Imaginative elaboration in agenesis of the corpus callosum: topic modeling and perplexity.

OBJECTIVE: Previous studies have found deficits in imaginative elaboration and social inference to be associated with agenesis of the corpus callosum (ACC; Renteria-Vasquez et al., 2022; Turk et al., 2009). In the current study, Thematic Apperception Test (TAT) responses from a neurotypical control group and a group of individuals with ACC were used to further study the capacity for imaginative elaboration and story coherence. METHOD: Topic modeling was employed utilizing Latent Diritchlet Allocation to characterize the narrative responses to the pictures used in the TAT. A measure of the difference between models (perplexity) was used to compare the topics of the responses of individual participants to the common core model derived from the responses of the control group. Story coherence was tested using sentence-to-sentence Latent Semantic Analysis. RESULTS: Group differences in perplexity were statistically significant overall, and for each card individually (p < .001). There were no differences between the groups in story coherence. CONCLUSIONS: TAT narratives from persons with ACC were normally coherent, but more conventional (i.e., more similar to the core text) compared to those of neurotypical controls. Individuals with ACC can make conventional social inferences about socially ambiguous stimuli, but are restricted in their imaginative elaborations, resulting in less topical variability (lower perplexity values) compared to neurotypical controls.

Verbal problem-solving in agenesis of the corpus callosum: Analysis using semantic similarity.

OBJECTIVE: Previous studies demonstrated that individuals with agenesis of the corpus callosum (AgCC) experience difficulties in novel and complex problem-solving. The present study investigated verbal problem-solving, deductive reasoning, and semantic inference in AgCC. METHOD: Capacity for semantic inference was tested in 25 individuals with AgCC and normal-range intelligence compared to 29 neurotypical controls. The Word Context Test (WCT) of Delis-Kaplan Executive Function System was used, employing a novel method of analysis (semantic similarity) to detect trial-by-trial progress toward a solution. RESULTS: With respect to the typical WCT scores, persons with AgCC had fewer total consecutive correct responses. In addition, semantic similarity to the correct word was significantly lower overall in persons with AgCC than in controls. CONCLUSION: These findings indicated that individuals with AgCC who have intelligence in the normal range are less able at the WCT taking all trials into account, although they often solve the problem eventually. This outcome is consistent with previous research indicating that callosal absence in AgCC results in a restricted imagination for possibilities, limiting their problem-solving and inferential capacities. The results also highlight the usefulness of semantic similarity as a means of scoring the WCT. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Social Inferences in Agenesis of the Corpus Callosum and Autism: Semantic Analysis and Topic Modeling.

Impoverished capacity for social inference is one of several symptoms that are common to both agenesis of the corpus callosum (AgCC) and Autism Spectrum Disorder (ASD). This research compared the ability of 14 adults with AgCC, 13 high-functioning adults with ASD and 14 neurotypical controls to accurately attribute social meaning to the interactions of animated triangles. Descriptions of the animations were analyzed in three ways: subjective ratings, Linguistic Inquiry and Word Count, and topic modeling (Latent Dirichlet Allocation). Although subjective ratings indicated that all groups made similar inferences from the animations, the index of perplexity (atypicality of topic) generated from topic modeling revealed that inferences from individuals with AgCC or ASD displayed significantly less social imagination than those of controls.

Feeling at Home in the Wilderness: Environmental Conditions, Well-Being and Aesthetic Experience.

Environmental conditions affect one's aesthetic experience in natural environments. Understanding that effect requires accounting for the conditions affecting one's attention and experience. Rather than attempt to reduce and control environmental factors, we compare two similar groups during naturally occurring, intense and overwhelming conditions and examine the relationship between common characteristics as well as environment and group differences. Participants undertook a 5-day, winter, wilderness adventure training course designed to challenge their considerable wilderness and leadership skills under two different extreme weather conditions but within the same wilderness area (n = 47 full participation). In addition to pre- and post-adventure questionnaires, participants responded daily during the wilderness experience to briefly describe a self-selected, strong experience of nature; characterize its associated feeling states; and answer questions probing eight aesthetic aspects of the experience. Participant strong experience of nature related to hedonic and eudaimonic feelings in different ways depending upon environmental conditions. In particular, strong correlations occurred between agreement ratings with "I felt at home in nature" daily experience reports and satisfaction with life and personal growth trait measures, but primarily during sunny and cold conditions on a high plateau (PG: Pearson r = 0.51; SWL: r = 0.70) and not significantly in stormy and wet weather in a mountain forest. In addition, experience narratives that correspond to strongest agreement to feeling at home in nature were examined for shared themes and synthesized into six dimensions: focus on sensory experiences at a particular moment, self-reflection, wonder, appreciation of beauty, positive emotions, and insight of relation to nature. These findings actualize the notion of wonder, aroused by sudden feelings or by reflection, as a salient ingredient in feeling at home in wilderness. The finding of feeling at home in nature, as the most important feature relating to feelings and well-being, is discussed in relation to self-awareness, philosophical thinking, and potential ethical awareness.

Quantitative Measurement of the Improvement Derived From a 10-Mo Progressive Exercise Program to Improve Balance and Function in Women at Increased Risk for Fragility Fractures.

INTRODUCTION/BACKGROUND: Osteoporosis is a common disorder and is associated with an increased risk of bone fracture. Falls are a proximate cause of a high proportion of medical costs and mortality. Improving balance can reduce the risk of falls and improve health outcomes, especially for the at-risk population of people with osteoporosis and osteopenia. The FrameWorksTM exercise program is a formal, standardized, informational and interventional 10-month exercise program. The purpose of this study was to quantitatively assess the improvement in standing balance, functional reach, and overall confidence in balance after participating in the 10-month program. METHODOLOGY: This study is a prospectively designed study with a pre and post study measurement of balance metrics. Sixty-two female participants, 45 years of age or older and at increased risk for fragility fractures, completed the 10-month program as well the pre and post program testing. Confidence was measured with the Activities-specific Balance Confidence Scale, a self-reported survey. Balance was measured digitally by means of testing with a NeuroCom® Basic Balance Master® system. Measurements were made of the Limits of Stability (LOS) Test and Modified Clinical Test of Sensory Interaction on Balance (mCTSIB). Balance was clinically assessed with the Functional Reach Test (FRT). RESULTS: Participation in the 10 months FrameWorksTM program resulted in improvement in quantitative measures of balance (Composite Sway Velocity, -12%, p < 0.001; End point excursion, 17.1%, p < 0.000001). A clinical measure of balance, the Functional Reach Test, improved, (2.9 cm, p < 0.0001). Participation also resulted in improvement in balance confidence (9.4 %, p < 0.00001). A height increase was observed (0.6 cm, p < 0.000001). CONCLUSIONS: The 10-month FrameWorksTM program improves balance and confidence in women at risk for fragility fractures. By improving balance and confidence, people are less likely to fall and therefore sustain fewer fractures and associated injuries.

Dynamic Alterations of Retinal EphA5 Expression in Retinocollicular Map Plasticity.

The topographically ordered retinocollicular projection is an excellent system for studying the mechanism of axon guidance. Gradients of EphA receptors in the retina and ephrin-As in the superior colliculus (SC) pattern the anteroposterior axis of the retinocollicular map, but whether they are involved in map plasticity after injury is unknown. Partial damage to the caudal SC at birth creates a compressed, complete retinotopic map in the remaining SC without affecting visual response properties. Previously, we found that the gradient of ephrin-A expression in compressed maps is steeper than normal, suggesting an instructive role in compression. Here we measured EphA5 mRNA and protein levels after caudal SC damage in order to test the hypothesis that changes in retinal EphA5 expression occur that are complementary to the changes in collicular ephrin-A expression. We find that the nasotemporal gradient of EphA5 receptor expression steepens in the retina and overall expression levels change dynamically, especially in temporal retina, supporting the hypothesis. This change in receptor expression occurs after the change in ephrin-A ligand expression. We propose that changes in the retinal EphA5 gradient guide recovery of the retinocollicular projection from early injury. This could occur directly through the change in EphA5 expression instructing retino-SC map compression, or through ephrin-A ligand signaling instructing a change in EphA5 receptor expression that in turn signals the retinocollicular map to compress. Understanding what molecular signals direct compensation for injury is essential to developing rehabilitative strategies and maximizing the potential for recovery.

2-Amino-4-(3,4-(methylenedioxy)benzylamino)-6-(3-methoxyphenyl)pyrimidine is an anti-inflammatory TLR-2, -4 and -5 response mediator in human monocytes.

OBJECTIVE AND DESIGN: To elucidate the influence of 2-amino-4-(3,4-(methylenedioxy)benzylamino)-6-(3-methoxyphenyl)pyrimidine (AMBMP), a canonical Wnt/ß-catenin pathway activator, on the inflammatory response of TLR-engaged innate cells in vitro. MATERIAL OR SUBJECT: Primary human monocytes. TREATMENT: AMPMB (0-10 µM), LPS (0-1.0 µg/ml), Pam3CSK4, FSL-1, or S. typhimurium flagellin (0-0.25 µg/ml). METHODS: TLR-induced cytokine release (TNF, IL-6, IL-12 p40) was monitored by ELISA while Wnt-related signals (GSK3ß, p65, IκB, ß-catenin) were assessed by Western blot, pharmaceutical inhibition and gene silencing. RESULTS: AMBMP induced the rapid phosphorylation of NFκB p65 at Ser(536) and abrogated total IκB, accompanied by a subsequent increase in pro-inflammatory cytokine production (TNF, IL-6, IL-12 p40) in otherwise naive monocytes. However, in TLR2, -4 and -5-engaged monocytes, AMBMP-suppressed cytokine production. In the context of LPS stimulation, this occurred concomitant with the phosphorylative inactivation of GSK3ß at Ser(9), ß-catenin accumulation and abrogation of NFκB p65 phosphorylation. AMBMP-mediated suppression of the TLR4 -induced inflammatory response was reversed by two pharmaceutical Wnt/ß-catenin pathway inhibitors, IWP-2 and PNU-74654 and by Wnt3a silencing. CONCLUSIONS: Herein, we show that AMBMP induces canonical Wnt signaling events and acts as a suppressor of inflammation in surface TLR-engaged primary human monocytes.

Metabolism and excretion of anacetrapib, a novel inhibitor of the cholesteryl ester transfer protein, in humans.

Anacetrapib is a novel cholesteryl ester transfer protein inhibitor being developed for the treatment of primary hypercholesterolemia and mixed dyslipidemia. The absorption, distribution, metabolism, and excretion of anacetrapib were investigated in an open-label study in which six healthy male subjects received a single oral dose of 150 mg and 165 microCi of [(14)C]anacetrapib. Plasma, urine, and fecal samples were collected at predetermined times for up to 14 days postdose and were analyzed for total radioactivity, the parent compound, and metabolites. The majority of the administered radioactivity (87%) was eliminated by fecal excretion, with negligible amounts present in urine (0.1%). The peak level of radioactivity in plasma (approximately 2 microM equivalents of [(14)C]anacetrapib) was achieved approximately 4 h postdose. The parent compound was the major radioactive component (79-94% of total radioactivity) in both plasma and feces. Three oxidative metabolites, M1, M2, and M3, were detected in plasma and feces and were identified as the O-demethylated species (M1) and two secondary hydroxylated derivatives of M1 (M2 and M3). Each metabolite was detected at low levels, representing