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Abstract Introduction The Appalachia region of North America is known to have significant health disparities, specifically, worse risk factors and outcomes for stroke. Appalachians are more likely to have comorbidities related to stroke, such as diabetes, obesity, and tobacco use, and are often less likely to have stroke interventions, such as mechanical thrombectomy (MT), for emergent large vessel occlusion (ELVO). As our Comprehensive Stroke Center directly serves stroke subjects from both Appalachian and non-Appalachian areas, inflammatory proteomic biomarkers were identified associated with stroke outcomes specific to subjects residing in Appalachia. Methods There were 81 subjects that met inclusion criteria for this study. These subjects underwent MT for ELVO, and carotid arterial blood samples acquired at time of intervention were sent for proteomic analysis. Samples were processed in accordance with the Blood And Clot Thrombectomy Registry And Collaboration (BACTRAC; clinicaltrials.gov; NCT 03153683). Statistical analyses were utilized to examine whether relationships between protein expression and outcomes differed by Appalachian status for functional (NIH Stroke Scale; NIHSS and Modified Rankin Score; mRS), and cognitive outcomes (Montreal Cognitive Assessment; MoCA). Results No significant differences were found in demographic data or co-morbidities when comparing Appalachian to non-Appalachian subjects. However, time from stroke onset to treatment (last known normal) was significantly longer and edema volume significantly higher in patients from Appalachia. Further, when comparing Appalachian to non-Appalachian subjects, there were significant unadjusted differences in the NIHSS functional outcome. A comprehensive analysis of 184 proteins from Olink proteomic (92 Cardiometabolic and 92 Inflammation panels) showed that the association between protein expression outcomes significantly differed by Appalachian status for seven proteins for the NIHSS, two proteins for the MoCA, and three for the mRS. Conclusion Our study utilizes an ELVO tissue bank and registry to investigate the intracranial/intravascular proteomic environment occurring at the time of thrombectomy. We found that patients presenting from Appalachian areas have different levels of proteomic expression at the time of MT when compared to patients presenting from non-Appalachian areas. These proteins differentially relate to stroke outcome and could be used as prognostic biomarkers, or as targets for novel therapies. The identification of a disparate proteomic response in Appalachian patients provides initial insight to the biological basis for health disparity. Nevertheless, further investigations through community-based studies are imperative to elucidate the underlying causes of this differential response.

Abstract There are numerous mechanisms by which glioblastoma cells evade immunological detection, underscoring the need for strategic combinatorial treatments to achieve appreciable therapeutic effects. However, developing combination therapies is difficult due to dose-limiting toxicities, blood-brain-barrier, and suppressive tumor microenvironment. Glioblastoma is notoriously devoid of lymphocytes driven in part by a paucity of lymphocyte trafficking factors necessary to prompt their recruitment and activation. Herein, we develop a recombinant adeno-associated virus (AAV) gene therapy that enables focal and stable reconstitution of the tumor microenvironment with C-X-C motif ligand 9 (CXCL9), a powerful call-and-receive chemokine for lymphocytes. By manipulating local chemokine directional guidance, AAV-CXCL9 increases tumor infiltration by cytotoxic lymphocytes, sensitizing glioblastoma to anti-PD-1 immune checkpoint blockade in female preclinical tumor models. These effects are accompanied by immunologic signatures evocative of an inflamed tumor microenvironment. These findings support AAV gene therapy as an adjuvant for reconditioning glioblastoma immunogenicity given its safety profile, tropism, modularity, and off-the-shelf capability.

Abstract Marine heatwaves are increasing in frequency and duration, threatening tropical reef ecosystems through intensified coral bleaching events. We examined a strikingly variable spatial pattern of bleaching in Moorea, French Polynesia following a heatwave that lasted from November 2018 to July 2019. In July 2019, four months after the onset of bleaching, we surveyed > 5000 individual colonies of the two dominant coral genera, Pocillopora and Acropora, at 10 m and 17 m water depths, at six forereef sites around the island where temperature was measured. We found severe bleaching increased with colony size for both coral genera, but Acropora bleached more severely than Pocillopora overall. Acropora bleached more at 10 m than 17 m, likely due to higher light availability at 10 m compared to 17 m, or greater daily temperature fluctuation at depth. Bleaching in Pocillopora corals did not differ with depth but instead varied with the interaction of colony size and Accumulated Heat Stress (AHS), in that larger colonies (> 30 cm) were more sensitive to AHS than mid-size (10–29 cm) or small colonies (5–9 cm). Our findings provide insight into complex interactions among coral taxa, colony size, and water depth that produce high spatial variation in bleaching and related coral mortality.

Abstract A network of marine reserves can enhance yield in depleted fisheries by protecting populations, particularly large, old spawners that supply larvae for interspersed fishing grounds. The ability of marine reserves to enhance sustainable fisheries is much less evident. We report empirical evidence of a marine reserve network improving yield regionally for a sustainable spiny lobster fishery, apparently through the spillover of adult lobsters and behavioral adaptation by the fishing fleet. Results of a Before-After, Control-Impact analysis found catch, effort, and Catch-Per-Unit Effort increased after the establishment of marine reserves in the northern region of the fishery where fishers responded by fishing intensively at reserve borders, but declined in the southern region where they vacated once productive fishing grounds. The adaptation of the northern region of the fishery may have been aided by a history of collaboration between fishers, scientists, and managers, highlighting the value of collaborative research and education programs for preparing fisheries to operate productively within a seascape that includes a large marine reserve network.

Collaborative fisheries research programs engage stakeholders in data collection efforts, often with the benefit of increasing transparency about the status and management of natural resources. These programs are particularly important in marine systems, where management of recreational and commercial fisheries have historically been contentious. One such program is the California Collaborative Fisheries Research Program (CCFRP), which was designed in 2006 to engage recreational anglers in the scientific process and evaluate the efficacy of California’s network of marine protected areas. CCFRP began on the Central Coast of California and expanded statewide in 2017 to include six partner institutions in three regions: Northern, Central, and Southern California. To date, over 2,000 volunteer anglers have participated in the program, with many anglers volunteering for multiple years. However, the impacts of outreach, education, and collaborative research on those anglers at the statewide scale are currently unknown. Thus, the objective of the current study was to survey the statewide pool of volunteer anglers to assess the degree to which participation in CCFRP has influenced angler perceptions of MPAs, fisheries management, and conservation. We received 259 completed surveys out of a pool of 1,386 active anglers, equating to an 18.7% response rate. Participation in CCFRP resulted in a significant, positive impact on anglers’ attitudes towards MPAs in California across all regions. Anglers who participated in six or more CCFRP fishing trips had a more positive perception of MPAs than those who participated in fewer trips. Volunteer anglers across all regions perceived that they caught larger fishes, a higher abundance of fishes, and a greater diversity of species inside MPAs, consistent with the ecological findings of the program. These results highlight the benefits of involving community members in collaborative scientific research. Collaboration between researchers and the broader community increases transparency and trust between stakeholders, and results in greater understanding of natural resource dynamics, ultimately producing better management outcomes.

Context. This commentary is based on an innovative approach to the development of predictive analytics. It is centered on the development of predictive models for varying stages of chronic disease through integrating all types of datasets, adds various new features to a theoretically driven data warehousing, creates purpose-specific prediction models, and integrates multi-criteria predictions of chronic disease progression based on a biomedical evolutionary learning platform. After merging across-center databases based on the risk factors identified from modeling the predictors of chronic disease progression, the collaborative investigators could conduct multi-center verification of the predictive model and further develop a clinical decision support system coupled with visualization of a shared decision-making feature for patient care. The Study Problem. The success of health services management research is dependent upon the stability of pattern detection and the usefulness of nosological classification formulated from big-data-to-knowledge research on chronic conditions. However, longitudinal observations with multiple waves of predictors and outcomes are needed to capture the evolution of polychronic conditions. Motivation. The transitional probabilities could be estimated from big-data analysis with further verification. Simulation or predictive models could then generate a useful explanatory pathogenesis of the end-stage-disorder or outcomes. Hence, the clinical decision support system for patient-centered interventions could be systematically designed and executed. Methodology. A customized algorithm for polychronic conditions coupled with constraints-oriented reasoning approaches is suggested. Based on theoretical specifications of causal inquiries, we could mitigate the effects of multiple confounding factors in conducting evaluation research on the determinants of patient care outcomes. This is what we consider as the mechanism for avoiding the black-box expression in the formulation of predictive analytics. The remaining task is to gather new data to verify the practical utility of the proposed and validated predictive equation(s). More specifically, this includes two approaches guiding future research on chronic disease and care management: (1) To develop a biomedical evolutionary learning platform to predict the risk of polychronic conditions at various stages, especially for predicting the micro- and macro-cardiovascular complications experienced by patients with Type 2 diabetes for multidisciplinary care; and (2) to formulate appropriate prescriptive intervention services, such as patient-centered care management interventions for a high-risk group of patients with polychronic conditions. Conclusions. The commentary has identified trends, challenges, and solutions in conducting innovative AI-based healthcare research that can improve understandings of disease-state transitions from diabetes to other chronic polychronic conditions. Hence, better predictive models could be further formulated to expand from inductive (problem solving) to deductive (theory based and hypothesis testing) inquiries in care management research.

Strenuous exercise involving eccentric muscle actions induces skeletal muscle damage resulting in delayed onset muscle soreness (DOMS). Antioxidant supplementation, such as astaxanthin (AX), may alleviate muscle injury following intense exercise. The purpose of this study was to investigate the effect of a four-week course of AX supplementation at 12 mg/day−1 on subjective markers of DOMS, recovery, and performance after a bout of muscle damaging eccentric exercise. Nineteen resistance-trained men (mean ± SD: age, 22.6 ± 2.2 y) completed a between-group design with a four-week supplementation period of 12 mg/day−1 of either AX or a placebo. Subjects completed four trials, with trials One and Three designed to induce muscle damage, consisting of a one repetition maximum test (1RM) for leg-press, followed by five sets of ten repetitions at 65% of 1RM. Trials Two and Four were performance trials, conducted 48 h later and consisting of repetitions to failure at 65%, 70%, and 75% of 1RM. Subjective markers of DOMS and recovery were collected at multiple timepoints post-trial for trials One and Three. Although performance was not affected (p > 0.05), AX supplementation significantly decreased subjective markers of DOMS (p = 0.01) compared to the placebo. The results demonstrated that AX may enhance recovery by reducing DOMS without detriment to performance in resistance-trained men.

Foundation species are essential to ecosystem function, but their role as habitat providers is predicated on their spatial dominance. Worldwide, kelps, seagrasses, corals, and other marine foundation species have declined. This is true also for rockweeds, the canopy-forming analog of subtidal kelp forests in temperate rocky intertidal ecosystems. On the west coast of North America, dense beds of the rockweed Silvetia compressa occur across large biogeographic regions, benefitting numerous species by ameliorating physical stress caused by sun exposure, desiccation, heat, and wave disturbance. Like many rockweed species, Silvetia is long-lived, slow-growing, and short-dispersing – characteristics that reduce its resilience to disturbance. Using a generalized additive mixed-effects model with explicit spatial effects, we analyzed canopy cover data from 30 sites spanning 18 years, and we tested the hypothesis that Silvetia population trends are tightly linked to atmospheric climate conditions, particularly Santa Ana wind events (SAWs): strong, hot, and dry downslope winds that originate inland and move offshore. We found that the rockweed had declined markedly, particularly at sites south of the major biogeographic break, Point Conception (PC), including the California Channel Islands and southern California mainland, and a highly significant negative effect of dewpoint depression, a measure of moisture content in the atmosphere, on Silvetia cover across all three regions in this study. Our results suggest that any increases in the frequency or intensity of SAWs are likely to lead to large declines and possible extirpation of Silvetia, as well as the important ecological services the species provides.

Photodynamic therapy (PDT) is a non-invasive anticancer treatment that uses special photosensitizer molecules (PS) to generate singlet oxygen and other reactive oxygen species (ROS) in a tissue under excitation with red or infrared light. Though the method has been known for decades, it has become more popular recently with the development of new efficient organic dyes and LED light sources. Here we introduce a ternary nanocomposite: water-soluble star-like polymer/gold nanoparticles (AuNP)/temoporfin PS, which can be considered as a third-generation PDT system. AuNPs were synthesized in situ inside the polymer molecules, and the latter were then loaded with PS molecules in an aqueous solution. The applied method of synthesis allows precise control of the size and architecture of polymer nanoparticles as well as the concentration of the components. Dynamic light scattering confirmed the formation of isolated particles (120 nm diameter) with AuNPs and PS molecules incorporated inside the polymer shell. Absorption and photoluminescence spectroscopies revealed optimal concentrations of the components that can simultaneously reduce the side effects of dark toxicity and enhance singlet oxygen generation to increase cancer cell mortality. Here, we report on the optical properties of the system and detailed mechanisms of the observed enhancement of the phototherapeutic effect. Combinations of organic dyes with gold nanoparticles allow significant enhancement of the effect of ROS generation due to surface plasmonic resonance in the latter, while the application of a biocompatible star-like polymer vehicle with a dextran core and anionic polyacrylamide arms allows better local integration of the components and targeted delivery of the PS molecules to cancer cells. In this study, we demonstrate, as proof of concept, a successful application of the developed PDT system for in vitro treatment of triple-negative breast cancer cells under irradiation with a low-power LED lamp (660 nm). We consider the developed nanocomposite to be a promising PDT system for application to other types of cancer.

Abstract Coral reefs offer natural coastal protection by attenuating incoming waves. Here we combine unique coral disturbance-recovery observations with hydrodynamic models to quantify how structural complexity dissipates incoming wave energy. We find that if the structural complexity of healthy coral reefs conditions is halved, extreme wave run-up heights that occur once in a 100-years will become 50 times more frequent, threatening reef-backed coastal communities with increased waves, erosion, and flooding.

This position stand aims to provide an evidence-based summary of the energy and nutritional demands of tactical athletes to promote optimal health and performance while keeping in mind the unique challenges faced due to work schedules, job demands, and austere environments. After a critical analysis of the literature, the following nutritional guidelines represent the position of the International Society of Sports Nutrition (ISSN). General Recommendations Nutritional considerations should include the provision and timing of adequate calories, macronutrients, and fluid to meet daily needs as well as strategic nutritional supplementation to improve physical, cognitive, and occupational performance outcomes; reduce risk of injury, obesity, and cardiometabolic disease; reduce the potential for a fatal mistake; and promote occupational readiness. Military Recommendations Energy demands should be met by utilizing the Military Dietary Reference Intakes (MDRIs) established and codified in Army Regulation 40-25. Although research is somewhat limited, military personnel may also benefit from caffeine, creatine monohydrate, essential amino acids, protein, omega-3-fatty acids, beta-alanine, and L-tyrosine supplementation, especially during high-stress conditions. First Responder Recommendations Specific energy needs are unknown and may vary depending on occupation-specific tasks. It is likely the general caloric intake and macronutrient guidelines for recreational athletes or the Acceptable Macronutrient Distribution Ranges for the general healthy adult population may benefit first responders. Strategies such as implementing wellness policies, setting up supportive food environments, encouraging healthier food systems, and using community resources to offer evidence-based nutrition classes are inexpensive and potentially meaningful ways to improve physical activity and diet habits. The following provides a more detailed overview of the literature and recommendations for these populations.

ABSTRACT Bacillus subtilis is a soil-dwelling bacterium that can form biofilms, or communities of cells surrounded by a self-produced extracellular matrix. In biofilms, genetically identical cells often exhibit heterogeneous transcriptional phenotypes, so that subpopulations of cells carry out essential yet costly cellular processes that allow the entire population to thrive. Surprisingly, the extent of phenotypic heterogeneity and the relationships between subpopulations of cells within biofilms of even in well-studied bacterial systems like B. subtilis remains largely unknown. To determine relationships between these subpopulations of cells, we created 182 strains containing pairwise combinations of fluorescent transcriptional reporters for the expression state of 14 different genes associated with potential cellular subpopulations. We determined the spatial organization of the expression of these genes within biofilms using confocal microscopy, which revealed that many reporters localized to distinct areas of the biofilm, some of which were co-localized. We used flow cytometry to quantify reporter co-expression, which revealed that many cells “multi-task,” simultaneously expressing two reporters. These data indicate that prior models describing B. subtilis cells as differentiating into specific cell types, each with a specific task or function, were oversimplified. Only a few subpopulations of cells, including surfactin and plipastatin producers, as well as sporulating and competent cells, appear to have distinct roles based on the set of genes examined here. These data will provide us with a framework with which to further study and make predictions about the roles of diverse cellular phenotypes in B. subtilis biofilms. IMPORTANCE Many microbes differentiate, expressing diverse phenotypes to ensure their survival in various environments. However, studies on phenotypic differentiation have typically examined only a few phenotypes at one time, thus limiting our knowledge about the extent of differentiation and phenotypic overlap in the population. We investigated the spatial organization and gene expression relationships for genes important in B. subtilis biofilms. In doing so, we mapped spatial gene expression patterns and expanded the number of cell populations described in the B. subtilis literature. It is likely that other bacteria also display complex differentiation patterns within their biofilms. Studying the extent of cellular differentiation in other microbes may be important when designing therapies for disease-causing bacteria, where studying only a single phenotype may be masking underlying phenotypic differentiation relevant to infection outcomes.

Abstract The loss of functional and accreting coral reefs reduces coastal protection and resilience for tropical coastlines. Coral restoration has potential for recovering healthy reefs that can mitigate risks from coastal hazards and increase sustainability. However, scaling up restoration to the large extent needed for coastal protection requires integrated application of principles from coastal engineering, hydrodynamics, and ecology across multiple spatial scales, as well as filling missing knowledge gaps across disciplines. This synthesis aims to identify how scientific understanding of multidisciplinary processes at interconnected scales can advance coral reef restoration. The work is placed within the context of a decision support framework to evaluate the design and effectiveness of coral restoration for coastal resilience. Successfully linking multidisciplinary science with restoration practice will ensure that future large‐scale coral reef restorations maximize protection for at‐risk coastal communities.

Abstract Human mobility is increasingly associated with environmental and climatic factors. One way to explore how mobility and the environment are linked is to review the research on different aspects of the topic. However, so many relevant articles are published that analysis of the literature using conventional techniques is becoming prohibitively arduous. To overcome this constraint, we have applied automated textual analysis. Using unsupervised topic modelling on 3197 peer-reviewed articles on the nexus between mobility and the environment published over the last 30 years, we identify 37 major topics. Based on their language use, the topics were deeply branched into two categories of focus: Impact and Adaptation. The Impact theme is further clustered into sub-themes on vulnerability and residential mobility, while articles within the Adaptation theme are clustered into governance, disaster management and farming. The analysis revealed opportunities for greater collaboration within environmental mobility research, particularly improved integration of adaptation and impact research. The topic analysis also revealed that, in the last 30 years, very little research appears to have been undertaken in migration destinations or on the fate of environmentally influenced migrants during their migration process and after arriving in a new location. There are also research gaps in gender and Indigenous issues within the Impact theme, as well as on adaptive capacity and capacity-building.

Introduction: Students applying for urology residency often have limited resources for obtaining information on prospective programs. Applicants commonly rely on institutional websites to compare program elements. The information on these websites can attract or deter applicants and can have a major impact on application costs, rank lists, and career goals. The objective of this study was to determine the accessibility and content of urology residency program websites. Materials and Methods: A list of accredited urology residency programs was obtained from the American Urological Association residency directory in 2020. A total of 141 program websites were evaluated for the presence of 53 criteria, which were categorized into five groups: Personnel information, applicant information, program information, training/research, and resident benefits. Residencies lacking an available website or functional links were excluded from the study. Results: Of the 53 criteria analyzed, only 24 were featured on more than 50% of the websites. Less than 10% of the programs had available information regarding resident contact information (5.67%), alumni contact information (2.84%), frequently asked questions (9.22%), electives (9.93%), night float (5.67%), and board pass rates (5.67%). The three factors most commonly available included program description (100%), coordinator contact information (88.65%), and clinical sites (87.94%). None of the 141 programs had all 53 criteria available on their website. Conclusions: The majority of current urology residency websites may lack the accessibility and content necessary for candidates to make application decisions for desired programs. Residency programs should consider revising their websites to enhance resident recruitment and facilitate applicants' decision-making process.

We examined the influence of significant 21st century warming on the radial growth patterns of shortleaf pine growing on adjacent north/northeast- and south/southwest-facing slopes (hereafter NS and SS), in the Uwharrie Mountains of North Carolina, USA. Using two chronologies developed from old-growth trees dating to the 1700s, we compared raw radial growth rates (hereafter radial growth) associated with earlywood, latewood, and totalwood during 1935–2020. Both chronologies exhibited similar (r = 0.951, p < 0.001) age-related growth decreases through the 20th century. However, both chronologies experienced abrupt increases in radial growth with less fidelity (r = 0.86, p < 0.001), correlating with the onset of warming mean annual temperatures (r = 0.58, p < 0.01) and warming winter temperatures (r = 0.55, p < 0.05) in 2002. These results show that shortleaf pine growing on both NS and SS have experienced significant radial growth increases since the early 21st century, but that aspect affected growth rates. During 2002–2020, NS radial growth increased significantly (p < 0.05) more than SS earlywood, latewood, and totalwood, indicating that the effects of warming were greater for NS trees. We conclude that old-growth shortleaf pine trees retain climatic sensitivity to significant environmental changes associated with a warming climate and can reverse age-related growth declines.

Abstract The conservation benefits of marine reserves are well established but their contribution to adjacent fisheries via spillover is less certain and context‐dependent. Theoretical predictions do not always match empirical evidence from individual reserves, so carefully designed studies are essential for accurately assessing spillover and its contribution to fisheries. Biomass buildup within reserves, and spillover from reserve borders, also usually takes time to develop. In 2003, a network of no‐take marine reserves was established in the Northern Channel Islands (NCI) of southern California (CA) to conserve biodiversity and to eventually enhance local fisheries through spillover of larvae, juveniles, and adults. The reserve network impacted the local CA spiny lobster (Panulirus interruptus) fishery by removing about 20% of fishing grounds in the NCI. In 2008, a collaborative fisheries research effort detected substantial lobster population increases within reserves, and an indication of the possible spillover of adult lobsters across reserve borders. To estimate whether and how much populations within reserves, and spillover from reserves, have increased through time, we repeated the sampling program 10 years later in 2018 at two of the three original reserves. Scientific trapping was conducted prior to the fishing season along a spatial gradient beginning deep within the reserves to reference sites located outside (≥2 km) of reserve borders. Results showed that legal‐sized lobster abundance in traps (catch per unit effort) increased by 125%–465% deep inside reserves, and by 223%–331% at sites near to reserve borders, and by nearly 400% just outside of reserve borders over the 10‐year period, thus indicating a substantial increase in spillover across reserve borders. A similar pattern was observed in lobster biomass caught in traps at the two reserves. This study demonstrates how spillover scales with biomass buildup and that collaborative fisheries research can be used to assess the efficacy of marine reserves as fishery management tools worldwide.

Abstract Marine Protected Areas (MPAs) are designed to enhance biodiversity and ecosystem services. Some MPAs are also established to benefit fisheries through increased egg and larval production, or the spillover of mobile juveniles and adults. Whether spillover influences fishery landings depend on the population status and movement patterns of target species both inside and outside of MPAs, as well as the status of the fishery and behavior of the fleet. We tested whether an increase in the lobster population inside two newly established MPAs influenced local catch, fishing effort, and catch-per-unit-effort (CPUE) within the sustainable California spiny lobster fishery. We found greater build-up of lobsters within MPAs relative to unprotected areas, and greater increases in fishing effort and total lobster catch, but not CPUE, in fishing zones containing MPAs vs. those without MPAs. Our results show that a 35% reduction in fishing area resulting from MPA designation was compensated for by a 225% increase in total catch after 6-years, thus indicating at a local scale that the trade-off of fishing ground for no-fishing zones benefitted the fishery.

Abstract Coastal marine habitats continue to be degraded, thereby compelling large‐scale restoration in many parts of the world. Whether restored habitats function similarly to natural habitats and fully recover lost ecosystem services is unclear. In estuaries, oyster reefs have been degraded by multiple anthropogenic activities including destructive fishing practices and reduced water quality, motivating restoration to maintain oyster fisheries and other ecosystem services, often at relatively high cost. We compared fish and invertebrate communities on recently restored (0–1 year post‐restoration), older restored (3–4 years post‐restoration), and natural oyster reefs to determine if and when restored reefs support functionally similar faunal communities. To test the influence of landscape setting on the faunal communities, the restored and natural reefs, as well as a control without reef present, were distributed among three landscapes (on the edge of salt marsh away from seagrass [salt marsh landscape], on mudflats [mudflat landscape], and near to seagrass and salt marsh [seagrass landscape]). Oyster density and biomass were greatest on restored reef habitat, as were those of non‐oyster bivalve species. Total abundance of invertebrates was much greater on oyster reefs than in control plots, regardless of reef or landscape type, yet were frequently highest on older restored reefs. Meanwhile, juvenile fish densities were greatest on natural reefs, at intermediate densities on older restored reefs, and least abundant on controls. When comparing the effects of reef age and landscape setting, juvenile fish densities were greatest on younger reefs within the mudflat landscape. Collectively, these results indicate that oyster reefs harbor higher densities of resident invertebrate prey, which may explain why reef habitat is also important for juvenile fish. Laboratory and field experiments supported the notion that gag grouper (a predatory demersal fish) forage more effectively on oyster reefs than on unstructured mud bottom, whereas our experiments suggest that flounders that utilize oyster reefs likely forage on adjacent mud bottom. Because landscape setting influenced fish and invertebrate communities on restored reefs, the ecological consequences of landscape setting should be incorporated into restoration decision making and site selection to enhance the recovery of ecosystem goods and services.

BackgroundAdult lead encephalopathy is a rare but critical condition to recognize in modern healthcare settings. Few reports have described the medical and neurosurgical management of severe adult lead encephalopathy.Case PresentationA 22 year old woman presented with severe headache, anemia, vomiting, 40-lb weight loss, and constipation. At the time of presentation, she had extensive colonic radiopaque material and a serum lead concentration of 87 mcg/dl (normal

Background: Seeding of pathology related to Alzheimer’s disease (AD) and Lewy body disease (LBD) by tissue homogenates or purified protein aggregates in various model systems has revealed prion-like properties of these disorders. Typically, these homogenates are injected into adult mice stereotaxically. Injection of brain lysates into newborn mice represents an alternative approach of delivering seeds that could direct the evolution of amyloid-β (Aβ) pathology co-mixed with either tau or α-synuclein (αSyn) pathology in susceptible mouse models. Methods: Homogenates of human pre-frontal cortex were injected into the lateral ventricles of newborn (P0) mice expressing a mutant humanized amyloid precursor protein (APP), human P301L tau, human wild type αSyn, or combinations thereof. The homogenates were prepared from AD and AD/LBD cases displaying variable degrees of Aβ pathology and co-existing tau and αSyn deposits. Behavioral assessments of APP transgenic mice injected with AD brain lysates were conducted. For comparison, homogenates of aged APP transgenic mice that preferentially exhibit diffuse or cored deposits were similarly injected into the brains of newborn APP mice. Results: We observed that lysates from the brains with AD (Aβ+, tau+), AD/LBD (Aβ+, tau+, αSyn+), or Pathological Aging (Aβ+, tau-, αSyn-) efficiently seeded diffuse Aβ deposits. Moderate seeding of cerebral amyloid angiopathy (CAA) was also observed. No animal of any genotype developed discernable tau or αSyn pathology. Performance in fear-conditioning cognitive tasks was not significantly altered in APP transgenic animals injected with AD brain lysates compared to nontransgenic controls. Homogenates prepared from aged APP transgenic mice with diffuse Aβ deposits induced similar deposits in APP host mice; whereas homogenates from APP mice with cored deposits induced similar cored deposits, albeit at a lower level. Conclusions: These findings are consistent with the idea that diffuse Aβ pathology, which is a common feature of human AD, AD/LBD, and PA brains, may arise from a distinct strain of misfolded Aβ that is highly transmissible to newborn transgenic APP mice. Seeding of tau or αSyn comorbidities was inefficient in the models we used, indicating that additional methodological refinement will be needed to efficiently seed AD or AD/LBD mixed pathologies by injecting newborn mice.

Abstract Background Recombinant adeno-associated virus (rAAV) is widely used in the neuroscience field to manipulate gene expression in the nervous system. However, a limitation to the use of rAAV vectors is the time and expense needed to produce them. To overcome this limitation, we evaluated whether unpurified rAAV vectors secreted into the media following scalable PEI transfection of HEK293T cells can be used in lieu of purified rAAV. Methods We packaged rAAV2-EGFP vectors in 30 different wild-type and mutant capsids and subsequently collected the media containing secreted rAAV. Genomic titers of each rAAV vector were assessed and the ability of each unpurified virus to transduce primary mixed neuroglial cultures (PNGCs), organotypic brain slice cultures (BSCs) and the mouse brain was evaluated. Results There was ~ 40-fold wide variance in the average genomic titers of the rAAV2-EGFP vector packaged in the 30 different capsids, ranging from a low ~ 4.7 × 1010 vector genomes (vg)/mL for rAAV2/5-EGFP to a high of ~ 2.0 × 1012 vg/mL for a capsid mutant of rAAV2/8-EGFP. In PNGC studies, we observed a wide range of transduction efficiency among the 30 capsids evaluated, with the rAAV2/6-EGFP vector demonstrating the highest overall transduction efficiency. In BSC studies, we observed robust transduction by wild-type capsid vectors rAAV2/6, 2/8 and 2/9, and by capsid mutants of rAAV2/1, 2/6, and 2/8. In the in vivo somatic brain transgenesis (SBT) studies, we found that intra-cerebroventricular injection of media containing unpurified rAAV2-EGFP vectors packaged with select mutant capsids resulted in abundant EGFP positive neurons and astrocytes in the hippocampus and forebrain of non-transgenic mice. We demonstrate that unpurified rAAV can express transgenes at equivalent levels to lysate-purified rAAV both in vitro and in vivo. We also show that unpurified rAAV is sufficient to drive tau pathology in BSC and neuroinflammation in vivo, recapitulating previous studies using purified rAAV. Conclusions Unpurified rAAV vectors secreted into the media can efficiently transduce brain cells in vitro and in vivo, providing a cost-effective way to manipulate gene expression. The use of unpurified virus will greatly reduce costs of exploratory studies and further increase the utility of rAAV vectors for standard laboratory use.

Abstract A long‐held paradigm is that water depth has a strong influence on coral performance mainly due to the rapid attenuation of light. Yet, many factors influence coral performance across reefscapes, including corallivory. How coral demographic performance changes with water depth and the intensity of corallivory has not been tested but is intriguing because fish abundance and community composition change substantially with water depth. We tested the independent and interactive effects of water depth and corallivory on the growth rates of a reef‐building coral, Acropora hyacinthus common throughout the Indo‐Pacific. Our study was conducted on the fore reef of Mo’orea, French Polynesia, where shallower coral populations have recovered more quickly than deeper populations after a major disturbance that culminated in 2010. Contrary to predictions of the light‐attenuation paradigm, water depth (5 vs. 10 vs. 17 m) did not influence coral growth, regardless from what depth corals were collected. However, the effects of corallivory varied by depth as coral predators significantly reduced the growth rates of A. hyacinthus at 5 and 10 m depth, where the abundance of corallivores and rates of corallivory were greatest. There were no effects of predation on coral growth rates at 17 m, where the intensity of corallivory was lowest. Our results imply that corallivory is not a dominant factor establishing the distribution of A. hyacinthus corals across water depth. Instead, we found that partial predation may limit the potential for recovery of A. hyacinthus in relatively shallow water, where this coral is most abundant. As the frequency and intensity of disturbances impacting coral reef ecosystems increase with climate change and other anthropogenic factors, chronic predation on corals by corallivorous fish may play an increasingly important role in coral community recovery.

Susan Cutter,1 Christine Guelcher,2 Susan Hunter,3 Dawn Rotellini,4 Spencer Dunn,5 David L Cooper61Penn Comprehensive Hemophilia and Thrombosis Program, Hospital of the University of Pennsylvania, Philadelphia, PA, USA; 2Comprehensive Hemostasis and Thrombosis Program, Children’s National Health System, Washington, DC, USA; 3Hemostasis and Thrombosis Center, University Hospitals Cleveland Medical Center, Cleveland, OH, USA; 4National Hemophilia Foundation, New York, NY, USA; 5Center for Comprehensive Care and Diagnosis of Inherited Bleeding Disorders, Orange, CA, USA; 6Novo Nordisk Inc., Plainsboro, NJ, USACorrespondence: Susan CutterPenn Comprehensive Hemophilia and Thrombosis Program, Hospital of the University of Pennsylvania, 3400 Spruce St – 3 rd Fl Dulles, Philadelphia, PA 19104, USATel +1 215 615 8007Email Susan.Cutter@uphs.upenn.eduBackground: The B-HERO-S study evaluated the impact of mild to severe hemophilia B on the lives of affected adults and children. Here, we assessed the impact of hemophilia B on relationships.Methods: US adults with hemophilia B and caregivers of affected children completed separate online surveys that included questions regarding impact of the disease on interpersonal relationships.Results: Most (88%) of the 299 adults completing the survey had mild to moderate hemophilia B. Of those, 54% were married or in a long-term relationship, and 44% were single. Most adults (87%) reported that hemophilia affected their ability to form close relationships with partners or prospective partners; 35% were very/quite dissatisfied with the support received from a previous partner. Nearly all participants (98%) were very/quite satisfied with the support received from their current partner. Most were very/quite satisfied with the support from family (87%) and friends (96%). Most participants reported a negative reaction or experience as a result of disclosing their hemophilia (friend/colleague/employer, 76%/80%/82%, respectively). Of 150 caregivers of children with mostly mild to moderate hemophilia (74%), 89% were married or in a long-term relationship, and most felt very well/quite supported by their partner (98%) and family (92%). Most felt very/quite satisfied with the support of teachers (94%), children at school (80%), and other adults in regular contact (72%). Most caregivers reported negative experiences telling a friend (76%) or having their child tell a friend (69%) about the child’s hemophilia; 43% reported that their child was bullied because of his/her hemophilia.Conclusion: Although the impact of severe hemophilia on relationships has been reported in HERO and other studies, B-HERO-S suggested that mild to moderate hemophilia B also significantly influences relationships of affected men/women and boys/girls, especially in disclosing their diagnosis, selecting a partner, and feeling bullied by peers/colleagues.Keywords: support, partners, relationship satisfaction, caregivers, interpersonal relationships

Abstract Purpose The purpose of this study is to evaluate the impact of two methods of reporting planned dose distributions on the Gamma analysis pass rates for comparison with measured 2D film dose and simulated delivered 3D dose for proton pencil beam scanning treatment of the Imaging and Radiation Oncology Core (IROC) proton lung and liver mobile phantoms. Methods and materials Four-dimensional (4D) computed-tomography (CT) image sets were acquired for IROC proton lung and liver mobile phantoms, which include dosimetry inserts that contains targets, thermoluminescent dosimeters and EBT2 films for plan dose verification. 4DCT measured fixed motion magnitudes were 1.3 and 1.0 cm for the lung and liver phantoms, respectively. To study the effects of motion magnitude on the Gamma analysis pass rate, three motion magnitudes for each phantom were simulated by creating virtual 4DCT image sets with motion magnitudes scaled from the scanned phantom motion by 50, 100, and 200%. The internal target volumes were contoured on the maximum intensity projection CTs of the 4DCTs for the lung phantom and on the minimum intensity projection CTs of the 4DCTs for the liver phantom. Treatment plans were optimized on the average intensity projection (AVE) CTs of the 4DCTs using the RayStation treatment planning system. Plan doses were calculated on the AVE CTs, which was defined as the planned AVE dose (method one). Plan doses were also calculated on all 10 phase CTs of the 4DCTs and were registered using target alignment to and equal-weight-summed on the 50% phase (T50) CT, which was defined as the planned 4D dose (method two). The planned AVE doses and 4D doses for phantom treatment were reported to IROC, and the 2D-2D Gamma analysis pass rates for measured film dose relative to the planned AVE and 4D doses were compared. To evaluate motion interplay effects, simulated delivered doses were calculated for each plan by sorting spots into corresponding respiratory phases using spot delivery time recorded in the log files by the beam delivery system to calculate each phase dose and accumulate dose to the T50 CTs. Ten random beam starting phases were used for each beam to obtain the range of the simulated delivered dose distributions. 3D-3D Gamma analyses were performed to compare the planned 4D/AVE doses with simulated delivered doses. Results The planned 4D dose matched better with the measured 2D film dose and simulated delivered 3D dose than the planned AVE dose. Using planned 4D dose as institution reported planned dose to IROC improved IROC film dose 2D-2D Gamma analysis pass rate from 92 to 96% on average for three films for the lung phantom (7% 5 mm), and from 92 to 94% in the sagittal plane for the liver phantom (7% 4 mm), respectively, compared with using the planned AVE dose. The 3D-3D Gamma analysis (3% 3 mm) pass rate showed that the simulated delivered doses for lung and liver phantoms using 10 random beam starting phases for each delivered beam matched the planned 4D dose significantly better than the planned AVE dose for phantom motions larger than 1 cm (p ≤ 0.04). Conclusions It is recommended to use the planned 4D dose as the institution reported planned dose to IROC to compare with the measured film dose for proton mobile phantoms to improve film Gamma analysis pass rate in the IROC credentialing process.

High-stress occupations (ie, firefighters, military personnel, police officers, etc.) are often plagued by cardiometabolic diseases induced by exposure to chronic stressors. Interrupted sleep cycles, poor dietary patterns, lack of physical activity, and smoke exposure along with simultaneous psychological stressors promote chronic low-grade inflammation and excessive oxidative stress. Collectively, these data suggest that practical interventions which might mitigate the underlying pathologies of these cardiometabolic diseases are warranted. Ketones, specifically R -βHB, modulates intracellular signaling cascades such as the cellular redox ratios of NAD + /NADH, the activity of NAD dependent deacetylases SIRT1 and SIRT3, and promotes a robust mitochondrial environment which favors reductions in oxidative stress and inflammation. To date, the literature examining R -βHB as a signaling metabolite has mostly been performed from endogenous R -βHB production achieved through nutritional ketosis or cell culture and mouse models using exogenous R -βHB. To the authors knowledge, only 1 study has attempted to report on the effects of exogenous ketones and the mitigation of oxidative stress/inflammation. Therefore, the scope of this review is to detail the mechanisms of R -βHB as a signaling metabolite and the role that exogenous ketones might play in mitigating diseases in individuals serving in high-stress occupations.

ABSTRACT Prebiotics confer benefits to human health, often by promoting the growth of gut bacteria that produce metabolites valuable to the human body, such as short-chain fatty acids (SCFAs). While prebiotic selection has strongly focused on maximizing the production of SCFAs, less attention has been paid to gases, a by-product of SCFA production that also has physiological effects on the human body. Here, we investigate how the content and volume of gas production by human gut microbiota are affected by the chemical composition of the prebiotic and the community composition of the microbiota. We first constructed a linear system model based on mass and electron balance and compared the theoretical product ranges of two prebiotics, inulin and pectin. Modeling shows that pectin is more restricted in product space, with less potential for H2 but more potential for CO2 production. An ex vivo experimental system showed pectin degradation produced significantly less H2 than inulin, but CO2 production fell outside the theoretical product range, suggesting fermentation of fecal debris. Microbial community composition also impacted results: methane production was dependent on the presence of Methanobacteria, while interindividual differences in H2 production during inulin degradation were driven by a Lachnospiraceae taxon. Overall, these results suggest that both the chemistry of the prebiotic and the composition of the microbiota are relevant to gas production. Metabolic processes that are relatively prevalent in the microbiome, such as H2 production, will depend more on substrate, while rare metabolisms such as methanogenesis depend more strongly on microbiome composition. IMPORTANCE Prebiotic fermentation in the gut often leads to the coproduction of short-chain fatty acids (SCFAs) and gases. While excess gas production can be a potential problem for those with functional gut disorders, gas production is rarely considered during prebiotic design. In this study, we combined the use of theoretical models and an ex vivo experimental platform to illustrate that both the chemical composition of the prebiotic and the community composition of the human gut microbiota can affect the volume and content of gas production during prebiotic fermentation. Specifically, more prevalent metabolic processes such as hydrogen production were strongly affected by the oxidation state of the probiotic, while rare metabolisms such as methane production were less affected by the chemical nature of the substrate and entirely dependent on the presence of Methanobacteria in the microbiota.

Abstract Tropical reefs often undergo acute disturbances that result in landscape-scale loss of coral. Due to increasing threats to coral reefs from climate change and anthropogenic perturbations, it is critical to understand mechanisms that drive recovery of these ecosystems. We explored this issue on the fore reef of Moorea, French Polynesia, following a crown-of-thorns seastar outbreak and cyclone that dramatically reduced cover of coral. During the five-years following the disturbances, the rate of re-establishment of coral cover differed systematically around the triangular-shaped island; coral cover returned most rapidly at sites where the least amount of live coral remained after the disturbances. Although sites differed greatly in the rate of return of coral, all showed at least some evidence of re-assembly to their pre-disturbance community structure in terms of relative abundance of coral taxa and other benthic space holders. The primary driver of spatial variation in recovery was recruitment of sexually-produced corals; subsequent growth and survivorship were less important in shaping the spatial pattern. Our findings suggest that, although the coral community has been resilient, some areas are unlikely to attain the coral cover and taxonomic structure they had prior to the most recent disturbances before the advent of another landscape-scale perturbation.

Abstract Alzheimer’s Disease (AD) is the most prevalent progressive neurodegenerative disease; to date, no AD therapy has proven effective in delaying or preventing the disease course. In the search for novel therapeutic targets in AD, it has been shown that increased chronic psychologic stress is associated with AD risk. Subsequently, biologic pathways underlying psychologic stress have been identified and shown to be able to exacerbate AD relevant pathologies. In this review, we summarize the literature relevant to the association between psychologic stress and AD, focusing on studies investigating the effects of stress paradigms on transgenic mouse models of Amyloid-β (Aβ) and tau pathologies. In recent years, a substantial amount of research has been done investigating a key stress-response mediator, corticotropin-releasing hormone (CRH), and its interactions with AD relevant processes. We highlight attempts to target the CRH signaling pathway as a therapeutic intervention in these transgenic mouse models and discuss how targeting this pathway is a promising avenue for further investigation.

Pre-mRNA alternative splicing is a conserved mechanism for eukaryotic cells to leverage existing genetic resources to create a diverse pool of protein products. It is regulated in coordination with other events in RNA metabolism such as transcription, polyadenylation, RNA transport, and nonsense-mediated decay via protein networks. SERINE/ARGININE-RICH 45 (SR45) is thought to be a neutral splicing regulator. It is orthologous to a component of the apoptosis and splicing-associated protein (ASAP) complex functioning to regulate RNA metabolism at multiple levels. Within this context, we try to understand why the sr45-1 mutant Arabidopsis has malformed flowers, delayed flowering time, and increased disease resistance. Prior studies revealed increased expression for some disease resistance genes and the flowering suppressor Flowering Locus C (FLC) in sr45-1 mutants and a physical association between SR45 and reproductive process-related RNAs. Here, we used Tandem Mass Tag-based quantitative mass spectrometry to compare the protein abundance from inflorescence between Arabidopsis wild-type (Col-0) and sr45-1 mutant plants. A total of 7,206 proteins were quantified, of which 227 proteins exhibited significantly different accumulation. Only a small percentage of these proteins overlapped with the dataset of RNAs with altered expression. The proteomics results revealed that the sr45-1 mutant had increased amounts of enzymes for glucosinolate biosynthesis which are important for disease resistance. Furthermore, the mutant inflorescence had a drastically reduced amount of the Sin3-associated protein 18 (SAP18), a second ASAP complex component, despite no significant reduction in SAP18 RNA. The third ASAP component protein, ACINUS, also had lower abundance without significant RNA changes in the sr45-1 mutant. To test the effect of SR45 on SAP18, a SAP18-GFP fusion protein was overproduced in transgenic Arabidopsis Col-0 and sr45-1 plants. SAP18-GFP has less accumulation in the nucleus, the site of activity for the ASAP complex, without SR45. Furthermore, transgenic sr45-1 mutants overproducing SAP18-GFP expressed even more FLC and had a more severe flowering delay than non-transgenic sr45-1 mutants. These results suggest that SR45 is required to maintain the wild-type level of SAP18 protein accumulation in the nucleus and that FLC-regulated flowering time is regulated by the correct expression and localization of the ASAP complex.

Marine protected areas (MPAs) are an important tool for conservation but can be victims of their own success—higher fish biomass within MPAs create incentives to poach. This insight underpins the finding that fishing persists in most MPAs worldwide, and it raises questions about MPA monitoring and enforcement. We propose a novel institution to enhance MPA design—a ‘Conservation Finance Area (CFA)’—that utilizes leased fishing zones inside of MPAs, fed by spillover, to finance monitoring and enforcement and achieve greater conservation success. Using a bioeconomic model we show that CFAs can fully finance enforcement, deter illegal fishing, and ultimately maximize fish biomass. Moreover, we show that unless a large, exogenous, and perpetual enforcement budget is available, implementing a CFA in a no-take MPA would always result in higher biomass than without. We also explore real-world enabling conditions, providing a plausible funding pathway to improve outcomes for existing and future MPAs.

Droplet generation has been widely used in conventional two-dimensional (2D) microfluidic devices, and has recently begun to be explored for 3D-printed droplet generators. A major challenge for 3D-printed devices is preventing water-in-oil droplets from sticking to the interior surfaces of the droplet generator when the device is not made from hydrophobic materials. In this study, two approaches were investigated and shown to successfully form droplets in 3D-printed microfluidic devices. First, several printing resin candidates were tested to evaluate their suitability for droplet formation and material properties. We determined that a hexanediol diacrylate/lauryl acrylate (HDDA/LA) resin forms a solid polymer that is sufficiently hydrophobic to prevent aqueous droplets (in a continuous oil flow) from attaching to the device walls. The second approach uses a fully 3D annular channel-in-channel geometry to form microfluidic droplets that do not contact channel walls, and thus, this geometry can be used with hydrophilic resins. Stable droplets were shown to form using the channel-in-channel geometry, and the droplet size and generation frequency for this geometry were explored for various flow rates for the continuous and dispersed phases.

Objective: This review evaluates current literature on intensity selection, perceptual responses, activity enjoyment and adherence rates of exergaming. Methods: The literature search identified manuscripts that investigated exercise intensity, perceptual responses, or exercise adherence of exergaming in young adults. Results: Based on results of 29 studies, the current review suggest some exergaming activities have the potential to elicit moderate to vigorous exercise intensity and could potentially be substituted for traditional exercise. Additionally, exergame activities may aid in the start of exercise adherence by lowering the individual's perceived exertion when playing exergames. Exergaming not only has the potential to enhance enjoyment through an exercise objective but also through the distracting nature of video games. Conclusions: Exergaming shows potential to be substituted for traditional exercise and could offer a new, varied form of exercise for sedentary individuals. Future research should examine the influence of exergaming experience on intensity selection and adherence rates.

The coordination of complex tumor processes requires cells to rapidly modify their phenotype and is achieved by direct cell-cell communication through gap junction channels composed of connexins. Previous reports have suggested that gap junctions are tumor suppressive based on connexin 43 (Cx43), but this does not take into account differences in connexin-mediated ion selectivity and intercellular communication rate that drive gap junction diversity. We find that glioblastoma cancer stem cells (CSCs) possess functional gap junctions that can be targeted using clinically relevant compounds to reduce self-renewal and tumor growth. Our analysis reveals that CSCs express Cx46, while Cx43 is predominantly expressed in non-CSCs. During differentiation, Cx46 is reduced, while Cx43 is increased, and targeting Cx46 compromises CSC maintenance. The difference between Cx46 and Cx43 is reflected in elevated cell-cell communication and reduced resting membrane potential in CSCs. Our data demonstrate a pro-tumorigenic role for gap junctions that is dependent on connexin expression.

Cu is an essential trace element but can be highly toxic to aquatic organisms at elevated concentrations. Greater use of CuO engineered nanoparticles (ENPs) may lead to increased concentrations of CuO ENPs in aquatic environments causing potential ecological injury. We examined the toxicity of CuO ENPs to marine mussels and the influence of mussels on the fate and transport of CuO ENPs. We exposed marine mussels to 1, 2, or 3 mg L−1 CuO ENPs for four weeks, and measured clearance rate, rejection, excretion and accumulation of Cu, and mussel shell growth. Mussel clearance rate was 48% less, and growth was 68% less, in mussels exposed to 3 mg L−1 than in control animals. Previous studies show 100% mortality at 1 mg Cu L−1, suggesting that CuO ENPs are much less toxic than ionic Cu, probably due to the slow dissolution rate of the ENPs. Mussels rejected and excreted CuO ENPs in biodeposits containing as much as 110 mg Cu g−1, suggesting the potential for magnification in sediments. Mussels exposed to 3 mg L−1 CuO ENPs accumulated 79.14 ± 12.46 µg Cu g−1 dry weight, which was 60 times more Cu than in control animals. Our results suggest that mussels have the potential to influence the fate and transport of CuO ENPs and potentially cause magnification of CuO ENPs in mussel bed communities, creating a significant source of Cu to marine benthos.

Background: Postural stability and cognitive performance are challenged in firefighters. The purpose of this investigation was to examine the impact of 7-day ketone supplementation on postural stability, cognitive performance, and muscular activation before and after a physiological workload. Methods: Nine professional firefighters completed two experimental sessions (pre- and post-workload) in a counterbalanced, double-blind design. Participants ingested either a ketone salt (KS) or placebo (PLA) daily for seven days, and had an eighth ingestion 30 min prior to testing. Each experimental testing consisted of maximal voluntary contractions (MVIC) for four muscles (knee flexors—BF, extensor—VM, ankle dorsiflexors—TA, and plantar flexors—MG) using electromyography and postural stability testing (eyes open (EO), eyes closed (EC), and eyes open-dual-task using a FitLight™ system (EOT)), before (pre-workload) and after (post-workload) a simulated physiological workload. The workload consisted of 35 min steady state exercise at 60% of peak oxygen consumption wearing firefighter personal protective equipment (PPE). Results: Significant differences were limited to time effects (pre-workload vs. post-workload), with no differences between groups (KS vs. PLA). Significantly lower muscle activity in VM, TA, and MG during MVIC, greater postural sway and muscle activity in BF during EC and EOT, and slower response time during EOT were evident post-workload. Conclusions: A 7-day ketone supplementation does not impact postural stability, muscle activity, and cognitive tasks, but a fatiguing workload causes significant performance reduction.

The increased use of engineered nanoparticles (ENPs) in consumer products raises the concern of environmental release and subsequent impacts in natural communities. We tested for physiological and demographic impacts of ZnO, a prevalent metal oxide ENP, on the mussel Mytilus galloprovincialis. We exposed mussels of two size classes,

Nanoparticulate titanium dioxide (TiO(2)) is highly photoactive, and its function as a photocatalyst drives much of the application demand for TiO(2). Because TiO(2) generates reactive oxygen species (ROS) when exposed to ultraviolet radiation (UVR), nanoparticulate TiO(2) has been used in antibacterial coatings and wastewater disinfection, and has been investigated as an anti-cancer agent. Oxidative stress mediated by photoactive TiO(2) is the likely mechanism of its toxicity, and experiments demonstrating cytotoxicity of TiO(2) have used exposure to strong artificial sources of ultraviolet radiation (UVR). In vivo tests of TiO(2) toxicity with aquatic organisms have typically shown low toxicity, and results across studies have been variable. No work has demonstrated that photoactivity causes environmental toxicity of TiO(2) under natural levels of UVR. Here we show that relatively low levels of ultraviolet light, consistent with those found in nature, can induce toxicity of TiO(2) nanoparticles to marine phytoplankton, the most important primary producers on Earth. No effect of TiO(2) on phytoplankton was found in treatments where UV light was blocked. Under low intensity UVR, ROS in seawater increased with increasing nano-TiO(2) concentration. These increases may lead to increased overall oxidative stress in seawater contaminated by TiO(2), and cause decreased resiliency of marine ecosystems. Phototoxicity must be considered when evaluating environmental impacts of nanomaterials, many of which are photoactive.

Fishing can trigger trophic cascades that alter community structure and dynamics and thus modify ecosystem attributes. We combined ecological data of sea urchin and macroalgal abundance with fishery data of spiny lobster (Panulirus interruptus) landings to evaluate whether: (1) patterns in the abundance and biomass among lobster (predator), sea urchins (grazer), and macroalgae (primary producer) in giant kelp forest communities indicated the presence of top-down control on urchins and macroalgae, and (2) lobster fishing triggers a trophic cascade leading to increased sea urchin densities and decreased macroalgal biomass. Eight years of data from eight rocky subtidal reefs known to support giant kelp forests near Santa Barbara, CA, USA, were analyzed in three-tiered least-squares regression models to evaluate the relationships between: (1) lobster abundance and sea urchin density, and (2) sea urchin density and macroalgal biomass. The models included reef physical structure and water depth. Results revealed a trend towards decreasing urchin density with increasing lobster abundance but little evidence that urchins control the biomass of macroalgae. Urchin density was highly correlated with habitat structure, although not water depth. To evaluate whether fishing triggered a trophic cascade we pooled data across all treatments to examine the extent to which sea urchin density and macroalgal biomass were related to the intensity of lobster fishing (as indicated by the density of traps pulled). We found that, with one exception, sea urchins remained more abundant at heavily fished sites, supporting the idea that fishing for lobsters releases top-down control on urchin grazers. Macroalgal biomass, however, was positively correlated with lobster fishing intensity, which contradicts the trophic cascade model. Collectively, our results suggest that factors other than urchin grazing play a major role in controlling macroalgal biomass in southern California kelp forests, and that lobster fishing does not always catalyze a top-down trophic cascade.

We tested whether three commercial forms (uncoated, organic coating, and iron oxide coating) of nano zero-valent iron (nZVI) are toxic to freshwater and marine organisms, specifically three species of marine phytoplankton, one species of freshwater phytoplankton, and a freshwater zooplankton species (Daphnia magna), because these organisms may be exposed downstream of where nZVI is applied to remediate polluted soil. The aggregation and reactivity of the three types of nZVI varied considerably, which was reflected in their toxicity. Since levels of Fe(2+) and Fe(3+) increase as the nZVI react, we also evaluated their toxicity independently. All four phytoplankton species displayed decreasing population growth rates, and Daphnia magna showed increasing mortality, in response to increasing levels of nZVI, and to a lesser degree with increasing Fe(2+) and Fe(3+). All forms of nZVI aggregated in soil and water, especially in the presence of a high concentration of calcium ions in groundwater, thus reducing their transports through the environment. However, uncoated nZVI aggregated extremely rapidly, thus vastly reducing the probability of environmental transport and potential for toxicity. This information can be used to design a risk management strategy to arrest the transport of injected nZVI beyond the intended remediation area, by injecting inert calcium salts as a barrier to transport.