Early menarche and other endocrine disrupting effects of per- and polyfluoroalkyl substances (PFAS) in adolescents from Northern Norway. The Fit Futures study.

BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) comprise a large group of chemicals that are ubiquitous in the environment and include recognized persistent organic pollutants. The aim of this cross-sectional study was to investigate possible endocrine disrupting effects of different PFAS in adolescents. METHODS: Serum concentrations of PFAS, thyroid, parathyroid and steroid hormones were measured in 921 adolescents aged 15-19 years in the Fit Futures study, Northern Norway. The questionnaire included data on self-reported age at menarche and puberty development score (PDS). Multiple linear and logistic regression analyses and principle component analyses (PCA) were used to assess associations of PFAS with hormones concentrations and puberty indices. RESULTS: In girls, total PFAS (∑PFAS), perfluorooctanoate (PFOA), perfluorooctane sulfonate (PFOS), perfluorononanoate (PFNA), perfluorodecanoate (PFDA) were positively associated with dehydroepiandrosterone sulfate (DHEAS) and negatively associated with 11-deoxycorticosterone (11-DOC)/DHEAS ratio. In boys, the associations with 11-DOC/DHEAS ratio were positive for ∑PFAS, perfluoroheptanoate (PFHpA), perfluoroheptane sulfonate (PFHpS), PFOA, and PFOS. Perfluoroundecanoate (PFUnDA) was negatively associated with free thyroxine (fT4) and free triiodothyronine (fT3) in boys. PFNA and PFDA were also negatively associated with fT3 in boys. Serum parathyroid hormone concentration (PTH) was negatively associated with ∑PFAS and perfluorohexane sulfonate (PFHxS) in girls, and with PFOS in boys. PFDA and PFUnDA were positively associated with early menarche, while ∑PFAS and PFOA were positively associated with PDS in boys. No associations of PFAS with serum testosterone, follicle-stimulating hormone, or luteinizing hormone were found in either sex. In girls, PFOA was positively associated with free testosterone index (FTI). In boys, PFOA was positively associated with androstendione and 17-OH-progesterone, while PFHpA was positively associated with estradiol. CONCLUSIONS: Serum concentrations of several PFAS were associated with parathyroid and steroid hormones in both sexes, and with thyroid hormones in boys, as well as with early menarche in girls and higher PDS in boys.

Structure and Conformation of Individual Molecules upon Adsorption of a Mixture of Benzoporphyrins on Ag(111), Cu(111), and Cu(110) Surfaces.

The front cover artwork is provided by the groups of Prof. Dr. Hans-Peter Steinrück and Prof. Dr. Norbert Jux at the Friedrich-Alexander-Universität (FAU) Erlangen-Nürnberg. The image shows a mixture of six 2H-tetrakis-(3, 5-di-tert-butyl-phenyl)(x)benzoporphyrins (2H-diTTBP(x)BPs, x = 0, 1, 2-cis, 2-trans, 3, or 4) molecules forming a porous square structure on Ag(111) as observed in scanning tunneling microscopy (STM) at room temperature. Read the full text of the Research Article at 10.1002/cphc.202300355.

Should we eat more fish - or less? / Bør vi spise mer fisk ­ eller mindre?

All food contains environmental toxins. The EU has set a new threshold for the level of environmental toxins that can be considered safe in the body. In Norway, the average intake exceeds this threshold, and fatty fish is the main source. Nevertheless, the Norwegian authorities recommend that all age groups eat more fish.

Structure and Conformation of Individual Molecules upon Adsorption of a Mixture of Benzoporphyrins on Ag(111), Cu(111), and Cu(110) Surfaces.

We investigated the adsorption behavior of a mixture of six 2H-tetrakis-(3, 5-di-tert-butylphenyl)(x)benzoporphyrins (2H-diTTBP(x)BPs, x=0, 1, 2-cis, 2-trans, 3, and 4) on Ag(111), Cu(111) and Cu(110) at room temperature by scanning tunneling microscopy (STM) under ultra-high vacuum conditions. On Ag(111), we observe an ordered two-dimensional square phase, which is stable up to 400 K. On Cu(111), the same square phase coexists with a stripe phase, which disappears at 400 K. In contrast, on Cu(110), 2H-diTTBP(x)BPs adsorb as immobile isolated molecules or dispersed short chains along the [1 1 ‾ ${\bar{1}}$ 0] substrate direction, which remain intact up to 450 K. The stabilization of the 2D supramolecular structures on Ag(111) and Cu(111), and of the 1D short chains on Cu(110) is attributed to van der Waals interactions between the tert-butyl and phenyl groups of neighboring molecules. From high-resolution STM, we can assign all six 2H-diTTBP(x)BPs within the ordered structures. Moreover, we deduce a crown shape quadratic conformation on Ag(111) and Cu(111), an additional saddle-shape on Cu(111), and an inverted structure and a quadratic appearance on Cu(110). The different conformations are attributed to the different degree of interaction of the iminic nitrogen atoms of the isoindole and pyrrole groups with the substrate atoms.

High level of heavy metals in crab meat. / Høyt nivå av tungmetaller i krabbe.

Crab meat is a popular seafood, but it sometimes contains large amounts of environmental toxins. The content is so high in many places in Norway that consumption of brown crab meat should generally be discouraged.

NT-ProBNP and high-sensitivity troponin T as screening tests for subclinical chronic heart failure in a general population.

AIMS: The aim of this study was to establish age-specific and sex-specific cut-off values for N-terminal pro-brain natriuretic peptide (NT-proBNP) and high-sensitivity troponin T (hs-troponin T) in healthy subjects and assess cardiac biomarkers as screening tools for subclinical heart failure (HF) in a general population. METHODS AND RESULTS: Altogether, 1936 participants were randomly selected from the general population Tromsø 7 study in Northern Norway. Diagnostic accuracy (sensitivity, specificity, and negative and positive predictive value) of cardiac markers for echocardiographically defined subclinical HF was evaluated. The receiver-operating characteristic analysis showed that areas under the curve were relatively low (under 0.75) for both NT-proBNP and hs-troponin T, suggesting that the diagnostic accuracy of these biomarkers for subclinical HF was not excellent, especially for mild forms of HF and younger age group 40-49 years. Sex-specific and age-specific cut-offs for hs-troponin T (99th percentiles) and NT-proBNP (97.5th percentiles) were established in healthy subjects from the same general population. The sex-specific and age-specific cut-offs for NT-proBNP had higher specificity for subclinical HF compared with the previously established single cut-off 125 pg/mL. Age-specific cut-off for hs-troponin T (18 ng/L) for men ≥60 years had also higher specificity than the single cut-off 14 ng/L. These cut-offs had high specificity, but low sensitivity, that makes hs-troponin T and NT-proBNP good biomarkers to rule in HF in case of a positive test, but not good enough to rule out all unrecognized HF due to false negative results. CONCLUSIONS: N-terminal pro-brain natriuretic peptide and hs-troponin T are suboptimal screening tools for subclinical HF in a general population due to low sensitivity.

Impaired gross motor development in infants with higher PFAS concentrations.

Industrial produced perfluoroalkyl substances (PFAS) are environmentally persistent and found in humans around the globe. PFAS is transferred from mother to child during pregnancy and lactation and PFAS concentrations are high in infants. PFAS exposure in early life has been linked to a range of negative health effects. In the present study we have investigated PFAS concentrations in mothers (pregnancy week 18, 28 and 36 and six weeks, four and six months postpartum, n = 114) and in infants at six months age (n = 94), and studied the effects of PFAS status on infant gross motor development by Alberta Infant Motor Scale (AIMS) at age six months. PFAS concentrations declined in the mothers during pregnancy and postpartum period, and the highest concentrations were seen in infants aged six months. Parity was a strong negative predictor and fish intake a strong positive predictor of maternal PFAS status, while maternal concentrations of PFAS in pregnancy week 18 and months of exclusive breastfeeding determined the PFAS concentrations in infants at six months. Infants who scored below the median on gross motor development had higher PFAS concentrations than infants with a better gross motor development. Ninety percent of the women reported having fish for dinner at least once a week, with fatty fish as the most popular choice (72%). A higher maternal fish intake in pregnancy week 18 was associated with a poorer gross motor development in the infants at six months. Infant gross motor development is a marker of later cognitive outcome and our findings indicate that higher PFAS concentrations in young infants and maternal fatty fish intake may impair neurodevelopment.

Quantitation of linear and branched perfluoroalkane sulfonic acids (PFSAs) in women and infants during pregnancy and lactation.

BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) are associated with negative health effects, and exposure during fetal life and infancy are of concern. A subgroup of PFAS, linear and branched perfluoroalkane sulfonic acids (PFSA), have significant differences in biochemical reactions, bioaccumulation and potential toxic exposure effects, and data on transfer of PFSA isomers from mother to baby through placenta or in breastmilk are scarce. OBJECTIVES: The objective was to investigate differences in branched and linear PFSA isomers in never-pregnant, pregnant and postpartum women and infants. METHODS: Serum concentrations of branched and linear, perfluorohexane sulfonate (PFHxS), perfluoroheptane sulfonate (PFHpS) and perfluorooctane sulfonate (PFOS) were measured in never-pregnant women (n = 158), pregnant and postpartum women (n = 114) and their infants (n = 94) at age six months. RESULTS: There was a linear relation between maternal PFSA concentrations in pregnancy week 18 and the infant at age six months. The PFSA concentrations in maternal and infant serum varied with a factor up to 20. The maternal branched/ linear PFHxS ratio increased in the latter part of pregnancy (+45%) and remained high postpartum, and was substantially lower in the infants. Branched/linear PFHpS ratio increased during pregnancy and was highest in the infants, while the branched/linear PFOS ratio decreased in the mothers and was high in the infants. DISCUSSION: The linear relations between PFSA concentrations in infants aged six months and mothers in pregnancy week 18 confirm that pregnancy and lactation are major excretion routes for PFSA, but accumulate in the infant. The observed great variability in PFSA burden among mothers and infants, as well as the reduced maternal transfer of branched PFHxS isoforms and increased transfer of branched PFOS isoforms compared to the respective linear isoforms to the infant, might impact adverse health effects associated with PFSA exposure, but this should be confirmed in future studies.

Per- and Polyfluoroalkyl Substances in Human Serum Samples of Selected Populations from Ghana.

The aims of this study were to assess serum concentrations of per- and polyfluoroalkyl substances (PFASs) in selected populations from Ghana, including workers engaged in the repair of electronic equipment (ERWs), and to elucidate PFAS concentrations in relation to blood mercury concentrations (B-Hg) as a biomarker of seafood consumption. In all, 219 participants were recruited into the study, of which 26 were women and 64 were ERWs. Overall, the PFAS concentrations were low. The most abundant components were perfluorooctane sulfonate (PFOS) and perfluorohexane sulfonic acid (PFHxS). Women had generally lower PFAS concentration than men. The ERWs had statistically significantly higher concentrations of perfluorooctanoate (PFOA), which was associated with the concentration of tin in urine. This could indicate exposure during soldering. The concentration of B-Hg was associated with several of the PFASs such as PFOA, PFOS and perfluoroheptane sulfonate (PFHpS). Additionally, the concentrations of perfluorodecanoic acid (PFDA) and perfluoroundecanoate (PFUnDA) were highly associated with the concentrations of B-Hg. It is noteworthy that the linear isomer of PFHxS was strongly associated with B-Hg while the branched isomers of PFHxS were not. In conclusion, the PFAS concentrations observed in the present study are low compared to other populations previously investigated, which also reflects a lower PFAS exposure within the Ghanaian cohorts. ERWs had significantly higher PFOA concentrations than the other participants. Several PFASs were associated with B-Hg, indicating that seafood consumption may be a source of PFAS exposure.

Exposure to perfluoroalkyl substances (PFAS) and dyslipidemia, hypertension and obesity in adolescents. The Fit Futures study.

BACKGROUND: Prevalence of obesity, hypertension and dyslipidemia has been increasing in children and adolescents worldwide. Exposure to environmental pollutants may contribute to this development. Our aim was to study associations between perfluoroalkyl substances (PFAS) and dyslipidemia, hypertension and obesity in a population-based sample of adolescents. METHODS: Serum PFAS concentrations were measured in 940 adolescents, mean age 16.4 (SD 1.3) years, from the cross-sectional Fit Futures study by the UHPLC-MS/MS method. The following endpoints were used: hypertension (systolic blood pressure over 130 mmHg and/or diastolic blood pressure over 80 mmHg); obesity (body mass index over 2 z-score, WHO charts for adolescents); dyslipidemia (total cholesterol ≥ 5.17 mmol/L, and/or LDL-cholesterol ≥ 3.36 mmol/l, and/or apolipoprotein B ≥ 1.10 g/L). RESULTS: Perfluorooctane sulfonate (PFOS), perfluorononanoate (PFNA), perfluorodecanoate (PFDA) and perfluoroundecanoate (PFUnDA) serum concentrations were positively associated with apolipoprotein B, total- and LDL cholesterol. The highest vs. lowest quartiles of total PFAS (∑PFAS), PFNA and PFDA concentrations were positively associated with the risk of dyslipidemia: OR 2.24 (95% CI 1.10-4.54), OR 2.30 (95% CI 1.16-4.57) and 2.36 (95% CI 1.08-5.16), respectively. The highest vs. lowest quartiles of ∑PFAS, perfluorohexane sulfonate (PFHxS), PFOS, perfluorooctanoate (PFOA) concentrations were positively associated with the risk of hypertension: OR 1.91 (95% CI 1.12-3.26), OR 2.06 (95% CI 1.16-3.65), 1.86 (95% CI 1.08-3.19) and 2.08 (95% CI 1.17-3.69) respectively. PFHxS and perfluoroheptane sulfonate (PFHpS) concentrations were positively associated with obesity. CONCLUSIONS: This cross-sectional study showed a possible link between several PFAS and dyslipidemia, hypertension and obesity in Norwegian adolescents.

Perfluoroalkyl substances (PFASs) and mercury in never-pregnant women of fertile age: association with fish consumption and unfavorable lipid profile.

OBJECTIVES: To examine concentrations of perfluoroalkyl substances (PFASs) and lifestyle factors that may contribute to higher levels of pollutants in never-pregnant women of fertile age. DESIGN: Observational cross-sectional study. SETTING: Participants were recruited among employees and students at Haukeland University Hospital and the University of Bergen, Norway. PARTICIPANTS: Healthy, never-pregnant Norwegian women (n=158) of fertile age (18-39 years). OUTCOMES: Concentrations of 20 different PFASs, mercury (Hg), lead, cadmium, total, high-density lipoprotein and low-density lipoprotein (LDL) cholesterol, in addition to self-reported data on dietary intake. RESULTS: Seven PFASs were detected in more than 95% of the women. Women aged 30-39 years had higher concentrations of sum PFAS compared with younger women. Serum PFASs were significantly intercorrelated (rho: 0.34-0.98, p<0.001) and six of them were significantly correlated to whole blood Hg (rho: 0.21-0.74, p<0.01). Fish consumption was the strongest predictor for most serum PFASs and for whole blood Hg. Fish consumption and serum perfluorooctanesulfonic acid (PFOS) concentrations were both positively associated with serum total and LDL cholesterol, established risk factors for cardiovascular disease. CONCLUSIONS: The majority of Norwegian never-pregnant women of fertile age had a mixture of seven different PFASs and Hg detected in their blood. PFAS concentrations were higher in older women and associated with fish intake. As the mean age of women at first birth is increasing, several factors require further consideration including diet, as this may influence the burden of PFAS to the next generation. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov ID: NCT03272022, Unique Protocol ID: 2011/2447, Regional Committee for Medical Research Ethics West (2011/2447), 12 January 2012.

Efficacy and Safety of Empagliflozin in Renal Transplant Recipients With Posttransplant Diabetes Mellitus.

OBJECTIVE: Sodium-glucose cotransporter 2 (SGLT2) inhibitors have lately become the recommended treatment in patients with type 2 diabetes and high cardiovascular risk. Patients with posttransplant diabetes mellitus (PTDM) also have high cardiovascular risk. The aim of this study was to investigate the safety and efficacy of empagliflozin in renal transplant recipients with PTDM. RESEARCH DESIGN AND METHODS: Forty-nine renal transplant recipients were included in an investigator-initiated, single-center, prospective, double-blind study and randomized to receive either 10 mg empagliflozin or placebo once daily for 24 weeks. Patients transplanted >1 year ago, diagnosed with PTDM, with stable renal function (estimated glomerular filtration rate [eGFR] >30 mL/min/1.73 m2), and with stable immunosuppressive therapy were studied. RESULTS: Forty-four renal transplant recipients (22 empagliflozin/22 placebo, 34 males) completed the study. Median (interquartile range) change in glycated hemoglobin (HbA1c) was significantly reduced with empagliflozin compared with placebo: -0.2% (-0.6, -0.1) (-2.0 mmol/mol [-6.5, -1.0]) vs. 0.1% (-0.1, 0.4) (1.0 mmol/mol [-0.75, 3.8]) (P = 0.025). The magnitude of glucose reduction was dependent on GFR and baseline HbA1c. The treatment also resulted in a significant reduction in body weight of -2.5 kg (-4.0, -0.05) compared with an increase of 1.0 kg (0.0, 2.0) in the placebo group (P = 0.014). There were no significant differences between the groups in adverse events, immunosuppressive drug levels, or eGFR. CONCLUSIONS: Empagliflozin appeared safe and improved glycemic control in renal transplant recipients with PTDM compared with placebo. A concomitant reduction in body weight was seen.

Serum perfluoroalkyl substances (PFAS) and risk of asthma and various allergies in adolescents. The Tromsø study Fit Futures in Northern Norway.

BACKGROUND: Exposure to environmental pollutants may contribute to the development of asthma and other allergies. The aim of this study was to investigate possible associations between asthma and other allergies with exposure to perfluoroalkyl substances (PFASs) in adolescents from the Arctic region of Norway. METHODS: The Tromsø study Fit Futures 1 (TFF1) and 3-year follow-up Fit Futures 2 study (TFF2) included 675 adolescents that completed a questionnaire about health conditions and underwent a clinical examination with blood tests and fractional nitric oxide (FeNO) measurement. Serum concentrations of 18 PFASs were measured by UHPLC-MS/MS method. RESULTS: Total PFASs (ΣPFAS) serum concentration over 4th quartile was positively associated with asthma in the TFF1 (OR 3.35 (95% CI 1.54-7.29), p = 0.002). Total perfluorooctane sulfonate (ΣPFOS), linear PFOS (linPFOS), linear perfluorohexane sulfonate (linPFHxS) concentrations over 4th quartiles were associated with 2 times higher odds of asthma in the TFF1. The positive associations between ΣPFAS, ΣPFOS, linPFOS and asthma remained statistically significant in the TFF2. ΣPFAS and linPFHxS concentrations over 3rd tertiles were associated with positive marker of eosinophilic airways inflammation FeNO> 25 ppb. Concentrations of ΣPFOS and linPFOS over 3rd quartiles were positively associated with self-reported nickel allergy (OR 2.25 (95% CI 1.17-4.35) p = 0.016 and OR 2.53 (95% CI 1.30-4.90) p = 0.006, respectively). Allergic rhinitis, self-reported pollen allergy, food allergy and atopic eczema were not associated with PFASs concentrations. CONCLUSIONS: This study of Norwegian adolescents showed a positive association between several PFASs and asthma, as well as between PFOS and nickel allergy.

C-reactive protein and risk of venous thromboembolism: results from a population-based case-crossover study.

Long-term, low-grade inflammation does not seem to be a risk factor for venous thromboembolism. The impact of acute inflammation, regardless of cause, on risk of venous thromboembolism is scarcely studied. We aimed to investigate the impact of acute inflammation, assessed by C-reactive protein, on short-term risk of venous thromboembolism. We conducted a case-crossover study of patients with venous thromboembolism (n=707) recruited from a general population. Information on triggers and C-reactive protein levels were retrieved from hospital records during the 90 days before the event (hazard period) and in four preceding 90-day control periods. Conditional logistic regression was used to obtain ß coefficients for change in natural log (ln) transformed C-reactive protein from control to hazard periods and to determine corresponding odds ratios for venous thromboembolism. Median C-reactive protein was 107 mg/L in the hazard period, and ranged from 7 mg/L to 16 mg/L in the control periods. The level of C-reactive protein was 58% (95% CI 39-77%) higher in the hazard period than in the control periods. A one-unit increase in ln-C-reactive protein was associated with increased risk of venous thromboembolism (OR 1.79, 95% CI 1.48-2.16). The risk estimates were only slightly attenuated after adjustment for immobilization and infection. In stratified analyses, ln-C-reactive protein was associated with increased risk of venous thromboembolism in cases with (OR 1.55, 95% CI 1.01-2.38) and without infection (OR 1.77, 95% CI 1.22-2.57). In conclusion, we found that acute inflammation, assessed by C-reactive protein, was a trigger for venous thromboembolism.

Perfluoroalkyl substances in adolescents in northern Norway: Lifestyle and dietary predictors. The Tromsø study, Fit Futures 1.

Perfluoroalkyl substances (PFASs) are environmentally persistent chemicals widely used in many consumer products due to water and oil proofing and fire-resistant properties. Several PFASs are recognized as environmental pollutants. This study investigated serum concentrations of 18 different PFASs and their associations with diet and lifestyle variables in 940 adolescents (age 15-19 years) who participated in the Fit Futures 1 study in the Troms arctic district of Norway. Serum concentrations of PFASs were analyzed by ultrahigh pressure liquid chromatography coupled to a triple quadrupole mass spectrometer (UHPLC-MS/MS). The most abundant PFASs in this population were perfluorooctane sulfonate (PFOS), perfluorooctanoate (PFOA), perfluorohexane sulfonate (PFHxS), perfluorononanoate (PFNA) and perfluorodecanoate (PFDA) that were found in 99% of the participants. Perfluoroheptane sulfonate (PFHpS) was found in 98% of the participants. Median concentrations were: PFOS 6.20 ng/mL, PFOA 1.92 ng/mL, PFHxS 0.71 ng/mL, PFNA 0.50 ng/mL, PFDA 0.21 ng/mL and PFHpS 0.15 ng/mL. Median of PFASs sum concentration (∑PFAS) was 10.7 ng/mL, the concentration range was 2.6-200.8 ng/mL. Intake of fat fish, fish liver, seagull eggs, reindeer meat and drinks with sugar were the main dietary predictors of several PFASs. Intake of junk food (pizza, hamburger, sausages) was positively associated with PFNA, intake of canned food was positively associated with PFHxS. Intake of fruits and vegetables, milk products, snacks and candy was not associated with PFASs concentrations. Lean fish intake was positively associated with PFUnDA, but not with other PFASs. There was a positive association of ∑PFAS, PFHxS, PFOA, PFNA and PFDA with chewed tobacco use.

Essential and non-essential trace elements among working populations in Ghana.

BACKGROUND: Lead battery repair workers (LBRW) and electronic repair workers (ERW) may be exposed to inorganic components during work. This study aimed at determining essential and non-essential trace elements in male LBRW, ERW, referents and a group of female petty traders (FPT) in Kumasi (Ghana), taking into account iron status and inflammation. METHODS: Altogether 64 LBRW, 64 ERW, 65 referents and 26 FPT were investigated in this cross-sectional study. Urine, whole blood and serum were collected for determination of trace elements. C-reactive protein and ferritin were determined in serum. RESULTS: The LBRW had higher blood concentrations of manganese (B-Mn) and lead (B-Pb) and antimony in urine (U-Sb), and lower concentrations of cobalt in blood (B-Co). Being ERW was associated with higher concentrations of blood cadmium (B-Cd), urinary tin (U-Sn) and serum chromium (S-Cr). Concentrations of selenium (B-Se), Co and mercury (B-Hg) in whole blood and iodine in urine (U-I) were relatively high. Marginal iron status appeared to be a determinant for elevated concentrations of Co in particular, but also Mn and Cd in blood. Systemic inflammation was associated with the concentrations of copper and Se. The concentrations of Hg in whole blood were highly associated with Se and arsenic (As) in whole blood, indicating fish consumption as a common source of intake of these elements. However, Hg in whole blood was only slightly associated with Se in serum. CONCLUSIONS: The ERW had elevated concentrations of B-Cd, S-Cr, and U-Sn, while B-Mn, B-Pb, and U-Sb concentrations were higher among the LBRW. Iron status and inflammation had substantial impact on some element concentration. This population had high concentrations of B-Se, B-Hg and B-Co and U-I.