Juvenile-Type Granulosa Cell Tumor in Pregnancy Presenting as a Ruptured Abdominal Mass.

Introduction: Granulosa cell tumors (GCTs) are part of the sex cord-stromal tumors occurring with a rare incidence rate that only makes up about 2-5% of all ovarian malignancies. Case Presentation: A 28-year-old woman, gravida 2, para 1, presented with a juvenile-type granulosa cell tumor at 31 weeks gestation, which appeared as a rapidly growing mass with rupture. She under-went an exploratory laparotomy with unilateral salpingo-oophorectomy, and consequently had a successful vaginal delivery. Post-operatively she was treated with paclitaxel and carboplatin chemotherapy regimen with no evidence of recurrence after one year. Conclusion: Radical surgical management is recommended for these tumors due to the high recurrence rate, but more conservative surgical options may be considered based on the fertility goals of the patient.

Applications of single-cell RNA sequencing in drug discovery and development.

Single-cell technologies, particularly single-cell RNA sequencing (scRNA-seq) methods, together with associated computational tools and the growing availability of public data resources, are transforming drug discovery and development. New opportunities are emerging in target identification owing to improved disease understanding through cell subtyping, and highly multiplexed functional genomics screens incorporating scRNA-seq are enhancing target credentialling and prioritization. ScRNA-seq is also aiding the selection of relevant preclinical disease models and providing new insights into drug mechanisms of action. In clinical development, scRNA-seq can inform decision-making via improved biomarker identification for patient stratification and more precise monitoring of drug response and disease progression. Here, we illustrate how scRNA-seq methods are being applied in key steps in drug discovery and development, and discuss ongoing challenges for their implementation in the pharmaceutical industry.

The Effect of Clinical Decision Prompts in Improving Human Papillomavirus Vaccination Rates in a Multispecialty Practice in a Predominantly Hispanic Population: Quasi-Experimental Study.

BACKGROUND: The human papillomavirus (HPV) is implicated in the causal pathway of cancers of the vulva, vagina, penis, cervix, anus, and oropharyngeal region. It is the most common sexually transmitted infection in the United States. Despite the documented safety and effectiveness of the HPV vaccine, rates lag behind those of other vaccines given at the same age. OBJECTIVE: Provider recommendation is identified as a robust predictor of HPV vaccine uptake, and physician-prompting is shown to increase the provision of preventive care services in general. Theoretically, providing reminders to providers should increase opportunities for providing HPV vaccine recommendations and therefore affect vaccination rates. The objective of our study was to assess the effectiveness of an electronic medical record (EMR) prompt in improving HPV vaccination rates in an academic clinic setting caring for a predominantly Hispanic border population. METHODS: We used a quasi-experimental design with a retrospective chart audit to evaluate the effect of a clinical decision prompt (CDP) on improving HPV immunization rates in different specialty settings. We introduced an EMR prompt to remind providers to recommend the HPV vaccine when seeing appropriate patients in an obstetrics and gynecology (OBGYN), pediatrics (PD), and family medicine (FM) clinic in a large multispecialty academic group located along the Texas-Mexico border. We assessed HPV vaccination rates in all the departments involved before and after introducing the prompts. Participants included male and female patients between the ages of 9 and 26 years, presenting at the clinics between January 2014 and December 2015. RESULTS: We reviewed over 2800 charts in all 3 clinics. After adjusting for age, ethnicity, race, type of insurance, preferred language, and clinic, the odds of immunization were 92% (P<.001) higher in patients after the prompt implementation of the EMR. In addition, there was an overall statistically significant increase in the overall HPV vaccination completion rates after implementing the CDP (31.96% vs 21.22%; P<.001). Again, OBGYN saw the most significant improvement in vaccination completion rates, with rates at follow-up 66.02% higher than baseline rates (P=.04). PD and FM had somewhat similar but no less impressive improvements (57.7% and 58.36%; P<.001). CONCLUSIONS: Implementing an EMR CDP improved our overall odds of HPV vaccination completion by 92%. We theorize that the decision prompts remind health care providers to discuss or recommend the HPV vaccination during clinical service delivery. CDPs in the EMR help increase HPV vaccination rates in multiple specialties and are a low-cost intervention for improving vaccination rates.

Efficacy of transcutaneous posterior tibial nerve stimulation in functional constipation.

Most children with functional constipation (FC) improve with conventional treatments. However, a proportion of children have poor treatment outcomes. Management of intractable FC may include botulinum toxin injections, transanal irrigation, antegrade enemas, colonic resections, and in some cases sacral nerve stimulation (SNS). SNS is surgically placed, not readily available and expensive. Posterior tibial nerve stimulation (PTNS) allows transmission of electronic impulses and retrograde stimulation to the sacral nerve plexus in a portable, simple and non-invasive fashion. To assess the efficacy and safety of transcutaneous PTNS for the treatment of FC in children. Single-center, prospective interventional study. Children 4-14 years with Rome IV diagnosis of FC received ten daily PTNS (30 min/day) sessions. Electrodes placed over skin of ankle. Strength of stimulus was below pain threshold. Outcomes were assessed during treatment and 7 days after. Twenty-three subjects enrolled. Two children excluded (acute gastroenteritis, COVID-19 contact). Twenty completed the study (4-14 years), (8.4 ± 3.2 years, 71.4% female). We found significant improvement in the consistency of bowel movements (BM) (p = 0.005), fecal incontinence (FI) (p = 0.005), abdominal pain presence (p = < 0.001) and intensity (p = 0.005), and a significant for improvement in blood in stools (p = 0.037). There was 86.3% improvement in abdominal pain. 96.7% reported treatment satisfaction. Only one child required rescue therapy. CONCLUSION: We found significant improvement in stool consistency, FI, abdominal pain, and hematochezia. This suggests that transcutaneous PTNS could be a promising noninvasive treatment for FC in children. Large studies are needed. WHAT IS KNOWN: • Functional constipation is one of the most common disorders in children. • Current management of functional constipation consists of an integrative approach that includes medications, diet and behavioral strategies. WHAT IS NEW: • Posterior tibial nerve stimulation is a novel noninvasive and easy to use therapy that can improve stool consistency, fecal incontinence and blood in stools.

Correction: Cuban history of CRF19 recombinant subtype of HIV-1.

[This corrects the article DOI: 10.1371/journal.ppat.1009786.].

Starting the Conversation About Healthcare Disparities.

Description The Accreditation Council for Graduate Medical Education (ACGME) put forth institutional requirements to implement healthcare disparity education in resident and fellow curricula in an effort to decrease these inequities. Healthcare disparities stem from many different factors. These may include access to care, insurance status, socioeconomic status, health literacy, language barriers, and the way healthcare systems function. These factors may have interactions that lead to poor health outcomes. As researchers and educators, we need to find a way to research these issues in more depth as well as teach these concepts to our resident physicians. Here, we discuss El Paso, Texas, a city located on the United States-Mexico border, which is predominately Latinx. We also discuss increased rates of diabetes, sexually transmitted diseases, and liver, stomach, and cervical cancers. Common obstacles to healthcare include language and literacy barriers, lack of transportation, and lack of healthcare professionals. We outline 4 strategies for change to address these disparities. By implementing these strategies in ACGME education for residents, healthcare disparities in the El Paso community can be addressed and eliminated.

Cuban history of CRF19 recombinant subtype of HIV-1.

CRF19 is a recombinant form of HIV-1 subtypes D, A1 and G, which was first sampled in Cuba in 1999, but was already present there in 1980s. CRF19 was reported almost uniquely in Cuba, where it accounts for ∼25% of new HIV-positive patients and causes rapid progression to AIDS (∼3 years). We analyzed a large data set comprising ∼350 pol and env sequences sampled in Cuba over the last 15 years and ∼350 from Los Alamos database. This data set contained both CRF19 (∼315), and A1, D and G sequences. We performed and combined analyses for the three A1, G and D regions, using fast maximum likelihood approaches, including: (1) phylogeny reconstruction, (2) spatio-temporal analysis of the virus spread, and ancestral character reconstruction for (3) transmission mode and (4) drug resistance mutations (DRMs). We verified these results with a Bayesian approach. This allowed us to acquire new insights on the CRF19 origin and transmission patterns. We showed that CRF19 recombined between 1966 and 1977, most likely in Cuban community stationed in Congo region. We further investigated CRF19 spread on the Cuban province level, and discovered that the epidemic started in 1970s, most probably in Villa Clara, that it was at first carried by heterosexual transmissions, and then quickly spread in the 1980s within the "men having sex with men" (MSM) community, with multiple transmissions back to heterosexuals. The analysis of the transmission patterns of common DRMs found very few resistance transmission clusters. Our results show a very early introduction of CRF19 in Cuba, which could explain its local epidemiological success. Ignited by a major founder event, the epidemic then followed a similar pattern as other subtypes and CRFs in Cuba. The reason for the short time to AIDS remains to be understood and requires specific surveillance, in Cuba and elsewhere.

Heritability of quantitative autism spectrum traits in adults: A family-based study.

Autism spectrum disorder (ASD) comprises a multi-dimensional set of quantitative behavioral traits expressed along a continuum in autistic and neurotypical individuals. ASD diagnosis-a dichotomous trait-is known to be highly heritable and has been used as the phenotype for most ASD genetic studies. But less is known about the heritability of autism spectrum quantitative traits, especially in adults, an important prerequisite for gene discovery. We sought to measure the heritability of many autism-relevant quantitative traits in adults high in autism spectrum traits and their extended family members. Among adults high in autism spectrum traits (n = 158) and their extended family members (n = 245), we calculated univariate and bivariate heritability estimates for 19 autism spectrum traits across several behavioral domains. We found nearly all tested autism spectrum quantitative traits to be significantly heritable (h2  = 0.24-0.79), including overall ASD traits, restricted repetitive behaviors, broader autism phenotype traits, social anxiety, and executive functioning. The degree of shared heritability varied based on method and specificity of the assessment measure. We found high shared heritability for the self-report measures and for most of the informant-report measures, with little shared heritability among performance-based cognition tasks. These findings suggest that many autism spectrum quantitative traits would be good, feasible candidates for future genetics studies, allowing for an increase in the power of autism gene discovery. Our findings suggest that the degree of shared heritability between traits depends on the assessment method (self-report vs. informant-report vs. performance-based tasks), as well as trait-specificity. LAY SUMMARY: We found that the scores from questionnaires and tasks measuring different types of behaviors and abilities related to autism spectrum disorder (ASD) were heritable (strongly influenced by gene variants passed down through a family) among autistic adults and their family members. These findings mean that these scores can be used in future studies interested in identifying specific genes and gene variants that are associated with different behaviors and abilities related with ASD.

Pain Management Strategies in Contemporary Penile Implant Recipients.

PURPOSE OF REVIEW: To review the most recent literature citing opioid-sparing multimodal analgesic strategies used to manage perioperative pain in patients who underwent inflatable penile prosthesis (IPP) surgery and to provide the penile implant surgeon a variety of non-opioid-based pain management strategies for IPP management. RECENT FINDINGS: Interventions performed in the pre-operative, intraoperative, and post-operative arenas have all been shown to effectively lower pain scores and reduce opioid consumption. Certain surgical techniques performed during IPP surgery have helped with post-operative discomfort patients may feel after surgery. Multimodal analgesia (MMA) protocols adopted from other surgical fields and other urologic subspecialties that are implemented in IPP surgery have promising results with regard to post-operative pain control and opioid consumption. Protocols that implement a combination of refined surgical technique and multimodal analgesia offer substantial benefit to patients undergoing IPP surgery. Further work is needed to assess long-term pain control and opioid use in patients that undergo IPP surgery using these innovative strategies.

Computational simulations establish a novel transducer array placement arrangement that extends delivery of therapeutic TTFields to the infratentorium of patients with brainstem gliomas.

BACKGROUND AND PURPOSE: Tumor treating fields (TTFields) are a non-invasive, efficacious treatment modality currently approved for supratentorial glioblastomas. Despite their ability to improve overall survival in supratentorial tumors, the current placement of arrays is limited to the supratentorial head, precluding its use in infratentorial tumors. Infratentorial malignancies are in need of new therapy modalities given their poor prognoses in both children and adults. The aim of this research is to determine whether rearrangement of TTFields may allow for management of infratentorial tumors. MATERIALS AND METHODS: Delivery of TTFields using Novocure's prototype Optune™ device human male head model was simulated based on brain MRIs from patients with brainstem gliomas to develop a novel array layout designed to extend adequate infratentorial coverage. RESULTS: Array placement on the vertex, bilateral posterolateral occiput, and superior-posterior neck achieved intensities above 1.1 V/cm (average 1.7 V/cm; maximum 2.3 V/cm) in the vertical field direction and above 1 V/cm (average 2 V/cm; maximum 2.8 V/cm) in the horizontal field direction of the infratentorium. The calculated field intensity within the simulated tumors were in the therapeutic range and demonstrated the effective delivery of TTFields to the infratentorial brain. CONCLUSIONS: Our findings suggest that rearrangement of the TTFields standard array with placement of electrodes on the vertex, bilateral posterolateral occiput, and superior-posterior neck allows for adequate electric field distribution in the infratentorium that is within the therapeutic range.

Treatment of Urinary Incontinence in Patients With Erectile Dysfunction.

INTRODUCTION: Concurrent urinary incontinence (UI) and erectile dysfunction (ED) can greatly damage a patient's quality of life. Owing to the intertwined anatomy, treatment options for one most certainly have implications on the other. OBJECTIVE: The aim of this review is to characterize and elucidate the treatment patients with postprostatectomy UI undergoing concurrent or subsequent treatment of ED. These principles can be extrapolated to all patients with UI and ED. METHODS: The literature on postprostatectomy UI treatment in the context of concurrent ED was reviewed through a Medline search. Original research using quantitative and qualitative methodologies was considered. RESULTS: The epidemiology, workup, and management of postprostatectomy UI being mindful of ongoing or future ED treatments are the main outcome measures. Owing to the intertwined anatomy, treatment options for UI and ED have implications on the other. It is essential for the surgeon to obtain an understanding of the patient's degree of bother for each process, personal preference on treatment options, and management of expectations. Surgical treatment options include a combination of the artificial urinary sphincter, sling, inflatable penile prosthesis, semi-rigid penile prosthesis, and new techniques such as the Mini-Jupette. The appropriate combinations will be determined by patient factors of dexterity, preference, degree of leakage, history of radiation, and so on. The decision of staged vs dual implant will be largely driven by the surgeons' preference, payor limitations, and comfort level. This issue is particularly challenging in redo cases where we advocate for cuff downsizing or tandem cuff before the transcorporal approach is used with the goal of preserving sexual function. CONCLUSION: The concurrent treatment of ED and UI requires thoughtful workup, meticulous attention to detail, and an armamentarium of surgical skills. It is crucial for the surgeon to understand and manage patient expectations in treating these delicate and difficult pathologies. Ajay D, Mendez MH, Wang R, et al. Treatment of Urinary Incontinence in Patients With Erectile Dysfunction. Sex Med Rev 2021;9:593-604.

Prostatic irradiation-induced sexual dysfunction: a review and multidisciplinary guide to management in the radical radiotherapy era (Part I defining the organ at risk for sexual toxicities).

Prostate cancer is the most common malignancy and the second leading cause of cancer-related death in men. Radiotherapy is a curative option that is administered via external beam radiation, brachytherapy, or in combination. Erectile, ejaculatory and orgasm dysfunction(s) is/are known potential and common toxicities associated with prostate radiotherapy. Our multidisciplinary team of physicians and/or scientists have written a three (3) part comprehensive review of the pathogenesis and management radiation-induced sexual dysfunction. Part I reviews pertinent anatomy associated with normal sexual function and then considers the pathogenesis of prostate radiation-induced sexual toxicities. Next, our team considers the associated radiobiological (including the effects of time, dose and fractionation) and physical (treatment planning and defining a novel Organ at Risk (OAR)) components that should be minded in the context of safe radiation treatment planning. The authors identify an OAR (i.e., the prostatic plexus) and provide suggestions on how to minimize injury to said OAR during the radiation treatment planning process.

Management of Priapism: A Contemporary Review.

INTRODUCTION: Current management of ischemic priapism revolves around 3 principles: resolving the acute event, preserving erectile function, and reducing the risk of future recurrences. Although more conservative management options, such as aspiration, irrigation, and surgical shunts, are effective in many patients, those who are refractory to these interventions or have prolonged priapism may benefit from placement of a penile prosthesis (PP). AIM: To provide a comprehensive overview of priapism management, highlight the current literature on the utility of penile implants for refractory priapism, and provide insight from a high-volume center on surgical decision making and technique. METHODS: A complete review of the current guidelines and associated literature was performed. Associated algorithms were evaluated, and our experience was overlaid on the data present in the literature. MAIN OUTCOME MEASURES: The current management algorithm for priapism was evaluated. Subsequently, the data on acute and delayed PP placement were assessed. Rates of postoperative infection, erectile dysfunction, and patient satisfaction were also examined. RESULTS: Overall, both delayed and early PP implants are associated with higher rates of failure than routine PP implants. In patients with refractory or prolonged priapism, early implantation may be technically easier, with decreased loss of penile length and associated complications. CONCLUSION: Patients should be evaluated on an individual basis and counseled on the risks and benefits of PP implantation in early and delayed time frames. Although there is no definitive evidence at this time regarding the ideal device or timing of implantation, there are well-established pros and cons of malleable vs inflatable prostheses and of acute vs delayed implantation. Mishra K, Loeb A, Bukavina L, et al. Management of Priapism: A Contemporary Review. Sex Med Rev 2020;8:131-139.

A Simulation-Based Workshop to Improve Residents' Collaborative Clinical Practice.

BACKGROUND: The Accreditation Council for Graduate Medical Education expects residents to attain competency in systems-based practice by advocating for quality patient care, working in interprofessional teams, and implementing system solutions to prevent errors. Diabetes in pregnancy was identified as an area for improvement through comprehensive interdisciplinary and interprofessional care. OBJECTIVE: An interdisciplinary and interprofessional workshop was created by 3 regional academic institutions to improve collaborative practice, clinical knowledge, and clinical judgment of residents. METHODS: A workshop consisting of 4 clinical simulation stations for ultrasound assessment, glycemic control, hyperglycemic emergencies, and macrosomia complications was designed to address gaps in quality of care. Workshop participants were residents from 6 programs and students in nursing, pharmacy, and sonography. Attitude and clinical knowledge were measured preworkshop and postworkshop, and at 3-month and 6- to 7-month follow-up. RESULTS: There were increases in average clinical knowledge scores across time points from residents: 56.4% preworkshop, 64.8% postworkshop, 66.0% at 3-month follow-up, and 68.1% at 6- to 7-month follow-up. Additionally, participants reported positive attitudes toward interprofessional education and indicated high overall satisfaction. CONCLUSIONS: Residents demonstrated improved knowledge and attitudes toward interprofessional training after participating in a large-scale simulation workshop focused on the care of patients with diabetes in pregnancy.

Unilateral Labial Edema in a Female Adolescent: A Gynecologic Presentation of Rhabdomyolysis.

BACKGROUND: Rhabdomyolysis can be the result of vigorous physical activity. Typical signs and symptoms at presentation are muscle pain, weakness, or dark colored urine. There is no scientific literature associating rhabdomyolysis with gynecologic signs and symptoms. CASE: We present a case of a 16-year-old girl who presented to our pediatric emergency department with complaints of progressive left vulvar swelling. The patient underwent magnetic resonance imaging, which showed polymyositis in the rectus abdominus, external and internal obliques, and bilateral vastus lateralis muscles. Laboratory evaluation showed elevated liver transaminases, creatine kinase, and myoglobin serum levels. SUMMARY AND CONCLUSION: Exertional rhabdomyolysis is associated with muscular damage after vigorous exercise. This case is an example of a patient with rhabdomyolysis presenting with an unusual external gynecological manifestation, as unilateral labial edema.

Correlates of long-acting reversible contraception versus sterilization use in advanced maternal age.

PURPOSE: To identify correlates associated with choosing long-acting reversible contraception (LARC) over female sterilization (FS) from a subsample of women aged 35 to 44 years in a nationally representative survey. METHODS: We analyzed data from women aged 35 to 44 years from the 2011-2013 National Survey of Family Growth Female Respondent File (n = 1532). Data were analyzed using SAS 9.3 software. All analyses accounted for the complex survey sample design. Multinomial logistic regression was used to identify factors associated with choosing LARC versus FS. A domain analysis was performed focusing on women aged 35 to 44 years. RESULTS: Approximately 90% of the surveyed women had not received counseling or information about birth control in the past 12 months. Factors associated with using an LARC method versus FS were higher level of education, birth outside of the United States, and higher number of lifetime male sexual partners. Factors associated with using FS versus an LARC method were non-Hispanic black race and women who had not had a checkup related to using a birth control method in the last 12 months. CONCLUSIONS: The results of our study suggest that a large proportion of women of advanced maternal age in the United States have not received contraceptive counseling in the past 12 months. Providers should focus on providing comprehensive contraceptive and sterilization counseling to women aged 35 to 44 years, especially those using unreliable, reversible contraception.

Immunohistochemical localization of 3ß-Hydroxysteroid dehydrogenase and progesterone receptors in the ovary and placenta during gestation of the placentotrophic lizard Mabuya sp (Squamata: Scincidae).

In squamates, progesterone (P) plays a key role in the inhibition of uterine mobility during egg retention in oviparous species, and during gestation in viviparous species. The corpus luteum (CL) is the main organ responsible for the production of P; however, in some species, the CL degenerates early and the P needed for gestation maintenance should be produced in other tissues. Mabuya sp (Scincidae) is a viviparous lizard with a prolonged gestation, it produces microlecithal eggs and, consequently, has an obligate placentotrophy related with a highly complex placenta. Its CL degenerates at early stages of gestation and therefore, other sources of P should exist. The aim of this study was to determine and localize by immunohistochemistry the production of P by detection of the enzyme 3ß-Hydroxysteroid dehydrogenase (3ß-HSD) and P receptors (PR) during gestation in the ovary and placenta of Mabuya sp. Positive and negative control sections were used. The ovary of this species localizes 3ß-HSD and PR in the same tissues. The CL of the ovaries of females at early stages of gestation were positive for both molecules, whereas they did not localize from mid gestation to the end of pregnancy. Previtellogenic and vitellogenic follicles labelled for both molecules in the follicular epithelium and thecae. The placenta of Mabuya sp. demonstrated the potential for P production from mid gestation to the end of gestation in the uterine and chorionic tissues. PR were located in the uterine tissues throughout gestation, with a decrease towards its completion. Western blot analysis confirmed the presence of 3ß-HSD mainly in the ovary of early pregnant females and in the placental tissues at mid gestation stages. Therefore, the chorioallantoic placenta of Mabuya sp. has an endocrine function producing the P needed for gestation and replacing the CL from mid gestation to the end of pregnancy.

Contemporary Review of Male and Female Climacturia and Urinary Leakage During Sexual Activities.

INTRODUCTION: Urinary leakage during sexual activity is a prevalent and often distressing condition that is under-addressed despite having a range of reasonable treatment options. AIM: To review the available literature on prevalence, pathophysiology, and treatment of urinary leakage during sexual activities. METHODS: A literature review was performed through PubMed from 1996 to 2017 regarding urinary leakage during sexual activities for men and women including foreplay incontinence, coital incontinence, and climacturia. MAIN OUTCOME MEASURES: To assess various physiologic and social factors of urinary leakage during sexual activities for men and women, treatment options, and their reported outcomes. RESULTS: Urinary leakage during sexual activity is a prevalent condition that is underdiagnosed and undertreated. The pathophysiology of sexual incontinence is very similar between men and women and is influenced by injury to the pelvic and pudendal nerves, pelvic floor and external sphincter incompetence, and detrusor overactivity. There are different treatment options that are effective and should be offered to patients bothered by their symptoms. CONCLUSION: Improved awareness is critical for better addressing the issue of sexual incontinence. There is likely a common pathophysiologic pathway between men and women and many treatment options are effective. However, further study is required to better elucidate this disease process and most effective treatment options. Mendez MH, Sexton SJ, Lentz AC. Contemporary Review of Male and Female Climacturia and Urinary Leakage During Sexual Activities. Sex Med Rev 2018;6:16-28.

The tell-tale heart: physiological reactivity during resolution of ambiguity in youth anxiety.

In the past decade, cognitive biases and physiological arousal have each been proposed as mechanisms through which paediatric anxiety develops and is maintained over time. Preliminary studies have found associations between anxious interpretations of ambiguity, physiological arousal, and avoidance, supporting theories that link cognition, psychophysiology, and behaviour. However, little is known about the relationship between youths' resolutions of ambiguity and physiological arousal during acute stress. Such information may have important clinical implications for use of verbal self-regulation strategies and cognitive restructuring during treatments for paediatric anxiety. In this brief report, we present findings suggesting that anxious, but not typically developing, youth select avoidant goals via non-threatening resolution of ambiguity during a stressor, and that this resolution of ambiguity is accompanied by physiological reactivity (heart rate, heart rate variability, and respiratory sinus arrhythmia). We propose future empirical research on the interplay between interpretation bias, psychophysiology, and child anxiety, as well as clinical implications.