Identifying subgroups of urge suppression in Obsessive-Compulsive Disorder using machine learning.

Obsessive-compulsive disorder (OCD) is phenomenologically heterogeneous. While predominant models suggest fear and harm prevention drive compulsions, many patients also experience uncomfortable sensory-based urges ("sensory phenomena") that may be associated with heightened interoceptive sensitivity. Using an urge-to-blink eyeblink suppression paradigm to model sensory-based urges, we previously found that OCD patients as a group had more eyeblink suppression failures and greater activation of sensorimotor-interoceptive regions than controls. However, conventional approaches assuming OCD homogeneity may obscure important within-group variability, impeding precision treatment development. This study investigated the heterogeneity of urge suppression failure in OCD and examined relationships with clinical characteristics and neural activation. Eighty-two patients with OCD and 38 controls underwent an fMRI task presenting 60-s blocks of eyeblink suppression alternating with free-blinking blocks. Latent profile analysis identified OCD subgroups based on number of erroneous blinks during suppression. Subgroups were compared on behavior, clinical characteristics, and brain activation during task. Three patient subgroups were identified. Despite similar overall OCD severity, the subgroup with the most erroneous eyeblinks had the highest sensory phenomena severity, interoceptive sensitivity, and subjective urge intensity. Compared to other subgroups, this subgroup exhibited more neural activity in somatosensory and interoceptive regions during the early phase (first 30 s) of blink suppression and reduced activity in the middle frontal gyrus during the late phase (second 30 s) as the suppression period elapsed. Heterogeneity of urge suppression in OCD was associated with clinical characteristics and brain function. Our results reveal potential treatment targets that could inform personalized medicine.

Decolonizing study-abroad programs in nursing in low- and middle-income countries.

Study abroad programs expose scholars, including nursing faculty and students, to different settings and cultures. However, the world of global health is rooted in colonial practices that have the potential to cause harm to communities. In this reflection, we provide lessons we have learned through study abroad that guide strategies for decolonizing our practice while working toward cultural safety and humility. We utilized a qualitative case study method. Authors discussed and reviewed study abroad programs through a series of virtual discussions. Discussions showed that study abroad programs present opportunities for students and faculty to grow and learn. However, unacknowledged privileges among visiting students and faculty, and lack of understanding of the impacts of colonialism, may lead to harm in communities and inequitable relationships with local providers. Understanding the privileges that we hold is important in advancing positive and equitable experiences in study abroad programs.

Evaluating language models for mathematics through interactions.

There is much excitement about the opportunity to harness the power of large language models (LLMs) when building problem-solving assistants. However, the standard methodology of evaluating LLMs relies on static pairs of inputs and outputs; this is insufficient for making an informed decision about which LLMs are best to use in an interactive setting, and how that varies by setting. Static assessment therefore limits how we understand language model capabilities. We introduce CheckMate, an adaptable prototype platform for humans to interact with and evaluate LLMs. We conduct a study with CheckMate to evaluate three language models (InstructGPT, ChatGPT, and GPT-4) as assistants in proving undergraduate-level mathematics, with a mixed cohort of participants from undergraduate students to professors of mathematics. We release the resulting interaction and rating dataset, MathConverse. By analyzing MathConverse, we derive a taxonomy of human query behaviors and uncover that despite a generally positive correlation, there are notable instances of divergence between correctness and perceived helpfulness in LLM generations, among other findings. Further, we garner a more granular understanding of GPT-4 mathematical problem-solving through a series of case studies, contributed by experienced mathematicians. We conclude with actionable takeaways for ML practitioners and mathematicians: models that communicate uncertainty, respond well to user corrections, and can provide a concise rationale for their recommendations, may constitute better assistants. Humans should inspect LLM output carefully given their current shortcomings and potential for surprising fallibility.

Ketamine vs Electroconvulsive Therapy for Treatment-Resistant Depression: A Secondary Analysis of a Randomized Clinical Trial.

Importance: The ELEKT-D: Electroconvulsive Therapy (ECT) vs Ketamine in Patients With Treatment Resistant Depression (TRD) (ELEKT-D) trial demonstrated noninferiority of intravenous ketamine vs ECT for nonpsychotic TRD. Clinical features that can guide selection of ketamine vs ECT may inform shared decision-making for patients with TRD. Objective: To evaluate whether selected clinical features were associated with differential improvement with ketamine vs ECT. Design, Setting, and Participants: This secondary analysis of an open-label noninferiority randomized clinical trial was a multicenter study conducted at 5 US academic medical centers from April 7, 2017, to November 11, 2022. Analyses for this study, which were not prespecified in the trial protocol, were conducted from May 10 to Oct 31, 2023. The study cohort included patients with TRD, aged 21 to 75 years, who were in a current nonpsychotic depressive episode of at least moderate severity and were referred for ECT by their clinicians. Exposures: Eligible participants were randomized 1:1 to receive either 6 infusions of ketamine or 9 treatments with ECT over 3 weeks. Main Outcomes and Measures: Association between baseline factors (including 16-item Quick Inventory of Depressive Symptomatology Self-Report [QIDS-SR16], Montgomery-Asberg Depression Rating Scale [MADRS], premorbid intelligence, cognitive function, history of attempted suicide, and inpatient vs outpatient status) and treatment response were assessed with repeated measures mixed-effects model analyses. Results: Among the 365 participants included in this study (mean [SD] age, 46.0 [14.5] years; 191 [52.3%] female), 195 were randomized to the ketamine group and 170 to the ECT group. In repeated measures mixed-effects models using depression levels over 3 weeks and after false discovery rate adjustment, participants with a baseline QIDS-SR16 score of 20 or less (-7.7 vs -5.6 points) and those starting treatment as outpatients (-8.4 vs -6.2 points) reported greater reduction in the QIDS-SR16 with ketamine vs ECT. Conversely, those with a baseline QIDS-SR16 score of more than 20 (ie, very severe depression) and starting treatment as inpatients reported greater reduction in the QIDS-SR16 earlier in course of treatment (-8.4 vs -6.7 points) with ECT, but scores were similar in both groups at the end-of-treatment visit (-9.0 vs -9.9 points). In the ECT group only, participants with higher scores on measures of premorbid intelligence (-14.0 vs -11.2 points) and with a comorbid posttraumatic stress disorder diagnosis (-16.6 vs -12.0 points) reported greater reduction in the MADRS score. Those with impaired memory recall had greater reduction in MADRS during the second week of treatment (-13.4 vs -9.6 points), but the levels of MADRS were similar to those with unimpaired recall at the end-of-treatment visit (-14.3 vs -12.2 points). Other results were not significant after false discovery rate adjustment. Conclusions and Relevance: In this secondary analysis of the ELEKT-D randomized clinical trial of ECT vs ketamine, greater improvement in depression was observed with intravenous ketamine among outpatients with nonpsychotic TRD who had moderately severe or severe depression, suggesting that these patients may consider ketamine over ECT for TRD.

Gafchromic EBT3 film provides equivalent dosimetric performance to EBT-XD film for stereotactic radiosurgery dosimetry.

The accurate assessment of film results is highly dependent on the methodology and techniques used to process film. This study aims to compare the performance of EBT3 and EBT-XD film for SRS dosimetry using two different film processing methods. Experiments were performed in a solid water slab and an anthropomorphic head phantom. For each experiment, the net optical density of the film was calculated using two different methods; taking the background (initial) optical density from 1) an unirradiated film from the same film lot as the irradiated film (stock to stock (S-S) method), and 2) a scan of the same piece of film taken prior to irradiation (film to film (F-F) method). EBT3 and EBT-XD performed similarly across the suite of experiments when using the green channel only or with triple channel RGB dosimetry. The dosimetric performance of EBT-XD was improved across all colour channels by using an F-F method, particularly for the blue channel. In contrast, EBT3 performed similarly well regardless of the net optical density method used. Across 21 SRS treatment plans, the average per-pixel agreement between EBT3 and EBT-XD films, normalised to the 20 Gy prescription dose, was within 2% and 4% for the non-target (2-10 Gy) and target (> 10 Gy) regions, respectively, when using the F-F method. At doses relevant to SRS, EBT3 provides comparable dosimetric performance to EBT-XD. In addition, an S-S dosimetry method is suitable for EBT3 while an F-F method should be adopted if using EBT-XD.

Predicting physical activity by the personality styles of the five-factor model.

OBJECTIVE: Low neuroticism, high extraversion, and high conscientiousness are related to physical activity (PA). We tested whether the small size and heterogeneity of these relationships result because personality traits influence one another as well as because some narrow facets rather than the broad domains contain more specific variance relevant to PA. METHOD: Participants were men and women enrolled in the University of North Carolina Alumni Heart Study who completed the Revised NEO Personality Inventory (NEO-PI-R) and reported their past month's average activity on an 8-point scale. In Study 1, we examined prospective correlations between the five NEO-PI-R domains and PA. In Studies 2 and 3, we used multinomial logistic regression to examine associations between PA and trait pair combinations (personality styles) controlling for age, sex, educational achievement, relationship status, and depression. RESULTS: Study 1 revealed that lower neuroticism (N) and agreeableness (A) and higher conscientiousness (C) predicted more PA. Taken together, Studies 2 and 3 found that the combination of high Extraversion (E) and high openness (O) was related to higher PA and that combinations of low E and high A and low E and low C were related to lower PA. Study 3, which examined the activity facet of E (E4), found that E4 is an important driver of E-PA associations. CONCLUSIONS: Personality traits do not operate in isolation. They may influence how other traits are expressed and such nonadditive effects can impact PA. Assessment of personality styles could help to identify individuals at risk for PA avoidance and may be useful for developing personalized interventions. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Molecular Transducers of Physical Activity Consortium (MoTrPAC): Human Studies Design and Protocol.

Physical activity, including structured exercise, is associated with favorable health-related chronic disease outcomes. While there is evidence of various molecular pathways that affect these responses, a comprehensive molecular map of these molecular responses to exercise has not been developed. The Molecular Transducers of Physical Activity Consortium (MoTrPAC) is a multi-center study designed to isolate the effects of structured exercise training on the molecular mechanisms underlying the health benefits of exercise and physical activity. MoTrPAC contains both a pre-clinical and human component. The details of the human studies component of MoTrPAC that include the design and methods are presented here. The human studies contain both an adult and pediatric component. In the adult component, sedentary participants are randomized to 12 weeks of Control, Endurance Exercise Training, or Resistance Exercise Training with outcomes measures completed before and following the 12 weeks. The adult component also includes recruitment of highly active endurance trained or resistance trained participants who only complete measures once. A similar design is used for the pediatric component; however, only endurance exercise is examined. Phenotyping measures include weight, body composition, vital signs, cardiorespiratory fitness, muscular strength, physical activity and diet, and other questionnaires. Participants also complete an acute rest period (adults only) or exercise session (adults, pediatrics) with collection of biospecimens (blood only for pediatrics) to allow for examination of the molecular responses. The design and methods of MoTrPAC may inform other studies. Moreover, MoTrPAC will provide a repository of data that can be used broadly across the scientific community.

Ultrasound-detected effusion-synovitis is associated with greater limb loading rate asymmetry during walking post-ACL reconstruction: A pilot study.

Objective: Chronic inflammation and altered walking biomechanics are common after ACL reconstruction (ACLR) and contribute to the development of osteoarthritis. Clinically accessible techniques are needed to monitor inflammation (ultrasound-assessed effusion-synovitis) and walking biomechanics (force-measuring insoles), and they must improve the translation of these assessments and determine whether inflammation and walking biomechanics are related in patients after ACLR. This study aimed to determine the association between ultrasound-detected knee effusion-synovitis and limb loading asymmetries during walking in patients 1-5 years post-ACLR. Design: 15 participants (9 women; age: 26 ± 6yrs; mass: 71 ± 15 kg; height: 173 ± 9 cm; months post-ACLR: 29 ± 13) were included in this cross-sectional study. Knee effusion-synovitis was assessed using a standardized protocol and graded using a validated scoring atlas (0 = absent, 1 = mild, 2 = moderate, 3 = severe) in the ACLR limb. Force-measuring insoles were used to capture the vertical ground reaction force (vGRF) during a one-minute treadmill walking trial. Limb symmetry indices (LSIs) were used to quantify limb loading asymmetry for the peak vGRF and the instantaneous loading rate (vGRF-LR). Spearman correlations determined whether effusion-synovitis grade was associated with peak vGRF and vGRF-LR LSI. Results: Effusion-synovitis was present in the ACLR limb of 13/15 (87 %) participants (Grade 0: n = 2; Grade 1: n = 8; Grade 2: n = 4, Grade 3: n = 1). Effusion-synovitis grade was not significantly associated with peak vGRF LSI (mean±sd: 98.0 ± 5.6; ρ = 0.38, p = 0.162), but was significantly associated with vGRF-LR LSI (98.2 ± 11.4; ρ = 0.55, p = 0.035). Conclusion: Most participants 1-5 years post-ACLR have ultrasound-detected effusion-synovitis. Participants with more severe effusion-synovitis load their ACLR limb more rapidly. This study highlights the utility of clinically accessible techniques in assessing inflammation and walking biomechanics in ACLR patients.

Genome-Wide Genetic Analysis of Dropout in a Controlled Exercise Intervention in Sedentary Adults With Overweight or Obesity and Cardiometabolic Disease.

BACKGROUND: Despite the benefits of exercise, many individuals are unable or unwilling to adopt an exercise intervention. PURPOSE: The purpose of this analysis was to identify putative genetic variants associated with dropout from exercise training interventions among individuals in the STRRIDE trials. METHODS: We used a genome-wide association study approach to identify genetic variants in 603 participants initiating a supervised exercise intervention. Exercise intervention dropout occurred when a subject withdrew from further participation in the study or was otherwise lost to follow-up. RESULTS: Exercise intervention dropout was associated with a cluster of single-nucleotide polymorphisms with the top candidate being rs722069 (T/C, risk allele = C) (unadjusted p = 2.2 × 10-7, odds ratio = 2.23) contained within a linkage disequilibrium block on chromosome 16. In Genotype-Tissue Expression, rs722069 is an expression quantitative trait locus of the EARS2, COG7, and DCTN5 genes in skeletal muscle tissue. In subsets of the STRRIDE genetic cohort with available muscle gene expression (n = 37) and metabolic data (n = 82), at baseline the C allele was associated with lesser muscle expression of EARS2 (p < .002) and COG7 (p = .074) as well as lesser muscle concentrations of C2- and C3-acylcarnitines (p = .026). CONCLUSIONS: Our observations imply that exercise intervention dropout is genetically moderated through alterations in gene expression and metabolic pathways in skeletal muscle. Individual genetic traits may allow the development of a biomarker-based approach for identifying individuals who may benefit from more intensive counseling and other interventions to optimize exercise intervention adoption. CLINICAL TRIAL INFORMATION: STRRIDE I = NCT00200993; STRRIDE AT/RT = NCT00275145; STRRIDE-PD = NCT00962962.

Regular participation in exercise can provide a myriad of health benefits. Although individuals recognize these benefits, many are unable or unwilling to adopt an exercise intervention once initiated. The purpose of this analysis was to identify genetic variants associated with dropout from an exercise training intervention. We found exercise intervention dropout to be genetically moderated through changes in gene expression and metabolic pathways in muscle. Thus, individual genetic traits may allow for the development of a biomarker-based targeted approach for identifying individuals who may benefit from more intensive counseling and interventions to optimize the adoption of an exercise intervention program.

Sensory over-responsivity and orbitofrontal cortex connectivity in obsessive-compulsive disorder.

BACKGROUND: Sensory over-responsivity (SOR) in obsessive-compulsive disorder (OCD) is associated with illness severity and functional impairment. However, the neural substrates of SOR in OCD have not yet been directly probed. METHODS: We examined resting-state global functional connectivity markers of SOR in 119 adults with OCD utilizing the CONN-fMRI Functional Connectivity Toolbox for SPM (v21a). We quantified SOR with the sensory sensitivity and sensory avoiding subscales of the Adult and Adolescent Sensory Profile (AASP). We also measured: OCD severity, with the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) and Obsessive-Compulsive Inventory-Revised (OCI-R); sensory phenomena with the Sensory Phenomena Scale (SPS); general anxiety, with the Beck Anxiety Inventory (BAI); and depressive symptomatology, with Quick Inventory of Depressive Symptoms, Self-Report (QIDS-SR). RESULTS: There was a significant positive relationship of SOR with global connectivity in anterior and medial OFC (Brodmanns area 11, k = 154, x = 14, y = 62, z = -18, whole-brain corrected at FWE p < 0.05). LIMITATIONS: Future investigations should explore neural responses to sensory stimulation tasks in OCD and compare findings with those obtained in other conditions also characterized by high SOR, such as autism spectrum disorder. CONCLUSIONS: This study implicates OFC functional connectivity as a neurobiological mechanism of SOR in OCD and suggests that the substrates of SOR in OCD may be dissociable from both that of other symptoms in OCD, and SOR in other disorders. With replication and extension, the finding may be leveraged to develop and refine treatments for OCD and investigate the pathophysiology of SOR in other conditions.

Persistent Early Knee Osteoarthritis Symptoms in the First Two Years After ACL Reconstruction.

CONTEXT: Early identification of knee osteoarthritis (OA) symptoms after anterior cruciate ligament reconstruction (ACLR) could enable timely interventions to improve long-term outcomes. However, little is known about the change in early OA symptoms from 6 to 12 months following ACLR. OBJECTIVE: To evaluate the change over time in meeting classification criteria for early knee OA symptoms from 6 to 12 months following ACLR. DESIGN: Prospective Cohort Study. SETTING: Research laboratory. PATIENTS OR OTHER PARTICIPANTS: 82 participants aged 13-35 years who underwent unilateral primary ACLR. On average, participants' 1st and 2nd visits were 6.2 and 12.1 months post-ACLR. MAIN OUTCOME MEASURES: Early OA symptoms were classified using generic (Luyten Original) and patient population-specific (Luyten PASS) thresholds on Knee Injury and Osteoarthritis Outcome Score (KOOS) subscales. Changes in meeting early OA criteria were compared between an initial and follow-up visit at an average of 6 and 12 months post-ACLR, respectively. RESULTS: Twenty-two percent of participants exhibited persistent early OA symptoms across both visits using both the Luyten Original and PASS criteria. From initial to follow-up visit, 18-27% had resolution of early OA symptoms while 4-9% developed incident symptoms. In total, 48-51% had no early OA symptoms at either visit. There were no differences between change in early OA status between adults and adolescents. CONCLUSIONS: Nearly one quarter of participants exhibited persistent early knee OA symptoms based on KOOS thresholds from 6 to 12 months post-ACLR. Determining if this symptom persistence predicts worse long-term outcomes could inform the need for timely interventions after ACLR. Future research should examine if resolving persistent symptoms in this critical window improves later outcomes. Tracking early OA symptoms over time may identify high-risk patients who could benefit from early treatment.

Lower Extremity Reaction Time in Individuals With Contact Versus Noncontact Anterior Cruciate Ligament Injuries After Reconstruction.

CONTEXT: Deficits in perceptual-motor function, like visuomotor reaction time (VMRT), are risk factors for primary and secondary anterior cruciate ligament (ACL) injury. Noncontact ACL injuries have been associated with slower reaction time, but whether this association exists for patients with contact ACL injuries is unknown. Exploring differences in VMRT among individuals with contact versus noncontact ACL injuries may provide a more comprehensive understanding of modifiable risk factors. OBJECTIVE: To compare lower extremity VMRT (LEVMRT) in individuals with contact or noncontact ACL injuries after ACL reconstruction (ACLR). DESIGN: Cross-sectional study. SETTING: Research laboratory. PATIENTS OR OTHER PARTICIPANTS: A total of 36 participants with primary, unilateral ACLR completed an LEVMRT assessment (contact ACL injury = 20 [56%], noncontact ACL injury = 16 [44%]). MAIN OUTCOME MEASURE(S): The LEVMRT was assessed bilaterally and collected using a series of wireless light discs deactivated by individuals with their feet. The ACLR-active LEVMRT (ie, ACLR limb is deactivating lights) and ACLR-stable LEVMRT were compared using separate analyses of covariance to determine the association with contact or noncontact injury using time since surgery as a covariate. RESULTS: After controlling for time since surgery, a difference and large effect size between groups was found for the ACLR-stable LEVMRT (P = .010; η2 = 0.250) but not for the ACLR-active (P = .340; η2 = 0.065) condition. The contact group exhibited slower ACLR-stable LEVMRT (521.7 ± 59.3 milliseconds) than the noncontact group (483.4 ± 83.9 milliseconds). CONCLUSIONS: Individuals with contact ACL injury demonstrated a slower LEVMRT while their ACLR limb was stabilizing. The group differences during the ACLR-stable LEVMRT task might indicate deficits in perceptual-motor function when the surgical limb maintains postural control during a reaction time task. After ACLR, individuals with contact injuries may need additional motor learning interventions to enhance perceptual-motor functioning.

Femoral cartilage ultrasound echo-intensity is a valid measure of cartilage composition.

This study aimed to create a conversion equation that accurately predicts cartilage magnetic resonance imaging (MRI) T2 relaxation times using ultrasound echo-intensity and common participant demographics. We recruited 15 participants with a primary anterior cruciate ligament reconstruction between the ages of 18 and 35 years at 1-5 years after surgery. A single investigator completed a transverse suprapatellar scan with the ACLR limb in max knee flexion to image the femoral trochlea cartilage. A single reader manually segmented the femoral cartilage cross-sectional area to assess the echo-intensity (i.e., mean gray-scale pixel value). At a separate visit, a T2 mapping sequence with the MRI beam set to an oblique angle was used to image the femoral trochlea cartilage. A single reader manually segmented the cartilage cross-sectional area on a single MRI slice to assess the T2 relaxation time. A stepwise, multiple linear regression was used to predict T2 relaxation time from cartilage echo-intensity and common demographic variables. We created a conversion equation using the regression betas and then used an ICC and Bland-Altman plot to assess agreement between the estimated and true T2 relaxation time. Cartilage ultrasound echo-intensity and age significantly predicted T2 relaxation time (F = 7.33, p = 0.008, R2 = 0.55). When using the new conversion equation to estimate T2 relaxation time from cartilage echo-intensity and age, there was strong agreement between the estimated and true T2 relaxation time (ICC2,k = 0.84). This study provides promising preliminary data that cartilage echo-intensity combined with age can be used as a clinically accessible tool for evaluating cartilage composition.

Psychological Readiness, Injury-Related Fear, and Persistent Knee Symptoms After Anterior Cruciate Ligament Reconstruction.

CONTEXT: Poor psychological responses after anterior cruciate ligament reconstruction (ACLR) have been associated with a failure to return to sport and increased secondary injury risk. However, we do not know whether poor psychological responses after ACLR influence patient-reported knee function and knee symptoms. OBJECTIVE: To examine the association between psychological factors (ie, psychological readiness and injury-related fear) and the presence of persistent knee symptoms in individuals 6 to 12 months after ACLR. DESIGN: Cross-sectional study. SETTING: Research laboratory. PATIENTS OR OTHER PARTICIPANTS: In total, 101 participants, aged 13 to 25 years old, between 6 and 12 months after primary unilateral ACLR were enrolled in the study. MAIN OUTCOME MEASURE(S): Persistent knee symptoms were identified using an established criterion based on the subscales of the Knee injury and Osteoarthritis Outcome Score. Participants also completed the Anterior Cruciate Ligament-Return to Sport after Injury (ACL-RSI) and the Tampa Scale of Kinesiophobia-11 (TSK-11) to assess psychological readiness and injury-related fear, respectively. Higher ACL-RSI scores indicate higher psychological readiness, and higher TSK-11 scores indicate higher injury-related fear. RESULTS: Twenty-nine participants (29%) met the criteria for persistent knee symptoms. For every 1 SD lower in the ACL-RSI score, participants had 2.1 times greater odds of persistent knee symptoms after ACLR (95% CI = 1.3, 3.6). For every 1 SD higher in the TSK-11 score, participants had 1.9 times greater odds of persistent knee symptoms after ACLR (95% CI = 1.1, 3.3). Both the ACL-RSI and TSK-11 were considered good at classifying persistent knee symptoms, as the areas under the curve were 0.78 and 0.73, respectively. CONCLUSIONS: Individuals with a lower level of psychological readiness and more injury-related fear after ACLR had greater odds of persistent knee symptoms. Overall, these results highlight the potential clinical benefit of a comprehensive, biopsychosocial approach to managing health and wellness for individuals after ACLR.

Demographic, Clinical, and Psychosocial Predictors of Exercise Adherence: The STRRIDE Trials.

Purpose: To identify baseline demographic, clinical, and psychosocial predictors of exercise intervention adherence in the Studies of a Targeted Risk Reduction Intervention through Defined Exercise (STRRIDE) trials. Methods: A total of 947 adults with dyslipidemia or prediabetes were enrolled into an inactive control group or one of ten exercise interventions with doses of 10-23 kcal/kg/week, intensities of 40-80% of peak oxygen consumption, and training for 6-8-months. Two groups included resistance training. Mean percent aerobic and resistance adherence were calculated as the amount completed divided by the prescribed weekly minutes or total sets of exercise times 100, respectively. Thirty-eight clinical, demographic, and psychosocial measures were considered for three separate models: 1) clinical + demographic factors, 2) psychosocial factors, and 3) all measures. A backward bootstrapped variable selection algorithm and multiple regressions were performed for each model. Results: In the clinical and demographic measures model (n=947), variables explained 16.7% of the variance in adherence (p<0.001); lesser fasting glucose explained the greatest amount of variance (partial R2 = 3.2%). In the psychosocial factors model (n=561), variables explained 19.3% of the variance in adherence (p<0.001); greater 36-Item Short Form Health Survey (SF-36) physical component score explained the greatest amount of variance (partial R2 = 8.7%). In the model with all clinical, demographic, and psychosocial measures (n=561), variables explained 22.1% of the variance (p<0.001); greater SF-36 physical component score explained the greatest amount of variance (partial R2 = 8.9%). SF-36 physical component score was the only variable to account for >5% of the variance in adherence in any of the models. Conclusions: Baseline demographic, clinical, and psychosocial variables explain approximately 22% of the variance in exercise adherence. The limited variance explained suggests future research should investigate additional measures to better identify participants who are at risk for poor exercise intervention adherence.

Rectus Femoris Ultrasound Echo Intensity Is a Valid Estimate of Percent Intramuscular Fat in Patients Following Anterior Cruciate Ligament Reconstruction.

OBJECTIVE: The aim of the work described here was to evaluate quadriceps muscle ultrasound metrics and common demographic variables to create a conversion equation that validly predicts magnetic resonance imaging (MRI) percent intramuscular fat after anterior cruciate ligament reconstruction (ACLR). METHODS: We recruited 15 participants between the ages of 18 and 35 y who were 1-5 y post-ACLR. For the MRI assessment, we used an iterative decomposition of water and fat with echo asymmetry and least-squares estimation (IDEAL) sequence to assess the mid-thigh. A single reader manually segmented the rectus femoris on two consecutive MRI slices using ITK-Snap to estimate the percent intramuscular fat. For the ultrasound assessment, a single investigator captured transverse panoramic ultrasound images of the mid-thigh with the participant positioned supine and the knee flexed to 30°. A separate single reader used ImageJ to manually segment the rectus femoris ultrasound images. Ultrasound metrics included muscle cross-sectional area, echo intensity and subcutaneous fat thickness. A stepwise linear multiple regression was used to develop an equation to predict MRI percent intramuscular fat using the ultrasound metrics and common demographics (i.e., age, sex, height, mass). Additionally, intraclass correlation coefficients (ICC2,k) and Bland-Altman plots were used to assess the agreement between true and estimated percent intramuscular fat. RESULTS: Echo intensity and age significantly predicted MRI intramuscular fat percent (p = 0.003, r2 = 0.62). When using the conversion equation, there was high agreement (ICC2,k = 0.87, 95% confidence interval: 0.62-0.96) between the estimated and true percent intramuscular fat. CONCLUSION: Our patient population-specific conversion equation that uses quadriceps muscle ultrasound echo intensity and age is a valid estimate of MRI percent intramuscular fat.

Affinity-enhanced RNA-binding domains as tools to understand RNA recognition.

Understanding how the RNA-binding domains of a protein regulator are used to recognize its RNA targets is a key problem in RNA biology, but RNA-binding domains with very low affinity do not perform well in the methods currently available to characterize protein-RNA interactions. Here, we propose to use conservative mutations that enhance the affinity of RNA-binding domains to overcome this limitation. As a proof of principle, we have designed and validated an affinity-enhanced K-homology (KH) domain mutant of the fragile X syndrome protein FMRP, a key regulator of neuronal development, and used this mutant to determine the domain's sequence preference and to explain FMRP recognition of specific RNA motifs in the cell. Our results validate our concept and our nuclear magnetic resonance (NMR)-based workflow. While effective mutant design requires an understanding of the underlying principles of RNA recognition by the relevant domain type, we expect the method will be used effectively in many RNA-binding domains.

Protocol Report on the Transcranial Photobiomodulation for Alzheimer's Disease (TRAP-AD) Study.

BACKGROUND: Alzheimer's disease's (AD) prevalence is projected to increase as the population ages and current treatments are minimally effective. Transcranial photobiomodulation (t-PBM) with near-infrared (NIR) light penetrates into the cerebral cortex, stimulates the mitochondrial respiratory chain, and increases cerebral blood flow. Preliminary data suggests t-PBM may be efficacious in improving cognition in people with early AD and amnestic mild cognitive impairment (aMCI). METHODS: In this randomized, double-blind, placebo-controlled study with aMCI and early AD participants, we will test the efficacy, safety, and impact on cognition of 24 sessions of t-PBM delivered over 8 weeks. Brain mechanisms of t-PBM in this population will be explored by testing whether the baseline tau burden (measured with 18F-MK6240), or changes in mitochondrial function over 8 weeks (assessed with 31P-MRSI), moderates the changes observed in cognitive functions after t-PBM therapy. We will also use changes in the fMRI Blood-Oxygenation-Level-Dependent (BOLD) signal after a single treatment to demonstrate t-PBM-dependent increases in prefrontal cortex blood flow. CONCLUSION: This study will test whether t-PBM, a low-cost, accessible, and user-friendly intervention, has the potential to improve cognition and function in an aMCI and early AD population.

Improving Domestic Violence Screening and Follow-Up in a Community Health Clinic.

PURPOSE: To implement an improved DV screening and follow-up protocol at a suburban community health clinic that is consistently used by staff with appropriate female patients as well as to assess provider/staff barriers to this. METHODS: The project was completed at a community health clinic and included 2 presentations: the first to outline current practices as well as the intervention plan at the pre-intervention time point and then to review results of the intervention and elicit feedback post intervention. Provider/staff barrier surveys were completed at both time points. The intervention consisted of completion of the HITS DV screening tool on all appropriate female patients and a system-level algorithm-based follow-up care plan for positive cases. RESULTS: Eligible patient screening increased by 3.1% and patients screening positive increased from 0 to 1 from baseline to intervention. Average scores on the barrier surveys improved for all questions and improved significantly for 3 of the questions. The algorithm implemented was utilized for the positive screening. CONCLUSIONS: Use of a DV screening tool, that has shown good concurrent and construct validity in the literature, a system-level algorithm for follow-up care and addressing provider/staff barriers to screening and follow-up are essential components of a successful DV screening and follow-up program.