Characterizing Hydroxyl Radical Formation from the Light-Driven Fe(II)-Peracetic Acid Reaction, a Key Process for Aerosol-Cloud Chemistry.

The reaction of peracetic acid (PAA) and Fe(II) has recently gained attention due to its utility in wastewater treatment and its role in cloud chemistry. Aerosol-cloud interactions, partly mediated by aqueous hydroxyl radical (OH) chemistry, represent one of the largest uncertainties in the climate system. Ambiguities remain regarding the sources of OH in the cloud droplets. Our research group recently proposed that the dark and light-driven reaction of Fe(II) with peracids may be a key contributor to OH formation, producing a large burst of OH when aerosol particles take up water as they grow to become cloud droplets, in which reactants are consumed within 2 min. In this work, we quantify the OH production from the reaction of Fe(II) and PAA across a range of physical and chemical conditions. We show a strong dependence of OH formation on ultraviolet (UV) wavelength, with maximum OH formation at λ = 304 ± 5 nm, and demonstrate that the OH burst phenomenon is unique to Fe(II) and peracids. Using kinetics modeling and density functional theory calculations, we suggest the reaction proceeds through the formation of an [Fe(II)-(PAA)2(H2O)2] complex, followed by the formation of a Fe(IV) complex, which can also be photoactivated to produce additional OH. Determining the characteristics of OH production from this reaction advances our knowledge of the sources of OH in cloudwater and provides a framework to optimize this reaction for OH output for wastewater treatment purposes.

Iron and Copper Alter the Oxidative Potential of Secondary Organic Aerosol: Insights from Online Measurements and Model Development.

The oxidative potential (OP) of particulate matter has been widely suggested as a key metric for describing atmospheric particle toxicity. Secondary organic aerosol (SOA) and redox-active transition metals, such as iron and copper, are key drivers of particle OP. However, their relative contributions to OP, as well as the influence of metal-organic interactions and particulate chemistry on OP, remains uncertain. In this work, we simultaneously deploy two novel online instruments for the first time, providing robust quantification of particle OP. We utilize online AA (OPAA) and 2,7-dichlorofluoroscein (ROSDCFH) methods to investigate the influence of Fe(II) and Cu(II) on the OP of secondary organic aerosol (SOA). In addition, we quantify the OH production (OPOH) from these particle mixtures. We observe a range of synergistic and antagonistic interactions when Fe(II) and Cu(II) are mixed with representative biogenic (ß-pinene) and anthropogenic (naphthalene) SOA. A newly developed kinetic model revealed key reactions among SOA components, transition metals, and ascorbate, influencing OPAA. Model predictions agree well with OPAA measurements, highlighting metal-ascorbate and -naphthoquinone-ascorbate reactions as important drivers of OPAA. The simultaneous application of multiple OP assays and a kinetic model provides new insights into the influence of metal and SOA interactions on particle OP.

Robust quantification of the burst of OH radicals generated by ambient particles in nascent cloud droplets using a direct-to-reagent approach.

Reactive oxygen species (ROS) play a central role in chemistry in cloud water, as well as in other aqueous phases such as lung fluid and in wastewater treatment. Recently, work simulating nascent cloud droplets showed that aerosol particles produce a large burst of OH radicals when they first take up water. This activity stops abruptly, within two minutes. The source of the OH radicals is not well understood, but it likely includes the aqueous phase chemistry of ROS and/or organic hydroperoxides and redox active metals such as iron and copper. ROS and their precursors are in general highly reactive and labile, and thus may not survive during traditional sampling methods, which typically involve multi-hour collection on a filter or direct sampling into water or another collection liquid. Further, these species may further decay during storage. Here, we develop a technique to grow aerosol particles into small droplets and capture the droplets directly into a vial containing the terephthalate probe in water, which immediately scavenges OH radicals produced by aerosol particles. The method uses a Liquid Spot Sampler. Extensive characterization of the approach reveals that the collection liquid picks up substantial OH/OH precursors from the gas phase. This issue is effectively addressed by adding an activated carbon denuder. We then compared OH formation measured with the direct-to-reagent approach vs. filter collection. We find that after a modest correction for OH formed in the collection liquid, the samples collected into the reagent produce about six times those collected on filters, for both PM2.5 and total suspended particulate. This highlights the need for direct-to-reagent measurement approaches to accurately quantify OH production from ambient aerosol particles.

Classic Phytochemical Antioxidant and Lipoxygenase Inhibitor, Nordihydroguaiaretic Acid, Activates Phospholipase D through Oxidant Signaling and Tyrosine Phosphorylation Leading to Cytotoxicity in Lung Vascular Endothelial Cells.

Nordihydroguaiaretic acid (NDGA), a dicatechol and phytochemical polyphenolic antioxidant and an established inhibitor of human arachidonic acid (AA) 5-lipoxygenase (LOX) and 15-LOX, is widely used to ascertain the role of LOXs in vascular endothelial cell (EC) function. As the modulatory effect of NDGA on phospholipase D (PLD), an important lipid signaling enzyme in ECs, thus far has not been reported, here we have investigated the modulation of PLD activity and its regulation by NDGA in the bovine pulmonary artery ECs (BPAECs). NDGA induced the activation of PLD (phosphatidic acid formation) in cells in a dose- and time-dependent fashion that was significantly attenuated by iron chelator and antioxidants. NDGA induced the formation of reactive oxygen species (ROS) in cells in a dose- and time-dependent manner as evidenced from fluorescence microscopy and fluorimetry of ROS and electron paramagnetic resonance spectroscopy of oxygen radicals. Also, NDGA caused a dose-dependent loss of intracellular glutathione (GSH) in BPAECs. Protein tyrosine kinase (PTyK)-specific inhibitors significantly attenuated NDGA-induced PLD activation in BPAECs. NDGA also induced a dose- and time-dependent phosphorylation of tyrosine in proteins in cells. NDGA caused in situ translocation and relocalization of both PLD1 and PLD2 isoforms, in a time-dependent fashion. Cyclooxygenase (COX) inhibitors were ineffective in attenuating NDGA-induced PLD activation in BPAECs, thus ruling out the activation of COXs by NDGA. NDGA inhibited the AA-LOX activity and leukotriene C4 (LTC4) formation in cells. On the other hand, the 5-LOX-specific inhibitors, 5, 8, 11, 14-eicosatetraynoic acid and kaempferol, were ineffective in activating PLD in BPAECs. Antioxidants and PTyK-specific inhibitors effectively attenuated NDGA cytotoxicity in BPAECs. The PLD-specific inhibitor, 5-fluoro-2-indolyl deschlorohalopemide (FIPI), significantly attenuated and protected against the NDGA-induced PLD activation and cytotoxicity in BPAECs. For the first time, these results demonstrated that NDGA, the classic phytochemical polyphenolic antioxidant and LOX inhibitor, activated PLD causing cytotoxicity in ECs through upstream oxidant signaling and protein tyrosine phosphorylation.

Redesigning Rural Acute Stroke Care: A Person-Centered Approach.

Stroke service delivery in rural areas in Australia lacks evidence-based, best practice care protocols as a result of limited resources and opportunity. Healthcare redesign is an approach to improving health services by understanding barriers and enablers to service provision and work with users to develop solutions for improvement. This research aimed to qualitatively evaluate stroke care in rural Tasmania using a person-centered approach, as part of a larger healthcare redesign initiative to improve acute stroke care. Semi-structured interviews, aimed at gaining insight into experiences of healthcare staff and users, were conducted. Thematic analysis revealed three global themes (communication, holistic care, and resourcing) that demonstrated some consistency between healthcare staff and user experience, highlighting that some needs and expectations were not being met. Results of this experiential study provide important perspectives for delivering needs-based improvements in service provision for acute stroke care. Overall, this study showed that systems of stroke care in rural areas could be improved by utilizing a redesign approach including healthcare staff and users in the development of solutions for health service improvement.

Dynamic Wood Smoke Aerosol Toxicity during Oxidative Atmospheric Aging.

Wildfires are a major source of biomass burning aerosol to the atmosphere, with their incidence and intensity expected to increase in a warmer future climate. However, the toxicity evolution of biomass burning organic aerosol (BBOA) during atmospheric aging remains poorly understood. In this study, we report a unique set of chemical and toxicological metrics of BBOA from pine wood smoldering during multiphase aging by gas-phase hydroxyl radicals (OH). Both the fresh and OH-aged BBOA show activity relevant to adverse health outcomes. The results from two acellular assays (DTT and DCFH) show significant oxidative potential (OP) and reactive oxygen species (ROS) formation in OH-aged BBOA. Also, radical concentrations in the aerosol assessed by electron paramagnetic resonance (EPR) spectroscopy increased by 50% following heterogeneous aging. This enhancement was accompanied by a transition from predominantly carbon-centered radicals (85%) in the fresh aerosol to predominantly oxygen-centered radicals (76%) following aging. Both the fresh and aged biomass burning aerosols trigger prominent antioxidant defense during the in vitro exposure, indicating the induction of oxidative stress by BBOA in the atmosphere. By connecting chemical composition and toxicity using an integrated approach, we show that short-term aging initiated by OH radicals can produce biomass burning particles with a higher particle-bound ROS generation capacity, which are therefore a more relevant exposure hazard for residents in large population centers close to wildfire regions than previously studied fresh biomass burning emissions.

Characterization and Quantification of Particle-Bound Criegee Intermediates in Secondary Organic Aerosol.

The ozonolysis of alkenes contributes substantially to the formation of secondary organic aerosol (SOA), which are important modulators of air quality and the Earth's climate. Criegee intermediates (CIs) are abundantly formed through this reaction. However, their contributions to aerosol particle chemistry remain highly uncertain. In this work, we present the first application of a novel methodology, using spin traps, which simultaneously quantifies CIs produced from the ozonolysis of volatile organic compounds in the gas and particle phases. Only the smallest CI with one carbon atom was detected in the gas phase of a ß-caryophyllene ozonolysis reaction system. However, multiple particle-bound CIs were observed in ß-caryophyllene SOA. The concentration of the most abundant CI isomer in the particle phase was estimated to constitute ∼0.013% of the SOA mass under atmospherically relevant conditions. We also demonstrate that the lifetime of CIs in highly viscous SOA particles is at least on the order of minutes, substantially greater than their gas-phase lifetime. The confirmation of substantial concentrations of large CIs with elongated lifetimes in SOA raises new questions regarding their influence on the chemical evolution of viscous SOA particles, where CIs may be a previously underestimated source of reactive species.

Vertical integration in the Australian community care setting: Can it work? A theoretical review of current literature.

Vertical integration (VI) is considered a strategic management plan whereby an organisation has ownership of its supply chain. It is utilised as a method for managing the economic needs and approaches of an organisation and ensuring that a product is readily available for use. From a healthcare perspective, this pertains to the coordination of services or levels of care and allows for adaptation to changing circumstances. This study reviews existing literature on VI in a healthcare setting to assess feasibility and effectiveness of this proposed solution. A theoretical literature review was performed utilising conceptual categorisation to understand how VI may benefit community care organisations, using the needs of a local organisation as an example. Seventeen articles were included from a range of databases and grey literature with findings categorised according to two research questions. The findings suggest that for VI to be effective and efficient it is important to consider the following themes: market failure, barriers to entry, productive capabilities and specific healthcare issues. In conclusion, from a management and economic perspective, when markets are not functioning efficiently and are in disequilibrium, VI may provide an appropriate avenue to address these problems, in particular for community care organisations.

Determining readiness for a reablement approach to care in Australia: Development of a pre-employment questionnaire.

Reablement is described as a goal directed intervention with a view to maintain or improve the independence of clients through "doing with, rather than doing for". As a relatively new concept in care, lack of specific skills in reablement is not uncommon, however, intrinsic values aligned with reablement are beneficial to organisations providing care and support to clients. The aim of this study is to develop a pre-employment questionnaire to assess readiness for a reablement approach to care as a step towards developing a reablement culture across organisations. A questionnaire based on activities of daily living (ADL), developed by the research team in consultation with a local community-based care organisation, was completed by 166 staff members at a community-based care organisation in Tasmania across several timepoints during and following reablement education sessions in 2018. The scores from these questionnaires were utilised to develop a questionnaire appropriate for determining readiness for reablement prior to employment within the organisation. Over a period of twelve months, a total of 407 Reablement Readiness Questionnaires were submitted by staff, indicating high levels of willingness to engage in reablement prior to and following the education sessions. Exploratory factor analyses were performed, and the construct validity and internal consistency of the emerging factors were assessed. An exploratory factor analysis indicated that ADL, in relation to reablement, consist of three dimensions-Lifestyle, My body and Connecting. The corresponding questions were subsequently built into an online questionnaire for pre-employment use. This questionnaire also has potential benefit in recruitment of staff to other community service organisations, to ascertain their readiness for reablement prior to beginning a variety of different roles within client care and support.

Atmospheric conditions and composition that influence PM2.5 oxidative potential in Beijing, China.

Epidemiological studies have consistently linked exposure to PM2.5 with adverse health effects. The oxidative potential (OP) of aerosol particles has been widely suggested as a measure of their potential toxicity. Several acellular chemical assays are now readily employed to measure OP; however, uncertainty remains regarding the atmospheric conditions and specific chemical components of PM2.5 that drive OP. A limited number of studies have simultaneously utilised multiple OP assays with a wide range of concurrent measurements and investigated the seasonality of PM2.5 OP. In this work, filter samples were collected in winter 2016 and summer 2017 during the atmospheric pollution and human health in a Chinese megacity campaign (APHH-Beijing), and PM2.5 OP was analysed using four acellular methods: ascorbic acid (AA), dithiothreitol (DTT), 2,7-dichlorofluorescin/hydrogen peroxidase (DCFH) and electron paramagnetic resonance spectroscopy (EPR). Each assay reflects different oxidising properties of PM2.5, including particle-bound reactive oxygen species (DCFH), superoxide radical production (EPR) and catalytic redox chemistry (DTT/AA), and a combination of these four assays provided a detailed overall picture of the oxidising properties of PM2.5 at a central site in Beijing. Positive correlations of OP (normalised per volume of air) of all four assays with overall PM2.5 mass were observed, with stronger correlations in winter compared to summer. In contrast, when OP assay values were normalised for particle mass, days with higher PM2.5 mass concentrations (µgm-3) were found to have lower mass-normalised OP values as measured by AA and DTT. This finding supports that total PM2.5 mass concentrations alone may not always be the best indicator for particle toxicity. Univariate analysis of OP values and an extensive range of additional measurements, 107 in total, including PM2.5 composition, gas-phase composition and meteorological data, provided detailed insight into the chemical components and atmospheric processes that determine PM2.5 OP variability. Multivariate statistical analyses highlighted associations of OP assay responses with varying chemical components in PM2.5 for both mass- and volume-normalised data. AA and DTT assays were well predicted by a small set of measurements in multiple linear regression (MLR) models and indicated fossil fuel combustion, vehicle emissions and biogenic secondary organic aerosol (SOA) as influential particle sources in the assay response. Mass MLR models of OP associated with compositional source profiles predicted OP almost as well as volume MLR models, illustrating the influence of mass composition on both particle-level OP and total volume OP. Univariate and multivariate analysis showed that different assays cover different chemical spaces, and through comparison of mass- and volume-normalised data we demonstrate that mass-normalised OP provides a more nuanced picture of compositional drivers and sources of OP compared to volume-normalised analysis. This study constitutes one of the most extensive and comprehensive composition datasets currently available and provides a unique opportunity to explore chemical variations in PM2.5 and how they affect both PM2.5 OP and the concentrations of particle-bound reactive oxygen species.

Ascorbate oxidation by iron, copper and reactive oxygen species: review, model development, and derivation of key rate constants.

Ascorbic acid is among the most abundant antioxidants in the lung, where it likely plays a key role in the mechanism by which particulate air pollution initiates a biological response. Because ascorbic acid is a highly redox active species, it engages in a far more complex web of reactions than a typical organic molecule, reacting with oxidants such as the hydroxyl radical as well as redox-active transition metals such as iron and copper. The literature provides a solid outline for this chemistry, but there are large disagreements about mechanisms, stoichiometries and reaction rates, particularly for the transition metal reactions. Here we synthesize the literature, develop a chemical kinetics model, and use seven sets of laboratory measurements to constrain mechanisms for the iron and copper reactions and derive key rate constants. We find that micromolar concentrations of iron(III) and copper(II) are more important sinks for ascorbic acid (both AH2 and AH-) than reactive oxygen species. The iron and copper reactions are catalytic rather than redox reactions, and have unit stoichiometries: Fe(III)/Cu(II) + AH2/AH- + O2 → Fe(III)/Cu(II) + H2O2 + products. Rate constants are 5.7 × 104 and 4.7 × 104 M-2 s-1 for Fe(III) + AH2/AH- and 7.7 × 104 and 2.8 × 106 M-2 s-1 for Cu(II) + AH2/AH-, respectively.

Challenges of delivering evidence-based stroke services for rural areas in Australia.

OBJECTIVE: The aim of this paper was to use current stroke care guidelines to identify and discuss current stroke care challenges in rural Australian health care and potential solutions for delivery of evidence-based practice. DESIGN AND SETTING: A review of national guidelines since 2002 for organised stroke care was undertaken to determine best practice for delivering primary stroke care. We then employed a narrative literature review strategy looking at relevant articles, based on keywords, outlining current stroke service availability in Australia, highlighting the challenges of implementing evidence-based stroke care in rural areas in Australia based on the current guidelines. RESULTS: Delivery of evidence-based stroke care in rural Australia is fraught with challenges. Although national best-practice guidelines for stroke care are well established, the recommendations made in these guidelines do not always reflect the resource availability in rural Australia. Redesigning processes and utilising available resources, such as telemedicine or local clinical pathways, can achieve an evidence-based standard; however, ultimately better resourcing of these areas is required. CONCLUSION: Evidence-based stroke care, aligned with current national standards is the key to providing adequate stroke services in rural Australia. Improved health service resourcing and better utilisation of currently available resources are options for achieving elements of evidence-based stroke care. IMPLICATIONS FOR PUBLIC HEALTH: Availability of adequate services for stroke patients directly impacts public health as it determines health outcomes for these patients. Indirect implications for public health include the effects on health professionals and the general public.

Development of a Physiologically Relevant Online Chemical Assay To Quantify Aerosol Oxidative Potential.

Large-scale epidemiological studies have shown a close correlation between adverse human health effects and exposure to ambient particulate matter (PM). The oxidative potential (OP) of ambient PM has been implicated in inducing toxic effects associated with PM exposure. In particular, reactive oxygen species (ROS), either bound to PM or generated by particulate components in vivo, substantially contribute to the OP and therefore toxicity of PM by lowering antioxidant concentrations in the lung, which can subsequently lead to oxidative stress, inflammation, and disease. Traditional methods for measuring aerosol OP are labor intensive and have poor time resolution, with significant delays between aerosol collection and ROS analysis. These methods may underestimate ROS concentrations in PM because of the potentially short lifetime of some ROS species; therefore, continuous online, highly time-resolved measurement of ROS components in PM is highly advantageous. In this work, we develop a novel online method for measuring aerosol OP based on ascorbic acid chemistry, an antioxidant prevalent in the lung, thus combining the advantages of continuous online measurement with a physiologically relevant assay. The method limit of detection is estimated for a range of atmospherically important chemical components such as Cu(II) 0.22 ± 0.03 µg m-3, Fe(II) 47.8 ± 5.5 µg m-3, Fe(III) 0.63 ± 0.05 µg m-3, and secondary organic aerosol 41.2 ± 6.9 µg m-3, demonstrating that even at this early stage of development, the online method is capable of measuring the OP of PM in polluted urban environments and smog chamber studies.

Quantification of Particle-Bound Organic Radicals in Secondary Organic Aerosol.

The chemical composition and evolution of secondary organic aerosol (SOA) in the atmosphere represents one of the largest uncertainties in our current understanding of air quality. Despite vast research, the toxicological mechanisms relating to adverse human health effects upon exposure to particulate matter are still poorly understood. Particle-bound reactive oxygen species (ROS) may substantially contribute to observed health effects by influencing aerosol oxidative potential (OP). The role of radicals in both the formation and aging of aerosol, as well as their contribution to aerosol OP, remains highly uncertain. The profluorescent spin trap BPEAnit (9,10-bis(phenylethynyl)anthracenenitroxide), previously utilized to study combustion-generated aerosol, has been applied to provide the first estimate of particle-bound radical concentrations in SOA. We demonstrate that SOA from different atmospherically important VOC precursors have different particle-bound radical concentrations, estimated for the ozonolysis of α-pinene (0.020 ± 0.0050 nmol/µg), limonene (0.0059 ± 0.0010 nmol/µg), and ß-caryophyllene (0.0025 ± 0.00080 nmol/µg), highlighting the potential importance of OH-initiated formation of particle-bound organic radicals. Additionally, the lifetime of particle-bound radical species in α-pinene SOA was estimated, and a pseudo-first-order rate constant of k = 7.3 ± 1.7 × 10-3 s-1 was derived, implying a radical lifetime on the order of minutes.

Point-of-Care Ultrasound in the Intensive Care Unit.

Spreading beyond the realm of tertiary academic medical centers, point-of-care ultrasound in the intensive care unit is an important diagnostic tool. The real-time feedback garnered can lead to critical and clinically relevant changes in management and decrease potential complications. Bedside ultrasound evaluation in the intensive care setting with a small, portable equipment is well-suited for placement of central lines, lumbar puncture, thoracentesis or other bedside ICU procedures and in the evaluation of cardiac activity, pleural and abdominal cavity and the overall fluid volume. Formalized curriculums centering on point-of-care ultrasound are emerging that will enhance its applicability and relevance.

Detection and identification of Criegee intermediates from the ozonolysis of biogenic and anthropogenic VOCs: comparison between experimental measurements and theoretical calculations.

Ozonolysis of alkenes is a key reaction in the atmosphere, playing an important role in determining the oxidising capacity of the atmosphere and acting as a source of compounds that can contribute to local photochemical "smog". The reaction products of the initial step of alkene-ozonolysis are Criegee intermediates (CIs), which have for many decades eluded direct experimental detection because of their very short lifetime. We use an innovative experimental technique, stabilisation of CIs with spin traps and analysis with proton transfer reaction mass spectrometry, to measure the gas phase concentration of a series of CIs formed from the ozonolysis of a range of both biogenic and anthropogenic alkenes in flow tube experiments. Density functional theory (DFT) calculations were used to assess the stability of the CI-spin trap adducts and show that the reaction of the investigated CIs with the spin trap occurs very rapidly except for the large ß-pinene CI. Our measurement method was used successfully to measure all the expected CIs, emphasising that this new technique is applicable to a wide range of CIs with different molecular structures that were previously unidentified experimentally. In addition, for the first time it was possible to study CIs simultaneously in an even more complex reaction system consisting of more than one olefinic precursor. Comparison between our new experimental measurements, calculations of stability of the CI-spin trap adducts and results from numerical modelling, using the master chemical mechanism (MCM), shows that our new method can be used for the quantification of CIs produced in situ in laboratory experiments.

Online Quantification of Criegee Intermediates of α-Pinene Ozonolysis by Stabilization with Spin Traps and Proton-Transfer Reaction Mass Spectrometry Detection.

Biogenic alkenes, which are among the most abundant volatile organic compounds in the atmosphere, are readily oxidized by ozone. Characterizing the reactivity and kinetics of the first-generation products of these reactions, carbonyl oxides (often named Criegee intermediates), is essential in defining the oxidation pathways of organic compounds in the atmosphere but is highly challenging due to the short lifetime of these zwitterions. Here, we report the development of a novel online method to quantify atmospherically relevant Criegee intermediates (CIs) in the gas phase by stabilization with spin traps and analysis with proton-transfer reaction mass spectrometry. Ozonolysis of α-pinene has been chosen as a proof-of-principle model system. To determine unambiguously the structure of the spin trap adducts with α-pinene CIs, the reaction was tested in solution, and reaction products were characterized with high-resolution mass spectrometry, electron paramagnetic resonance, and nuclear magnetic resonance spectroscopy. DFT calculations show that addition of the Criegee intermediate to the DMPO spin trap, leading to the formation of a six-membered ring adduct, occurs through a very favorable pathway and that the product is significantly more stable than the reactants, supporting the experimental characterization. A flow tube set up has been used to generate spin trap adducts with α-pinene CIs in the gas phase. We demonstrate that spin trap adducts with α-pinene CIs also form in the gas phase and that they are stable enough to be detected with online mass spectrometry. This new technique offers for the first time a method to characterize highly reactive and atmospherically relevant radical intermediates in situ.

Disseminated adenovirus infection causing severe ARDS.

A previously healthy young man with a rare genetic condition presented with severe acute respiratory distress syndrome secondary to pneumonia with septic shock. He did not improve with conventional therapy for his known causal organism thus prompting further workup. He was found to be profoundly immunosuppressed raising our suspicion for atypical organisms. A bronchoalveolar lavage sample was positive via PCR for adenovirus which we suspect exacerbated a pre-existing bacterial pneumonia and led to a severe and non-responsive respiratory failure. His serum adenovirus load was markedly elevated. Treatment was started once the diagnosis of disseminated adenovirus infection was made; however, at that time patient was suffering from refractory hypoxaemia, respiratory acidosis, right heart failure and septic shock. Despite maximal supportive measures our patient ultimately expired over the course of 6 days.

Genotypic characteristics of Staphylococcus aureus isolates from a multinational trial of complicated skin and skin structure infections.

The impact of bacterial genetic characteristics on the outcome of patients with Staphylococcus aureus infections is uncertain. This investigation evaluated potential associations between bacterial genotype and clinical outcome using isolates collected as part of an international phase 2 clinical trial (FAST II) evaluating telavancin for the treatment of complicated skin and skin structure infections (cSSSI). Ninety S. aureus isolates from microbiologically evaluable patients with cSSSI enrolled in the FAST II trial from 11 sites in the United States (56 isolates, or 62%) and 7 sites in South Africa (34 isolates, or 38%) were examined for staphylococcal cassette chromosome mec, agr, and the presence of 31 virulence genes and subjected to pulsed-field gel electrophoresis (PFGE). South African methicillin-susceptible S. aureus (MSSA) isolates were more likely to carry certain virulence genes, including sdrD (P = 0.01), sea (P < 0.01), and pvl (P = 0.01). All 44 (49%) methicillin-resistant S. aureus (MRSA) isolates were from the United States; 37 (84%) were strain USA 300 by PFGE. In the United States, MRSA isolates were more likely than MSSA isolates to carry genes for sdrC (P = 0.03), map/eap (P = 0.05), fnbB (P = 0.11), tst (P = 0.02), sea (P = 0.04), sed (P = 0.04), seg (P = 0.11), sej (P = 0.11), agr (P = 0.09), V8 (P = 0.06), sdrD, sdrE, eta, etb, and see (P < 0.01 for all). MRSA isolates were more often clonal than MSSA isolates by PFGE. Isolates from patients who were cured were significantly more likely to contain the pvl gene than isolates from patients that failed or had indeterminate outcomes (79/84 [94%] versus 3/6 [50%]; P = 0.01). S. aureus strains from different geographic regions have different distributions of virulence genes.