Dysfunction in differential reward-punishment responsiveness in conduct disorder relates to severity of callous-unemotional traits but not irritability.

BACKGROUND: Conduct disorder (CD) has been associated with dysfunction in reinforcement-based decision-making. Two forms of affective traits that reflect the components of CD severity are callous-unemotional (CU; reduced guilt/empathy) traits and irritability. The form of the reinforcement-based decision-making dysfunction with respect to CD and CU traits remains debated and has not been examined with respect to irritability in cases with CD. The goals of the current study were to determine the extent of dysfunction in differential (reward v. punishment) responsiveness in CD, and CU traits and irritability in participants with CD. METHODS: The study involved 178 adolescents [typically developing (TD; N = 77) and cases with CD (N = 101)]. Participants were scanned with fMRI during a passive avoidance task that required participants to learn to respond to (i.e. approach) stimuli that engender reward and refrain from responding to (i.e. passively avoid) stimuli that engender punishment. RESULTS: Adolescents with CD showed reduced differential reward-punishment responsiveness within the striatum relative to TD adolescents. CU traits, but not irritability, were associated with reduced differential reward-punishment responsiveness within the striatum, rostromedial, and lateral frontal cortices. CONCLUSIONS: The results suggest CD is associated with reduced differential reward-punishment responsiveness and the extent of this dysfunction in participants with CD is associated with the severity of CU traits but not irritability.

Latent profiles of substance use, early life stress, and attention/externalizing problems and their association with neural correlates of reinforcement learning in adolescents.

BACKGROUND: Adolescent substance use, externalizing and attention problems, and early life stress (ELS) commonly co-occur. These psychopathologies show overlapping neural dysfunction in the form of reduced recruitment of reward processing neuro-circuitries. However, it is unclear to what extent these psychopathologies show common v. different neural dysfunctions as a function of symptom profiles, as no studies have directly compared neural dysfunctions associated with each of these psychopathologies to each other. METHODS: In study 1, a latent profile analysis (LPA) was conducted in a sample of 266 adolescents (aged 13-18, 41.7% female, 58.3% male) from a residential youth care facility and the surrounding community to investigate substance use, externalizing and attention problems, and ELS psychopathologies and their co-presentation. In study 2, we examined a subsample of 174 participants who completed the Passive Avoidance learning task during functional magnetic resonance imaging to examine differential and/or common reward processing neuro-circuitry dysfunctions associated with symptom profiles based on these co-presentations. RESULTS: In study 1, LPA identified profiles of substance use plus rule-breaking behaviors, attention-deficit hyperactivity disorder, and ELS. In study 2, the substance use/rule-breaking profile was associated with reduced recruitment of reward processing and attentional neuro-circuitries during the Passive Avoidance task (p < 0.05, corrected for multiple comparisons). CONCLUSIONS: Findings indicate that there is reduced responsivity of striato-cortical regions when receiving outcomes on an instrumental learning task within a profile of adolescents with substance use and rule-breaking behaviors. Mitigating reward processing dysfunction specifically may represent a potential intervention target for substance-use psychopathologies accompanied by rule-breaking behaviors.

Impaired in vitro fertilization outcomes following testosterone treatment improve with washout in a mouse model of gender-affirming hormone treatment.

BACKGROUND: The impact of gender-affirming testosterone on fertility is poorly understood, with ovarian histopathologic studies showing variable results, some with a detrimental effect on reproductive capacity and uncertain reversibility. Assisted reproductive outcome data are restricted to small case series that lack the ability to inform clinical practice guidelines and limit fertility preservation counseling for transgender and nonbinary individuals. OBJECTIVE: This study aimed to determine the impact of current testosterone and testosterone washout on in vitro fertilization outcomes in a mouse model for gender-affirming hormone treatment. We hypothesized that current or previous testosterone treatment would not affect in vitro fertilization outcomes. STUDY DESIGN: C57BL/6N female mice (n=120) were assigned to 4 treatment groups: (1) current control, (2) current testosterone, (3) control washout, and (4) testosterone washout. Testosterone implants remained in situ for 6 or 12 weeks, representing the short- and long-term treatment arms, respectively. Current treatment groups underwent ovarian stimulation with implants in place, and washout treatment groups were explanted and had ovarian stimulation after 2 weeks. Oocytes were collected, fertilized, and cultured in vitro, with one arm continuing to the blastocyst stage and the other having transfer of cleavage-stage embryos. Statistical analysis was performed using GraphPad Prism, version 9.0 and R statistical software, version 4.1.2, with statistical significance defined by P<.05. RESULTS: Current long-term testosterone treatment impaired in vitro fertilization outcomes, with fewer mature oocytes retrieved (13.7±5.1 [standard deviation] vs 28.6±7.8 [standard deviation]; P<.0001) leading to fewer cleavage-stage embryos (12.1±5.1 vs 26.5±8.2; P<.0001) and blastocysts (10.0±3.2 vs 25.0±6.5; P<.0001). There was recovery of in vitro fertilization outcomes following washout in the short-term treatment cohort, with incomplete reversibility in the long-term cohort. Testosterone did not negatively affect maturity, fertilization, or blastulation rates. CONCLUSION: In a mouse model of gender-affirming hormone treatment, testosterone negatively affected oocyte yield without affecting oocyte quality. Our findings suggest that testosterone reversibility is duration-dependent. These results demonstrate the feasibility of in vitro fertilization without testosterone discontinuation while supporting a washout period for optimization of mature oocyte yield.

Reduced cortical volume of the default mode network in adolescents with generalized anxiety disorder.

BACKGROUND: Widespread structural alterations have been shown to be implicated in individuals with generalized anxiety disorder (GAD). However, there have been inconsistent findings in cortical volume (CV) differences. Most structural neuroimaging studies looking at GAD used region-based approach with relatively small sample sizes, let alone be specific to adolescents with GAD. We believe this is the first study to look at CV measures using a network-based approach in a larger sample of adolescents with GAD. The goal of the current study was to focus on three different brain networks (i.e., Limbic, Frontoparietal, and Default Mode Network [DMN]) in adolescents with GAD. METHOD: The study involved 81 adolescents with GAD and 112 typically developing (TD) comparison individuals matched on age (15.98 and 15.63 respective means), sex (42F/39M and 45F/67M), and IQ (101.90 and 103.94 respective means). Participants underwent structural MRI. Freesurfer was used to estimate CV (both network-specific and region-specific within networks) and region-specific sub-cortical volume measures. Multivariate analysis of covariance (MANCOVA; with sex, age, IQ, and intracranial volume [ICV] as potential covariates) was used to estimate group differences. RESULTS: We found significantly lower CV for the DMN in adolescents with GAD, compared with TD individuals. Adolescents with GAD also showed significantly lower hemispheric mean CV of the default-mode regions (particularly the prefrontal and temporal regions) and the hippocampus, compared with TD individuals. CONCLUSION: The current findings suggest structural alterations in adolescents with GAD. These structural alterations will need to be addressed when implementing and developing treatments for patients with GAD.

Emergency Department Utilization for Adnexal Torsion: An Analysis of the Nationwide Emergency Department Sample from 2006 to 2018.

STUDY OBJECTIVE: To characterize emergency department (ED) utilization for adnexal torsion (AT) among adult patients in the United States. DESIGN: Retrospective analysis to identify primary AT diagnoses and ED utilization. Other variables analyzed included primary payer type, income quartile by ZIP code, hospital teaching status, and urban vs rural location. Secondary analyses identified diagnosis codes associated with a primary diagnosis of AT. SETTING: Healthcare Cost and Utilization Project Nationwide Emergency Sample database. PATIENTS: Women aged 18 to 65 years presenting to the ED with AT from 2006 to 2018. INTERVENTIONS: Not applicable. MEASUREMENTS AND MAIN RESULTS: From 2006 to 2018, the annual number of ED visits for AT among women aged 18 to 65 years increased from 2791 to 5243. Hospital admission rates for AT declined over the study period from 76% to 37%. Patients with AT were less likely to be admitted if they had private insurance, but admission rates for AT were similar regardless of income quartile and hospital teaching status. Average ED charges for AT nearly quadrupled over the study period compared with ED charges overall, which doubled. The average charge for AT patients in 2006 was $5212 and in 2018 was $20 213-an average annual increase of 24.0%, compared with 14.3% for all other diagnoses in age-matched women. CONCLUSION: Although admission rates for AT decreased by 50% from 2006 to 2018, ED utilization nearly doubled, and the average associated charges quadrupled, summing to an annual weighted charge of over $500 million by 2018. The data suggest that women are evaluated similarly for AT regardless of income or insurance status.

Reduced neural differentiation of rewards and punishment during passive avoidance learning in adolescents with generalized anxiety disorder.

BACKGROUND: It has been proposed that individuals with generalized anxiety disorder (GAD) show dysfunctional computations related to approach-avoidance decision-making. However, few studies have examined the neural basis of this impairment, particularly in adolescents with GAD. The goal of the current study was to address this gap in the literature. METHOD: The study involved 51 adolescents with GAD and 51 typically developing (TD) comparison individuals matched on age (16.10 and 15.75 respective means), gender (30 F/21 M and 24 F/27 M), and IQ (103.20 and 103.18 respective means). Participants underwent functional magnetic resonance imaging during a passive avoidance task. RESULTS: We found a significant Group-by-Reinforcement interaction within reward-related brain regions including the caudate, putamen, mid cingulate/paracentral lobule, and superior and middle frontal gyrus. TD adolescents showed a greater differential response to reward versus punishment feedback within these regions relative to adolescents with GAD. In particular, this reflected reduced responses to rewards in the adolescents with GAD. There were no group differences in neural responses when making approach/avoidance responses. CONCLUSION: The results of this study suggest reduced differential responsiveness to reinforcement as a component of the pathophysiology seen in adolescents with GAD. This dysfunction likely underpins decision-making impairments that may exacerbate the participants' worry.

Reproductive potential and fertility preservation in transgender and nonbinary individuals.

PURPOSE OF REVIEW: To synthesize recent literature to better understand parenting desires and challenges of transgender individuals as well as the impact of gender-affirming care on reproductive potential. RECENT FINDINGS: Survey studies of transgender and nonbinary individuals demonstrate significant parenting interest, yet uptake in fertility preservation services remains low with potential for decisional regret. Masculinizing hormones have demonstrated variable effects on folliculogenesis and follicle distribution in the human ovary. In the mouse model, testosterone administration has demonstrated an increase in atretic late antral follicles without a reduction in primordial or total antral follicle counts and a preserved ability to respond to gonadotropin stimulation. Case series of transgender individuals undergoing oocyte or embryo cryopreservation are promising with outcomes similar to cisgender controls. Feminizing hormones have shown detrimental effects on sperm parameters at time of cryopreservation and spermatogenesis in orchiectomy samples with uncertainty regarding the reversibility of these changes. SUMMARY: Current evidence demonstrates variable effects of gender-affirming hormones on ovarian and testicular function with potential for detrimental impact on an individual's reproductive potential. As many individuals initiate gender-affirming care prior to or during their reproductive years it is imperative that they receive thorough fertility preservation counseling and improved access to reproductive care services.

Environmental Scan of Sleep Health in Early Childhood Programs.

OBJECTIVE: To ascertain how sleep health knowledge is translated to early care and education (ECE) programs, using a multi-component environmental scan. METHODS: A website scan identified organizations' sleep content re: recommended practices, developmental effects, and "actionable" ratings (0-2). ECE staff surveys assessed preparedness, practices, and beliefs about addressing sleep health and sleep problems in ECE programs. Semi-structured interviews with stakeholders from the ECE, pediatric and sleep communities assessed awareness, priorities, and practices at their organizations. RESULTS: Of 15 websites scanned, half lacked sleep content on links to development, optimal duration, or scientific background. ECE staff (n = 31) were comfortable speaking to parents about healthy sleep, and with incorporating sleep education and guidance into ECE. Stakeholders (n = 15) rated healthy sleep as a high relevance, but lower priority issue. Within ECE settings stakeholders reported that knowledge about specific links to health and development was poor and that sleep health was often obscured by "safe sleep" issues. Their recommendations included: linking sleep health to "hot topics" such as obesity or preschool suspensions and expulsions, integrating it with the teaching of routines, and raising public awareness. CONCLUSION: Despite understanding that healthy sleep promotes school readiness, there is insufficiently specific, actionable information in ECE training, programs, or policies. Findings suggest a need for an awareness campaign with clear, actionable messaging, dissemination of turnkey materials, and integration with policy and professional training systems. TRIAL REGISTRATION: - ClinicalTrials.Gov: NCT03556462.

Virtual resident showcase: leveraging an institutional repository during COVID-19 social distancing.

While institutional repositories are common in medical schools and academic health centers, they have been used by only a small number of health systems to track and promote their research and scholarly activity. This article describes how Providence System Library Services leveraged their existing institutional repository platform to substitute a virtual showcase for an annual in-person event.

Reduction in opioid use and postoperative pain scores after elective laparotomy with implementation of enhanced recovery after surgery protocol on a gynecologic oncology service.

OBJECTIVE: Enhanced Recovery After Surgery (ERAS) protocols are designed to mitigate the physiologic stress response created by surgery, to decrease the time to resumption of daily activities, and to improve overall recovery. This study aims to investigate postoperative recovery outcomes following gynecologic surgery before and after implementation of an ERAS protocol. METHODS: A retrospective chart review was performed of patients undergoing elective laparotomy at a major academic center following implementation of an ERAS protocol (11/4/2014-7/27/2016) with comparison to a historical cohort (6/23/2013-9/30/2014). The primary outcome was length of hospital stay. Secondary outcomes included surgical variables, time to recovery of baseline function, opioid usage, pain scores, and complication rates. Statistical analyses were performed using Wilcoxon rank sum, Fisher's exact, and chi squared tests. RESULTS: One hundred and thirty-three women on the ERAS protocol who underwent elective laparotomy were compared with 121 historical controls. There was no difference in length of stay between cohorts (median 4 days; P = 0.71). ERAS participants had lower intraoperative (45 vs 75 oral morphine equivalents; P < 0.0001) and postoperative (45 vs 154 oral morphine equivalents; P < 0.0001) opioid use. ERAS patients reported lower maximum pain scores in the post-anesthesia care unit (three vs six; P < 0.0001) and on postoperative day 1 (four vs six; P = 0.002). There was no statistically significant difference in complication or readmission rates. CONCLUSIONS: ERAS protocol implementation was associated with decreased intraoperative and postoperative opioid use and improved pain scores without significant changes in length of stay or complication rates.

Multisite collaboration using REDCap to capture library data.

In January 2018, library services at Providence St. Joseph Health merged to form a single, unified system, incorporating nine libraries and sixteen full-time staff. As a small, nonclinical team of librarians, we needed to make sure our work and value were visible to clinicians, administrators, and other nonlibrary stakeholders. Using REDCap, we developed a form to seamlessly collect statistics about our services.

Strengthening Health Systems While Responding to a Health Crisis: Lessons Learned by a Nongovernmental Organization During the Ebola Virus Disease Epidemic in Sierra Leone.

An epidemic of Ebola virus disease (EVD) beginning in 2013 has claimed an estimated 11 310 lives in West Africa. As the EVD epidemic subsides, it is important for all who participated in the emergency Ebola response to reflect on strengths and weaknesses of the response. Such reflections should take into account perspectives not usually included in peer-reviewed publications and after-action reports, including those from the public sector, nongovernmental organizations (NGOs), survivors of Ebola, and Ebola-affected households and communities. In this article, we first describe how the international NGO Partners In Health (PIH) partnered with the Government of Sierra Leone and Wellbody Alliance (a local NGO) to respond to the EVD epidemic in 4 of the country's most Ebola-affected districts. We then describe how, in the aftermath of the epidemic, PIH is partnering with the public sector to strengthen the health system and resume delivery of regular health services. PIH's experience in Sierra Leone is one of multiple partnerships with different stakeholders. It is also one of rapid deployment of expatriate clinicians and logistics personnel in health facilities largely deprived of health professionals, medical supplies, and physical infrastructure required to deliver health services effectively and safely. Lessons learned by PIH and its partners in Sierra Leone can contribute to the ongoing discussion within the international community on how to ensure emergency preparedness and build resilient health systems in settings without either.

Nitric oxide differentially affects proteasome activator 28 after arterial injury in type 1 and type 2 diabetic rats.

BACKGROUND: Diabetic patients display aggressive restenosis after vascular interventions, likely because of proproliferative influences of hyperglycemia and hyperinsulinemia. We have shown that nitric oxide (NO) inhibits neointimal hyperplasia in type 2, but not in type 1, diabetic rats. Here, we examined proteasome activator 28 (PA28) after arterial injury in different diabetic environments, with or without NO. We hypothesize that NO differentially affects PA28 levels based on metabolic environment. MATERIALS AND METHODS: Vascular smooth muscle cell (VSMC) lysates from male, nondiabetic Lean Zucker (LZ) and Zucker Diabetic Fatty (ZDF) rats were assayed for 26S proteasome activity with or without PA28 and S-nitroso-N-acetylpenicillamine. LZ and ZDF VSMCs were treated with (Z)-1-[N-(2-aminoethyl)-N-(2-ammonioethyl)amino]diazen-1-ium-1,2-diolate for 24 h. Balloon-injured carotid arteries from LZ, streptozotocin-injected LZ (STZ, type 1), and ZDF (type 2) rats treated with disodium 1-[2-(carboxylato)pyrrolidin-1-iyl]diazen-1-ium-1,2-diolate were harvested at 3 or 14 d. PA28α was assessed by Western blotting and immunofluorescent staining. RESULTS: S-nitroso-N-acetylpenicillamine reversed PA28-stimulated increases in 26S proteasome activity in LZ and ZDF VSMCs. Increased (Z)-1-[N-(2-aminoethyl)-N-(2-ammonioethyl)amino]diazen-1-ium-1,2-diolate lowered PA28α in LZ VSMCs but increased PA28α in ZDF VSMCs. At 3 d after injury, disodium 1-[2-(carboxylato)pyrrolidin-1-iyl]diazen-1-ium-1,2-diolate potentiated injury-induced PA28α decreases in LZ, STZ, and ZDF rats, suggesting VSMCs, depleted at this early time point, are major sources of PA28α. At 14 d after injury, total PA28α staining returned to baseline. However, although intimal and medial PA28α staining increased in injured STZ rats, adventitial PA28α staining increased in injured ZDF rats. CONCLUSIONS: PA28 dysregulation may explain the differential ability of NO to inhibit neointimal hyperplasia in type 1 versus type 2 diabetes.

Neural correlates of automatic emotion regulation and their association with suicidal ideation in adolescents during the first 90-days of residential care.

BACKGROUND: Suicide is the second leading cause of death for adolescents in the United States. However, relatively little is known about the forms of atypical neuro-cognitive function that are correlates of suicidal ideation (SI). One form of cognitive/affective function that, when dysfunctional, is associated with SI is emotion regulation. However, very little work has investigated the neural correlates of emotion dysregulation in adolescents with SI. METHODS: Participants (N = 111 aged 12-18, 32 females, 31 [27.9%] reporting SI) were recruited shortly after their arrival at a residential care facility where they had been referred for behavioral and mental health problems. Daily reports of SI were collected during the participants' first 90-days in residential care. Participants were presented with a task-fMRI measure of emotion regulation - the Affective Number Stroop task shortly after recruitment. Participants were divided into two groups matched for age, sex and IQ based on whether they demonstrated SI. RESULTS: Participants who demonstrated SI showed increased recruitment of regions including dorsomedial prefrontal cortex/supplemental motor area and parietal cortex during task (congruent and incongruent) relative to view trials in the context of emotional relative to neutral distracters. CONCLUSIONS: Participants with SI showed increased recruitment of regions implicated in executive control during the performance of a task indexing automatic emotion regulation. Such data might suggest a relative inefficiency in the recruitment of these regions in individuals with SI.

A Mouse Model to Investigate the Impact of Gender Affirming Hormone Therapy with Estradiol on Reproduction.

Gender-affirming hormone therapy (GAHT) can help transgender and/or gender diverse (TGD) individuals achieve emobidment goals that align with their transition needs. Clinical evidence from estradiol (E)-GAHT patients indicate widespread changes in tissues sensitive to E and testosterone (T), particularly in the reproductive system. Notably, E-GAHTs effects on hormones and reproduction vary greatly between patients. With the goal of informing clinical research and practice for TGD individuals taking E, this study examines intact male mice implanted with capsules containing one of three different E doses (low 1.25 mg; mid 2.5 mg; high 5 mg), or a blank control capsule. All E-GAHT doses suppress T and follicle stimulating hormone levels while elevating E levels. Only the high E-GAHT dose significantly supresses luteinizing hormone levels. All E-GAHT doses affect epididymis tubule size similarly while seminiferous tubule morphology and bladder weight changes are dose-dependent. E-GAHT does not alter the presence of mature sperm, though E-exposed sperm have altered motility. These data represent the first evidence that mouse models offer an effective tool to understand E-GAHTs impact on reproductive health and the dose-dependent effects of this model permit examinations of diverse patient outcomes.

Different forms of childhood maltreatment have different impacts on the neural systems involved in the representation of reinforcement value.

BACKGROUND: The current study aimed to address two gaps in the literature on child maltreatment, reinforcement processing and psychopathology. First, the extent to which compromised reinforcement processing might be particularly associated with either neglect or abuse. Second, the extent to which maltreatment-related compromised reinforcement processing might be associated with particular symptom sets (depression, conduct problems, anxiety) or symptomatology more generally. METHODS: A sample of adolescents (N = 142) aged between 14 and 18 years with varying levels of prior maltreatment participated in this fMRI study. They were scanned while performing a passive avoidance learning task, where the participant learns to respond to stimuli that engender reward and avoid responding to stimuli that engender punishment. Maltreatment (abuse and neglect) levels were assessed with the Childhood Trauma Questionnaire (CTQ). RESULTS: We found that: (i) level of neglect, but not abuse, was negatively associated with differential BOLD responses to reward-punishment within the striatum and medial frontal cortex; and (ii) differential reward-punishment responses within these neglect-associated regions were particularly negatively associated with level of conduct problems. CONCLUSION: Our findings demonstrate the adverse neurodevelopmental impact of childhood maltreatment, particularly neglect, on reinforcement processing. Moreover, they suggest a neurodevelopmental route by which neglect might increase the risk for conduct problems.

Toward Real-Time Muscle Force Inference and Device Control via Optical-Flow-Tracked Muscle Deformation.

Despite the utility of musculoskeletal dynamics modeling, there exists no safe, noninvasive method of measuring in vivo muscle output force in real time - limiting both biomechanical insight into dexterous motion and intuitive control of assistive devices. In this paper, we demonstrate that muscle deformation constitutes a promising, yet unexplored signal from which to 1) infer such forces and 2) build novel device control schemes. Through a case study of the elbow joint on a preliminary cohort of 10 subjects, we show that muscle deformation (specifically, thickness change of the brachioradialis, as measured via ultrasound and tracked via optical flow) correlates well with elbow output force to an extent comparable with standard surface electromyography (sEMG) activation during varied isometric elbow contraction. We then show that, given real-time visual feedback, subjects can readily perform a trajectory tracking task using this deformation signal, and that they largely prefer this method to a comparable sEMG-based control scheme and perform the tracking task with similar accuracy. Together, these contributions illustrate muscle deformation's potential utility for both biomechanical study of individual muscle dynamics and device control, in a manner that - thanks to, unlike sEMG, the localized nature of the signal and its tight mechanistic coupling to output force - is readily extensible to multiple muscles and device degrees of freedom. To enable such future extensions, all modeling, tracking, and visualization software described in this paper, as well as all raw and processed data, have been made available on SimTK as part of the Open-Arm project (https://simtk.org/projects/openarm) for general research use.

Callous-Unemotional Traits Moderate the Relationship Between Irritability and Threatening Responding.

Background: Irritability and callous-unemotional (CU; reduced guilt/empathy) traits vary dimensionally in the typically developing population but may be particularly marked in youth with conduct disorder (CD). While these dimensional traits are positively correlated, they have been associated with divergent forms of dysfunction, particularly with respect to threat processing (i.e., irritability with increased, and CU traits with decreased, threat responsiveness). This suggests that interactions between these two dimensions may be complex at the neurobiological level. However, this issue has received minimal empirical attention. Methods: The study included 105 adolescents (typically developing and cases with CD; N = 59). They were scanned with fMRI during a looming threat task that involved images of threatening and neutral human faces or animals that appeared to be either looming or receding. Results: Significant irritability-by-CU traits-by-Direction-by-Emotion interactions were seen within right thalamus/PAG, left lingual gyrus and right fusiform gyrus; irritability was positively associated with the BOLD response for Looming Threatening vs. Receding Threatening trials, particularly for youth with low CU traits. In contrast, CU traits were negatively associated with the same differential BOLD response but particularly for youth showing higher levels of irritability. Similar findings were seen within left ventral anterior and posterior cingulate cortices, though the addition of the interaction with CU traits was only seen at slightly more lenient thresholds. Conclusions: The results support previous work linking irritability to increased, and CU traits to reduced, threat responsiveness. However, for adolescents with high irritability, if CU traits are also high, the underlying neuropathology appears to relate to reduced, rather than increased, threat responsiveness.

Network-wise surface-based morphometric insight into the cortical neural circuitry underlying irritability in adolescents.

Previous studies examining structural brain correlates of irritability have taken a region-specific approach and have been relatively inconsistent. In a sample of adolescents with and without clinically impairing irritability, the current study examines: (i) cortical volume (CV) in canonical functional networks; (ii) the association between the CV of functional networks and severity of irritability; and (iii) the extent to which IQ mediates the association between structural abnormalities and severity of irritability. Structural MRI and IQ data were collected from 130 adolescents with high irritability (mean age = 15.54±1.83 years, 58 females, self-reported Affective Reactivity Index [ARI] ≥ 4) and 119 adolescents with low irritability (mean age = 15.10±1.93 years, 39 females, self-reported ARI < 4). Subject-specific network-wise CV was estimated after parcellating the whole brain into 17 previously reported functional networks. Our Multivariate Analysis of Covariance (MANCOVA) revealed that adolescents with high irritability had significantly reduced CV of the bilateral control and default-mode networks (p < 0.05) relative to adolescents with low irritability. Multiple regression analyses showed a significant negative association between the control network CV and the severity of irritability. Mediation analysis showed that IQ partially mediated the association between the control network CV and the severity of irritability. Follow-up analysis on subcortical volume (SCV) showed that adolescents with high irritability had reduced bilateral SCV within the amygdala relative to adolescents with low irritability. Reduced CV within bilateral control and default networks and reduced SCV within bilateral amygdala may represent core features of the pathophysiology of irritability. The current data also indicate the potential importance of a patient's IQ in determining how pathophysiology related to the control network is expressed.

A Pilot Study of Home-Based Exercise and Personalized Nutrition Counseling Intervention in Endometrial Cancer Survivors.

INTRODUCTION: To assess the feasibility of a home-based aerobic exercise and nutrition counseling intervention and effect on cardiorespiratory fitness, cardiovascular disease risk profile, and immune response in obese endometrial cancer survivors. METHODS: A longitudinal pilot study assessed a 12-week home-based aerobic exercise and nutrition counseling intervention in obese endometrial cancer survivors. The primary outcome was feasibility defined as 80% adherence to weekly walking sessions calculated among individuals that completed the intervention. Secondary outcomes comprised pre- and post-intervention differences in cardiorespiratory fitness, cardiovascular risk factors, and T-cell function. Descriptive statistics summarized data. Wilcoxon sign tests identified differences between and pre and post-intervention variables. RESULTS: Nineteen women with stage 1 endometrial cancer consented; 9 withdrew and one was a screen failure. Median adherence to weekly walking sessions was 83.3%. Body composition was significantly altered with a reduction in median fat mass from 52.5 kg to 46.9 kg (p=0.04), and BMI from 37.5 kg/m2 to 36.2 kg/m2 (p = 0.004). There was no significant difference in cardiorespiratory fitness or cardiovascular parameters. The percentage of CD4+ and CD8+ T-cells producing IFNγ towards MAGE-A4 significantly increased from and 5.9% to 7.2% (p=0.043) and 13.9% to 14.8% (p=0.046), respectively. There were 3 related adverse events: hip pain, back sprain, and abdominal pain. DISCUSSION: Our home-based exercise and nutrition counseling program was feasible based on 80% adherence to walking sessions and favored altered body composition. However, the discontinuation rate was high and further research is needed to overcome barriers to implementation. Improvement in cardiovascular parameters will most likely require longer and more intensive programs.