A pharmacokinetic-pharmacodynamic analysis of l-glutamine for the treatment of sickle cell disease: Implications for understanding the mechanism of action and evaluating response to therapy.

The mechanisms of action of l-glutamine for the treatment of sickle cell disease (SCD) are not well understood and there are no validated clinical biomarkers to assess response. We conducted a three-week, dose-ascending trial of glutamine and measured the pharmacokinetic (PK) exposure parameters, peak concentration (Cmax) and area under the curve (AUC). We used a panel of biomarkers to investigate the pharmacodynamics (PD) of glutamine and studied PK-PD relationships. There was no plasma accumulation of glutamine, glutamate, arginine or other amino acids over time, but modestly improved arginine bioavailability was observed. In standard analysis by dose levels over time, there were no measurable effects on blood counts, viscosity, ektacytometry or reactive oxygen species (ROS). In PK-PD analysis, however, higher glutamine exposure (Cmax or AUC) was associated with increased whole blood viscosity and cellular dehydration, yet also with higher haemoglobin concentration, increased haematocrit-to-viscosity ratio, decreased reticulocyte ROS, improved RBC deformability and decreased point of sickling. This novel PK-PD analysis identified biomarkers reflecting the positive and negative effects of glutamine, helping to elucidate its mechanisms of action in SCD. PK-optimized dosing to achieve glutamine exposure (AUC or Cmax) that is associated with salutary biological effects should be studied to support its therapeutic use.

Case report: Spinal cord stimulation for pain relief in two patients with locally recurrent pelvic malignancy.

Introduction: Chronic cancer-related pain from locally recurrent infiltrative cancers within the bony confines of the pelvis is a devastating and hard to manage condition that can be refractory to many conventional pain management methods. Spinal cord stimulation (SCS) is an evolving and safe method of pain management and can be trialled in a quick and well-tolerated operation under local anaesthesia. To date, this has not been reported in the setting of locally recurrent inoperable pelvic cancers. Case description: In the present study, we report two cases of patients with severe back and lower limb pain resulting from recurrent anal and rectal cancers involving the right lumbar and sacral nerve roots as well as the bony sacrum, which severely affected quality of life and daily functioning. Discussion: Following successful SCS, effective pain relief was observed. Conclusion: SCS could represent an effective supplementary or alternative technique to conventional pain management in this challenging group of patients, especially if other available methods have been exhausted.

Reliability of a Modified Watson-Jones Classification for Tibial Tubercle Fractures in Children.

OBJECTIVES: The first case report describing a pediatric fracture of the tibial tubercle was published in 1852 in the Medical Times and Gazette, a Journal of Medical Science, literature, criticism, and news. A century later, in 1955, Sir Watson-Jones introduced the first classification system for this fracture. Despite the existence of several classification systems for pediatric tibial tubercle fractures in the medical literature, a crucial aspect of their validation-reliability and reproducibility-has not yet been systematically evaluated. METHODS: In this study, a modified Watson-Jones (mWJ) classification system of tibial tubercle fractures in children was assessed for intraobserver and interobserver variability. Using the mWJ classification, 3 board-certified pediatric orthopaedic surgeons and 3 orthopaedic surgery residents, classified thirty tibial tubercle fractures based on anteroposterior and lateral radiographs on 2 separate occasions in a 2-week duration. Further comparison was made to evaluate the impact of advanced imaging, specifically computed tomography or magnetic resonance imaging, on diagnostic reliability and reproducibility. RESULTS: The study found substantial intraobserver reliability of the mWJ classification based on radiographs alone, with a Cohen weighted kappa (κw) coefficient of 0.733. When advanced imaging was utilized, the reliability of the classification improved to κw = 0.783. Similarly, interobserver reliability demonstrated substantial consistency among observers when using radiographs alone (κw = 0.69) and improved agreement with advanced imaging (κw = 0.75). Notably, there was no significant difference in reliability scores between senior-level attendings and residents when analyzed as separate groups. CONCLUSION: Fracture classification systems are clinically relevant tools that help organize and transfer knowledge efficiently, provide treatment guidance, propose prognostic expectations, and improve communication in academic literature. The present study demonstrated substantial reproducibility of an mWJ fracture classification system both between and within individual surgeon raters. LEVEL OF EVIDENCE: Level III-diagnostic.

Zoledronic acid for hip fracture during initial hospitalization.

Inpatient zoledronic acid (IP-ZA) administered during the initial fracture hospitalization significantly improves the osteoporosis treatment rate. Clinical outcomes of IP-ZA after hip fracture remains uncertain. Here we report a new-user active comparator cohort study that emulated a randomized controlled trial using real-world data and evaluated the risk of death of any cause and radiologically confirmed subsequent new fractures among patients hospitalized for a hip fracture who had received IP-ZA as compared with propensity-matched controls who were not treated with anti-osteoporosis medication within the first-year post fracture. 654 patients who had received IP-ZA and 6877 controls (for whom antiosteoporosis treatment was indicated but no IP-ZA started during index hospitalization) were included in the study. The primary cohort comprised 652 IP-ZA patients (IP-ZA group) and 1926 matched controls (Untreated group) with 71.7% female, 92.1% White, and mean age of 80.9 years. Cumulative all-cause-mortality over the 24 months follow-up for the IP-ZA group was 12.3%, and 20.7% for Untreated group [hazard ratio (HR), 0.62; 95% confidence interval (CI), 0.49-0.78, p < 0.001)]. 585 (89.7%) patients in IP-ZA group received only a single dose of ZA during the 24 months, and the death rate of this single dose group was 13.3%, which was significantly lower than that of the Untreated group (HR, 0.70; 95% CI, 0.55-0.89, p = 0.003). Rates of radiologically confirmed cumulative subsequent new vertebral fractures were 2.0% in IP-ZA group and 5.4% in Untreated group (HR, 0.40; 95% CI, 0.22-0.71, P = 0.001). A similarly lower rate of new vertebral fractures was seen in the single dose subgroup (1.9% vs. 5.4%. HR, 0.44; 95% 0.24-0.82, p = 0.008). IP-ZA, administered during the initial hospitalization for hip fracture, was associated with lower all-cause-mortality and risk of radiologically confirmed subsequent new vertebral fractures, and thus offers a mechanism to narrow the treatment gap in patients having sustained a hip fragility fracture.

Hip fracture is a serious complication of osteoporosis affecting approximately 300 000 Americans per year and is associated with a 20-30% one-year mortality rate. Most patients with hip fracture are elderly (average age 80-81 years), with multiple underlying medical conditions and are often unable to timely attend post-hospitalization outpatient follow-up to initiate anti-osteoporosis treatment. As a result, only ~10% of post-hip fracture patients receive treatment for underlying osteoporosis. We have previously reported that zoledronic acid (ZA) administered during initial fracture hospitalization (IP-ZA) is safe and can effectively improve the osteoporosis treatment rate to 70%. The present study analyzed the clinical outcomes of 652 patients who had sustained hip fractures and were treated with IP-ZA and 1926 matched controls and revealed significantly reduced rates of all-cause mortality and vertebral compression fracture (VCF) during a 2-year follow-up period. Of note, nearly 90% of the treated patients received only a single dose of ZA (namely, IP-ZA), suggesting that, for most patients, the only opportunity to receive anti-osteoporosis treatment was during the index fracture hospitalization. Importantly, reduced mortality and VCF rates were readily seen in this single-dose group of patients. Our data suggests that IP-ZA is beneficial for osteoporotic hip fracture.

Judicial Opinion 130.

Opinion 130 deals with a Request for an Opinion asking the Judicial Commission to clarify whether the genus name Rhodococcus Zopf 1891 (Approved Lists 1980) is illegitimate. The Request is approved and an answer is given. The name Rhodococcus Zopf 1891 (Approved Lists 1980) is illegitimate because it is a later homonym of the validly published cyanobacterial name Rhodococcus Hansgirg 1884. The Judicial Commission also clarifies that it has the means to resolve such cases by conserving a name over an earlier homonym. It is concluded that the name Rhodococcus Zopf 1891 (Approved Lists 1980) is significantly more important than the name Rhodococcus Hansgirg 1884 and therefore the former is conserved over the latter. This makes the name Rhodococcus Zopf 1891 (Approved Lists 1980) legitimate.

Pediatric Pharmacology for the Primary Care Provider: Advances and Limitations.

Despite >1 in 5 children taking prescription drugs in the United States, off-label drug use is common. To increase the study of drugs in children, regulatory bodies have enacted legislation to incentivize and require pediatric drug studies. As a result of this legislation, novel trial approaches, and an increase in personnel with pediatric expertise, there have been numerous advancements in pediatric drug development. With this review, we aim to highlight developments in pediatric pharmacology over the past 6 years for the most common disease processes that may be treated pharmacologically by the pediatric primary care provider. Using information extracted from label changes between 2018 and 2023, the published literature, and Clinicaltrials.gov, we discuss advances across multiple therapeutic areas relevant to the pediatric primary care provider, including asthma, obesity and related disorders, mental health disorders, infections, and dermatologic conditions. We highlight instances in which new drugs have been developed on the basis of a deeper mechanistic understanding of illness and instances in which labels have been expanded in older drugs on the basis of newly available data. We then consider additional factors that affect pediatric drug use, including cost and nonpharmacologic therapies. Although there is work to be done, efforts focused on pediatric-specific drug development will increase the availability of evidence-based, labeled guidance for commonly prescribed drugs and improve outcomes through the safe and effective use of drugs in children.

Trans-synaptic Association of Vesicular Zinc Transporter 3 and Shank3 Supports Synapse-Specific Dendritic Spine Structure and Function in the Mouse Auditory Cortex.

Shank3 is a synaptic scaffolding protein that assists in tethering and organizing structural proteins and glutamatergic receptors in the postsynaptic density of excitatory synapses. The localization of Shank3 at excitatory synapses and the formation of stable Shank3 complexes is regulated by the binding of zinc to the C-terminal sterile-alpha-motif (SAM) domain of Shank3. Mutations in the SAM domain of Shank3 result in altered synaptic function and morphology, and disruption of zinc in synapses that express Shank3 leads to a reduction of postsynaptic proteins important for synaptic structure and function. This suggests that zinc supports the localization of postsynaptic proteins via Shank3. Many regions of the brain are highly enriched with free zinc inside glutamatergic vesicles at presynaptic terminals. At these synapses, zinc transporter 3 (ZnT3) moves zinc into vesicles where it is co-released with glutamate. Alterations in ZnT3 are implicated in multiple neurodevelopmental disorders, and ZnT3 knock-out (KO) mice-which lack synaptic zinc-show behavioral deficits associated with autism spectrum disorder and schizophrenia. Here we show that male and female ZnT3 KO mice have smaller dendritic spines and miniature excitatory postsynaptic current amplitudes than wildtype (WT) mice in the auditory cortex. Additionally, spine size deficits in ZnT3 KO mice are restricted to synapses that express Shank3. In WT mice, synapses that express both Shank3 and ZnT3 have larger spines compared to synapses that express Shank3 but not ZnT3. Together these findings suggest a mechanism whereby presynaptic ZnT3-dependent zinc supports postsynaptic structure and function via Shank3 in a synapse-specific manner.

Preparation and Compositional Analysis of Lignocellulosic Plant Biomass as a Precursor for Food Production During Food Crises.

In the event of a sunlight-blocking, temperature-lowering global catastrophe, such as a global nuclear war, super-volcano eruption or large asteroid strike, normal agricultural practices would be severely disrupted with a devastating impact on the global food supply. Despite the improbability of such an occurrence, it is prudent to consider how to sustain the surviving population following a global catastrophe until normal weather and climate patterns resume. Additionally, the ongoing challenges posed by climate change, droughts, flooding, soil salinization, and famine highlight the importance of developing food systems with resilient inputs such as lignocellulosic biomass. With its high proportion of cellulose, the abundant lignocellulosic biomass found across the Earth's land surfaces could be a source of energy and nutrition, but it would first need to be converted into foods. To understand the potential of lignocellulosic biomass to provide energy and nutrition to humans in post-catastrophic and other food crisis scenarios, compositional analyses should be completed to gauge the amount of energy (soluble sugars) and other macronutrients (protein and lipids) that might be available and the level of difficulty in extracting them. Suitable preparation of the lignocellulosic biomass is critical to achieve consistent and comparable results from these analyses. Here we describe a compilation of protocols to prepare lignocellulosic biomass and analyze its composition to understand its potential as a precursor to produce post-catastrophic foods which are those that could be foraged, grown, or produced under the new climate conditions to supplement reduced availability of traditional foods. These foods have sometimes been referred to in the literature as emergency, alternate, or resilient foods. © 2024 The Authors. Current Protocols published by Wiley Periodicals LLC. Basic Protocol 1: Convection oven drying (1 to 2 days) Alternate Protocol 1: Air-drying (2 to 3 days) Alternate Protocol 2: Lyophilization (1 to 4 days) Support Protocol 1: Milling plant biomass Support Protocol 2: Measuring moisture content Basic Protocol 2: Cellulose determination Basic Protocol 3: Lignin determination Basic Protocol 4: Crude protein content by total nitrogen Basic Protocol 5: Crude fat determination via soxtec extraction system Basic Protocol 6: Sugars by HPLC Basic Protocol 7: Ash content.

Trends in Arthritis Prevalence and Associated Chronic Health Indicators Among Adults: Insights From the Behavioral Risk Factor Surveillance System (BRFSS) Database.

Background Arthritis is a prevalent, chronic condition with significant implications for morbidity and healthcare utilization. Understanding trends in arthritis prevalence and associated chronic health indicators is vital for informing public health interventions and healthcare policies. Objective This retrospective study aimed to analyze trends in arthritis prevalence and associated chronic health indicators among adults using data from the Behavioral Risk Factor Surveillance System (BRFSS) database. Methods This retrospective study utilized data from the BRFSS database covering 2019 to 2022. Participants included United States adults aged 18 years and older who completed BRFSS surveys during the specified period. Primary variables included arthritis prevalence and its correlation with chronic health indicators and demographics. Data collection involved standardized telephone questionnaires administered annually, with rigorous attention to data quality and consistency. Prevalence estimates were calculated using weighted proportions, and statistical analysis utilized analysis of variance (ANOVA). Results The study revealed relatively stable arthritis prevalence over the study period, with notable demographic variations. Arthritis prevalence remained stable (2019: 43.3%, 2021: 42.5%). Females consistently had higher rates than males (2019: 45%, 2021: 44.9%). Activity limitation, joint pain, and work limitation were more prevalent in arthritis patients. White, non-Hispanic individuals had higher rates than other groups. Physical inactivity increased from 2019 (29.4%) to 2022 (72.4%), particularly in males. Counseling for physical activity was lower in males. Targeted interventions are needed to address these disparities and improve arthritis management. Conclusion This study provides insights into trends in arthritis prevalence and associated chronic health indicators among United States adults. The findings underscore the importance of considering demographic factors in arthritis prevention and management strategies. Targeted interventions promoting physical activity counseling, particularly among high-risk populations, are warranted to address the rising trend of physical inactivity among individuals with arthritis.

Amplification of positivity for depression and anxiety: Neural prediction of treatment response.

Psychosocial treatments targeting the positive valence system (PVS) in depression and anxiety demonstrate efficacy in enhancing positive affect (PA), but response to treatment varies. We examined whether individual differences in neural activation to positive and negative valence incentive cues underlies differences in benefitting from a PVS-targeted treatment. Individuals with clinically elevated depression and/or anxiety (N = 88, ages 18 to 55) participated in one of two randomized, waitlist-controlled trials of Amplification of Positivity (AMP; NCT02330627, NCT03196544), a cognitive and behavioral intervention targeting the PVS. Participants completed a monetary incentive delay (MID) task during fMRI acquisition at baseline measuring neural activation to the possibility of gaining or losing money. Change in PA from before to after treatment was assessed using the Positive and Negative Affect Schedule. No significant associations were observed between baseline neural activation during gain anticipation and AMP-related changes in PA in regions of interest (striatum and insula) or whole-brain analyses. However, higher baseline striatal and insula activation during loss anticipation was associated with greater increases in PA post-AMP. This study provides preliminary evidence suggesting neural reactivity to negative valence cues may inform who stands to benefit most from treatments targeting the PVS.

User-Centered Framework for Implementation of Technology (UFIT): Development of an Integrated Framework for Designing Clinical Decision Support Tools Packaged With Tailored Implementation Strategies.

BACKGROUND: Electronic health record-based clinical decision support (CDS) tools can facilitate the adoption of evidence into practice. Yet, the impact of CDS beyond single-site implementation is often limited by dissemination and implementation barriers related to site- and user-specific variation in workflows and behaviors. The translation of evidence-based CDS from initial development to implementation in heterogeneous environments requires a framework that assures careful balancing of fidelity to core functional elements with adaptations to ensure compatibility with new contexts. OBJECTIVE: This study aims to develop and apply a framework to guide tailoring and implementing CDS across diverse clinical settings. METHODS: In preparation for a multisite trial implementing CDS for pediatric overweight or obesity in primary care, we developed the User-Centered Framework for Implementation of Technology (UFIT), a framework that integrates principles from user-centered design (UCD), human factors/ergonomics theories, and implementation science to guide both CDS adaptation and tailoring of related implementation strategies. Our transdisciplinary study team conducted semistructured interviews with pediatric primary care clinicians and a diverse group of stakeholders from 3 health systems in the northeastern, midwestern, and southeastern United States to inform and apply the framework for our formative evaluation. RESULTS: We conducted 41 qualitative interviews with primary care clinicians (n=21) and other stakeholders (n=20). Our workflow analysis found 3 primary ways in which clinicians interact with the electronic health record during primary care well-child visits identifying opportunities for decision support. Additionally, we identified differences in practice patterns across contexts necessitating a multiprong design approach to support a variety of workflows, user needs, preferences, and implementation strategies. CONCLUSIONS: UFIT integrates theories and guidance from UCD, human factors/ergonomics, and implementation science to promote fit with local contexts for optimal outcomes. The components of UFIT were used to guide the development of Improving Pediatric Obesity Practice Using Prompts, an integrated package comprising CDS for obesity or overweight treatment with tailored implementation strategies. TRIAL REGISTRATION: ClinicalTrials.gov NCT05627011; https://clinicaltrials.gov/study/NCT05627011.

Glycosylated Polyhydroxyproline Is a Potent Antifreeze Molecule.

Molecules that inhibit the growth of ice crystals are highly desirable for applications in building materials, foods, and agriculture. Antifreezes are particularly essential in biomedicine for tissue banking, yet molecules currently in use have known toxic effects. Antifreeze glycoproteins have evolved naturally in polar fish species living in subzero climates, but practical issues with collection and purification have limited their commercial use. Here, we present a synthetic strategy using polymerization of amino acid N-carboxyanhydrides to produce polypeptide mimics of these potent natural antifreeze proteins. We investigated a set of mimics with varied structural properties and identified a glycopolypeptide with potent ice recrystallization inhibition properties. We optimized for molecular weight, characterized their conformations, and verified their cytocompatibility in a human cell line. Overall, we present a material that will have broad applications as a biocompatible antifreeze.

Architecture and functions of stomatal cell walls in eudicots and grasses.

BACKGROUND: Like all plant cells, the guard cells of stomatal complexes are encased in cell walls that are composed of diverse, interacting networks of polysaccharide polymers. The properties of these cell walls underpin the dynamic deformations that occur in guard cells as they expand and contract to drive the opening and closing of the stomatal pore, the regulation of which is crucial for photosynthesis and water transport in plants. SCOPE: Our understanding of how cell wall mechanics are influenced by the nanoscale assembly of cell wall polymers in guard cell walls, how this architecture changes over stomatal development, maturation and ageing and how the cell walls of stomatal guard cells might be tuned to optimize stomatal responses to dynamic environmental stimuli is still in its infancy. CONCLUSION: In this review, we discuss advances in our ability to probe experimentally and to model the structure and dynamics of guard cell walls quantitatively across a range of plant species, highlighting new ideas and exciting opportunities for further research into these actively moving plant cells.

Application of an egocentric social network approach to examine changes in social connections following treatment for anxiety and depression: A novel measurement tool for clinical trials research?

The epidemic of loneliness and social isolation has been recognized as a public health crisis warranting the same prioritization as other public health issues today, such as obesity, substance use disorders, and tobacco use. Social disconnection is particularly prevalent and disabling among individuals with anxiety and depression, yet it is inadequately evaluated and addressed in most clinical psychology treatment research. Studies generally employ global measures of perceived connectedness, loneliness, or relationship satisfaction, limiting understanding about elements of one's social network that may change with treatment. This study examined changes in the degree (number of people nominated) and quality of one's social network from pre-to post-treatment using an egocentric social network approach in 59 adults (mean age = 30.8 years, range = 18 to 54) with clinically elevated anxiety or depression who were randomized to a cognitive and behavioral positive valence treatment versus waitlist. Participants (egos) named people in their lives (alters) with whom they discussed important issues or spent free time. For each alter, participants rated how close they felt, how close they thought the alter felt to them, and how frequently they communicated. Linear regressions, which included treatment group as a predictor, revealed no group differences in changes in network degree, perceived alter feelings of closeness, or communication frequency, despite prior findings from this sample indicating larger increases in perceived global connectedness in the treatment group. Unexpectedly, the control group reported a greater increase in perceived closeness to alters. Post-hoc analyses revealed this was explained by the treatment group identifying more distal social ties (e.g., extended family, colleagues, roommates) as alters following treatment - an outcome positively associated with global improvements in connectedness. This proof-of-concept study suggests egocentric social network surveys may provide unique information on treatment-related changes in social functioning. Suggestions are provided for adaptations to facilitate application of social network surveys to mental health treatment research.

High Blood Pressure in Children Aged 3 to 12 Years Old With Overweight or Obesity.

Objective: (1) To describe the prevalence of high blood pressure (BP) and the association with BMI in young children with overweight/obesity; (2) to evaluate the accuracy of a single high BP to diagnose sustained hypertension over three visits. Methods: We used pre-intervention data from the Improving Pediatric Obesity Practice Using Prompts (iPOP-UP) trial. We included children aged 3-12 years with BMI ≥85th percentile at well-visits in 2019-2021 at 84 primary care practices in 3 US health systems in the Northeast, Midwest, and South. BP percentiles were calculated from the first visit with BP recorded during the study period. Hypertensive-range BP was defined by the 2017 American Academy of Pediatrics guideline. We tested the association between BMI classification and hypertensive BP using multivariable logistic regression. Results: Of 78,280 children with BMI ≥85th percentile, 76,214 (97%) had BP recorded during the study period (mean 7.4 years, 48% female, 53% with overweight, and 13% with severe obesity). The prevalence of elevated or hypertensive BP was 31%, including 27% in children with overweight and 33%, 39%, and 49% with class I, II, and III obesity, respectively. Higher obesity severity was associated with higher odds of hypertensive BP in the multivariable model. Stage 2 hypertensive BP at the initial visit had specificity of 99.1% (95% confidence interval 98.9-99.3) for detecting sustained hypertension over ≥3 visits. Conclusions: High BP is common in 3- to 12-year-olds with overweight/obesity, with higher obesity severity associated with greater hypertension. Children with overweight/obesity and stage 2 BP are likely to have sustained hypertension and should be prioritized for evaluation. Trial Registration: ClinicalTrials.gov Identifier: NCT05627011.

Validation of the Approach-Avoidance Temperament Questionnaire in Individuals with Anxiety and Depression.

The Approach-Avoidance Temperament Questionnaire (ATQ) is a well-established measure assessing heightened sensitivity and reactivity to reward/positive stimuli (approach temperament) and to punishment/negative stimuli (avoidance temperament). These basic dimensions of personality are believed to be important for understanding the etiology and maintenance of anxiety and depressive disorders. Despite the ATQ's potential utility in clinical psychology research, its psychometric properties and factor structure have yet to be examined in a psychiatric sample. The aims of the present study were to 1) conduct confirmatory factor analysis to replicate the ATQ's factor structure in individuals diagnosed with an anxiety or depressive disorder (N = 244), 2) assess internal consistency and convergent and divergent validity, and 3) explore differences in approach and avoidance temperaments in individuals with versus without a diagnosis of anxiety or depression. Results confirmed the original two-factor structure of the ATQ in a clinical sample, with approach and avoidance temperaments representing orthogonal dimensions. The measure demonstrated strong internal consistency, convergent and divergent validity, and predictive validity. Individuals with anxiety and depression scored higher on avoidance items and lower on approach items compared to those without clinical diagnoses. This study supports the use of the ATQ in clinical populations.

A Mixed-Methods Evaluation of a Project ECHO Program for the Evidence-Based Management of Sickle Cell Disease.

Sickle cell disease (SCD) is a group of chronic, genetic disorders of the red blood cells with significant gaps in access to evidence-based clinical care. Sickle Treatment and Outcomes Research in the Midwest (STORM), a provider network, utilized Project ECHO (Extension for Community Health Outcomes), a telementoring model, to deliver evidence-based education about SCD management. The purpose of this mixed-methods study is to evaluate the utility of Project ECHO as an educational strategy for healthcare providers treating children and adults with SCD. Annual evaluations were administered to STORM TeleECHO participants from 2016 to 2021. Survey data showed a statistically significant change in self-reported provider confidence in the ability to provide care for adult patients with SCD; identify suitable candidates for disease-modifying therapies; and confidence to prescribe disease-modifying therapies. Participants who attended at least 10 sessions were invited to participate in a semi-structured interview. Qualitative data were analyzed using thematic analysis and several themes emerged about the benefits, including (1) increased confidence, (2) integrated best-practice care, (3) connection to provider network and access to experts, (4) high-quality educational presentations and (5) opportunities for collaboration and a sense of community. This suggests that Project ECHO is accessible and leads to increased confidence in providers caring for individuals with SCD. Overall, participant knowledge gains successfully demonstrated the utility of Project ECHO as an educational resource for providers.

Geographic Progression of Infant Respiratory Syncytial Virus Associated Bronchiolitis Across the United States Before and Since the Onset of COVID-19: Results From Four Health Systems, 2015-2023.

BACKGROUND: Respiratory syncytial virus (RSV) is a substantial cause of infant morbidity and mortality due to seasonal peaks of bronchiolitis across the United States. Clinical and viral surveillance plays a pivotal role in helping hospital systems prepare for expected surges in RSV bronchiolitis. Existing surveillance efforts have shown a geographic pattern of RSV positivity across the United States, with cases typically starting in the southeast and spreading north and west. Public health measures implemented due to the COVID-19 pandemic disrupted viral transmission across the nation and altered the expected seasonality of RSV. The impact of these changes on the geographic progression of infant RSV bronchiolitis across the United States has not been described. METHODS: Here, we used clinical and viral surveillance data from four health care systems located in different regions of the United States to describe the geographic progression of infant RSV bronchiolitis across the country from 2015 to 2023. RESULTS: Prior to widespread circulation of SARS-CoV-2, infant RSV bronchiolitis followed an established geographic pattern associated with seasonal epidemics originating in Florida and spreading north (North Carolina and New York) and later westward (Nevada). Although public health and social measures implemented during the COVID-19 pandemic disrupted the seasonality of RSV disease, infant RSV bronchiolitis epidemics progressed across the nation in a pattern identical to the prepandemic era. CONCLUSIONS: Our findings highlight the importance of ongoing clinical and viral surveillance to optimally track the onset of RSV epidemics and allow health care systems to prepare for expected RSV bronchiolitis surges.

Young guard cells function dynamically despite low mechanical anisotropy but gain efficiency during stomatal maturation in Arabidopsis thaliana.

Stomata are pores at the leaf surface that enable gas exchange and transpiration. The signaling pathways that regulate the differentiation of stomatal guard cells and the mechanisms of stomatal pore formation have been characterized in Arabidopsis thaliana. However, the process by which stomatal complexes develop after pore formation into fully mature complexes is poorly understood. We tracked the morphogenesis of young stomatal complexes over time to establish characteristic geometric milestones along the path of stomatal maturation. Using 3D-nanoindentation coupled with finite element modeling of young and mature stomata, we found that despite having thicker cell walls than young guard cells, mature guard cells are more energy efficient with respect to stomatal opening, potentially attributable to the increased mechanical anisotropy of their cell walls and smaller changes in turgor pressure between the closed and open states. Comparing geometric changes in young and mature guard cells of wild-type and cellulose-deficient plants revealed that although cellulose is required for normal stomatal maturation, mechanical anisotropy appears to be achieved by the collective influence of cellulose and additional wall components. Together, these data elucidate the dynamic geometric and biomechanical mechanisms underlying the development process of stomatal maturation.

Tissue oxygen saturation is positively correlated with oxygen delivery and cardiac output in a canine hemorrhagic shock and resuscitation model.

OBJECTIVE: To determine if tissue oxygen saturation (StO2) correlates with oxygen delivery (DO2) and/or cardiac output (CO) in a canine hemorrhagic shock model. ANIMALS: 8 healthy purpose-bred dogs. METHODS: Dogs were anesthetized, and hemorrhagic shock was induced by withdrawing up to 60% of total blood volume, targeting a mean arterial pressure (MAP) of 40 mm Hg. The withdrawn blood was returned to the patient in 2 equal aliquots. Data was collected at 4 time points: 10 minutes after MAP was stabilized under anesthesia (time point [TP]-1), 10 minutes after up to 60% of blood volume was removed to target a MAP of 40 mm Hg (TP2), 10 minutes after the return of 50% of shed blood (TP3), and 10 minutes after the return of the remaining 50% of shed blood (TP4). Total blood volume withdrawn, StO2, CO, heart rate, and MAP were recorded, and DO2 was calculated at each TP. RESULTS: Mean StO2 significantly decreased between TP1 (77.8% [± 9.54]) and TP2 (44.8% [± 19.5]; P < .001 vs TP1). Mean StO2 increased to 63.1% (± 9.85) at TP3, but remained significantly lower compared to TP1 (P = .002). There was no difference between mean StO2 at TP4 (82.5% [± 12.6]) versus TP1 (P = .466). StO2 has a strong, positive correlation to both CO (r = 0.80; P < .001) and DO2 (r = 0.75; P < .001). CLINICAL RELEVANCE: A decrease in StO2 may be used in conjunction with physical examination findings and diagnostic parameters to support a diagnosis of shock. The return of shed blood was correlated with increases in StO2, DO2, and CO, suggesting that StO2 may be used as a marker of adequate resuscitation.