Seasonal tourism's impact on wastewater composition: Evaluating the potential of alternating activated adsorption in primary treatment.

Primary treatment processes have gained attention in recent research and development due to their potential for redirecting carbon towards anaerobic digestion, which can subsequently be used for the production of biomethane. The alternating activated adsorption (AAA) process is implemented on full-scale at several wastewater treatment plants across Europe. However, there is a lack of full-scale studies of advanced carbon capture technology implementations in literature. This study demonstrates the ability of a full-scale AAA process to remove and redirect carbon in a region heavily influenced by tourism. Periods in high and off-season were compared to study the impact of tourism on the composition of the wastewater and the AAA-process. The wastewater characteristics of the high season differed significantly from the low season. During the high season, the PE increased by 37 %, total suspended solids went up by 75 % and chemical oxygen demand increased by 58 %, compared to the low season. Additionally, 80 % of the low volatile lipophilic substances (LVLS) measured were attributed to the impact of tourism. A mass-balance of primary treatment for chemical oxygen demand (COD) and LVLS was conducted for both trial periods. The primary treatment was able to eliminate 56 % of the COD and 62 % of the LVLS in the non-tourist season and 53 % of the COD and 54 % of the LVLS in the tourist season. The increased wastewater load was effectively managed in the AAA-process. Key process parameters like sludge settling characteristics, hydraulic retention time and total suspended solids removal rates remained stable during the high season in winter.

Diagnostic Accuracy of Bone Scintigraphy for the Histopathological Diagnosis of Cardiac Transthyretin Amyloidosis-A Retrospective Austrian Multicenter Study.

We aimed to ascertain the real-world diagnostic accuracy of bone scintigraphy in combination with free light chain (FLC) assessment for transthyretin (ATTR) cardiac amyloidosis (CA) using the histopathological diagnosis derived from endomyocardial biopsy (EMB) as a reference standard. We retrospectively analyzed 102 patients (22% women) with suspected CA from seven Austrian amyloidosis referral centers. The inclusion criteria comprised the available results of bone scintigraphy, FLC assessment, and EMB with histopathological analysis. ATTR and AL were diagnosed in 60 and 21 patients (59%, 21%), respectively, and concomitant AL and ATTR was identified in one patient. The specificity and positive predictive value (PPV) of Perugini score ≥ 2 for ATTR CA were 95% and 96%. AL was diagnosed in three out of 31 patients (10%) who had evidence of monoclonal proteins and a Perugini score ≥ 2. When excluding all patients with detectable monoclonal proteins (n = 62) from analyses, the PPV of Perugini score ≥ 2 for ATTR CA was 100% and the NPV of Perugini score < 2 for ATTR CA was 79%. Conclusively, ATTR CA can be diagnosed non-invasively in the case of a Perugini score ≥ 2 and an unremarkable FLC assessment. However, tissue biopsy is mandatory in suspected CA in any other constellation of non-invasive diagnostic work-up.

Long-term impact of delayed follow-up due to COVID-19 lockdown on patients with neovascular age-related macular degeneration.

BACKGROUND: During the first wave of the coronavirus disease 2019 (COVID-19) pandemic in 2020 outpatient care of neovascular age-related macular degeneration (nAMD) patients was severely reduced due to lockdown. Missed visits are known to be detrimental to patients in need of continued anti-vascular endothelial growth factor (VEGF) intravitreal injections (IVIs). The purpose of the study was to assess the effect of a month-long pause of regular visits and anti-VEGF IVIs in nAMD patients. METHODS: A retrospective study was performed. Patients were treated in a pro re nata ("as needed") scheme. Distance (logMAR) and near (logRAD) visual acuity (VA), optical coherence tomography, delay between planned and actual visit date and the indication for IVI were assessed for 3 continous visits in the 6 months before lockdown (V-3, -2, -1) and the 2 visits after lockdown (V0, V + 1). For analysis of long-term impact, records for visits 1 years before and after lockdown (V-3, V + 2) were gathered. RESULTS: We included 166 patients (120 female, 46 male) with a median (range) age of 80.88 (59.8-99.36) years. Compared to V-1, distance VA was significantly worse at both V0 (0.27 ± 0.21 vs 0.31 ± 0.23 logMAR, p < 0.001) and V + 1 (0.27 ± 0.21 vs 0.30 ± 0.23 logMAR, p = 0.021). Near VA was significantly worse at both V0 (0.31 ± 0.21 vs 0.34 ± 0.22 logRAD, p = 0.037) and V + 1 (0.31 ± 0.21 vs 0.34 ± 0.22 logRAD, p = 0.02). Visit delay (VD) at V0 was significantly longer than at V + 1 (30.81 ± 20.44 vs 2.02 ± 6.79 days, p < 0.0001). Linear regression analysis showed a significant association between visit delay and a reduction of near VA between V-1 and V + 1 (p = 0.0223). There was a significant loss of distance VA (p = 0.02) in the year after the lockdown period (n = 125) compared to the year before. Loss of reading acuity was not significantly increased (p = 0.3). One year post lockdown, there was no correlation between VA change and visit delay after lockdown (p > 0.05). CONCLUSIONS: In nAMD patients whose visits and treatment were paused for a month during the first wave of the COVID-19 pandemic, we found a loss of VA immediately after lockdown, which persisted during follow-up despite re-established anti-VEGF treatment. In the short term, length of delay was predictive for loss of reading VA. The comparison of development of VA during the year before and after the lockdown showed a progression of nAMD related VA loss which may have been accelerated by the disruption of regular visits and treatment. TRIAL REGISTRATION: This article does not report the outcome of a health care intervention. This retrospective study was therefore not registered in a clinical trials database.

[The Prestige of Housewives in Germany-A Quantitative-Empirical Analysis of Differential Perceptions]. / Das Ansehen von Hausfrauen in Deutschland ­ Eine quantitativ-empirische Analyse differenzieller Wahrnehmungen.

The employment rate of women has increased markedly over the past decades, both internationally and in Germany, whereas the classic male breadwinner model is eroding. Against this background, using current survey data, the aim of this study is to examine the social prestige of the shrinking group of housewives whose main activity is domestic and family work. The analyses address, on the one hand, the question of how high their reputation is generally rated by the population in Germany and, on the other hand, whether the perceptions differ systematically by raters' sociodemographic characteristics. The empirical findings show that the reputation of housewives in Germany is generally rated higher than that of the unemployed and of those in helper jobs but lower than for those in professional jobs at the skilled level. Moreover, the assessments of housewives' prestige vary significantly according to the social group (birth cohort, level of education, labor force participation, gender) to which the respondents belong. Further analyses of interaction effects also reveal a differentiated interaction of the gender variable with the other structural group characteristics. The paper concludes with a detailed discussion of the results and an outlook on future research.

Residual municipal solid waste as co-substrate at wastewater treatment plants: An assessment of methane yield, dewatering potential and microbial diversity.

Separately collected organic fraction of municipal solid waste, also known as biowaste, is typically used to fill the available capacity of digesters at wastewater treatment plants. However, this approach might impair the use of the ensuing digestate for fertilizer production due to the presence of sewage sludge, a contaminated substrate. Worldwide, unsorted municipal solid household waste, i.e. residual waste, is still typically disposed of in landfills or incinerated, despite its high content of biodegradables and recyclables. Once efficiently separated from residual waste by mechanical processes, the biodegradables might be appropriate to substitute biowaste at wastewater treatment plants. Thus, the biowaste would be available for fertilizer production and contribute to a reduction in the demand on non-renewable fertilizers. This study aimed at determining the technical feasibility of co-digesting the mechanically separated organic fraction of residual waste with sewage sludge. Further, key parameters for the implementation of co-digestion at wastewater treatment plants were determined, namely, degradation of the solids and organics, specific methane production, flocculant demand, and dewatered sludge production. The microbial community and diversity in both mono- and co-digestion was also investigated. Semi-continuous laboratory scale experiments showed that the co-substrate derived from the residual waste provided a stable anaerobic co-digestion process, producing 206 to 245 L of methane per kg of volatiles solids added to the digester. The dewaterability of the digestate increased by 4.8 percentage points when the co-substrate was added; however, there was also an increase in the flocculant demand. The specific dewatered sludge production was 955 kg per ton of total solids of co-substrate added to the digester. Amplicon sequencing analysis provided a detailed insight into the microbial communities, which were primarily affected by the addition of co-substrate. The microbiota was fully functional and no inhibition or problems in the anaerobic digestion process were observed after co-substrate addition.

The economic efficiency of the co-digestion at WWTPs: A full-scale study.

The methane and digestate production from biowaste (BW, 95% food waste and 5% garden waste based on fresh mass) and grease trap sludge (GTS) co-digestion at the Grossache-Nord WWTP (Austria) as a basis for a cost-benefit analysis was determined using two approaches: The first one was to determine the specific methane yields (SMY) and total solids (TS) removals (%) of the used substrates in biomethane potential (BMP) tests. In the second, the full-scale process data from a supervisory control and data acquisition (SCADA) system were analyzed. From these data, the SMY of the sewage sludge (SS) was calculated for a period without co-digestion and applied to the study period. Thus, it was possible to calculate the methane and digestate production from the co-substrates. Both approaches produced different co-substrate SMYs and TS degradation results. In the approach using the BMP, the SMY was 518 m3/t TSadded and the TS degradation was 77%. For the full-scale method, these values were found to be 620 m3/t TSadded and 66%, respectively. However, the cost-benefit analysis of both approaches indicated that electricity generation from co-digestion can cover the associated costs. The benefit to cost ratio was 1.14 and 1.08 for the BMP and full-scale approach, respectively. The application of the respective approach depends on the availability and quality of full-scale process SCADA data.

Determination of the dewatered digestate amounts and methane yields from the co-digestion of biowaste as a basis for a cost-benefit analysis.

Co-digestion is the simultaneous digestion of two or more substrates and a common practice at wastewater treatment plants (WWTPs). The amounts of methane and digested sludge produced are key parameters for evaluating the economic efficiency of co-digestion. However, the share of dewatered digestate produced from co-substrates is not known. Synergistic effects in co-digestion, i.e. a better biodegradability compared to the mono-digestion of each substrate, might reduce the amounts of digested sludge and increase methane yields. However, these effects might also influence the calculation of methane and digestate quantities from co-substrates. The main objective of this work was to provide a basis for the cost-benefit analysis of biowaste (BW) co-digestion at WWTPs for this data. Therefore, continuous and batch experiments with sewage sludge (SS) and BW co-digestion were conducted and evaluated for methane and digestate production, and possible synergistic effects. BW co-digestion led to an additional production of 0.35 t total solids (TS) of dewatered sludge per ton TSadded in continuous and 0.23 t TS of dewatered sludge per ton of TSadded in batch experiments. The methane yield from BW was 441 L/kg TSadded in continuous experiments and 482 L/kg TSadded batch test. No synergistic effects were observed in both batch and continuous co-digestion experiments. Batch tests were found to be suitable for a rough estimation of the co-digestion economic efficiency key parameters. Continuous experiments are recommended to obtain more robust data. A cost-benefit analysis found that electricity production from co-digestion can generate savings of 88-170 €/t TSadded compared to grid purchase.

Retinal pigment epithelial characteristics in eyes with neovascular age-related macular degeneration : Long-term retinal changes under anti-vascular endothelial growth factor treatment.

PURPOSE: The aim of this study was to assess retinal pigment epithelial (RPE) and retinal structural changes in eyes with neovascular age-related macular degeneration (AMD) treated with anti-vascular endothelial growth factor (anti-VEGF) during long-term follow-up and to evaluate morphological markers potentially influencing prognosis. METHODS: A total of 18 eyes of 18 patients with neovascular AMD were examined subsequent to completion of the Avastin Versus Lucentis in Age Related Macular Degeneration (MANTA) study following a mean period of 84 months (range 69-93 months). After receiving a loading dose of 3 intravitreal anti-VEGF injections subsequent to baseline of the MANTA study, patients were treated as needed (pro re nata, PRN). Functional and morphological changes were assessed, the latter using spectral domain optical coherence tomography (SD-OCT). RESULTS: Retinal/RPE atrophy generally increased significantly during follow-up compared to baseline (fibrosis 28% vs. 89%, p = 0.0001, geographic atrophy, GA 0% vs. 67%, p = 0.0002, RPE porosity 61% vs. 100%, p = 0.009) whereas regenerative alterations tendentially increased until 3 months and then subsequently declined until the last visit (RPE thickening 28% vs. 11%, p = 0.22 and intraretinal hyperreflective foci 89% vs. 78%, p = 0.39). CONCLUSION: Atrophic alterations of the retina and RPE are progressive and may partly be induced by anti-VEGF. Morphological findings may aid in the identification of prognostic markers in the progression of neovascular AMD. This could lead to a more targeted education of affected patients.

Diagnosis and treatment of cardiac amyloidosis: an interdisciplinary consensus statement.

The prevalence and significance of cardiac amyloidosis have been considerably underestimated in the past; however, the number of patients diagnosed with cardiac amyloidosis has increased significantly recently due to growing awareness of the disease, improved diagnostic capabilities and demographic trends. Specific therapies that improve patient prognosis have become available for certain types of cardiac amyloidosis. Thus, the earliest possible referral of patients with suspicion of cardiac amyloidosis to an experienced center is crucial to ensure rapid diagnosis, early initiation of treatment, and structured patient care. This requires intensive collaboration across several disciplines, and between resident physicians and specialized centers. The aim of this consensus statement is to provide guidance for the rapid and efficient diagnosis and treatment of light-chain amyloidosis and transthyretin amyloidosis, which are the most common forms of cardiac amyloidosis.

Heart failure from ATTRwt amyloid cardiomyopathy is associated with poor prognosis.

AIMS: Amyloid cardiomyopathy is an underappreciated cause of morbidity and mortality. Recent evidence suggests that ATTR wild-type cardiomyopathy (ATTRwt-CM) is probably much more common than widely appreciated. So far, no data are available on comparison of mortality from ATTRwt-CM and other heart failure aetiologies. METHODS AND RESULTS: This was a retrospective, observational, cohort study of 2251 patients and their data collected prospectively from May 2000 to June 2018. Long-term mortality was the main outcome measure. Underlying cardiomyopathies were classified as amyloid CM (6.1%) [ATTRwt 3.0%; light-chain amyloidosis (AL) 3.1%], dilated CM (dCMP) (46.4%), ischaemic heart disease (IHD) (24.4%), hypertensive heart disease (HHD) (14.6%), hypertrophic CM (HCM) (5.1%), and valvular heart disease (VHD) (3.4%). Median duration of follow-up was 7.1 years (interquartile range 3.4-11.3). Five-year overall survival in the whole cohort was 80.1%. In multivariate analysis, individuals with amyloid CM were 3.74 times [95% confidence interval (CI) 2.72-5.14; P < 0.001] more likely to die of any reason than were individuals with dCMP. Mortality was higher in AL-CM compared with ATTRwt-CM [hazard ratio (HR) 2.88; 95% CI 1.48-5.58; P = 0.002]. Mortality rates in patients with ATTRwt-CM were higher than in patients with dCMP (HR 1.96; 95% CI 1.24-3.22; P = 0.007), HCM (HR 2.94; 95% CI 1.28-6.67; P = 0.011), HHD (HR 2.08; 95% CI 1.27-3.45; P = 0.004), VHD (HR 2.38; 95% CI 1.30-4.35; P = 0.005), or left ventricular ejection fraction ≥ 40% (HR 1.99; 95% CI 1.12-3.52; P = 0.018). CONCLUSIONS: Our study demonstrates that amyloid CM is independently associated with poor survival among patients with various causes of heart failure. ATTRwt-CM had a better long-term prognosis than did AL-CM, but was associated with higher mortality than were dCMP, HCM, HHD, VHD, and heart failure with preserved or mid-range ejection fraction.

Active dendritic currents gate descending cortical outputs in perception.

The output of cortical columns is routed to different downstream targets via distinct pathways: cortico-cortical and cortico-subcortical. It is as yet unclear what roles these pathways play in perception, and which cellular and circuit mechanisms regulate their gating. We recently showed that activation of the apical dendrites of layer 5 (L5) pyramidal neurons correlates with the threshold for perception, but these neurons come in two classes that target either other cortical or subcortical areas. In the present study, we took advantage of transgenic mouse lines for these L5 subclasses to determine their relative contributions to the perceptual process. We found that the activation of apical dendrites in neurons of the somatosensory cortex, which project to subcortical regions, almost exclusively determined the detection of tactile stimuli in mice. Our results suggest that dendritic activation drives context-dependent interactions between cortex and subcortical regions, including the higher-order thalamus, superior colliculus and striatum, which are crucial for perception.

Cyclopentenone Prostaglandins and Structurally Related Oxidized Lipid Species Instigate and Share Distinct Pro- and Anti-inflammatory Pathways.

Oxidized lipids play a critical role in a variety of diseases with two faces: pro- and anti-inflammatory. The molecular mechanisms of this Janus-faced activity remain largely unknown. Here, we have identified that cyclopentenone-containing prostaglandins such as 15d-PGJ2 and structurally related oxidized phospholipid species possess a dual and opposing bioactivity in inflammation, depending on their concentration. Exposure of dendritic cells (DCs)/macrophages to low concentrations of such lipids before Toll-like receptor (TLR) stimulation instigates an anti-inflammatory response mediated by nuclear factor erythroid 2-related factor 2 (Nrf2)-dependent inhibition of nuclear factor κB (NF-κB) activation and downstream targets. By contrast, high concentrations of such lipids upon TLR activation of DCs/macrophages result in inflammatory apoptosis characterized by mitochondrial depolarization and caspase-8-mediated interleukin (IL)-1ß maturation independently of Nrf2 and the classical inflammasome pathway. These results uncover unexpected pro- and anti-inflammatory activities of physiologically relevant lipid species generated by enzymatic and non-enzymatic oxidation dependent on their concentration, a phenomenon known as hormesis.

Heart failure disease management programs in Austria 2019 : A systematic survey of the Heart Failure Working Group and the Working Group for Cardiological Assistance and Care Personnel of the Austrian Society of Cardiology.

Heart failure (HF) is common and is associated with high morbidity, mortality and high health expenditure. A multidisciplinary disease management plan (DMP) can reduce morbidity and mortality, save costs and improve the quality of life. In Austria, three HF-specific DMPs are currently in a project phase and four established DMPs are active. Although programs are widely heterogeneous with respect to their intervention type, they pursue the same interventional goal by supporting seamless care between inpatient and community care settings with a multidisciplinary team. This survey presents a systematic survey of the HF-specific DMPs in Austria. Disparities between programs are highlighted and discussed. The nationwide establishment of HF-specific DMPs that integrate primary care and cardiology services including a regulation of the remuneration of stakeholders and program infrastructure is needed to decrease the burden of HF for both the individual and society.

Unifying Long-Term Plasticity Rules for Excitatory Synapses by Modeling Dendrites of Cortical Pyramidal Neurons.

A large number of experiments have indicated that precise spike times, firing rates, and synapse locations crucially determine the dynamics of long-term plasticity induction in excitatory synapses. However, it remains unknown how plasticity mechanisms of synapses distributed along dendritic trees cooperate to produce the wide spectrum of outcomes for various plasticity protocols. Here, we propose a four-pathway plasticity framework that is well grounded in experimental evidence and apply it to a biophysically realistic cortical pyramidal neuron model. We show in computer simulations that several seemingly contradictory experimental landmark studies are consistent with one unifying set of mechanisms when considering the effects of signal propagation in dendritic trees with respect to synapse location. Our model identifies specific spatiotemporal contributions of dendritic and axo-somatic spikes as well as of subthreshold activation of synaptic clusters, providing a unified parsimonious explanation not only for rate and timing dependence but also for location dependence of synaptic changes.

High density of genuine growth twins in electrodeposited aluminum.

We demonstrate electrodeposition as a synthesis method for fabrication of Al coatings, up to 10 µm thick, containing a high density of genuine growth twins. This has not been expected since the twin boundary energy of pure Al is very high. TEM methods were used to analyze deposited Al and its nanoscaled twins. DFT methods confirmed that the influence of the substrate is limited to the layers close to the interface. Our findings are different from those achieved by sputtering of Al coatings restricted to a thickness less than 100 nm with twins dominated by epitaxial effects. We propose that in the case of electrodeposition, a high density of twins arises because of fast nucleation and is additionally promoted by a monolayer of adsorbed hydrogen originating from water impurities. Therefore, electrodeposition is a viable approach for tailoring the structure and properties of thicker, deposited Al coatings reinforced by twins.

Optically Induced Calcium-Dependent Gene Activation and Labeling of Active Neurons Using CaMPARI and Cal-Light.

The advent of optogenetic methods has made it possible to use endogeneously produced molecules to image and manipulate cellular, subcellular, and synaptic activity. It has also led to the development of photoactivatable calcium-dependent indicators that mark active synapses, neurons, and circuits. Furthermore, calcium-dependent photoactivation can be used to trigger gene expression in active neurons. Here we describe two sets of protocols, one using CaMPARI and a second one using Cal-Light. CaMPARI, a calcium-modulated photoactivatable ratiometric integrator, enables rapid network-wide, tunable, all-optical functional circuit mapping. Cal-Light, a photoactivatable calcium sensor, while slower to respond than CaMPARI, has the capacity to trigger the expression of genes, including effectors, activators, indicators, or other constructs. Here we describe the rationale and provide procedures for using these two calcium-dependent constructs (1) in vitro in dissociated primary neuronal cell cultures (CaMPARI & Cal-Light); (2) in vitro in acute brain slices for circuit mapping (CaMPARI); (3) in vivo for triggering photoconversion or gene expression (CaMPARI & Cal-Light); and finally, (4) for recovering photoconverted neurons post-fixation with immunocytochemistry (CaMPARI). The approaches and protocols we describe are examples of the potential uses of both CaMPARI & Cal-Light. The ability to mark and manipulate neurons that are active during specific epochs of behavior has a vast unexplored experimental potential.

Indications for and outcome in patients with the wearable cardioverter-defibrillator in a nurse-based training programme: results of the Austrian WCD Registry.

BACKGROUND: The wearable cardioverter-defibrillator is a treatment option for patients at temporarily high risk of sudden cardiac death or in whom implantation of a cardioverter-defibrillator is temporarily not possible. OBJECTIVES: The aim of this study was to provide real-world data on patients receiving this therapy in a nurse-based wearable cardioverter-defibrillator training programme. METHODS: A registry including all patients prescribed with a wearable cardioverter-defibrillator in Austria between 2010 and 2016. Overall, 448 patients received a wearable cardioverter-defibrillator in 48 centres. Patients received structured nurse-based wearable cardioverter-defibrillator educational initial training followed by remote monitoring. RESULTS: Main indications were: severe non-ischaemic cardiomyopathy (21%); recent myocardial infarction and percutaneous coronary intervention (20%); and stable coronary artery disease with percutaneous coronary intervention/coronary artery bypass grafting (14%). Eleven patients (2.5%) received 22 appropriate wearable cardioverter-defibrillator shocks. Two patients (0.4%) received three inappropriate shocks. The risk of sudden cardiac death varied between different aetiologies. Eight out of 11 (73%) patients received their first wearable cardioverter-defibrillator shock within 30 days. The main reasons for termination of the wearable cardioverter-defibrillator therapy were implantable cardioverter-defibrillator implantation (55.5%) and improvement of left ventricular ejection fraction to more than 35% (33%). CONCLUSION: The wearable cardioverter-defibrillator is an effective and safe treatment option in patients at either transiently elevated risk of ventricular tachycardia/ventricular fibrillation or mandated postponed implantable cardioverter-defibrillator implantation, with a 2.5% shock rate over a median 54 days wearable cardioverter-defibrillator treatment period. However, both the wearable cardioverter-defibrillator shock rate and implantable cardioverter-defibrillator implantation rate vary widely depending on the wearable cardioverter-defibrillator indication. Nurse-based wearable cardioverter-defibrillator training is associated with high patient adherence, with a median wearing duration per day of 23.5 (1-24) hours.

Identification of biologically active δ-lactone eicosanoids as paraoxonase substrates.

The mammalian paraoxonases (PONs 1, 2 and 3) are a family of esterases that are highly conserved within and between species. They exhibit antioxidant and anti-inflammatory activities. However, their physiological function(s) and native substrates are uncertain. Previous structure-activity relationship studies demonstrate that PONs have a high specificity for lipophilic lactones, suggesting that such compounds may be representative of native substrates. This report describes the ability of PONs to hydrolyze two bioactive δ-lactones derived from arachidonic acid, 5,6-dihydroxy-eicosatrienoic acid lactone (5,6-DHTL) and cyclo-epoxycyclopentenone (cyclo-EC). Both lactones were very efficiently hydrolyzed by purified PON3. PON1 efficiently hydrolyzed 5,6-DHTL, but with a specific activity about 15-fold lower than PON3. 5,6-DHTL was a poor substrate for PON2. Cyclo-EC was a poor substrate for PON1 and not hydrolyzed by PON2. Studies with the PON inhibitor EDTA and a serine esterase inhibitor indicated that the PONs are the main contributors to hydrolysis of the lactones in human and mouse liver homogenates. Studies with homogenates from PON3 knockout mouse livers indicated that >80% of the 5,6-DHTL and cyclo-EC lactonase activities were attributed to PON3. The findings provide further insight into the structural requirements for PONs substrates and support the hypothesis that PONs, particularly PON1 and PON3, evolved to hydrolyze and regulate a class of lactone lipid mediators derived from polyunsaturated fatty acids.

Ynol Ethers as Ketene Equivalents in Rhodium-Catalyzed Intermolecular [5 + 2] Cycloaddition Reactions.

The previously unexplored metal-catalyzed [5 + 2] cycloadditions of vinylcyclopropanes (VCPs) and electron-rich alkynes (ynol ethers) have been found to provide a highly efficient, direct route to dioxygenated seven-membered rings, a common feature of numerous natural and non-natural targets and building blocks for synthesis. The reactions proceed in high yield at room temperature and tolerate a broad range of functionalities. Substituted VCPs were found to react with high regioselectivity.