scholarly journals Blunted stress reactivity reveals vulnerability to early life adversity in young adults with a family history of alcoholism

Addiction ◽  
2018 ◽  
Vol 114 (5) ◽  
pp. 798-806 ◽  
Author(s):  
William R. Lovallo ◽  
Andrew J. Cohoon ◽  
Ashley Acheson ◽  
Kristen H. Sorocco ◽  
Andrea S. Vincent
Keyword(s):  
Young Adults ◽  
Family History ◽  
Early Life ◽  
Stress Reactivity ◽  
Early Life Adversity ◽  
History Of

scholarly journals 4535 Development of a Mouse Model to study interactions between parental history of alcohol use and early life adversity on behavioral and neurobiological development of offspring

2020 ◽  
Vol 4 (s1) ◽  
pp. 5-5
Author(s):  
Grace Porter ◽  
Juan Morales ◽  
Roslyn Valdespino ◽  
Ashley Acheson ◽  
Jason O’Connor
Keyword(s):  
Working Memory ◽  
Family History ◽  
Social Behavior ◽  
Mouse Model ◽  
Early Life ◽  
Immune Cell ◽  
Ethanol Exposure ◽  
Behavioral Changes ◽  
Early Life Adversity ◽  
History Of

OBJECTIVES/GOALS: Individuals with a family history of alcoholism (FH+) are more likely to develop an alcohol use disorder than those with no such history. Early life adversity has a high coincidence with FH+ making pathogenic studies difficult in clinical studies. Here, we developed a mouse model to study pathogenic mechanisms underlying these risk factors. METHODS/STUDY POPULATION: Male and female C57BL6/J mice were exposed to increasing concentrations of ethanol (3-21%) or water for 15 days prior to breeding. Ethanol was not present during gestation. Offspring were either removed from the home cage and isolated for 3 hours or left undisturbed from postnatal days 1-21. Beginning on PND 56 offspring mice were assessed for clinically relevant behavioral disruptions in social behavior, cognitive working memory, locomotor activity, anxiety-like phenotypes, ethanol preference and binge drinking behavior. In a separate experiment, brains of Cx3cr2+/GFPxCcr2+/RFP mice from ELA or control conditions were collected every 7 days after birth for assessment of neuroinflammation and central immune cell morphology and density. RESULTS/ANTICIPATED RESULTS: Mice with a family history of ethanol exposure and ELA are predicted to exhibit behavioral changes (impaired working memory, reduced social behavior, increased anxiety-like behaviors, increased ethanol consumption) to a greater extent than mice with a family history of ethanol exposure or ELA alone. We expect markers of neuroinflammation (cytokine expression, immune cell activation) to predict the behavioral changes in these mice. DISCUSSION/SIGNIFICANCE OF IMPACT: Alcohol consumption and stressful life events are known environmental precipitants to neuroinflammation, which in turns may predispose individuals to anti-social and risky behavior. A mouse model of these early postnatal conditions will allow basic scientists to unravel the biological underpinnings of the behaviors driven by these factors.

P1000Aetiology and efficacy of atrial fibrillation ablation in young adults

EP Europace ◽  
2020 ◽  
Vol 22 (Supplement_1) ◽  
Author(s):  
R Zhang ◽  
I T Fazmin ◽  
A Porto ◽  
K Divulwewa ◽  
A Reddy ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Young Adults ◽  
Family History ◽  
Sudden Cardiac Death ◽  
Pulmonary Vein ◽  
Cardiac Death ◽  
Univariate Analysis ◽  
Pulmonary Vein Stenosis ◽  
Af Ablation ◽  
History Of

Abstract Introduction Little is known regarding the aetiology or outcome of atrial fibrillation (AF) occurring in young adults. This retrospective analysis was performed to explore the demographics and efficacy of AF ablation in this population. Methods Patients were included who had undergone ≥1 AF ablation under the age of 40 between 2006-2018. Recurrence was defined as return of either documented AF or previous symptoms for >30s following a 3-month blanking period. Initial exploratory co-variates were included in a univariate analysis and those terms with P-value of <0.1 were then used to generate a Cox proportional-hazards multivariate model. Results 124 patients (33.6 ± 4.7 yrs, 77% men), initially presenting with paroxysmal AF (pAF; n = 97) or persistent AF (n = 27), underwent 175 AF ablation procedures. 22.6% (n = 28) also had atrial flutter. Time from symptom onset to first ablation was 50.7 ± 46.2 months. Relevant cardiovascular-related demographics were analysed: hypertension in 8.9% (n = 11); diabetes in 1.6% (n = 2); positive family history of AF in 12.9% (n = 16); and family history of sudden cardiac death in 2.4% (n = 3). Mean CHA2DS2-VASc score was 0.35. Of those patients with documented echocardiogram imaging (n = 91), 26.4% (n = 24) had LA dilatation and 6.6% (n = 6) had LV dysfunction. Patients with LA dilatation underwent more ablations (2.3 ± 0.3) compared to controls (1.5 ± 0.1; p < 0.001). Ablation strategy was pulmonary vein isolation (PVI) only in 67.2% (n = 119), with additional ablation in the remaining: roof line in 18.9% (n = 33); cavotricuspid isthmus line in 13.1% (n = 23); mitral isthmus line in 2.3% (n = 4); superior vena cava isolation in 2.3% (n = 4); complex fractionated atrial electrograms in 14.9% (n = 26). Mean procedure time was 155 ± 41 min, mean ablation time was 1657 ± 991 s and mean fluoroscopy time was 32.6 ± 23.4 min. General anaesthesia was used in 43.4% (n = 76). Complications included femoral haematoma (n = 2), tamponade (n = 1) and pulmonary vein stenosis (n = 2). 90 days of follow-up was available for 137 procedures performed for pAF (n = 105) and persistent AF (n = 32). For pAF, overall recurrence was 61.9% for first ablations and 62.9% overall. Recurrence was 56.3% for persistent AF. Factors significantly associated with increased AF recurrence in univariate analysis were male gender (hazard ratio (HR) 2.3, 95% confidence interval (CI): 1.2-4.4, p = 0.011), hypertension (HR 0.5, CI: 0.2-1.1, p = 0.067), family history of sudden cardiac death (HR 6.8, CI: 1.6-29.0 , p = 0.010) and enlarged LA size (HR 2.2, CI: 1.3-3.6, p = 0.003). In multivariate analysis, the only significant predictor of poor outcome was enlarged LA size (HR 2.0, 95% CI: 1.2-3.5, p = 0.011). Conclusions Young patients with AF may have structurally abnormal hearts, and therefore do not only present with lone AF. LA size may be used as a predictor for success. Surveillance imaging may be useful to detect future structural change, which will be the subject of future prospective studies. Abstract Figure. AF ablation recurrence in young adults

Inflammatory and Epigenetic Pathways for Perinatal Depression

2015 ◽  
Vol 18 (3) ◽  
pp. 331-343 ◽  
Author(s):  
Lindsey Garfield ◽  
Herbert L. Mathews ◽  
Linda Witek Janusek
Keyword(s):  
Early Life ◽  
Infant Health ◽  
Perinatal Depression ◽  
Life Experiences ◽  
Perinatal Period ◽  
Early Life Adversity ◽  
Targeted Interventions ◽  
Increased Risk ◽  
History Of ◽  
The Impact

Depression during the perinatal period is common and can have adverse consequences for women and their children. Yet, the biobehavioral mechanisms underlying perinatal depression are not known. Adverse early life experiences increase the risk for adult depression. One potential mechanism by which this increased risk occurs is epigenetic embedding of inflammatory pathways. The purpose of this article is to propose a conceptual model that explicates the linkage between early life adversity and the risk for maternal depression. The model posits that early life adversity embeds a proinflammatory epigenetic signature (altered DNA methylation) that predisposes vulnerable women to depression during pregnancy and the postpartum period. As proposed, women with a history of early life adversity are more likely to exhibit higher levels of proinflammatory cytokines and lower levels of oxytocin in response to the demands of pregnancy and new motherhood, both of which are associated with the risk for perinatal depression. The model is designed to guide investigations into the biobehavioral basis for perinatal depression, with emphasis upon the impact of early life adversity. Testing this model will provide a better understanding of maternal depressive risk and improve identification of vulnerable women who would benefit from targeted interventions that can reduce the impact of perinatal depression on maternal–infant health.

scholarly journals Early‐Life Adversity and Blunted Stress Reactivity as Predictors of Alcohol and Drug use in Persons With COMT (rs4680) Val158Met Genotypes

2019 ◽  
Vol 43 (7) ◽  
pp. 1519-1527 ◽  
Author(s):  
William R. Lovallo ◽  
Andrew J. Cohoon ◽  
Kristen H. Sorocco ◽  
Andrea S. Vincent ◽  
Ashley Acheson ◽  
...  
Keyword(s):  
Drug Use ◽  
Early Life ◽  
Stress Reactivity ◽  
Early Life Adversity ◽  
Alcohol And Drug Use

scholarly journals Bedside clinical assessment predicts recurrence after hospitalization due to viral lower respiratory tract infection in young children

2019 ◽  
Vol 68 (3) ◽  
pp. 756-761 ◽  
Author(s):  
Maria Arroyo ◽  
Kyle P Salka ◽  
Geovanny F Perez ◽  
Carlos E Rodriguez-Martinez ◽  
Jose A Castro-Rodriguez ◽  
...  
Keyword(s):  
Risk Factors ◽  
Family History ◽  
Tract Infection ◽  
Young Children ◽  
Early Life ◽  
Lower Respiratory Tract ◽  
Individual Risk ◽  
Respiratory Illnesses ◽  
History Of ◽  
Individual Risk Factors

Infants requiring hospitalization due to a viral lower respiratory tract infection (LRTI) have a high risk of developing recurrent respiratory illnesses in early life and asthma beyond childhood. Notably, all validated clinical scales for viral LRTI have focused on predicting acute severity instead of recurrence. We present a novel clinical approach combining individual risk factors with bedside clinical parameters to predict recurrence after viral LRTI hospitalization in young children. A retrospective longitudinal cohort of young children (≤3 years) designed to define clinical predictive factors of recurrent respiratory illnesses within 12 months after hospitalization due to PCR-confirmed viral LRTI. Data collection was through electronic medical record. We included 138 children hospitalized with viral LRTI. Using automatic stepwise logistic model selection, we found that the strongest predictors of recurrence in infants hospitalized for the first time were severe prematurity (≤32 weeks’ gestational age, OR=5.19; 95% CI 1.76 to 15.32; p=0.002) and a clinical score that weighted hypoxemia, subcostal retractions and wheezing (OR=3.33; 95% CI 1.59 to 6.98; p<0.001). After the first hospitalization, the strongest predictors of subsequent episodes were wheezing (OR=5.62; 95% CI 1.03 to 30.62; p=0.04) and family history of asthma (OR=5.39; 95% CI 1.04 to 27.96; p=0.04). We found that integrating individual risk factors (eg, prematurity or family history of asthma) with bedside clinical assessment (eg, wheezing, subcostal retractions or hypoxemia) can predict the risk of recurrence after viral LRTI hospitalization in infants. This strategy may enable clinically oriented subsetting of infants with viral LRTI based on individual predictors for recurrent respiratory illnesses during early life.

scholarly journals 346. Factors Associated with Hypertension in Young Adults with Perinatally-Acquired HIV Infection: a Case–Control Study

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S184-S184
Author(s):  
Patrick O’Neil ◽  
Patrick Ryscavage ◽  
Kristen A Stafford
Keyword(s):  
Risk Factors ◽  
Young Adults ◽  
Family History ◽  
Case Control Study ◽  
Case Control ◽  
Systemic Hypertension ◽  
Early Management ◽  
Factors Associated ◽  
History Of ◽  
Control Study

Abstract Background The incidence of systemic hypertension (HTN) among perinatally-HIV-infected (PHIV) patients appears to increase as they enter adulthood. Among non-perinatally HIV-infected adults both traditional and HIV-associated risk factors have been found to contribute to HTN. Whether these same factors contribute to HTN in PHIV is unknown. The purpose of this study was to determine the socio-demographic, clinical, virologic, and immunologic factors associated with HTN among a cohort of PHIV adolescents and young adults, aged ≥18 years. Methods We conducted a case–control study among a population of 160 PHIV adults with and without HTN who were receiving care at the University of Maryland and aged 18–35 years as of December 31, 2017. Covariates assessed included traditional risk factors such as age, family history of HTN, and smoking, as well as HIV- and antiretroviral-associated covariates. Results We identified 49 HTN cases (30.6%) and 111 (69.4%) controls. There were no significant differences in the odds of most traditional (age, gender, race, family history of HTN, tobacco, alcohol, and/or other drug use) or HIV-associated (CD4 nadir <100 cells/mm3, individual ART exposure, ART interruption) risk factors among PHIV adults with HTN compared with those with no diagnosis of HTN. Cases had lower odds of a history of treatment with lopinavir/ritonavir (LPV/r). Cases had 3.7 (95% CI 1.11, 12.56) times the odds of a prior diagnosis of chronic kidney disease (CKD) compared with controls after controlling for CD4 nadir and ARV treatment history. Conclusion The results of this study suggest that most traditional and HIV-related risk factors do not appear to increase the odds of having HTN in this PHIV cohort. However, HTN among PHIV may be driven in part by CKD, and a focus on the prevention and early management of CKD in this group may be necessary to prevent the development of HTN. Additionally, there may be as yet unidentified risk factors for HTN among PHIV which require further exploration. Given the large and growing population of PHIV entering adulthood worldwide, it is imperative to explore risk factors for and effects of HTN in large, diverse PHIV populations. Disclosures All authors: No reported disclosures.

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