Teprotumumab for Thyroid Eye Disease-related Strabismus.

PURPOSE: To assess and quantify teprotumumab's effect on thyroid eye disease-related strabismus by change in measured horizontal and vertical deviations and change in extraocular motility. METHODS: We reviewed a series of patients with thyroid eye disease-related strabismus treated with teprotumumab. Exclusion criteria included age under 18 years, strabismus of alternate etiology, or thyroid eye disease-related reconstructive surgery during the treatment course. Primary outcomes were absolute (prism diopters) and relative (%) differences in horizontal and vertical deviations in primary position at distance, as well as change in ductions of the more affected eye. Secondary outcomes included incidence and timing of strabismus surgery postteprotumumab. RESULTS: Thirty-one patients were included, with mean age 63 years and thyroid eye disease duration 10 months. After teprotumumab, there was 6 prism diopters (39%) mean reduction in vertical deviation ( p < 0.001), without significant change in mean horizontal deviation ( p = 0.75). Supraduction, abduction, adduction, and infraduction significantly improved in the more restricted eye ( p < 0.01, p < 0.01, p = 0.04, and p = 0.01, respectively). Thirty-five percent of patients underwent strabismus surgery posttreatment, at an average 10 months after last infusion. CONCLUSIONS: Teprotumumab produced a statistically significant reduction in vertical but not horizontal strabismus angles in primary position at distance. Extraocular motility in all 4 ductions also improved. A substantial minority of patients still required strabismus surgery following teprotumumab.

Sleep and Daytime Function in People with Spinal Cord Injury.

Study Design: Cross-sectional cohort study. Objectives: To determine the role of sleep-disordered breathing (SDB), insomnia symptoms and sleep quality in the daytime function and quality of life of veterans with spinal cord injury (SCI). Setting: A Veterans Administration (VA) medical center in the Midwestern US. Methods: Thirty-eight male veterans with SCI (22 cervical, 16 thoracic; mean [SD] age = 62.9[9.5] years) completed baseline assessments within a larger clinical trial. Measures assessed sleep apnea severity (apnea-hypopnea index, AHI), insomnia symptoms (Insomnia Severity Index, ISI), self-reported sleep quality (Pittsburg Sleep Quality Index, PSQI), daytime sleepiness (Epworth Sleepiness Scale, ESS), fatigue (Flinders Fatigue Scale, FFS), depression (Patient Health Questionnaire-9 item, PHQ-9 excluding sleep item), functioning (Spinal Cord Independence Measure, SCIM), and quality of life (World Health Organization Quality of Life, WHOQOL-BREF). Bivariate correlations (alpha p<.05) were used to assess relationships between sleep (AHI, ISI, PSQI, ESS) and function (FFS, PHQ-9, SCIM, WHOQOL-BREF). Results: Mean AHI was 29.9(26.6), mean ISI was 9.38(6.2), mean PSQI was 9.0(4.6), and mean ESS was 7.0(5.2). There were no significant relationships between AHI and function measures. Significant relationships emerged between ISI and PHQ-9, some WHOQOL-BREF subscales, and SCIM as well as between PSQI and FFS, PHQ-9, and some WHOQOL-BREF subscales. Conclusions: Among Veterans with SCI, insomnia symptom severity and poor sleep quality were associated with worse functioning, whereas SDB severity was not. Insomnia and poor sleep quality represent modifiable contributors to poor daytime function. Research evaluating the impact of evidence-based insomnia treatments among individuals living with SCI is warranted.

Cenozoic seeds of Vitaceae reveal a deep history of extinction and dispersal in the Neotropics.

The remarkably diverse plant communities of the Neotropics are the result of diversification driven by multiple biotic (for example, speciation, extinction and dispersal) and abiotic (for example, climatic and tectonic) processes. However, in the absence of a well-preserved, thoroughly sampled and critically assessed fossil record, the associated processes of dispersal and extinction are poorly understood. We report an exceptional case study documenting patterns of extinction in the grape family (Vitaceae Juss.) on the basis of fossil seeds discovered in four Neotropical palaeofloras dated between 60 and 19 Ma. These include a new species that provides the earliest evidence of Vitaceae in the Western Hemisphere. Eight additional species reveal the former presence of major clades of the family that are currently absent from the Neotropics and elucidate previously unknown dispersal events. Our results indicate that regional extinction and dispersal have substantially impacted the evolutionary history of Vitaceae in the Neotropics. They also suggest that while the Neotropics have been dynamic centres of diversification through the Cenozoic, extant Neotropical botanical diversity has also been shaped by extensive extinction over the past 66 million years.

Mobile toolbox (MTB) remote measures of executive function and processing speed: development and validation.

OBJECTIVE: The ability to remotely monitor cognitive skills is increasing with the ubiquity of smartphones. The Mobile Toolbox (MTB) is a new measurement system that includes measures assessing Executive Functioning (EF) and Processing Speed (PS): Arrow Matching, Shape-Color Sorting, and Number-Symbol Match. The purpose of this study was to assess their psychometric properties. METHOD: MTB measures were developed for smartphone administration based on constructs measured in the NIH Toolbox® (NIHTB). Psychometric properties of the resulting measures were evaluated in three studies with participants ages 18 to 90. In Study 1 (N = 92), participants completed MTB measures in the lab and were administered both equivalent NIH TB measures and other external measures of similar cognitive constructs. In Study 2 (N = 1,021), participants completed the equivalent NIHTB measures in the lab and then took the MTB measures on their own, remotely. In Study 3 (N = 168), participants completed MTB measures twice remotely, two weeks apart. RESULTS: All three measures exhibited very high internal consistency and strong test-retest reliability, as well as moderately high correlations with comparable NIHTB tests and moderate correlations with external measures of similar constructs. Phone operating system (iOS vs. Android) had a significant impact on performance for Arrow Matching and Shape-Color Sorting, but no impact on either validity or reliability. CONCLUSIONS: Results support the reliability and convergent validity of MTB EF and PS measures for use across the adult lifespan in remote, self-administered designs.

The effectiveness of cognitive behavioral therapy for insomnia on sleep outcomes in the context of pain among older adult veterans.

BACKGROUND: Cognitive behavioral therapy for insomnia (CBT-I) is the gold-standard treatment for insomnia disorder in adults. Compared to young adults, older adults have increased risk for the development of conditions associated with chronic pain, which may impact the efficacy of CBT-I in improving insomnia symptoms in older adults. This study evaluated the effect of participant-rated pain on sleep-related outcomes of a supervised, non-clinician administered CBT-I program in older adult patients with chronic insomnia disorder. METHODS: Secondary analysis was conducted using data from a randomized controlled trial among 106 community-dwelling older adult veterans (N = 106; mean age 72.1 years, 96% male, 78.3% White, 6.6% Hispanic, 5.7% African American) with chronic (≥3 months) insomnia disorder. Participants engaged in five sessions of manual-based CBT-I in individual or group format within one Department of Veterans Affairs healthcare system, provided by non-clinician "sleep coaches" who had weekly telephone supervision by behavioral sleep medicine specialists. Insomnia symptoms (Insomnia Severity Index), perceived sleep quality (Pittsburgh Sleep Quality Index), fatigue (Flinder's Fatigue Scale), daytime sleepiness (Epworth Sleepiness Scale), and perceived pain severity (items from the Geriatric Pain Measure) were assessed at 4 time points: baseline, one-week posttreatment, 6-month follow-up, and 12-month follow-up. Mixed effects models with time invariant and time varying predictors were employed for analyses. RESULTS: CBT-I improved insomnia symptoms, perceived sleep quality, fatigue, and daytime sleepiness among older veterans with chronic insomnia. Participant-reported pain was associated with greater improvements in insomnia symptoms following CBT-I. Pain did not affect improvements in other sleep-related outcomes (-0.38 ≤ b ≤ 0.07, p > 0.05). Between-subjects differences in pain, but not within-subject changes in pain over time, appeared to play a central role in insomnia symptom improvement at posttreatment, with individuals with higher-than-average pain showing greater insomnia symptom improvement (ISI score reduction; -0.32 ≤ b ≤ -0.28, p ≤ 0.005). CONCLUSIONS: Pain did not meaningfully hinder the effects of CBT-I on sleep outcomes. Among older veterans with chronic insomnia disorder, individuals with higher pain exhibited slightly greater improvement in insomnia than those with lower levels of pain. These findings suggest that experiencing pain does not impair treatment response and should not preclude older adults with insomnia from being offered CBT-I.

Treatment of acromegaly with the nonpeptide, highly selective somatostatin receptor type 2 agonist paltusotine.

Injectable first-generation somatostatin receptor ligands (fg-SRLs) are the standard of care of medical treatment for acromegaly. While fg-SRLs control acromegaly in up to 50 % of patients, they may lead to bothersome injection pain and site reactions. Paltusotine is an investigational, highly selective somatostatin receptor subtype 2 agonist, which is administered orally once a day. To date, phase 2 and 3 clinical trials suggest paltusotine treatment can achieve biochemical and symptom control in acromegaly, with a safety profile comparable to those of the fg-SRLs. Since paltusotine is a once-daily oral drug, it may represent a future treatment option for addressing patient preference or improving quality of life.

Acromegaly Disease Control Maintained After Switching From Injected Somatostatin Receptor Ligands to Oral Paltusotine.

CONTEXT: Paltusotine is a nonpeptide selective somatostatin receptor 2 agonist in development as once-daily oral treatment for acromegaly. OBJECTIVE: To evaluate the efficacy and safety of paltusotine in the treatment of patients with acromegaly previously controlled with injected somatostatin receptor ligands (SRLs). METHODS: This phase 3, randomized, double-blind, placebo-controlled trial enrolled adults with acromegaly who had insulin-like growth factor I (IGF-I) ≤1.0 times the upper limit of normal (×ULN) while receiving a stable dose of depot octreotide or lanreotide. Patients were switched from injected SRLs and randomized to receive paltusotine or placebo orally for 36 weeks. The primary endpoint was proportion of patients maintaining IGF-I ≤1.0×ULN. Secondary endpoints were change in IGF-I level, change in Acromegaly Symptom Diary (ASD) score, and maintenance of mean 5-sample growth hormone (GH) <1.0 ng/mL. RESULTS: The primary endpoint was met: 83.3% (25/30) of patients receiving paltusotine and 3.6% (1/28) receiving placebo maintained IGF-I ≤1.0×ULN (odds ratio: 126.53; 95% CI: 13.73, >999.99; P<.0001). Paltusotine was also superior to placebo for all secondary endpoints: mean (±SE) change in IGF-I of 0.04±0.09×ULN versus 0.83±0.1×ULN (P<.0001); mean (±SE) change in ASD score of -0.6±1.5 versus 4.6±1.6 (P=.02); mean GH maintained at <1.0 ng/mL in 20/23 (87.0%) versus 5/18 (27.8%) patients (odds ratio: 16.61; 95% CI: 2.86, 181.36; P=.0003). The most common adverse events were acromegaly symptoms and gastrointestinal effects characteristic of SRLs. CONCLUSION: Replacement of injected SRLs by once-daily oral paltusotine was effective in maintaining both biochemical and symptom control in patients with acromegaly and was well tolerated.

More Than Skin Deep: Patient-Provider Racial and Ethnic Concordance and Discordance in Collegiate Athletics and Concussion Management.

CONTEXT: There is strong evidence that racial and ethnic disparities exist in multiple arenas of health and wellness. The causes of racial and ethnic differences in health care are multidimensional; one factor that may affect injury/illness communication, interactions, and outcomes is patient-provider racial and ethnic concordance. At present, it is unclear what role patient-provider racial and ethnic concordance and discordance plays in facilitating concussion care for collegiate athletes. OBJECTIVE: To investigate the presence of athlete-athletic trainer (AT) racial and ethnic concordance and discordance among diagnosed concussion cases and examine if racial and ethnic concordance and discordance influences time (in days) until diagnosis, symptom resolution, or return-to-sport clinical milestones in collegiate athletes. DESIGN: Retrospective cohort study. SETTING: Collegiate athletics. PATIENTS OR OTHER PARTICIPANTS: A total of 694 concussion cases (38.6% [n = 268] sustained by women, 61.4% [n = 426] sustained by men) that occurred within the 2015-2016 through 2019-2020 sport seasons at 9 institutions. MAIN OUTCOME MEASURE(S): The number of days from the date of injury to diagnosis, symptom resolution, and return to sport and from the date of diagnosis to symptom resolution and return to sport. RESULTS: Overall, 68.4% (n = 475) of concussion cases had patient-provider racial and ethnic concordance, and 31.6% (n = 219) were discordant. All concordant pairs included a White athlete and White AT. Time to diagnosis differed between the concordant and discordant groups (median [interquartile range] = 1 [0-2] versus 0 [0-1], respectively) only in the model adjusted for sex, sport type, and availability of an AT (odds ratio [95% CI] = 1.46 [1.07-1.85]). There were no other group differences. CONCLUSIONS: One-third of concussion cases had athlete-AT racial and ethnic discordance. Although this group was diagnosed with a concussion 1 day sooner than the concordant group, no differences were observed for any concussion recovery milestones. These findings suggest that patient-provider racial and ethnic concordance may play a minor role in concussion recognition or reporting but not necessarily in the management and recovery thereafter.

Enhancing starch functionality through synergistic modification via sequential treatments with cold plasma and electron beam irradiation.

The impact of dual sequential modifications using radio-frequency (RF) plasma and electron beam irradiation (EBI) on starch properties was investigated and compared with single treatments within an irradiation dose range of 5-20 kGy. Regardless of sequence, dual treatments synergistically affected starch properties, increasing acidity, solubility, and paste clarity, while decreasing rheological features with increasing irradiation dose. The molecular weight distribution was also synergistically influenced. Amylopectin distribution broadened particularly below 10 kGy. Amylose narrowed its distribution across all irradiation doses. This was due to dominating EBI-induced degradation and molecular rearrangements from RF plasma. With the highest average radiation-chemical yield (G) and degradation rate constant (k) of (2.12 ± 0.14) × 10-6 mol·J-1 and (3.43 ± 0.23) × 10-4 kGy-1, respectively, upon RF plasma pre-treatment, amylose underwent random chain scission. In comparison to single treatments, dual modification caused minor alterations in spectral characteristics and crystal short-range order structure, along with increased granule aggregation and surface irregularities. The synergistic effect was dose-dependent, significant up to 10 kGy, irrespective of treatment sequence. The highest synergistic ratio was observed when RF plasma preceded irradiation, demonstrating the superior efficiency of plasma pre-treatment in combination with EBI. This synergy has the potential to lower costs and extend starch's technological uses by enhancing radiation sensitivity and reducing the irradiation dose.

Development and validation of an episodic memory measure in the Mobile Toolbox (MTB): Arranging Pictures.

INTRODUCTION: Arranging Pictures is a new episodic memory test based on the NIH Toolbox (NIHTB) Picture Sequence Memory measure and optimized for self-administration on a personal smartphone within the Mobile Toolbox (MTB). We describe evidence from three distinct validation studies. METHOD: In Study 1, 92 participants self-administered Arranging Pictures on study-provided smartphones in the lab and were administered external measures of similar and dissimilar constructs by trained examiners to assess validity under controlled circumstances. In Study 2, 1,021 participants completed the external measures in the lab and self-administered Arranging Pictures remotely on their personal smartphones to assess validity in real-world contexts. In Study 3, 141 participants self-administered Arranging Pictures remotely twice with a two-week delay on personal iOS smartphones to assess test-retest reliability and practice effects. RESULTS: Internal consistency was good across samples (ρxx = .80 to .85, p < .001). Test-retest reliability was marginal (ICC = .49, p < .001) and there were significant practice effects after a two-week delay (ΔM = 3.21 (95% CI [2.56, 3.88]). As expected, correlations with convergent measures were significant and moderate to large in magnitude (ρ = .44 to .76, p < .001), while correlations with discriminant measures were small (ρ = .23 to .27, p < .05) or nonsignificant. Scores demonstrated significant negative correlations with age (ρ = -.32 to -.21, p < .001). Mean performance was slightly higher in the iOS compared to the Android group (MiOS = 18.80, NiOS = 635; MAndroid = 17.11, NAndroid = 386; t(757.73) = 4.17, p < .001), but device type did not significantly influence the psychometric properties of the measure. Indicators of potential cheating were mixed; average scores were significantly higher in the remote samples (F(2, 850) = 11.415, p < .001), but there were not significantly more perfect scores. CONCLUSION: The MTB Arranging Pictures measure demonstrated evidence of reliability and validity when self-administered on personal device. Future research should examine the potential for cheating in remote settings and the properties of the measure in clinical samples.

Interactions of cumulative load with biomarkers of cartilage turnover predict knee cartilage change over 2 years: data from the osteoarthritis initiative.

The purpose was to investigate relationships of cumulative load and cartilage turnover biomarkers with 2-year changes in cartilage in knee osteoarthritis. From participants with Kellgren-Lawrence (KL) grades of 1 to 3, cartilage thickness and transverse relaxation time (T2) were computed from 24-month (baseline) and 48-month magnetic resonance images. Cumulative load was the interaction term of the Physical Activity Scale for the Elderly (PASE) and body mass index (BMI). Serum cartilage oligomeric matrix protein (COMP) and the nitrated form of type II collagen (Coll2-1 NO2) were collected at baseline. Multiple regressions (adjusted for baseline age, KL grade, cartilage measures, pain, comorbidity) evaluated the relationships of cumulative load and biomarkers with 2-year changes. In 406 participants (63.7 (8.7) years), interactions of biomarkers with cumulative load weakly predicted 2-year cartilage changes: (i) COMP × cumulative load explained medial tibia thickness change (R2 increased 0.062 to 0.087, p < 0.001); (ii) Coll2-1 NO2 × cumulative load explained central medial femoral T2 change (R2 increased 0.177 to 0.210, p < 0.001); and (iii) Coll2-1 NO2 × cumulative load explained lateral tibia T2 change (R2 increased 0.166 to 0.188, p < 0.001). Moderate COMP or Coll2-1 NO2 at baseline appeared protective. High COMP or Coll2-1 NO2, particularly with high BMI and low PASE, associated with worsening cartilage. Moderate serum concentrations of cartilage turnover biomarkers, at high and low physical activity, associated with maintained cartilage outcomes over 2 years. In conclusion, high concentrations of cartilage turnover biomarkers, particularly with high BMI and low physical activity, associated with knee cartilage thinning and increasing T2 over 2 years. Key Points • Higher quality cartilage may be better able to tolerate a larger cumulative load than poor quality cartilage. • Among participants enrolled in the Osteoarthritis Initiative Biomarkers Consortium Project, a representation of cumulative load exposure and its interaction with cartilage turnover biomarkers were weakly related with 2-year change in knee cartilage. • These findings suggest that cartilage turnover is a factor that modifies the relationship between loading exposure and cartilage loss in knee OA.

Primary Care Providers' Experiences Recommending and Performing Cervical Cancer Screening for Women with Intellectual Disabilities: A Qualitative Study.

Women with intellectual and developmental disabilities (I/DD) are less likely to receive cervical cancer screening (CCS) relative to women without disabilities. Primary care providers (PCPs) play key roles in recommending CCS. The purpose of this study was to identify factors PCPs consider when recommending and performing CCS for women with I/DD. Using a qualitative approach, in-depth semi-structured interviews (N = 13) were conducted with majority family medicine-trained PCPs. Through inductive data analysis, it was found that most PCPs reported recommending CCS; however, follow-through for performing CCS varied. PCPs attempted to align their CCS recommendations with national guidelines and provided counseling and education to families and patients about CCS while taking an individualized risk-benefit approach. Despite most PCPs reporting a lack of knowledge or training related to providing I/DD-specific care, PCPs attempted to draw upon experiences with similar populations to recommend and perform CCS. There is an opportunity to improve knowledge of PCPs related to performing CCS for women with I/DD.

Non-invasive biomarkers for sperm retrieval in non-obstructive patients: a comprehensive review.

Recent advancements in reproductive medicine have guided novel strategies for addressing male infertility, particularly in cases of non-obstructive azoospermia (NOA). Two prominent invasive interventions, namely testicular sperm extraction (TESE) and microdissection TESE (micro-TESE), have emerged as key techniques to retrieve gametes for assisted reproduction technologies (ART). Both heterogeneity and complexity of NOA pose a multifaceted challenge to clinicians, as the invasiveness of these procedures and their unpredictable success underscore the need for more precise guidance. Seminal plasma can be aptly regarded as a liquid biopsy of the male reproductive tract, encompassing secretions from the testes, epididymides, seminal vesicles, bulbourethral glands, and prostate. This fluid harbors a variety of cell-free nucleic acids, microvesicles, proteins, and metabolites intricately linked to gonadal activity. However, despite numerous investigations exploring potential biomarkers from seminal fluid, their widespread inclusion into the clinical practice remains limited. This could be partially due to the complex interplay of diverse clinical and genetic factors inherent to NOA that likely contributes to the absence of definitive biomarkers for residual spermatogenesis. It is conceivable that the integration of clinical data with biomarkers could increase the potential in predicting surgical procedure outcomes and their choice in NOA cases. This comprehensive review addresses the challenge of sperm retrieval in NOA through non-invasive biomarkers. Moreover, we delve into promising perspectives, elucidating innovative approaches grounded in multi-omics methodologies, including genomics, transcriptomics and proteomics. These cutting-edge techniques, combined with the clinical and genetics features of patients, could improve the use of biomarkers in personalized medical approaches, patient counseling, and the decision-making continuum. Finally, Artificial intelligence (AI) holds significant potential in the realm of combining biomarkers and clinical data, also in the context of identifying non-invasive biomarkers for sperm retrieval.

Myocardial B cells have specific gene expression and predicted interactions in dilated cardiomyopathy and arrhythmogenic right ventricular cardiomyopathy.

Introduction: Growing evidence from animal models indicates that the myocardium hosts a population of B cells that play a role in the development of cardiomyopathy. However, there is minimal data on human myocardial B cells in the context of cardiomyopathy. Methods: We integrated single-cell and single-nuclei datasets from 45 healthy human hearts, 70 hearts with dilated cardiomyopathy (DCM), and 8 hearts with arrhythmogenic right ventricular cardiomyopathy (ARVC). Interactions between B cells and other cell types were investigated using the CellChat Package. Differential gene expression analysis comparing B cells across conditions was performed using DESeq2. Pathway analysis was performed using Ingenuity, KEGG, and GO pathways analysis. Results: We identified 1,100 B cells, including naive B cells and plasma cells. Cells showed an extensive network of interactions within the healthy myocardium that included outgoing signaling to macrophages, T cells, endothelial cells, and pericytes, and incoming signaling from endothelial cells, pericytes, and fibroblasts. This niche relied on ECM-receptor, contact, and paracrine interactions; and changed significantly in the context of cardiomyopathy, displaying disease-specific features. Differential gene expression analysis showed that in the context of DCM both naive and plasma B cells upregulated several pathways related to immune activation, including upregulation of oxidative phosphorylation, upregulation of leukocyte extravasation, and, in naive B cells, antigen presentation. Discussion: The human myocardium contains naive B cells and plasma cells, integrated into a diverse and dynamic niche that has distinctive features in healthy, DCM, and ARVC. Naive myocardial-associated B cells likely contribute to the pathogenesis of human DCM.

Relationship of serum and dietary vitamin D with high cardiometabolic risk in Mexican systemic lupus erythematosus patients: A cross-sectional study.

Objetive: Serum and dietary vitamin D could influence clinical disease activity and cardiometabolic outcomes in systemic lupus erythematosus (SLE). This study aimed to assess the relationship of serum and dietary vitamin D with cardiometabolic risk in Mexican SLE patients and healthy subjects (HS).Methods: 224 SLE patients and 201 HS were included in this cross-sectional study. Serum calcidiol was measured using a competitive enzyme-linked immunosorbent assay (ELISA). Vitamin D dietary intake was assessed by collecting three 24h food records. Dietary patterns (DPs) were identified using principal component analysis (PCA). Cardiometabolic status was analyzed through biochemical measurements and cardiometabolic indexes.Results: Calcidiol deficiency (<20 ng/mL) was associated with 1.66-fold higher risk of excess weight by body mass index (BMI) (≥25 kg/m2) (p = .02), 2.25-fold higher risk to low high-density lipoprotein-cholesterol (HDL-C) (<40 mg/dL) (p < .001), and 1.74-fold higher risk to high triglycerides (TG) ≥150 mg/dL (p = .02). Inadequate vitamin D dietary intake was associated with 1.92-fold higher risk of presenting non-healthy waist circumference (WC) (>80 cm) (p < .01), 2.05-fold higher risk of android waist to hip ratio (WHR ≥85) (p < .01), and 1.72-fold higher risk to excess weight (p = .02). Non-adherence to a DP rich in vitamin D food sources was associated with higher WC, WHR, triglycerides, and lower high-density lipoprotein-cholesterol (HDL-C); furthermore, in HS, non-adherence to the DP rich in vitamin D food sources provided 2.11-fold higher risk to calcidiol deficiency.In Cconclusion: A pattern of Calcidiol deficiency, inadequate vitamin D dietary intake, and non-adherence to a DP rich in vitamin D food sources was related to high cardiometabolic risk in SLE patients and HS.

Whole-genome assembly of a hybrid Trypanosoma cruzi strain assembled with Nanopore sequencing alone.

Trypanosoma cruzi is the causative agent of Chagas disease, which causes 10,000 deaths per year. Despite the high mortality associated with Chagas, relatively few parasite genomes have been assembled to date, with genome assemblies unavailable even for some commonly used laboratory strains. This is at least partially due to T. cruzi's highly complex and highly repetitive genome, which defies investigation using traditional short-read sequencing methods. In this study, we have generated a high-quality whole-genome assembly of the hybrid Tulahuen strain, a commercially available type VI strain, using long-read Nanopore sequencing without short-read scaffolding. The assembled genome contains 25% repeat regions, 17% variable multigene family members, and 27% transposable elements (TEs) and is of comparable quality with T. cruzi genome assemblies that utilized both long- and short-read data. Notably, we find that regions with TEs are significantly enriched for multicopy surface proteins, and that surface proteins are, on average, closer to TEs than to other coding regions. This finding suggests that mobile genetic elements such as transposons may drive recombination within surface protein gene families. This work demonstrates the feasibility of Nanopore sequencing to resolve complex regions of T. cruzi genomes, and with these resolved regions, provides support for a possible mechanism for genomic diversification.

Baseline higher hair cortisol moderated some effects in a healthy lifestyle intervention.

Children and families from socioeconomically marginalized background experience high levels of stress, especially persistent chronic stress, due to unstable housing, employment, and food insecurity. Although consistent evidence supports a stress-obesity connection, little research has examined the potential moderation role of stress in childhood obesity interventions. Therefore, this study aimed to explore how chronic stress (hair cortisol) moderated the effects of a healthy lifestyle intervention on improving behavioral and anthropometric outcomes among 95 socioeconomically marginalized parent-child dyads. Data were collected in a cluster randomized controlled trial with 10 Head Start childcare centers being randomized into intervention and control. The child sample (3-5 years old) included 57.9 % female, 12.6 % Hispanic, and 40.0 % Black. For the parents, 91.6 % were female, 8.4 % were Hispanic, 36.8 % were Black, and 56.8 % were single. Parent baseline hair cortisol significantly moderated the intervention effects on child fruit intake (B = -1.56, p = .030) and parent nutrition self-efficacy (B = 1.49, p = .027). Specifically, higher parent hair cortisol lowered the increases in child fruit intake but improved the increases in parent nutrition self-efficacy in the intervention group compared to control group. Child higher baseline hair cortisol was significantly associated with the decreases in child fruit intake (B = -0.60, p = .025). Child baseline hair cortisol significantly moderated the intervention effects on parent physical activity (PA) self-efficacy (B = -1.04, p = .033) and PA parental support (B = -0.50, p = .016), with higher child hair cortisol decreasing the improvement on these two outcomes in the intervention group compared to control group. Results from this study shed lights on the moderation role of chronic stress on impacting healthy lifestyle intervention effects. Although needing further investigation, the adverse effects of chronic stress on intervention outcomes should be considered when developing healthy lifestyle interventions for preschoolers and their families.

Remote olfactory assessment using the NIH Toolbox Odor Identification test and the brain health registry.

BACKGROUND: Early identification of deficits in our ability to perceive odors is important as many normal (i.e., aging) and pathological (i.e., sinusitis, viral, neurodegeneration) processes can result in diminished olfactory function. To realistically enable population-level measurements of olfaction, validated olfaction tests must be capable of being administered outside the research laboratory and clinical setting. AIM: The purpose of this study was to determine the feasibility of remotely testing olfactory performance using a test that was developed with funding from the National Institutes of Health as part of a ready-to-use, non-proprietary set of measurements useful for epidemiologic studies (NIH Toolbox Odor ID Test). MATERIALS AND METHODS: Eligible participants older than 39 years and active (within 6 months) in the Brain Health Registry (BHR), an online cognitive assessment platform which connects participants with researchers, were recruited for this study. Interested participants were mailed the NIH Toolbox Odor ID Test along with instructions on accessing a website to record their responses. Data obtained from subjects who performed the test at home was compared to the normative data collected when the NIH Toolbox Odor ID Test was administered by a tester in a research setting and validated against the Smell Identification Test. The age-range and composition of the population ensured we had the ability to observe both age-related decline and gender-related deficits in olfactory ability, as shown in the experimental setting. RESULTS: We observed that age-associated olfactory decline and gender-associated performance was comparable to performance on the administered test. Self-administration of this test showed the age-related loss in olfactory acuity, F(4, 1156)=14.564, p<.0001 as well as higher accuracy for women compared to men after controlling for participants' age, F(1, 1160) = 22.953, p <.0001. The effect size calculated as Hedge's g, was 0.41. CONCLUSION: These results indicate that the NIH Toolbox Odor ID Test is an appropriate instrument for self-administered assessment of olfactory performance. The ability to self-administer an inexpensive olfactory test increases its utility for inclusion in longitudinal epidemiological studies and when in-person testing is not feasible.

Differences in Out-of-Hospital Cardiac Arrest Outcomes Among 5 Racial/Ethnic Groups.

OBJECTIVE: Out-of-hospital cardiac arrest (OHCA) is a major health problem and one of the leading causes of death in adults older than 40. Multiple prior studies have demonstrated survival disparities based on race/ethnicity, but most of these focus on a single racial/ethnic group. This study evaluated OHCA variables and outcomes among on 5 racial/ethnic groups. METHODS: This is a retrospective review of data for adult patients in the Cardiac Arrest Registry to Enhance Survival (CARES) from 3 racially diverse urban counties in the San Francisco Bay Area from May 2009 to October 2021. Stratifying by 5 racial/ethnic groups, we evaluated patient survival outcomes based on patient demographics, emergency medical services response location, cardiac arrest characteristics, and hospital interventions. Adjusted risk ratios were calculated for survival to hospital discharge, controlling for sex, age, response locations, median income of response location, arrest witness, shockable rhythm, and bystander cardiopulmonary resuscitation as well as clustering by census tract. RESULTS: There were 10,757 patient entries analyzed: 42% White, 24% Black, 18% Asian, 9.3% Hispanic, 6.0% Pacific Islander, 0.7% American Indian/Alaska Native, and 0.1% multiple races selected; however, only the first 5 racial/ethnic groups had sufficient numbers for comparison. The adjusted risk ratio for survival to hospital discharge was lower among the 4 racial/ethnic groups compared with the White reference group: Black (0.79, p = 0.003), Asian (0.78 p = 0.004), Hispanic (0.79, p = 0.018), and Pacific Islander (0.78, p = 0.041) groups. The risk difference for positive neurologic outcome was also lower among all 4 racial/ethnic groups compared with the White reference group. CONCLUSIONS: The Black, Asian, Hispanic, and Pacific Islander groups were less likely to survive to hospital discharge from OHCA when compared with the White reference group. No variables were associated with decreased survival across any of these 4 groups.