Introduction Vasectomy is a widely used, safe, effective method of permanent contraception and contributes to healthy sexuality. Aims We have conducted a 3-step observational clinical study to develop a vasectomy regret risk score and guide patients and clinicians when discussing a vasectomy. Methods A 3-step approach has been followed. First, experts involved in male health have proposed risk factors for regret (remorse) after vasectomy, defined by a vasectomy reversal surgery or medically assisted reproduction. The selected factors were evaluated in 1200 patients vasectomized in the last 15 years. Finally, the expert panel has constructed a score for predicting regret after vasectomy. Results Fifty-two international experts identified 17 risk factors for vasectomy regret. Five of the risk factors were significant: an age <35 years old, a high Barrat Impulsivity Score, a low level of education, and a patient who didn't understand that the vasectomy might not be reversible or for whom the contraception responsibility is ideally feminine, or no responsible partner. On multivariate analysis, 3 risk factors and 2 "sine qua non" conditions were used to build the decision algorithm. A risk score >= 4 required information on sperm cryopreservation before vasectomy, and those with a risk score >= 7 required extra time for reflection. The scoring system was proposed to 52 international experts and accepted with 86.7% strongly agreeing. The model's sensitivity and specificity were 0.98 and 0.53, respectively. Conclusion A decisional algorithm was established to identify patients requiring information on sperm cryopreservation before vasectomy or additional time for reflection to reduce the risk of vasectomy regret. The algorithm contains 3 risk factors and 2 "sine qua non" conditions.

Malaria is a parasitic disease that remains a global concern and the subject of many studies. Metabolomics has emerged as an approach to better comprehend complex pathogens and discover possible drug targets, thus giving new insights that can aid in the development of antimalarial therapies. However, there is no standardized method to extract metabolites from in vitro Plasmodium falciparum intraerythrocytic parasites, the stage that causes malaria. Additionally, most methods are developed with either LC-MS or NMR analysis in mind, and have rarely been evaluated with both tools. In this work, three extraction methods frequently found in the literature were reproduced and samples were analyzed through both LC-MS and 1H NMR, and evaluated in order to reveal which is the most repeatable and consistent through an array of different tools, including chemometrics, peak detection and annotation. The most reliable method in this study proved to be a double extraction with methanol and methanol/water (80:20, v/v). Metabolomic studies in the field should move towards standardization of methodologies and the use of both LC-MS and 1H NMR in order to make data more comparable between studies and facilitate the achievement of biologically interpretable information.

Background: Growing evidence links brain-MRI enlarged perivascular spaces (EPVS) and multiple sclerosis (MS), but their role remains unclear. Objective: This study aimed to investigate the cross-sectional associations of EPVS with several neuroinflammatory and neurodegenerative features in a large multicentric-MS cohort. Methods: In total, 207 patients underwent 3T axial-T2-weighted brain-MRI for EPVS assessment (EPVS dichotomized into high/low according to >= 2/< 2 rating categories). MRI biomarkers included brain-predicted age and brain-predicted age difference (brain-PAD), central vein sign (CVS)-positive lesion percentage (CVS%), paramagnetic rim and cortical lesions, T2-lesion load, and brain volumetry. The variable relative importance for EPVS-category prediction was explored using a classification random forest approach. Results: High EPVS patients were older (49 vs 44 years, p = 0.003), had >= 1 vascular risk factors (VRFs; p = 0.005), lower CVS% (67% vs 78%, p < 0.001), reduced brain volumes (whole brain: 0.63 vs 0.73, p = 0.01; gray matter: 0.36 vs 0.40; p = 0.002), and older brain-predicted age (58 vs 50 years, p < 0.001). No differences were found for neuroinflammatory markers. After adjusting for age and VFRs (multivariate analyses), the high EPVS category correlated with lower CVS% (odds ratio (OR) = 0.98, 95% confidence interval (CI) = 0.96-0.99; p = 0.02), lower whole brain (OR = 0.01, 95% CI = 0.0003-0.5; p = 0.02), gray matter (OR = 0.0004, 95% CI = 0.0000004-0.4; p = 0.03) volumes, and higher brain-PAD (OR = 1.05, 95% CI = 1.01-1.09; p = 0.02). Random forest identified brain-PAD as the most important predictor of high EPVS. Conclusion: EPVS in MS likely reflect microangiopathic disease rather than neuroinflammation, potentially contributing to accelerated neurodegeneration.

AbstractObjectivePrevious studies reveal heterogeneity in terms of paramagnetic rim lesions (PRL) associated tissue damage. We investigated the physiopathology and clinical implications of this heterogeneity.MethodsIn 103 MS patients (72 relapsing and 31 progressive), brain lesions were manually segmented on 3T 3D‐FLAIR and rim visibility was assessed with a visual confidence level score (VCLS) on 3D‐EPI phase. Using T1 relaxation time maps, lesions were categorized in long‐T1 and short‐T1. Lesion age was calculated from time of first gadolinium enhancement (N = 84 lesions). Results on clinical scores were validated in an extended cohort of 167 patients using normalized T1w‐MPRAGE lesion values.ResultsRim visibility (VCLS analysis) was associated with increasing lesional T1 (P/PFDR < 0.001). Of 1680 analyzed lesions, 427 were categorized as PRL. Long‐T1 PRL were older than short‐T1 PRL (average 0.8 vs. 2.0 years, P/PFDR = 0.005/0.008), and featured larger lesional volume (P/PFDR < 0.0001) and multi‐shell diffusion‐measured axonal damage (P/PFDR < 0.0001). The total volume of long‐T1‐PRL versus PRL showed 2× predictive power for both higher MS disability (EDSS; P/PFDR = 0.003/0.005 vs. P/PFDR = 0.042/0.057) and severity (MSSS; P/PFDR = 0.0006/0.001 vs. P/PFDR = 0.004/0.007). In random forest, having ≥1 long‐T1‐PRL versus ≥4 PRL showed 2‐4× higher performance to predict a higher EDSS and MSSS. In the validation cohort, long‐T1 PRL outperformed (~2×) PRL in predicting both EDSS and MSSS.InterpretationPRL show substantial heterogeneity in terms of intralesional tissue damage. More destructive, likely older, long‐T1 PRL improve the association with MS clinical scales. This PRL heterogeneity characterization was replicated using standard T1w MRI, highlighting its potential for clinical translation.

Background and Objectives The diagnosis of multiple sclerosis (MS) can be challenging in clinical practice because MS presentation can be atypical and mimicked by other diseases. We evaluated the diagnostic performance, alone or in combination, of the central vein sign (CVS), paramagnetic rim lesion (PRL), and cortical lesion (CL), as well as their association with clinical outcomes. Methods In this multicenter observational study, we first conducted a cross-sectional analysis of the CVS (proportion of CVS-positive lesions or simplified determination of CVS in 3/6 lesions-Select3*/Select6*), PRL, and CL in MS and non-MS cases on 3T-MRI brain images, including 3D T2-FLAIR, T2*-echo-planar imaging magnitude and phase, double inversion recovery, and magnetization prepared rapid gradient echo image sequences. Then, we longitudinally analyzed the progression independent of relapse and MRI activity (PIRA) in MS cases over the 2 years after study entry. Receiver operating characteristic curves were used to test diagnostic performance and regression models to predict diagnosis and clinical outcomes. Results The presence of >= 41% CVS-positive lesions/>= 1 CL/>= 1 PRL (optimal cutoffs) had 96%/90%/93% specificity, 97%/84%/60% sensitivity, and 0.99/0.90/0.77 area under the curve (AUC), respectively, to distinguish MS (n = 185) from non-MS (n = 100) cases. The Select3*/Select6* algorithms showed 93%/95% specificity, 97%/89% sensitivity, and 0.95/0.92 AUC. The combination of CVS, CL, and PRL improved the diagnostic performance, especially when Select3*/Select6* were used (93%/94% specificity, 98%/96% sensitivity, 0.99/0.98 AUC; p = 0.002/p < 0.001). In MS cases (n = 185), both CL and PRL were associated with higher MS disability and severity. Longitudinal analysis (n = 61) showed that MS cases with >4 PRL at baseline were more likely to experience PIRA at 2-year follow-up (odds ratio 17.0, 95% confidence interval: 2.1-138.5; p = 0.008), whereas no association was observed between other baseline MRI measures and PIRA, including the number of CL. Discussion The combination of CVS, CL, and PRL can improve MS differential diagnosis. CL and PRL also correlated with clinical measures of poor prognosis, with PRL being a predictor of disability accrual independent of clinical/MRI activity.

Background Chronic active lesions (CAL) in multiple sclerosis (MS) have been observed even in patients taking high efficacy disease-modifying therapy, including B-cell depletion. Given that CAL are a major determinant of clinical progression, including progression independent of relapse activity (PIRA), understanding the predicted activity and real-world effects of targeting specific lymphocyte populations is critical for designing next-generation treatments to mitigate chronic inflammation in MS.Methods We analyzed published lymphocyte single-cell transcriptomes from MS lesions and bioinformatically predicted the effects of depleting lymphocyte subpopulations (including CD20 B-cells) from CAL via gene regulatory-network machine-learning analysis. Motivated by the results, we performed in vivo MRI assessment of PRL changes in 72 adults with MS, 46 treated with anti-CD20 antibodies and 26 untreated, over & SIM;2 years.Findings Although only 4.3% of lymphocytes in CAL were CD20 B-cells, their depletion is predicted to affect microglial genes involved in iron/heme metabolism, hypoxia, and antigen presentation. In vivo, tracking 202 PRL (150 treated) and 175 non-PRL (124 treated), none of the treated paramagnetic rims disappeared at follow-up, nor was there a treatment effect on PRL for lesion volume, magnetic susceptibility, or T1 time. PIRA occurred in 20% of treated patients, more frequently in those with & GE;4 PRL (p = 0.027).Interpretation Despite predicted effects on microglia-mediated inflammatory networks in CAL and iron metabolism, anti-CD20 therapies do not fully resolve PRL after 2-year MRI follow up. Limited tissue turnover of B-cells, inefficient passage of anti-CD20 antibodies across the blood-brain-barrier, and a paucity of B-cells in CAL could explain our findings.Funding Intramural Research Program of NINDS, NIH; NINDS grants R01NS082347 and R01NS082347; Dr. Miriam and Sheldon G. Adelson Medical Research Foundation; Cariplo Foundation (grant #1677), FRRB Early Career Award (grant #1750327); Fund for Scientific Research (FNRS).Copyright & COPY; 2023 The Author(s). Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). 2023;94: Published https://doi.org/10. 1016/j.ebiom.2023. 104701

Objective: To evaluate the residual effect of partial remission (PR) on immediate post-PR glycemic control according to its occurrence and duration in a cohort of children with type 1 diabetes mellitus (T1DM). Patients and Methods: Values of glycemic control parameters [i.e. HbA 1C , insulin dose–adjusted hemoglobin A 1C (IDAA 1C ), glycemic target–adjusted HbA 1C (GTAA 1C )] and data from glucose monitoring devices from 189 pediatric patients with new-onset type 1 diabetes were collected retrospectively from 24 months. Patients were characterized according to their remission status (PR + and PR − ). PR + patients were subdivided into three subgroups regarding PR duration [i.e. short (⩾3–⩽6 months), intermediate (>6–⩽12 months), and long PR (>12–⩽14 months)]. We compared glycemic control data from each PR + subgroup at +6 and +12 months post-PR with PR − patients at the same postdiagnosis time. Second, PR + subgroups were compared with each other. Results: PR + patients showed improved glycemic control (i.e. HbA 1C , IDAA 1C , and GTAA 1C ) at + 6 months post-PR when compared with nonremitters (PR − ), independently of the PR duration subgroups (p < 0.05). Interestingly, patients in long PR + subgroup exhibited higher positive residual effect than short PR + subgroup with lower GTAA 1C scores (p = 0.02), better time in range (TIR) (p = 0.003), less time in hypoglycemia (10.45 versus 16.13%, p = 0.03) and less glycemic variability (83.1 mg/dl versus 98.84 mg/dl, p = 0.03). No significant differences were found for glucose control between PR + and PR − patients at +12 months post-PR. Conclusion: This study supports the positive impact of PR occurrence and duration on short-term metabolic control (better HbA 1C levels, IDAA 1C and GTAA 1C scores, TIR, and less glycemic variability) with the residual effect increasing according to PR duration.

Une importante partie des activités réalisées dans le cadre du développement de vaccins a pour but d'assurer la maintenance de la qualité des vaccins enregistrés malgré les nombreuses modifications dans la chaine de production. L'impact des changements doit pouvoir être évalué sur base de paramètres techniques qui sont utilisés comme indicateurs de l'impact clinique. D'où la nécessité de développer des outils statistiques permettant une analyse multivariée complexe adaptée aux activités liées au cycle de vie des vaccins afin de déterminer si les résultats d'une étude clinique, utilisant une formulation récente d'un vaccin, sont en ligne avec les données historiques ou sont aberrantes. L'objectif de cette recherche est de comparer trois méthodes de détection d'étude aberrante dans une méta-analyse d'un point de vue théorique, via une étude de simulation ainsi que via leur application sur des données réelles. Dans le cadre d'une méta-analyse d'essais cliniques de vaccins, un modèle mixte est ajusté aux données pour prédire la moyenne géométrique du titre d'anticorps dans le sang des individus vaccinés. Sur la base d'une revue de la littérature, nous avons sélectionné trois méthodes prometteuses pour détecter si une nouvelle étude présente une moyenne géométrique aberrante par rapport aux autres: (1) le modèle de variation de la variance aberrante (VSOM), (2) la méthode des résidus externes standardisés (RES) et (3) le modèle de mélange robuste (RMM). Sur 500 bases de données simulées, la méthode RES présente une erreur de type I de 4,6% et une puissance de 100%, la méthode VSOM une erreur de type I de 4% et une puissance de 99,4% alors que la méthode RMM présente une erreur de type I de 0,6% et une puissance de 99,6%. Sur les données réelles, les deux premières méthodes identifient les mêmes études comme étant aberrantes tandis que la troisième en détectent quelques unes supplémentaires. La méthode RES est plus simple, plus rapide à mettre en œuvre et s'est montrée plus précise dans le contexte de nos données simulées (distribution normale). Les méthodes RMM et VSOM nécessitent l'estimation de paramètres de variance supplémentaires et sont plus fastidieuses à mettre en oeuvre. La méthode RMM ne semble pas appropriée au contexte car elle est poussée à sa limite de détection d'une seule étude aberrante par opposition à un groupe d'études aberrantes. A noter que ces trois méthodes sont implémentées sur des données agrégées ce qui engendre une perte d'informations par rapport aux données individuelles des patients disponibles. Dans la suite de ce travail, nous aimerions donc étendre les méthodes RES et VSOM aux méta-analyses en données individuelles. Mots clés étude aberrante ; meta-analyse ; résidus externes ; VSOM Déclaration de liens d'intérêts Les auteurs n'ont pas précisé leurs éventuels liens d'intérêts

Background: The central vein sign (CVS) is an imaging biomarker able to differentiate multiple sclerosis (MS) from other conditions causing similar appearance lesions on magnetic resonance imaging (MRI), including cerebral small vessel disease (CSVD). However, the impact of vascular risk factors (VRFs) for CSVD on the percentage of CVS positive (CVS+) lesions in MS has never been evaluated. Objective: To investigate the association between different VRFs and the percentage of CVS+ lesions in MS. Methods: In 50 MS patients, 3T brain MRIs (including high-resolution 3-dimensional T2*-weighted images) were analyzed for the presence of the CVS and MRI markers of CSVD. A backward stepwise regression model was used to predict the combined predictive effect of VRF (i.e. age, hypertension, diabetes, obesity, ever-smoking, and hypercholesterolemia) and MRI markers of CSVD on the CVS. Results: The median frequency of CVS+ lesions was 71% (range: 35%–100%). In univariate analysis, age ( p < 0.0001), hypertension ( p < 0.001), diabetes ( p < 0.01), obesity ( p < 0.01), smoking ( p < 0.05), and the presence of enlarged-perivascular-spaces on MRI ( p < 0.005) were all associated with a lower percentage of CVS+ lesions. The stepwise regression model showed that age and arterial hypertension were both associated with the percentage of CVS+ lesions in MS (adjusted R2 = 0.46; p < 0.0001 and p = 0.01, respectively). Conclusion: The proportion of CVS+ lesions significantly decreases in older and hypertensive MS patients. Although this study was conducted in patients with an already established MS diagnosis, the diagnostic yield of the previously proposed 35% CVS proportion-based diagnostic threshold appears to be not affected. Overall these results suggest that the presence of VRF for CSVD should be taken into account during the CVS assessment.

General practitioners (GPs) are among the main actors involved in early melanoma diagnosis. However, melanoma diagnostic accuracy and management are reported to be insufficient among GPs in Europe. The primary aim of this observational prospective study was to shed light on melanoma diagnostic practices among French-speaking Belgian GPs. The second aim was to specifically analyse these GPs’ pigmented skin lesion diagnostic accuracy and management. GPs from the five French-speaking districts of Belgium were asked to complete a questionnaire, before taking part in a melanoma diagnostic training session. First, we assessed the GPs’ current melanoma diagnostic practices. Then, their pigmented skin lesion diagnostic accuracy and management were evaluated, through basic theoretical questions and clinical images. These results were subsequently analysed, according to the GPs’ sociodemographic characteristics and medical practice type. In total, 89 GPs completed the questionnaire. Almost half of the GPs (43%; CI = [33;54]) were confronted with a suspicious skin lesion as the main reason for consultation once every 3 months, while 33% (CI = [24;43]) were consulted for a suspicious lesion as a secondary reason once a month. Prior to training, one-third of the GPs exhibited suboptimal diagnostic accuracy in at least one of six “life-threatening” clinical cases among two sets of 10 clinical images of pigmented skin lesions, which can lead to inadequate patient management (i.e. incorrect treatment and/or inappropriate reinsurance). This study underlines the need to train GPs in melanoma diagnosis. GPs’ pigmented skin lesion diagnostic accuracy and management should be improved to increase early melanoma detection.

AllergyVolume 75, Issue 5 p. 1264-1266 LETTER TO THE EDITOR Atopic Dermatitis Score 7 (ADS7): A promising tool for daily clinical assessment of atopic dermatitis Anne-Sophie Darrigade, Anne-Sophie Darrigade orcid.org/0000-0003-4034-0395 Dermatology Department, Cliniques Universitaires Saint-Luc, Brussels, BelgiumSearch for more papers by this authorCaroline Colmant, Caroline Colmant Dermatology Department, Cliniques Universitaires Saint-Luc, Brussels, BelgiumSearch for more papers by this authorLaurence de Montjoye, Laurence de Montjoye orcid.org/0000-0003-0673-0728 Dermatology Department, Cliniques Universitaires Saint-Luc, Brussels, BelgiumSearch for more papers by this authorAnne Herman, Anne Herman Dermatology Department, Cliniques Universitaires Saint-Luc, Brussels, BelgiumSearch for more papers by this authorCéline Bugli, Céline Bugli Plateforme Technologique de Support en Méthodologie et Support Statistique (SMCS), Université Catholique de Louvain, Louvain-la-Neuve, BelgiumSearch for more papers by this authorIsabelle Tromme, Isabelle Tromme Dermatology Department, Cliniques Universitaires Saint-Luc, Brussels, BelgiumSearch for more papers by this authorMarie Baeck, Corresponding Author Marie Baeck marie.baeck@uclouvain.be orcid.org/0000-0003-0499-7939 Dermatology Department, Cliniques Universitaires Saint-Luc, Brussels, Belgium Correspondence Marie Baeck, Dermatology Department, Cliniques Universitaires Saint-Luc, Avenue Hippocrate, 10, 1200 Brussels, Belgium. Email: marie.baeck@uclouvain.beSearch for more papers by this author Anne-Sophie Darrigade, Anne-Sophie Darrigade orcid.org/0000-0003-4034-0395 Dermatology Department, Cliniques Universitaires Saint-Luc, Brussels, BelgiumSearch for more papers by this authorCaroline Colmant, Caroline Colmant Dermatology Department, Cliniques Universitaires Saint-Luc, Brussels, BelgiumSearch for more papers by this authorLaurence de Montjoye, Laurence de Montjoye orcid.org/0000-0003-0673-0728 Dermatology Department, Cliniques Universitaires Saint-Luc, Brussels, BelgiumSearch for more papers by this authorAnne Herman, Anne Herman Dermatology Department, Cliniques Universitaires Saint-Luc, Brussels, BelgiumSearch for more papers by this authorCéline Bugli, Céline Bugli Plateforme Technologique de Support en Méthodologie et Support Statistique (SMCS), Université Catholique de Louvain, Louvain-la-Neuve, BelgiumSearch for more papers by this authorIsabelle Tromme, Isabelle Tromme Dermatology Department, Cliniques Universitaires Saint-Luc, Brussels, BelgiumSearch for more papers by this authorMarie Baeck, Corresponding Author Marie Baeck marie.baeck@uclouvain.be orcid.org/0000-0003-0499-7939 Dermatology Department, Cliniques Universitaires Saint-Luc, Brussels, Belgium Correspondence Marie Baeck, Dermatology Department, Cliniques Universitaires Saint-Luc, Avenue Hippocrate, 10, 1200 Brussels, Belgium. Email: marie.baeck@uclouvain.beSearch for more papers by this author First published: 14 November 2019 https://doi.org/10.1111/all.14104Citations: 5 Anne-Sophie Darrigade and Caroline Colmant contributed equally to this work. Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article.Citing Literature Volume75, Issue5May 2020Pages 1264-1266 RelatedInformation

OBJECTIVES:To assess the value of a radiographic score for the detection of delayed union in nailed fractures.METHODS:The modified radiographic union score (mRUS) values were determined by three separate radiologists on 259 radiographic sets of 58 nailed tibial or femoral fractures obtained at different timepoints after fracture (mean of 4.5 radiographic sets per fracture). A surgeon determined fracture outcome (normal or delayed union) at a mean of 192days after injury. Mean radiographic scores obtained at different timepoints after fracture were compared between fractures with normal or abnormal healing at follow-up.RESULTS:The mean score values increased significantly over time for fractures with normal healing for all readers (p<0.001). The mean score values determined 11-14 weeks after injury were higher in fractures with normal healing than in fractures with delayed union at follow-up (p<0.05). Scoring of radiographs obtained at about 3 months after injury or later enabled detection of fractures with delayed union with a sensitivity of 0.63-0.77 and a specificity of 1.0 (area under curve: 0.77- 0.88).CONCLUSIONS:The mRUS score can contribute to the detection of delayed union at a delay of about 3 months after injury in nailed shaft fractures.

OBJECTIVES:To determine whether body fat distribution, measured by waist circumference (WC) and waist/hip ratio (WHR), is a better predictor of mortality and morbidity after colorectal surgery than body mass index (BMI) or body surface area (BSA).BACKGROUND:Obesity measured by BMI is not a consistent risk factor for postoperative mortality and morbidity after abdominal surgery. Studies in metabolic and cardiovascular diseases have shown WC and WHR to be better outcome predictors than BMI.METHODS:A prospective multicenter international study was conducted among patients undergoing elective colorectal surgery. The WHR, BMI, and BSA were derived from body weight, height, and waist and hip circumferences measured preoperatively. Uni- and multivariate analyses were performed to identify risk factors for postoperative outcomes.RESULTS:A total of 1349 patients (754 men) from 38 centers in 11 countries were included. Increasing WHR significantly increased the risk of conversion [odds ratio (OR) = 15.7, relative risk (RR) = 4.1], intraoperative complications (OR = 11.0, RR = 3.2), postoperative surgical complications (OR = 7.7, RR = 2.0), medical complications (OR = 13.2, RR = 2.5), anastomotic leak (OR = 13.7, RR = 3.3), reoperations (OR = 13.3, RR = 2.9), and death (OR = 653.1, RR = 21.8). Both BMI (OR = 39.5, RR = 1.1) and BSA (OR = 4.9, RR = 3.1) were associated with an increased risk of abdominal wound complication. In multivariate analysis, the WHR predicted intraoperative complications, conversion, medical complications, and reinterventions, whereas BMI was a risk factor only for abdominal wall complications; BSA did not reach significance for any outcome.CONCLUSIONS:The WHR is predictive of adverse events after elective colorectal surgery. It should be used in routine clinical practice and in future risk-estimating systems.

Polychlorobiphenyls (PCBs), polybromodiphenylethers (PBDEs) and organochlorine pesticides (OCPs), such as dichlorodiphenyltrichloroethane (DDT) and hexachlorobenzene (HCB), are considered as endocrine disruptors in laboratory and wild animals. This study investigated whether these compounds and their hydroxylated metabolites (HO-PCBs and HO-PBDEs) may affect the homoeostasis of vitamin A, a dietary hormone, in the blubber and serum of twenty lactating grey seals sampled at early and late lactation on the Isle of May, Scotland. The effect of naturally produced compounds such as the methoxylated (MeO)-PBDEs was also examined. Vitamin A levels in inner blubber (37±9μg/g wet weight (ww) and 92±32μg/g ww at early and late lactation, respectively) and serum (408±143 and 390±98ng/ml at early and late lactation, respectively) appeared to be positively related to ΣPCBs, ΣPBDEs and several individual PCB and PBDE congeners in inner blubber and serum. These findings may suggest enhanced mobilisation of hepatic retinoid stores and redistribution in the blubber, a storage site for vitamin A in marine mammals. We have also reported that serum concentrations of ΣHO-PCBs and 4-OH-CB107 tended to increase with circulating vitamin A levels. Although the direction of the relationships may sometimes differ from those reported in the literature, our results are in agreement with previous findings highlighting a disruption of vitamin A homoeostasis in the blubber and bloodstream following exposure to environmental pollutants. The fact that vitamin A and PCBs appeared to share common mechanisms of mobilisation and transfer during lactation in grey seals (Debier et al., 2002b, Vanden Berghe et al., 2012) may also play a role in the different relationships observed between vitamin A and lipophilic pollutants.

Twenty grey seal (Halichoerus grypus) mother–pup pairs from the colony of the Isle of May (Scotland) were sampled at early and late lactation in order to study the transfer of polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs) and their metabolites (HO-PCBs and HO-PBDEs) as well as organochlorine pesticides (OCPs), such as DDT and metabolites (DDXs) and hexachlorobenzene (HCB). The transfer of the naturally produced MeO-PBDEs was also investigated. Generally, concentrations (on a lipid weight basis) of the sum of PCBs, PBDEs and DDXs tended to be higher in all tissues at late lactation (for maternal outer blubber ΣPCBs = 3860 ± 2091 ng/g, ΣPBDEs = 120 ± 74 ng/g and ΣDDXs = 559 ± 207 ng/g; for maternal inner blubber ΣPCBs = 4229 ± 3274 ng/g, ΣPBDEs = 148 ± 118 ng/g and ΣDDXs = 704 ± 353 ng/g; for maternal serum ΣPCBs = 1271 ± 796 ng/g, ΣPBDEs = 27 ± 16 ng/g and ΣDDXs = 242 ± 125 ng/g; for milk ΣPCBs = 1190 ± 747 ng/g, ΣPBDEs = 55 ± 36 ng/g and ΣDDXs = 357 ± 160 ng/g; for pup serum ΣPCBs = 1451 ± 901 ng/g, ΣPBDEs = 48 ± 31 ng/g and ΣDDXs = 395 ± 201 ng/g). In all tissues, ΣMeO-PBDEs were found at very low levels or even undetected and their concentrations appeared to increase at late lactation only in maternal inner blubber (2.7 ± 1.3 to 5.3 ± 2.9 ng/g for early and late lactation, respectively) and milk (0.6 ± 0.3 to 1.1 ± 0.5 ng/g for early and late lactation, respectively). The transfer from inner blubber to maternal serum was selective and strongly depended on the log Kow value of the compounds, with less lipophilic compounds being more efficiently released. Only a limited amount of HO-PCBs was transferred during lactation as 4-HO-CB-107 was the only metabolite detected in milk (29 to 40 pg/g lw). On the contrary, most of HO-PCB metabolites found in maternal serum were also detected in pup serum. These findings suggest not only a transplacental transfer of HO-PCBs from mothers to pups but also the possibility of endogenous biotransformation in suckling pups or accumulation of undetectable low amounts from milk.