Glycerol Metabolism Contributes to Competition by Oral Streptococci through Production of Hydrogen Peroxide.

As a biological byproduct from both humans and microbes, glycerol's contribution to microbial homeostasis in the oral cavity remains understudied. Here we examined glycerol metabolism by Streptococcus sanguinis, a commensal associated with oral health. Genetic mutants of glucose-PTS enzyme II ( manL ), glycerol metabolism ( glp and dha pathways), and transcriptional regulators were characterized with regard to glycerol catabolism, growth, production of hydrogen peroxide (H 2 O 2 ), transcription, and competition with Streptococcus mutans . Biochemical assays identified the glp pathway as a novel source of H 2 O 2 production by S. sanguinis that is independent of pyruvate oxidase (SpxB). Genetic analysis indicated that the glp pathway requires glycerol and a transcriptional regulator, GlpR, for expression and is negatively regulated by PTS, but not the catabolite control protein, CcpA. Conversely, deletion of either manL or ccpA increased expression of spxB and a second, H 2 O 2 -non-producing glycerol metabolic pathway ( dha ), indicative of a mode of regulation consistent with conventional carbon catabolite repression (CCR). In a plate-based antagonism assay and competition assays performed with planktonic and biofilm-grown cells, glycerol greatly benefited the competitive fitness of S. sanguinis against S. mutans. The glp pathway appears to be conserved in several commensal streptococci and actively expressed in caries-free plaque samples. Our study suggests that glycerol metabolism plays a more significant role in the ecology of the oral cavity than previously understood. Commensal streptococci, though not able to use glycerol as a sole carbohydrate for growth, benefit from catabolism of glycerol through production of both ATP and H 2 O 2 . Importance: Glycerol is an abundant carbohydrate found in oral cavity, both due to biological activities of humans and microbes, and as a common ingredient of foods and health care products. However, very little is understood regarding the metabolism of glycerol by some of the most abundant oral bacteria, commensal streptococci. This was in part because most streptococci cannot grow on glycerol as the sole carbon source. Here we show that Streptococcus sanguinis , an oral commensal associated with dental health, can degrade glycerol for persistence and competition through two independent pathways, one of which generates hydrogen peroxide at levels capable of inhibiting a dental pathobiont, Streptococcus mutans . Preliminary studies suggest that several other commensal streptococci are also able to catabolize glycerol, and glycerol-related genes are being actively expressed in human dental plaque samples. Our findings reveal the potential of glycerol to significantly impact microbial homeostasis which warrants further exploration.

Deep Learning Models for Abdominal CT Organ Segmentation in Children: Development and Validation in Internal and Heterogeneous Public Datasets.

BACKGROUND. Deep learning abdominal organ segmentation algorithms have shown excellent results in adults; validation in children is sparse. OBJECTIVE. The purpose of this article is to develop and validate deep learning models for liver, spleen, and pancreas segmentation on pediatric CT examinations. METHODS. This retrospective study developed and validated deep learning models for liver, spleen, and pancreas segmentation using 1731 CT examinations (1504 training, 221 testing), derived from three internal institutional pediatric (age ≤ 18 years) datasets (n = 483) and three public datasets comprising pediatric and adult examinations with various pathologies (n = 1248). Three deep learning model architectures (SegResNet, DynUNet, and SwinUNETR) from the Medical Open Network for Artificial Intelligence (MONAI) framework underwent training using native training (NT), relying solely on institutional datasets, and transfer learning (TL), incorporating pretraining on public datasets. For comparison, TotalSegmentator, a publicly available segmentation model, was applied to test data without further training. Segmentation performance was evaluated using mean Dice similarity coefficient (DSC), with manual segmentations as reference. RESULTS. For internal pediatric data, the DSC for TotalSegmentator, NT models, and TL models for normal liver was 0.953, 0.964-0.965, and 0.965-0.966, respectively; for normal spleen, 0.914, 0.942-0.945, and 0.937-0.945; for normal pancreas, 0.733, 0.774-0.785, and 0.775-0.786; and for pancreas with pancreatitis, 0.703, 0.590-0.640, and 0.667-0.711. For public pediatric data, the DSC for TotalSegmentator, NT models, and TL models for liver was 0.952, 0.871-0.908, and 0.941-0.946, respectively; for spleen, 0.905, 0.771-0.827, and 0.897-0.926; and for pancreas, 0.700, 0.577-0.648, and 0.693-0.736. For public primarily adult data, the DSC for TotalSegmentator, NT models, and TL models for liver was 0.991, 0.633-0.750, and 0.926-0.952, respectively; for spleen, 0.983, 0.569-0.604, and 0.923-0.947; and for pancreas, 0.909, 0.148-0.241, and 0.699-0.775. The DynUNet TL model was selected as the best-performing NT or TL model considering DSC values across organs and test datasets and was made available as an open-source MONAI bundle (https://github.com/cchmc-dll/pediatric_abdominal_segmentation_bundle.git). CONCLUSION. TL models trained on heterogeneous public datasets and fine-tuned using institutional pediatric data outperformed internal NT models and Total-Segmentator across internal and external pediatric test data. Segmentation performance was better in liver and spleen than in pancreas. CLINICAL IMPACT. The selected model may be used for various volumetry applications in pediatric imaging.

Time Delay in Motor Vehicle Accident Arrival: A Critical Analysis of Trauma Team Activation.

Introduction This research aims to investigate the role of time since trauma (TST) in refining trauma team activation (TTA) criteria within a level I trauma center. We analyze the association between TST and post-emergency department (ED) disposition, proposing new insights for the enhancement of TTA criteria. Methods A retrospective analysis was conducted on a dataset comprising 3,693 patients presenting to a level I trauma center following motor vehicle accidents (MVAs) from 2016 to 2021. Data from a trauma registry, encompassing time of injury, time of ED arrival, TTA status, and post-ED disposition, were utilized. TST was calculated as the difference between the time of injury and the time of ED arrival. Patients that received TTA, full or partial, were categorized based on TST (less than one hour, one to two hours, and two or more hours). Statistical analyses, including chi-square tests, were performed using the Statistical Analysis System (SAS) (version 3.8, SAS Institute Inc., Cary, NC). Results Of the 1,261 patients meeting the criteria, 98.3% received TTA, with decreasing TTA rates observed with increasing TST (p = 0.0076). A significant association was found between TST and post-ED disposition for patients who received TTA (p = 0.0007). Compared to the other TST groups, a higher proportion of patients with a TST of two or more hours were admitted, sent to the intensive care unit (ICU), and sent to the operating room (OR).  Conclusion The study indicates a statistically significant relationship between TST and TTA rates, challenging our assumptions about the decreased need for TTA over time. While a longer TST was associated with a lower percentage of TTA, patients with a TST of two or more hours demonstrated increased rates of admission, ICU utilization, and surgical interventions. This suggests that TTA criteria may benefit from refinement to include patients with longer TST. Acknowledging study limitations, such as a small sample size and retrospective design, this research contributes valuable insights into potential considerations for optimizing trauma care protocols.

Assessment of Dosing Strategies for Pediatric Drug Products.

Pediatric drug dosing is challenged by the heterogeneity of developing physiology and ethical considerations surrounding a vulnerable population. Often, pediatric drug dosing leverages findings from the adult population; however, recent regulatory efforts have motivated drug sponsors to pursue pediatric-specific programs to meet an unmet medical need and improve pediatric drug labeling. This paradigm is further complicated by the pathophysiological implications of obesity on drug distribution and metabolism and the roles that body composition and body size play in drug dosing. Therefore, we sought to understand the landscape of pediatric drug dosing by characterizing the dosing strategies from drug products recently approved for pediatric indications identified using FDA Drug Databases and analyze the impact of body size descriptors (age, body surface area, weight) on drug pharmacokinetics for several selected antipsychotics approved in pediatric patients. Our review of these pediatric databases revealed a dependence on body size-guided dosing, with 68% of dosing in pediatric drug labelings being dependent on knowing either the age, body surface area, or weight of the patient to guide dosing for pediatric patients. This dependence on body size-guided dosing drives the need for special consideration when dosing a drug in overweight and obese patients. Exploratory pharmacokinetic analyses in antipsychotics illustrate possible effects of drug exposure when applying different dosing strategies for this class of drugs. Future efforts should aim to further understand the pediatric drug dosing and obesity paradigm across pediatric age ranges and drug classes to optimize drug development and clinical care for this patient population.

Injury Patterns in Vehicle Crashes: The Significance of Occupant Seating Position.

OBJECTIVES:  Investigating patterns among the outcomes of patients involved in motor vehicle accidents (MVAs) can provide information necessary to guide targeted interventions to improve road traffic safety. Our purpose is to identify any differences between passenger and driver injury severity and overall clinical course after MVAs. METHODS:  We performed a retrospective review and analysis of 3,693 patients involved in MVAs from 2016 to 2021. We divided the data into two groups, drivers and passengers, and compared the Injury Severity Score (ISS), Revised Trauma Score (RTS) on admission, days in the Intensive Care Unit (ICU), length of hospital stay (LOS), post Emergency Department (ED) disposition, discharge (DC) disposition, and signs of life on arrival (SOLA) to the ED. We compared mean ISS, New Injury Severity Score (NISS), RTS, length in ICU and LOS using a student's T-test and SOLA, post-ED and DC disposition using Chi-square analysis. RESULTS:  We did not find any statistically significant difference in ISS, RTS, days in ICU, LOS, or SOLA between the drivers and passengers. However, we did find a statistically significant difference in the post-ED (X2= 113.743, p=<0.0001) and DC disposition (X2=41.172, p=<0.0001) of drivers and passengers. After the ED and DC, more passengers were transferred to a higher level of care than expected, while the inverse was true for drivers. The number of drivers discharged to Skilled Nursing Facilities (SNFs) was also higher than expected, further contributing to the observed difference in DC disposition.  Conclusion: Our study found no statistically significant difference between driver and passenger injury severity, length of hospital stay, days in ICU, and SOLA after an MVA. The clinical courses of the two groups were found to be significantly different based on post-ED and DC disposition data. We identified limitations, such as a relatively small sample size and insufficient data on specific car seat locations for passengers, underscoring the need for a more nuanced exploration. Future research must broaden its scope to encompass diverse crash scenarios, vehicle design and safety technologies, seat belt dynamics, and age- and gender-specific vulnerabilities.

COVID-19 Vaccine Related Cervical Radiculitis and Parsonage-Turner Syndrome: Case Report and Review of the Literature.

Parsonage-Turner Syndrome, or neuralgic amyotrophy, is an acute-onset upper limb and shoulder girdle palsy that can occur in a post-viral, post-surgical or idiopathic setting. There have also been some reported cases of the syndrome occurring following vaccinations. The pathophysiology of neuralgic amyotrophy is not completely understood and many of the commonly used diagnostic imaging modalities we use to try and diagnose this syndrome are inaccurate and misleading. We present the case of a 40-year-old gentleman who presented with acute onset burning pain and fasciculations in his right upper extremity following vaccination with the second dose of the Pfizer-BioNTech COVID-19 vaccine. His symptoms progressed to weakness in isolated muscle groups with electromyographic evidence of decreased nerve conduction. MRI of the cervical spine demonstrated multilevel central and foraminal stenosis, suggesting a diagnosis of cervical radiculopathy. The patient underwent a C4-5/C5-6 and C6-7 laminoforaminotomy and tolerated the procedure well. Post-operatively, the patient has experienced gradual symptom improvement with residual right triceps and pectoralis muscle weakness as well as paresthesias of the right elbow and forearm. Parsonage-Turner Syndrome is a brachial plexus palsy that can affect one or multiple branches of the brachial plexus. It causes acute-onset pain and weakness, and the diagnosis can be difficult to make with the commonly used diagnostic imaging methods. We reviewed other case reports about neuralgic amyotrophy following vaccinations as well as the current literature on more accurate diagnostic imaging modalities that may help our diagnosis and understanding of the pathophysiology of this condition.

CYP2D6 Phenotype Influences Pharmacokinetic Parameters of Venlafaxine: Results from a Population Pharmacokinetic Model in Older Adults with Depression.

In this study, we aimed to improve upon a published population pharmacokinetic (PK) model for venlafaxine (VEN) in the treatment of depression in older adults, then investigate whether CYP2D6 metabolizer status affected model-estimated PK parameters of VEN and its active metabolite O-desmethylvenlafaxine. The model included 325 participants from a clinical trial in which older adults with depression were treated with open-label VEN (maximum 300 mg/day) for 12 weeks and plasma levels of VEN and O-desmethylvenlafaxine were assessed at weeks 4 and 12. We fitted a nonlinear mixed-effect PK model using NONMEM to estimate PK parameters for VEN and O-desmethylvenlafaxine adjusted for CYP2D6 metabolizer status and age. At both lower doses (up to 150 mg/day) and higher doses (up to 300 mg/day), CYP2D6 metabolizers impacted PK model-estimated VEN clearance, VEN exposure, and active moiety (VEN + O-desmethylvenlafaxine) exposure. Specifically, compared with CYP2D6 normal metabolizers, (i) CYP2D6 ultra-rapid metabolizers had higher VEN clearance; (ii) CYP2D6 intermediate metabolizers had lower VEN clearance; (iii) CYP2D6 poor metabolizers had lower VEN clearance, higher VEN exposure, and higher active moiety exposure. Overall, our study showed that including a pharmacogenetic factor in a population PK model could increase model fit, and this improved model demonstrated how CYP2D6 metabolizer status affected VEN-related PK parameters, highlighting the importance of genetic factors in personalized medicine.

Wavefront-modified vector beams for THz cornea spectroscopy.

Terahertz spectroscopy is a promising method to diagnose ocular diseases, where the cornea is typically imaged by Gaussian beams. However, the beam's mismatch with the cornea's spherical surface produces a 5-10 % error in analysis. We investigate cornea spectroscopy with wavefront-modified vector beams, reducing the original analysis error to less than 0.5 %. Vector beams are synthesized by our developed 3D Angular Spectrum Method expanded to vector spherical harmonic presentation, allowing wavefront modification and scattering analysis from 100-layer cornea models. We show that wavefront-modified spherical vector beams possess increased accuracy and non-sensitive focusing on cornea spectroscopy compared to the Gaussian beams. Additionally, we investigate wavefront-modified cylindrical vector beams, which show frequency-dependent scattering power arising from s- and p-polarizations. As a result, these beams are unsuitable for cornea spectroscopy, although they have potential for optical force applications. Wavefront-modified vector beams can be applied to spherical target spectroscopy and optical force applications, such as medicine, medical imaging, and optical tweezers.

Mie scattering with 3D angular spectrum method.

Mie theory is a powerful method to model electromagnetic scattering from a multilayered sphere. Usually, the incident beam is expanded to its vector spherical harmonic representation defined by beam shape coefficients, and the multilayer sphere scattering is obtained by the T-matrix method. However, obtaining the beam shape coefficients for arbitrarily shaped incident beams has limitations on source locations and requires different methods when the incident beam is defined inside or outside the computational domain or at the scatterer surface. We propose a 3D angular spectrum method for defining beam shape coefficients from arbitrary source field distributions. This method enables the placement of the sources freely within the computational domain without singularities, allowing flexibility in beam design. We demonstrate incident field synthesis and spherical scattering by comparing morphology-dependent resonances to known values, achieving excellent matching and high accuracy. The proposed method has significant benefits for optical systems and inverse beam design. It allows for the analysis of electromagnetic forward/backward propagation between optical elements and spherical targets using a single method. It is also valuable for optical force beam design and analysis.

S100a9 Protects Against the Effects of Repeated Social Defeat Stress.

Background: Posttraumatic stress disorder, a consequence of psychological trauma, is associated with increased inflammation and an elevated risk of developing comorbid inflammatory diseases. However, the mechanistic link between this mental health disorder and inflammation remains elusive. We previously found that S100a8 and S100a9 messenger RNA, genes that encode the protein calprotectin, were significantly upregulated in T lymphocytes and positively correlated with inflammatory gene expression and the mitochondrial redox environment in these cells. Therefore, we hypothesized that genetic deletion of calprotectin would attenuate the inflammatory and redox phenotype displayed after psychological trauma. Methods: We used a preclinical mouse model of posttraumatic stress disorder known as repeated social defeat stress (RSDS) combined with pharmacological and genetic manipulation of S100a9 (which functionally eliminates calprotectin). A total of 186 animals (93 control, 93 RSDS) were used in these studies. Results: Unexpectedly, we observed worsening of behavioral pathology, inflammation, and the mitochondrial redox environment in mice after RSDS compared with wild-type animals. Furthermore, loss of calprotectin significantly enhanced the metabolic demand on T lymphocytes, suggesting that this protein may play an undescribed role in mitochondrial regulation. This was further supported by single-cell RNA sequencing analysis demonstrating that RSDS and loss of S100a9 primarily altered genes associated with mitochondrial function and oxidative phosphorylation. Conclusions: These data demonstrate that the loss of calprotectin potentiates the RSDS-induced phenotype, which suggests that its observed upregulation after psychological trauma may provide previously unexplored protective functions.

Tutorial on model selection and validation of model input into precision dosing software for model-informed precision dosing.

There has been rising interest in using model-informed precision dosing to provide personalized medicine to patients at the bedside. This methodology utilizes population pharmacokinetic models, measured drug concentrations from individual patients, pharmacodynamic biomarkers, and Bayesian estimation to estimate pharmacokinetic parameters and predict concentration-time profiles in individual patients. Using these individualized parameter estimates and simulated drug exposure, dosing recommendations can be generated to maximize target attainment to improve beneficial effect and minimize toxicity. However, the accuracy of the output from this evaluation is highly dependent on the population pharmacokinetic model selected. This tutorial provides a comprehensive approach to evaluating, selecting, and validating a model for input and implementation into a model-informed precision dosing program. A step-by-step outline to validate successful implementation into a precision dosing tool is described using the clinical software platforms Edsim++ and MwPharm++ as examples.

Evaluating Trends in Strangles Outbreaks Using Temperature and Precipitation Data in the United States of America for 2018-2022.

Strangles is a highly contagious upper respiratory infection of equids that is globally distributed. The causative agent of strangles, Streptococcus equi subspecies equi, can be spread through indirect contact with infected fomites, and studies have shown this microbe to live well in varying environmental conditions. The purpose of this study was to analyze strangles case numbers across the United States of America from 2018 to 2022 to investigate potential temporal or weather patterns associated with outbreaks. Diagnosed case records were obtained from the Equine Disease Communication Center, university databases, government agencies, or veterinary diagnostic labs, and geographic information systems (GISs) were used to map cases and to acquire relevant meteorological data from outbreak areas. These data were analyzed using logistic regression to explore trends that occur between outbreaks and changes in temperature and precipitation. Initial review of weather data suggested monthly changes in strangles case numbers corresponded with changing seasons. Logistic regression indicated that changes in monthly average temperature and minimum temperature were significantly associated with increased or decreased odds of strangles outbreaks, respectively. Future analyses should focus on weather data isolated within a smaller region or state to better resolve trends in strangles outbreaks throughout the continental USA.

Escitalopram and Sertraline Population Pharmacokinetic Analysis in Pediatric Patients.

BACKGROUND AND OBJECTIVE: Escitalopram and sertraline are commonly prescribed for anxiety and depressive disorders in children and adolescents. The pharmacokinetics (PK) of these medications have been evaluated in adults and demonstrate extensive variability, but studies in pediatric patients are limited. Therefore, we performed a population PK analysis for escitalopram and sertraline in children and adolescents to characterize the effects of demographic, clinical, and pharmacogenetic factors on drug exposure. METHODS: A PK dataset was generated by extracting data from the electronic health record and opportunistic sampling of escitalopram- and sertraline-treated psychiatrically hospitalized pediatric patients aged 5-18 years. A population PK analysis of escitalopram and sertraline was performed using NONMEM. Concentration-time profiles were simulated using MwPharm++ to evaluate how covariates included in the final models influence medication exposure and compared to adult therapeutic reference ranges. RESULTS: The final escitalopram cohort consisted of 315 samples from 288 patients, and the sertraline cohort consisted of 265 samples from 255 patients. A one-compartment model with a proportional residual error model best described the data for both medications. For escitalopram, CYP2C19 phenotype and concomitant CYP2C19 inhibitors affected apparent clearance (CL/F), and normalizing CL/F and apparent volume of distribution (V/F) to body surface area (BSA) improved estimations. The final escitalopram model estimated CL/F and V/F at 14.2 L/h/1.73 m2 and 428 L/1.73 m2, respectively. For sertraline, CYP2C19 phenotype and concomitant CYP2C19 inhibitors influenced CL/F, and empirical allometric scaling of patient body weight on CL/F and V/F was significant. The final sertraline model estimated CL/F and V/F at 124 L/h/70 kg and 4320 L/70 kg, respectively. Normalized trough concentrations (Ctrough) for CYP2C19 poor metabolizers taking escitalopram were 3.98-fold higher compared to normal metabolizers (151.1 ng/mL vs 38.0 ng/mL, p < 0.0001), and normalized Ctrough for CYP2C19 poor metabolizers taking sertraline were 3.23-fold higher compared to normal, rapid, and ultrarapid metabolizers combined (121.7 ng/mL vs 37.68 ng/mL, p < 0.0001). Escitalopram- and sertraline-treated poor metabolizers may benefit from a dose reduction of 50-75% and 25-50%, respectively, to normalize exposure to other phenotypes. CONCLUSION: To our knowledge, this is the largest population PK analysis of escitalopram and sertraline in pediatric patients. Significant PK variability for both medications was observed and was largely explained by CYP2C19 phenotype. Slower CYP2C19 metabolizers taking escitalopram or sertraline may benefit from dose reductions given increased exposure.

Clinical covariates that improve the description of high dose methotrexate pharmacokinetics in a diverse population to inform MTXPK.org.

The MTXPK.org webtool was launched in December 2019 and was developed to facilitate model-informed supportive care and optimal use of glucarpidase following the administration of high-dose methotrexate (HDMTX). One limitation identified during the original development of the MTXPK.org tool was the perceived generalizability because the modeled population comprised solely of Nordic pediatric patients receiving 24-h infusions for the treatment of acute lymphoblastic leukemia. The goal of our study is to describe the pharmacokinetics of HDMTX from a diverse patient population (e.g., races, ethnicity, indications for methotrexate, and variable infusion durations) and identify meaningful factors that account for methotrexate variability and improve the model's performance. To do this, retrospectively analyzed pharmacokinetic and toxicity data from pediatric and adolescent young adult patients who were receiving HDMTX (>0.5 g/m2 ) for the treatment of a cancer diagnosis from three pediatric medical centers. We performed population pharmacokinetic modeling referencing the original MTXPK.org NONMEM model (includes body surface area and serum creatinine as covariates) on 1668 patients, 7506 administrations of HDMTX, and 30,250 concentrations. Our results support the parameterizations of short infusion duration (<8 h) and the presence of Down syndrome on methotrexate clearance, the parameterization of severe hypoalbuminemia (<2.5 g/dL) on the intercompartmental clearance (Q2 and Q3), and the parameterization of pleural effusion on the volume of distribution (V1 and V2). These novel parameterizations will increase the generalizability of the MTXPK.org model once they are added to the webtool.

Dynamic asymmetry in cerebrospinal fluid pressure: An indicator of regional differences in compliance.

Background: Dural compliance influences the shape and magnitude of the cerebrospinal fluid (CSF) pulsations. In humans, cranial compliance is approximately 2× greater than spinal compliance; the differential has been attributed to the associated vasculature. In alligators, the spinal cord is surrounded by a large venous sinus, which suggests that the spinal compartment may have higher compliance than is found in mammals. Methods: Pressure catheters were surgically implanted into the cranial and spinal subdural spaces of eight subadult American alligators (Alligator mississippiensis). The CSF was propelled through the subdural space by orthostatic gradients and rapid changes in linear acceleration. Results: CSF pressure recordings taken from the cranial compartment were consistently, and significantly, larger than those taken from the spinal compartment. After the myodural bridge of Alligator was surgically released, the asymmetry in CSF pressure was decreased. Conclusion: Unlike the situation in humans, the spinal compartment of Alligator has greater compliance than the cranial compartment, presumably due to the presence of the large spinal venous sinus surrounding the dura. The change in CSF pressures after myodural surgical release supports the hypothesis that the myodural bridge functions, at least in part, to modulate dural compliance and the exchange of CSF between the cranial and spinal compartments.

Sharing Perspectives in African American Communities to Reduce Stroke Risk Through Community Listening Circles.

PURPOSE: To build trust and explore community perception on stroke disparities as well as barriers and strengths to stroke prevention. DESIGN: Mixed methods study. METHODS: A convenience sample (n = 54) of African Americans responded to questionnaires and participated in focus groups. FINDINGS: Although a majority of participants had some knowledge of stroke warning signs and risk factors, there were misconceptions identified through the Community Listening Circles (CLCs). Misconceptions about stroke were identified. Six key themes emerged. CONCLUSIONS: Focus groups provided a better understanding of stroke perception. CLINICAL EVIDENCE: Community health nurses may be able to use this information to provide care appropriately.

Description of the mantle lure and novel mimicry of the endangered Cumberlandian Combshell (Epioblasma brevidens) in the Clinch River, eastern United States.

The Cumberlandian Combshell (Epioblasma brevidens) is an endangered freshwater mussel endemic to the Tennessee and Cumberland River drainages, major tributaries of the Ohio River of the eastern United States. We conducted mask and snorkel surveys in May and June of 2021 and 2022 to locate, observe, photograph, and video female E. brevidens to document their unique mantle lures at sites in the Clinch River in Tennessee and Virginia. The mantle lure is morphologically specialized mantle tissue that mimics prey items of the host fish. The mantle lure of E. brevidens appears to mimic four distinct characteristics of the reproductive anatomy of the underside (ventral) of a gravid female crayfish, to include: (1) the external apertures of the oviducts located on the base of the third pair of walking legs, (2) crayfish larvae still encased in the egg membrane, (3) pleopods or claws, and (4) postembryonic eggs. Surprisingly, we observed males of E. brevidens displaying mantle lures that were anatomically complex and closely resembled the female mantle lure. The male lure similarly mimics oviducts, eggs, and pleopods but is diminutive (2-3 mm smaller in length or diameter) to those same structures in females. We describe for the first time the mantle lure morphology and mimicry of E. brevidens, showing its close resemblance to the reproductive anatomy of a gravid female crayfish, and a novel form of mimicry in males. To our knowledge, mantle lure displays in males have not been previously documented in freshwater mussels.

Effects of obesity on the pharmacology of proton pump inhibitors: current understanding and future implications for patient care and research.

INTRODUCTION: In the United States, obesity affects approximately ⅖ adults and ⅕ children, leading to increased risk for comorbidities, like gastroesophageal reflux disease (GERD), treated increasingly with proton pump inhibitors (PPIs). Currently, there are no clinical guidelines to inform PPI dose selection for obesity, with sparse data regarding whether dose augmentation is necessary. AREAS COVERED: We provide a review of available literature regarding the pharmacokinetics (PK), pharmacodynamics (PD), and/or metabolism of PPIs in children and adults with obesity, as a step toward informing PPI dose selection. EXPERT OPINION: Published PK data in adults and children are limited to first-generation PPIs and point toward reduced apparent oral drug clearance in obesity, with equipoise regarding obesity impact on drug absorption. Available PD data are sparse, conflicting, and limited to adults. No studies are available to inform the PPI PK→PD relationship in obesity and if/how it differs compared to individuals without obesity. In the absence of data, best practice may be to dose PPIs based on CYP2C19 genotype and lean body weight, so as to avoid systemic overexposure and potential toxicities, while monitoring closely for efficacy.

Faster induction of photosynthesis increases biomass and grain yield in glasshouse-grown transgenic Sorghum bicolor overexpressing Rieske FeS.

Sorghum is one of the most important crops providing food and feed in many of the world's harsher environments. Sorghum utilizes the C4 pathway of photosynthesis in which a biochemical carbon-concentrating mechanism results in high CO2 assimilation rates. Overexpressing the Rieske FeS subunit of the Cytochrome b6 f complex was previously shown to increase the rate of photosynthetic electron transport and stimulate CO2 assimilation in the model C4 plant Setaria viridis. To test whether productivity of C4 crops could be improved by Rieske overexpression, we created transgenic Sorghum bicolor Tx430 plants with increased Rieske content. The transgenic plants showed no marked changes in abundances of other photosynthetic proteins or chlorophyll content. The steady-state rates of electron transport and CO2 assimilation did not differ between the plants with increased Rieske abundance and control plants, suggesting that Cytochrome b6 f is not the only factor limiting electron transport in sorghum at high light and high CO2 . However, faster responses of non-photochemical quenching as well as an elevated quantum yield of Photosystem II and an increased CO2 assimilation rate were observed from the plants overexpressing Rieske during the photosynthetic induction, a process of activation of photosynthesis upon the dark-light transition. As a consequence, sorghum with increased Rieske content produced more biomass and grain when grown in glasshouse conditions. Our results indicate that increasing Rieske content has potential to boost productivity of sorghum and other C4 crops by improving the efficiency of light utilization and conversion to biomass through the faster induction of photosynthesis.

Special Report: The Moore Pediatric Surgery Center: An Evolving Model for Pediatric Orthopaedic Surgical Care in a Limited Resource Environment.

ABSTRACT: The authors describe their 11-year experience with 1 model for providing short-term (about 1 wk/y in country) pediatric orthopaedic surgical care in a limited resource environment. This paper provides a detailed narrative of 1 team's pediatric orthopaedic work at the Moore Pediatric Surgery Center in Guatemala City, how it has evolved over these 11 years, financial aspects of the model, and examines patient follow-up data for a consecutive 8-year period. The authors have reviewed financial records, case lists, patient charts from 2014 to 2022, and patient photographic records from The Moore Center and as provided via internet by a local contracted Guatemalan pediatric orthopaedic fellowship-trained surgeon to present a complete picture of how the service functions. Specific follow-up data included: last follow-up date, date discharged from follow-up, and major complications including infection, surgical wound dehiscence, return for unplanned surgery, major nerve injury, and recurrent hip dislocation for cases of closed or open reduction of developmental hip dislocation. A total of 297 consecutive pediatric orthopaedic surgical patients were identified from 2014 to 2022. Of these, charts were found for 235 patients (135 female, 110 male), of which 43% were from the urban Guatemala City region. Two hundred sixteen (72%) had at least 1 follow-up clinic visit, and 87 (37%) had at least 1-year follow-up or were discharged. All complications identified by this retrospective chart review included 4 recurrent hip dislocations (3 after closed reduction), 1 femur fracture after implant removal, 1 superficial infection requiring antibiotics, 1 partial dehiscence treated only with dressings, 1 thumb subluxation, and 1 failed graft with internal fixation for congenital pseudoarthrosis of tibia. CONCLUSIONS: The Moore Pediatric Surgery Center is a financially viable, sustainable, safe, and effective model for delivering short-term surgical care for many pediatric orthopaedic conditions in a limited resource environment. LEVEL OF EVIDENCE: None (descriptive).