Reciprocal Association Research Articles

Which comes first? Modeling the longitudinal association between mindfulness and neuroticism

Mindfulness-based interventions have been found to mitigate neuroticism. However, the temporal order of these relationships in non-clinical individuals without mindfulness training remains unclear. This four-wave longitudinal study examined whether within-person changes in mindfulness precede or follow changes in neuroticism in a large sample of Chinese college students (Wave 1: Mage = 21.12 ± 1.45, 60.7% female, N = 1074). Using a random intercept cross-lagged panel model, we found a reciprocal association between mindfulness and neuroticism at the within-person level, which corroborated the dynamic personality theories. Changes in mindfulness were negatively correlated with subsequent changes in neuroticism (B = −0.11, p < .001, β = −0.11 to −0.09); and changes in neuroticism were also negatively correlated with subsequent changes in mindfulness (B = −0.14, p < .001, β = −0.15 to −0.11). At the between-person level, higher neuroticism was correlated with lower mindfulness (r = −0.51, SE = 0.04, p < .001). These findings suggest that RI-CLPM modeling techniques are suitable for interpreting mindfulness and neuroticism associations both at the between- and within-person level.

Does #Tamojunto alter the dynamic between drug use and school violence among youth? Secondary analysis from a large cluster-randomized trial

The present study investigated how intervention might alter the relationship between perpetrating violence and later drug use. A cluster-randomized controlled trial design involving 72 schools (38 intervention, 34 control) and 6390 students attending grades 7 and 8 was employed in Brazil. Drug use and violence were assessed at three points. A random-intercept cross-lagged panel model examined the reciprocal association between drug use and school violence domains across the three data collection waves. For both groups, we found that the cross-lagged effect of perpetration on further drug use in adolescents was stronger than the reverse, but the interrelationship was not statistically significant between #Tamojunto and control schools. The carry-over effects of drug use and violence were also not significantly different between groups. There is a lack of evidence showing that #Tamojunto can modify the dynamics between drug use and school violence across the 21-month period. The direction of the causal effect (i.e., the more perpetration behavior, the more subsequent drug use behavior) is present, but weak in both groups. The trial registration protocol at the national Brazilian Register of Clinical Trials (REBEC) is #RBR-4mnv5g.

Innovation mediating relationship between TQM and performance: cases of industrial certified companies

PurposeThe purpose of this research is to analyze the reciprocal relation between total quality management (TQM) and innovation (product innovation and process innovation) and their impact on operational and financial performance.Design/methodology/approachThe data were obtained from a survey of 205 manufacturing companies. Structural equation modeling (SEM) was performed to evaluate the research model.FindingsThe results reveal that there is a reciprocal relationship between TQM and innovation. Moreover, the findings indicate a significant positive effect of product innovation and process innovation on operational performance and insignificant direct impact of TQM on operational performance. However, this effect is significant when it is mediated through product innovation and process innovation.Research limitations/implicationsThis paper helps practitioners to understand how TQM practices support both product and process innovation and the role of the latter in promoting the implementation of TQM practices and ensuring operational performance.Originality/valueThis study presents an innovative approach since it is among the first research studies that provide empirical evidence to a reciprocal association between TQM and innovation. Additionally, this paper examines the dimensions studied in different aspects. It considered financial performance and operational performance, and with respect to innovation, this dimension was analyzed through two different perspectives, namely product innovation and process innovation. This study is also among the first and few research studies that have studied the mediating effect of innovation.

Assessment of surveillance versus etiologic factors in the reciprocal association between papillary thyroid cancer and breast cancer

BackgroundMutually increased risks for thyroid and breast cancer have been reported, but the contribution of etiologic factors versus increased medical surveillance to these associations is unknown. MethodsLeveraging large-scale US population-based cancer registry data, we used standardized incidence ratios (SIRs) to investigate the reciprocal risks of thyroid and breast cancers among adult females diagnosed with a first primary invasive, non-metastatic breast cancer (N = 652,627) or papillary thyroid cancer (PTC) (N = 92,318) during 2000–2017 who survived ≥1-year. ResultsPTC risk was increased 1.3-fold [N = 1434; SIR = 1.32; 95 % confidence interval (CI) = 1.25–1.39] after breast cancer compared to the general population. PTC risk declined significantly with time since breast cancer (Poisson regression = Ptrend <0.001) and was evident only for tumors ≤2 cm in size. The SIRs for PTC were higher after hormone-receptor (HR)+ (versus HR-) and stage II or III (versus stage 0-I) breast tumors. Breast cancer risk was increased 1.2-fold (N = 2038; SIR = 1.21; CI = 1.16–1.26) after PTC and was constant over time since PTC but was only increased for stage 0-II and HR + breast cancers. ConclusionAlthough some of the patterns by latency, stage and size are consistent with heightened surveillance contributing to the breast-thyroid association, we cannot exclude a role of shared etiology or treatment effects.

Normal and Abnormal Sharp Wave Ripples in the Hippocampal-Entorhinal Cortex System: Implications for Memory Consolidation, Alzheimer's Disease, and Temporal Lobe Epilepsy

The appearance of hippocampal sharp wave ripples (SWRs) is an electrophysiological biomarker for episodic memory encoding and behavioral planning. Disturbed SWRs are considered a sign of neural network dysfunction that may provide insights into the structural connectivity changes associated with cognitive impairment in early-stage Alzheimer's disease (AD) and temporal lobe epilepsy (TLE). SWRs originating from hippocampus have been extensively studied during spatial navigation in rodents, and more recent studies have investigated SWRs in the hippocampal-entorhinal cortex (HPC-EC) system during a variety of other memory-guided behaviors. Understanding how SWR disruption impairs memory function, especially episodic memory, could aid in the development of more efficacious therapeutics for AD and TLE. In this review, we first provide an overview of the reciprocal association between AD and TLE, and then focus on the functions of HPC-EC system SWRs in episodic memory consolidation. It is posited that these waveforms reflect rapid network interactions among excitatory projection neurons and local interneurons and that these waves may contribute to synaptic plasticity underlying memory consolidation. Further, SWRs appear altered or ectopic in AD and TLE. These waveforms may thus provide clues to understanding disease pathogenesis and may even serve as biomarkers for early-stage disease progression and treatment response.

Effects of aerobic exercise on gut microbiota in adolescents with subthreshold mood syndromes and healthy adolescents: A 12-week, randomized controlled trial

BackgroundAnimal and human studies have revealed reciprocal association between exercise and gut-brain axis. However, the clinical evidence from randomized controlled trials (RCT) are still limited to directly assess the effects of aerobic exercise on gut microbiota. To fill this gap, we conducted this 12-week RCT in both groups of adolescents with and without sub-threshold mood symptoms. MethodsA total of 224 adolescents were randomized to the aerobic exercise intervention or psychoeducation-controlled arm. 49 adolescents with subthreshold symptoms and 142 clinically-well adolescents provided the sample for microbiota assessed by metagenomic sequencing. Aerobic exercise of running at the moderate-intensity for 30 min per day, 5 days a week, were conducted for 12 weeks. ResultsAdolescents with subthreshold symptoms had significantly lower beta diversity than clinically-well adolescents in both the exercise intervention and psychoeducation-controlled arms (p<0.05). After intervention, no difference in gut microbiota diversity, phylum, genus, species level abundancies or gut microbial functions were found in both of the symptomatic or non-symptomatic groups. Metagenome-wide association study analysis showed no significant difference in metagenomic linkage groups. LimitationsThe sample size is relatively small. The exercise intensity we employed may be insufficient to result in observable effects on intestinal microbiota. ConclusionWe conclude that a 12-week moderate-intensity aerobic exercise intervention showed no significant beneficial effect on the gut microbiota in clinically-well adolescents as well as in adolescents with subthreshold symptoms. The beta diversity of gut microbiota in adolescents with subthreshold mood syndromes may be impaired when compared with clinically-well adolescents.

The association between obesity and depression in adults: a meta-review

AimsObesity and depression are increasing in prevalence and have become key issues in the public health of the modern day. We performed a meta-review to summarise the association between obesity and depression in adults.MethodA systematic literature search was undertaken on MEDLINE, PsychINFO, EMBASE and Web of Science for systematic reviews (SRs) with or without meta-analyses (MA) on the association between obesity and depression in adults (&gt;18 years) published before 18 September 2018. Any approach to define depressive disorders (e.g. via structured interview or code in medical file) was accepted. Likewise, any method to assess obesity was accepted. Screening, data extraction and quality assessment was completed by two reviewers independently, with a third reviewer to arbitrate any disagreement. AMSTAR 2 tool was used to assess the methodological quality and risk of bias of the pertinent SRs/MAs.ResultAfter duplicate removal, we identified 6007 potentially pertinent citations. Following, title, abstract and full-text screening, 10 studies were included in the review; nine SRs with MAs and one SR. A statistically significant association between obesity and depression was reported in all nine SRs with MAs, with odds ratios ranging from 1.18 (95% CI = 1.11-1.26) to 1.57 (95% CI = 1.53-2.01). Increased severity of obesity (body mass index over 40) was associated with a greater odds of becoming depressed. Odds of developing depression were greater for obese females, compared to obese males, but this difference was not statistically significant. Depression was shown to be a significant risk factor for future obesity in all four relevant MAs with odds ratios ranging from 1.18 (95% CI = 1.13-1.23) to 1.40 (95% CI = 1.14-1.71) . Depressed adolescent females had the highest odds of becoming obese, significantly more so than depressed adolescent males and depressed adults. The quality of the included studies were mixed with five scoring moderate quality, three low quality and two critically low quality.ConclusionThe findings suggest a reciprocal association between depression and obesity, which may be modulated by age and gender. Future research should assess the potential effect of obesity and depression severity more carefully while also exploring the underlying mechanisms. These results warrant the investigation of the effect of obesity or depression intervention on the outcomes of the other.FUNDINGThis research received no financial sponsorship.

Attention deficit and hyperactivity disorder and nocturnal enuresis co-occurrence in the pediatric population: a systematic review and meta-analysis.

Attention deficit and hyperactivity/impulsivity disorder (ADHD) and enuresis are common behavioral disorders in childhood, impacting adolescence and adult life. Enuresis (NE) is an incontinence disorder frequently observed in children with ADHD. The relationship between ADHD and NE has been a matter of debate. We aimed to verify the relationship between ADHD and enuresis and how these conditions can modify each other during development. Using PRISMA guidelines, under the PROSPERO registration number CRD42020208299, we systematically searched the literature and conducted a meta-analysis to answer the following question: how frequent is ADHD and enuresis comorbidity? Twenty-five studies were fully read, and data from seven less heterogeneous case-control studies were pooled to estimate enuresis prevalence comparing ADHD and control samples, whereas six studies were combined to evaluate ADHD frequencies in children with and without enuresis. We found the ADHD rates in children with enuresis are similar to the enuresis rates in the group of children with ADHD. The presence of ADHD and enuresis comorbidity does not seem to play a role in gender distribution and the presence of other comorbidities in comparison to controls. However, enuresis seems to persist for more time in children with ADHD. The selected papers differed in study type, research question, samples, and controls utilized. Our systematic review with meta-analysis supports the reciprocal association between enuresis and ADHD. Further studies are necessary to build more robust evidence.

Pain Intensity Predicts Pain Catastrophizing During the Postpartum Period: A Longitudinal Random Intercept Cross-Lagged Panel Study.

Pain catastrophizing is an important psychological predictor of pain. Recent evidence suggests the relationship between catastrophizing and pain intensity could be bidirectional, but most studies have been conducted on chronic pain patients and using criticized statistical methods. The present study aimed to examine if the relationship between pain intensity and catastrophizing was bidirectional in the context of childbirth. A total of 504 women without chronic pain were recruited on their 32-37 gestational week. They completed measures of catastrophizing and pain intensity on the first encounter and then again at 1, 3, and 6 months postpartum. The temporal relationship between the variables was assessed using a random intercept cross-lagged panel model. The hypothesis of reciprocal association did not receive support, as pain intensity predicted catastrophizing during the postpartum period, but catastrophizing did not show an effect over pain intensity at any moment. Pain intensity predicting catastrophizing is consistent with previous literature, while the lack of effect of catastrophizing over pain intensity is an unexpected result, which may suggest that catastrophizing plays a different role in the postpartum period. These results highlight the importance of timely efforts for pain management during the postpartum period and contribute to the theoretical conceptualization of catastrophizing.

Cardiac-specific experiential avoidance predicts change in general psychological well-being among patients completing cardiac rehabilitation.

Previous studies have shown that experiential avoidance (EA) is associated with physical and psychological well-being in medical and non-medical samples. The aims of the present study were to evaluate the reciprocal association between psychological well-being and EA over time among cardiac rehabilitation (CR) patients with moderately to severely low levels of psychological well-being. Pre-CR data on demographic characteristics, measures of psychological well-being, and cardiac-specific EA were collected from 915 CR patients, as well as post-CR psychological well-being and EA data, from 800 of these patients. A cross-lagged model was estimated to examine the relationship between EA and psychological well-being among patients with moderately to severely low levels of psychological well-being based on questionnaire scores. Both EA and psychological well-being significantly changed during CR and were negatively associated with each other at both pre- and post-CR. Results from cross-lagged structural equation modeling supported a nonreciprocal association between EA and psychological well-being during CR. Pre-CR assessment of EA in patients showing low levels of well-being at the beginning of CR could help to identify patients at risk for worse psychological outcomes. EA could be a promising target of psychological treatments administered during CR.

Reciprocal association of serum Mac-2 binding protein and HDL-cholesterol concentrations

BackgroundMac-2 binding protein (Mac-2BP) is used as a serum biomarker of nonalcoholic steatohepatitis, considered to be a liver phenotype of metabolic syndrome (MetS). In this study, we investigated the serum Mac-2BP concentrations-correlated MetS-related clinical parameters in vivo, and the underlying mechanism in vitro. Materials & methodsWe enrolled 54 healthy Japanese men who underwent health examination at Osaka University Health Care Center in this study. Physical and serum biochemical parameters were obtained from all the subjects. In the cultured HepG2 cells, the effects of interferon (IFN)-γ on the expression of Mac-2BP, apolipoprotein (apo) A-I, and ATP binding cassette transporter A1 (ABCA1) were studied. ResultsSerum Mac-2BP concentrations correlated negatively with HDL-C, and positively with body mass index and systolic blood pressure in univariate analysis. These results suggested the association between Mac-2BP and MetS, although none of these 3 parameters had significant correlation with serum Mac-2BP concentrations in multivariate analysis. In HepG2 cells, IFN-γ stimulation resulted in the increased Mac-2BP and the decreased ABCA1 and apo A-I mRNA concentrations, while Mac-2BP had no effects on ABCA1 and apo A-I concentrations. ConclusionsThe serum Mac-2BP concentrations are negatively correlated with HDL-C concentrations in healthy subjects, as a result of chronic inflammation.

Estimating the relationship between collateral and interest rate: A comparison of methods

This paper uses a variety of estimation methods to explore the empirical relationship between interest rate and collateral requirements in bank loan contracts. Methods that do not allow for endogenous contract terms detect a positive reciprocal association between interest rate and collateral. Methods that allow for endogenous contract terms point to a strong positive effect of interest rate on collateral but the effect of collateral on interest rate is weaker. This highlights the importance of incorporating the endogenous nature of contract terms in empirical work.

Bidirectional association between asthma and otitis media in children

BackgroundThis study explored the reciprocal association between otitis media and asthma in children.MethodsThe 2002–2013 Korean Health Insurance Review and Assessment Service-National Sample Cohort participants < 15 years old were used. In study I, 14,665 asthma patients from 2002 through 2005 were selected. The asthma patients were matched 1:1 with the control I group, and the occurrence of otitis media was followed until 2013. In study II, 27,043 otitis media patients from 2002 through 2005 were selected. The otitis media patients were matched 1:1 with the control II group, and the occurrence of asthma was followed until 2013. Stratified Cox proportional hazard models were used to analyze the hazard ratio (HRs) of asthma for otitis media (study I) and otitis media for asthma (study II).ResultsThe HR for otitis media was 1.46 in asthma patients (95% confidence interval [CI] = 1.40–1.52, P < 0.001). The HR for asthma was 1.43 in otitis media patients (95% confidence interval [CI] = 1.36–1.50, P < 0.001).ConclusionAsthma and otitis media have a bidirectional association in children.

MicroRNA-27b inhibits cell proliferation and invasion in bladder cancer by targeting engrailed-2.

Background: Bladder cancer is considered a malignant tumour characterised by great heterogeneity. Engrailed-2 may be a gene implicated in bladder cancer. Bioinformatics analysis found base pair complementation between microRNA-27b and engrailed-2. The present study aimed to investigate the reciprocal association between microRNA-27b and engrailed-2 in bladder cancer.Methods: The microRNA-27b and the protein of engrailed-2 in the tissues and cells of the bladder were detected. The processes of apoptosis, proliferation, invasion, and migration of tumour cells were evaluated. The co-action between microRNA-27b and engrailed-2 was detected by a luciferase reporter system. Finally, the interaction between microRNA-27b and engrailed-2 was further verified in vivo.Results: The study found that the expression level of microRNA-27b is lower in bladder cancer tissues and cells than that in neighbouring ordinary tissues, whereas the opposite outcome was observed regarding the expression level of engrailed-2. Furthermore, microRNA-27b expression level is not significantly linked to the age of patients with bladder cancer; however, it is significantly associated with the clinicopathological grade of bladder cancer. Notably, engrailed-2 is negatively regulated by microRNA-27b. Transfection with microRNA-27b was associated with a significant reduction in the activity of bladder cancer cells and promoted apoptosis, while engrailed-2 restoration effectively reversed the above effects of microRNA-27b on bladder cancer in vitro and in vivo.Conclusions: In conclusion, engrailed-2 is engaged in the development and process of bladder cancer through the negative mediation of microRNA-27b; additionally, microRNA-27b/engrailed-2 could form a signalling pathway with a significant effect on the process of bladder cancer.

Prevalence of Pseudoexfoliation Syndrome in Patients with Sensorineural Hearing Loss

Background: Pseudoexfoliation syndrome (PEX) is a complex systemic disorder of the extracellular matrix primarily affecting the eye and visceral organs. In this age-related disease fibrillar extracellular material is produced and accumulates in many ocular and extraocular tissues. Objective: To study the prevalence of pseudoexfoliation syndrome among patients with sensorineural hearing loss. Patients and Methods: A cross-sectional study, conducted on 50 patients with sensorineural hearing loss at the departments of Ophthalmology and Otolaryngology of Aswan University Hospital, was performed among patients aged 50 years and older and both sexes were included while patients with a history of acute ear disease, head trauma, long term exposure to heavy noise, intake of ototoxic drugs and chronic suppurative otitis media (cholesteatoma) were excluded. Results: The prevalence of PEX among SNHL patients was estimated in the current study as 36%. The mean age was 61 (±7.1) years and ranged from 50 to 77 years old. The majority of participants (35 patients, 70%) were female. Thirty-three patients (66%) of participants had chronic co-morbidities. Unilateral PEX was represented by 10 patients (55.6%), while bilateral PEX was represented by 8 patients (44.4%). Conclusion: This study establishes the reciprocal association between pseudoexfoliation and sensorineural hearing loss. The main reason for this association remains unclear although the infiltrative nature of PEX can still explain this concurrence.

Prevalence of Pseudoexfoliation Syndrome in Patients with Sensorineural Hearing Loss

Background: Pseudoexfoliation syndrome (PEX) is a complex systemic disorder of the extracellular matrix primarily affecting the eye and visceral organs. In this age-related disease fibrillar extracellular material is produced and accumulates in many ocular and extraocular tissues. Objective: To study the prevalence of pseudoexfoliation syndrome among patients with sensorineural hearing loss. Patients and Methods: A cross-sectional study, conducted on 50 patients with sensorineural hearing loss at the departments of Ophthalmology and Otolaryngology of Aswan University Hospital, was performed among patients aged 50 years and older and both sexes were included while patients with a history of acute ear disease, head trauma, long term exposure to heavy noise, intake of ototoxic drugs and chronic suppurative otitis media (cholesteatoma) were excluded. Results: The prevalence of PEX among SNHL patients was estimated in the current study as 36%. The mean age was 61 (±7.1) years and ranged from 50 to 77 years old. The majority of participants (35 patients, 70%) were female. Thirty-three patients (66%) of participants had chronic co-morbidities. Unilateral PEX was represented by 10 patients (55.6%), while bilateral PEX was represented by 8 patients (44.4%). Conclusion: This study establishes the reciprocal association between pseudoexfoliation and sensorineural hearing loss. The main reason for this association remains unclear although the infiltrative nature of PEX can still explain this concurrence.

Temporal dynamics of the association between financial stress and depressive symptoms throughout the emerging adulthood

BackgroundEmerging adulthood is a life stage with elevated risk for both mental disorders and financial distress. Although a positive link between financial stress and depressive symptoms has been identified, there is a lack of delineation on the temporal dynamics of this link spanning the entire stage of emerging adulthood (roughly ages 18 to 29). MethodsUsing a statistical approach that partitions between-person from within-person variation and based on four waves of data from a college cohort (N = 2,098) throughout emerging adulthood, this study addresses this gap. ResultsLatent growth curve model analyses indicate that the trajectory of financial stress throughout emerging adulthood followed an inverted “U” shape, whereas that of depressive symptoms displayed a linear, decreasing trend. The positive correlations of both intercepts and slopes between financial stress and depressive symptoms indicated a co-development pattern. Classical, cross-lagged panel model analyses (i.e., a model aggregating between-person and within-person variation) demonstrated a reciprocal positive association between financial stress and depressive symptoms across waves. Random intercept, cross-lagged panel model analyses (i.e., a model disaggregating between-person and within-person effects) indicated a unidirectional positive within-person effect from depressive symptoms to financial stress across waves, controlling for between-person effects. LimitationsShared-method and shared-informant variance may inflate the identified associations, and the correlational data precludes casual inferences. ConclusionImproving young adults’ mental well-being, specifically intervening depressive symptoms, could be an avenue for reducing their financial stress. Future research is pressing to examine mechanisms via which depression symptoms manifest as financial stress during transition to adulthood.

Reciprocal Association Between Cognitive Function and Oral Health: A Systematic Review and Meta-Analysis

Increasing evidence suggests that there is a linkage between cognitive function and oral health. However, there are few systematic reviews with meta-analysis have been conducted to evaluate the strength of this association. Moreover, existing studies usually focused on unidirectional associations between cognitive function and oral health; no research has demonstrated this inter-relationship in a longitudinal study. This study aims to systematically assess the magnitude of the bidirectional association between oral health and cognitive decline for studies using longitudinal data. Six international databases were searched up until December 31, 2019. Random-effects pooled Risk Ratios (RRs) with 95% confidence intervals (CIs) were calculated. The grading of recommendations assessment, development, and evaluation (GRADE) system was used to assess the quality of evidence. From 13,251 potentially eligible articles, 54 longitudinal studies were included in the systematic review and 18 were in meta-analysis. Meta-analysis was performed for tooth loss and periodontitis disease. Random effects analysis showed, with statistically low heterogeneity, Risks of cognitive decline included suboptimal dentition (<20 teeth) (RR 1.44, 95% CI 1.03-3.65) and periodontitis diseases (RR 1.48, 95% CI 1.22-1.81). Cognitive decline was a risk factor for tooth loss (RR 1.54, 95% CI 1.23-9.69). The overall quality of evidence, however, was rated as very low. The result of this review highlights that cognitive decline is a risk factor for poor oral health, and older adults with suboptimal oral health appear to have an increased risk of cognitive impairment. More studies with rigorous designs are needed to further examine this association.

Patterns of bi-directional relations across alcohol use, religiosity, and self-control in adolescent girls

Examining predictors of alcohol use among adolescent girls is increasingly important to enhance prevention efforts, given that the gender gap in alcohol use is steadily closing. While both religiosity and self-control have been independently associated with decreased alcohol use, little research has explored 1) whether religiosity and self-control are reciprocally related and 2) whether the reciprocal association between these constructs may indicate different patterns in the development of alcohol use. As such, this study examined whether there are multiple patterns of reciprocal relationships across religiosity, self-control, and alcohol use among adolescent girls. Latent variable mixture modeling was combined with an autoregressive cross-lagged panel model to identify discrete, prototypical patterns of longitudinal associations (i.e., subgroups) across religiosity, self-control, and alcohol use among 2,122 girls ages 13–17. Psychosocial covariates (e.g., conduct problems) were examined as predictors of each subgroup. Two subgroups were identified. Self-control was associated with reduced alcohol use in both the majority (87.56% of the sample) and minority (12.44% of the sample) subgroups, but only the majority subgroup also demonstrated associations between religiosity, self-control, and alcohol use. Religiosity may predict lower alcohol use in a majority of adolescent girls but this association may not be present among all girls, suggesting that there is a qualitative difference in how religiosity is associated with self-control and alcohol use between subgroups. Results also suggest that higher levels of conduct problems may predict which girls are more likely to demonstrate associations between only self-control and alcohol use, and demonstrate no significant associations with religiosity.

Abstract 15023: Junctophilin-2 (JPH2) Interactome in Ventricular Myocytes is Subcellular Compartment-dependent and Subject to Remodeling During Hypertrophy Leading to Heart Failure

Introduction: Junctions between sarco/endoplasmic reticulum (SR/ER) and sarcolemma (SL), where Ca-induced Ca release (CICR) takes place, are important for myocardial contractility. JPH2 is the major SR/SL tether in cardiomyocytes. Hypothesis: JPH2 interacts with diverse proteins depending on its subcellular location. Furthermore, JPH2's distribution and relations with its interactors are subject to remodeling in diseased state. Methods: We studied spontaneously hypertensive rats: 2-3 months (SY, healthy) and ≥ 20 months (SO, in heart failure). We used immunoprecipitation (IP) and global unbiased search (proteomics) to identify JPH2's interactors in cardiomyocytes. We used high-resolution structured illumination microscopy (SIM) followed by deconvolution and object-based segmentation in 3 dimension (OBS3D) to quantify spatial relationships between JPH2 and interactors. Results: Based on proteomics JPH2's interactors are involved in: SR/ER function, vesicular transport, sub-sarcolemma scaffold, ion transporters/channels, intercalated disc (ICD) organization and mitochondrial function. We quantified spatial relationships between JPH2 and 6 interactors representing distinct subcellular compartments: RyR2 (junctional SR), Cav1.2 (t-tubules), dystrophin (peripheral SL), caveolin-3 (caveolae), connexin-43 (ICD), and prohibitin-1 (mitochondria). In SY myocytes, JPH2 clusters are organized along the z-lines and peripheral SL, consistent with close and reciprocal association in JPH2/RyR2 and JPH2/dystrophin. In SO myocytes, JPH2 is dispersed from z-lines but stays close to peripheral SL and clusters to ICD. This leads to reduced proximity between JPH2 and Cav1.2 or RyR2, but closer proximity to connexin-43. Conclusions: In failing heart, a portion of JPH2 shifts from t-tubule/SR junctions (where CICR occurs) to ICDs (where store-operated Ca entry 'SOCE' occurs), likely contributing to dysregulation of intracellular Ca handling.