JTH in Clinic: Management of Low-risk PE.

Pulmonary embolism (PE) is a common cardiovascular disease diagnosis in emergency departments that can be associated with significant morbidity and mortality. One of the first steps after diagnosing PE is to risk stratify for adverse outcomes using risk scores such as PE Severity Index and European Society of Cardiology risk scheme. While intermediate and high-risk PE patients should be admitted to the hospital, there is increasing evidence to support early discharge and home-based anticoagulation therapy for low-risk patients. The Hestia criteria encompass many of the clinicians' considerations for who may be suitable for early discharge, considering both medical and social factors. Additionally, professional guidelines have provided algorithms on determining which low risk patients may be suitable. Despite this, low risk acute PE patients are still often admitted for inpatient treatment. In this review, we present a case-based approach on how to risk stratify and evaluate patients who may be good candidates for early discharge and home therapy.

Evaluation of the Goss-modified solvation parameter model for the characterization of biphasic systems and descriptor assignments.

The solvation parameter model uses six descriptors identified as excess molar refraction, E, dipolarity/polarizability, S, overall hydrogen-bond acidity, A, overall hydrogen-bond basicity, B, McGowan's characteristic volume, V, and the gas-liquid partition constant on hexadecane at 25 °C, L to model the distribution of neutral compounds in biphasic systems. Abraham's version of this model uses all six descriptors with two separate linear free energy relationship models for the transfer of compounds from a gas phase to a condensed phase and between condensed phases. Goss proposed a modification to this model that uses a single calibration model regardless of the physical state for each phase and five of the descriptors employed in Abraham's model (E descriptor is eliminated). The capability of Abraham's model and the Goss-modified model to characterize the contribution of intermolecular interaction to retention for gas and reversed-phase liquid chromatographic systems and distribution in liquid-liquid partition systems is evaluated using the WSU compound descriptor database. These more accurate values for the Abraham descriptors have not been utilized previously for the evaluation of the Goss-modified model and should be more capable of discerning subtle differences in model performance. It is shown that model quality defined by statistical parameters favors Abraham's model over the Goss-modified model with differences in model quality greater for systems in which Abraham's model indicates a significant contribution from electron lone pair interactions and for systems in which one phase is a solvent containing perfluoroalkyl substituents. There is a small systematic difference for the terms describing the combined contributions of cavity formation and dispersion interactions and for interactions of a dipole-type. The contribution of hydrogen-bonding interactions is virtually identical for the two models. The model intercepts are generally different and potentially assigned to a larger contribution from lack-of-fit for the Goss-modified model. Although the Abraham model descriptors have been routinely employed for applications using the Goss-modified model the possibility that Goss-model specific descriptors should be employed was evaluated. Using the Solver method and Goss-model specific calibration models for chromatographic and liquid-liquid partition systems a new set of Goss-specific descriptors was calculated for 28 varied compounds. These descriptors show good statistical agreement with the Abraham descriptor values with an average deviation of 0.009, -0.003, -0.004, and -0.023, respectively, for the S, A, B, and L descriptors, corresponding to a relative absolute deviation in percent of 2.2 %, 3.9 %, 4.3 %, and 1.2 %, respectively.

Perceived warmth and competence predict callback rates in meta-analyzed North American labor market experiments.

Extensive literature probes labor market discrimination through correspondence studies in which researchers send pairs of resumes to employers, which are closely matched except for social signals such as gender or ethnicity. Upon perceiving these signals, individuals quickly activate associated stereotypes. The Stereotype Content Model (SCM; Fiske 2002) categorizes these stereotypes into two dimensions: warmth and competence. Our research integrates findings from correspondence studies with theories of social psychology, asking: Can discrimination between social groups, measured through employer callback disparities, be predicted by warmth and competence perceptions of social signals? We collect callback rates from 21 published correspondence studies, varying for 592 social signals. On those social signals, we collected warmth and competence perceptions from an independent group of online raters. We found that social perception predicts callback disparities for studies varying race and gender, which are indirectly signaled by names on these resumes. Yet, for studies adjusting other categories like sexuality and disability, the influence of social perception on callbacks is inconsistent. For instance, a more favorable perception of signals like parenthood does not consistently lead to increased callbacks, underscoring the necessity for further research. Our research offers pivotal strategies to address labor market discrimination in practice. Leveraging the warmth and competence framework allows for the predictive identification of bias against specific groups without extensive correspondence studies. By distilling hiring discrimination into these two dimensions, we not only facilitate the development of decision support systems for hiring managers but also equip computer scientists with a foundational framework for debiasing Large Language Models and other methods that are increasingly employed in hiring processes.

Clinically relevant doses of tiludronate do not affect bone remodelling in pasture-exercised horses.

BACKGROUND: Bisphosphonates are widely used in equine athletes to reduce lameness associated with skeletal disorders. Widespread off-label use has led to concern regarding potential negative effects on bone healing, but little evidence exists to support or refute this. OBJECTIVES: To investigate the influence of clinically relevant doses of tiludronate on bone remodelling and bone healing. STUDY DESIGN: Randomised, controlled in vivo experiments. METHODS: Each horse had a single tuber coxae biopsied (Day 0), then were divided into a treatment (IV tiludronate) or control (IV saline) group. Treatments were administered 30 and 90 days following initial biopsy. Biopsy of the tuber coxae was repeated on Day 60 to evaluate bone healing following a single treatment. Oxytetracycline was administered on Days 137 and 147 to label bone formation. The contralateral tuber coxae was biopsied on Day 150 to evaluate effects of repeated treatment. Bone biopsies were evaluated with micro-computed tomography and/or dynamic histomorphometry using standard techniques. RESULTS: Nineteen horses completed the study, with no complications following the biopsies and treatments. No significant differences in the trabecular bone parameters or bone formation rate were observed between treatment groups. MAIN LIMITATIONS: The use of a first-generation bisphosphonate may mean some effects of these drugs are underrepresented using this model. The results pertain to the tuber coxae and may not reflect injury or the healing response that occurs in long bones in training or racing. CONCLUSIONS: In this model, tiludronate did not affect normal bone remodelling in the horse, despite repeat dosages.

Guidelines for descriptor assignments for the solvation parameter model by separation techniques.

The solvation parameter model uses six compound descriptors to model equilibrium properties in biphasic systems formally defined as excess molar refraction, E, dipolarity/polarizability, S, overall hydrogen-bond acidity, A, overall hydrogen-bond basicity, B, McGowan's characteristic volume, V, and the gas-liquid partition constant on hexadecane at 25 °C, L. The V descriptor can be assigned from structure and the E descriptor for compounds liquid at 20 °C can be calculated from its refractive index and characteristic volume. The E descriptor for compounds solid at 20 °C and the S, A, B, and L descriptors are assigned from experimental properties traditionally obtained by chromatographic, liquid-liquid partition, and solubility measurements. Here I report an efficient experimental design using the Solver method for the accurate assignment of descriptors for neutral compounds that simultaneously minimizes laboratory resources. This multi-technique approach requires 3 retention factor measurements in a 60 °C temperature range per compound on four columns by gas chromatography, 3 retention factor measurements in a 30 % (v/v) acetonitrile composition range per compound on two columns by reversed-phase liquid chromatography, and eight partition constant measurements by liquid-liquid partition in totally organic and aqueous biphasic systems for a total of 26 experimental measurements. The accuracy of the descriptor assignments was validated by comparison with the values in the Wayne State University (WSU) descriptor database taken as the best estimate of the true descriptor values. The E, S, A, B and L descriptors were assigned simultaneously by the Solver method using the above approach without significant bias and with an average absolute deviation (AAD) of 0.054, 0.018, 0.015, 0.013, and 0.040, respectively, compared with the WSU database values, corresponding to a relative absolute average deviation in percent (RAAD) of 7.2, 1.9, 3.6, 5.1, and 0.84 %, respectively, for 32 varied compounds. This streamlined approach represents a significant improvement on earlier single-technique approaches used as the starting point for the development of the multi-technique approach. For compounds of variable hydrogen-bond basicity modifications to the multi-technique approach were implemented while maintaining the same number of experimental measurements. Acceptable descriptor assignments for B/B° were obtained for compounds liquid at 20 °C for which the E descriptor was available by calculation. For solid compounds at 20 °C the E and B/B° descriptors are restricted to qualitative application where approximate values may be acceptable.

Optimizing Use of High-Sensitivity Troponin for Risk-Stratification of Acute Pulmonary Embolism.

BACKGROUND: High-sensitivity troponin T (HS-TnT) may improve risk-stratification in hemodynamically stable acute pulmonary embolism (PE), but an optimal strategy for combining this biomarker with clinical risk-stratification tools has not been determined. STUDY HYPOTHESIS: We hypothesized that different HS-TnT cutoff values may be optimal for identifying (1) low-risk patients who may be eligible for outpatient management and (2) patients at increased risk of clinical deterioration who might benefit from advanced PE therapies. METHODS: Retrospective analysis of hemodynamically stable patients in the University of Michigan acute ED-PE registry with available HS-TnT values. Primary and secondary outcomes were 30-day mortality and need for intensive care unit-level care. Receiver operating characteristic curves were used to determine optimal HS-TnT cutoffs in the entire cohort, and for those at higher risk based on the simplified Pulmonary Embolism Severity Index (PESI) or imaging findings. RESULTS: The optimal HS-TnT cutoff in the full cohort, 12 pg/mL, was significantly associated with 30-day mortality (odds ratio [OR]: 3.94, 95% confidence interval [CI]: 1.48-10.50) and remained a significant predictor after adjusting for the simplified PESI (sPESI) score and serum creatinine (adjusted OR: 3.05, 95% CI: 1.11-8.38). A HS-TnT cutoff of 87 pg/mL was associated with 30-day mortality (OR: 5.01, 95% CI: 2.08-12.06) in patients with sPESI ≥1 or right ventricular dysfunction. CONCLUSION: In this retrospective, single-center study of acute PE patients, we identified distinct optimal HS-TnT values for different clinical uses-a lower cutoff, which identified low-risk patients even in the absence of other risk-stratification methods, and a higher cutoff, which was strongly associated with adverse outcomes in patients at increased risk.

Possible Effects of Volcanic Eruptions on the Modern Atmosphere of Venus.

This work reviews possible signatures and potential detectability of present-day volcanically emitted material in the atmosphere of Venus. We first discuss the expected composition of volcanic gases at present time, addressing how this is related to mantle composition and atmospheric pressure. Sulfur dioxide, often used as a marker of volcanic activity in Earth's atmosphere, has been observed since late 1970s to exhibit variability at the Venus' cloud tops at time scales from hours to decades; however, this variability may be associated with solely atmospheric processes. Water vapor is identified as a particularly valuable tracer for volcanic plumes because it can be mapped from orbit at three different tropospheric altitude ranges, and because of its apparent low background variability. We note that volcanic gas plumes could be either enhanced or depleted in water vapor compared to the background atmosphere, depending on magmatic volatile composition. Non-gaseous components of volcanic plumes, such as ash grains and/or cloud aerosol particles, are another investigation target of orbital and in situ measurements. We discuss expectations of in situ and remote measurements of volcanic plumes in the atmosphere with particular focus on the upcoming DAVINCI, EnVision and VERITAS missions, as well as possible future missions.

Assessment of liquid-liquid partition for the assignment of descriptors for the solvation parameter model.

The solvation parameter model uses five system independent descriptors to characterize compound properties defined as excess molar refraction, E, dipolarity/polarizability, S, hydrogen-bond acidity, A, hydrogen-bond basicity, B, and McGowan's characteristic volume, V, to model transfer properties between condensed phases. The V descriptor is assigned from structure. For compounds liquid at 20 °C the E descriptor can be assigned from the characteristic volume and its refractive index. The E descriptor for compounds solid at 20 °C and the S, A, and B descriptors are experimental properties traditionally assigned from chromatographic, liquid-liquid partition, and solubility measurements. In this report liquid-liquid partition constants in totally organic and aqueous biphasic systems are evaluated as a standalone technique for descriptor assignments. Using six totally organic biphasic systems the S, A, and B descriptors were assigned with an average absolute deviation (AAD) of about 0.04, 0.03, and 0.04, respectively, compared with the best estimate of the true descriptor values for 65 compounds. The E descriptor for compounds solid at 20 °C can only be estimated with an AAD of approximately 0.1. For six aqueous biphasic systems the B descriptor is assigned with a lower AAD of 0.028 and higher AAD of 0.08 and 0.05 for the S and A descriptors, respectively, than for the totally organic biphasic systems for compounds with a reliable value for the E descriptor. The preferred system for descriptor assignments utilizes both totally organic biphasic systems (heptane-1,1,1-trifluoroethanol, isopentyl ether-propylene carbonate, isopentyl ether-ethanolamine, heptane-ethylene glycol, heptane-formamide, and 1,2-dichloroethane-ethylene glycol) and aqueous biphasic systems (octanol-water, cyclohexane-water) with the possible substitution of some systems with alternative systems of similar selectivity. For 55 varied compounds this combination of eight organic and aqueous biphasic systems resulted in an AAD of approximately 0.03, 0.02, and 0.02 for the S, A, and B descriptors compared to the best estimate of the true descriptor value. For 30 compounds solid at 20 °C the AAD for the E descriptor of 0.11 is poorly assigned. The relative average absolute deviation in percent (RAAD) corresponds to 9.7 %, 3.1 %. 4.0 % and 8.3 % for E, S, A, and B, respectively, for the eight biphasic systems. Liquid-liquid partition is compared to reversed-phase liquid and gas chromatography as a standalone technique for descriptor assignments.

Affinity targeting of therapeutic proteins to the bone surface-local delivery of sclerostin-neutralizing antibody enhances efficacy.

Currently available biotherapeutics for the treatment of osteoporosis lack explicit mechanisms for bone localization, potentially limiting efficacy and inducing off-target toxicities. While various strategies have been explored for targeting the bone surface, critical aspects remain poorly understood, including the optimal affinity ligand, the role of binding avidity and circulation time, and, most importantly, whether or not this strategy can enhance the functional activity of clinically relevant protein therapeutics. To investigate, we generated fluorescent proteins (eg, mCherry) with site-specifically attached small molecule (bisphosphonate) or peptide (deca-aspartate, D10) affinity ligands. While both affinity ligands successfully anchored fluorescent protein to the bone surface, quantitative radiotracing revealed only modest femoral and vertebral accumulation and suggested a need for enhanced circulation time. To achieve this, we fused mCherry to the Fc fragment of human IgG1 and attached D10 peptides to each C-terminus. The mCherry-Fc-D10 demonstrated an ~80-fold increase in plasma exposure and marked increases in femoral and vertebral accumulation (13.6% ± 1.4% and 11.4% ± 1.3% of the injected dose/g [%ID/g] at 24 h, respectively). To determine if bone surface targeting could enhance the efficacy of a clinically relevant therapeutic, we generated a bone-targeted sclerostin-neutralizing antibody, anti-sclerostin-D10. The targeted antibody demonstrated marked increases in bone accumulation and retention (20.9 ± 2.5% and 19.5 ± 2.5% ID/g in femur and vertebrae at 7 days) and enhanced effects in a murine model of ovariectomy-induced bone loss (bone volume/total volume, connectivity density, and structure model index all increased [P < .001] vs untargeted anti-sclerostin). Collectively, our results indicate the importance of both bone affinity and circulation time in achieving robust targeting of therapeutic proteins to the bone surface and suggest that this approach may enable lower doses and/or longer dosing intervals without reduction in biotherapeutic efficacy. Future studies will be needed to determine the translational potential of this strategy and its potential impact on off-site toxicities.

Several biologic therapies have been approved for osteoporosis, but they lack means of localization to bone tissue, potentially limiting their efficacy and leading to off-target toxicities. This manuscript investigates strategies for targeting biotherapeutics to the bone surface and asks the question of whether or not this approach can enhance functional activity and allow for lower or less frequent dosing. To define the key determinants of bone surface targeting, we begin by synthesizing fluorescent model proteins with different bone targeting tags. We show that even 1 tag is enough to make the surface of the femur and vertebrae fluorescent following systemic administration. The results are relatively modest at first, but when we combine the bone targeting tag with a second modification that makes the protein circulate in the body for a longer period of time, we observe a huge increase in bone surface delivery. We then synthesize a bone surface targeted version of a sclerostin-inhibiting antibody and show that it is more effective than the untargeted antibody and provides near complete protection of bone density despite relatively low dose. Our findings could have translational implications for existing bone therapies and help guide design of future strategies for optimized bone surface targeting.

Sputum metagenomics of people with bronchiectasis.

Background: The microbiota in the sputum of people with bronchiectasis has repeatedly been investigated in cohorts of different geographic origin, but so far has not been studied to the species level in comparison to control populations including healthy adults and smokers without lung disease. Methods: The microbial metagenome from sputa of 101 European Bronchiectasis Registry (EMBARC) study participants was examined by using whole-genome shotgun sequencing. Results: Our analysis of the metagenome of people with bronchiectasis revealed four clusters characterised by a predominance of Haemophilus influenzae, Pseudomonas aeruginosa or polymicrobial communities with varying compositions of nonpathogenic commensals and opportunistic pathogens. The metagenomes of the severely affected patients showed individual profiles characterised by low alpha diversity. Importantly, nearly 50% of patients with severe disease were grouped in a cluster characterised by commensals. Comparisons with the sputum metagenomes of healthy smokers and healthy nonsmokers revealed a gradient of depletion of taxa in bronchiectasis, most often Neisseria subflava, Fusobacterium periodonticum and Eubacterium sulci. Conclusion: The gradient of depletion of commensal taxa found in healthy airways is a key feature of bronchiectasis associated with disease severity.

Determination of solvation parameter model compound descriptors by gas chromatography.

The solvation parameter model uses five system independent descriptors to characterize compound properties defined as excess molar refraction, E, dipolarity/polarizability, S, hydrogen-bond acidity, A, hydrogen-bond basicity, B, and the gas-liquid partition constant at 25 °C on n-hexadecane, L, to model transfer properties in gas-condensed phase biphasic systems. The E descriptor for compounds liquid at 20 °C is available by calculation using a refractive index value while E for solid compounds at 20 °C and the S, A, B, and L descriptors are determined by experiment. As a single-technique approach, it is shown that with up to 20 retention factor measurements on four columns comprising a poly(siloxane) containing methyloctyl or dimethyldiphenylsiloxane monomers (SPB-Octyl or HP-5), a poly(siloxane) containing methyltrifluoropropylsiloxane monomers (Rtx-OPP or DB-210), a poly(siloxane) containing bis(cyanopropylsiloxane) monomers (HP-88 or SGE BPX-90), and a poly(ethylene glycol) stationary phase (DB-WAXetr or HP-INNOWAX) are suitable for assigning the S, A, and L descriptors. Using the descriptors in the updated WSU compound descriptor database as target values the average absolute error in the descriptor assignments for 52 varied compounds in the temperature range 60-140 °C was 0.072 for E, 0.016 for S, 0.008 for A, and 0.022 for L corresponding to 30 %, 3.5 %, and 0.6 % as a relative average absolute error for E, S, and L, respectively. For the higher temperature range of 160-240 °C and 34 varied compounds that are liquid at 20 °C the average absolute error for the S, A and L descriptors was 0.026, 0.020, and 0.031, respectively, with the largest relative average absolute error for S of 3.2 % (< 1 % for the L descriptor). For 35 varied compounds that are solid at 20 °C the relative absolute error for the E, S, A, and L descriptors in the higher temperature range was 0.068, 0.035, 0.020, and 0.020, respectively, with a relative average absolute error for E (6.5 %), S (3.5 %) and L (0.88 %). The S, A, and L descriptor can be accurately assigned on the four-column system over a wide temperature range. The E descriptor for solid compounds at 20 °C exhibits greater variability than desirable. The B descriptor cannot be assigned by the four-column system, which lack hydrogen-bond acid functional groups, and is only poorly assigned on the weak hydrogen-bond acid ionic liquid column SLB-IL100.

Virome analysis of New Zealand's bats reveals cross-species viral transmission among the Coronaviridae.

The lesser short-tailed bat (Mystacina tuberculata) and the long-tailed bat (Chalinolobus tuberculatus) are Aotearoa New Zealand's only native extant terrestrial mammals and are believed to have migrated from Australia. Long-tailed bats arrived in New Zealand an estimated two million years ago and are closely related to other Australian bat species. Lesser short-tailed bats, in contrast, are the only extant species within the Mystacinidae and are estimated to have been living in isolation in New Zealand for the past 16-18 million years. Throughout this period of isolation, lesser short-tailed bats have become one of the most terrestrial bats in the world. Through a metatranscriptomic analysis of guano samples from eight locations across New Zealand, we aimed to characterise the viromes of New Zealand's bats and determine whether viruses have jumped between these species over the past two million years. High viral richness was observed among long-tailed bats with viruses spanning seven different viral families. In contrast, no bat-specific viruses were identified in lesser short-tailed bats. Both bat species harboured an abundance of likely dietary- and environment-associated viruses. We also identified alphacoronaviruses in long-tailed bat guano that had previously been identified in lesser short-tailed bats, suggesting that these viruses had jumped the species barrier after long-tailed bats migrated to New Zealand. Of note, an alphacoronavirus species discovered here possessed a complete genome of only 22,416 nucleotides with entire deletions or truncations of several non-structural proteins, thereby representing what may be the shortest genome within the Coronaviridae identified to date. Overall, this study has revealed a diverse range of novel viruses harboured by New Zealand's only native terrestrial mammals, in turn expanding our understanding of bat viral dynamics and evolution globally.

Determination of the hydrogen-bond basicity descriptor by reversed-phase liquid chromatography.

Except for alkanes, most organic compounds are hydrogen-bond bases. The B° descriptor of the solvation parameter model provides a convenient measure of the effective (or summation) hydrogen-bond basicity of organic compounds. A fast and convenient method to assign the B° descriptor is required to support studies of hydrogen-bonding in separation systems. A two-column system with acetonitrile-water mobile phase compositions and the measurement of up to eleven isocratic retention factors is proposed for this purpose. Several reversed-phase column chemistries and mobile phases were evaluated with the two-column system consisting of a pentafluorophenylpropylsiloxane-bonded and octadecylsiloxane-bonded silica columns recommended for this purpose. To assess the accuracy of the method values for B° were taken from the Wayne State University (WSU) compound descriptor database, which were assigned using conventional multi-technique methods and large datasets. The two-column systems provided an unbiased assignment of B° with an average deviation of 0.008 and an average absolute deviation of 0.021 compared with the target value for 55 varied compounds. The two-column system is unsuitable for assigning the other descriptors used in the solvation parameter model and results in erroneous assignments of B° for nitrogen-containing compounds capable of electrostatic interactions on silica-based reversed-phase columns.

Bispecific antibody shuttles targeting CD98hc mediate efficient and long-lived brain delivery of IgGs.

The inability of antibodies to penetrate the blood-brain barrier (BBB) is a key limitation to their use in diverse applications. One promising strategy is to deliver IgGs using a bispecific BBB shuttle, which involves fusing an IgG to a second affinity ligand that engages a cerebrovascular endothelial target and facilitates transport across the BBB. Nearly all prior efforts have focused on shuttles that target transferrin receptor (TfR-1) despite inherent delivery and safety challenges. Here, we report bispecific antibody shuttles that engage CD98hc, the heavy chain of the large neutral amino acid transporter (LAT1), and efficiently transport IgGs into the brain. Notably, CD98hc shuttles lead to much longer-lived brain retention of IgGs than TfR-1 shuttles while enabling more specific targeting due to limited CD98hc engagement in the brain parenchyma, which we demonstrate for IgGs that either agonize a neuronal receptor (TrkB) or target other endogenous cell-surface proteins on neurons and astrocytes.

Aging microplastics enhances the adsorption of pharmaceuticals in freshwater.

Plastic pollution is an increasing environmental concern. Pollutants such as microplastics (< 5 mm) and pharmaceuticals often co-exist in the aquatic environment. The current study aimed to elucidate the interaction of pharmaceuticals with microplastics and ascertain how the process of photo-oxidation of microplastics affected the adsorption of the pharmaceuticals. To this end, a mixture containing ibuprofen, carbamazepine, fluoxetine, venlafaxine and ofloxacin (16 µmol L-1 each) was placed in contact with one of six either virgin or aged microplastic types. The virgin microplastics were acquired commercially and artificially aged in the laboratory. Polypropylene, polyethylene, polyethylene terephthalate, polyamide, polystyrene, and polyvinyl chloride microparticles at two sizes described as small (D50 < 35 µm) and large (D50 95-157 µm) were evaluated. Results demonstrated that the study of virgin particles may underestimate the adsorption of micropollutants onto microplastics. For virgin particles, only small microparticles of polypropylene, polyethylene, polyvinyl chloride, and both sizes of polyamide adsorbed pharmaceuticals. Aging the microplastics increased significantly the adsorption of pharmaceuticals by microplastics. Fluoxetine adsorbed onto all aged microplastics, from 18 % (large polyethylene terephthalate) to 99 % (small polypropylene). The current investigation highlights the potential of microplastics to act as a vector for pharmaceuticals in freshwater, especially after aging.

Determination of descriptors for the principal flavor compounds of the cinnamons of commerce by gas chromatography and liquid-liquid partition.

Descriptors for fourteen semivolatile organic compounds associated with the authenticity, botanical origin, and flavor potential of the cinnamons of commerce were determined using the Solver method and experimental retention factors determined by gas chromatography at several temperatures on a minimum of seven selectivity-selected, open-tubular columns and liquid-liquid partition constants in up to twenty totally organic biphasic systems. The six descriptors that encode the solvation properties of the compounds were used to predict water-gas, octanol-gas, and octanol-water partition constants commonly employed to assess environmental distribution properties. For octanol-water partition constants, log KOW, the predicted partition constants exhibited an average absolute deviation of 0.12 for log KOW experimental - log KOW predicted (n = 14). Soil-water, soil-air, urban aerosol-air, skin-water permeation, and non-specific toxicity to the fathead minnow were predicted for the same compounds to assess their potential environmental impact. The product terms of the solvation parameter model provide a useful insight into the contribution of individual intermolecular interactions to the distribution properties of the cinnamon compounds and their environmental impact.

Revised descriptors for polycyclic aromatic and related hydrocarbons for the prediction of environmental properties using the solvation parameter model.

Revised descriptors for twenty-five polycyclic aromatic and related hydrocarbons (PAHs) forming a component of the Wayne State University (WSU) descriptor database are provided for use with the solvation parameter model. The descriptors are determined by the Solver method using experimental data for calibrated gas-liquid and reversed-phase liquid chromatographic retention factors and liquid-liquid partition constants in totally organic biphasic systems. The characteristic solvation properties of the PAHs are accounted for mainly by the additional dispersion interactions (E descriptor) and dipole-type interactions (S descriptor) resulting from the availability of easily polarizable electrons that complement typical dispersion interactions for saturated hydrocarbons. The descriptors afford acceptable prediction of the water-air partition constant (average absolute deviation AAD = 0.17, n = 22), octanol-air partition constant (AAD = 0.12, n = 20), and water-octanol partition constant (AAD = 0.10, n = 23). A two-parameter model containing only the V and B descriptors provides an unbiased prediction of aqueous solubility for the PAHs with an AAD = 0.26 (n = 22). The descriptors estimated by convenient chromatographic and partition constant measurements are demonstrated to be a viable alternative to the experimental determination of environmental properties otherwise only available by tedious, expensive, and low data throughput experimental techniques.

Coagulofibrinolytic effects of recombinant soluble thrombomodulin in prolonged porcine cardiac arrest.

Aim: To evaluate coagulofibrinolytic abnormalities and the effects of ART-123 (recombinant human thrombomodulin alpha) in a porcine model of cardiac arrest and prolonged cardiopulmonary resuscitation (CA/CPR). Methods: Fifteen pigs (n = 5 per group) underwent 8 minutes of no-flow CA followed by 50 minutes of mechanical CPR, while 2 pigs underwent sham arrest. CA/CPR animals were randomized to receive saline or 1 mg/kg ART-123 pre-arrest (5 minutes prior to ventricular fibrillation) or post-arrest (2 minutes after initiation of CPR). Arterial and venous blood samples were drawn at multiple time points for blood gas analysis and measurement of plasma and whole blood markers of coagulation and fibrinolysis. Results: In saline-treated CA/CPR, but not sham animals, robust and persistent activation of coagulation and fibrinolysis was observed throughout resuscitation. After 50 minutes of CPR, plasma tests and thromboelastography indicated a mix of hypercoagulability and consumptive coagulopathy. ART-123 had a robust anticoagulant effect, reducing both thrombin-antithrombin (TAT) complexes and d-dimer (p < 0.05 for each). The duration of anticoagulant effect varied depending on the timing of ART-123 administration. Similarly, ART-123 when given prior to cardiac arrest was found to have pro-fibrinolytic effects, increasing free tissue plasminogen activator (tPA, p = 0.02) and decreasing free plasminogen activator inhibitor-1 (PAI-1, p = 0.04). Conclusion: A porcine model of prolonged CA/CPR reproduces many of the coagulofibrinolytic abnormalities observed in human cardiac arrest patients. ART-123 demonstrates a combination of anticoagulant and profibrinolytic effects, depending on the timing of its administration relative to cardiac arrest.

Core-Labeling (Radio) Synthesis of Phenols.

We report a method that enables the fast incorporation of carbon isotopes into the ipso carbon of phenols. Our approach relies on the synthesis of a 1,5-dibromo-1,4-pentadiene precursor, which upon lithium-halogen exchange followed by treatment with carbonate esters results in a formal [5 + 1] cyclization to form the phenol product. Using this strategy, we have prepared 12 1-13C-labeled phenols, show proof-of-concept for the labeling of phenols with carbon-14, and demonstrate phenol synthesis directly from cyclotron-produced [11C]CO2.

Understanding the potential causes of gastrointestinal dysfunctions in multiple system atrophy.

Multiple system atrophy (MSA) is a rare, progressive neurodegenerative disorder characterised by autonomic, pyramidal, parkinsonian and/or cerebellar dysfunction. Autonomic symptoms of MSA include deficits associated with the gastrointestinal (GI) system, such as difficulty swallowing, abdominal pain and bloating, nausea, delayed gastric emptying, and constipation. To date, studies assessing GI dysfunctions in MSA have primarily focused on alterations of the gut microbiome, however growing evidence indicates other structural components of the GI tract, such as the enteric nervous system, the intestinal barrier, GI hormones, and the GI-driven immune response may contribute to MSA-related GI symptoms. Here, we provide an in-depth exploration of the physiological, structural, and immunological changes theorised to underpin GI dysfunction in MSA patients and highlight areas for future research in order to identify more suitable pharmaceutical treatments for GI symptoms in patients with MSA.