The Watch List (WL) is a monitoring program under the European Water Framework Directive (WFD) to obtain high-quality Union-wide monitoring data on potential water pollutants for which scarce ...monitoring data or data of insufficient quality are available. The main purpose of the WL data collection is to determine if the substances pose a risk to the aquatic environment at EU level and subsequently to decide whether a threshold, the Environmental Quality Standards (EQS) should be set for them and, potentially to be listed as priority substance in the WFD. The first WL was established in 2015 and contained 10 individual or groups of substances while the 4th WL was launched in 2022. The results of monitoring the substances of the first WL showed that some countries had difficulties to reach an analytical Limit of Quantification (LOQ) below or equal to the Predicted No-Effect Concentrations (PNEC) or EQS. The Joint Research Centre (JRC) of the European Commission (EC) organised a series of workshops to support the EU Member States (MS) and their activities under the WFD. Sharing the knowledge among the Member States on the analytical methods is important to deliver good data quality. The outcome and the discussion engaged with the experts are described in this paper, and in addition a literature review of the most important publications on the analysis of 17-alpha-ethinylestradiol (EE2), amoxicillin, ciprofloxacin, metaflumizone, fipronil, metformin, and guanylurea from the last years is presented.
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The MIMO clinical trial showed that patients with acute cardiogenic pulmonary edema (ACPE) treated with midazolam had fewer serious adverse events than those treated with morphine. Atrial ...fibrillation (AF) is a common comorbidity in heart failure and affects patient's outcome.
The primary endpoint of this substudy is to know if AF modified the reduced risk of serious adverse events in the midazolam arm compared to morphine. The first secondary endpoint is to know if AF modified the reduced risk of serious adverse events or death at 30 days in the midazolam arm. The second secondary objective of this substudy is to analyze whether AF modified the reduced risk of midazolam against morphine on the total number of serious adverse events per patient.
We conducted a secondary analysis of the MIMO trial. Patients more than 18 years old clinically diagnosed with ACPE and with dyspnea and anxiety were randomized (1:1) at emergency department arrival to receive either intravenous midazolam or morphine.
In this post hoc analysis, we calculated the relative risk (RR) of serious adverse events in patients with and without AF. Calculating the Cochran-Mantel-Haenszel interaction test, we evaluated if AF modified the reduced risk of serious adverse events in the midazolam arm compared to morphine.
One hundred eleven patients (median = 78.9 years; IQR, 72.3-83.7; women, 52.2%) were randomized in the MIMO trial, 55 to receive midazolam and 56 to morphine. All randomized patients received the assigned drug and there were no losses to follow-up. Forty-four patients (39.6%) had AF. In the AF group, the RR for the incidence of serious adverse events in the midazolam versus morphine arm was 0.42 (95% CI, 0.14-1.3). In the group without AF, the RR was 0.46 (95% CI, 0.21-1). The presence of AF did not modify the reduced risk of serious adverse events in the midazolam arm compared with morphine ( P for interaction = 0.88).
This post hoc analysis of the MIMO trial suggests that the reduced risk of serious adverse events in the midazolam group compared to morphine is similar in patients with and without AF.
The neuromodulatory subcortical system (NSS) nuclei are critical hubs for survival, hedonic tone, and homeostasis. Tau‐associated NSS degeneration occurs early in Alzheimer's disease (AD) ...pathogenesis, long before the emergence of pathognomonic memory dysfunction and cortical lesions. Accumulating evidence supports the role of NSS dysfunction and degeneration in the behavioral and neuropsychiatric manifestations featured early in AD. Experimental studies even suggest that AD‐associated NSS degeneration drives brain neuroinflammatory status and contributes to disease progression, including the exacerbation of cortical lesions. Given the important pathophysiologic and etiologic roles that involve the NSS in early AD stages, there is an urgent need to expand our understanding of the mechanisms underlying NSS vulnerability and more precisely detail the clinical progression of NSS changes in AD. Here, the NSS Professional Interest Area of the International Society to Advance Alzheimer's Research and Treatment highlights knowledge gaps about NSS within AD and provides recommendations for priorities specific to clinical research, biomarker development, modeling, and intervention.
Highlights
Neuromodulatory nuclei degenerate in early Alzheimer's disease pathological stages.
Alzheimer's pathophysiology is exacerbated by neuromodulatory nuclei degeneration.
Neuromodulatory nuclei degeneration drives neuropsychiatric symptoms in dementia.
Biomarkers of neuromodulatory integrity would be value‐creating for dementia care.
Neuromodulatory nuclei present strategic prospects for disease‐modifying therapies.
Lavandula stoechas L. and Lavandula dentata L. have been widely used as popular herbal medicines in the Mediterranean region to treat digestive disorders and kidney diseases. Both species have quite ...a similar morphology, which makes them too frequently share the same popular name and be often used indistinctly in traditional medicine although they have different properties. The aim of this study was to use metabolomics approaches, followed by multivariate analyses to facilitate the taxonomical classifications. A non-targeted metabolomic strategy based on high-performance liquid chromatography coupled with high-resolution quadrupole time-of-flight mass spectrometry (LC-QTOF/MS) has been applied to two hydroalcoholic extracts from Lavandula species (L. dentata L. and L. stoechas L.) with the aim of elucidating the major discriminatory metabolites. The principal component analysis of the LC-QTOF/MS data showed a clear discrimination between both species, using the first two principal components. The key compounds responsible for the discrimination were tentatively identified as sucrose and glycosylated flavonoids by comparison with spectral data bases and previous studies. These results clearly show that both plant species have a different expression pattern for these marker metabolites that might be potentially used as a novel chemotaxonomical tool, in addition to classical approaches.
Abstract Background Asticot maggot (Blowfly, Calliphoridae family) is the most important live bait used for angling in our country. Prevalence of allergy to live fish bait in occupationally exposed ...workers has been described. The purpose of this study was to determine the prevalence of asticot allergy in amateur fishermen and the identification of marketed asticot species in Cáceres, Spain. Materials and Methods Seventy-two randomised selected patients (Angler's Society of Cáceres) completed a questionnaire about fishing habits and allergic symptoms related with live bait handling. Skin prick test (SPT) with local asticot and common earthworm extracts were performed. Serum IgE levels to imported species ( Protophormia terraenovae, Calliphora vomitoria, Lucilia sericata, Lumbricus terrestris ) were measured. Local asticot and common earthworm samples were obtained for taxonomic identification. Data were analysed using the SPSS 12.0 software. Results Five patients (7 %) reported allergic symptoms caused by asticot maggots. All of them were positive for SPT to asticot and specific IgE to P. terraenovae . Sensitisation to P. terraenovae was found in 40 patients (58.8 %). No associated factors for asticot allergy were observed. Larvae and adult flies of local asticot samples were identified as P. terraenovae. Conclusions Commercially available asticot, in Cáceres, is composed by P. terraenovae larvae (Diptera. Calliphoridae ). A 7 % prevalence of P. terraenovae allergy in amateur fishermen of Cáceres was obtained. The allergenic potential of P. terraenovae seems to be greater than that of other blowflies and L. terrestris . The SPT with P. terraenovae extract is a very sensitive and specific technique in the diagnosis of live bait allergy in fishermen.
Experimental studies have shown the beneficial effects of antioxidant supplementation on endothelial function in the presence of increased endogenous oxidative stress, whereas limited data are ...available under normal conditions. The present study tested the hypothesis that in normal pigs long-term antioxidants would have deleterious effects on the cardiovascular system. Normal domestic pigs (V, n=6) were studied 12 weeks after dietary supplementation with vitamin E (100 IU/kg per day) and vitamin C (1 g/day) and compared with normal controls (C, n=7). Myocardial perfusion and permeability index were evaluated by electron beam computed tomography after intravenous adenosine and dobutamine. Coronary endothelial function was evaluated in vitro by organ chamber and coronary tissue studied by immunoblotting and staining. Myocardial perfusion response was lower in V than in C after adenosine (10.1+/-4.5 versus 53.4+/-5.2%; P<0.01) and dobutamine (V, 78.4+/-8.1; C, 193.0+/-39.0%; P<0.05). The permeability index increased in V after adenosine (48.8+/-5.1%) and dobutamine (59.9+/-13.6%) and did not change in C. Coronary vasodilation to bradykinin and substance P was lower in V than in C. Moreover, in V, coronary nitrotyrosine and superoxide content was significantly higher than in C. The groups had similar total monomer expression of endothelial nitric oxide synthase, whereas the dimerized form, reflecting coupled enzyme, was lower in V. These findings suggest that long-term experimental antioxidant vitamin supplementation in normal pigs impairs myocardial perfusion and coronary endothelial function via an increased level of oxidative stress in the arterial wall, which may be partly related to the uncoupling of endothelial nitric oxide synthase and/or the direct prooxidant effect of vitamin radicals.
We report a case of anaphylaxis caused by cloxacillin in a 13-year-old patient. The basophil activation test, performed 25 days after the anaphylactic reaction, was positive to cloxacillin, ...amoxicillin, and penicillin G and negative to ibuprofen, tolerated by the patient. The analysis was performed 17 days after the reaction was not conclusive because 74% of the basophil population was activated in basal conditions. The abnormally high activation was similar to that found in an analysis before the reaction, exactly 4 days after finishing a well-tolerated treatment with amoxicillin. This first analysis was available because a patient's sample was taken from the emergency laboratory as a blind control for a study to assess the basophil activation test reliability in diagnosis of hypersensitivity to NSAIDs. The high number of activated basophils in basal conditions after treatment with amoxicillin and before the anaphylactic reaction to cloxacillin probably reflects the beginning of the sensitization. Until now, no cases of hypersensitivity to cloxacillin have been diagnosed by means of the basophil activation test.
Abstract Objectives The effects of hypercholesterolemia (HC) on the myocardium and the underlying mechanisms are unclear. We tested the hypothesis that diet-induced HC-induced myocardial fibrosis by ...regulating the transforming growth factor (TGF)-β pathway and apoptosis through increased oxidative stress, and that these would be functionally consequential. Methods Three groups of pigs ( n = 6 each) were studied after 12 weeks of normal or 2% HC diet, or HC + antioxidant supplementation. Cardiac function was evaluated by electron beam computed tomography, while fibrogenic mechanisms and apoptosis were evaluated in myocardial tissue. Results HC-induced myocardial fibrosis was accompanied by increased ratio of interstitial collagen I/III (1.4 ± 0.3 versus 0.5 ± 0.1 in normal, p < 0.05), expression of TGF-β1 and its downstream smad mediators, as well as myocyte apoptosis. These alterations were also associated with a decrease in diastolic filling rate compared to normal (134.0 ± 10.6 ml/s versus 70.3 ± 14.3 ml/s, p < 0.05), but were attenuated in HC animals chronically supplemented with antioxidants. Conclusions Myocardial injury elicited by experimental HC includes redox-sensitive increases in TGF-β1 expression and apoptosis, which are associated with diastolic dysfunction. These observations underscore a role of increased oxidative stress in modulating myocardial tissue remodeling and dysfunction in vivo in HC.
We tested the hypothesis that in early hypertension (HT), increased oxidative stress leads to myocardial microvascular remodeling.
Pigs were studied after a 12-week observation: normal (n=8), ...untreated renovascular HT (n=8), or HT+chronic antioxidant supplementation (HT+A, n=6). Left ventricular muscle mass (LVMM) and myocardial blood flow (MBF) reserve were determined using electron beam computer tomography (CT), and the spatial density and tortuousity of myocardial microvessels (<500 microm) was then measured in myocardial samples with micro-CT. Myocardial microvascular morphology, oxidative stress, inflammation, and growth factor expression were determined in vitro. HT and HT+A had similarly increased arterial pressure and LVMM, but only HT showed impaired MBF response to adenosine. Compared with normal, HT had increased spatial density of myocardial microvessels, which was preserved in HT+A (111.8+/-7.8, 166.3+/-15.7, and 106.4+/-6.1 vessels per cm2, respectively). HT also showed microvascular wall thickening, increased systemic and tissue oxidative stress, inflammation, and expression of vascular endothelial growth factor and its receptor Flk-1, most of which were attenuated by antioxidants.
Myocardial microvascular remodeling in early HT is accompanied by tissue oxidative stress, inflammation, and altered growth factor expression, and attenuated by antioxidant intervention. This study underscores a role of increased oxidative stress in modulating myocardial microvascular architecture in early HT.
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