Thyroid Cancer and Endocrine Disruptive Chemicals: A Case-Control Study on Per-fluoroalkyl Substances (PFAS) and Other Persistent Organic Pollutants (POPs).

OBJECTIVE: To evaluate the possible association between some endocrine disruptive chemicals and thyroid cancer (TC) in an Italian case-control cohort. METHODS: We enrolled 112 TC patients and 112 sex- and age-matched controls without known thyroid diseases. Per- and poly-fluoroalkyl substances (PFAS), poly-chlorinated biphenyls (PCBs), and dichlorodiphenyltrichloroethane (4,4'-DDT, and 4,4'-DDE) were measured in the serum by liquid or gas chromatography-mass spectrometry. Unconditional logistic regression, Bayesan Kernel Machine Regression and Weighted Quantile Sum models were used to estimate the association between TC and pollutants' levels, considered individually or as mixture. BRAFV600E mutation was assessed by standard methods. RESULTS: The detection of perfluorodecanoic acid (PFDA) was positively correlated to TC (OR= 2.03, 95% CI 1.10-3.75, p=0.02), while a negative association was found with perfluorohexanesulfonic acid (PFHxS) levels (OR=0.63, 95% CI 0.41-0.98, p=0.04). Moreover, perfluorononanoic acid (PFNA) was positively associated with the presence of thyroiditis, while PFHxS and perfluorooctane sulfonic acid (PFOS) with higher levels of pre-surgical Thyroid-Stimulating Hormone (TSH). PFHxS, PFOS, PFNA and PFDA were correlated with less aggressive TC, while poly-chlorinated biphenyls (PCB-105 and PCB-118) with larger and more aggressive tumours. Statistical models showed a negative association between pollutants' mixture and TC. BRAFV600E mutations resulted associated with PCB-153, PCB-138 and PCB-180. CONCLUSIONS: Our study suggests, for the first time in a case-control population, that exposure to some PFAS and PCBs associates with TC and some clinical and molecular features. On the contrary, an inverse correlation was found with both PFHxS and pollutants' mixture, likely due to a potential reverse causality.

Three-minute nebulization of gentamicin in healthy dogs results in therapeutic concentrations in bronchoalveolar lavage fluid while remaining below the toxic range values in blood.

OBJECTIVE: To determine and compare the concentration of gentamicin in the lower airways and serum of healthy spontaneously breathing dogs after nebulization with 5% undiluted gentamicin during 3 versus 10 minutes. ANIMALS: 10 healthy experimental Beagles. METHODS: This was a prospective crossover study. A standardized bronchoalveolar lavage (BAL) procedure was performed in each dog after 1 week of administration of each of 2 different gentamicin nebulization protocols separated by a 1-week washout period. The 2 protocols consisted of nebulization of 5% undiluted gentamicin (50 mg/mL) twice daily either during 10 minutes per session (± 95 mg; 10-minute protocol) or 3 minutes per session (± 28 mg; 3-minute protocol). BAL fluid (BALF) was obtained under general anesthesia using a bronchoscope within 15 minutes after administration of the last nebulization. Blood was collected within 5 minutes after BALF collection. BALF and serum gentamicin concentrations were determined by particle-enhanced turbidimetric inhibition immunoassay. Concentrations between protocols were compared using a paired t test. RESULTS: Both BALF and serum gentamicin concentrations were higher after the 10-minute protocol compared with the 3-minute protocol (mean ± SD: 2.41 ± 0.87 mg/L vs 1.25 ± 0.31 mg/L, P = .001; and 1.02 ± 0.59 mg/L vs 0.31 ± 0.24 mg/L, P < .0001 in BALF and serum, respectively), while the BALF-to-serum ratio did not differ between the protocols (3.75 [1.37 to 5.75] (median [IQR]) in the 3-minute protocol vs 2.48 [2.02 to 2.67] in the 10-minute protocol; P = .754). CLINICAL RELEVANCE: A 3-minute nebulization of gentamicin seems to achieve sufficient concentrations of gentamicin in the BALF to have good efficacy against aminoglycoside-sensitive bacteria while remaining below the toxic range values in blood.

[Risks of magistral preparations in pediatrics]. / Risques des préparations magistrales en pédiatrie.

Vasoreactive pulmonary arterial hypertension (PAH) in children is a form of idiopathic PAH that responds to vasoreactive testing with nitric oxide (NO) by a significant decrease of pulmonary vascular resistances and pressure. Oral calcium channel antagonists (CCA) that allow pulmonary arterial vasodilation are the treatment of choice. The therapeutic effect is strongly depending on adequate drug intake. In growing children, drug dose must be adapted to weight. In case of unavailability of low-dose pharmaceutical preparations, officinal formulations become mandatory. Officinal formulations may be related to a multitude of errors at different steps including prescription, transcription, preparation and administration. This may have life-threatening consequences for the child.To illustrate this, we report a case of a compounding error with underdosage of CCA, leading to acute cardiovascular failure in an adolescent with vasoreactive PAH.

L'hypertension artérielle pulmonaire (HTAP) vasoréactive chez l'enfant est une forme d'HTAP idiopathique qui répond au test de vasoréactivité au monoxyde d'azote (NO) par une diminution significative des pressions et résistances vasculaires pulmonaires. Le traitement de choix de cette forme d'HTAP est l'administration d'antagonistes des canaux calciques (ACC) par voie orale. Ce traitement entraîne une vasodilatation artérielle pulmonaire, elle-même étroitement dépendante de la prise adéquate du médicament. Chez les enfants en croissance, la dose du médicament doit être adaptée au poids. De façon générale, en l'absence de préparation à faible dose disponible dans les laboratoires pharmaceutiques, l'utilisation de formulations officinales devient obligatoire. De la prescription à l'administration, en passant par la transcription et la préparation, de nombreuses erreurs humaines et techniques peuvent survenir qui peuvent impacter la morbi-mortalité de l'enfant. Nous rapportons le cas d'une adolescente avec HTAP vasoréactive chez qui une erreur de préparation magistrale avec sous-dosage de l'ACC a conduit à une décompensation cardio-vasculaire aiguë et discutons de mesures préventives potentielles.

An Intravenous Pharmacokinetic Study of Cannabidiol Solutions in Piglets through the Application of a Validated Ultra-High-Pressure Liquid Chromatography Coupled to Tandem Mass Spectrometry Method for the Simultaneous Quantification of CBD and Its Carboxylated Metabolite in Plasma.

Cannabidiol (CBD) has multiple therapeutic benefits that need to be maximized by optimizing its bioavailability. Numerous formulations are therefore being developed and their pharmacokinetics need to be studied, requiring analytical methods and data from intravenous administration. As CBD is susceptible to hepatic metabolism, the requirement of any method is to quantify metabolites such as 7-COOH-CBD. We demonstrated that CBD and 7-COOH-CBD could be simultaneously and correctly quantified in piglet plasma by using an UHPLC-MS/MS technique. The validated method allowed for an accurate bioanalysis of an intravenously injected solution consisting of CBD-HPßCD complexes. The experimental pharmacokinetic profile of CBD showed multi-exponential decay characterized by a fast apparent distribution half-life (0.25 h) and an elimination half-life of two hours. The profile of 7-COOH-CBD was not linked with the first-pass metabolism, since 80% of the maximum metabolite concentration was reached at the first sampling time point, without any decrease during the period of study. A two-compartment model was optimal to describe the experimental CBD profile. This model allowed us to calculate macro-micro constants and volumes of distribution (Vss = 3260.35 ± 2286.66 mL) and clearance (1514.5 ± 261.16 mL·h-1), showing that CBD is rapidly distributed to peripheral tissues once injected and slowly released into the bloodstream.

Repeated Human Exposure to Semivolatile Organic Compounds by Inhalation: Novel Protocol for a Nonrandomized Study.

BACKGROUND: Semivolatile organic compounds (SVOCs) comprise several different chemical families used mainly as additives in many everyday products. SVOCs can be released into the air as aerosols and deposit on particulate matter during use by dispersion, evaporation, or abrasion. Phthalates are SVOCs of growing concern due to their endocrine-disrupting effects. Human data on the absorption, distribution, metabolism, and excretion (ADME) of these compounds upon inhalation are almost nonexistent. OBJECTIVE: The goal of this study is to develop a method for repeated inhalation exposures to SVOCs to characterize their ADME in humans. METHODS: We will use diethylhexyl phthalate (DEHP), a major indoor air pollutant, as a model SVOC in this novel protocol. The Swiss official Commission on Ethics in Human Research, Canton de Vaud, approved the study on October 14, 2020 (project-ID 2020-01095). Participants (n=10) will be repeatedly exposed (2 short daily exposures over 4 days) to isotope-labeled DEHP (DEHP-d4) to distinguish administered exposures from background exposures. DEHP-d4 aerosols will be generated with a small, portable, aerosol-generating device. Participants will inhale DEHP-d4-containing aerosols themselves with this device at home. Air concentrations of the airborne phthalates will be less than or equal to their occupational exposure limit (OEL). DEHP-d4 and its metabolites will be quantified in urine and blood before, during, and after exposure. RESULTS: Our developed device can generate DEHP-d4 aerosols with diameters of 2.5 µm or smaller and a mean DEHP-d4 mass of 1.4 (SD 0.2) µg per puff (n=6). As of May 2023, we have enrolled 5 participants. CONCLUSIONS: The portable device can be used to generate phthalate aerosols for repeated exposure in human studies. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/51020.

Intranasal and Serum Gentamicin Concentration: Comparison of Three Topical Administration Protocols in Dogs.

Antimicrobials' topical administration efficacy has not been assessed in dogs with upper respiratory tract disease. The aim was to compare the concentration of gentamicin in nasal lavage fluid (NALF) and in serum after three topical protocols. This was a prospective crossover study of ten healthy dogs. Gentamicin was nebulized for a duration of 1 week, twice a day, for 10 min in the first protocol (10-min protocol) and for 3 min in the second protocol (3-min protocol), while the third protocol consisted of the administration of 0.25 mL of gentamicin in each nostril (drop protocol). Median concentrations of gentamicin in NALF were 9.39 µg/mL (8.12-19.97 interquartile range), 4.96 µg/mL (4.60-6.43) and 137.00 µg/mL (110.5-162.00) in the 10-min protocol, 3-min protocol and drop protocol, respectively. The result for the drop protocol was significantly higher than those of both nebulization protocols in NALF (p = 0.039). In serum, the gentamicin concentration was 0.98 µg/mL (0.65-1.53) and 0.25 µg/mL (0.25-0.44) in the 10-min and 3-min protocols, respectively. Gentamicin was not detected in the serum of seven out of ten dogs in the drop protocol, and gentamicin was significantly higher in the 10-min protocol compared to the drop protocol (p = 0.001). This study found that the 10-min, 3-min and drop protocols achieved superior concentrations in NALF compared to the minimum inhibitory concentration for gentamicin-sensitive bacteria, while remaining below the toxic values in blood.

A Pilot Study on Oxidative Stress during the Recovery Phase in Critical COVID-19 Patients in a Rehabilitation Facility: Potential Utility of the PAOT® Technology for Assessing Total Anti-Oxidative Capacity.

BACKGROUND: Oxidative stress (OS) could cause various COVID-19 complications. Recently, we have developed the Pouvoir AntiOxydant Total (PAOT®) technology for reflecting the total antioxidant capacity (TAC) of biological samples. We aimed to investigate systemic oxidative stress status (OSS) and to evaluate the utility of PAOT® for assessing TAC during the recovery phase in critical COVID-19 patients in a rehabilitation facility. MATERIALS AND METHODS: In a total of 12 critical COVID-19 patients in rehabilitation, 19 plasma OSS biomarkers were measured: antioxidants, TAC, trace elements, oxidative damage to lipids, and inflammatory biomarkers. TAC level was measured in plasma, saliva, skin, and urine, using PAOT and expressed as PAOT-Plasma, -Saliva, -Skin, and -Urine scores, respectively. Plasma OSS biomarker levels were compared with levels from previous studies on hospitalized COVID-19 patients and with the reference population. Correlations between four PAOT scores and plasma OSS biomarker levels were analyzed. RESULTS: During the recovery phase, plasma levels in antioxidants (γ-tocopherol, ß-carotene, total glutathione, vitamin C and thiol proteins) were significantly lower than reference intervals, whereas total hydroperoxides and myeloperoxidase (a marker of inflammation) were significantly higher. Copper negatively correlated with total hydroperoxides (r = 0.95, p = 0.001). A similar, deeply modified OSS was already observed in COVID-19 patients hospitalized in an intensive care unit. TAC evaluated in saliva, urine, and skin correlated negatively with copper and with plasma total hydroperoxides. To conclude, the systemic OSS, determined using a large number of biomarkers, was always significantly increased in cured COVID-19 patients during their recovery phase. The less costly evaluation of TAC using an electrochemical method could potentially represent a good alternative to the individual analysis of biomarkers linked to pro-oxidants.

Exposure to endocrine disrupters and cardiometabolic health effects in preschool children: Urinary parabens are associated with wider retinal venular vessels.

BACKGROUND AND AIM: Parabens are widely used as antimicrobial preservatives in personal care products. Studies investigating obesogenic or cardiovascular effects of parabens show discordant results, while data on preschool children are lacking. Paraben exposure during early childhood could have profound cardiometabolic effects later in life. METHODS: In this cross-sectional study paraben concentrations [methyl (MeP), ethyl (EtP), propyl (PrP), butyl (BuP)] were measured by ultra-performance liquid chromatography/tandem mass spectrometry in 300 urinary samples of 4-6-year-old children of the ENVIRONAGE birth cohort. Paraben values below the limit of quantitation (LOQ) were imputed by censored likelihood multiple imputation. The associations between log-transformed paraben values and cardiometabolic measurements (BMI z-scores, waist circumference, blood pressure and retinal microvasculature) were analyzed in multiple linear regression models with a priori selected covariates. Effect modification by sex was investigated by including interaction terms. RESULTS: Geometric means (geometric SD) of urinary MeP, EtP, and PrP levels above the LOQ were 32.60 (6.64), 1.26 (3.45), and 4.82 (4.11) µg/L, respectively. For BuP more than 96% of all measurements were below the LOQ. Regarding the microvasculature, we found direct associations between MeP and central retinal venular equivalent (ß = 1.23, p = 0.039) and PrP with the retinal tortuosity index (x103)(ß = 1.75, p = 0.0044). Furthermore, we identified inverse associations between MeP and ∑parabens with BMI z-scores (ß = -0.067, p = 0.015 and ß = -0.070, p = 0.014 respectively), and EtP with mean arterial pressure (ß = -0.69, p = 0.048). The direction of association between EtP and BMI z-scores showed evidence for sex-specific differences with a direct trend in boys (ß = 0.10, p = 0.060). CONCLUSIONS: Already at young age paraben exposure is associated with potentially adverse changes in the retinal microvasculature.

Associations between endocrine disruptor contamination and thyroid hormone homeostasis in Belgian type 1 diabetic children.

PURPOSE: Humans are daily exposed to many environmental pollutants, some of which being suspected to be thyroid disruptors. Some populations could be particularly susceptible to thyroid disruption, such like diabetics due to the well-known relation between the thyroid function and the control of carbohydrate homeostasis by pancreas. Therefore, the aim of this study was to investigate the associations between the exposure to several persistent and non-persistent chemicals and thyroid hormones levels in children with type 1 diabetes. METHODS: Blood and urine sample were collected from 54 children diagnosed for type 1 diabetes mellitus. The concentrations of 7 phthalate metabolites, 4 parabens, 7 bisphenols, benzophenone 3 and triclosan were measured in urine, while 15 organochlorine pesticides, 4 polychlorinated biphenyls (PCBs) and 7 perfluoroalkyl substances were analyzed in serum samples. In the same time, the blood levels of free thyroxine (fT4), thyroid stimulating hormone (TSH) and glycated hemoglobin (Hb1Ac) were determined. RESULTS: We highlighted positive associations between serum perfluorohexane sulfonate and urinary monoethylphthalate levels, and TSH level in blood. We also found that PCB 138 was positively associated to fT4 while urinary levels of bisphenol F were negatively correlated to this hormone. Finally, we observed positive associations between Hb1Ac levels and the contamination by PCB 153 and two urinary phthalate metabolites: mono-2-ethyl-5-hydroxyhexyl phthalate and mono-2-ethyl-5-oxoxyhexyl phthalate. CONCLUSION: Our results showed that our small cohort of children with type 1 diabetes mellitus is potentially susceptible to thyroid disruptions by some pollutants. Moreover, for these children, both di-(2-ethylhexyl) phthalate metabolites would potentially hamper the glucose homeostasis. Nevertheless, additional studies are mandatory to further explore these findings.

Cannabidiol in urine is not a proof of CBD consumption-lesson learned from urine sample analysis in routine caseworks.

PURPOSE: Cannabidiol (CBD) has been gaining popularity in recent years. Knowing that CBD products can contain more tetrahydrocannabinol (THC) than expected, interpretation of cannabinoids concentration in urine can be tricky, especially when low amounts of THC and CBD are found. Moreover, interpretation can also be difficult due to interindividual variation in pharmacokinetics. The objective of this work was to take a critical look at the data from our daily practice as a toxicology laboratory. METHODS: We have collected results obtained in a first batch of 1074 urine samples submitted to cannabinoids analysis, and results of cannabinoids content of a second batch of 719 seized materials. RESULTS: CBD was detected in 163 urine specimens (15%). Its concentration was higher than the limit of quantification of 5 ng/mL in 108 samples only (10% of the sampling population). Most of CBD-positive samples were associated with a high THC-COOH concentration (> 500 ng/mL in 63.8% of CBD-positive samples) suggesting only a few CBD consumers in our population. Cannabinoids composition of seized plant materials (drug type at first glance) revealed CBD in 110 of them (15% of the sampling population), with a concentration mostly below 1%. All of the resin samples were CBD positive, and contained more THC compared to flowers. CONCLUSIONS: We can conclude that urine samples from drug-type cannabis users contained a low amount of CBD, what was not described previously. These findings are useful for the interpretation of cannabinoids results in daily practice.

Human biomonitoring survey (Pb, Cd, As, Cu, Zn, Mo) for urban gardeners exposed to metal contaminated soils.

Eighty eight adult gardeners and their relatives volunteered to provide urine and blood samples for a human biomonitoring survey among users of one of the biggest allotment garden from Wallonia, showing high trace metal(oid) concentrations in soils. The purpose was to determine if environmental levels of lead (Pb), cadmium (Cd) and arsenic (As) led to concentrations of potential health concern in the study population. Blood and urine biomarkers were compared to reference and intervention cut-off values selected from the literature. The study population exhibited (i) moderately high blood lead levels with median value of 23.1 µg/L, (ii) high urinary concentrations of speciated As (inorganic arsenic and its metabolites) with a median value of 7.17 µg/g.cr., i.e. twice the median values usually observed in general populations, and (iii) very high Cd levels in urine with a median value of 1.23 µg/L, in the range of 95th-97.5th percentiles measured in general adult populations. Biomarker levels in the study population were also mostly above those measured in adults from local populations living on contaminated soils, as reported in the current literature. All biomarkers of Pb, Cd and As showed weak to strong statistically significant correlations, pointing towards a joint environmental source to these three contaminants as being at least partially responsible for the high exposure levels observed. Urine and blood biomarkers show statistically significant associations with variables related to individual characteristics (age, smoking status, …) and Pb domestic sources (Pb pipes, cosmetics, …) but involves also behavioral and consuming habits related to gardening activities on the contaminated allotment garden. At such levels, owing to co-exposure and additive effects of Cd, As and Pb regarding renal toxicity known from literature, the study strongly suggests that this population of gardeners is at risk with respect to chronic kidney diseases.

Urinary levels of parabens, phthalate metabolites, bisphenol A and plasticizer alternatives in a Belgian population: Time trend or impact of an awareness campaign?

A human biomonitoring study was carried out in 2015 within an adult population living in Liege (Belgium). Some phthalate metabolites and parabens were measured in the urine of 252 participants, and information were collected about their food habits, life styles and home environment to identify some predictors of exposure. Concomitantly, an awareness campaign was initiated by the Provincial Authorities of Liege and spread over 2 years. Three years later (2018), 92 of the initial participants provided again urine samples, and the levels of phthalate metabolites, phthalate substitute (DINCH), parabens, bisphenol-A and bisphenol alternatives (bisphenol-S, -F, -Z, -P) were determined and compared to those obtained in 2015 to assess time trends. In 2015, methyl- and ethylparaben were the most abundant parabens (P50 = 9.12 µg/L and 1.1 µg/L respectively), while propyl- and butylparaben were sparsely detected. Except for mono-2-ethylhexyl phthalate and 6-OH-mono-propyl-heptyl phthalate, all other targeted phthalate metabolites were positively quantified in most of the urine samples (between 89 and 98%) with median concentrations ranging between 2.7 µg/L and 21.3 µg/L depending on the metabolite. The multivariate regression models highlighted some significant associations between urinary phthalate metabolite or paraben levels and age, rural or urban character of the residence place, and the use of some personal care products. However, all determination coefficients were weak meaning that the usual covariates included in the models only explained a small part of the variance. Between 2015 and 2018, levels of parabens and phthalate metabolites significantly decreased (from 1.3 to 2.5 fold) except for monoethyl phthalate which seemed to remain quite constant. Contrariwise, all bisphenol alternatives and DINCH metabolites were measured in higher concentrations in 2018 vs 2015 while BPA levels did not differ significantly. However, it was not feasible to unequivocally highlight an impact of the awareness campaign on the exposure levels of the population.

Analytical performance of eight enzymatic assays for ethanol in serum evaluated by data from the Belgian external quality assessment scheme.

OBJECTIVES: Fast and reliable ethanol assays analysis are used in a clinical context for patients suspected of ethanol intoxication. Mostly, automated systems using an enzymatic reaction based on ethanol dehydrogenase are used. The manuscript focusses on the evaluation of the performance of these assays. METHODS: Data included 30 serum samples used in the Belgian EQA scheme from 2019 to 2021 and concentrations ranged from 0.13 to 3.70 g/L. A regression line between target concentrations and reported values was calculated to evaluate outliers, bias, variability and measurement uncertainty. RESULTS: A total of 1,611 results were taken into account. Bias was the highest for Alinity c over the whole concentration range and the lowest for Vitros for low concentrations and Cobas 8000 using the c702 module for high concentrations. The Architect and Cobas c501/c502 systems showed the lowest variability over the whole concentration range. Highest variability was observed for Cobas 8000 using the 702 module, Thermo Scientific and Alinity c. Cobas 8000 using the c702 module showed the highest measurement uncertainty for lower concentrations. For higher concentrations, Alinity c, Thermo Scientific and Vitros were the methods with the highest measurement uncertainty. CONCLUSIONS: The bias of the enzymatic techniques is nearly negligible for all methods except Alinity c. Variability differs strongly between measurement procedures. This study shows that the Alinity c has a worse measurement uncertainty than other systems for concentrations above 0.5 g/L. Overall, we found the differences in measurement uncertainty to be mainly influenced by the differences in variability.

Biochip array technology for new psychoactive substances detection in biological samples: Evaluation of the specificity of the Randox Evidence Investigator®.

BACKGROUND: The need to detect new psychoactive substances in biological samples is of crucial interest. In this paper, the specificity of a benchtop immunoanalyzer commercialized by Randox was evaluated on real patient samples. METHOD: The Evidence Investigator was assessed to screen for NPS on 80 serum and urine samples coming from patients admitted to the emergency department. Targeted NPS were included in various categories such as synthetic cannabinoids, opioids and benzodiazepines. Results were compared with a chromatographic technique coupled with mass spectrometry. RESULTS: No NPS was detected by the reference technique. Concerning immunoanalysis, some piperazines were positive, caused by the presence of medicine containing this chemical structure. Clonazepam and fentanyl derivatives were confirmed in some cases, but sometimes the positivity was explained by other opiates or benzodiazepines, which also explained two samples falsely positive for etizolam. CONCLUSIONS: The Randox Evidence Investigator was rapid and easy to use. It can be used as a first intention but always followed by a more specific technique in order to detect false positive result.

Determination of contamination levels for multiple endocrine disruptors in hair from a non-occupationally exposed population living in Liege (Belgium).

Today, the interest in hair as alternative matrix for human biomonitoring of environmental pollutants has increased, but available data on chemical levels in hair remain scarce. In this study, the measurement of 2 bisphenols (A and S), 3 parabens (methyl-, ethyl- and propylparabens) and 8 perfluroralkyl compounds (PFCs) namely perfluoroctanesulfonate (PFOS), perfluorohexanesulfonate (PFHxS), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), perfluroroheptanoic acid (PFHpA), perfluoropentanoic acid (PFPeA) and perfluorohexanoic acid (PFHxA) was carried out, using a thoroughly validated UPLC-MS/MS method, in the hair from 114 adults living in Liege (Belgium) and surrounding areas. The most frequently quantified compounds in the population were: bisphenol S (97.4%, median = 31.9 pg·mg-1), methylparaben (94.7%, median = 28.9 pg·mg-1), bisphenol A (93.9%, median = 46.6 pg·mg-1), ethylparaben (66.7%, median = 5.2 pg·mg-1), propylparaben (54.8%, median = 16.4 pg·mg-1) and PFOA (46.4%, median < 0.2 pg·mg-1). The other PFCs were detected only in few samples although current exposure of the Belgian population to PFCs was previously demonstrated using blood analyses. Nonparametric statistical analyses were performed to evaluate the influence of gender, hair treatments and hair length, but no significant difference was observed. Only age was positively correlated with the propylparaben contamination. Although blood seems to remain more suitable for PFCs exposure assessment, the results of this study suggest that hair can be an appropriate matrix for biomonitoring of organic pollutants such as parabens or bisphenols.

Potential 2-Aminoindane Fatality Invalidated by Careful Mass Spectrometric Analysis.

We describe herewith the case of a patient presenting to the emergency department for worsening ear-nose-throat symptoms. As chemsex was evocated by the family, patient's serum was submitted to a new psychoactive substances screening. After a simple liquid-liquid extraction, serum was injected on a high-resolution mass spectrometer using quite usual conditions (C18 column, gradient mode with acidic buffer, methanol and acetonitrile). An almost perfect match with 2-aminoindane (2-AI) was observed considering that the precursor ion was present in the sample but absent in the commercial library. Literature concerning 2-AI is sparse, and further investigations were undertaken. After injection of the reference standard, a small retention time shift has been observed (0.3 min) between the standard and the sample. The case was only closed while spiking the sample with the standard, giving rise to two distinct peaks. As a result, 2-AI was then considered as absent from the sample and death was attributed only to infection. Moreover, a rapid liquid chromatography-tandem mass spectrometry method dedicated to 2-AI was developed. It generated the same false-positive result highlighted by significant differences observed in ion ratios (2.37 for the sample versus 6.62 for the neat standard).

Bio-surveillance of environmental pollutants in the population of Kinshasa, Democratic Republic of Congo (DRC): a small pilot study.

BACKGROUND: Environmental pollutants are known to be ubiquitous and may present toxic effects (endocrine-disruption properties, carcinogenicity …) and represent a real threat to human health. The aim of the present pilot study was to assess the content of environmental pollutants (inorganic, persistent, and non-persistent pollutants) in biological samples (urine, serum, and whole blood), collected from volunteers in Kinshasa, capital of Democratic Republic of Congo, in order to identify pollutants of interest and to design a protocol for a larger scale study. METHODS: From randomly selected 15 volunteers living in Kinshasa, aged from 25 to 66 years, (mean age = 43.4 years), including 10 men and 5 women, urine, whole blood, and serum samples were used in this study to estimate the contents in these environmental pollutants, using inductively coupled plasma mass spectrometry, gas chromatography coupled to mass spectrometry, and liquid chromatography coupled to mass spectrometry. RESULTS: When compared to data nationally and internationally available, the preliminary outcomes of this study indicated a very high level of exposure to environmental pollutants in the population of Kinshasa, especially for heavy metals, parabens and triclosan. To a lesser extent, contamination measured for glyphosate, phthalates, organochlorine pesticides, pyrethroids and dialkylphosphate pesticides was also significant. In contrast, the investigated population of Kinshasa was found to be weakly exposed to other persistent organic pollutants like polychlorinated biphenyls, brominated flame retardants, phenolic organohalogens, and perfluoroalkyl substances. CONCLUSION: Although the biologic fluids were collected from a limited number of volunteers (n = 15), the results of the present report clearly indicate that the population of Kinshasa is not spared by the investigated environmental pollutants. Moreover, this study gives us important information to design a larger scale study protocol.

Population pharmacokinetics of cefazolin in maternal and umbilical cord plasma, and simulated exposure in term neonates.

BACKGROUND: Intra-partum cefazolin is used to prevent group B Streptococcus (GBS) vertical transmission in mothers allergic to penicillin without a history of anaphylaxis. OBJECTIVES: To investigate the maternal cefazolin dose-exposure relationship and subsequent maternal and neonatal target attainment at delivery. METHODS: Data were obtained from 24 healthy, GBS-colonized pregnant women (20-41 years), undergoing vaginal delivery (gestational age ≥37 weeks). During labour, all women received a 2 g cefazolin IV infusion. Eight hours later, eight women received another 1 g in the event of delayed (>8 h) delivery. Next to maternal plasma concentrations (up to 10 per dosing interval, until delivery), venous and arterial umbilical cord concentrations were determined at delivery. Target attainment in maternal/neonatal plasma was set at 1 mg/L for 60% of the dosing interval (unbound cefazolin, worst-case clinical breakpoint). A population pharmacokinetic (popPK) model was built (NONMEM 7.4). ClinicalTrials.gov Identifier: NCT01295606. RESULTS: At delivery, maternal blood and arterial umbilical cord unbound cefazolin concentrations were >1 mg/L in 23/24 (95.8%) and 11/12 (91.7%), respectively. The popPK of cefazolin in pregnant women was described by a two-compartment model with first-order elimination. Two additional compartments described the venous and arterial umbilical cord concentration data. Cefazolin target attainment was adequate in the studied cohort, where delivery occurred no later than 6.5 h after either the first or the second dose. PopPK simulations showed adequate maternal and umbilical cord exposure for 12 h following the first dose. CONCLUSIONS: PopPK simulations showed that standard pre-delivery maternal cefazolin dosing provided adequate target attainment up to the time of delivery.

Oxidative Stress Status in COVID-19 Patients Hospitalized in Intensive Care Unit for Severe Pneumonia. A Pilot Study.

BACKGROUND: A key role of oxidative stress has been highlighted in the pathogenesis of COVID-19. However, little has been said about oxidative stress status (OSS) of COVID-19 patients hospitalized in intensive care unit (ICU). MATERIAL AND METHODS: Biomarkers of the systemic OSS included antioxidants (9 assays), trace elements (3 assays), inflammation markers (4 assays) and oxidative damage to lipids (3 assays). RESULTS: Blood samples were drawn after 9 (7-11) and 41 (39-43) days of ICU stay, respectively in 3 and 6 patients. Vitamin C, thiol proteins, reduced glutathione, γ-tocopherol, ß-carotene and PAOT® score were significantly decreased compared to laboratory reference values. Selenium concentration was at the limit of the lower reference value. By contrast, the copper/zinc ratio (as a source of oxidative stress) was higher than reference values in 55% of patients while copper was significantly correlated with lipid peroxides (r = 0.95, p < 0.001). Inflammatory biomarkers (C-reactive protein and myeloperoxidase) were significantly increased when compared to normals. CONCLUSIONS: The systemic OSS was strongly altered in critically ill COVID-19 patients as evidenced by increased lipid peroxidation but also by deficits in some antioxidants (vitamin C, glutathione, thiol proteins) and trace elements (selenium).

Background contamination of perfluoralkyl substances in a Belgian general population.

The few Belgian studies on the human exposure to perfluoroalkyl substances (PFASs) have until now concerned the Northern part of Belgium (Flanders), while data related to Wallonia (South region) are missing. To fill this gap, 8 perfluorinated carboxylic acids and 3 perfluorinated alkyl sulfonates were measured in the serum of 242 adults (>18 years old) recruited in 2015 and living in the Province of Liege. Some multivariate regression models were also built with the PFAS levels and the participant's answers to a questionnaire about their diet and lifestyle habits in order to identify some predictors of exposure. The results obtained showed that although PFAS levels observed in our population seemed to be similar or lower than those reported in other countries, and especially lower than in the Northern part of Belgium, half of the population showed PFOS and PFOA serum levels above the health guidance values set by the German HBM Commission. As expected, age and gender were the main covariates explaining the different PFAS serum levels between participants, while breastfeeding (for women), consumption of fish and seafood, consumption of rice, and use of nail polish seemed also to impact the PFAS body burden of our population. Nevertheless, the statistical models were poorly predictive suggesting that the main sources of exposure were not taken into account.