Musculoskeletal injuries during trail sports: Sex- and age-specific analyses over 20 years from a national injury database.

INTRODUCTION: Musculoskeletal (MSK) injuries in US trail sports are understudied as trail sport popularity grows. This study describes MSK injury patterns among hikers, trail runners, and mountain bikers from 2002 through 2021 and investigates MSK injury trends acquired during mountain sports. METHODS: The National Electronic Injury Surveillance System (NEISS) was used to identify US emergency department (ED) patients from 2002-2021 (inclusive) who endured MSK injuries during hiking, trail running, or mountain biking. Injury rates and national estimates were calculated across demographics. RESULTS: 9835 injuries were included (48.4% male, 51.6% female). Injuries increased over time, with 1213 from 2002-2005 versus 2417 from 2018-2021. No sex differences existed before 2010, after which female injury rates exceeded those of males. The following findings were statistically significant, with P<0.05: females endured more fractures and strains/sprains; males endured more lacerations; concussions and head injuries were higher among those <18 y; dislocations and strains/sprains were higher for 18 to 65 y; fractures were higher for >65 y; <18 y had high mountain-biking and low running rates; 18 to 65 y had high running rates; and >65 y had low biking and running rates. Although all diagnoses increased in number over time, no significant differences existed in the proportion of any given diagnosis relative to total injuries. CONCLUSIONS: MSK injuries during trail sports have increased since 2002. Males endured more injuries until 2009, after which females endured more. Significant sex and age differences were found regarding injury diagnosis and body parts. Further studies are needed to confirm these trends and their causes.

Structural racism in primary schools and changes in epigenetic age acceleration among Black and White youth.

Structural racism generates racial inequities in U.S. primary education, including segregated schools, inequitable funding and resources, racial disparities in discipline and achievement, and hostile racial climates, which are risk factors for adverse youth health and development. Black youth are disproportionately exposed to adverse school contexts that may become biologically embedded via stress-mediated epigenetic pathways. This study examined whether childhood exposure to adverse school contexts is associated with changes in epigenetic aging during adolescent development. DNA methylation-based epigenetic clocks were calculated from saliva samples at ages 9 and 15 among Black (n = 774) and White (n = 287) youth in the Future of Families and Child Wellbeing Study (2009-2015). We performed latent class analyses to identify race-specific primary school contexts using administrative data on segregation, discipline, achievement, resources, economic disadvantage, and racial harassment. We then estimated change in epigenetic age acceleration from childhood to adolescence across school typologies using GrimAge, PhenoAge, and DunedinPACE epigenetic clocks. Three distinct school contexts were identified for Black youth: segregated and highly-disadvantaged (17.0%), segregated and moderately-disadvantaged (52.1%), and integrated and moderately-disadvantaged (30.8%). Two school contexts emerged for White youth: integrated and unequal (46.5%) and predominantly White & advantaged (53.5%). At age 15, Black youth who attended segregated and highly-disadvantaged primary schools experienced increases in their speed of epigenetic aging with GrimAge and DunedinPACE. Slowed epigenetic aging with GrimAge was observed for Black youth who attended integrated and moderately-disadvantaged schools. School contexts were not associated with changes in epigenetic age acceleration for White youth. Our findings suggest that manifestations of structural racism in primary school contexts are associated with early-life epigenetic age acceleration and may forecast future health inequities.

Machine-Guided Discovery of Acrylate Photopolymer Compositions.

Additive manufacturing (AM) can be advanced by the diverse characteristics offered by thermoplastic and thermoset polymers and the further benefits of copolymerization. However, the availability of suitable polymeric materials for AM is limited and may not always be ideal for specific applications. Additionally, the extensive number of potential monomers and their combinations make experimental determination of resin compositions extremely time-consuming and costly. To overcome these challenges, we develop an active learning (AL) approach to effectively choose compositions in a ternary monomer space ranging from rigid to elastomeric. Our AL algorithm dynamically suggests monomer composition ratios for the subsequent round of testing, allowing us to efficiently build a robust machine learning (ML) model capable of predicting polymer properties, including Young's modulus, peak stress, ultimate strain, and Shore A hardness based on composition while minimizing the number of experiments. As a demonstration of the effectiveness of our approach, we use the ML model to drive material selection for a specific property, namely, Young's modulus. The results indicate that the ML model can be used to select material compositions within at least 10% of a targeted value of Young's modulus. We then use the materials designed by the ML model to 3D print a multimaterial "hand" with soft "skin" and rigid "bones". This work presents a promising tool for enabling informed AM material selection tailored to user specifications and accelerating material discovery using a limited monomer space.

Environmental enrichment promotes adaptive responding during tests of behavioral regulation in male heterogeneous stock rats.

Organisms must regulate their behavior flexibly in the face of environmental challenges. Failure can lead to a host of maladaptive behavioral traits associated with a range of neuropsychiatric disorders, including attention deficit hyperactivity disorder, autism, and substance use disorders. This maladaptive dysregulation of behavior is influenced by genetic and environmental factors. For example, environmental enrichment produces beneficial neurobehavioral effects in animal models of such disorders. The present study determined the effects of environmental enrichment on a range of measures related to behavioral regulation using a large cohort of male, outbred heterogeneous stock (HS) rats as subjects. Subjects were reared from late adolescence onwards either in pairs in standard housing with minimal enrichment (n = 200) or in groups of 16 in a highly enriched environment consisting of a large multi-level cage filled with toys, running wheels, and shelters (n = 64). Rats were subjected to a battery of tests, including: (i) locomotor response to novelty, (ii) light reinforcement, (iii) social reinforcement, (iv) reaction time, (v) a patch-depletion foraging test, (vi) Pavlovian conditioned approach, (vii) conditioned reinforcement, and (viii) cocaine conditioned cue preference. Results indicated that rats housed in the enriched environment were able to filter out irrelevant stimuli more effectively and thereby regulate their behavior more efficiently than standard-housing rats. The dramatic impact of environmental enrichment suggests that behavioral studies using standard housing conditions may not generalize to more complex environments that may be more ethologically relevant.

Oystershell scale (Hemiptera: Diaspididae) population growth, spread, and phenology on aspen in Arizona, USA.

Oystershell scale (OSS; Lepidosaphes ulmi L.) is an invasive insect that threatens sustainability of aspen (Populus tremuloides Michx.) in the southwestern United States. OSS invasions have created challenges for land managers tasked with maintaining healthy aspen ecosystems for the ecological, economic, and aesthetic benefits they provide. Active management is required to suppress OSS populations and mitigate damage to aspen ecosystems, but before management strategies can be implemented, critical knowledge gaps about OSS biology and ecology must be filled. This study sought to fill these gaps by addressing 3 questions: (i) What is the short-term rate of aspen mortality in OSS-infested stands in northern Arizona, USA? (ii) What are the short-term rates of OSS population growth on trees and OSS spread among trees in aspen stands? (iii) What is the phenology of OSS on aspen and does climate influence phenology? We observed high levels of aspen mortality (annual mortality rate = 10.4%) and found that OSS spread rapidly within stands (annual spread rate = 10-12.3%). We found first, second, and young third instars throughout the year and observed 2 waves of first instars (i.e., crawlers), one throughout the summer and a second in mid-winter. The first wave appeared to be driven by warming seasonal temperatures, but the cause of the second wave is unknown and might represent a second generation. We provide recommendations for future OSS research, including suggestions for more precise quantification of OSS phenology, and discuss how our results can inform management of OSS and invaded aspen ecosystems.

Relationships of brain cholesterol and cholesterol biosynthetic enzymes to Alzheimer's pathology and dementia in the CFAS population-derived neuropathology cohort.

Altered cholesterol metabolism is implicated in brain ageing and Alzheimer's disease. We examined whether key genes regulating cholesterol metabolism and levels of brain cholesterol are altered in dementia and Alzheimer's disease neuropathological change (ADNC). Temporal cortex (n = 99) was obtained from the Cognitive Function and Ageing Study. Expression of the cholesterol biosynthesis rate-limiting enzyme HMG-CoA reductase (HMGCR) and its regulator, SREBP2, were detected using immunohistochemistry. Expression of HMGCR, SREBP2, CYP46A1 and ABCA1 were quantified by qPCR in samples enriched for astrocyte and neuronal RNA following laser-capture microdissection. Total cortical cholesterol was measured using the Amplex Red assay. HMGCR and SREBP2 proteins were predominantly expressed in pyramidal neurones, and in glia. Neuronal HMGCR did not vary with ADNC, oxidative stress, neuroinflammation or dementia status. Expression of HMGCR neuronal mRNA decreased with ADNC (p = 0.022) and increased with neuronal DNA damage (p = 0.049), whilst SREBP2 increased with ADNC (p = 0.005). High or moderate tertiles for cholesterol levels were associated with increased dementia risk (OR 1.44, 1.58). APOE ε4 allele was not associated with cortical cholesterol levels. ADNC is associated with gene expression changes that may impair cholesterol biosynthesis in neurones but not astrocytes, whilst levels of cortical cholesterol show a weak relationship to dementia status.

Sociodemographic profiles and organ damage accural in the Black Women's Experience Living with Lupus study.

OBJECTIVE: Black/African American women with systemic lupus erythematosus (SLE) experience greater organ damage and at younger ages than white women. The objective of this study was to advance research on SLE inequities by identifying sociodemographic risk profiles associated with organ damage accrual specifically among Black/African American women. METHODS: Latent profile analysis was conducted among 438 Black/African American women with SLE living in Atlanta, GA and enrolled in the Black Women's Experiences Living with Lupus (BeWELL) Study (May 2015 to April 2017). Proportional hazard and Poisson regression models examined prospective associations between sociodemographic profiles and the timing and degree of organ damage accrual over 2 years. RESULTS: Four profiles emerged: (1) "Younger/Lower SES with Uncontrolled SLE" (44.8%), (2) "Older/Lower SES with Uncontrolled SLE" (23.3%), (3) "Mid-SES with Controlled SLE" (19.6%), and (4) "Higher SES with Controlled SLE" (11.2%). Approximately 42% of participants experienced new organ damage during the follow-up period. Proportional hazard models indicated that "Older/Lower SES with Uncontrolled SLE" participants were at greatest risk of new organ damage (HR = 2.41; 95% CI = 1.39, 4.19), followed by "Younger/Lower SES with Uncontrolled SLE" participants (HR = 1.56; 95% CI = 0.92, 2.67), compared to those in the "Higher SES with Controlled SLE" profile. Poisson regression models revealed that these two groups also exhibited greater organ damage accrual (b = 0.98, SE = 0.24, 95% CI = 0.52, 1.44 and b = 0.72, SE = 0.23, 95% CI = 0.27, 1.17, respectively). CONCLUSIONS: Black/African American women with fewer socioeconomic resources and uncontrolled SLE are at greatest risk for increasing disease severity over time. Social inequities likely contribute to racial inequities in SLE progression.

Genetic Ablation of Dentate Hilar Somatostatin-Positive GABAergic Interneurons is Sufficient to Induce Cognitive Impairment.

Aging is often associated with a decline in cognitive function. A reduction in the number of somatostatin-positive (SOM+) interneurons in the dentate gyrus (DG) has been described in cognitively impaired but not in unimpaired aged rodents. However, it remains unclear whether the reduction in SOM + interneurons in the DG hilus is causal for age-related cognitive dysfunction. We hypothesized that hilar SOM+ interneurons play an essential role in maintaining cognitive function and that a reduction in the number of hilar SOM + interneurons might be sufficient to induce cognitive dysfunction. Hilar SOM+ interneurons were ablated by expressing a diphtheria toxin transgene specifically in these interneurons, which resulted in a reduction in the number of SOM+ /GAD-67+ neurons and dendritic spine density in the DG. C-fos and Iba-1 immunostainings were increased in DG and CA3, but not CA1, and BDNF protein expression in the hippocampus was decreased. Behavioral testing showed a reduced recognition index in the novel object recognition test, decreased alternations in the Y maze test, and longer latencies and path lengths in the learning and reversal learning phases of the Morris water maze. Our results show that partial genetic ablation of SOM+ hilar interneurons is sufficient to increase activity in DG and CA3, as has been described to occur with aging and to induce an impairment of learning and memory functions. Thus, partial ablation of hilar SOM + interneurons may be a significant contributing factor to age-related cognitive dysfunction. These mice may also be useful as a cellularly defined model of hippocampal aging.

Wrist EMG Improves Gesture Classification for Stroke Patients.

Electromyography (EMG) is a popular human-machine interface for hand gesture control of assistive and rehabilitative technology. EMG can be used to estimate motor intent even when an individual cannot physically move due to weakness or paralysis. EMG is traditionally recorded from the extrinsic hand muscles located in the forearm. However, the wrist has become an increasingly attractive recording location for commercial applications as EMG sensors can be integrated into wrist-worn wearables (e.g., watches, bracelets). Here we explored the impact that recording EMG from the wrist, instead of the forearm, has on stroke patients with upper-limb hemiparesis. We show that EMG signal-to-noise ratio is significantly worse at the paretic wrist relative to the paretic forearm and non-paretic wrist. Despite this, we also show that the ability to classify hand gestures from EMG was significantly better at the paretic wrist relative to the paretic forearm. Our results also provide guidance as to the ideal gestures for each recording location. Namely, single-digit gestures appeared easiest to classify from both forearm and wrist EMG on the paretic side. These results suggest commercialization of wrist-worn EMG would benefit stroke patients by providing more accurate EMG control in a more widely adopted wearable formfactor.

Correcting Temporal Inaccuracies in Labeled Training Data for Electromyographic Control Algorithms.

Electromyographic (EMG) control relies on supervised-learning algorithms that correlate EMG to motor intent. The quality of the training dataset is critical to the runtime performance of the algorithm, but labeling motor intent is imprecise and imperfect. Traditional EMG training data is collected while participants mimic predetermined movements of a virtual hand with their own hand. This assumes participants are perfectly synchronized with the predetermined movements, which is unlikely due to reaction time and signal-processing delays. Prior work has used cross-correlation to globally shift and re-align kinematic data and EMG. Here, we quantify the impact of this global re-alignment on both classification algorithms and regression algorithms with and without a human in the loop. We also introduce a novel trial-by-trial re-alignment method to re-align EMG with kinematics on a per-movement basis. We show that EMG and kinematic data are inherently misaligned, and that reaction time is inconsistent throughout data collection. Both global and trial-by-trial re-alignment significantly improved offline performance for classification and regression. Our trial-by-trial re-alignment further improved offline classification performance relative to global realignment. However, online performance, with a human actively in the loop, was no different with or without re-alignment. This work highlights inaccuracies in labeled EMG data and has broad implications for EMG-control applications.

Automated Quantifiable Assessments of Sensorimotor Function Using an Instrumented Fragile Object.

Accurate assessment of hand dexterity plays a critical role in informing rehabilitation and care of upper-limb hemiparetic stroke patients. Common upper-limb assessments, such as the Box and Blocks Test and Nine Hole Peg Test, primarily evaluate gross motor function in terms of speed. These assessments neglect an individual's ability to finely regulate grip force, which is critical in activities of daily living, such as manipulating fragile objects. Here we present the Electronic Grip Gauge (EGG), an instrumented fragile object that assesses both gross and fine motor function. Embedded with a load cell, accelerometer, and Hall-effect sensor, the EGG measures grip force, acceleration, and relative position (via magnetic fields) in real time. The EGG can emit an audible "break" sound when the applied grip force exceeds a threshold. The number of breaks, transfer duration, and applied forces are automatically logged in real-time. Using the EGG, we evaluated sensorimotor function in implicit grasping and gentle grasping for the non-paretic and paretic hands of 3 hemiparetic stroke patients. For all participants, the paretic hand took longer to transfer the EGG during implicit grasping. For 2 of 3 participants, grip forces were significantly greater for the paretic hand during gentle grasping. Differences in implicit grasping forces were unique to each participant. This work constitutes an important step towards more widespread and quantitative measures of sensorimotor function, which may ultimately lead to improved personalized rehabilitation and better patient outcomes.

Relating Antimicrobial Resistance and Virulence in Surface-Water E. coli.

The role of the environment in the emergence and spread of antimicrobial resistance (AMR) is being increasingly recognized, raising questions about the public health risks associated with environmental AMR. Yet, little is known about pathogenicity among resistant bacteria in environmental systems. Existing studies on the association between AMR and virulence are contradictory, as fitness costs and genetic co-occurrence can be opposing influences. Using Escherichia coli isolated from surface waters in eastern North Carolina, we compared virulence gene prevalence between isolates resistant and susceptible to antibiotics. We also compared the prevalence of isolates from sub-watersheds with or without commercial hog operations (CHOs). Isolates that had previously been evaluated for phenotypic AMR were paired by matching isolates resistant to any tested antibiotic with fully susceptible isolates from the same sample date and site, forming 87 pairs. These 174 isolates were evaluated by conventional PCR for seven virulence genes (bfp, fimH, cnf-1, STa (estA), EAST-1 (astA), eae, and hlyA). One gene, fimH, was found in 93.1% of isolates. Excluding fimH, at least one virulence gene was detected in 24.7% of isolates. Significant negative associations were found between resistance to at least one antibiotic and presence of at least one virulence gene, tetracycline resistance and presence of a virulence gene, resistance and STa presence, and tetracycline resistance and STa presence. No significant associations were found between CHO presence and virulence, though some sub-significant associations merit further study. This work builds our understanding of factors controlling AMR dissemination through the environment and potential health risks.

Global mosquito observations dashboard (GMOD): creating a user-friendly web interface fueled by citizen science to monitor invasive and vector mosquitoes.

BACKGROUND: Mosquitoes and the diseases they transmit pose a significant public health threat worldwide, causing more fatalities than any other animal. To effectively combat this issue, there is a need for increased public awareness and mosquito control. However, traditional surveillance programs are time-consuming, expensive, and lack scalability. Fortunately, the widespread availability of mobile devices with high-resolution cameras presents a unique opportunity for mosquito surveillance. In response to this, the Global Mosquito Observations Dashboard (GMOD) was developed as a free, public platform to improve the detection and monitoring of invasive and vector mosquitoes through citizen science participation worldwide. METHODS: GMOD is an interactive web interface that collects and displays mosquito observation and habitat data supplied by four datastreams with data generated by citizen scientists worldwide. By providing information on the locations and times of observations, the platform enables the visualization of mosquito population trends and ranges. It also serves as an educational resource, encouraging collaboration and data sharing. The data acquired and displayed on GMOD is freely available in multiple formats and can be accessed from any device with an internet connection. RESULTS: Since its launch less than a year ago, GMOD has already proven its value. It has successfully integrated and processed large volumes of real-time data (~ 300,000 observations), offering valuable and actionable insights into mosquito species prevalence, abundance, and potential distributions, as well as engaging citizens in community-based surveillance programs. CONCLUSIONS: GMOD is a cloud-based platform that provides open access to mosquito vector data obtained from citizen science programs. Its user-friendly interface and data filters make it valuable for researchers, mosquito control personnel, and other stakeholders. With its expanding data resources and the potential for machine learning integration, GMOD is poised to support public health initiatives aimed at reducing the spread of mosquito-borne diseases in a cost-effective manner, particularly in regions where traditional surveillance methods are limited. GMOD is continually evolving, with ongoing development of powerful artificial intelligence algorithms to identify mosquito species and other features from submitted data. The future of citizen science holds great promise, and GMOD stands as an exciting initiative in this field.

Frequency of serrated polyposis syndrome recognition by community endoscopists.

Background and study aims Some data indicate serrated polyposis syndrome (SPS) is underdiagnosed. We determined the frequency of SPS diagnosis by community endoscopists prior to referral to a tertiary center. Patients and methods We performed a retrospective analysis of a prospectively collected database of SPS patients at a tertiary academic hospital. There were 212 patients who were referred to our center for resection of one or more lesions detected at a prior colonoscopy and who had records available that allowed determination of whether SPS was diagnosed before referral. Results Only 25 of 212 patients (11.8%) had a diagnosis or suspicion of a polyposis syndrome prior to referral, and only 12 patients (5.7%) had a specific SPS diagnosis made prior to referral. Among 187 patients diagnosed at our center, 39 had sufficient serrated lesions removed and documented in outside records to meet SPS criteria prior to referral, but the diagnosis was not made by the referring physician despite adequate numbers of lesions resected. The remaining cases required lesions removed at our center to meet SPS diagnostic criteria. Limitations were a single center, single expert endoscopist. Conclusions SPS is the most common colorectal polyposis syndrome, but it remains underdiagnosed by community endoscopists. Underdiagnosis may contribute to post-colonoscopy colorectal cancer in patients with SPS.

Impact of Sports Participation on Achievement of Clinically Relevant Outcomes 2 Years After ACL Reconstruction.

Background: Clinically relevant threshold values associated with patient-reported outcome measures after orthopaedic procedures such as anterior cruciate ligament reconstruction (ACLR) are important for relating these scores to meaningful postoperative improvement. Purpose/Hypothesis: The purpose of this study was to determine the Patient Acceptable Symptom State (PASS) for the Patient-Reported Outcomes Measurement Information System Computer Adaptive Test (PROMIS-CAT) after ACLR. It was hypothesized that preoperative sport participation would have an impact on PASS achievement. Study Design: Case series; Level of evidence, 4. Methods: Included were consecutive patients who underwent primary assisted ACLR between January 4 and August 1, 2016. Patients were administered the PROMIS-CAT Physical Function (PF) and Pain Interference domains preoperatively and at a minimum 2 years postoperatively, with external anchor questions used to determine the PASS. Receiver operating characteristic (ROC) curves were constructed for the entire study population as well as separately for athletes and nonathletes to determine PROMIS PASS thresholds for each population. A previously published PROMIS-PF minimal clinically important difference was used to evaluate postoperative improvement. A post hoc multivariate nominal logistic multivariate analysis was constructed to assess the effects of preoperative patient characteristics on the likelihood of attaining both the minimal clinically important difference and PASS. Results: In total, 112 patients were included in the study, with 79 (71%) having recreational or higher levels of athletic participation. The PASS for the study population was 56.0 (area under the ROC curve, 0.86) and was unaffected by baseline PROMIS-PF scores but was affected by preoperative athletic participation (56.0 for athletes, 49.0 for nonathletes). A post hoc analysis found 57 patients (51%) achieved the PASS for the PROMIS-PF (cutoff, 56.0), but when the athlete and nonathlete thresholds were applied to their respective patient groups, 66% of athletes and 64% of nonathletes achieved the PASS postoperatively. The multivariate analysis found that sport participation (odds ratio, 6.2; P = .001) but not age, sex, body mass index, or preoperative PROMIS affected the likelihood of achieving the PASS on the PROMIS-PF. Conclusion: Preoperative athletic participation significantly affected the ability to achieve PASS.

Optoα1AR activation in astrocytes modulates basal hippocampal synaptic excitation and inhibition in a stimulation-specific manner.

Astrocytes play active roles at synapses and can monitor, respond, and adapt to local synaptic activity. While there is abundant evidence that astrocytes modulate excitatory transmission in the hippocampus, evidence for astrocytic modulation of hippocampal synaptic inhibition remains more limited. Furthermore, to better investigate roles for astrocytes in modulating synaptic transmission, more tools that can selectively activate native G protein signaling pathways in astrocytes with both spatial and temporal precision are needed. Here, we utilized AAV8-GFAP-Optoα1AR-eYFP (Optoα1AR), a viral vector that enables activation of Gq signaling in astrocytes via light-sensitive α1-adrenergic receptors. To determine if stimulating astrocytic Optoα1AR modulates hippocampal synaptic transmission, recordings were made in CA1 pyramidal cells with surrounding astrocytes expressing Optoα1AR, channelrhodopsin (ChR2), or GFP. Both high-frequency (20 Hz, 45-ms light pulses, 5 mW, 5 min) and low-frequency (0.5 Hz, 1-s pulses at increasing 1, 5, and 10 mW intensities, 90 s per intensity) blue light stimulation were tested. 20 Hz Optoα1AR stimulation increased both inhibitory and excitatory postsynaptic current (IPSC and EPSC) frequency, and the effect on miniature IPSCs (mIPSCs) was largely reversible within 20 min. However, low-frequency stimulation of Optoα1AR did not modulate either IPSCs or EPSCs, suggesting that astrocytic Gq -dependent modulation of basal synaptic transmission in the hippocampus is stimulation-dependent. By contrast, low-frequency stimulation of astrocytic ChR2 was effective in increasing both synaptic excitation and inhibition. Together, these data demonstrate that Optoα1AR activation in astrocytes changes basal GABAergic and glutamatergic transmission, but only following high-frequency stimulation, highlighting the importance of temporal dynamics when using optical tools to manipulate astrocyte function.

Effects of Cell-Adhesive Ligand Presentation on Pentapeptide Supramolecular Assembly and Gelation: Simulations and Experiments.

The extracellular matrix (ECM) is a complex, hierarchical material containing structural and bioactive components. This complexity makes decoupling the effects of biomechanical properties and cell-matrix interactions difficult, especially when studying cellular processes in a 3D environment. Matrix mechanics and cell adhesion are both known regulators of specific cellular processes such as stem cell proliferation and differentiation. However, more information is required about how such variables impact various neural lineages that could, upon transplantation, therapeutically improve neural function after a central nervous system injury or disease. Rapidly Assembling Pentapeptides for Injectable Delivery (RAPID) hydrogels are one biomaterial approach to meet these goals, consisting of a family of peptide sequences that assemble into physical hydrogels in physiological media. In this study, we studied our previously reported supramolecularly-assembling RAPID hydrogels functionalized with the ECM-derived cell-adhesive peptide ligands RGD, IKVAV, and YIGSR. Using molecular dynamics simulations and experimental rheology, we demonstrated that these integrin-binding ligands at physiological concentrations (3-12 mm) did not impact the assembly of the KYFIL peptide system. In simulations, molecular measures of assembly such as hydrogen bonding and pi-pi interactions appeared unaffected by cell-adhesion sequence or concentration. Visualizations of clustering and analysis of solvent-accessible surface area indicated that the integrin-binding domains remained exposed. KYFIL or AYFIL hydrogels containing 3 mm of integrin-binding domains resulted in mechanical properties consistent with their non-functionalized equivalents. This strategy of doping RAPID gels with cell-adhesion sequences allows for the precise tuning of peptide ligand concentration, independent of the rheological properties. The controllability of the RAPID hydrogel system provides an opportunity to investigate the effect of integrin-binding interactions on encapsulated neural cells to discern how hydrogel microenvironment impacts growth, maturation, or differentiation.

Analysis of a Community Health Screening Program and the Factors Affecting Access to Care.

Introduction Free community health fairs and screening initiatives can be effective in broadening access to care and improving health outcomes in historically marginalized communities. UTHealthCares is a community health-focused organization developed at the University of Texas Health Science Center in Houston. At the beginning of 2023, UTHealthCares oversaw a free community health fair in the Eastex-Jensen Area - a medically underserved area in Northeast Houston. The health fair consisted of four stations - vitals and body mass index collection, vision screening, blood glucose screening, and dental screening. Participants also received coronavirus disease 2019 vaccinations, referrals, and health education. The purpose of this study is to evaluate the effectiveness of the UTHealthCares community health fair while assessing the factors that influence participants' access to medical care. Methods After completing the health fair, participants filled out an optional questionnaire. The questionnaire contained items that assessed satisfaction with the health fair, improvements in managing health, and access to resources. We calculated descriptive statistics, including mean response and 95% confidence intervals for rating scale questions. We used the chi-squared test to evaluate the independence of categorical variables and the Mann-Whitney U test to evaluate differences in means between distributions. Results A total of 111 people participated in the health fair, 91 of which completed a questionnaire. When participants rated their satisfaction with the health fair, the average response was 4.62 out of five. Participants also reported that they were more comfortable managing areas of health related to the stations offered at the fair. Many participants reported limited access to fresh food and long travel times to the physician. Participants that traveled further to reach one resource also tended to have significantly higher travel times for the other: X2 (4, N=78)=28.04, p<0.0001. However, 77.8% of respondents reported that the lack of insurance or cost was their greatest barrier to seeing a medical provider, while only 2.47% reported the lack of transportation as their greatest barrier. Participants who reported having health insurance also had a significantly higher probability of visiting a medical provider when they had a health issue: U=928.5, p=0.0006. Conclusion Overall, participants reported high satisfaction with the health fair. Participants also gave valuable feedback for improving future community health initiatives. Although many participants reported travel times greater than 30 minutes to reach community resources, very few participants indicated that transportation was their largest barrier to accessing medical care. Instead, the lack of insurance and high costs seem to be participants' most significant hindrances. Therefore, interventions in the Eastex-Jensen area focused on expanding access to care should also include components that improve access to insurance.

Peptide Stereocomplexation Orchestrates Supramolecular Assembly of Hydrogel Biomaterials.

Stereocomplexation, or specific interactions among complementary stereoregular macromolecules, is burgeoning as an increasingly impactful design tool, exerting exquisite control of material structure and properties. Since stereocomplexation of polymers produces remarkable transformations in mechanics, morphology, and degradation, we sought to leverage stereocomplexation to tune these properties in peptide-based biomaterials. We found that blending the pentapeptides l- and d-KYFIL triggers dual mechanical and morphological transformations from stiff fibrous hydrogels into less stiff networks of plates, starkly contrasting prior reports that blending l- and d-peptides produces stiffer fibrous hydrogels than the individual constituents. The morphological transformation of KYFIL in phosphate-buffered saline from fibers that entangle into hydrogels to plates that cannot entangle explains the accompanying mechanical transformation. Moreover, the blends shield l-KYFIL from proteolytic degradation, producing materials with comparable proteolytic stability to d-KYFIL but with distinct 2D plate morphologies that in biomaterials may promote unique therapeutic release profiles and cell behavior. To confirm that these morphological, mechanical, and stability changes arise from differences in molecular packing as in polymer stereocomplexation, we acquired X-ray diffraction patterns, which showed l- and d-KYFIL to be amorphous and their blends to be crystalline. Stereocomplexation is particularly apparent in pure water, where l- and d-KYFIL are soluble random coils, and their blends form ß-sheets and gel within minutes. Our results highlight the role of molecular details, such as peptide sequence, in determining the material properties resulting from stereocomplexation. Looking forward, the ability of stereocomplexation to orchestrate supramolecular assembly and tune application-critical properties champions stereochemistry as a compelling design consideration.

Tracking B cell responses to the SARS-CoV-2 mRNA-1273 vaccine.

Protective immunity following vaccination is sustained by long-lived antibody-secreting cells and resting memory B cells (MBCs). Responses to two-dose SARS-CoV-2 mRNA-1273 vaccination are evaluated longitudinally by multimodal single-cell analysis in three infection-naïve individuals. Integrated surface protein, transcriptomics, and B cell receptor (BCR) repertoire analysis of sorted plasmablasts and spike+ (S-2P+) and S-2P- B cells reveal clonal expansion and accumulating mutations among S-2P+ cells. These cells are enriched in a cluster of immunoglobulin G-expressing MBCs and evolve along a bifurcated trajectory rooted in CXCR3+ MBCs. One branch leads to CD11c+ atypical MBCs while the other develops from CD71+ activated precursors to resting MBCs, the dominant population at month 6. Among 12 evolving S-2P+ clones, several are populated with plasmablasts at early timepoints as well as CD71+ activated and resting MBCs at later timepoints, and display intra- and/or inter-cohort BCR convergence. These relationships suggest a coordinated and predictable evolution of SARS-CoV-2 vaccine-generated MBCs.