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Microalgae are multi-purpose microbial agents due to their capability to efficiently sequester carbon dioxide and produce valuable biomass such as protein and single-cell oils. Formulation and tuning of microalgae kinetics models can significantly contribute to the successful design and operation of microalgae reactors. This work aimed to demonstrate the capability of self-organizing map (SOM) algorithm to elucidate the patterns of parameter rankings in microalgae models subject to stochastic variations of input forcing functions–bioprocess influent component concentration levels. These stochastic variations were implemented on a modeled chemostat with a deterministic microalgae kinetic model consists of ten time-dependent variables and eighteen model parameters. The methodology consists of two major stages: (1) global sensitivity analysis (GSA) on the importance of model parameters with stochastic sampling of bioreactor influent component concentrations, and (2) training of self-organizing maps on the datasets of model parameter rankings derived from the GSA indices. Results reveal that functional principal components analysis can project at least 99% of the time-dependent dynamic patterns of the model variables on B-splines basis functions. The component planes for hexagonal lattice SOMs reveal that the sensitivity rankings some parameters in the algae model tested can be stable over a wide range of variations in the levels of influent component concentrations. Therefore, SOM can be used to reveal the trends in multi-dimensional data arrays arising from the implementation of GSA of kinetic models under stochastic perturbation of input forcing functions.

Previous studies support using two abbreviated tests of the Test of Memory Malingering (TOMM), including (a) Trial 1 (T1) and (b) the number of errors on the first 10 items of T1 (T1e10), as performance validity tests (PVTs). In this study, we examined the independent and aggregated predictive utility of TOMM T1 and T1e10 for identifying invalid neuropsychological test performance across two clinical samples. We employed cross-sectional research to examine two independent and demographically diverse mixed samples of military veterans and civilians (VA = 108; academic medical center = 234) of patients who underwent neuropsychological evaluations. We determined validity groups by patient performance on four independent criterion PVTs. We established concordances between passing/failing the TOMM T1e10 and T1, followed by logistic regression to determine individual and aggregated accuracy of T1e10 and T1 for predicting validity group membership. Concordance between passing T1e10 and T1 was high, as was overall validity (87–98%) across samples. By contrast, T1e10 failure was more highly concordant with T1 failure (69–77%) than with overall invalidity status (59–60%) per criterion PVTs, whereas T1 failure was more highly concordant with invalidity status (72–88%) per criterion PVTs. Logistic regression analyses demonstrated similar results, with T1 accounting for more variance than T1e10. However, combining T1e10 and T1 accounted for the most variance of any model, with T1e10 and T1 each emerging as significant predictors. TOMM T1 and, to a lesser extent, T1e10 were significant predictors of independent criterion-derived validity status across two distinct clinical samples, but they did not offer improved classification accuracy when aggregated.

Objective High intelligence (IQ) adults with attention-deficit/hyperactivity disorder (ADHD) often perform better on neuropsychological tests relative to average IQ adults with ADHD, despite commensurate functional impairment. This study compared adults with ADHD and high versus average IQ on the Rey Auditory Verbal Learning Test (RAVLT) to specifically assess this proposed masking effect of IQ on verbal learning/memory performance among those undergoing neuropsychological evaluation. Method RAVLT performance between patients with ADHD and average versus high Test of Premorbid Function-estimated IQ were compared. Latent growth curve modeling (LGCM) evaluated learning acquisition across trials. Results RAVLT total learning, immediate, and delayed free recall performances were significantly better in the high IQ relative to the average IQ group. LGCM showed similar quadradic growth trajectories for both IQ groups. Both groups reported equivalent symptom severity and functional complaints in childhood and adulthood. Conclusions Adults with ADHD and high IQ performed normally on a verbal learning/memory test compared to adults with average IQ, who scored 0.5-1.0 standard deviations below the mean. These results suggest a masking of performance-based memory deficits in the context of higher IQ in adults with ADHD, supporting growing evidence that higher IQ masks neurocognitive deficits during the assessment of adults with ADHD.

SummaryAnnual rings from 30 year old vines in a California rootstock trial were measured to determine the effects of 15 different rootstocks on Chardonnay and Cabernet Sauvignon scions. Viticultural traits measuring vegetative growth, yield, berry quality, and nutrient uptake were collected at the beginning (1995 to 1999) and end (2017 to 2020) of the lifetime of a vineyard initially planted in 1991 and removed in 2021. X-ray Computed Tomography (CT) was used to measure ring widths in 103 vines. Ring width was modeled as a function of ring number using a negative exponential model. Early and late wood ring widths, cambium width, and scion trunk radius were correlated with 27 traits. Modeling of annual ring width shows that scions alter the width of the first rings but that rootstocks alter the decay of later rings, consistently shortening ring width throughout the lifetime of the vine. Ravaz index, juice pH, photosynthetic assimilation and transpiration rates, and instantaneous water use efficiency are correlated with scion trunk radius. Ultimately, our research indicates that rootstocks modulate secondary growth over years, altering physiology and agronomic traits. Rootstocks act in similar but distinct ways from climate to modulate ring width, which borrowing techniques from dendrochronology, can be used to monitor both genetic and environmental effects in woody perennial crop species.

This study investigated a combination of eight embedded performance validity tests (PVTs) derived from commonly administered neuropsychological tests to optimize sensitivity/specificity for detecting invalid neuropsychological test performance. The goal of this study was to evaluate what combination of these common embedded PVTs that have the most robust predictive power for detecting invalid neuropsychological test performance in a single diverse clinical sample.Eight previously validated memory- and nonmemory-based embedded PVTs were examined among 231 patients undergoing neuropsychological evaluation. Patients were classified into valid/invalid groups based on four independent criterion PVTs. Embedded PVT accuracy was assessed using standard and stepwise multiple logistic regression models.Three PVTs, the Brief Visuospatial Memory Test-Revised Recognition Discrimination (BVMT-R-RD), Rey Auditory Verbal Learning Test Forced Choice, and WAIS-IV Digit Span Age Corrected Scaled Score, predicted 45.5% of the variance in validity group membership. BVMT-RD independently accounted for 32% of the variance in prediction of independent, criterion-defined validity group membership.This study demonstrated the incremental predictive power of multiple embedded PVTs derived from common neuropsychological measures in detecting invalid test performance and those measures accounting for the greatest portion of the variance. These results provide guidance for evaluating the most fruitful embedded PVTs and proof of concept to better guide selection of embedded validity indices. Further, this offers clinicians an efficient, empirically derived approach to assessing performance validity when time restraints potentially limit the use of freestanding PVTs.

Emergency medicine (EM) investigators lag in research funding from the National Institutes of Health (NIH) when compared to other specialties. NIH funding determinations are made in part by a process of NIH study section peer review. Low participation by EM investigators in NIH peer review could be one explanation for low levels of NIH funding by EM investigators. The objective of this study was to establish a current-state metric of EM faculty researchers serving on standing NIH study sections from 2019 to 2020. Publicly available lists of NIH study section membership rosters within the Center for Scientific Review and within individual NIH institutions were reviewed for standing members. Committee members listed as being members of a department of emergency medicine were identified as emergency care researchers. Special emphasis panels and ad hoc members were excluded. Members degrees were categorized as PhD, MD (with or without non-PhD degree), MD/PhD, and other. Similar analysis was performed of AHRQ study sections. A total of 6,113 members on NIH study sections were identified. Degrees held by committee members included PhDs 74% (4,547), MDs 14%(883), MD/PhDs 10% (584), and other (99). Twenty (0.3%) NIH study section members were identified as members of an emergency department (ED). A total of 20% (four) held PhDs, 75% (15) held MDs, and 5%(one) held MD/PhD degrees. A total of 25% (five) of EM faculty were pediatric and 75% (15) were adult. Clustering of study sections within similar institutions was noted with 40% (two) of the pediatric faculty at the same institution while 27% (four) of the adult faculty were at the same institution. AHRQ study section review identified 3% (four/127) as members of an ED. Our data show that 20 EM faculty comprised 0.3% of NIH standing study section members and four EM faculty comprised 3% of AHRQ standing study section members from 2019 to 2020 and that these members were clustered at a few institutions.

Cellular metabolism is a critical regulator of macrophage effector function. Tissue-resident alveolar macrophages (TR-AMs) inhabit a unique niche marked by high oxygen and low glucose. We have recently shown that in contrast to bone marrow-derived macrophages (BMDMs), TR-AMs do not utilize glycolysis and instead predominantly rely on mitochondrial function for their effector response. It is not known how changes in local oxygen concentration that occur during conditions such as acute respiratory distress syndrome (ARDS) might affect TR-AM metabolism and function; however, ARDS is associated with progressive loss of TR-AMs, which correlates with the severity of disease and mortality. Here, we demonstrate that hypoxia robustly stabilizes HIF-1α in TR-AMs to promote a glycolytic phenotype. Hypoxia altered TR-AM metabolite signatures, cytokine production, and decreased their sensitivity to the inhibition of mitochondrial function. By contrast, hypoxia had minimal effects on BMDM metabolism. The effects of hypoxia on TR-AMs were mimicked by FG-4592, a HIF-1α stabilizer. Treatment with FG-4592 decreased TR-AM death and attenuated acute lung injury in mice. These findings reveal the importance of microenvironment in determining macrophage metabolic phenotype and highlight the therapeutic potential in targeting cellular metabolism to improve outcomes in diseases characterized by acute inflammation.

SummaryAnnual rings from 30 year old vines in a California rootstock trial were measured to determine the effects of 15 different rootstocks on Chardonnay and Cabernet Sauvignon scions. Viticultural traits measuring vegetative growth, yield, berry quality, and nutrient uptake were collected at the beginning and end of the lifetime of the vineyard.X-ray Computed Tomography (CT) was used to measure ring widths in 103 vines. Ring width was modeled as a function of ring number using a negative exponential model. Early and late wood ring widths, cambium width, and scion trunk radius were correlated with 27 traits.Modeling of annual ring width shows that scions alter the width of the first rings but that rootstocks alter the decay thereafter, consistently shortening ring width throughout the lifetime of the vine. The ratio of yield to vegetative growth, juice pH, photosynthetic assimilation and transpiration rates, and stomatal conductance are correlated with scion trunk radius.Rootstocks modulate secondary growth over years, altering hydraulic conductance, physiology, and agronomic traits. Rootstocks act in similar but distinct ways from climate to modulate ring width, which borrowing techniques from dendrochronology, can be used to monitor both genetic and environmental effects in woody perennial crop species.

The objective of this study was to determine the etiology of febrile illnesses among patients from October 1, 1993 through September 30, 1999, in the urban community of Iquitos in the Amazon River Basin of Peru. Epidemiological and clinical data as well as blood samples were obtained from consenting patients at hospitals, health clinics and private residences. Samples were tested for arboviruses in cell cultures and for IgM and IgG antibodies by ELISA. Blood smears were examined for malaria, and sera were tested for antibodies to Leptospira spp. by ELISA and microscopic agglutination. Among 6,607 febrile patients studied, dengue viruses caused 14.6% of the cases, and Venezuelan equine encephalitis virus caused 2.5%, Oropouche virus 1.0%, Mayaro virus 0.4%, and other arboviruses caused 0.2% of the cases. Also, 22.9% of 4,844 patients tested were positive for malaria, and of 400 samples tested, 9% had evidence of acute leptospirosis. Although the study was not designed to assess the importance of these pathogens as a cause of human morbidity in the total population, these results indicate that arboviruses, leptospirosis, and malaria were the cause of approximately 50% of the febrile cases. Although the arboviruses that were diagnosed can produce asymptomatic infections, our findings increased the overall understanding of the relative health burden of these infections, as well as baseline knowledge needed for designing and implementing further studies to better assess the health impact and threat of these pathogens in the Amazon Basin of Peru.

Cellular metabolism is a critical regulator of macrophage effector function. Tissue-resident alveolar macrophages (TR-AMs) inhabit a unique niche marked by high oxygen and low glucose. We have recently shown that in contrast to bone marrow-derived macrophages (BMDMs), TR-AMs cannot utilize glycolysis and predominantly rely on mitochondrial function for their effector response. It is not known how changes in local oxygen concentration that occur during conditions such as acute respiratory distress syndrome (ARDS) might affect TR-AM metabolism and function; however, ARDS is associated with progressive loss of TR-AMs, which correlates with the severity of disease and mortality. Here, we demonstrate that hypoxia robustly stabilizes HIF-1α in TR-AMs to promote a glycolytic phenotype. Hypoxia altered TR-AM metabolite signatures, cytokine production, and decreased their sensitivity to the inhibition of mitochondrial function. By contrast, hypoxia had minimal effects on BMDM metabolism. The effects of hypoxia on TR-AMs were mimicked by FG-4592, a HIF-1α stabilizer. Treatment with FG-4592 decreased TR-AM death and attenuated acute lung injury in mice. These findings reveal the importance of microenvironment in determining macrophage metabolic phenotype, and highlight the therapeutic potential in targeting cellular metabolism to improve outcomes in diseases characterized by acute inflammation.

Macroautophagy (hereafter autophagy) degrades and recycles intracellular components to sustain metabolism and survival during starvation. Host autophagy promotes tumor growth by providing essential tumor nutrients. Autophagy also regulates immune cell homeostasis and function and suppresses inflammation. Although host autophagy does not promote a T-cell antitumor immune response in tumors with low tumor mutational burden (TMB), whether this was the case in tumors with high TMB was not known. Here we show that autophagy, especially in the liver, promotes tumor immune tolerance by enabling regulatory T-cell function and limiting stimulator of interferon genes, T-cell response and interferon-γ, which enables growth of high-TMB tumors. We have designated this as hepatic autophagy immune tolerance. Autophagy thereby promotes tumor growth through both metabolic and immune mechanisms depending on mutational load and autophagy inhibition is an effective means to promote an antitumor T-cell response in high-TMB tumors. White and colleagues identify a role for host autophagy in restraining T-cell-dependent immune responses, specifically against tumors with high mutational burden.

BackgroundCardiac arrest (CA) patients who survived by cardiopulmonary resuscitation (CPR) can present different levels of neurological deficits ranging from minor cognitive impairments to persistent vegetative state and brain death. The pathophysiology of the resulting brain injury is poorly understood and whether changes in post-CA brain metabolism contribute to the injury are unknown. Here we utilized [18F]FDG-PET to study in vivo cerebral glucose metabolism 72 hours following CA in a murine cardiac arrest model.MethodsAnesthetized and ventilated adult C57BL/6 mice underwent 12-minute KCl-induced CA followed by CPR. Seventy-two hours following cardiac arrest, surviving mice were intraperitoneally injected with [18F]FDG (~186 μCi/200 μL) and imaged on Molecubes preclinical micro PET/CT imaging systems after a 30-minute awake uptake period. Brain [18F]FDG uptake was determined by the VivoQuant software on fused PET/CT images with the 3D brain atlas. Upon completion of PET imaging, remaining [18F]FDG radioactivity in the brain, heart, and liver was determined using a gamma counter.ResultsGlobal increases in brain [18F]FDG uptake in post-CA mice were observed compared to shams and controls. The median standardized uptake value (SUV) of [18F]FDG for CA animals was 1.79 vs. sham 1.25 (p18F]FDG uptake for brain were 7.04%ID/g tissue for CA mice vs 5.537%ID/g tissue for sham animals, pConclusionsThis study has successfully applied [18F]FDG-PET/CT to measure changes in brain metabolism in a murine model of asystolic CA. Our results demonstrate increased [18F]FDG uptake in the brain 72 hours following CA, suggesting increased metabolic demand in the case of severe neurological injury. Further study is warranted to determine the etiology of these changes.

Post-activation potentiation has proven to be an effective strategy to enhance performance for many tasks, but little research has been conducted specifically concerning endurance sport performance. This study examined whether 5-km run performance could be improved by completing pre-run strides while wearing a 6.8 kg weighted compression garment (LOAD). A counter-balanced crossover field study design was incorporated with NCAA Division I Cross Country runners (n = 10) during coach-led, official team pre-season “speed day” practices. On Monday of Week 1, testing participants completed a course preview run and strategy session with their coach as they would do in preparation for a meet. The following two Mondays, participants completed the 5-km run as quickly as possible while blinded to pace. The team’s habitual warmup routine was used, which included a 3.22-km run followed by a series of dynamic warm-up movements before four, 80-m strides were completed with LOAD or without load (CON). Average wet-bulb globe temperature for both sessions was 22.3 °C. CON did not differ (p>0.05) from LOAD in split times for kilometres 0.00-1.61 (339±13 vs 341±13 s), 1.61-3.22 (312±15 vs 312±16 s), 3.22-4.83 (339±21 vs 338±22 s), or the 0.17 km distance kick at the end of the run (71±16 vs 69±14 s). Overall time was also not improved for LOAD (1060±49 s) versus CON (1062±55 s). The ~10% body mass LOAD warm-up strategy failed to improve early, mid-, or finishing kick performance in a 5-km time-trial with well-trained runners.

Supplemental Digital Content is available in the text., Objectives: Cardiogenic shock following cardiopulmonary resuscitation for sudden cardiac arrest is common, occurring even in the absence of acute coronary artery occlusion, and contributes to high rates of postcardiopulmonary resuscitation mortality. The pathophysiology of this shock is unclear, and effective therapies for improving clinical outcomes are lacking. Design: Laboratory investigation. Setting: University laboratory. Subjects: C57BL/6 adult female mice. Interventions: Anesthetized and ventilated adult female C57BL/6 wild-type mice underwent a 4, 8, 12, or 16-minute potassium chloride-induced cardiac arrest followed by 90 seconds of cardiopulmonary resuscitation. Mice were then blindly randomized to a single IV injection of vehicle (phosphate-buffered saline) or suppressor of site IQ electron leak, an inhibitor of superoxide production by complex I of the mitochondrial electron transport chain. Suppressor of site IQ electron leak and vehicle were administered during cardiopulmonary resuscitation. Measurements and Main Results: Using a murine model of asystolic cardiac arrest, we discovered that duration of cardiac arrest prior to cardiopulmonary resuscitation determined postresuscitation success rates, degree of neurologic injury, and severity of myocardial dysfunction. Post-cardiopulmonary resuscitation cardiac dysfunction was not associated with myocardial necrosis, apoptosis, inflammation, or mitochondrial permeability transition pore opening. Furthermore, left ventricular function recovered within 72 hours of cardiopulmonary resuscitation, indicative of myocardial stunning. Postcardiopulmonary resuscitation, the myocardium exhibited increased reactive oxygen species and evidence of mitochondrial injury, specifically reperfusion-induced reactive oxygen species generation at electron transport chain complex I. Suppressor of site IQ electron leak, which inhibits complex I-dependent reactive oxygen species generation by suppression of site IQ electron leak, decreased myocardial reactive oxygen species generation and improved postcardiopulmonary resuscitation myocardial function, neurologic outcomes, and survival. Conclusions: The severity of cardiogenic shock following asystolic cardiac arrest is dependent on the length of cardiac arrest prior to cardiopulmonary resuscitation and is mediated by myocardial stunning resulting from mitochondrial electron transport chain complex I dysfunction. A novel pharmacologic agent targeting this mechanism, suppressor of site IQ electron leak, represents a potential, practical therapy for improving sudden cardiac arrest resuscitation outcomes.

Introduction: The ductus arteriosus (DA) allows placentally oxygenated blood to bypass the non-ventilated fetal lungs and enter the systemic circulation. The fetus’ systemic pO 2 is ~40 mmHg, maintaining the DA in a state of hypoxic vasodilation. As pO 2 rises, with the first breath, the DA constricts and achieves functional closure within minutes. We have identified a mitochondrial O 2 -sensor controlling functional closure within DA smooth muscle cells (DASMC). Increased pO 2 leads to increased reactive oxygen species (ROS) production by complexes I and III of the electron transport chain (ETC). These ROS are diffusible signaling molecules and inhibit redox sensitive potassium channels causing DASMC depolarization and vasoconstriction. We propose this reflects electron leak from ETC complexes. Using the term rabbit model, we investigated the differential function of ETC I vs III complex-specific electron leak suppressors (S1QEL vs S3QEL) on vascular tone in DA rings. Methods: DA’s from term rabbits (n=11 rabbits, n=29 individual DA rings) were mounted on a force transducer at ~800 mg in Krebs at a PO 2 of ~40mmHg. DA’s were subject to varying pO 2 levels (from 35-155 mmHg) and at peak O 2 constriction were treated with ETC leak suppressors, ETC complex inhibitors or vehicle controls (DMSO). Results: Exposure to normoxia caused an average 1100±62 mg increase in DA tension. S1QEL (50 μM) caused an average 20.9±6.2% reduction in DA tension (n=8) whereas S3QEL (100 μM) only reduced DA tension by 4.4±2.2% (n=4). Rotenone (complex I inhibitor) and antimycin A (complex III inhibitor) also relaxed the DA while vehicle had minimal effect (-2.6±1.5%). Conclusions: Electron leak from complex 1, but not complex 3, is implicated in DA O 2 -sensing.

Evidence suggests the range of Spilogale putorius (Eastern Spotted Skunk) has contracted and its abundance has declined in the past 70 years, leading to conservation concerns. We summarized county records of Eastern Spotted Skunks collected during 2000–2020 to determine the current range and relative abundance of the species. We accumulated 1174 records from 257 counties across its historic range in the United States, with 901 records from 197 counties considered verified. Verified records included museum specimens, photo-documented occurrences, and captures by researchers. We created 2 distribution maps: one of their current range based on all occurrence records and another from only verified records. Records indicated the Eastern Spotted Skunk persisted across a large portion of its historic range, and is relatively abundant in the Interior Highlands, Appalachian Mountains, central Texas, central South Dakota, and south Florida. Our results also suggest that the species' overall range has contracted since 1959. Regions with a relatively high abundance of current records covered a variety of ecosystems, including agricultural areas, grasslands, woodlands, and forests. These data provide managers with information concerning where research and conservation efforts can be focused for this potentially declining species.

Extracorporeal cardiopulmonary resuscitation (ECPR) is a resource-intensive tool that provides haemodynamic and respiratory support in patients who have suffered cardiac arrest. In this study, we investigated the cost-utility of ECPR (cost/QALY) in cardiac arrest patients treated at our institution.We performed a retrospective review of patients who received ECPR following cardiac arrest between 2012 and 2018. All medical care-associated charges with ECPR and subsequent hospital admission were recorded. The quality-of-life of survivors was assessed with the Health Utilities Index Mark II. The cost-utility of ECPR was calculated with cost and quality-of-life data.ECPR was used in 32 patients (15/32 in-hospital, 47%) with a median age of 55.0 years (IQR 46.3-63.3 years), 59% male and 66% African American. The median duration of ECPR support was 2.1 days (IQR 0.9-3.8 days). Survival to hospital discharge was 16%. The median score of the Health Utilities Index Mark II at discharge for the survivors was 0.44 (IQR 0.32-0.52). The median operating cost for patients undergoing ECMO was $125,683 per patient (IQR $49,751-$206,341 per patient). The calculated cost-utility for ECPR was $56,156/QALY gained.The calculated cost-utility is within the threshold considered cost-effective in the United States ($150,000/QALY gained). These results are comparable to the cost-effectiveness of heart transplantation for end-stage heart failure. Larger studies are needed to assess the cost-utility of ECPR and to identify whether other factors, such as patient characteristics, affect the cost-utility benefit.

The integrator SSS performs accurate N-body simulations of the Solar System when there is a mix of massive bodies and test particles. The orbital motion of all bodies at all times is integrated using a 12-10 explicit Runge-Kutta Nystrom (RKN) pair. The test particles are divided into sets and each set integrated on a different processor. The explicit RKN pair uses an order 12 interpolant for the position and velocity when checking for collisions. We report on two significant improvements to SSS. The first improvement reduced the local round-off error in interpolated values by approximately four orders of magnitude, permitting more accurate modelling of collisions. The technique used to reduce the round-off error can be applied to other high-order interpolants. The second improvement is hand optimization of the implementation of SSS. This optimization increased the speed of SSS by approximately 60%, permitting more accurate modelling through the use of more test particles. We also present a summary of the numerical performance of SSS on a simulation of the Sun, the planets Earth to Neptune, and 500,000 test particles over 100 million years.

A forced-choice (FC) recognition trial was recently developed as an embedded validity indicator for the Rey Auditory Verbal Learning Test (RAVLT), although it has not been replicated outside of the initial validation study. This study cross-validated the RAVLT FC trial for detecting invalid neuropsychological test performance and assessed the degree to which material-specific verbal memory impairment severity impacts its classification accuracy as a performance validity test (PVT). This cross-sectional study included 172 neuropsychiatric patients who completed the RAVLT and 4 independent criterion PVTs, which were used to classify validity groups (134 valid/38 invalid). Overall results showed the RAVLT FC had excellent classification accuracy for detecting invalid performance at a ≤13 cut-score (66% sensitivity/87% specificity). When patients were subdivided by memory impairment status, FC retained excellent classification accuracy among the normal memory and mild memory impairment groups with 66%-82% sensitivity and ≥89% specificity. Accuracy decreased among those with severe memory impairment, but remained significant with a lower, alternative cut-score of ≤11 (37% sensitivity/88% specificity). Findings were consistent with FC trials developed for other memory measures and support the utility of this novel RAVLT FC index for reliably identifying invalid performance, even in the context of significant verbal memory impairment. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

The susceptibility of Myotis austroriparius (Southeastern Myotis) to infection with Pseudogymnoascus destructans, the fungus that causes white-nose syndrome (WNS), is unresolved. Our goal was to provide an initial insight on WNS susceptibility of Southeastern Myotis through a combination of fungal swabbing, ultraviolet light (UV) photography, and seasonal counts of hibernating bats in 2 caves known to harbor P. destructans. We swabbed and photographed 61 Southeastern Myotis in 2 Alabama caves during the winter of 2017–2018 and photographed an additional 38 bats at 1 of these sites the subsequent winter. Of the bats swabbed during the first field season, 77% (n = 41) tested positive for P. destructans. None of the 99 bats examined and transilluminated with UV light exhibited any yellow-orange fluorescence characteristic of P. destructans infection. However, other bat species present at both sites had visible white fungal growth. Winter counts of Southeastern Myotis did not decline following the discovery of P. destructans at the hibernaculum where we had winter survey data predating WNS. Although our observations were limited in scope, these data suggest low susceptibility of Southeastern Myotis to WNS compared to other cave-hibernating species.

Objective We aimed to identify socioeconomic and clinical risk factors for post-intensive care unit (ICU)-related long-term cognitive impairment (LTCI). Summary background data After delirium during ICU stay, LTCI has been increasingly recognized, but without attention to socioeconomic factors. Methods We enrolled a prospective, multicenter cohort of ICU survivors with shock or respiratory failure from surgical and medical ICUs across 5 civilian and Veteran Affairs (VA) hospitals from 2010 to 2016. Our primary outcome was LTCI at 3- and 12 months post-hospital discharge defined by the Repeatable Battery for Assessment of Neuropsychological Symptoms (RBANS) global score. Covariates adjusted using multivariable linear regression included age, sex, race, AHRQ socioeconomic index, Charlson comorbidity, Framingham stroke risk, Sequential Organ Failure Assessment, duration of coma, delirium, hypoxemia, sepsis, education level, hospital type, insurance status, discharge disposition, and ICU drug exposures. Results Of 1040 patients, 71% experienced delirium, and 47% and 41% of survivors had RBANS scores >1 standard deviation below normal at 3- and 12 months, respectively. Adjusted analysis indicated that delirium, non-White race, lower education, and civilian hospitals (as opposed to VA), were associated with at least a half standard deviation lower RBANS scores at 3- and 12 months (P ≤ 0.03). Sex, AHRQ socioeconomic index, insurance status, and discharge disposition were not associated with RBANS scores. Conclusions Socioeconomic and clinical risk factors, such as race, education, hospital type, and delirium duration, were linked to worse PICS ICU-related, LTCI. Further efforts may focus on improved identification of higher-risk groups to promote survivorship through emerging improvements in cognitive rehabilitation.

Sharp, DW, Swain, JC, Boy, TG, Killen, LG, Green, JM, and O'Neal, EK. Effects of 2.4 kg of proximal external loading on 5-km running performance. J Strength Cond Res 36(7): 1833-1838, 2022-Racing weight is a popular topic in the running community. This study examined effects of modest loading via a ∼2.4-kg soft and malleable weighted compression garment on overground running performance. Former and current collegiate cross-country runners (5 women and 6 men) completed 2 outdoor, solo road course runs 7 days apart on a familiar training route. During the first run (CON) subjects ran as closely as possible to their goal pace for a "hard speed day" workout based on predetermined paces according to current training level. During a subsequent run, subjects attempted to match their pace with aid from global positioning system watches and splits verbally announced on the course while wearing the weighted compression garment (LOAD). Metabolic data was later assessed during 5-minute running bouts on a treadmill with CON and LOAD conditions at subject's CON run pace. LOAD was slower (p0.01) at the 1.6-km mark (6:03 ± 0:37 vs. 6:13 ± 0:40) and finish (18:29 ± 2:06 vs. 19:15 ± 2:16). There was no differentiation (p0.05) between V̇o2 (CON 3.47 ± 0.86; LOAD 3.56 ± 0.77 L·min-1) or respiratory exchange ratio (CON 1.05 ± 0.06; LOAD 1.06 ± 0.04) during the 5-minute running economy bouts. There was an inverse (r = -0.42) but nonsignificant (p = 0.22) relationship between percent difference in body mass and percent difference in performance. Metabolic variable differentiation was not detectable at race pace, but 2.4 kg of proximal loading resulted in an approximately 4% acute performance impairment.

Background Cardiopulmonary resuscitation (CPR) in adults following non-traumatic out of hospital cardiac arrest (OHCA) can cause thoracic complications including rib fractures, sternal fractures, and pneumothorax. Post-CPR complication rates are poorly studied and the optimum imaging modality to detect these complications post-resuscitation has not been established. Methods We performed a retrospective review of adult patients transported to a single, urban, academic hospital following atraumatic OHCA between September 2015 and January 2020. Patients who achieved sustained return of spontaneous circulation (ROSC) and who underwent computed tomography (CT) imaging of the chest following radiographic chest x-ray were included in the analyses. Patient demographics and prehospital data were collected. Descriptive statistics and multivariate logistic regression analysis were performed. Sensitivity and specificity of chest x-ray for the detection of thoracic injury in this population were estimated. Results 786 non-traumatic OHCA patients were transported to the ED, 417 of whom obtained sustained ROSC and were admitted to the hospital (53%). 137 (32.9%) admitted patients underwent CT imaging of the chest in the ED. Of these imaged patients median age was 62 years old (IQR 53–70) with 54.0% female and 38.0% of patients having received bystander CPR. 40/137 (29.2%) patients had skeletal fractures noted on CT imaging and 12/137 (8.8%) had pneumothorax present on CT imaging. X-ray yielded a sensitivity of 7.5% for rib fracture and 50% for pneumothorax with a specificity of 100% for both. Logistic regression analysis revealed no significant association between age, sex, bystander CPR, or resuscitation length with thoracic fractures or pneumothorax. Conclusions Complications from OHCA CPR were high with 29.2% of CT imaged patients having rib fractures and 8.8% having pneumothoraces. X-ray had poor sensitivity for these post-resuscitation complications. Post-CPR CT imaging of the chest should be considered for detecting post-CPR complications.

Introduction: Impaired endothelial function leads to the progression of heart failure after Ischemia-reperfusion (IR). Kinin activation of bradykinin receptor 1 (B1R), a G protein-coupled receptor that has been found to induce capillary leakage, may serve as a critical mediator in cardiac microvascular barrier dysfunction. However, the underlying mechanisms are not clear. We found that B1R inhibition abolished IR-induced endothelial matrix metalloprotease (MMP3) expression and improved endothelial barrier formation. Thus, we hypothesized that B1R antagonist protects against cardiac IR injury through an MMP3 pathway. Methods and Results: MMP3-/- mice and their littermate controls (WT) were subjected to either cardiac IR or sham control. The baseline characteristics of these mice showed minimal phenotypes. Cardiac function was determined at 3, 7 and 24 days post-IR by echocardiography. The MMP3-/- mice displayed improved cardiac function compared to the control mice, as determined by fractional shortening (26% ± 1.1 MMP3-/- vs. 21% ± 0.9 WT, p Conclusions: MMP3 is a critical regulator of cardiac microvascular barrier function, and B1R/MMP3 could potentially serve as a novel therapeutic target for heart failure in response to IR injury.

Background Neurological injury following successful resuscitation from sudden cardiac arrest (CA) is common. The pathophysiological basis of this injury remains poorly understood, and treatment options are limited. Microglial activation and neuroinflammation are established contributors to many neuropathologies, such as Alzheimer disease and traumatic brain injury, but their potential role in post-CA injury has only recently been recognized. Here, we hypothesize that microglial activation that occurs following brief asystolic CA is associated with neurological injury and represents a potential therapeutic target. Methods Adult C57BL/6 male and female mice were randomly assigned to 12-min, KCl-induced asystolic CA, under anesthesia and ventilation, followed by successful cardiopulmonary resuscitation (n = 19) or sham intervention (n = 11). Neurological assessments of mice were performed using standardized neurological scoring, video motion tracking, and sensory/motor testing. Mice were killed at 72 h for histological studies; neuronal degeneration was assessed using Fluoro-Jade C staining. Microglial characteristics were assessed by immunohistochemistry using the marker of ionized calcium binding adaptor molecule 1, followed by ImageJ analyses for cell integrity density and skeletal analyses. Results Neurological injury in post-cardiopulmonary-resuscitation mice vs. sham mice was evident by poorer neurological scores (difference of 3.626 ± 0.4921, 95% confidence interval 2.618–4.634), sensory and motor functions (worsened by sixfold and sevenfold, respectively, compared with baseline), and locomotion (75% slower with a 76% decrease in total distance traveled). Post-CA brains demonstrated evidence of neurodegeneration and neuroinflammatory microglial activation. Conclusions Extensive microglial activation and neurodegeneration in the CA1 region and the dentate gyrus of the hippocampus are evident following brief asystolic CA and are associated with severe neurological injury.

BACKGROUND: Cardiac arrest (CA) patients who survived by cardiopulmonary resuscitation (CPR) can present different levels of neurological deficits ranging from minor cognitive impairments to persistent vegetative state and brain death. The pathophysiology of the resulting brain injury is poorly understood and whether changes in post-CA brain metabolism contribute to the injury are unknown. Here we utilized [(18)F]FDG-PET to study in vivo cerebral glucose metabolism 72 hours following CA in a murine cardiac arrest model. METHODS: Anesthetized and ventilated adult C57BL/6 mice underwent 12-minute KCl-induced CA followed by CPR. Seventy-two hours following cardiac arrest, surviving mice were intraperitoneally injected with [(18)F]FDG (~186 μCi/200 μL) and imaged on Molecubes preclinical micro PET/CT imaging systems after a 30-minute awake uptake period. Brain [(18)F]FDG uptake was determined by the VivoQuant software on fused PET/CT images with the 3D brain atlas. Upon completion of PET imaging, remaining [(18)F]FDG radioactivity in the brain, heart, and liver was determined using a gamma counter. RESULTS: Global increases in brain [(18)F]FDG uptake in post-CA mice were observed compared to shams and controls. The median standardized uptake value (SUV) of [(18)F]FDG for CA animals was 1.79 vs. sham 1.25 (p

Objective: In-hospital mortality rates in patients successfully resuscitated following out-of-hospital cardiac arrest (OHCA) remains high. Little has been published regarding the timing and putative causes of in-hospital death during the post-cardiac arrest resuscitation phase of care. In this study, we aimed to develop a novel two-stage categorization system and investigate the timing and factors associated with post-CA in-hospital death. Design: Single-centered retrospective observational human study. Setting: Adult Emergency Department and ICU in a university affiliated hospital. Patients: Two hundred and forty-one adult, non-traumatic OHCA patients. Interventions: None. Measurements and Main Results: Through an expert consensus process, a two-stage classification system of hospital deaths was developed. Data abstraction was performed by two researchers and inter-reliability was 0.858. We categorized deaths as being due to withdrawal of life sustaining treatment (WOLST) 159 (66.0%), recurrent in-hospital cardiac arrest 51 (21.1%), and declared dead by neurological criteria 31 (12.9%). Half of WOLST decisions occurred primarily in the setting of isolated neurological injury. Early in-hospital death (≤ 3 days) was associated with recurrent in-hospital cardiac arrest and WOLST with refractory shock or multi-organ injury. Late in-hospital death (> 3 days) was associated with WOLST due to neurological injury. Age, initial lactate level, duration of CPR exceeding 30 minutes, and vasopressor dependence post ROSC was found to be the dependent predictors for Early death during hospital stay. Conclusions: Our novel two-stage categorization scheme for post-CA deaths demonstrated high inter-rater reliability. The majority of in-hospital post-CA deaths were due to neurological injury associated with WOLST. Early deaths were largely attributed to recurrent in-hospital cardiac arrest, and WOLST due to refractory shock or multi-organ injury while Late deaths occurred in the context of neurological injury demonstrating two phases of injury in the post-CA syndrome.

Our understanding of the health effects of disasters and populations disrupted by war or civil strife and how to respond effectively and responsibly to them has expanded greatly in the last several decades and continues to grow. Most of the morbidity and mortality in disasters of all types result from population displacement. Displaced populations, especially those in resource-poor areas with little or no developed civil and public health infrastructure, almost always experience significantly higher morbidity and mortality than their pre-disaster status. Since the mid-1990s the international humanitarian community has developed scientifically based consensus standards (The Sphere Project and others) for providing water and sanitation, shelter, and primary health care to these populations, focused on meeting the highest-priority needs that include prevention and treatment of acute diarrhea and dehydration, measles, malnutrition, vitamin A deficiency, and several other conditions. Health care professionals responding to humanitarian crises must be prepared to adapt their practices to provide care that is appropriate to the type of disaster and the particular circumstances and resources available.

Autophagy captures intracellular components and delivers them to lysosomes, where they are degraded and recycled to sustain metabolism and to enable survival during starvation1-5. Acute, whole-body deletion of the essential autophagy gene Atg7 in adult mice causes a systemic metabolic defect that manifests as starvation intolerance and gradual loss of white adipose tissue, liver glycogen and muscle mass1. Cancer cells also benefit from autophagy. Deletion of essential autophagy genes impairs the metabolism, proliferation, survival and malignancy of spontaneous tumours in models of autochthonous cancer6,7. Acute, systemic deletion of Atg7 or acute, systemic expression of a dominant-negative ATG4b in mice induces greater regression of KRAS-driven cancers than does tumour-specific autophagy deletion, which suggests that host autophagy promotes tumour growth1,8. Here we show that host-specific deletion of Atg7 impairs the growth of multiple allografted tumours, although not all tumour lines were sensitive to host autophagy status. Loss of autophagy in the host was associated with a reduction in circulating arginine, and the sensitive tumour cell lines were arginine auxotrophs owing to the lack of expression of the enzyme argininosuccinate synthase 1. Serum proteomic analysis identified the arginine-degrading enzyme arginase I (ARG1) in the circulation of Atg7-deficient hosts, and in vivo arginine metabolic tracing demonstrated that serum arginine was degraded to ornithine. ARG1 is predominantly expressed in the liver and can be released from hepatocytes into the circulation. Liver-specific deletion of Atg7 produced circulating ARG1, and reduced both serum arginine and tumour growth. Deletion of Atg5 in the host similarly regulated [corrected] circulating arginine and suppressed tumorigenesis, which demonstrates that this phenotype is specific to autophagy function rather than to deletion of Atg7. Dietary supplementation of Atg7-deficient hosts with arginine partially restored levels of circulating arginine and tumour growth. Thus, defective autophagy in the host leads to the release of ARG1 from the liver and the degradation of circulating arginine, which is essential for tumour growth; this identifies a metabolic vulnerability of cancer.

Turf toe is a spectrum of injury involving the first metatarsophalangeal joint originally described in football players on artificial surfaces. A detailed description of the complex anatomy and pathology involved in the turf toe injury is presented. We highlight potential pitfalls of image interpretation and emphasize what the referring physician needs to know.

Micro-architectured Ni-based superalloy structures, with Ni-20Cr-3Ti-2Al (wt.%) composition and γ/γ′-microstructure, are created by a multi-step process: (i) non-crimp orthogonal 3D-weaving of ductile, 202 μm diameter Ni-20%Cr wires, (ii) gas-phase alloying with Al and Ti, (iii) simultaneous transient-liquid phase (TLP) bonding between wires and homogenization within wires via interdiffusion, (iv) solutionizing to create a single-phase solid solution, and (v) aging to precipitate the γ′ phase. The creep behavior of these 3D-woven γ/γ′ nickel-based superalloys is studied under uniaxial compression via experiments at 825 °C and via finite element (FE) analysis, using a 3D model of the woven structures obtained through X-ray micro-tomography. The creep strain rate for the woven Ni-based superalloy is higher than that for the bulk superalloy due to the lower solid volume fraction of the woven structure, while the creep exponents are identical. The compressive creep behavior is sensitive to the geometry of the woven structures: fewer wires perpendicular to the load and fewer bonds between wires cause lower creep resistance of the woven structure, due to a reduction in load transfer from the longitudinal wires (which are primarily load-bearing) and the perpendicular wires. Creep buckling of longitudinal wires drastically reduces creep resistance of the woven structure, confirming the importance of maintaining longitudinal wires vertical and parallel to the uniaxial compression direction. Finally, reducing wire cross-section, e.g., via oxidation, reduces creep resistance. The oxidation kinetics of the wire structures at 750, 825, and 900 °C displayed parabolic rate constants comparable to commercial Ni-based superalloys, but indicates that up to 35% of the wire cross-section is oxidized after 7 days at 825 °C, such that oxidation-resistant coatings are needed for long-term use in oxidative environment.

Porous NiTi is of interest for bone implants because of its unique combination of biocompatibility (encouraging osseointegration), high strength (to prevent fracture), low stiffness (to reduce stress shielding), and shape memory or superelasticity (to deploy an implant). A promising method for creating NiTi structures with regular open channels is via 3D weaving of NiTi wires. This paper presents a processing method to bond woven NiTi wire structures at contact points between wires to achieve structural integrity: (i) a slurry consisting of a blend of NiTi and Nb powders is deposited on the surface of the NiTi wires after the weaving operation; (ii) the powders are melted to create a eutectic liquid phase which collects at contact points; and (iii) the liquid is solidified and binds the NiTi woven structures. The bonded NiTi wire structures exhibited lower transformation temperatures compared to the as-woven NiTi wires because of Nb diffusion into the NiTi wires. A bonded woven sample was deformed in bending and showed near-complete recovery up to 6% strain and recovered nearly half of the deformation up to 19% strain.

Background Low protein amounts are used in ketogenic diets (KDs), where an essential (indispensable) amino acid (IAA) can become limiting. Because the chemically sensitive, seizurogenic, anterior piriform cortex (APC) is excited by IAA limitation, an imbalanced KD could exacerbate seizure activity. Objective We questioned whether dietary IAA depletion worsens seizure activity in rodents fed KDs. Methods In a series of 6 trials, male rats or gerbils of both sexes (6-8/group) were given either control diets (CDs) appropriate for each trial, a KD, or a threonine-devoid (ThrDev) diet for ≥7 d, and tested for seizures using various stimuli. Microchip analysis of rat APCs was also used to determine if changes in transcripts for structures relevant to seizurogenesis are affected by a ThrDev diet. Glutamate release was measured in microdialysis samples from APCs during the first meal after 7 d on a CD or a ThrDev diet. Results Adult rats showed increased susceptibility to seizures in both chemical (58%) and electroshock (doubled) testing after 7 d on a ThrDev diet compared with CD (each trial, P ≤ 0.05). Seizure-prone Mongolian gerbils had fewer seizures after receiving a KD, but exacerbated seizures (68%) after 1 meal of KD minus Thr (KD-T compared with CD, P

Braided tubes of Ni-based superalloys are fabricated via three-dimensional (3-D) braiding of ductile Ni-20Cr (wt pct) wires followed by post-textile gas-phase alloying with Al and Ti to create, after homogenization and aging, γ/γ′ strengthened lightweight, porous structures. Tensile tests reveal an increase in strength by 100 MPa compared to as-braided Ni-20Cr (wt pct). An interrupted tensile test, combined with X-ray tomographic scans between each step, sheds light on the failure behavior of the braided superalloy tubes.