Effects of Acute Guarana (Paullinia cupana) Ingestion on Mental Performance and Vagal Modulation Compared to a Low Dose of Caffeine.

Guarana (GUA), a Brazilian seed extract, contains caffeine and other bioactive compounds that may have psychoactive effects. To assess the acute effects of GUA compared to a low dose of caffeine (CAF) on cognitive and mood parameters, twenty participants completed a double-blind, crossover experiment where they ingested capsules containing the following: (1) 100 mg CAF, (2) 500 mg GUA containing 130 mg caffeine, or (3) placebo (PLA). Cognitive tests (Simon and 2N-Back Task) were performed at the baseline (pre-ingestion) and 60 min after ingestion. The response time for the cognitive tests and heart rate variability were unaffected (p > 0.05) by treatment, although 2N-Back was overall faster (p = 0.001) across time. The accuracy in the 2N-Back Task showed a significant interaction effect (p = 0.029) due to higher post-ingestion versus pre-ingestion levels (p = 0.033), but only with the PLA. The supplements also had no effect on cognitive measures following physical fatigue (n = 11). There was an interaction effect on perceived mental energy, where the pre-ingestion of GUA had lower mental pep ratings compared to post-ingestion (p = 0.006) and post-exercise (p = 0.018) levels. Neither the acute ingestion of GUA nor low dose of CAF influenced cognitive performance or provided consistent benefit on mood or mental workload through vagal modulation. Additional investigations are beneficial to determining the lowest effective dose for CAF or GUA to influence mood and/or cognitive performance.

Delineating the functional activity of antibodies with cross-reactivity to SARS-CoV-2, SARS-CoV-1 and related sarbecoviruses.

The recurring spillover of pathogenic coronaviruses and demonstrated capacity of sarbecoviruses, such SARS-CoV-2, to rapidly evolve in humans underscores the need to better understand immune responses to this virus family. For this purpose, we characterized the functional breadth and potency of antibodies targeting the receptor binding domain (RBD) of the spike glycoprotein that exhibited cross-reactivity against SARS-CoV-2 variants, SARS-CoV-1 and sarbecoviruses from diverse clades and animal origins with spillover potential. One neutralizing antibody, C68.61, showed remarkable neutralization breadth against both SARS-CoV-2 variants and viruses from different sarbecovirus clades. C68.61, which targets a conserved RBD class 5 epitope, did not select for escape variants of SARS-CoV-2 or SARS-CoV-1 in culture nor have predicted escape variants among circulating SARS-CoV-2 strains, suggesting this epitope is functionally constrained. We identified 11 additional SARS-CoV-2/SARS-CoV-1 cross-reactive antibodies that target the more sequence conserved class 4 and class 5 epitopes within RBD that show activity against a subset of diverse sarbecoviruses with one antibody binding every single sarbecovirus RBD tested. A subset of these antibodies exhibited Fc-mediated effector functions as potent as antibodies that impact infection outcome in animal models. Thus, our study identified antibodies targeting conserved regions across SARS-CoV-2 variants and sarbecoviruses that may serve as therapeutics for pandemic preparedness as well as blueprints for the design of immunogens capable of eliciting cross-neutralizing responses.

Photorefractive Keratectomy and Laser-Assisted In Situ Keratomileusis on 6-Month Space Missions.

BACKGROUND: This article documents the stability of photorefractive keratectomy (PRK) and laser-assisted in situ keratomileusis (LASIK) in two astronauts during 6-mo missions to the International Space Station.CASE REPORTS: Ocular examinations including visual acuity, cycloplegic refraction, slit lamp examination, corneal topography, central corneal thickness, optical biometry (axial length/keratometry), applanation tonometry, and dilated fundus examination were performed on each astronaut before and after their missions, and in-flight visual acuity testing was done on flight day 30, 90, and R-30 (30 d before return). They were also questioned regarding visual changes during flight.DISCUSSION: We documented stable vision in both PRK and LASIK astronauts during liftoff, entry into microgravity, 6 mo on the International Space Station, descent, and landing. Our results suggest that both PRK and LASIK are stable and well tolerated during long-duration spaceflight.Gibson CR, Mader TH, Lipsky W, Schallhorn SC, Tarver WJ, Suresh R, Hauge TN, Brunstetter TJ. Photorefractive keratectomy and laser-assisted in situ keratomileusis on 6-month space missions. Aerosp Med Hum Perform. 2024; 95(5):278-281.

Effect of age on ankle biomechanics and tibial compression during stair descent.

BACKGROUND: Stress fracture is a concern among older adults, as age-related decrements in ankle neuromuscular function may impair their ability to attenuate tibial compressive forces experienced during daily locomotor tasks, such as stair descent. Yet, it is unknown if older adults exhibit greater tibial compression than their younger counterparts when descending stairs. RESEARCH QUESTION: Do older adults exhibit differences in ankle biomechanics that alter their tibial compression during stair descent compared to young adults, and is there a relation between tibial compression and specific changes in ankle biomechanics? METHODS: Thirteen young (18-25 years) and 13 older (> 65 years) adults had ankle joint biomechanics and tibial compression quantified during a stair descent. Discrete ankle biomechanics (peak joint angle and moment, and joint stiffness) and tibial compression (maximum and impulse) measures were submitted to an independent t-test, while ankle joint angle and moment, and tibial compression waveforms were submitted to an independent statistical parametric mapping t-test to determine group differences. Pearson correlation coefficients (r) determined the relation between discrete ankle biomechanics and tibial compression measures for all participants, and each group. RESULTS: Older adults exhibited smaller maximum tibial compression (p = 0.004) from decreases in peak ankle joint angle and moment between 17 % and 34 % (p = 0.035), and 20-31 % of stance (p < 0.001) than young adults. Ankle biomechanics exhibited a negligible to weak correlation with tibial compression for all participants, with peak ankle joint moment and maximum tibial compression (r = -0.48 ±â€¯0.32) relation the strongest. Older adults typically exhibited a stronger relation between ankle biomechanics and tibial compression (e.g., r = -0.48 ±â€¯0.47 vs r = -0.27 ±â€¯0.52 between peak ankle joint moment and maximum tibial compression). SIGNIFICANCE: Older adults altered ankle biomechanics and decreased maximum tibial compression to safely execute the stair descent. Yet, specific alterations in ankle biomechanics could not be identified as a predictor of changes in tibial compression.

Active Darcy's Law.

While bacterial swarms can exhibit active turbulence in vacant spaces, they naturally inhabit crowded environments. We numerically show that driving disorderly active fluids through porous media enhances Darcy's law. While purely active flows average to zero flux, hybrid active/driven flows display greater drift than purely pressure-driven flows. This enhancement is nonmonotonic with activity, leading to an optimal activity to maximize flow rate. We incorporate the active contribution into an active Darcy's law, which may serve to help understand anomalous transport of swarming in porous media.

Epistasis facilitates functional evolution in an ancient transcription factor.

A protein's genetic architecture - the set of causal rules by which its sequence produces its functions - also determines its possible evolutionary trajectories. Prior research has proposed that the genetic architecture of proteins is very complex, with pervasive epistatic interactions that constrain evolution and make function difficult to predict from sequence. Most of this work has analyzed only the direct paths between two proteins of interest - excluding the vast majority of possible genotypes and evolutionary trajectories - and has considered only a single protein function, leaving unaddressed the genetic architecture of functional specificity and its impact on the evolution of new functions. Here, we develop a new method based on ordinal logistic regression to directly characterize the global genetic determinants of multiple protein functions from 20-state combinatorial deep mutational scanning (DMS) experiments. We use it to dissect the genetic architecture and evolution of a transcription factor's specificity for DNA, using data from a combinatorial DMS of an ancient steroid hormone receptor's capacity to activate transcription from two biologically relevant DNA elements. We show that the genetic architecture of DNA recognition consists of a dense set of main and pairwise effects that involve virtually every possible amino acid state in the protein-DNA interface, but higher-order epistasis plays only a tiny role. Pairwise interactions enlarge the set of functional sequences and are the primary determinants of specificity for different DNA elements. They also massively expand the number of opportunities for single-residue mutations to switch specificity from one DNA target to another. By bringing variants with different functions close together in sequence space, pairwise epistasis therefore facilitates rather than constrains the evolution of new functions.

Clodronate disodium does not produce measurable effects on bone metabolism in an exercising, juvenile, large animal model.

Bisphosphonates are commonly used to treat and prevent bone loss, but their effects in active, juvenile populations are unknown. This study examined the effects of intramuscular clodronate disodium (CLO) on bone turnover, serum bone biomarkers (SBB), bone mineral density (BMD), bone microstructure, biomechanical testing (BT), and cartilage glycosaminoglycan content (GAG) over 165 days. Forty juvenile sheep (253 ± 6 days of age) were divided into four groups: Control (saline), T0 (0.6 mg/kg CLO on day 0), T84 (0.6 mg/kg CLO on day 84), and T0+84 (0.6 mg/kg CLO on days 0 and 84). Sheep were exercised 4 days/week and underwent physical and lameness examinations every 14 days. Blood samples were collected for SBB every 28 days. Microstructure and BMD were calculated from tuber coxae (TC) biopsies (days 84 and 165) and bone healing was assessed by examining the prior biopsy site. BT and GAG were evaluated postmortem. Data, except lameness data, were analyzed using a mixed-effects model; lameness data were analyzed as ordinal data using a cumulative logistic model. CLO did not have any measurable effects on the skeleton of sheep. SBB showed changes over time (p ≤ 0.03), with increases in bone formation and decreases in some bone resorption markers. TC biopsies showed increasing bone volume fraction, trabecular spacing and thickness, and reduced trabecular number on day 165 versus day 84 (p ≤ 0.04). These changes may be attributed to exercise or growth. The absence of a treatment effect may be explained by the lower CLO dose used in large animals compared to humans. Further research is needed to examine whether low doses of bisphosphonates may be used in active juvenile populations for analgesia without evidence of bone changes.

Broadly neutralizing antibodies against emerging delta-coronaviruses.

Porcine deltacoronavirus (PDCoV) spillovers were recently detected in children with acute undifferentiated febrile illness, underscoring recurrent zoonoses of divergent coronaviruses. To date, no vaccines or specific therapeutics are approved for use in humans against PDCoV. To prepare for possible future PDCoV epidemics, we isolated human spike (S)-directed monoclonal antibodies from transgenic mice and found that two of them, designated PD33 and PD41, broadly neutralized a panel of PDCoV variants. Cryo-electron microscopy structures of PD33 and PD41 in complex with the PDCoV receptor-binding domain and S ectodomain trimer provide a blueprint of the epitopes recognized by these mAbs, rationalizing their broad inhibitory activity. We show that both mAbs inhibit PDCoV by competitively interfering with host APN binding to the PDCoV receptor-binding loops, explaining the mechanism of viral neutralization. PD33 and PD41 are candidates for clinical advancement, which could be stockpiled to prepare for possible future PDCoV outbreaks.

Medicaid Inmate Exclusion Policy and Infectious Diseases Care for Justice-Involved Populations.

The Medicaid Inmate Exclusion Policy (MIEP) prohibits using federal funds for ambulatory care services and medications (including for infectious diseases) for incarcerated persons. More than one quarter of states, including California and Massachusetts, have asked the federal government for authority to waive the MIEP. To improve health outcomes and continuation of care, those states seek to cover transitional care services provided to persons in the period before release from incarceration. The Massachusetts Sheriffs' Association, Massachusetts Department of Correction, Executive Office of Health and Human Services, and University of Massachusetts Chan Medical School have collaborated to improve infectious disease healthcare service provision before and after release from incarceration. They seek to provide stakeholders working at the intersection of criminal justice and healthcare with tools to advance Medicaid policy and improve treatment and prevention of infectious diseases for persons in jails and prisons by removing MIEP barriers through Section 1115 waivers.

Lock-key microfluidics: simulating nematic colloid advection along wavy-walled channels.

Liquid crystalline media mediate interactions between suspended particles and confining geometries, which not only has potential to guide patterning and bottom-up colloidal assembly, but can also control colloidal migration in microfluidic devices. However, simulating such dynamics is challenging because nemato-elasticity, diffusivity and hydrodynamic interactions must all be accounted for within complex boundaries. We model the advection of colloids dispersed in flowing and fluctuating nematic fluids confined within 2D wavy channels. A lock-key mechanism between homeotropic colloids and troughs is found to be stronger for planar anchoring on the wavy walls compared to homeotropic anchoring on the wavy walls due to the relative location of the colloid-associated defects. Sufficiently large amplitudes result in stick-slip trajectories and even permanent locking of colloids in place. These results demonstrate that wavy walls not only have potential to direct colloids to specific docking sites but also to control site-specific resting duration and intermittent elution.

Weak coupling between energetic status and the timing of reproduction in an Arctic ungulate.

Bioenergetic constraints are the ultimate determinant of the timing of reproduction, and seasonal breeding is consequently a widely observed trait. Consistent with this, attention has focused on plasticity in reproductive phenology conceptualized as a response to concomitant advances in the phenology of the environmental energy supply caused by climate change. Few studies, however, have directly compared timing of reproduction with energetic status in free-living wild animals. Here we demonstrate that neither body mass nor adiposity are strong proximate predictors of date of conception in wild reindeer (Rangifer tarandus). Weak coupling between energetic status and the phenology of reproduction accounts for the increasing discrepancy between the phenology of forage (energy supply) and the phenology of reproduction (energy demand) observed across the last 2-4 decades in two populations of this species. The results emphasise that phenological plasticity is not a passive response to changes in energy supply but derives from the way in which environmental factors interact with the core control mechanisms that govern timing. Central in this respect is integration, within the rheostatic centres of the hypothalamus, of information on nutritional status with the circannual life-history calendar.

Rifampin- and Silymarin-Mediated Pharmacokinetic Interactions of Exogenous and Endogenous Substrates in a Transgenic OATP1B Mouse Model.

Organic anion-transporting polypeptides (OATP) 1B1 and OATP1B3, encoded by the SLCO gene family of the solute carrier superfamily, are involved in the disposition of many exogenous and endogenous compounds. Preclinical rodent models help assess risks of pharmacokinetic interactions, but interspecies differences in transporter orthologs and expression limit direct clinical translation. An OATP1B transgenic mouse model comprising a rodent Slco1a/1b gene cluster knockout and human SLCO1B1 and SLCO1B3 gene insertions provides a potential physiologically relevant preclinical tool to predict pharmacokinetic interactions. Pharmacokinetics of exogenous probe substrates, pitavastatin and pravastatin, and endogenous OATP1B biomarkers, coproporphyrin-I and coproporphyrin-III, were determined in the presence and absence of known OATP/Oatp inhibitors, rifampin or silymarin (an extract of milk thistle [Silybum marianum]), in wild-type FVB mice and humanized OATP1B mice. Rifampin increased exposure of pitavastatin (4.6- and 2.8-fold), pravastatin (3.6- and 2.2-fold), and coproporphyrin-III (1.6- and 2.1-fold) in FVB and OATP1B mice, respectively, but increased coproporphyrin-I AUC0-24h only (1.8-fold) in the OATP1B mice. Silymarin did not significantly affect substrate AUC, likely because the silymarin flavonolignan concentrations were at or below their reported IC50 values for the relevant OATPs/Oatps. Silymarin increased the Cmax of pitavastatin 2.7-fold and pravastatin 1.9-fold in the OATP1B mice. The data of the OATP1B mice were similar to those of the pitavastatin and pravastatin clinical data; however, the FVB mice data more closely recapitulated pitavastatin clinical data than the data of the OATP1B mice, suggesting that the OATP1B mice are a reasonable, though costly, preclinical strain for predicting pharmacokinetic interactions when doses are optimized to achieve clinically relevant plasma concentrations.

Pharmacokinetic Effects of Different Models of Nonalcoholic Fatty Liver Disease in Transgenic Humanized OATP1B Mice.

Organic anion transporting polypeptide (OATP) 1B1 and OATP1B3 (collectively, OATP1B) transporters encoded by the solute carrier organic anion transporter (SLCO) genes mediate uptake of multiple pharmaceutical compounds. Nonalcoholic steatohepatitis (NASH), a severe form of nonalcoholic fatty liver disease (NAFLD), decreases OATP1B abundance. This research characterized the pathologic and pharmacokinetics effects of three diet- and one chemical-induced NAFLD model in male and female humanized OATP1B mice, which comprises knock-out of rodent Oatp orthologs and insertion of human SLCO1B1 and SLCO1B3. Histopathology scoring demonstrated elevated steatosis and inflammation scores for all NAFLD-treatment groups. Female mice had minor changes in SLCO1B1 expression in two of the four NAFLD treatment groups, and pitavastatin (PIT) area under the concentration-time curve (AUC) increased in female mice in only one of the diet-induced models. OATP1B3 expression decreased in male and female mice in the chemical-induced NAFLD model, with a coinciding increase in PIT AUC, indicating the chemical-induced model may better replicate changes in OATP1B3 expression and OATP substrate disposition observed in NASH patients. This research also tested a reported multifactorial pharmacokinetic interaction between NAFLD and silymarin, an extract from milk thistle seeds with notable OATP-inhibitory effects. Males showed no change in PIT AUC, whereas female PIT AUC increased 1.55-fold from the diet alone and the 1.88-fold from the combination of diet with silymarin, suggesting that female mice are more sensitive to pharmacokinetic changes than male mice. Overall, the humanized OATP1B model should be used with caution for modeling NAFLD and multifactorial pharmacokinetic interactions. SIGNIFICANCE STATEMENT: Advanced stages of NAFLD cause decreased hepatic OATP1B abundance and increase systemic exposure to OATP substrates in human patients. The humanized OATP1B mouse strain may provide a clinically relevant model to recapitulate these observations and predict pharmacokinetic interactions in NAFLD. This research characterized three diet-induced and one drug-induced NAFLD model in a humanized OATP1B mouse model. Additionally, a multifactorial pharmacokinetic interaction was observed between silymarin and NAFLD.

The type IV pilus chemoreceptor PilJ controls chemotaxis of one bacterial species towards another.

Bacteria live in social communities, where the ability to sense and respond to interspecies and environmental signals is critical for survival. We previously showed the pathogen Pseudomonas aeruginosa detects secreted peptides from bacterial competitors and navigates through interspecies signal gradients using pilus-based motility. Yet, it was unknown whether P. aeruginosa utilizes a designated chemosensory system for this behavior. Here, we performed a systematic genetic analysis of a putative pilus chemosensory system, followed by high-speed live-imaging and single-cell tracking, to reveal behaviors of mutants that retain motility but are blind to interspecies signals. The enzymes predicted to methylate (PilK) and demethylate (ChpB) the putative pilus chemoreceptor, PilJ, are necessary for cells to control the direction of migration. While these findings implicate PilJ as a bona fide chemoreceptor, such function had yet to be experimentally defined, as full-length PilJ is essential for motility. Thus, we constructed systematic genetic modifications of PilJ and found that without the predicted ligand binding domains or predicted methylation sites, cells lose the ability to detect competitor gradients, despite retaining pilus-mediated motility. Chemotaxis trajectory analysis revealed that increased probability and size of P. aeruginosa pilus-mediated steps towards S. aureus peptides, versus steps away, determines motility bias in wild type cells. However, PilJ mutants blind to interspecies signals take less frequent steps towards S. aureus or steps of equal size towards and away. Collectively, this work uncovers the chemosensory nature of PilJ, provides insight into how cell movements are biased during pilus-based chemotaxis, and identifies chemotactic interactions necessary for bacterial survival in polymicrobial communities, revealing putative pathways where therapeutic intervention might disrupt bacterial communication.

Green Tea Catechins Decrease Solubility of Raloxifene In Vitro and Its Systemic Exposure in Mice.

PURPOSE: Green tea is a widely consumed beverage. A recent clinical study reported green tea decreased systemic exposure of raloxifene and its glucuronide metabolites by 34-43%. However, the underlying mechanism(s) remains unknown. This study investigated a change in raloxifene's solubility as the responsible mechanism. METHODS: The effects of green tea extract, (-)-epigallocatechin gallate (EGCG), and (-)-epigallocatechin (EGC) on raloxifene's solubility were assessed in fasted state simulated intestinal fluids (FaSSIF) and fed state simulated intestinal fluids (FeSSIF). EGCG and EGC represent green tea's main bioactive constituents, flavan-3-gallate and flavan-3-ol catechins respectively, and the tested concentrations (mM) match the µg/mg of each compound in the extract. Our mouse study (n = 5/time point) evaluated the effect of green tea extract and EGCG on the systemic exposure of raloxifene. RESULTS: EGCG (1 mM) and EGC (1.27 mM) decreased raloxifene's solubility in FaSSIF by 78% and 13%, respectively. Micelle size in FaSSIF increased with increasing EGCG concentrations (> 1000% at 1 mM), whereas EGC (1.27 mM) did not change micelle size. We observed 3.4-fold higher raloxifene solubility in FeSSIF compared to FaSSIF, and neither green tea extract nor EGCG significantly affected raloxifene solubility or micelle size in FeSSIF. The mice study showed that green tea extract significantly decreased raloxifene Cmax by 44%, whereas EGCG had no effect. Green tea extract and EGCG did not affect the AUC0-24 h of raloxifene or the metabolite-to-parent AUC ratio. CONCLUSIONS: This study demonstrated flavan-3-gallate catechins may decrease solubility of poorly water-soluble drugs such as raloxifene, particularly in the fasted state.

Semisynthesis, Characterization, and Biological Evaluation of Fluorinated Analogues of the Spirobisnaphthalene, Diepoxin-η.

Diepoxin-η (1) is a cytotoxic fungal metabolite belonging to the spirobisnaphthalene structural class. In this study, four mono fluorinated analogues (2-5) of diepoxin-η (1) were semisynthesized in a single-step by selectively fluorinating the naphthalene moiety with Selectfluor. The structures of 2-5 were elucidated using a set of spectroscopic and spectrometric techniques and were further confirmed by means of TDDFT-ECD and isotropic shielding tensors calculations. Compounds 2-5 showed equipotent cytotoxic activity to 1 when tested against OVCAR3 (ovarian) and MDA-MB-435 (melanoma) cancer cell lines with IC50 values that range from 5.7-8.2 µM.

Characteristics and co-morbidities associated with hospital discharges for opioid and methamphetamine co-use, United States 2016-2019.

Introduction: The US overdose crisis is increasingly characterized by opioid and methamphetamine co-use. Hospitalization is an important opportunity to engage patients in substance use treatment. Understanding characteristics of co-use-related hospital stays can inform the development of services to better support this growing patient population. Methods: We used 2016-2019 National Inpatient Sample data to conduct a cross sectional analysis of hospitalizations involving use of opioids, methamphetamine, or both. We used bivariate analysis to compare patient demographics. We then used multinomial logistic regressions to compare the proportion of hospital stays which indicated co-morbid diagnosis. To account for correlated data, we used generalized linear models to compare outcomes in hospital mortality, patient-directed discharge, and length of stay. Results: Co-use-related stays had a higher proportion of co-morbid mental health (60.7%; 95% CI: 59.9-61.4%) and infectious diseases (41.5%; 95% CI: 40.8-42.2%), than opioid- or methamphetamine-related stays. Co-use-related stays increased between 2016 and 2019 and were associated with a higher proportion of patient directed discharge (10.7%; 95% CI: 10.4-11.0%) and longer length of stay (6.3 days; 95% CI: 6.2-6.4 days) compared to opioid (8.1%; 95% CI: 7.9-8.3% and 5.8 days; 95% CI: 5.8-5.9 days) and methamphetamine-related stays (6.5%; 95% CI: 6.3-6.6% and 5.5 days; 95% CI: 5.4-5.5 days). Conclusion: Patients discharged with co-use differ from patients with opioid or methamphetamine use alone, representing a range of challenges and opportunities. In addition to offering treatment for both substance use disorders, hospital-based services that address co-occurring conditions may better support patients with co-use through targeted and tailored approaches.

Health Care Access and Use Among U.S. Children Exposed to Neighborhood Violence.

INTRODUCTION: Neighborhood violence is an adverse childhood experience which impacts millions of U.S. children and is associated with poor health outcomes across the life course. These effects may be mitigated by access to care. Yet, the ways in which exposure to neighborhood violence shapes children's health care access have been understudied. METHODS: This is a cross-sectional analysis of 16,083 children (weighted N=67,214,201) ages 1 to <18 years from the 2019 and 2021 National Health Interview Survey. Guardians were asked about preventive care access, unmet health needs, and health care utilization in the last year. Changes associated with exposure to neighborhood violence were estimated using marginal effects from multivariable logistic regression models adjusted for year, age, sex, race/ethnicity, parental education, family structure, rurality, income, insurance type, insurance discontinuity, and overall reported health. RESULTS: Of 16,083 sample children, 863 (weighted 5.3% [95% CI 4.8-5.7]) reported exposure to neighborhood violence, representing a weighted population of ∼3.5 million. In adjusted analyses, exposure to violence was associated with forgone prescriptions (adjusted difference 1.2 percentage-points (pp) [95%CI 0.1-2.3]; weighted national population impact 42,833 children), trouble paying medical bills (7.7pp [4.4-11.0]; 271,735), delayed medical (1.5pp [0.2-2.9]; 54,063) and mental health care (2.8pp [1.1-4.6]; 98,627), and increased urgent care (4.5pp [0.9-8.1]; 158,246) and emergency department utilization (6.4pp [3.1-9.8]; 227,373). CONCLUSIONS: In this nationally representative study, neighborhood violence exposure among children was associated with unmet health needs and increased acute care utilization. Evidence-based interventions to improve access to care and reduce economic precarity in communities impacted by violence are needed to mitigate downstream physical and mental health consequences.

Nationwide Aquatic Envenomations Reported to US Poison Control Centers from 2011 to 2020.

INTRODUCTION: Aquatic envenomations are common injuries along the coastal United States that pose a public health risk and can cause significant morbidity. We examined aquatic envenomation exposures that were called in to poison control centers (PCC) in the United States from 2011 to 2020. METHODS: The Association of Poison Control Center's (AAPCC) National Poison Data System was queried for all aquatic envenomations reported during the 10 y period from January 1, 2011, to December 31, 2020. Data collected included date, exposure and geographic location, patient age and sex, signs and symptoms, management setting, treatments, and clinical outcome. Duplicated records, confirmed nonexposure, and reports not originating within the United States were excluded. RESULTS: There were 8517 human aquatic envenomations reported during the study period, 62% (5243) of whom were male; 56% (4264) of patients were 30 y or younger. There were an average of 852 calls per year, with 46% of calls occurring during June to August. California, Texas, and Florida had the highest number of envenomations during the study period. Fish (61%; 5159) and Cnidaria (30%; 2519) envenomations were the most common exposures. Overall, 37% (3151) of exposures were treated in healthcare facilities, with no deaths reported. CONCLUSIONS: The highest proportion of aquatic envenomations occurred among younger males (≤30 y) during the summer months. While rarely leading to major adverse events, aquatic envenomations were commonly reported injuries to PCC and occurred in all 50 states. Poison control centers continue to be real-time sources of information and data regarding aquatic envenomation trends.

Anisotropic run-and-tumble-turn dynamics.

Run-and-tumble processes successfully model several living systems. While studies have typically focused on particles with isotropic tumbles, recent examples exhibit "tumble-turns", in which particles undergo 90° tumbles and so possess explicitly anisotropic dynamics. We study the consequences of such tumble-turn anisotropicity at both short and long-time scales. We model run-and-tumble-turn particles as self-propelled particles subjected to an angular potential that favors directions of movement parallel to Cartesian axes. Using agent-based simulations, we study the effects of the interplay between rotational diffusion and an aligning potential on the particles' trajectories, which leads to the right-angled turns. We demonstrate that the long-time effect is to alter the tumble-turn time, which governs the long-time dynamics. In particular, when normalized by this timescale, trajectories become independent of the underlying details of the potential. As such, we develop a simplified continuum theory, which quantitatively agrees with agent-based simulations. We find that the purely diffusive hydrodynamic limit still exhibits anisotropic features at intermediate times and conclude that the transition to diffusive dynamics precedes the transition to isotropic dynamics. By considering short-range repulsive and alignment particle-particle interactions, we show how the anisotropic features of a single particle are inherited by the global order of the system. We hope this work will shed light on how active systems can extend local anisotropic properties to macroscopic scales, which might be important in biological processes occurring in anisotropic environments.