Profiles of Autonomic Activity in Autism Spectrum Disorder with and without Anxiety.

Both anxiety and autism spectrum disorder (ASD) are associated with atypical physiological activity. Few studies have systematically assessed the resting physiological activity in ASD with co-occurring anxiety disorders. We tested 75 participants divided in four groups: youth with ASD, with (ASD + Anxiety = 22, 6F, 12.29 ± 2.83 years old) and without co-occurring anxiety (ASD Alone = 15, 6F, 11.59 ± 2.85 years old) and compared their physiological profile with that of matched typically developing controls (TDC) with (Anxiety Alone = 16, 6F, 11.24 ± 3.36 years old) and without co-occurring anxiety disorders (TDC = 22, 8F, 11.88 ± 2.88 years old). Results indicated reduced sympathetic and parasympathetic activity at rest in ASD as compared to TDC youth. ASD + Anxiety and Anxiety Alone groups showed different sympathetic, but similar parasympathetic activity. These findings suggest that autonomic profile-based approaches may advance research, diagnosis, and treatment of ASD and anxiety.

The first 24 h: opioid administration in people with spinal cord injury and neurologic recovery.

STUDY DESIGN: Retrospective chart review. OBJECTIVES: The objective of this study was to characterize opioid administration in people with acute SCI and examine the association between opioid dose and (1) changes in motor/functional scores from hospital to rehabilitation discharge, and (2) pain, depression, and quality of life (QOL) scores 1-year post injury. SETTING: Spinal Cord Injury Model System (SCIMS) inpatient acute rehabilitation facility. METHODS: Patients included in the SCIMS from 2008 to 2011 were linked to the National Trauma Registry and the electronic medical record. Three opioid dose groups (low, medium, and high) were defined based on the total morphine equivalence in milligrams at 24 h. The associations between opioid dose groups and functional/motor outcomes were assessed, as well as 1-year follow-up pain and QOL surveys. RESULTS: In all, 85/180 patients had complete medication records. By 24 h, all patients had received opioids. Patients receiving higher amounts of opioids had higher pain scores 1 year later compared with medium- and low-dose groups (pain levels 5.5 vs. 4 vs. 1, respectively, p = 0.018). There was also an 8× greater risk of depression 1 year later in the high-dose group compared with the low-dose group (OR: 8.1, 95% CI: 1.2-53.7). In analyses of motor scores, we did not find a significant interaction between opioid dose and duration of injury. CONCLUSIONS: These preliminary findings suggest that higher doses of opioids administered within 24 h of injury are associated with increased pain in the chronic phase of people with SCI.

Amygdala Volume Differences in Autism Spectrum Disorder Are Related to Anxiety.

Recent studies suggest that longstanding findings of abnormal amygdala morphology in ASD may be related to symptoms of anxiety. To test this hypothesis, fifty-three children with ASD (mean age = 11.9) underwent structural MRI and were divided into subgroups to compare those with at least one anxiety disorder diagnosis (n = 29) to those without (n = 24) and to a typically developing control group (TDC; n = 37). Groups were matched on age and intellectual level. The ASD and anxiety group showed decreased right amygdala volume (controlled for total brain volume) relative to ASD without anxiety (p = .04) and TDCs (p = .068). Results suggest that youth with ASD and co-occurring anxiety have a distinct neurodevelopmental trajectory.

COMPUTED TOMOGRAPHIC CHARACTERISTICS OF THE THYROID GLANDS IN EIGHT HYPERTHYROID CATS PRE- AND POSTMETHIMAZOLE TREATMENT COMPARED WITH SEVEN EUTHYROID CATS.

Hyperthyroidism is the most common feline endocrinopathy; thyroid computed tomography (CT) may improve disease detection and methimazole dose selection. Objectives of this experimental pre-post with historical case-control study were to perform thyroid CT imaging in awake or mildly sedated hyperthyroid cats, compare thyroid gland CT appearance in euthyroid and hyperthyroid cats pre- and postmethimazole treatment, and determine whether thyroid size or attenuation correlate with methimazole dose needed for euthyroidism. Premethimazole treatment, eight hyperthyroid cats received CT scans from the head to heart, which were compared to CT of seven euthyroid cats. Total thyroxine levels were monitored every 3-4 weeks. Postmethimazole CT was performed 30 days after achieving euthyroid status. Computed tomography parameters recorded included thyroid length, width, height, attenuation, and heterogeneity. Median time between CT was 70 days (53-213 days). Mild sedation was needed in five hyperthyroid cats premethimazole, and none postmethimazole. Thyroid volume was significantly larger in hyperthyroid cats compared to euthyroid cats (785.0 mm3 vs. 154.9 mm3 ; P = 0.002) and remained unchanged by methimazole treatment (-4.5 mm3; P = 0.50). Thyroid attenuation and heterogeneity decreased with methimazole treatment (96.1 HU vs. 85.9 HU; P = 0.02. 12.4 HU vs. 8.1 HU; P = 0.009). Methimazole dose ranged from 2.5 to 10 mg daily with a positive correlation between pretreatment thyroid gland volume and dose needed to achieve euthyroidism (P = 0.03). Euthyroid and hyperthyroid cats are easily imaged awake or mildly sedated with CT. Methimazole in hyperthyroid cats significantly lowers thyroid attenuation and heterogeneity, but not size.

Increment Threshold Functions in Retinopathy of Prematurity.

PURPOSE: To assess scotopic background adaptation in subjects with a history of preterm birth and retinopathy of prematurity (ROP). Retinopathy of prematurity is known to have long-term effects on rod photoreceptor and rod mediated postreceptor retinal function. METHODS: Rod-mediated thresholds for detection of 3° diameter, 50 ms stimuli presented 20° from fixation were measured using a spatial forced choice method in 36 subjects (aged 9-17 years) with a history of preterm birth and 11 age similar term-born subjects. Thresholds were measured first in the dark-adapted condition and then in the presence of 6 steady background lights (-2.8 to +2.0 log scot td). A model of the increment threshold function was fit to each subject's thresholds to estimate the dark-adapted threshold (TDA) and the Eigengrau (A0, the background that elevates threshold 0.3 log unit above TDA). RESULTS: In subjects with a history of severe ROP, both TDA and A0 were significantly elevated relative to those in former preterms who never had ROP and term-born control subjects. Subjects who had mild ROP had normal TDA but elevated A0. Neither TDA nor A0 differed significantly between former preterms who never had ROP and term-born controls. CONCLUSIONS: The results suggest that in severe ROP, threshold is affected at a preadaptation site, possibly the rod outer segment. In mild ROP, changes in the Eigengrau may reflect increased intrinsic noise in the photoreceptor or postreceptor circuitry or both.

Extrafoveal Cone Packing in Eyes With a History of Retinopathy of Prematurity.

PURPOSE: To study the density and packing geometry of the extrafoveal cone photoreceptors in eyes with a history of retinopathy of prematurity (ROP). We used a multimodal combination of adaptive optics (AO) scanning light ophthalmoscopy (SLO) and optical coherence tomography (OCT). METHODS: Cones were identified in subjects (aged 14-26 years) with a history of ROP that was either severe and treated by laser ablation of avascular peripheral retina (TROP; n = 5) or mild and spontaneously resolved, untreated (UROP; n = 5), and in term-born controls (CT; n = 8). The AO-SLO images were obtained at temporal eccentricities 4.5°, 9°, 13.5°, and 18° using both confocal and offset apertures with simultaneous, colocal OCT images. Effects of group, eccentricity, and aperture were evaluated and the modalities compared. RESULTS: In the SLO images, cone density was lower and the packing pattern less regular in TROP, relative to CT and UROP retinae. Although SLO image quality appeared lower in TROP, root mean square (RMS) wavefront error did not differ among the groups. In TROP eyes, cone discrimination was easier in offset aperture images. There was no evidence of cone loss in the TROP OCT images. CONCLUSIONS: Low cone density in TROP confocal SLO images may have resulted from lower image quality. Since AO correction in these eyes was equivalent to that of the control group, and OCT imaging showed no significant cone loss, the optical properties of the inner retina or properties of the cones themselves are likely altered in a way that affects photoreceptor imaging.

Viewing Complex, Dynamic Scenes "Through the Eyes" of Another Person: The Gaze-Replay Paradigm.

We present a novel "Gaze-Replay" paradigm that allows the experimenter to directly test how particular patterns of visual input-generated from people's actual gaze patterns-influence the interpretation of the visual scene. Although this paradigm can potentially be applied across domains, here we applied it specifically to social comprehension. Participants viewed complex, dynamic scenes through a small window displaying only the foveal gaze pattern of a gaze "donor." This was intended to simulate the donor's visual selection, such that a participant could effectively view scenes "through the eyes" of another person. Throughout the presentation of scenes presented in this manner, participants completed a social comprehension task, assessing their abilities to recognize complex emotions. The primary aim of the study was to assess the viability of this novel approach by examining whether these Gaze-Replay windowed stimuli contain sufficient and meaningful social information for the viewer to complete this social perceptual and cognitive task. The results of the study suggested this to be the case; participants performed better in the Gaze-Replay condition compared to a temporally disrupted control condition, and compared to when they were provided with no visual input. This approach has great future potential for the exploration of experimental questions aiming to unpack the relationship between visual selection, perception, and cognition.

Including lifestyle medicine in undergraduate medical curricula.

PURPOSE: Currently, there is no model to integrate the discipline of lifestyle medicine (LM) into undergraduate medical education. Furthermore, there are no guidelines, validated assessment tools, or evaluation or implementation plans in place. BACKGROUND: The World Health Organization predicts that by 2020, two-thirds of disease worldwide will be the result of poor lifestyle choices. Fewer than 50% of US primary care physicians routinely provide specific guidance on nutrition, physical activity, or weight control. METHODS: We are establishing a plan to integrate LM into medical school education in collaboration with the investing stakeholders, including medical school deans and students, medical curriculum developers and researchers, medical societies, governing bodies, and policy institutes. Three planning and strategy meetings are being held to address key areas of focus - with a particular interest in nutrition, physical activity, student self-care, and behavior change - to develop specific implementation guidelines and landmarks. RESULTS: After the first two meetings, the proposed areas of focus were determined to be: 1) supporting of deans and key personnel, 2) creation of federal and state policy commitments, 3) use of assessment as a driver of LM, 4) provision of high-quality evidence-based curricular material on an easily navigated site, and 5) engaging student interest. Implementation strategies for each focus area will be addressed in an upcoming planning meeting in early 2015. CONCLUSION: This initiative is expected to have important public health implications by efficiently promoting the prevention and treatment of non-communicable chronic disease with a scalable and sustainable model to educate physicians in training and practice.

Temporal summation in children with a history of retinopathy of prematurity.

PURPOSE: To assess temporal summation in children with a history of retinopathy of prematurity (ROP) by determining the critical duration (tCRIT) for complete temporal summation under rod-mediated conditions. From prior ERG studies, it is known that the kinetics of activation of phototransduction are prolonged in the ROP rod photoreceptor. METHODS: Dark-adapted thresholds for detecting 10° diameter stimuli with durations from 10 to 640 ms were measured. A two-alternative, spatial, forced-choice psychophysical procedure was used. The tCRIT for complete summation was estimated in former preterm subjects with a history of severe ROP (n = 7), mild ROP (n = 23), and no ROP (n = 15). The subjects ranged in age from 10.4 to 17.6 (median 15.6) years. Age-similar term-born control subjects (n = 5) were also tested. RESULTS: Critical duration was significantly longer in subjects with a history of ROP than in subjects who never had ROP or who were born at term. Mean tCRIT in the mild ROP group [127.5 (SD = 19.9) ms] and severe group [147.6 (SD = 18.9) ms] did not differ significantly, but both were significantly longer than in former preterms who never had ROP [101.1 (SD = 16.5) ms] and in term-born controls [101.0 (SD = 19.5) ms]. CONCLUSIONS: In ROP subjects, tCRIT is significantly prolonged. This is likely due to abnormal kinetics in the rod outer segment.

The broad autism phenotype predicts child functioning in autism spectrum disorders.

BACKGROUND: Broad autism phenotype (BAP) is a milder expression of the social and communication impairments seen in autism spectrum disorders (ASD). While prior studies characterized the BAP in unaffected family members of probands with ASD, the relationship between parental BAP traits and proband symptomatology remains poorly understood. This study utilizes the Broad Autism Phenotype Questionnaire (BAPQ) in parents and the Social Responsiveness Scale (SRS) in children to examine this connection. We hypothesized that in families affected by ASD, elevated maternal and paternal BAPQ scores would correlate with greater autism symptomatology in diagnosed children. In an extension of prior research, we also explored this relationship in families with typically developing children (TDC). METHODS: Two hundred and forty-five children with ASD, 129 TDC and all parents were recruited as part of a larger study investigating relationships between genes, brain and behavior. The Autism Diagnostic Interview-Revised (ADI-R), Autism Diagnostic Observation Schedule (ADOS) and expert clinical judgment confirmed ASD diagnoses in children. SRS was collected for all children. Parents completed a self-report BAPQ and an informant report BAPQ for their spouse; an average of self-report and informant report for each parent was used in all analyses. RESULTS: Mothers and fathers of children with ASD had significantly higher rates of BAP traits as compared to parents of TDC. Maternal and paternal BAPQ total scores were not correlated with child IQ in either group. In the ASD group, 10% of mothers and 21% of fathers scored above the established BAP threshold compared to 4% of TDC parents. Crude regression analyses showed that maternal and paternal BAPQ total scores accounted for significant variance in child SRS scores in both ASD (17.1%) and TDC (19.8%) families. CONCLUSIONS: Our results suggest that broad autism symptomatology in parents is moderately associated with their child's autism symptomatology. This result extended to TDC families, suggesting that the BAPQ and SRS capture subtle, subclinical social variation in both children and adults. These findings could help define multi-generational social impairments in future phenotypic and genetic studies.

Clinical correlates of the weight bias internalization scale in a sample of obese adolescents seeking bariatric surgery.

The aim of this study was to evaluate psychometric properties and clinical correlates of the Weight Bias Internalization Scale (WBIS) in a sample of obese adolescents seeking bariatric surgery. Sixty five adolescents enrolled in a bariatric surgery program at a large, urban medical center completed psychiatric evaluations, self-report questionnaires including the WBIS and other measures of psychopathology and physical assessments. The WBIS had high internal consistency (Cronbach's α = 0.92). As in previous research with adults, the one underlying factor structure was replicated and 10 of the original 11 items were retained. The scale had significant partial correlations with depression (r = 0.19), anxiety (r = 0.465), social, and behavioral problems (r = 0.364), quality of life (r = -0.480), and eating (r = 0.579), shape (r = 0.815), and weight concerns (r = 0.545), controlling for BMI. However, WBIS scores did not predict current or past psychiatric diagnosis or treatment or past suicidal ideation. Overall, the WBIS had excellent psychometric properties in a sample of obese treatment-seeking adolescents and correlated significantly with levels of psychopathology. These findings suggest that the WBIS could be a useful tool for healthcare providers to assess internalized weight bias among treatment-seeking obese youth. Assessment of internalized weight bias among this clinical population has the potential to identify adolescents who might benefit from information on coping with weight stigma, which in turn may augment weight loss efforts.

A latent class analysis of psychiatric symptoms among 125 adolescents in a bariatric surgery program.

OBJECTIVE: The purpose of this study was to examine whether subgroups could be identified among a sample of adolescents presenting for bariatric surgery. METHODS: Participants were 125 severely obese adolescents enrolled in a bariatric surgery program referred for a psychiatric evaluation. A latent class analysis was conducted with self-report and clinician-rated measures of depressive symptoms, total problems by the Youth Self-Report Scale, anxiety severity, eating pathology, psychiatric diagnoses, quality of life, and family functioning. RESULTS: A 3-class model yielded the best overall fit to the data. Adolescents in the ?eating pathology? class demonstrated high levels of both eating disordered and other psychopathology. The second class, or ?low psychopathology? class exhibited the fewest psychosocial problems, whereas adolescents in the third class were intermediate on measures of psychopathology, which is consistent with ?non-specific psychopathology.? CONCLUSIONS: The latent class analysis identified homogeneous subgroups with different levels of psychopathology among a heterogeneous sample of severely obese adolescents. The identification of clinically relevant subgroups in this study offers an important initial means for examining psychopathology among adolescent bariatric surgery candidates and suggests a number of avenues for future research. CLINICAL TRIALS REGISTRY: Laparoscopic Adjustable Gastric Banding (LAGB) as a Treatment for Morbid Obesity in Adolescents, NCT01045499.

In vivo evidence for a dependence on interleukin 15 for survival of natural killer cells.

Cellular homeostasis requires a balance between cell production, cell survival, and cell death. Production of natural killer (NK) cells from bone marrow precursor cells requires interleukin 15 (IL-15); however, very little is known about the factors controlling survival of mature NK cells in vivo. Because mice deficient in IL-15 (IL-15(-/-) mice) fail to develop NK cells, it is not known whether mature NK cells can survive in an environment lacking IL-15. We hypothesized that IL-15 might indeed be required for survival of mature NK cells in vivo. Freshly isolated NK cells labeled with 5-(and-6)-carboxyfluorescein diacetate, succinimidyl ester (CFSE) were adoptively transferred into IL-15(-/-) mice and littermate control (IL-15(+/-)) mice. Within 36 hours after transfer, NK cells were detected in both IL-15(-/-) and IL-15(+/-) mice; however, significantly more (P <.003) CFSE-positive (CFSE(+)) NK cells were found in control mice than in IL-15(-/-) mice. By 5 days, similar numbers of CFSE(+) NK cells were still easily detected in IL-15(+/-) mice, whereas no CFSE(+) NK cells survived in IL-15(-/-) mice. Furthermore, mice with severe combined immunodeficiency treated with the Fab fragment of a blocking antibody recognizing a signaling subunit of the IL-15 receptor, IL-2/15Rbeta, had a significant ( approximately 90%) loss of NK cells compared with control mice. Finally, NK cells from Bcl-2 transgenic mice that were adoptively transferred into IL-15(-/-) mice did survive. These results show conclusively that IL-15 is required for mature NK cell survival in vivo and suggest that IL-15 mediates its effect on NK cell survival by means of Bcl-2.