The lack of knowledge about the onset and progression of Parkinson’s disease (PD) hampers its early diagnosis and treatment. Metabolomics might shed light on the PD imprint seeking a broader view of the biochemical remodeling induced by this disease in an early and pre-symptomatic stage and unveiling potential biomarkers. To achieve this goal, we took advantage of the great potential of the European Prospective Study on Nutrition and Cancer (EPIC) cohort to apply metabolomics searching for early diagnostic PD markers. This cohort consisted of healthy volunteers that were followed for around 15 years until June 2011 to ascertain incident PD. For this untargeted metabolomics-based study, baseline preclinical plasma samples of 39 randomly selected individuals that developed PD (Pre-PD group) and the corresponding control group were analyzed using a multiplatform approach. Data were statistically analyzed and exposed alterations in 33 metabolites levels, including significantly lower levels of free fatty acids (FFAs) in the preclinical samples from PD subjects. These results were then validated by adopting a targeted HPLC-QqQ-MS approach. After integrating all the metabolites affected, our finding revealed alterations in FFAs metabolism, mitochondrial dysfunction, oxidative stress, and gut–brain axis dysregulation long before the development of PD hallmarks. Although the biological purpose of these events is still unknown, the remodeled metabolic pathways highlighted in this work might be considered worthy prognostic biomarkers of early prodromal PD. The findings revealed by this work are of inestimable value since this is the first study conducted with samples collected many years before the disease development.

There is an increasing awareness about the presence of per- and polyfluoroalkyl substances (PFAS) in many environmental and biological compartments, including human biofluids and tissues. However, the increase of PFAS replacements, including alternatives with shorter chain or less bioaccumulative potential, has broaden the exposure and the need for wider identification procedures. Moreover, the low volumes available for human blood or plasma, and the high number of samples needed to assess adequately epidemiologic studies, require particularly fast, reproducible and, if possible, miniaturized protocols. Therefore, accurate and robust analytical methods are still needed to quantify the PFAS's burden in humans and to understand potential health risks. In this study, we have developed and validated the analysis of 42 PFAS in human plasma by means of a Captiva 96-well micro extraction plate and a LC-q-Orbitrap. For the optimization of the analytical workflow, three extraction/clean-up methods were tested, and the selected one was validated using spiked artificial and bovine plasma at four concentration levels. The final method showed high absolute recoveries for the 42 PFAS, ranging from 52% to 130%, instrumental detection limits between 0.001-0.6 ng mL^-1, overall good precision (CV < 20% for most of the PFAS) and a low uncertainty (< 30% of relative expanded deviation, k = 2). The method was further validated both with the NIST plasma Standard Reference Material 1950, showing that the accuracy of the provided results was between 63%-101%, and by the proficiency test arranged by the Arctic Monitoring Assessment Program (AMAP, 2022) obtaining satisfactory results within 95% confidence interval of the assigned value.

Many of the infectious diseases that affect livestock have bacteria as etiological agents. Thus, therapy is based on antimicrobials that leave the animal’s tissues mainly via urine, reaching the environment through slurry and waste water. Once there, antimicrobial residues may lead to antibacterial resistance as well as toxicity for plants, animals, or humans. Hence, the objective was to describe the rate of antimicrobial excretion in urine in order to select the most appropriate molecule while reducing harmful effects. Thus, 62 pigs were treated with sulfamethoxypyridazine, oxytetracycline, and enrofloxacin. Urine was collected through the withdrawal period and analysed via LC-MS/MS. Oxytetracycline had the slowest rate of degradation (a half-life time of 4.18 days) and the most extended elimination period in urine (over 2 months), followed by enrofloxacin (a half-life time of 1.48 days, total urine elimination in ca. 3 weeks) and sulfamethoxypyridazine (a half-life time of 0.49 days, total urine elimination in ca. 1 week). Bacterial sensitivity and recommendations for responsible use are limiting when selecting the treatment. Nevertheless, with similar effectiveness, sulfamethoxypyridazine would be the choice, as waste treatment would only need to be implemented for 1 week after treatment. Thus, more in-depth knowledge regarding antibacterial elimination would improve resource management, while protecting animals and consumers’ health.

The aim of this work was to determine and study the concentration of different groups of disinfection by-products (DBPs): trihalomethanes, haloacetic acids, haloacetonitriles, haloacetones and combined chlorine (as an indicator of chloramine levels), in the water of 175 public swimming pools in Gipuzkoa (Basque Country, Spain). The study included chlorinated and brominated pools, indoor and outdoor, used for recreational and sports purposes, and filled with water from calcareous and siliceous soils. The most abundant were haloacetic acids, followed by trihalomethanes, with chlorinated or brominated forms predominating depending on whether the pools were disinfected by chlorination or bromination, respectively. All the 75th percentiles of DBPs were below the limits established by the European Chemical Agency (ECHA), although the maximum values of trihalomethanes exceeded them. The same was true for dichloroacetonitrile in chlorinated pools and dibromoacetonitrile in brominated pools. All families of DBPs showed positive associations with each other, all being significant except for combined chlorine. Their mean levels were higher in outdoor pools than in indoor pools, significantly so in all except combined chlorine. Recreational pools showed higher levels of haloacetic acids and combined chlorine than sports pools. The concentrations of the different groups of DBPs were higher in the pools than in the mains water that fed them. This increase, especially that of the haloacetonitriles, as well as the high concentrations of brominated forms in the pools disinfected by bromination, make it necessary to focus on their toxicological implication. The differences in the DBP profiles of the filling network water were not transferred to the pool water.

The introduction of antimicrobial residues in the food chain has a significant impact on human health. An innovative solution to avoid their presence in meat is the adaptation of current control methods for use with in vivo matrixes. Thus, the aim was to obtain paired blood and muscle samples from pigs treated with some of the main antimicrobials currently used in veterinary medicine (oxytetracycline, sulfamethoxypyridazine, enrofloxacin, amoxicillin), and to compare their rate of depletion in both matrixes. Antimicrobial concentrations in paired samples of blood and muscle were determined by liquid chromatography with tandem mass spectrometry (LC–MS/MS) or high performance liquid chromatography with fluorescence detection (HPLC-FLD). A comparison between values obtained in muscle and blood showed a similar distribution in both matrixes for oxytetracycline; for sulfamethoxypyridazine, a similar decrease rate but a concentration three times higher in blood compared to muscle was found; for enrofloxacin, we found significant differences in the rate of depletion, with similar antimicrobial concentrations in both matrixes with values close to the maximum residue limit (MRL) and higher amounts in muscle for values that lay considerably over the MRL. Conversely, amoxicillin depletion was so rapid that its appearance in carcasses does not seem to pose a risk. Therefore, blood would be a feasible matrix for the development of new in vivo tests.