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Abstract Neurological and cardiac injuries are significant contributors to morbidity and mortality following pediatric in-hospital cardiac arrest (IHCA). Preservation of mitochondrial function may be critical for reducing these injuries. Dimethyl fumarate (DMF) has shown potential to enhance mitochondrial content and reduce oxidative damage. To investigate the efficacy of DMF in mitigating mitochondrial injury in a pediatric porcine model of IHCA, toddler-aged piglets were subjected to asphyxia-induced CA, followed by ventricular fibrillation, high-quality cardiopulmonary resuscitation, and random assignment to receive either DMF (30 mg/kg) or placebo for four days. Sham animals underwent similar anesthesia protocols without CA. After four days, tissues were analyzed for mitochondrial markers. In the brain, untreated CA animals exhibited a reduced expression of proteins of the oxidative phosphorylation system (CI, CIV, CV) and decreased mitochondrial respiration (p

Summary: In humans, dietary patterns impact weight and metabolism differentially across individuals. To uncover genetic determinants for differential dietary effects, we subjected four genetically diverse mouse strains to humanized diets (American, Mediterranean, vegetarian, and vegan) with similar macronutrient composition, and performed body weight, metabolic parameter, and RNA-seq analysis. We observed pronounced diet- and strain-dependent effects on weight, and triglyceride and insulin levels. Differences in fat mass, adipose tissue, and skeletal muscle glucose uptake, and gene expression changes in most tissues were strain-dependent. In visceral adipose tissue, ∼400 genes responded to diet in a strain-dependent manner, many of them in metabolite transport and lipid metabolism pathways and several previously identified to modify diet effects in humans. Thus, genetic background profoundly impacts metabolism, though chosen dietary patterns modify the strong genetic effects. This study paves the way for future mechanistic investigations into strain-diet interactions in mice and translation to precision nutrition in humans.

Background: This retrospective study evaluated the efficacy and safety of intraoperative methadone compared with short-acting opioids. Methods: Patients undergoing cardiac surgery with cardiopulmonary bypass (n=11 967) from 2018 to 2023 from a single health system were categorised into groups based on intraoperative opioid administration: no methadone (Group O), methadone plus other opioids (Group M+O), and methadone only (Group M). Results: Patients in Groups M and M+O had lower mean pain scores until postoperative day (POD) 7 compared with Group O after adjusting for covariates (P

Abstract Background Stroke is one of the leading causes of death in the USA and is a major cause of serious disability for adults. This randomized crossover study examines the effect of targeted high-definition transcranial direct current transcranial brain stimulation (tDCS) on upper extremity motor recovery in patients in the post-acute phase of stroke recovery. Methods This randomized double-blinded cross-over study includes four intervention arms: anodal, cathodal, and bilateral brain stimulation, as well as a placebo stimulation. Participants receive each intervention in a randomized order, with a 2-week washout period between each intervention. The primary outcome measure is change in Motor Evoked Potential. Secondary outcome measures include the Fugl-Meyer Upper Extremity (FM-UE) score, a subset of FM-UE (A), related to the muscle synergies, and the Modified Ashworth Scale. Discussion We hypothesize that anodal stimulation to the ipsilesional primary motor cortex will increase the excitability of the damaged cortico-spinal tract, reducing the UE flexion synergy and enhancing UE motor function. We further hypothesize that targeted cathodal stimulation to the contralesional premotor cortex will decrease activation of the cortico-reticulospinal tract (CRST) and the expression of the upper extremity (UE) flexion synergy and spasticity. Finally, we hypothesize bilateral stimulation will achieve both results simultaneously. Results from this study could improve understanding of the mechanism behind motor impairment and recovery in stroke and perfect the targeting of tDCS as a potential stroke intervention. With the use of appropriate screening, we anticipate no ethical or safety concerns. We plan to disseminate these research results to journals related to stroke recovery, engineering, and medicine. Trial registration ClinicalTrials.gov NCT05479006 . Registered on 26 July 2022.

Muscle strength declines ∼3% per year after the age of 70. Resistance training guidelines for older adults are often based on free-weight and machine exercises, which may be inaccessible and lack carryover to activities of daily living. We tested the hypothesis that resistance training adaptations in older adults are task-specific. Thirty adults (8 males, 22 females; mean age = 71 years) were randomly assigned to participate in 6 weeks of supervised, high-intensity resistance training (twice per week) utilizing free-weight and machine exercises (traditional) versus functional activities that were overloaded with a weighted vest (functional). Participants were thoroughly familiarized with the exercises and testing prior to beginning the study. Major outcome measures included assessments of functional performance, five-repetition maximum strength, isometric knee extensor force, and quadriceps muscle size. Physical activity and nutrition were monitored. The study results demonstrate that the magnitude of improvement within a given outcome was largely dependent on group assignment, with greater improvements in gait speed and the timed-up-and-go in the functional group, but 2-3× greater five repetition maximum strength improvements for the trap bar deadlift, leg press, and leg extension following traditional resistance training. Both groups showed improvements in isometric knee extensor force and muscle size, suggesting that some aspects of the observed adaptations were generic, rather than specific. Overall, these novel findings suggest that, among older adults, 1) resistance training adaptations exhibit a high degree of task specificity and 2) significant improvements in functional outcomes can be achieved with the use of a weighted vest.

Abstract Astrocytic tau aggregates are seen in several primary and secondary tauopathies, including progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), and chronic traumatic encephalopathy (CTE). In all of these diseases, astrocytic tau consists mostly of the longer (4R) tau isoform, even when adjacent neuronal aggregates consist of a mixture of 3- and 4R tau, as in CTE. Even the rare astrocytic tau aggregates seen in Pick’s disease appear to contain both 3R and 4R tau. The reasons for this, and the mechanisms by which astrocytic tau aggregates form, remain unclear. We used a combination of RNA in situ hybridization and immunofluorescence in post-mortem human brain tissue, as well as tau uptake studies in human stem cell-derived astrocytes, to determine the origins of astrocytic tau in 4R tauopathies. We found no differences in tau mRNA expression between diseases or between tau positive and negative astrocytes within PSP. We then found that stem cell-derived astrocytes preferentially take up long isoform (4R) recombinant tau and that this uptake is impaired by induction of reactivity with inflammatory stimuli or nutritional stress. Astrocytes exposed to either 3R or 4R tau also showed downregulation of genes related to astrocyte differentiation. Our findings suggest that astrocytes preferentially take up neuronal 4R tau from the extracellular space, potentially explaining why 4R tau is the predominant isoform in astrocytic tau aggregates.

The continued acceleration of time-to-market product development and rising demand for biotherapeutics have hastened the need for higher throughput within the biopharmaceutical industry. Automated liquid handlers (ALH) are increasingly popular due to flexible programming that enables processing of multiple samples with an array of functions. This flexibility is useful in streamlining research that requires chromatographic procedures to achieve product purity for downstream analysis. However, purification of biologics often requires additional off-deck buffer exchange steps due to undesirable elution conditions such as high acid or high salt content. Expanding the capability of ALHs to perform purification in sequence with buffer exchange would, therefore, increase workflow efficiency by eliminating the need for manual intervention, thus expediting sample preparation. Here we demonstrate two different automated purifications using pipet-based dispersive solid-phase extraction (dSPE). The first is an affinity purification of His-tagged proteins from bacterial lysate. The second is an anion-exchange purification of plasmid DNA. Both methods are followed by buffer exchange performed by an ALH. Percent recoveries for the three purified recombinant proteins ranged from 51 ± 1.2 to 86 ± 10%. The yields were inversely correlated to starting sample load and protein molecular weight. Yields for plasmid purification ranged between 11.4 ± 0.8 and 13.7 ± 0.9 µg, with the largest plasmid providing the highest yield. Both programs were rapid, with protein purification taking

The precise quantification of a dielectric waveguide core thickness, core width, core refractive index, and cladding refractive index across a wafer is critical for greater consistency and accuracy in photonic circuit fabrication. However, accurate wafer-scale measurements of these parameters have not yet been demonstrated. We have previously described a method for extracting these four parameters simultaneously from silicon nitride waveguides using unbalanced Mach–Zehnder interferometers on a single die. In this work, we show that this technique can be scaled to characterize these photonic parameters across an entire 300 mm wafer. The refractive indices of the core and cladding materials are found with relative standard deviations of the mean of 0.07% and 0.03%, respectively. The core width offset (bias) and thickness are found with relative standard deviations of 0.3% (2.6 nm) and 0.5% (1.1 nm), respectively. The extracted parameter maps suggest a radial variation of material indices and a planar variation of geometric parameters. We verify the extracted parameters by accurately predicting the performance of an unbalanced Mach–Zehnder interferometer and the degeneracy between different modes in straight waveguides.

Background: Adolescent brains are sensitive to stressors. However, under certain circumstances, developmental stress can promote an adaptive phenotype, allowing individuals to cope better with adverse situations in adulthood, thereby contributing to resilience. Methods: Sprague Dawley rats (50 males, 48 females) were subjected to adolescent chronic variable stress (adol CVS) for 2 weeks at postnatal day 45. At postnatal day 85, a group was subjected to single prolonged stress (SPS). After a week, animals were evaluated in an auditory-cued fear conditioning paradigm, and neuronal recruitment during reinstatement was assessed by Fos expression. Patch clamp electrophysiology (17–35 cells/group) was performed in male rats to examine physiological changes associated with resilience. Results: Adol CVS blocked fear potentiation evoked by SPS. We observed that SPS impaired extinction (males) and enhanced reinstatement (both sexes) of the conditioned freezing response. Prior adol CVS prevented both effects. SPS effects were associated with a reduction of infralimbic (IL) cortex neuronal recruitment after reinstatement in males and increased engagement of the central amygdala in females, both also prevented by adol CVS, suggesting different neurocircuits involved in generating resilience between sexes. We explored the mechanism behind reduced IL recruitment in males by studying the intrinsic excitability of IL pyramidal neurons. SPS reduced excitability of IL neurons, and prior adol CVS prevented this effect. Conclusions: Our data indicate that adolescent stress can impart resilience to the effects of traumatic stress on neuroplasticity and behavior. Our data provide a mechanistic link behind developmental stress-induced behavioral resilience and prefrontal (IL) cortical excitability in males.

IntroductionPrevious studies found that post-stroke motor impairments are associated with damage to the lesioned corticospinal tract (CST) and hyperexcitability of the contralesional cortico-reticulospinal tract (CRST). This proof-of-concept study aims to develop a non-invasive brain stimulation protocol that facilitates the lesioned CST and inhibits the contralesional CRST to improve upper extremity rehabilitation in individuals with moderate-to-severe motor impairments post-stroke.MethodsFourteen individuals (minimum 3 months post ischemic stroke) consented. Physician decision of the participants baseline assessment qualified eight to continue in a randomized, double-blind cross-over pilot trial (ClinicalTrials.gov Identifier: NCT05174949) with: (1) anodal high-definition transcranial direct stimulation (HD-tDCS) over the ipsilesional primary motor cortex (M1), (2) cathodal HD-tDCS over contralesional dorsal premotor cortex (PMd), (3) sham stimulation, with a two-week washout period in-between. Subject-specific MR images and computer simulation were used to guide HD-tDCS and verified by Transcranial Magnetic Stimulation (TMS) induced Motor Evoked Potential (MEP). The motor behavior outcome was evaluated by an Fugl-Meyer Upper Extremity score (primary outcome measure) and the excitability of the ipslesoinal CST and contralesional CRST was determined by the change of MEP latencies and amplitude (secondary outcome measures).ResultsThe baseline ipsilesional M1 MEP latency and amplitude were correlated with FM-UE. FM-UE scores were improved post HD-tDCS, in comparison to sham stimulation. Both anodal and cathodal HD-tDCS reduced the latency of the ipsilesional M1 MEP. The contralesional PMd MEP disappeared/delayed after HD-tDCS.DiscussionThese results suggest that HD-tDCS could improve the function of the lesioned corticospinal tract and reduce the excitability of the contralesional cortico-reticulospinal tract, thus, improving motor function of the upper extremity in more severely impaired individuals.

Richter’s Transformation is a treatment-resistant and fatal progression from Chronic Lymphocytic Leukemia (CLL) to an aggressive lymphoma. Here, the authors show that PRMT5 is upregulated months prior to and after transformation, PRMT5 overexpression in a CLL mouse model leads to increased risk of transformation, and that targeted PRMT5 inhibition prolongs survival and delays disease development.

Early infant growth trajectories have been linked to obesity risk. The aim of this study was to examine early infant feeding practices in association with anthropometric measures and risk of overweight/obesity in childhood. A total of 2492 children from Upstate KIDS, a population-based longitudinal cohort, were included for the analysis. Parents reported breastfeeding and complementary food introduction from 4 to 12 months on questionnaires. Weight and height were reported at 2–3 years of age and during later follow-up at 7–9 years of age. Age and sex z-scores were calculated. Linear mixed models were conducted, adjusting for maternal and child sociodemographic factors. Approximately 54% of infants were formula-fed at

Measurements of oxygen abundance throughout galaxies provide insight to the formation histories and ongoing processes. Here we present a study of the gas-phase oxygen abundance in the H ii regions and diffuse gas of the nearby starburst dwarf galaxy, IC 10. Using the Keck Cosmic Web Imager at W. M. Keck Observatory, we map the central region of IC 10 from 3500 to 5500 Å. The auroral [O III ] 4363 Å line is detected with a high signal-to-noise ratio in 12 of 46 H II regions observed, allowing for direct measurement of the oxygen abundance, yielding a median and standard deviation of $12+\mathrm{log}({\rm{O}}/{\rm{H}})=8.37\pm 0.25$ . We investigate trends between these directly measured oxygen abundances and other H II region properties, finding weak negative correlations with the radius, velocity dispersion, and luminosity. We also find weak negative correlations between the oxygen abundance and the derived quantities of turbulent pressure and ionized gas mass, and a moderate correlation with the derived dynamical mass. Strong line, R _23 abundance estimates are used in the remainder of the H II regions and on a resolved spaxel-by-spaxel basis. There is a large offset between the abundances measured with R _23 and the auroral line method. We find that the R _23 method is unable to capture the large range of abundances observed via the auroral line measurements. The extent of this variation in the measured abundances further indicates a poorly mixed interstellar medium in IC 10, which is not typical of dwarf galaxies and may be partly due to the ongoing starburst, accretion of pristine gas, or a late stage merger.

We examine star formation and dust properties for a sample of 660 galaxies at 1.37 ≤ z ≤ 2.61 in the MOSDEF survey by dividing them into groups with similarly shaped spectral energy distributions (SEDs). For each group, we combine the galaxy photometry into a finely sampled composite SED, and stack their spectra. This method enables the study of more complete galaxy samples, including galaxies with very faint emission lines. We fit these composite SEDs with Prospector to measure the stellar attenuation and SED-based star formation rates (SFRs). We also derive emission-line properties from the spectral stacks, including Balmer decrements, dust-corrected SFRs, and metallicities. We find that stellar attenuation correlates most strongly with mass, while nebular attenuation correlates strongly with both mass and SFR. Furthermore, the excess of nebular compared to stellar attenuation correlates most strongly with SFR. The highest SFR group has 2 mag of excess nebular attenuation. Our results are consistent with a model in which star-forming regions become more dusty as galaxy mass increases. To explain the increasing excess nebular attenuation, we require a progressively larger fraction of star formation to occur in highly obscured regions with increasing SFR. This highly obscured star formation could occur in dusty clumps or central starbursts. Additionally, as each galaxy group represents a different evolutionary stage, we study their locations on the UVJ and SFR-mass diagrams. As mass increases, metallicity and dust attenuation increase, while sSFR decreases. However, the most massive group moves towards the quiescent region of the UVJ diagram, while showing less obscuration, potentially indicating removal of dust.

Stellar flares from K and M dwarfs release panchromatic radiation characterized by a significantly higher brightness temperature (∼9–20 kK) than the star. The increased frequency of magnetic activity on young low-mass stars results in the energy released during flaring events becoming a notable contributor to the radiation environment. This study focuses on the β Pictoris moving group ( β PMG; 24 ± 3 Myr) for the analysis of young low-mass star flaring rates within the framework of larger flare studies. The calibration of long-term optical flare statistics is crucial to updating flare activity–age relations and the interpretation of exoplanet atmosphere observations. Using the β PMG, we develop a modular flare-extraction pipeline sensitive to low-mass stellar flares in observations from the Transiting Exoplanet Survey Satellite (TESS). This pipeline is built to characterize the flare properties of these stars such as total energy and cumulative flare rate. Consistent with previous studies, this sample ( N = 49) shows higher cumulative flare rates than early-type and old field stars by at least an order of magnitude. Fitted flare frequency distributions for both early- and late-type M dwarfs show an average slope of 1.58 ± 0.23, with earlier stars flaring with lower or similar rates to late types. A typical member in this sample has daily (∼1 day ^−1 ) flares with TESS band energies of 10 ^32 –10 ^33 erg. The optical flare rates and energies for this group provide essential context into the coevolution of host stars and associated planets.

Abstract Background Depression and obesity are highly prevalent, often co-occurring conditions marked by inflammation. Microbiome perturbations are implicated in obesity-inflammation-depression interrelationships, but how the microbiome mechanistically contributes to pathology remains unclear. Metabolomic investigations into microbial neuroactive metabolites may offer mechanistic insights into host-microbe interactions. Using 16S sequencing and untargeted mass spectrometry of saliva, and blood monocyte inflammation regulation assays, we identified key microbes, metabolites and host inflammation in association with depressive symptomatology, obesity, and depressive symptomatology-obesity comorbidity. Results Gram-negative bacteria with inflammation potential were enriched relative to Gram-positive bacteria in comorbid obesity-depression, supporting the inflammation-oral microbiome link in obesity-depression interrelationships. Oral microbiome was more highly predictive of depressive symptomatology-obesity co-occurrences than of obesity or depressive symptomatology independently, suggesting specific microbial signatures associated with obesity-depression co-occurrences. Mass spectrometry analysis revealed significant changes in levels of signaling molecules of microbiota, microbial or dietary derived signaling peptides and aromatic amino acids among depressive symptomatology, obesity and comorbid obesity-depression. Furthermore, integration of the microbiome and metabolomics data revealed that key oral microbes, many previously shown to have neuroactive potential, co-occurred with potential neuropeptides and biosynthetic precursors of the neurotransmitters dopamine, epinephrine and serotonin. Conclusions Together, our findings offer novel insights into oral microbial-brain connection and potential neuroactive metabolites involved.

Major depressive disorder (MDD) is a highly prevalent, debilitating disorder with a high rate of treatment resistance. One strategy to improve treatment outcomes is to identify patient-specific, pre-intervention factors that can predict treatment success. Neurophysiological measures such as electroencephalography (EEG), which measures the brain’s electrical activity from sensors on the scalp, offer one promising approach for predicting treatment response for psychiatric illnesses, including MDD. In this study, a secondary data analysis was conducted on the publicly available Two Decades Brainclinics Research Archive for Insights in Neurophysiology (TDBRAIN) database. Logistic regression modeling was used to predict treatment response, defined as at least a 50% improvement on the Beck’s Depression Inventory, in 119 MDD patients receiving repetitive transcranial magnetic stimulation (rTMS). The results show that both age and baseline symptom severity were significant predictors of rTMS treatment response, with older individuals and more severe depression scores associated with decreased odds of a positive treatment response. EEG measures contributed predictive power to these models; however, these improvements in outcome predictability only trended towards statistical significance. These findings provide confirmation of previous demographic and clinical predictors, while pointing to EEG metrics that may provide predictive information in future studies.

Green infrastructure on rooftops in urban areas can enhance important ecosystem services. In addition to mitigating water runoff and regulating building temperatures, green roofs can provide food and nesting resources for wildlife. Rooftop gardens can also be utilized to cultivate food crops, giving them the potential to attenuate instances of food insecurity which are commonplace in many urban areas. Given that many crops depend on bee pollination, it is imperative to characterize the rooftop bee community. Therefore, we sampled three urban food roofs near downtown St. Louis, MO during the 2017 and 2018 growing seasons. We found 38 bee species utilizing the rooftop farms. We then compared the rooftop bee communities to those of two nearby ground-level community gardens. The roofs had lower abundances of Bombus species than the ground-level sites while non-native cavity nesters in the genus Megachile were overrepresented. These results indicate that the rooftop bee communities represent a nested subset of the species found at ground level. This has important implications for the management of green roofs for growing crops, as this shift in bee community structure may play a role in determining which crops can be adequately supported with pollination services.

BackgroundHigh sensitivity C-reactive protein (hsCRP) is a marker of systemic inflammation that has been associated with persistent depressive symptoms. Depression and anxiety are frequently associated with a chronic inflammatory state, yet the nature of this relationship has not been rigorously examined in diverse Hispanic/Latino populations. We aimed to study the association of anxiety and depressive symptoms as well as comorbid presentations, with circulating high sensitivity C-reactive protein (hsCRP) levels in a large Latino cohort of diverse heritages. We hypothesized a significant positive associations of both anxiety and depressive symptoms and hsCRP levels and potential variations among the heritage groups.MethodsDepressive symptoms and anxiety were measured by the Center for Epidemiological Studies Depression Scale (CES-D) and State-Trait Anxiety Inventory (STAI), respectively. Serum hsCRP (hsCRP) levels of 15,448 participants (age 18 to 75 years; 52.3% women) from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) were measured and categorized based on the established cardiovascular disease (CVD) risk reference values (< 1mg/L, low; 1-ResultsMean CES-D, STAI scores, and hsCRP levels were 7.0 (SD = 5.9), 17.0 (SD = 5.7), and 3.84 (SD = 7.85), respectively. Generalized linear modeling, adjusted for sociodemographic characteristics revealed significant associations between depression (exp(β) = 1.12; pConclusionWe found modest associations between anxiety and depressive symptoms and systemic inflammation measured by hsCRP among diverse Hispanics/Latinos that did not appreciably differ between heritage groups.

l-lactate is an important intercellular energy currency. Here the authors report a genetically encoded biosensor eLACCO1.1 to monitor extracellular l-lactate; they use eLACCO1.1 to image extracellular l-lactate in cultured mammalian cells and brain tissue.

Some genes that are part of balanced translocations are reported as drivers for tumourigenesis. Here, the authors report a translocation involving MTCP1 in chronic lymphocytic leukemia and show that MTCP1 overexpression leads to the disease in a murine model.

Walking speed is a useful surrogate for health status across the population. Walking speed appears to be governed in part by interlimb coordination between propulsive (FP) and braking (FB) forces generated during step-to-step transitions and is simultaneously optimized to minimize metabolic cost. Of those forces, FP generated during push-off has received significantly more attention as a contributor to walking performance. Our goal was to first establish empirical relations between FP and walking speed and then to quantify their effects on metabolic cost in young adults. To specifically address any link between FP and walking speed, we used a self-paced treadmill controller and real-time biofeedback to independently prescribe walking speed or FP across a range of condition intensities. Walking with larger and smaller FP led to instinctively faster and slower walking speeds, respectively, with ~80% of variance in walking speed explained by FP. We also found that comparable changes in either FP or walking speed elicited predictable and relatively uniform changes in metabolic cost, together explaining ~53% of the variance in net metabolic power and ~14% of the variance in cost of transport. These results provide empirical data in support of an interdependent relation between FP and walking speed, building confidence that interventions designed to increase FP will translate to improved walking speed. Repeating this protocol in other populations may identify other relations that could inform the time course of gait decline due to age and disease.

Few studies have examined the time-dependent effects of stress on fear learning. Previously, we found that stress immediately before fear conditioning enhanced fear learning. Here, we aimed to extend these findings by assessing the effects of stress 30 min prior to fear conditioning on fear learning and fear generalization. Two hundred and twenty-one healthy adults underwent stress (socially evaluated cold pressor test) or a control manipulation 30 min before completing differential fear conditioning in a fear-potentiated startle paradigm. One visual stimulus (CS+), but not another (CS−), was associated with an aversive airblast to the throat (US) during acquisition. The next day, participants were tested for their fear responses to the CS+, CS−, and several generalization stimuli. Stress impaired the acquisition of fear on Day 1 but had no significant impact on fear generalization. The stress-induced impairment of fear learning was particularly evident in participants who exhibited a robust cortisol response to the stressor. These findings are consistent with the notion that stress administered 30 min before learning impairs memory formation via corticosteroid-related mechanisms and may help us understand how fear memories are altered in stress-related psychological disorders.

This paper presents a new hybrid PPSOGSA algorithm based on the phasor particle swarm optimization (PPSO) and gravitational search algorithm (GSA) for solving the Volt/VAr/THDv control optimization problem in radial distribution systems with non-linear loads. The PPSOGSA’s performance is analyzed and evaluated using the standard IEEE 30-bus radial distribution test system. The optimal solutions are obtained based on the following three optimization criteria: minimization of total active power losses, minimization of the voltage deviation, and a simultaneous minimization of total active power losses and voltage deviation. The voltage total harmonic distortion levels (THDv) are estimated using the decoupled harmonic power flow (DHPF) algorithm. Simulation results, obtained using the proposed PPSOGSA-based approach, are compared with those obtained using the other optimization algorithms such as PSO, PPSO, GSA, and PSOGSA. It is shown that the PPSOGSA-based approach has better performance in comparison to the other optimization techniques.

Abstract Background Exportin 1 (XPO1/CRM1) is a key mediator of nuclear export with relevance to multiple cancers, including chronic lymphocytic leukemia (CLL). Whole exome sequencing has identified hot-spot somatic XPO1 point mutations which we found to disrupt highly conserved biophysical interactions in the NES-binding groove, conferring novel cargo-binding abilities and forcing cellular mis-localization of critical regulators. However, the pathogenic role played by change-in-function XPO1 mutations in CLL is not fully understood. Methods We performed a large, multi-center retrospective analysis of CLL cases (N = 1286) to correlate nonsynonymous mutations in XPO1 (predominantly E571K or E571G; n = 72) with genetic and epigenetic features contributing to the overall outcomes in these patients. We then established a mouse model with over-expression of wildtype (wt) or mutant (E571K or E571G) XPO1 restricted to the B cell compartment (Eµ-XPO1). Eµ-XPO1 mice were then crossed with the Eµ-TCL1 CLL mouse model. Lastly, we determined crystal structures of XPO1 (wt or E571K) bound to several selective inhibitors of nuclear export (SINE) molecules (KPT-185, KPT-330/Selinexor, and KPT-8602/Eltanexor). Results We report that nonsynonymous mutations in XPO1 associate with high risk genetic and epigenetic features and accelerated CLL progression. Using the newly-generated Eµ-XPO1 mouse model, we found that constitutive B-cell over-expression of wt or mutant XPO1 could affect development of a CLL-like disease in aged mice. Furthermore, concurrent B-cell expression of XPO1 with E571K or E571G mutations and TCL1 accelerated the rate of leukemogenesis relative to that of Eµ-TCL1 mice. Lastly, crystal structures of E571 or E571K-XPO1 bound to SINEs, including Selinexor, are highly similar, suggesting that the activity of this class of compounds will not be affected by XPO1 mutations at E571 in patients with CLL. Conclusions These findings indicate that mutations in XPO1 at E571 can drive leukemogenesis by priming the pre-neoplastic lymphocytes for acquisition of additional genetic and epigenetic abnormalities that collectively result in neoplastic transformation.

Neuromuscular electrical stimulation (NMES) allows activation of muscle fibers in the absence of voluntary force generation. NMES could have the potential to promote muscle homeostasis in the context of muscle disease, but the impacts of NMES on diseased muscle are not well understood. We used the zebrafish Duchenne muscular dystrophy (dmd) mutant and a longitudinal design to elucidate the consequences of NMES on muscle health. We designed four neuromuscular stimulation paradigms loosely based on weightlifting regimens. Each paradigm differentially affected neuromuscular structure, function, and survival. Only endurance neuromuscular stimulation (eNMES) improved all outcome measures. We found that eNMES improves muscle and neuromuscular junction morphology, swimming, and survival. Heme oxygenase and integrin alpha7 are required for eNMES-mediated improvement. Our data indicate that neuromuscular stimulation can be beneficial, suggesting that the right type of activity may benefit patients with muscle disease.

Globally, relationships between avian richness and elevation in mountain ecosystems typically reflect one of four well‐documented patterns, but the mechanisms responsible for these patterns are poorly understood. We investigated which pattern best described bird species richness in peatlands of the Upper Bow Basin of the Canadian Rocky Mountains (1300–2000 m a.s.l.) and used a model competition framework to investigate possible mechanisms. Avian richness displayed a plateauing (cubic) relationship in response to increasing elevation (AICc weight = 0.48). Log richness was significantly positively related to log peatland area (R2 = 0.42, p = 0.001); however, and once we accounted for the richness–area relationship (area was not related to elevation (R2 = 0.13, p = 0.083)), the richness–elevation relationship was best described by a negative linear model rather than a cubic model (AICc weight = 0.69, R2 = 0.39). Consequently, we reject the neutral model of the mid‐domain effect and conclude that peatland area and one or more environmental filters are simultaneously driving relationships between avian richness and elevation in Rocky Mountain peatlands. Multicausality likely explains why researchers in different geographies observe inconsistent patterns between richness and elevation: drivers and interactions among drivers may vary spatially. Importantly, Natural Subregion was a stronger predictor of avian species richness than elevation per se (AICc weight = 0.96), suggesting that the responsible environmental filter(s) is relatively homogenous within ecological land classes (e.g. primary productivity) rather than directly variable with elevation (e.g. temperature). The results also lend insight into priorities for future research on richness–elevation patterns in mountain birds.

Summary:. Upper lip reconstruction represents a unique challenge for the reconstructive plastic surgeon. Given its prominent aesthetic role in addition to its functional role in facial expression, speech, and oral intake, preservation of this region’s natural form and function is paramount. In this report, we present a novel technique for the reconstruction of a complex central upper lip defect, restoring the natural aesthetic of this essential structure. We describe the case of a 51-year-old woman who presented with recurrence of a previously resected basal cell carcinoma center on the upper lip at the level of the white roll and philtral depression. Following surgical resection via Mohs micrographic surgery, a 1.8 × 1.6 cm partial-thickness defect centered around the Cupid bow involving both cutaneous and vermillion tissues remained. Reconstruction was achieved through a novel quadruple rhomboid flap primarily based on the preservation of the aesthetic subunits of the upper lip. A functional and aesthetic reconstruction was achieved through local tissue rearrangement, restoring the appearance of the white roll and red line. Native perfusion and innervation were preserved during the reconstruction of the Cupid bow, recreating this region’s natural appearance. The design of the flap resembles a jumping frog, which is the etiology of the “Frogger flap” moniker. The Frogger flap recreates the natural aesthetic of the central upper lip through the geometric transposition of tissue commensurate with native anatomy. Through the application of aesthetic subunit principles, it reliably reconstructs central upper lip defects while preserving function and providing an aesthetically pleasing outcome.

Benzo[a]pyrene (BaP) is formed by incomplete combustion of organic materials (petroleum, coal, tobacco, etc.). BaP is designated by the International Agency for Research on Cancer as a group 1 known human carcinogen; a classification supported by numerous studies in preclinical models and epidemiology studies of exposed populations. Risk assessment relies on toxicokinetic and cancer studies in rodents at doses 5–6 orders of magnitude greater than average human uptake. Using a dose–response design at environmentally relevant concentrations, this study follows uptake, metabolism, and elimination of [14C]-BaP in human plasma by employing UPLC - accelerator mass spectrometry (UPLC-AMS). Volunteers were administered 25, 50, 100, and 250 ng (2.7–27 nCi) of [14C]-BaP (with interceding minimum 3-week washout periods) with quantification of parent [14C]-BaP and metabolites in plasma measured over 48 h. [14C]-BaP median Tmax was 30 min with Cmax and area under the curve (AUC) approximating dose-dependency. Marked inter-individual variability in plasma pharmacokinetics following a 250 ng dose was seen with 7 volunteers as measured by the Cmax (8.99 ± 7.08 ng × mL−1) and AUC0-48hr (68.6 ± 64.0 fg × hr−1 × mL−1). Approximately 3–6% of the [14C] recovered (AUC0-48 hr) was parent compound, demonstrating extensive metabolism following oral dosing. Metabolite profiles showed that, even at the earliest time-point (30 min), a substantial percentage of [14C] in plasma was polar BaP metabolites. The best fit modeling approach identified non-compartmental apparent volume of distribution of BaP as significantly increasing as a function of dose (p = 0.004). Bay region tetrols and dihydrodiols predominated, suggesting not only was there extensive first pass metabolism but also potentially bioactivation. AMS enables the study of environmental carcinogens in humans with de minimus risk, allowing for important testing and validation of physiologically based pharmacokinetic models derived from animal data, risk assessment, and the interpretation of data from high-risk occupationally exposed populations.

Syringocystadenocarcinoma papilliferum (SCACP) is a rare malignant neoplasm arising from adnexal tissues and is the malignant complement to the benign neoplasm syringocystadenoma papilliferum (SCAP). SCACP lesions appear as raised nodules or inflammatory plaques and can be associated with SCAP or nevus sebaceous. There have been fewer than 100 described cases of this neoplasm in the literature, and all previously published cases have been described in adults, with the majority occurring in the elderly. We present a case of an adolescent female with a syringocystadenocarcinoma papilliferum arising from a large thigh mass harboring an in-frame alteration in MAP2K1 along with a brief review of the literature.

We investigate dust attenuation and its dependence on viewing angle for 308 star-forming galaxies at 1.3 ≤ z ≤ 2.6 from the MOSFIRE Deep Evolution Field survey. We divide galaxies with a detected H α emission line and coverage of H β into eight groups by stellar mass, star formation rate (SFR), and inclination (i.e., axis ratio), and we then stack their spectra. From each stack, we measure the Balmer decrement and gas-phase metallicity, and then we compute the median A _V and UV continuum spectral slope ( β ). First, we find that none of the dust properties (Balmer decrement, A _V , or β ) varies with the axis ratio. Second, both stellar and nebular attenuation increase with increasing galaxy mass, showing little residual dependence on SFR or metallicity. Third, nebular emission is more attenuated than stellar emission, and this difference grows even larger at higher galaxy masses and SFRs. Based on these results, we propose a three-component dust model in which attenuation predominantly occurs in star-forming regions and large, dusty star-forming clumps, with minimal attenuation in the diffuse ISM. In this model, nebular attenuation primarily originates in clumps, while stellar attenuation is dominated by star-forming regions. Clumps become larger and more common with increasing galaxy mass, creating the above mass trends. Finally, we argue that a fixed metal yield naturally leads to mass regulating dust attenuation. Infall of low-metallicity gas increases the SFR and lowers the metallicity, but leaves the dust column density mostly unchanged. We quantify this idea using the Kennicutt–Schmidt and fundamental metallicity relations, showing that galaxy mass is indeed the primary driver of dust attenuation.

We combine our dynamical modeling black-hole mass measurements from the Lick AGN Monitoring Project 2016 sample with measured cross-correlation time lags and line widths to recover individual scale factors, f , used in traditional reverberation-mapping analyses. We extend our sample by including prior results from Code for AGN Reverberation and Modeling of Emission Lines ( caramel ) studies that have utilized our methods. Aiming to improve the precision of black-hole mass estimates, as well as uncover any regularities in the behavior of the broad-line region (BLR), we search for correlations between f and other AGN/BLR parameters. We find (i) evidence for a correlation between the virial coefficient ${\mathrm{log}}_{10}({f}_{\mathrm{mean},\sigma })$ and black-hole mass, (ii) marginal evidence for a similar correlation between ${\mathrm{log}}_{10}({f}_{\mathrm{rms},\sigma })$ and black-hole mass, (iii) marginal evidence for an anticorrelation of BLR disk thickness with ${\mathrm{log}}_{10}({f}_{\mathrm{mean},\mathrm{FWHM}})$ and ${\mathrm{log}}_{10}({f}_{\mathrm{rms},\mathrm{FWHM}})$ , and (iv) marginal evidence for an anticorrelation of inclination angle with ${\mathrm{log}}_{10}({f}_{\mathrm{mean},\mathrm{FWHM}})$ , ${\mathrm{log}}_{10}({f}_{\mathrm{rms},\sigma })$ , and ${\mathrm{log}}_{10}({f}_{\mathrm{mean},\sigma })$ . Last, we find marginal evidence for a correlation between line-profile shape, when using the root-mean-square spectrum, ${\mathrm{log}}_{10}{(\mathrm{FWHM}/\sigma )}_{\mathrm{rms}}$ , and the virial coefficient, ${\mathrm{log}}_{10}({f}_{\mathrm{rms},\sigma })$ , and investigate how BLR properties might be related to line-profile shape using caramel models.

ABSTRACT Ebselen, a reactive organoselenium compound, was shown to inhibit toxins TcdA and TcdB by covalently binding to their cysteine protease domains. It was suggested that ebselen lacked antimicrobial activity against Clostridioides difficile. However, this perception conflicts with C. difficile having essential cysteine-containing enzymes that could be potential targets and the reported antimicrobial activity of ebselen against other species. Hence, we reevaluated the anti-C. difficile properties of ebselen. Susceptibility testing revealed that its activity was either slightly reduced by pyruvate found in Wilkins-Chalgren agar or obliterated by blood in brucella agar. In brain heart infusion (BHI) agar, ebselen inhibited most C. difficile strains (MICs of 2 to 8 μg/ml), except for ribotype 078 that was intrinsically resistant (MIC = 32 to 128 μg/ml). Against C. difficile R20291, at concentrations below its minimal bactericidal concentration (MBC), 16 μg/ml, ebselen inhibited production of toxins and spores. Transcriptome analysis revealed that ebselen altered redox-associated processes and cysteine metabolism and enhanced expression of Stickland proline metabolism, likely to regenerate NAD+ from NADH. In cellular assays, ebselen induced uptake of cysteine, depleted nonprotein thiols, and disrupted the NAD+/NADH ratio. Taken together, killing of C. difficile cells by ebselen occurs by a multitarget action that includes disrupting intracellular redox, which is consistent with ebselen being a reactive molecule. However, the physiological relevance of these antimicrobial actions in treating acute C. difficile infection (CDI) is likely to be undermined by host factors, such as blood, which protect C. difficile from killing by ebselen. IMPORTANCE We show that ebselen kills pathogenic C. difficile by disrupting its redox homeostasis, changing the normal concentrations of NAD+ and NADH, which are critical for various metabolic functions in cells. However, this antimicrobial action is hampered by host components, namely, blood. Future discovery of ebselen analogues, or mechanistically similar compounds, that remain active in blood could be drug leads for CDI or probes to study C. difficile redox biology in vivo.

Obesity and its associated metabolic syndrome are a leading cause of morbidity and mortality. Given the disease's heavy burden on patients and the healthcare system, there has been increased interest in identifying pharmacological targets for the treatment and prevention of obesity. Towards this end, genome-wide association studies (GWAS) have identified hundreds of human genetic variants associated with obesity. The next challenge is to experimentally define which of these variants are causally linked to obesity, and could therefore become targets for the treatment or prevention of obesity. Here we employ high-throughput in vivo RNAi screening to test for causality 293 C. elegans orthologs of human obesity-candidate genes reported in GWAS. We RNAi screened these 293 genes in C. elegans subject to two different feeding regimens: (1) regular diet, and (2) high-fructose diet, which we developed and present here as an invertebrate model of diet-induced obesity (DIO). We report 14 genes that promote obesity and 3 genes that prevent DIO when silenced in C. elegans. Further, we show that knock-down of the 3 DIO genes not only prevents excessive fat accumulation in primary and ectopic fat depots but also improves the health and extends the lifespan of C. elegans overconsuming fructose. Importantly, the direction of the association between expression variants in these loci and obesity in mice and humans matches the phenotypic outcome of the loss-of-function of the C. elegans ortholog genes, supporting the notion that some of these genes would be causally linked to obesity across phylogeny. Therefore, in addition to defining causality for several genes so far merely correlated with obesity, this study demonstrates the value of model systems compatible with in vivo high-throughput genetic screening to causally link GWAS gene candidates to human diseases.

Background:. Prosthetic vascular graft infection is a serious complication associated with significant morbidity and mortality often requiring graft excision and numerous additional operations. Pedicled flaps are often used for the coverage of exposed deep tissue or hardware for graft salvage. In the absence of pedicled options, the properties of omentum make it an excellent choice for free flap tissue coverage, particularly in cases involving implanted prostheses. Methods:. A 63-year-old woman developed a mycotic right subclavian arterial aneurysm requiring ligation and extra-anatomic bypass grafting to restore right-sided intracranial and right upper extremity arterial perfusion. Subsequent wound breakdown and poor healing left the grafts exposed, resulting in contamination. Given the profound risks associated with graft excision in this patient, salvage was attempted with IV antibiotics, serial wound/graft washouts, and graft coverage with an omental free flap. Results:. The patient tolerated the procedure well. The remainder of her hospital course was uneventful, and she was discharged home in good clinical condition. She will remain on long-term suppressive antibiotics per Infectious Disease recommendations. Conclusions:. Contemporary literature reporting novel and effective applications of omental free flap coverage is rare. This report demonstrates that omental free flap coverage is safe and can provide healthy tissue to protect implanted grafts and even aid in the salvage of infected extra-anatomic bypass grafts.

Abstract Background When suspended in cell culture medium, nano-objects composed of soluble metals such as silver can dissolve resulting in ion formation, altered particle properties (e.g. mass, morphology, etc.), and modulated cellular dose. Cultured cells are exposed not just to nanoparticles but to a complex, dynamic mixture of altered nanoparticles, unbound ions, and ion-ligand complexes. Here, three different cell types (RAW 264.7 macrophages and bone marrow derived macrophages from wild-type C57BL/6 J mice and Scavenger Receptor A deficient (SR-A(−/−)) mice) were exposed to 20 and 110 nm silver nanoparticles, and RAW 264.7 cells were exposed to freshly mixed silver ions, aged silver ions (ions incubated in cell culture medium), and ions formed from nanoparticle dissolution. The In Vitro Sedimentation, Diffusion, Dissolution, and Dosimetry Model (ISD3) was used to predict dose metrics for each exposure scenario. Results Silver nanoparticles, freshly mixed ions, and ions from nanoparticle dissolution were toxic, while aged ions were not toxic. Macrophages from SR-A(−/−) mice did not take up 20 nm silver nanoparticles as well as wild-types but demonstrated no differences in silver levels after exposure to 110 nm nanoparticles. Dose response modeling with ISD3 predicted dose metrics suggest that amount of ions in cells and area under the curve (AUC) of ion amount in cells are the most predictive of cell viability after nanoparticle and combined nanoparticle/dissolution-formed-ions exposures, respectively. Conclusions Results of this study suggest that the unbound silver cation is the ultimate toxicant, and ions formed extracellularly drive toxicity after exposure to nanoparticles. Applying computational modeling (ISD3) to better understand dose metrics for soluble nanoparticles allows for better interpretation of in vitro hazard assessments.

The emerging sector of offshore kelp aquaculture represents an opportunity to produce biofuel feedstock to help meet growing energy demand. Giant kelp represents an attractive aquaculture crop due to its rapid growth and production, however precision farming over large scales is required to make this crop economically viable. These demands necessitate high frequency monitoring to ensure outplant success, maximum production, and optimum quality of harvested biomass, while the long distance from shore and large necessary scales of production makes in person monitoring impractical. Remote sensing offers a practical monitoring solution and nascent imaging technologies could be leveraged to provide daily products of the kelp canopy and subsurface structures over unprecedented spatial scales. Here, we evaluate the efficacy of remote sensing from satellites and aerial and underwater autonomous vehicles as potential monitoring platforms for offshore kelp aquaculture farms. Decadal-scale analyses of the Southern California Bight showed that high offshore summertime cloud cover restricts the ability of satellite sensors to provide high frequency direct monitoring of these farms. By contrast, daily monitoring of offshore farms using sensors mounted to aerial and underwater drones seems promising. Small Unoccupied Aircraft Systems (sUAS) carrying lightweight optical sensors can provide estimates of canopy area, density, and tissue nitrogen content on the time and space scales necessary for observing changes in this highly dynamic species. Underwater color imagery can be rapidly classified using deep learning models to identify kelp outplants on a longline farm and high acoustic returns of kelp pneumatocysts from side scan sonar imagery signal an ability to monitor the subsurface development of kelp fronds. Current sensing technologies can be used to develop additional machine learning and spectral algorithms to monitor outplant health and canopy macromolecular content, however future developments in vehicle and infrastructure technologies are necessary to reduce costs and transcend operational limitations for continuous deployment in an offshore setting.

Cortical neural activity is coupled to local arterial diameter and blood flow. However, which neurons control the dynamics of cerebral arteries is not well understood. We dissected the cellular mechanisms controlling the basal diameter and evoked dilation in cortical arteries in awake, head-fixed mice. Locomotion drove robust arterial dilation, increases in gamma band power in the local field potential (LFP), and increases calcium signals in pyramidal and neuronal nitric oxide synthase (nNOS)-expressing neurons. Chemogenetic or pharmocological modulation of overall neural activity up or down caused corresponding increases or decreases in basal arterial diameter. Modulation of pyramidal neuron activity alone had little effect on basal or evoked arterial dilation, despite pronounced changes in the LFP. Modulation of the activity of nNOS-expressing neurons drove changes in the basal and evoked arterial diameter without corresponding changes in population neural activity.

Offshore aquaculture of giant kelp (Macrocystis pyrifera) has been proposed by the US Department of Energy for large scale biofuel production along the west coast of California. The Southern Californian Bight provides an ideal area for offshore kelp aquaculture as the upwelling and advection of cool, nutrient-rich waters supports the growth of vast native giant kelp populations. However, concentrations of nutrients vary greatly across space, can be limiting for kelp growth over seasonal to interannual time scales, and inputs of nutrients to surface waters may be subject to local circulation processes. Therefore, it is important to understand both the spatiotemporal variability of seawater nitrate concentrations and the appropriate scale of observation in order for offshore kelp aquaculture to be successful. Here, we use a combination of satellite sea surface temperature imagery, in situ measurements, and modeling to determine seawater nitrate fields across multiple spatial and temporal scales. We then combine this information with known giant kelp physiological traits to develop a kelp stress index (KSI) for the optimal siting of offshore kelp aquaculture over seasonal to decadal scales. Temperature to nitrate relationships were determined from in situ measurements using generalized additive models and validated with buoy data. Summer and winter relationships were significantly different, and satellite-derived products compared well to buoy validations. Surface nitrate patterns, as derived from satellite temperature products, reveal the spatial variability in nitrate concentrations, and indicate areas that that may cause nutrient stress seasonally and during the negative phase of the North Pacific Gyre Oscillation. As the spatial scale of the surface nitrate product decreased, the negative bias increased and fine scale spatial variability was lost. Similarly, the averaging of daily nitrate concentration determinations over longer time scales increased the negative bias. We found that daily, 1 km spatial resolution nitrate products were most sufficient for identifying localized upwelling and areas of consistently high surface nitrate concentrations, and that areas in the northern and western-most portions of the Southern California Bight are the most suitable for sustained offshore kelp aquaculture.

Platelets play a central role in primary hemostasis affecting tumor survival and metastases. Tumors induce platelets to aggregate and bind to the cancer cells, resulting in protection from immune surveillance and often leading to thrombocytosis. In ovarian cancer (OvCa), one-third of patients present with thrombocytosis, a diagnosis that correlates with shorter survival. SUSD2 (SUShi Domain containing 2), a type I transmembrane protein, shown to inhibit metastatic processes in high-grade serous ovarian carcinoma (HGSOC), is expressed on endothelial cells and thus may influence platelet reactivity. As such, we hypothesized that SUSD2 levels in ovarian cancer-derived cell lines influence platelet activation. We incubated OvCa non-targeting (NT) and SUSD2 knockdown (KD) cell lines with labeled platelets and quantified platelet binding, as well as GPIIb/IIIa integrin activation. The role of GPIIb/IIIa in tumor cell/platelet interaction was also examined by measuring cell–cell adhesion in the presence of eptifibatide. We found that platelets exposed to OvCa cells with low SUSD2 expression display increased tumor cell-platelet binding along with an increase in GPIIb/IIIa receptor activation. As such, platelet activation and binding to HGSOC cells was inversely correlated with the presence of SUSD2. This represents one of the first tumor proteins known to provide differential platelet interaction based on protein status.

Abstract Background The development of particokinetic models describing the delivery of insoluble or poorly soluble nanoparticles to cells in liquid cell culture systems has improved the basis for dose-response analysis, hazard ranking from high-throughput systems, and now allows for translation of exposures across in vitro and in vivo test systems. Complimentary particokinetic models that address processes controlling delivery of both particles and released ions to cells, and the influence of particle size changes from dissolution on particle delivery for cell-culture systems would help advance our understanding of the role of particles and ion dosimetry on cellular toxicology. We developed ISD3, an extension of our previously published model for insoluble particles, by deriving a specific formulation of the Population Balance Equation for soluble particles. Results ISD3 describes the time, concentration and particle size dependent dissolution of particles, their delivery to cells, and the delivery and uptake of ions to cells in in vitro liquid test systems. We applied the model to calculate the particle and ion dosimetry of nanosilver and silver ions in vitro after calibration of two empirical models, one for particle dissolution and one for ion uptake. Total media ion concentration, particle concentration and total cell-associated silver time-courses were well described by the model, across 2 concentrations of 20 and 110 nm particles. ISD3 was calibrated to dissolution data for 20 nm particles as a function of serum protein concentration, but successfully described the media and cell dosimetry time-course for both particles at all concentrations and time points. We also report the finding that protein content in media affects the initial rate of dissolution and the resulting near-steady state ion concentration in solution for the systems we have studied. Conclusions By combining experiments and modeling, we were able to quantify the influence of proteins on silver particle solubility, determine the relative amounts of silver ions and particles in exposed cells, and demonstrate the influence of particle size changes resulting from dissolution on particle delivery to cells in culture. ISD3 is modular and can be adapted to new applications by replacing descriptions of dissolution, sedimentation and boundary conditions with those appropriate for particles other than silver.

COVID-19 pandemic-related traumatic stress (PRTS) symptoms are reported in various populations, but risk factors in older adults with chronic medical conditions, remain understudied. We therefore examined correlates and pre-pandemic predictors of PRTS in older adults with hypertension during COVID-19. Participants in California, aged 61-92 years (n = 95), participated in a pre-pandemic healthy aging trial and later completed a COVID-19 assessment (May to September 2020). Those experiencing ⩾1 PRTS symptom (n = 40), and those without PRTS symptoms (n = 55), were compared. The PRTS+ group had poorer mental and general health and greater impairment in instrumental activities of daily living. Pre-pandemic biomarkers of vascular inflammation did not predict increased odds of PRTS; however, greater pre-pandemic anxiety and female gender did predict PRTS during COVID-19. Our findings highlight PRTS as a threat to healthy aging in older adults with hypertension; targeted approaches are needed to mitigate this burden, particularly for females and those with pre-existing anxiety.

Objective Sports-related injuries, such as facial fractures, are potentially debilitating and may lead to long-term functional and aesthetic deficits in a pediatric patient. In this study, we analyze sports-related facial fractures in the urban pediatric population in an effort to characterize patterns of injury and improve management strategies and outcomes. Methods Retrospective chart review was performed for all facial fractures resulting from sports injuries in the pediatric population at a level-1 trauma center (University Hospital, Newark, NJ). Results Seventeen pediatric patients were identified as having sustained a fracture of the facial skeleton due to sports injury. Mean age was 13.9 years old. A total of 29 fractures were identified. Most common fracture sites included the orbit (n = 12), mandible (n = 5), nasal bone (n = 5), and zygomaticomaxillary complex (n = 3). The most common concomitant injuries included skull fracture (n = 3), intracranial hemorrhage (n = 4), and traumatic brain injury (n = 4). One patient was intubated upon arrival to the emergency department. Hospital admission was required in 13 patients, 4 of which were admitted to an intensive care setting. Nine patients required operative intervention. Mean length of hospital stay was 2.4 days. No patients were expired. Conclusions Sports-related facial fractures are potentially debilitating injuries in the pediatric population. Analysis of fracture pattern and concomitant injuries is imperative to develop effective management strategies and prevention techniques.