections, which may offer novel insights into disease mechanisms and therapeutic strategies for treating maladaptive neuroendocrine responses.

Evaluation of the cell death markers for aberrated cell free DNA release in high altitude pulmonary edema.

The effect of high altitude (HA, altitude >2500 m) can trigger a maladaptive response in unacclimatized individuals, leading to various HA illnesses such as high altitude pulmonary edema (HAPE). The present study investigates circulating cell free (cf) DNA, a minimally invasive biomarker that can elicit a pro-inflammatory response. Our earlier study observed altered cfDNA fragment patterns in HAPE patients and the significant correlation of these patterns with peripheral oxygen saturation levels. However, the unclear release mechanisms of cfDNA in circulation limit its characterization and clinical utility. The present study not only observed a significant increase in cfDNA levels in HAPE patients (27.03 ± 1.37 ng/ml; n = 145) compared to healthy HA sojourners (controls, 14.57 ± 0.74 ng/ml; n = 65) and highlanders (HLs, 15.50 ± 0.8 ng/ml; n = 34) but also assayed the known cell death markers involved in cfDNA release at HA. The study found significantly elevated levels of the apoptotic marker, annexin A5, and secondary necrosis or late apoptotic marker, High mobility group box 1, in HAPE patients. In addition, we observed ahigher oxidative DNA damage marker, 8-hydroxy-2'-deoxyguanosine, in HAPE compared to controls, suggestive of the role of oxidative DNA status in promoting the inflammatory potential of cfDNA fragments and their plausible role in manifesting HAPE pathophysiology. Extensive in vitro future assays can confirm theimmunogenic role of cfDNA fragments that may act as a danger-associated molecular pattern and associate with markers of cellular stresses in HAPE.

Residual post-infarct myocardial inflammation detected by 68Ga-DOTATATE PET/MRI predicts long-term adverse cardiac remodelling

Abstract Background Maladaptive inflammatory responses are associated with adverse cardiac remodelling after myocardial infarction (MI), but clinical methods for detecting residual myocardial inflammation post-MI are lacking. Purpose To investigate somatostatin receptor subtype 2 (SST2) positron emission tomography (PET)/magnetic resonance imaging (MRI) using 68Ga-DOTATATE after MI. Methods In a prospective observational cohort study, infarct-related myocardial inflammation detected by 68Ga-DOTATATE PET at 2wk and 3mo post-MI was compared with MRI characteristics including left ventricular (LV) volumetric changes at 1yr, as well circulating immune cell phenotyping and serum proteomic markers. Patients with a prior history of MI or heart failure were excluded. Histological SST2 expression was assessed in myocardial biopsies. Results 38 participants (mean age 60 [SD 9] years; 84% male) with recent MI were enrolled, of whom 58% had an ST-segment elevation MI. Mean peak Troponin I was 16,665 (range 408 to >25,000) ng/L and mean post-infarct LV ejection fraction was 51 (SD 9) %. 68Ga-DOTATATE maximum standardized uptake values (SUVmax) at 10 (SD 4) days accurately localised infarcted myocardial segments defined by late-gadolinium enhancement MRI (LGE; Fig. 1); were 14.2% higher in akinetic/hypokinetic vs. normo-kinetic segments (p<0.0001); and were correlated both with peak segmental strain (r=0.47, p=0.003) and segmental T1 values (r=0.51, p=0.02). Mean infarct SUVmax was 19.7% lower on repeat PET/MRI after a mean 102 (SD 22) days (p<0.0001), and this change was in keeping with parallel reductions in T2-weighted oedema signal on MRI and serum biomarkers of cardiac injury and systemic inflammation. Residual inflammation assessed by mean infarct SUVmax at 3mo was correlated with ΔLV indexed end-diastolic volume at 369 (SD 14) days, after adjustment for baseline infarct size and other clinical variables (p=0.038). The 3mo:2wk ratio of mean infarct SUVmax was an even stronger predictor of adverse myocardial remodelling (p=0.0025). Circulating SST2+ classical monocytes were correlated with infarct 68Ga-DOTATATE signal (r=0.47, p=0.02), and SST2 was co-expressed with CD68+ macrophages in inflamed myocardial specimens of patients with recent MI and ischaemic heart failure. After statistical feature selection and multiple comparisons adjustments, among the blood markers associated with 3mo:2wk infarct SUVmax was CCL25, a chemokine involved in macrophage recruitment which has been implicated in adverse cardiac remodelling. Conclusions Here, in the first prospective clinical study of serial SST2 PET/MRI after MI, we show that 68Ga-DOTATATE can identify and track resolving infarct-related myocardial inflammation. Moreover, residual inflammation detected by 68Ga-DOTATATE is associated with long-term adverse myocardial remodelling and could provide a potential future imaging biomarker to help stratify high-risk patients for emerging immunomodulatory therapies.Figure 1.68Ga-DOTATATE PET-MRI after MI

Enhanced diagnostic accuracy of cardiovascular magnetic resonance in identifying heart failure with preserved ejection fraction through assessment of right ventricular systolic dysfunction

Abstract Backgrounds Right ventricular maladaptive response to increased afterload affects exercise performance in heart failure with preserved ejection fraction (HFpEF). We investigated its role in the diagnosis of early stage of HFpEF with cardiac magnetic resonance (CMR) and invasive cardiopulmonary exercise testing (iCPET). Methods One hundred forty-five patients with suspected HFpEF were prospectively recruited from two centers and 113 of them completely underwent echocardiography, iCPET, and CMR. The diagnosis of HFpEF was based on the result of iCPET (pulmonary capillary wedge pressure > 15mmHg at resting and >25mmHg at peak exercise). Area under the curve (AUC) was determined by comparing HFpEF with non-HFpEF patients. Results Seventy-two HFpEF (68±10 years) and forty-one non-HFpEF (66±11 years) were identified. The resting pulmonary artery compliance was significantly reduced in HFpEF. CMR right ventricle longitudinal strain and left atrial reservoir strain had the highest diagnostic accuracy (AUCs 0.805 and 0.776, respectively). There is a sex disparity in the diagnosis accuracy of left atrial (LA) reservoir strain, with male patients exhibiting a significantly increased AUC (0.801) compared to females (AUC 0.559). Conclusions Right ventricular systolic dysfunction is an early indicator of HFpEF, accompanied by impaired LA filling. The diminished LA filling may be more prevalent in male patients, suggesting distinct early pathophysiological progressions between genders.

Fathers' rejection sensitivity: Links with fathers' and children's social information processing

AbstractObjectiveJoining efforts to reveal how fathers affect their children's social competence, we examined whether fathers' rejection sensitivity was associated with biases in their children's social information processing. We also explored whether this link was indirect via biases in fathers' social information processing of their children's peer interactions and, in particular, fathers' behavioral responses.BackgroundChildren's social information processing biases predict their social competence and well‐being. Studies have explored how mothers' rejection sensitivity may impact children's social information processing. Yet, little is known about the role of fathers in this context.MethodParticipants were 85 fathers living in Israel (68.24% Jewish; 31.76% Arab) and their kindergarten children (55.29% female; MChild age in months = 68.70, SD = 5.59). Fathers completed the Adult Rejection Sensitivity Questionnaire and reported their attributions, emotions, and likely behaviors in ambiguous hypothetical scenarios that might suggest a rejection of their child by peers using the Peer Rejection Scenarios measure. Children were interviewed using the Social Information Processing Interview–Preschool Version, tapping hypothetical peer interactions.ResultsFathers' rejection sensitivity was indirectly related to children's generation of maladaptive responses to ambiguous peer interactions through fathers' reports of their more negative emotions and overinvolved behavioral responses.ConclusionResults underscore the role of fathers' rejection sensitivity and emotional and behavioral responses in children's social information processing.ImplicationsThe study points to the need to consider paternal rejection sensitivity in research and interventions focused on promoting children's social competence.

Muscle Mass and Glucagon-Like Peptide-1 Receptor Agonists: Adaptive or Maladaptive Response to Weight Loss?

Recent studies have shown that pharmacologic weight loss with glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and combination therapies is approaching magnitudes achieved with surgery. However, as more weight loss is achieved, there is concern for potential adverse effects on muscle quantity, composition, and function. This primer aims to address whether muscle-related changes associated with weight loss treatments such as GLP-1 RAs may be maladaptive (ie, adversely affecting muscle health or function), adaptive (ie, a physiologic response to weight loss maintaining or minimally affecting muscle health or function), or perhaps an enhanced response to weight loss (ie, improved muscle health or function after treatment). Based on contemporary evidence with the addition of studies using magnetic resonance imaging, skeletal muscle changes with GLP-1 RA treatments appear to be adaptive: changes in muscle volume z-score indicate a change in muscle volume that is commensurate with what is expected given aging, disease status, and weight loss achieved, and the improvement in insulin sensitivity and muscle fat infiltration likely contributes to an adaptive process with improved muscle quality, lowering the probability for loss in strength and function. Nevertheless, factors such as older age and prefrailty may influence the selection of appropriate candidates for these therapies because of risk for sarcopenia. Several pharmacologic treatments to maintain or improve muscle mass designed in combination with GLP-1-based therapies are under development. For future development of GLP-1-based therapies (and other therapies) designed for weight loss, as well as for patient-centered treatment optimization, the introduction of more objective and comprehensive ways of assessing muscle health (including accurate and meaningful assessments of muscle quantity, composition, function, mobility, and strength) is important for the substantial numbers of patients who will likely be taking these medications well into the future.

Accumbal Dopamine Responses Are Distinct between Female Rats with Active and Passive Coping Strategies.

There is a gap in existing knowledge of stress-triggered neurochemical and behavioral adaptations in females. This study was designed to explore the short-term consequences of a single social defeat (SD) on accumbal dopamine (DA) dynamics and related behaviors in female Wistar rats. During the SD procedure, rats demonstrated different stress-handling strategies, which were defined as active and passive coping. The "active" subjects expressed a significantly higher level of activity directed toward handling stress experience, while the "passive" ones showed an escalated freezing pattern. Remarkably, these opposite behavioral manifestations were negatively correlated. Twenty-four hours following the SD exposure, decreased immobility latency in the Porsolt test and cognitive augmentation in the new object recognition evaluation were evident, along with an increase in electrically evoked mesolimbic DA release in passive coping rats. Rats exhibiting an active pattern of responses showed insignificant changes in immobility and cognitive performance as well as in evoked mesolimbic DA response. Furthermore, the dynamics of the decline and recovery of DA efflux under the depletion protocol were significantly altered in the passive but not active female rats. Taken together, these data suggest that female rats with a passive coping strategy are more susceptible to developing behavioral and neurochemical alterations within 24 h after stress exposure. This observation may represent both maladaptive and protective responses of an organism on a short timescale.

Molecular Thumbprints: Biological Signatures That Measure Loss of Identity.

Each life is challenged to adapt to an ever-changing environment with integrity-simply put, to maintain identity. We hypothesize that this mission statement of adaptive homeostasis is particularly poignant in an adaptive response, like inflammation. A maladaptive response of unresolved inflammation can seed chronic disease over a lifetime. We propose the concept of a molecular thumbprint: a biological signature of loss of identity as a measure of incomplete return to homeostasis after an inflammatory response. Over time, personal molecular thumbprints can measure dynamic and precise trajectories to chronic inflammatory diseases and further loss of self to cancer. Why is this important? Because the phenotypes and molecular signatures of established complex inflammatory diseases are a far cry from the root of the complex problem, let alone the initial seed. Understanding the science behind key germinating seeds of disease helps to identify molecular factors of susceptibility, resilience, and early dietary or drug intervention. We pilot this hypothesis in a rat colitis model that is well-established for understanding molecular mechanisms of colonic health, disease, and transition of colitis to cancer.

Glucocorticoids induce a maladaptive epithelial stress response to aggravate acute kidney injury.

Acute kidney injury (AKI) is a frequent and challenging clinical condition associated with high morbidity and mortality and represents a common complication in critically ill patients with COVID-19. In AKI, renal tubular epithelial cells (TECs) are a primary site of damage, and recovery from AKI depends on TEC plasticity. However, the molecular mechanisms underlying adaptation and maladaptation of TECs in AKI remain largely unclear. Here, our study of an autopsy cohort of patients with COVID-19 provided evidence that injury of TECs by myoglobin, released as a consequence of rhabdomyolysis, is a major pathophysiological mechanism for AKI in severe COVID-19. Analyses of human kidney biopsies, mouse models of myoglobinuric and gentamicin-induced AKI, and mouse kidney tubuloids showed that TEC injury resulted in activation of the glucocorticoid receptor by endogenous glucocorticoids, which aggravated tubular damage. The detrimental effect of endogenous glucocorticoids on injured TECs was exacerbated by the administration of a widely clinically used synthetic glucocorticoid, dexamethasone, as indicated by experiments in mouse models of myoglobinuric- and folic acid-induced AKI, human and mouse kidney tubuloids, and human kidney slice cultures. Mechanistically, studies in mouse models of AKI, mouse tubuloids, and human kidney slice cultures demonstrated that glucocorticoid receptor signaling in injured TECs orchestrated a maladaptive transcriptional program to hinder DNA repair, amplify injury-induced DNA double-strand break formation, and dampen mTOR activity and mitochondrial bioenergetics. This study identifies glucocorticoid receptor activation as a mechanism of epithelial maladaptation, which is functionally important for AKI.

Senescence suppresses the integrated stress response and activates a stress-remodeled secretory phenotype.

Senescence is a state of indefinite cell-cycle arrest associated with aging, cancer, and age-related diseases. Here, we find that translational deregulation, together with a corresponding maladaptive integrated stress response (ISR), is a hallmark of senescence that desensitizes senescent cells to stress. We present evidence that senescent cells maintain high levels of eIF2α phosphorylation, typical of ISR activation, but translationally repress production of the stress response activating transcription factor 4 (ATF4) by ineffective bypass of the inhibitory upstream open reading frames (uORFs). Surprisingly, ATF4 translation remains inhibited even after acute proteotoxic and amino acid starvation stressors, resulting in a highly diminished stress response. We also find that stress augments the senescence-associated secretory phenotype with sustained remodeling of inflammatory factors expression that is suppressed by non-uORF carrying ATF4 mRNA expression. Our results thus show that senescent cells possess a unique response to stress, which entails an increase in their inflammatory profile.

Sucrose binge-eating and increased anxiety-like behavior in Sprague–Dawley rats exposed to repeated LPS administration followed by chronic mild unpredictable stress

Exposure to persistent mild stress is a frequently encountered chronic challenge in a rapidly evolving society. Depending on various factors including sex, the response to stressors varies and is closely linked to the phenomenon of resilience. Depression and anxiety can be considered maladaptive responses to such stress. In this rat study, we investigated the sex-dependent effects of low-grade systemic inflammation during 1 week in combination with chronic unpredictable mild stress during the following 4 weeks on anxiety-like behavior and episodic feeding behavior. Increased anxiety-like behavior and increased sucrose intake were identified in stressed compared to control animals regardless of sex. Interestingly, two nearly equally distributed subpopulations were found in the stressed groups within each sex at the end of the 5-week protocol of combined stress exposure: the resistant and the susceptible, which were characterized by unchanged and increased sucrose intake, respectively. This difference in susceptibility to protracted combined mild stress and ensuing response to a sucrose eating binge demonstrates the complexity of the underlying regulatory mechanisms associated with emotional hyperreactivity. This model carries the potential for further investigation of the molecular basis of resilience and susceptibility to combined stressors and for testing treatments with potential preventive or therapeutic effects.

Gut Microbiota Mediates Neuroinflammation in Alzheimer's Disease: Unraveling Key Factors and Mechanistic Insights.

The gut microbiota, the complex community of microorganisms that inhabit the gastrointestinal tract, has emerged as a key player in the pathogenesis of neurodegenerative disorders, including Alzheimer's disease (AD). AD is characterized by progressive cognitive decline and neuronal loss, associated with the accumulation of amyloid-β plaques, neurofibrillary tangles, and neuroinflammation in the brain. Increasing evidence suggests that alterations in the composition and function of the gut microbiota, known as dysbiosis, may contribute to the development and progression of AD by modulating neuroinflammation, a chronic and maladaptive immune response in the central nervous system. This review aims to comprehensively analyze the current role of the gut microbiota in regulating neuroinflammation and glial cell function in AD. Its objective is to deepen our understanding of the pathogenesis of AD and to discuss the potential advantages and challenges of using gut microbiota modulation as a novel approach for the diagnosis, treatment, and prevention of AD.

Neurotic Anxiety of Submissive Personalities: A Psychoneurotic Analysis of Mary Dedalus in James Joyce’s A Portrait of the Artist as a Young Man

Motivated by the insights of Karen Horney into submissive and compliant personalities, this study delves into the perpetual vulnerability, fear of helplessness, and isolation portrayed in James Joyce’s A Portrait of the Artist as a Young Man through the lens of psychoneurosis theory. Individuals with obsessive appeasement tendencies experience excessive dependency and restlessness, reinforcing their feelings of helplessness and often resulting in manipulative attachments to powerful figures and self-defeating behaviours. Neurosis amplifies these maladaptive responses, intensifying anxiety stemming from individual, familial, social, or religious fears, thereby significantly impacting social functioning. This study aims to analyse the submissive personality of Mary Dedalus in Joyce’s novel from the three distinct perspectives of need for approval, sense of unsupportedness, and fear of the church. An in-depth exploration of these aspects not only enriches our comprehension of Joyce’s work but also offers valuable insights into the portrayal of neurosis and its impact on human behaviour within a competitive societal framework.

Neural adaptation of the reward system in primary dysmenorrhea.

Introduction: The brain's reward system (RS) reacts differently to pain and its alleviation. This study examined the correlation between RS activity and behavior during both painful and pain-free periods in individuals with primary dysmenorrhea (PDM) to elucidate their varying responses throughout the menstrual cycle. Methods: Ninety-two individuals with PDM and 90 control participants underwent resting-state functional magnetic resonance imaging (rsfMRI) scans during their menstrual and peri-ovulatory phases. Regional homogeneity (ReHo) and amplitude of low-frequency fluctuation (ALFF) analyses were used to evaluate RS responses. Psychological evaluations were conducted using the McGill Pain Questionnaire and the Pain Catastrophizing Scale. Results: ReHo analysis showed higher values in the left putamen and right amygdala of the PDM group during the peri-ovulatory phase compared to the menstrual phase. ALFF analysis revealed lower values in the putamen of the PDM group compared to controls, regardless of phase. ReHo and ALFF values in the putamen, amygdala, and nucleus accumbens were positively correlated with pain scales during menstruation, while ALFF values in the ventral tegmental area inversely correlated with pain intensity. Those with severe PDM (pain intensity ≥7) displayed distinct amygdala ALFF patterns between pain and pain-free phases. PDM participants also had lower ReHo values in the left insula during menstruation, with no direct correlation to pain compared to controls. Discussion: Our study highlights the pivotal role of the RS in dysmenorrhea management, exhibiting varied responses between menstrual discomfort and non-painful periods among individuals with PDM. During menstruation, the RS triggers mechanisms for pain avoidance and cognitive coping strategies, while it transitions to processing rewards during the peri-ovulatory phase. This demonstrates the flexibility of the RS in adapting to the recurring pain experienced by those with PDM.

The Mpox Vaccine Hesitancy Scale for Mpox: Links with Vaccination Intention among Men Who Have Sex with Men in Six Cities of China.

Vaccine hesitancy is a significant barrier to achieving high vaccination rates, particularly among men who have sex with men (MSM), a group at increased risk for Mpox. This study aimed to develop and validate a Mpox vaccine hesitancy scale specifically tailored for Chinese MSM, grounded in the protection motivation theory (PMT). An online survey through snowball sampling was conducted from October 2023 to March 2024, collecting 2403 valid responses across six representative regions in China. Exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) were conducted to evaluate the scale's construct validity, while reliability was assessed using Cronbach's α coefficient. The predictive validity of the scale was analyzed using Receiver Operating Characteristic (ROC) analysis. EFA ultimately retained 22 items in the Mpox vaccination scale and identified four distinct dimensions: Maladaptive Rewards (seven items), Self-efficacy (seven items), Response Efficacy (four items), and Response Costs (four items). These dimensions were confirmed by CFA, which demonstrated satisfactory model fit indices (χ²/df = 4.382, RMSEA = 0.053, SRMR = 0.048, GFI = 0.935, CFI = 0.967, NFI = 0.958, TLI = 0.963, and IFI =0.967). All indices were within acceptable ranges. The scale exhibited good internal consistency, with a Cronbach's alpha of 0.906, and strong content validity, with an S-CVI/Ave of 0.952. The scale's predictive accuracy was evaluated using Receiver Operating Characteristic (ROC) analysis. When used to evaluate the scale's predictive accuracy, it yielded an area under the curve (AUC) of 0.854 after adjustments, indicating good predictive ability between high and low hesitancy. This scale provides a reliable and valid tool for assessing Mpox vaccine hesitancy among MSM and can be used to gauge Mpox vaccination intention within this group.

CERS1 is a biomarker of Staphylococcus aureus abundance and atopic dermatitis severity

BackgroundAtopic dermatitis (AD) is an inflammatory skin condition characterized by widely variable cutaneous Staphylococcus aureus abundance that contributes to disease severity and rapidly responds to type 2 immune blockade (i.e., dupilumab). The molecular mechanisms regulating S. aureus levels between AD subjects remain poorly understood. ObjectiveTo investigate host genes that may be predictive of S. aureus abundance and correspond with AD severity. MethodsData derived from the NIH/NIAID-funded (NCT03389893 [ADRN-09]) randomized, double-blind, and placebo-controlled multicenter study of dupilumab in adults (n=71 subjects) with moderate-severe AD. Bulk RNA-sequencing of skin biopsies (n=57 lesional, 55 non-lesional) was compared to epidermal S. aureus abundance, lipidomics, and AD clinical measures. ResultsS. aureus abundance and ceramide synthase 1 (CERS1) expression positively correlated at baseline across both non-lesional (r=0.29, p=0.030) and lesional (r=0.41, p=0.0015) skin. Lesional CERS1 expression also positively correlated with AD severity (i.e., SCORing AD [SCORAD] r=0.44, p=0.0006) and skin barrier dysfunction (transepidermal water loss area under the curve [TEWL AUC] r=0.31, p=0.025) at baseline. CERS1 expression (forms C18:0-sphingolipids) was negatively associated with elongation of very long chain fatty acids (ELOVL6; C16:0→C18:0) expression and corresponded with a shorter chain length sphingolipid composition. Dupilumab rapidly reduced CERS1 expression (day 7) and ablated the relationship with S. aureus abundance and ELOVL6 expression by day 21. ConclusionCERS1 is a unique molecular biomarker of S. aureus abundance and AD severity that may contribute to dysfunctional skin barrier and shorter chain sphingolipid composition through fatty acid sequestration as a maladaptive compensatory response to reduced ELOVL6.

Mixed-method examination of early maladaptive schemas and coping among children at a child advocacy center.

The present study examined (a) the presence of early maladaptive schemas and coping responses in children who have experienced maltreatment, (b) the relationship between early maladaptive schemas and coping responses, and (c) how qualitative findings compare to previous theoretical structures in quantitative studies. There were 100 participants (Mage = 10.72 years, SD = 3.35; 64 girls, 30 boys, six transgender/nonbinary), with 70% identifying as White. Data were collected in collaboration with a community child advocacy center through forensic interviews in cases of reported child abuse. Early maladaptive schemas were assessed using an adapted version of the Dusseldorf Illustrated Schema Questionnaire for Children. Coping responses were assessed using the COPE Inventory. Information about individual and abuse factors was gathered from case reports. Child advocacy center staff completed the measures based on information obtained during forensic interviews. All assessed early maladaptive schemas were endorsed in this sample; children reported an ability to adapt through the use of socially supported and self-sufficient coping responses. Hierarchical cluster analysis examining word similarity within coded texts demonstrated that subjugation and self-sacrifice were most strongly related. This mixed-method study integrating children's voices contributes a new perspective on early maladaptive schemas and coping responses that can provide education to multidisciplinary teams involved in forensic interviews. However, limits to generalizability must be considered given that the sample was derived from one region in the U.S. Midwest. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Response styles to positive affect during a positive psychology intervention for veterans with PTSD and moral injury: Preliminary results from a moral elevation intervention pilot trial.

Veterans with posttraumatic stress disorder (PTSD) or moral injury are at risk of maladaptive response styles to positive emotions, such as emotional numbing. A potential pathway to target problematic responses to positive affect is a positive psychology intervention that elicits moral elevation-feeling inspired after witnessing someone perform a virtuous act. This study aims to examine responses to positive affect in a pilot trial of a web-based moral elevation intervention titled, MOVED: Moral Elevation Online Intervention for Veterans Experiencing Distress Related to PTSD and Moral Injury. Method: Veterans who reported moral injury distress and probable PTSD were randomized into an intervention or control condition (n = 48). We examined repeated measures data during the trial and focused on three subscales of the Response to Positive Affect Questionnaire: rumination on positive mood and somatic experiences (emotion-focus), rumination on positive aspects of the self and pursuit of relevant goals (self-focus), and efforts to dampen positive moods (dampening). Three multilevel models were fitted with time and condition as predictors and subscale scores as outcomes. Qualitative data reported at intervention sessions was also reviewed and coded based on the three subscales. Veterans in the MOVED condition reported more positive rumination than the control condition for both emotion-focus (b = 2.70, p = .023) and self-focus styles (b = 2.90, p = .003). There was no group difference in the dampening style. Qualitative responses after elevation-eliciting exercises and session-based goals were most frequently coded as including emotion-focused positive rumination, followed by dampening, then self-focused rumination. These results provide preliminary evidence that a moral elevation intervention might contribute to positive responses to positive affect in a sample predisposed to emotional numbing. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Aftercare following second trimester abortion procedures.

The purpose of this review is to examine patient experiences following second-trimester abortion care to identify clinical interventions to improve aftercare. Early validation of a five-question Reproductive Grief Screen suggests that this instrument may be useful for clinicians to identify patients with maladaptive grief responses following a second-trimester abortion. Patients want to talk with their healthcare providers about grief following abortion and desire frequent mental health check-ins. Most people will have breast symptoms following a second-trimester abortion; a one-time dose of cabergoline at time of abortion appears to be an effective intervention to prevent bothersome breast symptoms. As patient desires vary regarding disposition of fetal remains, clinicians should be prepared to discuss donation for research or cremation/ burial as alternatives to routine disposal. With significant variation in availability and cost of ceremonial disposition, clinicians and healthcare systems should identify local resources to facilitate this aspect of aftercare. Clinical practices and healthcare systems should prioritize the aftercare experience including the management of breast symptoms, bereavement, disposition of fetal remains, and follow-up care.

Dysfunctional mechanotransduction regulates the progression of PIK3CA-driven vascular malformations.

Somatic activating mutations in PIK3CA are common drivers of vascular and lymphatic malformations. Despite common biophysical signatures of tissues susceptible to lesion formation, including compliant extracellular matrix and low rates of perfusion, lesions vary in clinical presentation from localized cystic dilatation to diffuse and infiltrative vascular dysplasia. The mechanisms driving the differences in disease severity and variability in clinical presentation and the role of the biophysical microenvironment in potentiating progression are poorly understood. Here, we investigate the role of hemodynamic forces and the biophysical microenvironment in the pathophysiology of vascular malformations, and we identify hemodynamic shear stress and defective endothelial cell mechanotransduction as key regulators of lesion progression. We found that constitutive PI3K activation impaired flow-mediated endothelial cell alignment and barrier function. We show that defective shear stress sensing in PIK3CA E542K endothelial cells is associated with reduced myosin light chain phosphorylation, junctional instability, and defective recruitment of vinculin to cell-cell junctions. Using 3D microfluidic models of the vasculature, we demonstrate that PIK3CA E542K microvessels apply reduced traction forces and are unaffected by flow interruption. We further found that draining transmural flow resulted in increased sprouting and invasion responses in PIK3CA E542K microvessels. Mechanistically, constitutive PI3K activation decreased cellular and nuclear elasticity resulting in defective cellular tensional homeostasis in endothelial cells which may underlie vascular dilation, tissue hyperplasia, and hypersprouting in PIK3CA-driven venous and lymphatic malformations. Together, these results suggest that defective nuclear mechanics, impaired cellular mechanotransduction, and maladaptive hemodynamic responses contribute to the development and progression of PIK3CA-driven vascular malformations.