Parsing the toxicity paradox: Composition and duration of exposure alter predicted oil spill effects by orders of magnitude.

Oil spilled into an aquatic environment produces oil droplet and dissolved component concentrations and compositions that are highly variable in space and time. Toxic effects on aquatic biota vary with sensitivity of the organism, concentration, composition, environmental conditions, and frequency and duration of exposure to the mixture of oil-derived dissolved compounds. For a range of spill (surface, subsea, blowout) and oil types under different environmental conditions, modeling of oil transport, fate, and organism behavior was used to quantify expected exposures over time for planktonic, motile, and stationary organisms. Different toxicity models were applied to these exposure time histories to characterize the influential roles of composition, concentration, and duration of exposure on aquatic toxicity. Misrepresenting these roles and exposures can affect results by orders of magnitude. Well-characterized laboratory studies for <24-hour exposures are needed to improve toxicity predictions of the typically short-term exposures that characterize spills.

Successful topical treatment of human biofilms using multiple antibiotic elution from a collagen-rich hydrogel.

Chronic non-healing wounds significantly strain modern healthcare systems, affecting 1-2% of the population in developed countries with costs ranging between $28.1 and $96.8 billion annually. Additionally, it has been established that chronic wounds resulting from comorbidities, such as peripheral vascular disease and diabetes mellitus, tend to be polymicrobial in nature. Treatment of polymicrobial chronic wounds with oral and IV antibiotics can result in antimicrobial resistance, leading to more difficult-to-treat wounds. Ideally, chronic ulcers would be topically treated with antibiotic combinations tailored to the microbiome of a patient's wound. We have previously shown that a topical collagen-rich hydrogel (cHG) can elute single antibiotics to inhibit bacterial growth in a manner that is nontoxic to mammalian cells. Here, we analyzed the microbiology of cultures taken from human patients diagnosed with diabetes mellitus suffering from chronic wounds present for more than 6 weeks. Additionally, we examined the safety of the elution of multiple antibiotics from collagen-rich hydrogel in mammalian cells in vivo. Finally, we aimed to create tailored combinations of antibiotics impregnated into cHG to successfully target and treat infections and eradicate biofilms cultured from human chronic diabetic wound tissue. We found that the majority of human chronic wounds in our study were polymicrobial in nature. The elution of multiple antibiotics from cHG was well-tolerated in mammalian cells, making it a potential topical treatment of the polymicrobial chronic wound. Finally, combinations of antibiotics tailored to each patient's microbiome eluted from a collagen-rich hydrogel successfully treated bacterial cultures isolated from patient samples via an in vitro assay.

Modeling Instantaneous Firing Rate of Deep Brain Stimulation Target Neuronal Ensembles in the Basal Ganglia and Thalamus.

OBJECTIVE: Deep brain stimulation (DBS) is an effective treatment for movement disorders, including Parkinson disease and essential tremor. However, the underlying mechanisms of DBS remain elusive. Despite the capability of existing models in interpreting experimental data qualitatively, there are very few unified computational models that quantitatively capture the dynamics of the neuronal activity of varying stimulated nuclei-including subthalamic nucleus (STN), substantia nigra pars reticulata (SNr), and ventral intermediate nucleus (Vim)-across different DBS frequencies. MATERIALS AND METHODS: Both synthetic and experimental data were used in the model fitting; the synthetic data were generated by an established spiking neuron model that was reported in our previous work, and the experimental data were provided using single-unit microelectrode recordings (MERs) during DBS (microelectrode stimulation). Based on these data, we developed a novel mathematical model to represent the firing rate of neurons receiving DBS, including neurons in STN, SNr, and Vim-across different DBS frequencies. In our model, the DBS pulses were filtered through a synapse model and a nonlinear transfer function to formulate the firing rate variability. For each DBS-targeted nucleus, we fitted a single set of optimal model parameters consistent across varying DBS frequencies. RESULTS: Our model accurately reproduced the firing rates observed and calculated from both synthetic and experimental data. The optimal model parameters were consistent across different DBS frequencies. CONCLUSIONS: The result of our model fitting was in agreement with experimental single-unit MER data during DBS. Reproducing neuronal firing rates of different nuclei of the basal ganglia and thalamus during DBS can be helpful to further understand the mechanisms of DBS and to potentially optimize stimulation parameters based on their actual effects on neuronal activity.

An Untargeted Metabolomics Workflow that Scales to Thousands of Samples for Population-Based Studies.

The success of precision medicine relies upon collecting data from many individuals at the population level. Although advancing technologies have made such large-scale studies increasingly feasible in some disciplines such as genomics, the standard workflows currently implemented in untargeted metabolomics were developed for small sample numbers and are limited by the processing of liquid chromatography/mass spectrometry data. Here we present an untargeted metabolomics workflow that is designed to support large-scale projects with thousands of biospecimens. Our strategy is to first evaluate a reference sample created by pooling aliquots of biospecimens from the cohort. The reference sample captures the chemical complexity of the biological matrix in a small number of analytical runs, which can subsequently be processed with conventional software such as XCMS. Although this generates thousands of so-called features, most do not correspond to unique compounds from the samples and can be filtered with established informatics tools. The features remaining represent a comprehensive set of biologically relevant reference chemicals that can then be extracted from the entire cohort's raw data on the basis of m/z values and retention times by using Skyline. To demonstrate applicability to large cohorts, we evaluated >2000 human plasma samples with our workflow. We focused our analysis on 360 identified compounds, but we also profiled >3000 unknowns from the plasma samples. As part of our workflow, we tested 14 different computational approaches for batch correction and found that a random forest-based approach outperformed the others. The corrected data revealed distinct profiles that were associated with the geographic location of participants.

Characterization of Risk Factors Among Individuals with a History of Incarceration Presenting to a Sexually Transmitted Infections Clinic: Implications for HIV and STI Prevention and Care.

More than 2 million people are incarcerated in the United States with many millions more processed through correctional facilities annually. Communities impacted by incarceration are also disproportionately impacted by the HIV and sexually transmitted infection (STI) epidemics. However, relatively little is known about the behaviors that place individuals with a history of incarceration at risk for HIV/STI acquisition. We utilized clinical data from patients presenting to an STI clinic located in Providence, Rhode Island. A latent class analysis was conducted on reported HIV acquisition risk behavior and STI testing results on a total of 1129 encounters where a history of incarceration was reported. A total of three classes were identified. Class 1 (N = 187, 11%), more frequently reported 10+ sexual partners (45%), an STI diagnosis (48%) and sex while intoxicated (86%) in the past year as well as identifying as a man who has sex with other men (60%). Class 2 (N = 57, 5%) was more likely to report giving (53%) and receiving (44%) money/drugs for sex in the past year as well as a history of injecting drugs (61%) and using methamphetamine (60%). Class 3 (N = 885, 78%) most frequently reported 0-2 sexual partners (48%), identified as Black (27%), Hispanic/Latino (69%) and a man who only has sex with women (80%). Class 1 had significantly higher odds ratio (1.8, 95% confidence interval = 1.3-2.5) of testing HIV/STI positive. The results provide important insights into risk subgroups for those with a history of incarceration at risk of HIV/STI acquisition.

Evolutionary history limits species' ability to match colour sensitivity to available habitat light.

The spectrum of light that an animal sees-from ultraviolet to far red light-is governed by the number and wavelength sensitivity of a family of retinal proteins called opsins. It has been hypothesized that the spectrum of light available in an environment influences the range of colours that a species has evolved to see. However, invertebrates and vertebrates use phylogenetically distinct opsins in their retinae, and it remains unclear whether these distinct opsins influence what animals see, or how they adapt to their light environments. Systematically using published visual sensitivity data from across animal phyla, we found that terrestrial animals are more sensitive to shorter and longer wavelengths of light than aquatic animals and that invertebrates are more sensitive to shorter wavelengths of light than vertebrates. Using phylogenetically controlled analyses, we found that closed and open canopy habitat species have different spectral sensitivities when comparing across the Metazoa and excluding habitat generalists, while deepwater animals are no more sensitive to shorter wavelengths of light than shallow-water animals. Our results suggest that animals do adapt to their light environment; however, the invertebrate-vertebrate evolutionary divergence may limit the degree to which animals can perform visual tuning.

Engaging the Community in Pollinator Research: The Effect of Wing Pattern and Weather on Butterfly Behavior.

Community science, which engages students and the public in data collection and scientific inquiry, is often integrated into conservation and long-term monitoring efforts. However, it has the potential to also introduce the public to, and be useful for, sensory ecology and other fields of study. Here we describe a community science project that exposes participants to animal behavior and sensory ecology using the rich butterfly community of Northwest Arkansas, United States. Butterflies use visual signals to communicate and to attract mates. Brighter colors can produce stronger signals for mate attraction but can also unintentionally attract negative attention from predators. Environmental conditions such as weather can affect visual signaling as well, by influencing the wavelengths of light available and subsequent signal detection. However, we do not know whether the signals butterflies present correlate broadly with how they behave. In this study, we collaborated with hundreds of students and community members at the University of Arkansas (UARK) and the Botanical Gardens of the Ozarks (BGO) for over 3.5 years to examine relationships among wing pattern, weather, time of day, behavior, and flower choice. We found that both weather and wing color influenced general butterfly behavior. Butterflies were seen feeding more on cloudy days than on sunny or partly cloudy days. Brown butterflies fed or sat more often, while white butterflies flew more often relative to other butterfly colors. We also found that there was an interaction between the effects of weather and wing color on butterfly behavior. Furthermore, butterfly color predicted the choice of flower colors that butterflies visited, though this effect was influenced by the observer group (UARK student or BGO participant). These results suggest that flower choice may be associated with butterfly wing pattern, and that different environmental conditions may influence butterfly behavior in wing-pattern-specific ways. They also illustrate one way that public involvement in behavioral studies can facilitate the identification of coarse-scale, community-wide behavioral patterns, and lay the groundwork for future studies of sensory niches.

Gay and Bisexual Men's Recommendations for Effective Digital Social Marketing Campaigns to Enhance HIV Prevention and Care Continuity.

Because use of geosocial-networking smartphone applications ('apps') is ubiquitous among men who have sex with men (MSM), online-to-offline service models that include advertisements on these apps may improve engagement with effective HIV prevention and treatment services. Through our formative qualitative study, we conducted individual in-depth interviews (n = 30) and focus group discussions (n = 18) with MSM in Rhode Island to develop a digital social marketing campaign aimed at increasing HIV testing, including how best to reach men by advertising on apps. Qualitative data analysis revealed that participants were frequently exposed to pop-up advertisements on apps. These advertisements are viewed as invasive and, as such, many expressed a preference for other formats (e.g., direct messages, banner advertisements). Men expressed a preference for provocative images and phrases to catch their attention followed with fact-driven messaging to motivate them to engage with services offline. Findings from this study offer several practical recommendations for developing a social marketing campaign that uses advertisements on apps to increase HIV testing among MSM, including using formats other than pop-up advertisements and pairing fact-driven messaging with eye-catching images to direct them to trusted local clinical services.

Leaving Group Effects in a Series of Electrosprayed CcHhN1 Anthracene Derivatives.

We investigate the gas-phase structures and fragmentation pathways of model compounds of anthracene derivatives of the general formula CcHhN1 utilizing tandem mass spectrometry and computational methods. We vary the substituent alkyl chain length, composition, and degree of branching. We find substantial experimental and theoretical differences between the linear and branched congeners in terms of fragmentation thresholds, available pathways, and distribution of products. Our calculations predict that the linear substituents initially isomerize to form lower energy branched isomers prior to loss of the alkyl substituents as alkenes. The rate-determining chemistry underlying these related processes is dominated by the ability to stabilize the alkene loss transition structures. This task is more effectively undertaken by branched substituents. Consequently, analyte lability systematically increased with degree of branching (linear < secondary < tertiary). The resulting anthracen-9-ylmethaniminium ion generated from these alkene loss reactions undergoes rate-limiting proton transfer to enable expulsion of either hydrogen cyanide or CNH. The combination of the differences in primary fragmentation thresholds and degree of radical-based fragmentation processes provide a potential means of distinguishing compounds that contain branched alkyl chain substituents from those with linear ones.

Widespread cerebral haemodynamics disturbances occur early in amyotrophic lateral sclerosis.

We wished to longitudinally assess early changes in cerebral perfusion (CP) and its relationship to cognitive impairment (CI) in ALS. Fourteen ALS patients at time of diagnosis and 11 spousal controls, both without CI, were longitudinally assessed to determine a relationship between CP and incidence of CI in early stage disease. Neuropsychological testing and CP measurements were performed in both ALS and control groups at the initial assessment (T0) and two time-periods post initial assessment, T1 and T2, taken on average 6.1 and 17.0 months after initial assessment (T0), respectively. CT perfusion was used to measure cerebral blood flow, blood volume, and mean transit time (MTT) for all cortical lobes, and subcortical grey and white matter. Two of 14 ALS patients progressed to CI. No differences in CP measurements existed at T0 or T1 between the ALS and control groups. At T2, widespread cortical differences in MTT were present between the two groups. The ALS group had significantly increased MTT in all cortical regions, as well as the thalamus, compared with the control group. Our findings suggest early widespread changes in CP occur outside the motor area in the absence of CI in ALS.

Mean transit time as an index of cerebral perfusion pressure in experimental systemic hypotension.

Early diagnosis of cerebrovascular disease requires the accurate identification of brain regions with compromised cerebral perfusion pressure (CPP). Current clinical measures of CPP are invasive and lack regional information. Dynamic contrast-enhanced imaging provides a means of looking at regional cerebral hemodynamics. The purpose of this study was to determine if any of the parameters associated with dynamic contrast-enhanced imaging could be used as an index for CPP under graded systemic hypotension in a rabbit model. Cerebral blood flow (CBF), cerebral blood volume, mean transit time (MTT), and cerebrovascular reserve (CVR) were measured using Computed Tomography Perfusion in three groups: normotensive (n = 14), mild hypotensive (n = 9), and moderate hypotensive (n = 6). MTT demonstrated the strongest correlation with CPP (ρ = -0.642, P < 0.05). CBF was the only other parameter to demonstrate a statistically significant correlation (ρ = 0.575, P < 0.05). CVR is gaining momentum for diagnosing cerebrovascular disease; however, the technique requires patients to be given a hemodynamic challenge, which could aggravate symptoms and even trigger stroke. The results of this study suggest that the use of MTT, not requiring hemodynamic manipulation, is more sensitive to subtle changes in CPP, as would occur in the early stages of cerebrovascular disease.

Cerebral haemodynamic changes accompanying cognitive impairment in primary lateral sclerosis.

Our objective was to elucidate the relationship between cognitive decline and cerebral haemodynamics in patients with PLS. We examined 18 patients with PLS and contrasted both neuropsychological and cerebral perfusion findings with seven age- and education-matched non-PLS controls. PLS patients were stratified into two groups based on the number of abnormal neuropsychological test scores: 1) cognitively intact PLS patients (PLS; those having zero or one abnormal scores (n =14)), and 2) cognitively-impaired PLS patients (PLSci; those having two or more abnormal test scores (n =4)). There was considerable heterogeneity in level of cognitive functioning with four patients meeting the criteria for cognitive impairment. The findings were highly consistent with a frontotemporal lobar dysfunction. Using CT perfusion to assess cerebral haemodynamics, the PLSci group had increased cerebral blood volume (CBV) and mean transit time (MTT) with reduced cerebral blood flow (CBF). More specifically, MTT was significantly increased (p<0.05) in the PLSci group compared with controls in all regions and affected both grey and white matter, with the exception of the temporal lobe and subcortical parietal white matter. These observations suggest that a subset of PLS patients is subject to cognitive decline and that this process is associated with changes in cerebral haemodynamics.