Genetic basis of thermal nociceptive sensitivity and brain weight in a BALB/c reduced complexity cross.

Thermal nociception involves the transmission of temperature-related noxious information from the periphery to the CNS and is a heritable trait that could predict transition to persistent pain. Rodent forward genetics complement human studies by controlling genetic complexity and environmental factors, analysis of end point tissue, and validation of variants on appropriate genetic backgrounds. Reduced complexity crosses between nearly identical inbred substrains with robust trait differences can greatly facilitate unbiased discovery of novel genes and variants. We found BALB/cByJ mice showed enhanced sensitivity on the 53.5°C hot plate and mechanical stimulation in the von Frey test compared to BALB/cJ mice and replicated decreased gross brain weight in BALB/cByJ versus BALB/cJ. We then identified a quantitative trait locus (QTL) on chromosome 13 for hot plate sensitivity (LOD = 10.7; p < 0.001; peak = 56 Mb) and a QTL for brain weight on chromosome 5 (LOD = 8.7; p < 0.001). Expression QTL mapping of brain tissues identified H2afy (56.07 Mb) as the top transcript with the strongest association at the hot plate locus (FDR = 0.0002) and spliceome analysis identified differential exon usage within H2afy associated with the same locus. Whole brain proteomics further supported decreased H2AFY expression could underlie enhanced hot plate sensitivity, and identified ACADS as a candidate for reduced brain weight. To summarize, a BALB/c reduced complexity cross combined with multiple-omics approaches facilitated identification of candidate genes underlying thermal nociception and brain weight. These substrains provide a powerful, reciprocal platform for future validation of candidate variants.

The Potential Role of Preoperative Pain, Catastrophizing, and Differential Gene Expression on Pain Outcomes after Pediatric Spinal Fusion.

BACKGROUND: Adolescent idiopathic scoliosis is one of the most common spinal deformities in children and adolescents requiring extensive surgical intervention. Due to the nature of surgery, spinal fusion increases their risk of experiencing persistent postsurgical pain. Up to 20% of adolescents report pain for months or years after corrective spinal fusion surgery. AIMS: To examine the influence of preoperative psychosocial factors and mRNA expression profiles on persistent postoperative pain in adolescents undergoing corrective spinal fusion surgery. DESIGN: Prospective, longitudinal cohort study. SETTING: Two freestanding academic children's hospitals. METHODS: Utilizing a longitudinal approach, adolescents were evaluated at baseline (preoperatively) and postoperatively at ±1 month and ±4-6 months. Self-report of pain scores, the Pain Catastrophizing Scale-Child, and whole blood for RNA sequencing analysis were obtained at each time point. RESULTS: Of the adolescents enrolled in the study, 36% experienced persistent pain at final postoperative follow-up. The most significant predictors of persistent pain included preoperative pain severity and helplessness. Gene expression analysis identified HLA-DRB3 as having increased expression in children who experienced persistent pain postoperatively, as opposed to those whose pain resolved. A prospective validation study with a larger sample size is needed to confirm these findings. CONCLUSIONS: While adolescent idiopathic scoliosis is not often classified as a painful condition, providers must be cognizant of pre-existing pain and anxiety that may precipitate a negative recovery trajectory. Policy and practice change are essential for early identification and subsequent intervention.

Investigating key predictors of persistent low back pain: A focus on psychological stress.

AIM: To investigate the degree to which psychological stress, self-reported pain scores, and pain sensitivity during an acute state of low back pain (LBP) predict the development of persistent LBP trajectories. BACKGROUND: Identifying which factors influence LBP trajectories is critical to understand why some individuals experience persistent LBP and to illuminate areas for nursing intervention. METHODS: A secondary data analysis of a prospective study examining trajectories of LBP was conducted. The sample was comprised of 217 adults with acute-onset LBP recruited from the community and followed over 24 weeks. Variables of interest included demographic data, perceived stress scores, self-reported pain scores, and somatosensory characteristics collected within the first 4 weeks of LBP onset. The data were analyzed using non-parametric bivariate comparisons and a semi-parametric Cox proportional hazards model with interval-censoring. RESULTS: Individuals with higher psychological stress scores were less likely to experience pain resolution (Hazard ratio [HR] = 0.555, 95% confidence interval [CI] = 0.36-0.85, p = 0.02). After adjustment for covariates in the final model, the analysis revealed household income (HR = 2.79, 95% CI [1.63-4.67], p < 0.001) to be the dominant predictor of LBP persistence in this sample. CONCLUSION: Heightened psychological stress and pain severity as well as decreased pressure pain thresholds were indicated as influential factors of LBP trajectories. Household income was identified as the dominant predictor, demonstrating that individuals with a higher household income were more likely to resolve their pain. Strategies which integrate assessment of stress, self-reported pain scores, pain sensitivity, and social determinants for patients experiencing pain are needed to advance nursing care.

Effects of Physical Activity on Neurophysiological and Gene Expression Profiles in Chronic Back Pain: Study Protocol.

BACKGROUND: Despite the emphasis on exercise to reduce pain and improve function among people with chronic low back pain (cLBP), little is known about the underlying mechanism of the impact of exercise on the neurophysiological and gene transcription alterations that characterize cLBP. OBJECTIVES: To present a study protocol to examine the feasibility, acceptability, and initial efficacy of Problem-Solving Pain to Enhance Living Well (PROPEL) with the support of nurse consultations and wearable activity-tracking technology on self-management (SM) knowledge, skills, physical activity, and pain and to examine the differential neurophysiological and gene expression profiles in cLBP participants from pre- to post-PROPEL. METHODS: A pretest and posttest study is employed on 40 adults ages 18-60 years with cLBP who do not have serious complications and/or comorbidities that affect sensorimotor function. Participants will receive video modules focused on SM and biweekly phone consultations to facilitate symptom monitoring and problem-solving while increasing physical activity frequency and duration. Participants will be assessed for outcomes including SM skills, physical activity, and pain every 2 weeks for 12 weeks. We will examine the participants' differential neurophysiological and gene expression profiles at 12 weeks postintervention and correlate these outcomes with the total duration of physical activity. RESULTS: The study began in September 2018. Of the 99 subjects that were screened, 23 were enrolled and 8 completed data collection. DISCUSSION: Comparing the neurophysiological and gene expression profiles of people with cLBP exposed to PROPEL could inform the development of interventions that offer personalized physical activity dosage along with general SM support. Web-based programs such as PROPEL have the potential to enhance accessibility of evidence-based interventions that improve functionality and quality of life among people living with cLBP.

The Influence of Race, Ethnicity and Genetic Variants on Postoperative Pain Intensity: An Integrative Literature Review.

OBJECTIVES: Chronic postsurgical pain is pain that develops and persists for at least 3 months after a surgical procedure. The purpose of this review was to discover what evidence exists regarding the influence of race and ethnicity on postoperative pain intensity and what evidence exists regarding the influence of genetic polymorphisms on postoperative pain intensity. DESIGN: Integrative literature review. DATA SOURCES: CINAHL, PsychInfo, SCOPUS, and PubMed/Medline databases were searched for entries within the last 10 years. Sources included primary research investigating the relationship among race, ethnicity, and genetics in postoperative pain outcomes. REVIEW/ANALYSIS METHODS: Studies adhered to a strict inclusion and exclusion criteria. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were utilized to evaluate and assess manuscripts for inclusion. RESULTS: Twelve manuscripts were included for final review. There are significantly higher preoperative and postoperative pain intensity scores reported between African American and Hispanic individuals compared with non-Hispanic whites. Although some studies identified that non-Hispanic whites consumed more opioids and reported increased pain, there were no significant differences in opioid requirements in Hispanic and non-Hispanic individuals. COMT and OPRM1 were the most identified genetic polymorphisms associated with postoperative pain intensity. CONCLUSIONS: The literature varies with respect to race, ethnicity, and postoperative pain perception. Perioperative pain intensity has been suggested as a significant predictor of chronic postsurgical pain. COMT and OPRM1 may be associated with higher pain perception after surgical procedures.

Pain self-management plus nurse-led support in young adults with irritable bowel syndrome: Study protocol for a pilot randomized control trial.

Irritable bowel syndrome (IBS) is a functional gut disorder that typically manifests in early adult years. IBS patients report that pain is the most distressing symptom with the greatest impact on quality of life. Pain-sensitivity genes and the gut microbiome may influence severity of symptoms as well as response to self-management (SM) interventions. Based on current understanding of the science of SM, pain neurophysiology, and the gut-brain axis, our team developed a pain SM intervention to be added to evidence-based self-management instruction to increase the individual's SM knowledge and skills (self-efficacy, self-regulation, and goal-setting). The purpose of this randomized controlled longitudinal pilot study is to examine the feasibility, acceptability, and preliminary effectiveness of the IBS-pain SM intervention on IBS-pain SM behaviors and related health outcomes. A sample of 80 young adults (age 18-29 years old) will be recruited and randomly assigned to the experimental or control group. Both groups will receive 10 electronic video modules focused on IBS-pain SM knowledge and skills. The experimental group also will receive nurse-led one-on-one phone consultations to facilitate monitoring and problem-solving. All participants will be followed over 12 weeks. Primary outcomes will be measured at baseline, 6 weeks, and 12 weeks, including IBS-pain SM behaviors, quality of life, and well-being. The influence of pain-sensitivity genes and the gut microbiome on IBS-pain SM behaviors and health outcomes also will be assessed.

FKBP5 genotype and early life stress exposure predict neurobehavioral outcomes for preterm infants.

PROBLEM: This study evaluated the relationship between stressful early life neonatal intensive care unit (NICU) experiences, genetic variation of a stress response-associated gene (FKBP5), and neurobehavioral outcomes. METHOD: The impact of genetic variation and stress experience on neurobehavioral outcomes was examined for 41 preterm infants. Statistical analyses explored the main effects of FKBP5 genotype and NICU stress experience, as well as their interaction on infant neurobehavioral development prior to discharge. RESULTS: Statistical analyses demonstrated a relationship between both FKPB5 genotype and stress related to NICU care that were independently associated with neurobehavioral outcomes; indicating a main effect of genotype and a main effect of stress on neurodevelopment. Additionally, we found an interaction between the minor allele genotype and NICU stress potentially associated with less favorable developmental progress at discharge. IMPLICATIONS: Evidence of genetic and environmental risk factors for neurodevelopmental impairment suggests the need for improved evidence-based practice initiatives to protect those most vulnerable to the combination of genetic susceptibility to stress and medical fragility.

Neurobiological Consequences of Early Painful Experience: Basic Science Findings and Implications for Evidence-Based Practice.

As healthcare teams have worked to improve infant survival rates, the management of painful events experienced by these hospitalized neonates has increased and yet pain management remains highly variable between healthcare institutions. At the same time, emerging evidence suggests that these early painful experiences may alter the trajectory of development for pain-processing pathways both peripherally and centrally. This concise review highlights findings from both the basic and clinical science literature supporting the hypothesis that early painful experiences can have long-lasting negative effects on biological, psychological, and socioemotional functions. Implications for pain management in neonates and considerations for evidence-based practice change are discussed.

UNPACKING THE BURDEN OF CARE FOR INFANTS IN THE NICU.

Infants who begin early life in the medicalized environment of the neonatal intensive care unit (NICU) experience disruption to numerous fundamental expectancies. In the NICU, infants are exposed to chronic, extreme stressors that include painful medical procedures and parental separation. Due to their preverbal stage of development, infants are unable to fully express these experiences, and linking these experiences to long-term outcomes has been difficult. This clinical article proposes the terminology Infant Medical Trauma in the NICU (IMTN) to describe the infant experience. Following a discussion of the NICU as an adverse childhood event, the article has three sections: (a) the unique and critical factors that define the newborn period, (b) a review of the IMTN conceptual model, and (c) recommendations for supportive neuroprotective strategies to moderate the intensity of adverse NICU infant experiences.

Chronic Prostatitis Induces Bladder Hypersensitivity and Sensitizes Bladder Afferents in the Mouse.

PURPOSE: Chronic prostatitis/chronic pelvic pain syndrome causes symptoms that include the frequent and urgent need to urinate, pain or burning during urination and pain radiating to the back, abdomen and/or colorectum. These bladder symptoms suggest that chronic prostatitis/chronic pelvic pain syndrome is associated with sensitization of adjacent organs, termed cross-organ sensitization. The objective of this study was to determine the extent of 1) changes in immunomodulatory mediators in the prostate and bladder after inflammation of the prostate and 2) bladder function and bladder afferent sensitization. MATERIALS AND METHODS: Prostate and bladder histology, immunohistochemistry and expression of immunomodulatory targets were examined weekly after zymosan or vehicle was injected in the dorsal lobe of the mouse prostate. Cystometry, bladder and bladder afferent sensitivity were also assessed weekly. RESULTS: Prostate inflammation induced significant up-regulation in proinflammatory and anti-inflammatory cytokines TNF-α (tumor necrosis factor-α) and IL-10 (interleukin-10), growth factor NGF (nerve growth factor), and T-lymphocyte markers FoxP3, CD4 and CD8 in the prostate and the bladder. Notably, prostatitis significantly increased urinary voiding frequency, induced hypersensitivity to bladder distension and sensitized bladder afferents. We also examined sensory (afferent) co-innervation by injecting retrograde tracers DiI and Fast Blue in the bladder wall and the prostate, respectively. This showed that a significant proportion (approximately 17%) of dorsal root ganglion afferent somata contained tracers from the bladder and the prostate. CONCLUSIONS: These observations support an afferent contribution to chronic prostatitis/chronic pelvic pain syndrome and cross-organ sensitization from prostate to bladder.

Infant Medical Trauma in the Neonatal Intensive Care Unit (IMTN): A Proposed Concept for Science and Practice.

BACKGROUND: Trauma is an innately subjective experience ensuing from a deeply distressing event. Research has demonstrated that while the environment of the neonatal intensive care unit (NICU) is capable of providing extraordinary lifesaving measures following birth, the experience may be disruptive to several key aspects of early development, placing infants at risk for adverse behavioral, cognitive, and emotional outcomes. PURPOSE: This article provides rationale for the concept of Infant Medical Trauma in the NICU (IMTN) as a means of describing this unique stress experience. A triad of cumulative early life NICU experiences (stress, parental separation, and pain) is proposed to influence an infant's swinging neurodevelopmental pendulum amid the potential outcomes of risk and resilience. IMPLICATIONS FOR PRACTICE AND RESEARCH: Creating language that describes the infant experience brings meaning and calls caregivers and parents to action to consider strategies that may improve long-term health. Actively seeking opportunities to decrease the allostatic load of at-risk infants may support an infant's pendulum to swing toward a path of resilience, thereby moderating his or her early life adverse experience.

Chlorogenic Acid Oxidation and Its Reaction with Sunflower Proteins to Form Green-Colored Complexes.

Sunflower seeds are used to produce oil for human consumption, but its protein meal by-product has long been used as animal feed. Formation of green-colored complexes through oxidized chlorogenic acid(CGA)-protein interactions is a primary reason why defatted sunflower protein has not been widely utilized by the food industry. Sunflower protein possesses many properties that make it an appealing alternative protein source from both a marketing and formulation perspective, including its low cost, absence of major allergens, low antitrypsin inhibitors, and its status as both vegan and "clean" label friendly. With the global demand for sunflower oil and novel protein sources expected to increase and waste recovery a concern for many, providing uses for the sunflower meal and its fiber and polyphenol components would provide added value to by-products from sunflower oil processing. This review addresses the unique green pigmentation associated with the interaction of sunflower protein and oxidized CGA by outlining the sunflower oil and protein meal market, CGA reactions contributing to greening, methods for CGA extraction, and the effect of processing on sunflower protein quality and the greening reaction. This review also addresses potential food applications of sunflower protein-based ingredients, such as addition of texturized protein to food products; a microencapsulation matrix for antioxidants; edible, flexible biodegradable films; and even use of sunflower butter as an alternative to peanut butter where the green color is not considered undesirable. Continued studies are needed to make sunflower-based products and CGA-extraction processes available across the global marketplace.

Effect of written emotional disclosure on secondary hyperalgesia in women with trauma history.

OBJECTIVE: This study investigated the effects of written emotional disclosure on a model of chronic pain in healthy women with and without trauma history. METHOD: Participants were prescreened for their trauma history (N = 78) and randomized to a disclosure or a control writing condition. Pain testing occurred either 1 day or 1 month after disclosure. Capsaicin was applied to the forearm to evoke spontaneous burning pain at the application site and mechanical secondary hyperalgesia in the surrounding untreated skin. RESULTS: As hypothesized, the effect of disclosure on the area and intensity of secondary hyperalgesia depended on trauma history and time of testing (F(1,69) ≥ 7.37, p = .008). Disclosure increased secondary hyperalgesia in participants with trauma history compared with those without trauma when testing occurred 1 day after writing (F(1,69) ≥ 5.27, p ≤ .025), whereas the opposite pattern was observed 1 month later (F(1,69) ≥ 4.88, p ≤ .031). Of the participants with trauma history in the disclosure condition, secondary hyperalgesia was reduced at 1 month compared with 1 day after writing (p = .001). Moreover, greater use of positive emotional words predicted reduced secondary hyperalgesia at 1 month (ß = -0.71, p = .022). In contrast, disclosure had no effect on spontaneous pain. CONCLUSIONS: Disclosure modulates secondary hyperalgesia observed in women with trauma history, producing a short-term enhancement and a long-term reduction. This suggests that disclosure has a long-term protective effect that reduces sensitization of pain, which may explain the therapeutic effects of disclosure in patients with chronic pain.

COMT Variants are Associated With Breast and Nipple Pain.

Estimates suggest that only 24.9% of infants born in 2019 were exclusively breastfed before 6 months of age, despite the known health benefits of exclusive breastfeeding. Breast and nipple pain is one of the primary determinants of exclusive breastfeeding. Environmental contributions to breastfeeding success have been reported extensively in the literature, but the contribution(s) of maternal genetics has yet to be discovered. The purpose of the study was to identify an association between pain and lactation-related gene variants with exclusive breastfeeding determinants. We selected 4 genes having single nucleotide polymorphisms (SNPs) with potential functional significance in breastfeeding and pain: prolactin receptor (PRLR), oxytocin receptor (OXTR), catechol-O-methyltransferase (COMT), and milk fat globule epidermal growth factor and factor V/VIII domain containing (MFGE8). We performed a cross-sectional secondary analysis of a longitudinal randomized controlled trial study, Promoting Self-Management of Breast and Nipple Pain with Biomarkers and Technology for Breastfeeding Women (NCT05262920). Breast and nipple pain, perceived insufficient milk, and breastfeeding self-efficacy were examined using total scale scores for the Brief Pain Inventory, Visual Analog Scale, H&H Lactation Scale, and the Breastfeeding Self-efficacy Scale-short form, respectively. Of the candidate genes examined, SNPs within COMT were significantly associated with breastfeeding-related outcomes. Specifically, COMT rs4633 and rs4680 minor allele carriers (T, A) reported higher breast and nipple pain intensity than women homozygous for the major allele (C, G). COMT is the most widely researched "pain gene" and has been linked to cold, postoperative, and postpartum pain. This study is the first to identify a contribution of COMT variants to breast and nipple pain and, as a result, to breastfeeding exclusivity. PERSPECTIVE: Two SNPs in the pain gene COMT are associated with breast and nipple pain. Clinically, a minor allele in COMT rs4633 and rs4680 may increase a woman's rating of moderate breast and nipple pain. TRIAL REGISTRATION: PROMPT was registered in ClinicalTrials.gov (protocol #NCT05262920).

Identification of Arginine-Vasopressin Receptor 1a (Avpr1a/Avpr1a) as a Novel Candidate Gene for Chronic Visceral Pain Sheds Light on the Potential Role of Enteric Neurons in the Development of Visceral Hypersensitivity.

Chronic abdominal pain in the absence of ongoing disease is the hallmark of disorders of gut-brain interaction (DGBIs), including irritable bowel syndrome (IBS). While the etiology of DGBIs remains poorly understood, there is evidence that both genetic and environmental factors play a role. In this study, we report the identification and validation of arginine-vasopressin receptor 1A (Avpr1a) as a novel candidate gene for visceral hypersensitivity (VH), a primary peripheral mechanism underlying abdominal pain in DGBI/IBS. Comparing 2 C57BL/6 (BL/6) substrains (C57BL/6NTac and C57BL/6J) revealed differential susceptibility to the development of chronic VH following intrarectal zymosan instillation, a validated preclinical model for postinflammatory IBS. Using whole-genome sequencing, we identified a single-nucleotide polymorphism differentiating the 2 strains in the 5' intergenic region upstream of Avpr1a, encoding the protein Avpr1a. We used behavioral, histological, and molecular approaches to identify distal colon-specific gene expression and neuronal hyperresponsiveness covarying with Avpr1a genotype and VH susceptibility. While the 2 BL/6 substrains did not differ across other gastrointestinal phenotypes (eg, fecal water retention), VH-susceptible BL/6NTac mice had higher colonic Avpr1a mRNA and protein expression. These results parallel findings that patients' colonic Avpr1a mRNA expression corresponded to higher pain ratings. Moreover, neurons of the enteric nervous system were hyperresponsive to the Avpr1a agonist arginine-vasopressin, suggesting a role for enteric neurons in the pathology underlying VH. Taken together, these findings implicate differential regulation of Avpr1a as a novel mechanism of VH susceptibility as well as a potential therapeutic target specific to VH. PERSPECTIVE: This article presents evidence of Avpr1a as a novel candidate gene for VH in a mouse model of IBS. Avpr1a genotype and/or tissue-specific expression represents a potential biomarker for chronic abdominal pain susceptibility.

Spinal cord injury-induced neurogenic bowel: A role for host-microbiome interactions in bowel pain and dysfunction.

Background and aims: Spinal cord injury (SCI) affects roughly 300,000 Americans with 17,000 new cases added annually. In addition to paralysis, 60% of people with SCI develop neurogenic bowel (NB), a syndrome characterized by slow colonic transit, constipation, and chronic abdominal pain. The knowledge gap surrounding NB mechanisms after SCI means that interventions are primarily symptom-focused and largely ineffective. The goal of the present studies was to identify mechanism(s) that initiate and maintain NB after SCI as a critical first step in the development of evidence-based, novel therapeutic treatment options. Methods: Following spinal contusion injury at T9, we observed alterations in bowel structure and function reflecting key clinical features of NB. We then leveraged tissue-specific whole transcriptome analyses (RNAseq) and fecal 16S rRNA amplicon sequencing in combination with histological, molecular, and functional (Ca2+ imaging) approaches to identify potential mechanism(s) underlying the generation of the NB phenotype. Results: In agreement with prior reports focused on SCI-induced changes in the skin, we observed a rapid and persistent increase in expression of calcitonin gene-related peptide (CGRP) expression in the colon. This is suggestive of a neurogenic inflammation-like process engaged by antidromic activity of below-level primary afferents following SCI. CGRP has been shown to disrupt colon homeostasis and negatively affect peristalsis and colon function. As predicted, contusion SCI resulted in increased colonic transit time, expansion of lymphatic nodules, colonic structural and genomic damage, and disruption of the inner, sterile intestinal mucus layer corresponding to increased CGRP expression in the colon. Gut microbiome colonization significantly shifted over 28 days leading to the increase in Anaeroplasma, a pathogenic, gram-negative microbe. Moreover, colon specific vagal afferents and enteric neurons were hyperresponsive after SCI to different agonists including fecal supernatants. Conclusions: Our data suggest that SCI results in overexpression of colonic CGRP which could alter colon structure and function. Neurogenic inflammatory-like processes and gut microbiome dysbiosis can also sensitize vagal afferents, providing a mechanism for visceral pain despite the loss of normal sensation post-SCI. These data may shed light on novel therapeutic interventions targeting this process to prevent NB development in patients.

Genetic basis of pain variability: recent advances.

An estimated 15-50% of the population experiences pain at any given time, at great personal and societal cost. Pain is the most common reason patients seek medical attention, and there is a high degree of individual variability in reporting the incidence and severity of symptoms. Research suggests that pain sensitivity and risk for chronic pain are complex heritable traits of polygenic origin. Animal studies and candidate gene testing in humans have provided some progress in understanding the heritability of pain, but the application of the genome-wide association methodology offers a new tool for further elucidating the genetic contributions to normal pain responding and pain in clinical populations. Although the determination of the genetics of pain is still in its infancy, it is clear that a number of genes play a critical role in determining pain sensitivity or susceptibility to chronic pain. This review presents an update of the most recent findings that associate genetic variation with variability in pain and an overview of the candidate genes with the highest translational potential.

Genetic Variation, Stress, and Physiological Stress Response in Adults With Food Allergy or Celiac Disease.

BACKGROUND: Persistently high chronic stress can lead to maladaptive psychological, behavioral, and physiological stress responses and poor mental and physical health, highlighting the importance of identifying individuals at increased risk. Chronic health condition diagnosis and genetics are 2 characteristics that can influence stress, stress response, and health outcomes. PURPOSE: Food allergy (FA) and celiac disease (CD) require constant vigilance in daily life and can lead to increased stress. The purpose of this exploratory analysis was to examine the association of variants in selected stress-related genes with stress exposures, stress, clinical measures of physiological stress response, and mental health symptoms in adults with and without FA or CD. METHODS: We compared stress exposures, symptoms of PTSD, depression, anxiety, and stress, BMI, and waist-hip ratio between cases and controls. We analyzed the association of SNPs in genes with known or hypothesized associations with stress-related measures in 124 cases and 124 matched controls: CRHBP (rs7718461, rs10474485), CRHR1 (rs242940) and OXTR (rs2268490). For this exploratory study, p-values ≤ 0.10 were considered suggestive. RESULTS: For cases and controls, rs7718461 was associated with stress symptoms, rs2268490 with symptoms of stress and PTSD, and rs242940 with symptoms of stress, PTSD, anxiety, and depression. Further analyses found that stress-related outcomes in individuals with FA or CD may be influenced by SNP genotype. CONCLUSIONS: Given these suggestive findings, larger prospective studies should examine similar relationships in individuals with other chronic health conditions, incorporating factors such as environmental exposures, individual experiences, and epigenetic modifications.

Physician Perception of the Importance of Medical Genetics and Genomics in Medical Education and Clinical Practice.

PURPOSE: The objective of this study was to determine physician perceptions regarding the importance of and comfort with the use of medical genetics and genomics in medical education and practice, as well as physician expectations for medical trainees. METHODS: A retrospective survey was sent to physicians employed by a health system associated with a public medical school to assess their perceived training in medical genetics and genomics and their comfort level with ordering genetic testing. METHODS: Despite reporting formal genetics training in medical schools, clinicians' comfort with and knowledge in this content area does not meet personal expectations of competency. Though physicians report some discomfort with the use of medical genetics and genomics, the majority also believe that its impact on practice will increase in the next five years. Survey recipients were also asked about their expectations for preparation in the same domains for medical students and incoming residents. The surveyed physicians expect a high level of competency for medical students and incoming residents. METHODS: Our study revealed that practicing physicians feel current medical curricula do not produce physicians with the necessary competency in medical genetics and genomics. This is despite physicians' perceived importance of this domain in medical practice. Our findings suggest a need for re-evaluation of medical genetics and genomics education at all levels of training.