Multivariate Analysis of Factors Associated with Feeding Mother's Own Milk at Discharge in Preterm Infants: A Retrospective Cohort Study.

OBJECTIVE: This study aimed to develop a predictive model of feeding mother's own milk (MOM) at discharge using social determinants of health (SDOH), maternal and neonatal factors after deliveries at <33 weeks of gestational age (GA), or birth weight <1,500 g. STUDY DESIGN: Secondary analysis of a retrospective cohort in an inner-city hospital before (Epoch-1, 2018-2019) and after (Epoch-2, 2020-2021) implementing a donor human milk (DHM) program. RESULTS: Among 986 neonates, 495 were born in Epoch-1 (320 Hispanic White, 142 Non-Hispanic Black, and 33 Other) and 491 in Epoch-2 (327, 137, and 27, respectively). Feeding any MOM was less frequent in infants of non-Hispanic Black mothers than in those of Hispanic mothers (p < 0.05) but did not change with epoch (p = 0.46). Among infants who received any MOM, continued feeding MOM to the time of discharge was less frequent in infants of non-Hispanic Black mothers versus those of Hispanic mothers, 94/237 (40%) versus 339/595 (57%; p < 0.05), respectively. In multivariate analysis including SDOH and maternal variables, the odds of feeding MOM at discharge were lower with SDOH including neighborhoods with higher poverty levels, multiparity, substance use disorder, non-Hispanic Black versus Hispanic and young maternal age and increased with GA but did not change after implementing DHM. The predictive model including SDOH, maternal and early neonatal variables had good discrimination (area under the curve 0.85) and calibration and was internally validated. It showed the odds of feeding MOM at discharge were lower in infants of non-Hispanic Black mothers and with feeding DHM, higher need for respiratory support and later initiation of feeding MOM. CONCLUSION: Feeding MOM at discharge was associated with SDOH, and maternal and neonatal factors but did not change after implementing DHM. Disparity in feeding MOM at discharge was explained by less frequent initiation and shorter duration of feeding MOM but not by later initiation of feeding MOM. KEY POINTS: · In this cohort study of preterm infants, factors of feeding MOM at discharge included (1) SDOH; (2) postnatal age at initiation of feeding MOM; and (3) maternal and neonatal factors.. · Feeding MOM at the time of discharge was less frequent in infants of non-Hispanic Black mothers versus those of Hispanic mothers.. · Disparity in feeding MOM at discharge was explained by less frequent initiation and shorter duration of MOM feeding but not by later postnatal age at initiation of feeding MOM..

Current patterns of care and outcomes for dermatofibrosarcoma protuberans: An international multi-institutional collaborative.

BACKGROUND: Dermatofibrosarcoma protuberans (DFSP) is a cutaneous sarcoma with an infiltrative growth pattern that makes it challenging to clear margins. High quality data regarding DFSP natural history, management, and outcomes are limited. METHODS: Data were retrospectively collected for adult DFSP patients who underwent resection at 10 institutions in eight countries. Demographics, tumor characteristics, treatment strategies, and outcomes were analyzed. RESULTS: Analysis included 347 patients consisting of young (median, 42 years), White (76.2%), males (54.2%) with truncal lesions (57.3%). The majority (76.8%) were symptomatic at presentation. Preoperative imaging was used in 55.9% of cases. Diagnosis was established with excisional biopsy in 50.9% versus incisional biopsy in 25.0% of cases. Despite planned margins of >1.0 cm in 67.4% of cases, only 69.0% of patients achieved R0 resection. Twenty-two percent of patients underwent at least one re-excision. R0 resection was achieved at a second procedure in 80.2% and a third procedure in 86.2%. Ultimately, R0 resection was feasible in 89.5% of all patients. Fibrosarcomatous transformation (FST) was observed in 12.6%. In total, 6.6% (N = 23) recurred (17 local, six distant). Of the six distant recurrences, 50.0% had FST. With a median follow-up of 47.0 months, disease-specific survival rate was 98.8%. In multivariable analysis, R0 margins at index resection were associated with wider circumferential margins and non-FST histology. CONCLUSIONS: In this international, multicenter collaborative, DFSP practice patterns were heterogeneous but achieved favorable recurrence rates and survival. Multiple excisions to clear margins remain commonplace and can inform future efforts to optimize margin selection.

Temperature sensitivity of bat antibodies links metabolic state of bats with antigen-recognition diversity.

The bat immune system features multiple unique properties such as dampened inflammatory responses and increased tissue protection, explaining their long lifespan and tolerance to viral infections. Here, we demonstrated that body temperature fluctuations corresponding to different physiological states in bats exert a large impact on their antibody repertoires. At elevated temperatures typical for flight, IgG from the bat species Myotis myotis and Nyctalus noctula show elevated antigen binding strength and diversity, recognizing both pathogen-derived antigens and autoantigens. The opposite is observed at temperatures reflecting inactive physiological states. IgG antibodies of human and other mammals, or antibodies of birds do not appear to behave in a similar way. Importantly, diversification of bat antibody specificities results in preferential recognition of damaged endothelial and epithelial cells, indicating an anti-inflammatory function. The temperature-sensitivity of bat antibodies is mediated by the variable regions of immunoglobulin molecules. Additionally, we uncover specific molecular features of bat IgG, such as low thermodynamic stability and implication of hydrophobic interactions in antigen binding as well as high prevalence of polyreactivity. Overall, our results extend the understanding of bat tolerance to disease and inflammation and highlight the link between metabolism and immunity.

Evolutionary genomic analyses of canine E. coli infections identify a relic capsular locus associated with resistance to multiple classes of antimicrobials.

Infections caused by antimicrobial-resistant Escherichia coli are the leading cause of death attributed to antimicrobial resistance (AMR) worldwide, and the known AMR mechanisms involve a range of functional proteins. Here, we employed a pan-genome wide association study (GWAS) approach on over 1,000 E. coli isolates from sick dogs collected across the US and Canada and identified a strong statistical association (empirical P < 0.01) of AMR, involving a range of antibiotics to a group 1 capsular (CPS) gene cluster. This cluster included genes under relaxed selection pressure, had several loci missing, and had pseudogenes for other key loci. Furthermore, this cluster is widespread in E. coli and Klebsiella clinical isolates across multiple host species. Earlier studies demonstrated that the octameric CPS polysaccharide export protein Wza can transmit macrolide antibiotics into the E. coli periplasm. We suggest that the CPS in question, and its highly divergent Wza, functions as an antibiotic trap, preventing antimicrobial penetration. We also highlight the high diversity of lineages circulating in dogs across all regions studied, the overlap with human lineages, and regional prevalence of resistance to multiple antimicrobial classes. IMPORTANCE: Much of the human genomic epidemiology data available for E. coli mechanism discovery studies has been heavily biased toward shiga-toxin producing strains from humans and livestock. E. coli occupies many niches and produces a wide variety of other significant pathotypes, including some implicated in chronic disease. We hypothesized that since dogs tend to share similar strains with their owners and are treated with similar antibiotics, their pathogenic isolates will harbor unexplored AMR mechanisms of importance to humans as well as animals. By comparing over 1,000 genomes with in vitro antimicrobial susceptibility data from sick dogs across the US and Canada, we identified a strong multidrug resistance association with an operon that appears to have once conferred a type 1 capsule production system.

Spatiotemporal patterns in cortical development: Age, puberty, and individual variability from 9 to 13 years of age.

Humans and nonhuman primate studies suggest that timing and tempo of cortical development varies neuroanatomically along a sensorimotor-to-association (S-A) axis. Prior human studies have reported a principal S-A axis across various modalities, but largely rely on cross-sectional samples with wide age-ranges. Here, we investigate developmental changes and individual variability in cortical organization along the S-A axis between the ages of 9-13 years using a large, longitudinal sample (N = 2487-3747, 46-50% female) from the Adolescent Brain Cognitive Development Study (ABCD Study®). This work assesses multiple aspects of neurodevelopment indexed by changes in cortical thickness, cortical microarchitecture, and resting-state functional fluctuations. First, we evaluated S-A organization in age-related changes and, then, computed individual-level S-A alignment in brain changes and assessing differences therein due to age, sex, and puberty. Varying degrees of linear and quadratic age-related brain changes were identified along the S-A axis. Yet, these patterns of cortical development were overshadowed by considerable individual variability in S-A alignment. Even within individuals, there was little correspondence between S-A patterning across the different aspects of neurodevelopment investigated (i.e., cortical morphology, microarchitecture, function). Some of the individual variation in developmental patterning of cortical morphology and microarchitecture was explained by age, sex, and pubertal development. Altogether, this work contextualizes prior findings that regional age differences do progress along an S-A axis at a group level, while highlighting broad variation in developmental change between individuals and between aspects of cortical development, in part due to sex and puberty. Significance Statement: Understanding normative patterns of adolescent brain change, and individual variability therein, is crucial for disentangling healthy and abnormal development. We used longitudinal human neuroimaging data to study several aspects of neurodevelopment during early adolescence and assessed their organization along a sensorimotor-to-association (S-A) axis across the cerebral cortex. Age differences in brain changes were linear and curvilinear along this S-A axis. However, individual-level sensorimotor-association alignment varied considerably, driven in part by differences in age, sex, and pubertal development.

Venoarterial Extracorporeal Membrane Oxygenation for "Protected" Percutaneous Coronary Intervention Secondary to Refractory Polymorphic Ventricular Tachycardia and Cardiac Arrest.

ABSTRACT: We present a case of cardiogenic shock secondary to refractory polymorphic ventricular tachycardia associated with coronary ischemia resulting in cardiac arrest. Following the return of spontaneous circulation, the patient was cannulated for peripheral venoarterial extracorporeal membrane oxygenation (V-A ECMO) in anticipation of high-risk "protected" percutaneous coronary intervention (PCI). Under full V-A ECMO support, inotropes and vasopressors were weaned off, and the patient underwent uneventful PCI of left circumflex and obtuse marginal lesions. After 48 hours, the patient was decannulated and could be discharged home alive 16 days after his initial cardiac arrest.

Binding Promiscuity of Therapeutic Factor VIII.

The binding promiscuity of proteins defines their ability to indiscriminately bind multiple unrelated molecules. Binding promiscuity is implicated, at least in part, in the off-target reactivity, nonspecific biodistribution, immunogenicity, and/or short half-life of potentially efficacious protein drugs, thus affecting their clinical use. In this review, we discuss the current evidence for the binding promiscuity of factor VIII (FVIII), a protein used for the treatment of hemophilia A, which displays poor pharmacokinetics, and elevated immunogenicity. We summarize the different canonical and noncanonical interactions that FVIII may establish in the circulation and that could be responsible for its therapeutic liabilities. We also provide information suggesting that the FVIII light chain, and especially its C1 and C2 domains, could play an important role in the binding promiscuity. We believe that the knowledge accumulated over years of FVIII usage could be exploited for the development of strategies to predict protein binding promiscuity and therefore anticipate drug efficacy and toxicity. This would open a mutational space to reduce the binding promiscuity of emerging protein drugs while conserving their therapeutic potency.

Increasing Adoption of Left Atrial Appendage Occlusion in Isolated Coronary Artery Bypass Grafting.

BACKGROUND: Recent randomized trial data showed fewer strokes with left atrial appendage occlusion (LAAO) following cardiac surgery in patients with atrial fibrillation. We developed a quality initiative to increase LAAO adoption. METHODS: Among 11,099 patients undergoing isolated CABG between January 2019-March 2021 at 33 hospitals in Michigan, those with atrial fibrillation undergoing first-time, on-pump CABG were eligible (n=1,241). A goal LAAO rate of 75% was selected as a quality improvement target through a statewide collaborative. An interrupted time series analysis evaluated the change in LAAO rate before (January-December 2019) versus after (January 2020-March 2021) implementation. RESULTS: Implementation of the quality metric improved LAAO rate from 61% (357/581) before to 79% (520/660) after implementation (p<0.001). Compared to patients not undergoing concomitant LAAO, LAAO patients (71%, 877/1,241) were older, more frequently male, and had a lower STS-PROM (2.9±3.5% vs. 3.7±5.7%, p=0.003), while other baseline characteristics including CHA2DS2-VASc scores were similar. Mean bypass and cross-clamp times were 7 and 6 minutes longer, respectively, in the LAAO group among those who did not undergo concomitant ablation. Operative mortality, major morbidity, blood product administration, and thromboembolic events were similar between groups. Interrupted time series analysis showed a significant increase in LAAO rate after implementation (p=0.009). CONCLUSIONS: LAAO in patients with atrial fibrillation undergoing isolated CABG did not add operative risk versus isolated CABG without LAAO. A statewide quality improvement initiative was successful in increasing the rate of concomitant LAAO and could be further evaluated as a potential quality metric in cardiac surgery.

"We're one small piece of the puzzle": evaluating the impact of short-term funding for tier two weight management services.

Introduction: Overweight and obesity are a global health epidemic and many attempts have been made to address the rising prevalence. In March 2021 the UK government announced £100 million of additional funding for weight management provisions. Of this, £30.5 million was split across local authorities in England to support the expansion of tier two behavioural weight management services for adults. The present work aimed to explore how this funding was used within the Yorkshire and Humber region to consolidate learning, collate best practice, and provide recommendations for future funding use. Method: One-hour semi-structured interviews were conducted with 11 weight management service commissioners representing 9 of the 15 local authorities in the region. Interviews were recorded, transcribed and analysed using an established health inequality framework. From this, recommendations were co-developed with the commissioner group to establish best practice for future funding use. Results: Commissioners recognised that targeted weight management services were only one small piece of the puzzle for effectively managing obesity. Therefore, recommendations include targeting underserved communities, focussing on early prevention, addressing weight management in a whole systems context, and embracing innovative and holistic approaches to weight management. Discussion: Current short-term funding and restrictive commissioning processes of tier two services prevents sustainable and innovative weight management practice which is detrimental to patients, falls short of addressing health inequalities and negatively impacts staff health and wellbeing.

Exploring the Relationships Between Body Image, Sexual Well-Being, and Community Connectedness among Gay, Bisexual and Queer+ Men.

Sexual minority (SM) men are more likely than heterosexual men to experience body dissatisfaction due to prevailing body ideals (e.g. lean and muscular) within the SM community. Negative body image can have harmful effects on well-being, and, by extension, sexual well-being. The current study aimed to investigate whether SM men's minority identification and LGBTQ+ community connectedness moderates the relationship between drives for muscularity and sexual anxiety. To address this aim, 298 Australian-residing SM men completed an online survey that examined drive for muscularity, sexual anxiety, and connectedness or identification with the LGBTQ+ and SM-specific communities. As hypothesized, the results showed a positive relationship between drive for muscularity and sexual anxiety. Additionally, LGBTQ+ community connectedness, but importantly not SM identification, was found to moderate this relationship, showing a positive association only when connection was at low or average levels. These results highlight the beneficial effects that LGBTQ+ community connection can have for SM men, such as protecting them against the harmful impacts of poor body image on sexual well-being. These results also provide preliminary insights into the need to expand the understandings of bodily diversity, and diversity of sexual well-being experiences, among SM men less connected to the broader LGBTQ+ community.

Natural language processing pipeline to extract prostate cancer-related information from clinical notes.

OBJECTIVES: To develop an automated pipeline for extracting prostate cancer-related information from clinical notes. MATERIALS AND METHODS: This retrospective study included 23,225 patients who underwent prostate MRI between 2017 and 2022. Cancer risk factors (family history of cancer and digital rectal exam findings), pre-MRI prostate pathology, and treatment history of prostate cancer were extracted from free-text clinical notes in English as binary or multi-class classification tasks. Any sentence containing pre-defined keywords was extracted from clinical notes within one year before the MRI. After manually creating sentence-level datasets with ground truth, Bidirectional Encoder Representations from Transformers (BERT)-based sentence-level models were fine-tuned using the extracted sentence as input and the category as output. The patient-level output was determined by compilation of multiple sentence-level outputs using tree-based models. Sentence-level classification performance was evaluated using the area under the receiver operating characteristic curve (AUC) on 15% of the sentence-level dataset (sentence-level test set). The patient-level classification performance was evaluated on the patient-level test set created by radiologists by reviewing the clinical notes of 603 patients. Accuracy and sensitivity were compared between the pipeline and radiologists. RESULTS: Sentence-level AUCs were ≥ 0.94. The pipeline showed higher patient-level sensitivity for extracting cancer risk factors (e.g., family history of prostate cancer, 96.5% vs. 77.9%, p < 0.001), but lower accuracy in classifying pre-MRI prostate pathology (92.5% vs. 95.9%, p = 0.002) and treatment history of prostate cancer (95.5% vs. 97.7%, p = 0.03) than radiologists, respectively. CONCLUSION: The proposed pipeline showed promising performance, especially for extracting cancer risk factors from patient's clinical notes. CLINICAL RELEVANCE STATEMENT: The natural language processing pipeline showed a higher sensitivity for extracting prostate cancer risk factors than radiologists and may help efficiently gather relevant text information when interpreting prostate MRI. KEY POINTS: When interpreting prostate MRI, it is necessary to extract prostate cancer-related information from clinical notes. This pipeline extracted the presence of prostate cancer risk factors with higher sensitivity than radiologists. Natural language processing may help radiologists efficiently gather relevant prostate cancer-related text information.

Neighborhood racial income inequality and cognitive health.

INTRODUCTION: Neighborhood socioeconomic status (SES) has been linked to dementia, but the distribution of SES within a neighborhood may also matter. METHODS: Data from 460 (47% Black, 46% White) older adults from the Michigan Cognitive Aging Project were linked to census tract-level data from the National Neighborhood Data Archive (NaNDA). Neighborhood SES included two composites reflecting disadvantage and affluence. Neighborhood racial income inequality was the ratio of median incomes for White versus Black residents. Generalized estimating equations examined associations between neighborhood factors and cognitive domains. RESULTS: Neighborhood racial income inequality was uniquely associated with worse cognitive health, and these associations did not differ by participant race. Neighborhood disadvantage was only associated with worse cognitive health among Black participants. DISCUSSION: Both the level and racial distribution of SES within a neighborhood may be relevant for dementia risk. Racial differences in the level and impact of neighborhood SES contribute to dementia inequalities. HIGHLIGHTS: Black participants lived in neighborhoods with lower socioeconomic status (SES) than White participants, on average. Neighborhood SES and racial income inequality were associated with worse cognition. Effects of neighborhood racial income inequality did not differ across racial groups. Effects of neighborhood SES were only evident among Black participants.

Clock gene homologs lin-42 and kin-20 regulate circadian rhythms in C. elegans.

Circadian rhythms are endogenous oscillations in nearly all organisms, from prokaryotes to humans, allowing them to adapt to cyclical environments for close to 24 h. Circadian rhythms are regulated by a central clock, based on a transcription-translation feedback loop. One important protein in the central loop in metazoan clocks is PERIOD, which is regulated in part by Casein kinase 1ε/δ (CK1ε/δ) phosphorylation. In the nematode Caenorhabditis elegans, period and casein kinase 1ε/δ are conserved as lin-42 and kin-20, respectively. Here, we studied the involvement of lin-42 and kin-20 in the circadian rhythms of the adult nematode using a bioluminescence-based circadian transcriptional reporter. We show that mutations of lin-42 and kin-20 generate a significantly longer endogenous period, suggesting a role for both genes in the nematode circadian clock, as in other organisms. These phenotypes can be partially rescued by overexpression of either gene under their native promoter. Both proteins are expressed in neurons and epidermal seam cells, as well as in other cells. Depletion of LIN-42 and KIN-20, specifically in neuronal cells after development, was sufficient to lengthen the period of oscillating sur-5 expression. Therefore, we conclude that LIN-42 and KIN-20 are critical regulators of the adult nematode circadian clock through neuronal cells.

The enteroendocrine axis and its effect on gastrointestinal function, nutrition, and inflammation.

PURPOSE OF REVIEW: Gastrointestinal (GI) dysfunction limits enteral nutrition (EN) delivery in critical illness and contributes to systemic inflammation. The enteroendocrine (EE) axis plays an integral role in this interface between nutrition, inflammation, and GI function in critical illness. In this review, we present an overview of the EE system with a focus on its role in GI inflammation and function. RECENT FINDINGS: Enteroendocrine cells have been primarily described in their role in macronutrient digestion and absorption. Recent research has expanded on the diverse functions of EE cells including their ability to sense microbial peptides and metabolites and regulate immune function and inflammation. Therefore, EE cells may be both affected by and contribute to many pathophysiologic states and interventions of critical illness such as dysbiosis , inflammation, and alternative EN strategies. In this review, we present an overview of EE cells including their growing role in nonnutrient functions and integrate this understanding into relevant aspects of critical illness with a focus on EN. SUMMARY: The EE system is key in maintaining GI homeostasis in critical illness, and how it is impacted and contributes to outcomes in the setting of dysbiosis , inflammation and different feeding strategies in critical illness should be considered.

Structural basis for inhibition of coagulation factor VIII reveals a shared antigenic hotspot on the C1 domain.

BACKGROUND: Hemophilia A arises from dysfunctional or deficient coagulation factor (F)VIII and leads to inefficient fibrin clot formation and uncontrolled bleeding events. The development of antibody inhibitors is a clinical complication in hemophilia A patients receiving FVIII replacement therapy. LE2E9 is an anti-C1 domain inhibitor previously isolated from a mild/moderate hemophilia A patient and disrupts FVIII interactions with von Willebrand factor and FIXa, though the intermolecular contacts that underpin LE2E9-mediated FVIII neutralization are undefined. OBJECTIVES: To determine the structure of the complex between FVIII and LE2E9 and characterize its mechanism of inhibition. METHODS: FVIII was bound to the antigen binding fragment (Fab) of NB2E9, a recombinant construct of LE2E9, and its structure was determined by cryogenic electron microscopy. RESULTS: This report communicates the 3.46 Å structure of FVIII bound to NB2E9, with its epitope comprising FVIII residues S2040 to Y2043, K2065 to W2070, and R2150 to H2155. Structural analysis reveals that the LE2E9 epitope overlaps with portions of the epitope for 2A9, a murine-derived inhibitor, suggesting that these residues represent a shared antigenic region on the C1 domain between FVIII-/- mice and hemophilia A patients. Furthermore, the FVIII:NB2E9 structure elucidates the orientation of the LE2E9 glycan, illustrating how the glycan sterically blocks interactions between the FVIII C1 domain and the von Willebrand factor D' domain. A putative model of the FVIIIa:FIXa complex suggests potential clashing between the NB2E9 glycan and FIXa light chain. CONCLUSION: These results describe an antigenic "hotspot" on the FVIII C1 domain and provide a structural basis for engineering FVIII replacement therapeutics with reduced antigenicity.

SEMA3: A free smartphone platform for daily life surveys.

Traditionally, behavioral, social, and health science researchers have relied on global/retrospective survey methods administered cross-sectionally (i.e., on a single occasion) or longitudinally (i.e., on several occasions separated by weeks, months, or years). More recently, social and health scientists have added daily life survey methods (also known as intensive longitudinal methods or ambulatory assessment) to their toolkit. These methods (e.g., daily diaries, experience sampling, ecological momentary assessment) involve dense repeated assessments in everyday settings. To facilitate research using daily life survey methods, we present SEMA3 ( http://www.SEMA3.com ), a platform for designing and administering intensive longitudinal daily life surveys via Android and iOS smartphones. SEMA3 fills an important gap by providing researchers with a free, intuitive, and flexible platform with basic and advanced functionality. In this article, we describe SEMA3's development history and system architecture, provide an overview of how to design a study using SEMA3 and outline its key features, and discuss the platform's limitations and propose directions for future development of SEMA3.

A narrative review of telemedicine and its adoption across specialties.

Background and Objective: Telemedicine and video consultation are crucial advancements in healthcare, allowing remote delivery of care. Telemedicine, encompassing various technologies like wearable devices, mobile health, and telemedicine, plays a significant role in managing illnesses and promoting wellness. The corona virus disease 2019 (COVID-19) pandemic accelerated the adoption of telemedicine, ensuring convenient access to medical services while maintaining physical distance. Legislation has supported its integration into clinical practice and addressed compensation issues. However, ensuring clinical appropriateness and sustainability of telemedicine post-expansion has gained attention. We south to identify the most friendly and resistant specialties to telemedicine and to understand areas of interest within those specialties to grasp potential barriers to its use. Methods: We aimed to identify articles that incorporated telemedicine in any medical or surgical specialty and determine the adoption rate and intent of this new form of care. Additionally, a secondary search within these databases was conducted to analyze the advantages, disadvantages, and implementation of telemedicine in the healthcare system. Non-English articles and those without full text were excluded. The study selection and data collection process involved using search terms such as "medicine", "surgery", "specialties", "telemedicine", and "telemedicine". Key Content and Findings: Telemedicine adoption varies among specialties. The pandemic led to increased usage, with telemedicine consultations comprising 30.1% of all visits, but specialties like mental health, gastroenterology, and endocrinology showed higher rates of adoption compared to optometry, physical therapy, and orthopedic surgery. Conclusions: The data shows that telemedicine uptake varies by specialty and condition due to the need for physical exams. In-person visits still dominate new patient visits despite increased telemedicine use. Telemedicine cannot fully replace in-person care but has increased visit volume and is secure. The adoption of telemedicine is higher in medical practices than in surgical practices, with neurosurgery and urology leading. Further research is needed to assess telemedicine's suitability and effectiveness in different specialties and conditions.

Comparing preferences to evaluations of barrier self-efficacy for two strength training programs in US older adults.

BACKGROUND/OBJECTIVES: Engagement in regular physical activity is one of the best strategies for older adults to remain healthy. Unfortunately, only 35% of older adults meet guidelines for muscle strengthening activities. Eliciting participant preferences is one possible way to improve physical activity engagement. However, other sources of participant input to improve uptake and maintenance remain uninvestigated. This study compared preferences to self-efficacy ratings for two strength training programs. METHODS: We conducted a national cross-sectional survey of 611 US adults over age 65. We compared two participant evaluations (the preferred program and the program for which they had higher barrier self-efficacy) of two hypothetical strength training programs (45 minutes performed three times per week (traditional) and 5 minutes performed daily (brief)). RESULTS: Most participants (68%) preferred the brief strength training program. The difference in self-efficacy ratings was an average of 1.2 (SD = 0.92). One in five participants preferred a strength training program for which they had less self-efficacy; nearly all of these participants (92%) preferred the traditional strength training program but had more self-efficacy for the brief strength training program. CONCLUSION: Older adults reported preferring and having more self-efficacy for a brief compared to a traditional strength training program. Differences in self-efficacy ratings between the two strength training programs were large. Preferences were often not congruent with ratings of self-efficacy. SIGNIFICANCE/IMPLICATIONS: Preferences for strength training programming may not always reflect the program most likely to be maintained. Future investigations should evaluate differences in behavioral uptake, maintenance, and outcomes from two comparative strength training interventions using preferences and self-efficacy.

MLT-11 is a transient apical extracellular matrix component required for cuticle patterning and function.

Apical extracellular matrices (aECMs) are associated with all epithelia and form a protective layer against biotic and abiotic threats in the environment. Despite their importance, we lack a deep understanding of their structure and dynamics in development and disease. C. elegans molting offers a powerful entry point to understanding developmentally programmed aECM remodeling. A transient matrix is formed in embryos and at the end of each larval stage, presumably to pattern the new cuticle. Focusing on targets of NHR-23, a key transcription factor which drives molting, we identified the Kunitz family protease inhibitor gene mlt-11 as an NHR-23 target. We identified NHR-23-binding sites that are necessary and sufficient for epithelial expression. mlt-11 is necessary to pattern every layer of the adult cuticle, suggesting a broad patterning role prior to the formation of the mature cuticle. MLT-11::mNeonGreen::3xFLAG transiently localized to the aECM in the cuticle and embryo. It was also detected in lining openings to the exterior (vulva, rectum, mouth). Reduction of mlt-11 function disrupted the barrier function of the cuticle. Tissue-specific RNAi suggested mlt-11 activity is primarily necessary in seam cells and we observed alae and seam cell fusion defects upon mlt-11 inactivation. Predicted mlt-11 null mutations caused fully penetrant embryonic lethality and elongation defects suggesting mlt-11 also plays an important role in patterning the embryonic sheath. Finally, we found that mlt-11 inactivation suppressed the blistered cuticle phenotype of mutants of bli-4 mutants, a subtilisin protease gene but did not affect BLI-4::sfGFP expression. These data could suggest that MLT-11 may be necessary to assure proper levels of BLI-4 activity.