The role of positive facial feedback in the stress response

This study investigated whether the old adage "grin and bear it" has proven value by testing how covert and overt manipulation of facial expression influences affective and physiological responses to stress. One hundred and sixty-nine healthy college students were recruited for a "multitasking study," which involved holding chopsticks in the mouth while simultaneously completing two stressful tasks. Participants were randomly assigned to one of the following conditions per the orientation of the chopsticks in their mouths: no smiling (control), Duchenne smiling, or non-Duchenne smiling. Awareness was also manipulated with one half of participants in each smiling condition specifically told to smile and the other half not (N=55 and 57, respectively). State affect changes were assessed at baseline and after each stress task using a short form of the Profile of Mood States, and change scores for positive and negative affect (average PA and NA during each task minus average baseline PA and NA) were used in an analysis of variance to test whether individuals experienced emotional changes concordant with their condition. Group differences in cardiovascular reactivity were examined using analysis of variance with change scores (average cardiovascular activity (heart rate, pulse, and blood pressure) during each task minus average cardiovascular activity at baseline). Repeated measures analysis of variance was employed with pulse and heart rate time points throughout each recovery period to examine group differences in cardiovascular recovery. In all analyses, the following variables were controlled for based on associations with the relevant cardiovascular DV: age; race; sex; body mass index (BMI); baseline perceived stress; sleep; smoking; alcohol use; exercise; condition adherence; perceived task difficulty; reported task facial muscle fatigue; and perceived task stress. Results indicated that non-aware participants in the smiling conditions (M = -0.32) reported less of a decrease in positive affect during a stressful task than individuals in the neutral group (M = -0.65), F(1, 71) = 4.21, p < 0.05, supporting the facial feedback hypothesis (i.e., smiling buffered the negative impact of stress). Generally, smiling had no consistent impact on the stress reactivity of participants as compared to non-smilers across cardiovascular outcomes and tasks. On the other hand, smiling showed widespread effects on cardiovascular recovery, with the smiling groups, regardless of awareness or type of smile, consistently returning closer to baseline levels of cardiovascular activity at the end of the recovery periods following both stress tasks. Practical implications of this relationship between facial feedback, affect, and the stress response are discussed

Automatic and Effortful Facial Expression Mimicry and Dysphoric Mood

Clinical depression has been widely associated with difficulty building and maintaining healthy social relationships (e.g., Lewinsohn, Mischel, Chaplin, & Barton, 1980; Libet & Lewinsohn, 1973; Segrin, 2000). Although many factors contribute to the development of positive social relationships, successful mimicry of others' facial expressions plays a key role in developing rapport and intimacy with others (Izard, 1989; Keltner & Haidt, 1999, Manstead, 1991), and multiple studies have noted important deficits for adults and children with depression in the ability to accurately mimic positive facial expressions (e.g., Lautzenhiser, 2003; Sloan, Bradley, Dimoulas, & Lang, 2002; Wexler, Levenson, Warrenburg, & Price, 1993). To date, published data has noted clear deficits in automatic facial expression mimicry in this population but has not examined effortful mimicry. The current study aimed to fill this gap in the literature by examining both automatic and effortful facial expression mimicry in individuals reporting dysphoria, a mild form of clinical depression. One hundred thirty-six participants were shown a series of happy, sad, and neutral faces, while electromyography (EMG) recorded automatic muscle response in the corrugator supercilii, zygomaticus major, and orbicularis oculi facial muscles. To assess effortful mimicry, participants were shown the series of images again with explicit instruction to mimic the faces appearing on the screen, while EMG again recorded effortful muscle responses. Associations between dysphoria and automatic and effortful facial expression mimicry were examined. Additionally, change in positive and negative emotions throughout the study, associations between facial expression mimicry and self-reported social functioning, and recognition of images presented in the study were also examined. Results indicated that high dysphoric mood was associated with deficits in automatic and effortful mimicry of happy, sad, and neutral facial expressions. Inaccurate automatic and effortful mimicry of faces was also associated with lower self-reported social support and greater loneliness. Results are discussed in light of current efforts to improve depressive symptoms via social skills training

The Whole is Not the Sum of Its Parts: Specific Types of Positive Affect Influence Sleep Differentially

Given the known detrimental effects of poor sleep on an array of psychological and physical health processes, it is critical to understand the factors that protect sleep, especially during times of stress when sleep particularly suffers. Positive affect (PA) arises as a variable of interest given its known associations with health and health behaviors and its ability to buffer stress. In two studies, we examined which types of PA (distinguished by arousal level and trait/state measurement) were most beneficial for sleep and whether these associations varied depending on the stress context. In Study 1, college students (N = 99) reported on their PA and sleep during the week of a major exam. In Study 2, two weeks of daily PA and sleep data were collected during a period with no examinations in a similar sample of students (N = 83). Results indicated that high trait vigor was tied to better sleep efficiency and quality, especially during high stress. Trait calm was generally unhelpful to sleep, and was related negatively to sleep duration. State calm, on the other hand, interacted with stress in Study 2 to predict more efficient day-to-day sleep on days with higher average stress. These findings illustrate the importance of considering arousal level, affect duration, and stress context in studies of PA and health

Ethanol Pharmacokinetics in Neonates Secondary to Medication Administration

Purpose: Ethanol serves as a solvent and microbial preservative in oral liquid medications and is the second most commonly used solvent in liquid medications following water. Despite widespread use of ethanol in liquid medications for neonates, the pharmacokinetics and toxicity of ethanol in young children are not well described. The aim of the current study is to quantify blood ethanol levels in neonates secondary to oral ethanol containing medications. Methods: Neonates who received either oral phenobarbital (15% ethanol) and/or oral dexamethasone (30% ethanol) per standard of care were eligible for enrollment. A maximum of 6 blood samples per patient (4.5 mL total) were taken over the study period. Blood samples were collected via heel stick at the time of clinical laboratory collections or following a specific collection for study purposes. In addition, blood samples were collected from neonates receiving sublingual buprenorphine (30% ethanol) for neonatal abstinence syndrome from a separate clinical study. Blood ethanol levels were measured using a validated headspace gas chromatography-mass spectrometry method utilizing micro-volume ( ̴100uL) plasma samples. The limit of detection and lower limit of quantification for the assay were 0.1 mg/L and 0.5 mg/L respectively. Results: A total of 39 plasma samples from 15 neonates who were on ethanol containing medications were collected over the study period. Four neonates were exposed to phenobarbital and/or dexamethasone, while eleven neonates were exposed to buprenorphine alone or in combination with phenobarbital. Patients were exposed to an average of 71.6 mg/kg (range 13.1 to 215 mg/kg) of ethanol after a single dose of an ethanol containing medication. Blood ethanol levels were detectable in 98% (38/39) of samples, quantifiable in 67% (26/39) of samples, and ranged from below detection to 85.4 mg/L. Ethanol was rapidly cleared and did not accumulate with current dosing regimens. Conclusion: Ethanol intake secondary to medication administration varied widely. Blood ethanol levels in neonates were low and ethanol was eliminated rapidly after a single dose of oral medications that contained a sizable fraction of ethanol.https://jdc.jefferson.edu/petposters/1000/thumbnail.jp

The association of negative mood with automatic and effortful facial expression mimicry

The natural process of mimicking the facial expressions of others is well established, as are the deficits in this reflexive behavior for individuals with clinical disorders such as depression. This study examines the extent of this deficit in non-clinical individuals with high transient negative mood, and whether it extends to both automatic and effortful emotion expression behavior. One hundred and thirty-six participants were shown happy, sad, and neutral faces, while electromyography (EMG) recorded facial muscle responses. Automatic (reflexive) mimicry was assessed while participants simply viewed facially expressive photographs, while effortful mimicry was monitored when individuals were told to intentionally copy the expressions in the photographs. Results indicated that high levels of negative mood were primarily associated with deficits in effortful mimicry of happy expressions, although some similar evidence was found in automatic mimicry of happy faces. Surprisingly, there were also ties between negative moods and inaccuracies in effortful mimicry of sad expressions (but not automatic mimicry). Inaccurate automatic and effortful mimicry were also tied with lower self-reported social support and greater loneliness. These results indicate that even in healthy individuals, transient and minor changes in negative mood are tied to deficiencies in facial mimicry at both the automatic and effortful level

Efficacy of Tezepelumab in Patients with Severe, Uncontrolled Asthma Across Multiple Clinically Relevant Subgroups in the NAVIGATOR Study

INTRODUCTION: Many patients with severe asthma continue to experience symptoms and exacerbations despite treatment with standard-of-care therapy. In the phase 3 NAVIGATOR study, tezepelumab significantly reduced exacerbations over 52 weeks compared with placebo in patients with severe, uncontrolled asthma. This analysis assessed the efficacy of tezepelumab in reducing asthma exacerbations in various clinically relevant subgroups of patients in NAVIGATOR. METHODS: NAVIGATOR was a phase 3, multicentre, randomized, double-blind, placebo-controlled study. Participants (12-80 years old) with severe, uncontrolled asthma were randomized 1:1 to receive tezepelumab 210 mg or placebo subcutaneously every 4 weeks for 52 weeks. Pre-specified and post hoc analyses were performed to evaluate the annualized asthma exacerbation rate (AAER) over 52 weeks in clinically relevant subgroups of patients defined by baseline patient characteristics, medical history, exacerbation triggers, medication eligibility and medication use before and during the study. RESULTS: Tezepelumab reduced the AAER over 52 weeks compared with placebo across a wide range of patient subgroups assessed. Reductions in exacerbations were similar across subgroups defined by baseline patient characteristics, ranging from 48% (95% confidence interval [CI]: 21, 65) to 60% (95% CI: 44, 71) in subgroups analysed by sex, smoking history and body mass index. Among the asthma-related comorbidity subgroups investigated, patients with aspirin or NSAID sensitivity had the greatest reductions in AAER with tezepelumab compared with placebo (83%; 95% CI: 66, 91). In patients eligible to receive dupilumab, tezepelumab reduced exacerbations compared with placebo by 64% (95% CI: 54, 71). Reductions in the AAER with tezepelumab compared with placebo were also observed irrespective of exacerbation trigger category and the number of asthma controller medications patients were receiving at baseline. CONCLUSION: These findings further support the benefits of tezepelumab in patients with severe, uncontrolled asthma and can help to inform healthcare providers\u27 treatment decisions

The Next PAGE in Understanding Complex Traits: Design for the Analysis of Population Architecture Using Genetics and Epidemiology (PAGE) Study

Genetic studies have identified thousands of variants associated with complex traits. However, most association studies are limited to populations of European descent and a single phenotype. The Population Architecture using Genomics and Epidemiology (PAGE) Study was initiated in 2008 by the National Human Genome Research Institute to investigate the epidemiologic architecture of well-replicated genetic variants associated with complex diseases in several large, ethnically diverse population-based studies. Combining DNA samples and hundreds of phenotypes from multiple cohorts, PAGE is well-suited to address generalization of associations and variability of effects in diverse populations; identify genetic and environmental modifiers; evaluate disease subtypes, intermediate phenotypes, and biomarkers; and investigate associations with novel phenotypes. PAGE investigators harmonize phenotypes across studies where possible and perform coordinated cohort-specific analyses and meta-analyses. PAGE researchers are genotyping thousands of genetic variants in up to 121,000 DNA samples from African-American, white, Hispanic/Latino, Asian/Pacific Islander, and American Indian participants. Initial analyses will focus on single nucleotide polymorphisms (SNPs) associated with obesity, lipids, cardiovascular disease, type 2 diabetes, inflammation, various cancers, and related biomarkers. PAGE SNPs are also assessed for pleiotropy using the “phenome-wide association study” approach, testing each SNP for associations with hundreds of phenotypes. PAGE data will be deposited into the National Center for Biotechnology Information's Database of Genotypes and Phenotypes and made available via a custom browser

Identification of four novel susceptibility loci for oestrogen receptor negative breast cancer

Common variants in 94 loci have been associated with breast cancer including 15 loci with genome-wide significant associations (P<5 × 10−8) with oestrogen receptor (ER)-negative breast cancer and BRCA1-associated breast cancer risk. In this study, to identify new ER-negative susceptibility loci, we performed a meta-analysis of 11 genome-wide association studies (GWAS) consisting of 4,939 ER-negative cases and 14,352 controls, combined with 7,333 ER-negative cases and 42,468 controls and 15,252 BRCA1 mutation carriers genotyped on the iCOGS array. We identify four previously unidentified loci including two loci at 13q22 near KLF5, a 2p23.2 locus near WDR43 and a 2q33 locus near PPIL3 that display genome-wide significant associations with ER-negative breast cancer. In addition, 19 known breast cancer risk loci have genome-wide significant associations and 40 had moderate associations (P<0.05) with ER-negative disease. Using functional and eQTL studies we implicate TRMT61B and WDR43 at 2p23.2 and PPIL3 at 2q33 in ER-negative breast cancer aetiology. All ER-negative loci combined account for ∼11% of familial relative risk for ER-negative disease and may contribute to improved ER-negative and BRCA1 breast cancer risk prediction

The FANCM:p.Arg658* truncating variant is associated with risk of triple-negative breast cancer.

Breast cancer is a common disease partially caused by genetic risk factors. Germline pathogenic variants in DNA repair genes BRCA1, BRCA2, PALB2, ATM, and CHEK2 are associated with breast cancer risk. FANCM, which encodes for a DNA translocase, has been proposed as a breast cancer predisposition gene, with greater effects for the ER-negative and triple-negative breast cancer (TNBC) subtypes. We tested the three recurrent protein-truncating variants FANCM:p.Arg658*, p.Gln1701*, and p.Arg1931* for association with breast cancer risk in 67,112 cases, 53,766 controls, and 26,662 carriers of pathogenic variants of BRCA1 or BRCA2. These three variants were also studied functionally by measuring survival and chromosome fragility in FANCM -/- patient-derived immortalized fibroblasts treated with diepoxybutane or olaparib. We observed that FANCM:p.Arg658* was associated with increased risk of ER-negative disease and TNBC (OR = 2.44, P = 0.034 and OR = 3.79; P = 0.009, respectively). In a country-restricted analysis, we confirmed the associations detected for FANCM:p.Arg658* and found that also FANCM:p.Arg1931* was associated with ER-negative breast cancer risk (OR = 1.96; P = 0.006). The functional results indicated that all three variants were deleterious affecting cell survival and chromosome stability with FANCM:p.Arg658* causing more severe phenotypes. In conclusion, we confirmed that the two rare FANCM deleterious variants p.Arg658* and p.Arg1931* are risk factors for ER-negative and TNBC subtypes. Overall our data suggest that the effect of truncating variants on breast cancer risk may depend on their position in the gene. Cell sensitivity to olaparib exposure, identifies a possible therapeutic option to treat FANCM-associated tumors

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms